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Sudden cardiac death (SCD) is a sudden, unexpected death caused by a change in heart rhythm (sudden cardiac arrest). It is the largest cause of natural death in the U.S., causing about 325,000 adult deaths in the U.S. each year. SCD is responsible for half of all heart disease deaths. How Is Sudden Cardiac Arrest Different from a Heart Attack? Sudden cardiac arrest is not a heart attack (myocardial infarction) but can occur during a heart attack. Heart attacks occur when there is a blockage in one or more of the arteries to the heart, preventing the heart from receiving enough oxygen-rich blood. If the oxygen in the blood cannot reach the heart muscle, the heart becomes damaged. In contrast, sudden cardiac arrest occurs when the electrical system to the heart malfunctions and suddenly becomes very irregular. The heart beats dangerously fast. The ventricles may flutter or quiver (ventricular fibrillation), and blood is not delivered to the body. In the first few minutes, the greatest concern is that blood flow to the brain will be reduced so drastically that a person will lose consciousness. Death follows unless emergency treatment is begun immediately. Emergency treatment includes cardiopulmonary resuscitation (CPR) and defibrillation. CPR is a manual technique using repetitive pressing to the chest and breathing into the person's airways that keeps enough oxygen and blood flowing to the brain until the normal heart rhythm is restored with an electric shock to the chest, a procedure called defibrillation. Emergency squads use portable defibrillators and frequently there are public access defibrillators (AEDs, automated external defibrillators) in public locations that are intended to be available for use by citizens who observe cardiac arrest. What Are the Symptoms of Sudden Cardiac Arrest? Some people may experience symptoms of sudden cardiac arrest, such as a racing heartbeat or feeling dizzy, alerting them that a potentially dangerous heart rhythm problem has started. In over half of the cases, however, sudden cardiac arrest occurs without prior symptoms. What Causes Sudden Cardiac Death? Most sudden cardiac deaths are caused by abnormal heart rhythms called arrhythmias. The most common life-threatening arrhythmia is ventricular fibrillation, which is an erratic, disorganized firing of impulses from the ventricles (the heart's lower chambers). When this occurs, the heart is unable to pump blood and death will occur within minutes, if left untreated. What Are the Risk Factors of Sudden Cardiac Arrest? There are many risk factors that can increase a person's risk of sudden cardiac arrest and sudden cardiac death, including the following: - Previous heart attack with a large area of the heart damaged (75% of SCD cases are linked to a previous heart attack.) - A person's risk of SCD is higher during the first 6 months after a heart attack. - Coronary artery disease (80% of SCD cases are linked with this disease.) - Risk factors for coronary artery disease include smoking, hypertension, family history of heart disease, and high cholesterol. Other risk factors of sudden cardiac arrest include: - Ejection fraction -- a measure of how much blood the left ventricle pumps out with each contraction -- of under 40%, particularly in combination with ventricular tachycardia - Prior episode of sudden cardiac arrest - Family history of sudden cardiac arrest or SCD - Personal or family history of certain abnormal heart rhythms, including long or short QT syndrome, Wolff-Parkinson-White syndrome, extremely low heart rates, or heart block - Ventricular tachycardia or ventricular fibrillation after a heart attack - History of congenital heart defects or blood vessel abnormalities - History of syncope (fainting episodes of unknown cause) - Heart failure: a condition in which the heart's pumping power is weaker than normal. Patients with heart failure are 6 to 9 times more likely than the general population to experience ventricular arrhythmias that can lead to sudden cardiac arrest - Hypertrophic cardiomyopathy: a thickened heart muscle that especially affects the ventricles - Significant changes in blood levels of potassium and magnesium (from using diuretics, for example), even if there is not underlying heart disease - Recreational drug abuse - Taking drugs that are "pro-arrhythmic" may increase the risk for life-threatening arrhythmias Can Sudden Cardiac Death Be Prevented? If you have any of the risk factors for sudden cardiac death (listed above), it is important that you speak with your doctor about possible steps to reduce your risk. Keeping regular follow-up appointments with your doctor, making certain lifestyle changes, taking medications as prescribed, and having interventional procedures or surgery (as recommended) are ways you can reduce your risk. Follow-Up Care With Your Doctor: Your doctor will tell you how often you need to have follow-up visits. To prevent future episodes of sudden cardiac arrest, your doctor will want to perform diagnostic tests to determine what caused the cardiac event. Tests may include electrocardiogram (ECG or EKG), ambulatory monitoring, echocardiogram, cardiac catheterization, and electrophysiology studies. Ejection Fraction (EF): EF is a measurement of the percentage (fraction) of blood pumped (ejected) out of the heart with each beat. EF can be measured in your doctor's office during an echocardiogram (echo) or during other tests such as a MUGA (multiple gated acquisition) scan, cardiac catheterization, nuclear stress test, or magnetic resonance imaging (MRI) scan of the heart. The EF of a healthy heart ranges from 55% to 75%. Your EF can go up and down, based on your heart condition and the effectiveness of the therapies that have been prescribed. If you have heart disease, it is important to have your EF measured initially, and then as needed, based on changes in your condition. Ask your doctor how often you should have your EF checked. Reducing Your Risk Factors: If you have coronary artery disease -- and even if you do not -- there are certain lifestyle changes you can make to reduce your risk of sudden cardiac arrest. These lifestyle changes include: - Quitting smoking - Losing weight - Exercising regularly - Following a heart-healthy diet - Managing diabetes - Managing other health conditions including high blood pressure and cholesterol If you have questions or are unsure how make these changes, talk to your doctor. Patients and families should know the signs and symptoms of coronary artery disease and the steps to take if symptoms occur. Medications: To help reduce the risk of sudden cardiac arrest, doctors may prescribe medications to people who have had heart attacks or who have heart failure or arrhythmias such as irregular heart rhythms. These drugs may include ACE inhibitors, beta-blockers, calcium-channel blockers, and other antiarrhythmics. For patients with high cholesterol and coronary artery disease, statin drugs may be prescribed. If medication is prescribed, your doctor will give you more specific instructions. It is important that you know the names of your medications and any directions that you need to follow when taking them. If you have any questions, be sure to ask your doctor or pharmacist. Implantable cardioverter-defibrillator (ICD): For people whose risk factors put them at great risk for sudden cardiac death, an ICD may be inserted as a preventive treatment. An ICD is a small machine similar to a pacemaker that is designed to correct arrhythmias. It detects and then corrects a fast heart rate. The ICD constantly monitors the heart rhythm. When it detects a very fast or slow heart rhythm, it delivers energy (a small, but powerful shock) to the heart muscle to cause the heart to beat in a normal rhythm again. The ICD also records the data of each abnormal heartbeat, which can be viewed by the doctor using a special machine kept at the hospital. The ICD may be used in patients who have survived sudden cardiac arrest and need their heart rhythms constantly monitored. It may also be combined with a pacemaker to treat other underlying irregular heart rhythms. Interventional Procedures or Surgery: For patients with coronary artery disease, an interventional procedure such as angioplasty (blood vessel repair) or bypass surgery may be needed to improve blood flow to the heart muscle and reduce the risk of SCD. For patients with other conditions, such as hypertrophic cardiomyopathy or congenital heart defects, an interventional procedure or surgery may be needed to correct the problem. Other procedures may be used to treat abnormal heart rhythms, including electrical cardioversion and catheter ablation. When a heart attack occurs in the left ventricle (left lower pumping chamber of the heart), a scar forms. The scarred tissue may increase the risk of ventricular tachycardia. The electrophysiologist (doctor specializing in electrical disorders of the heart) can determine the exact area causing the arrhythmia. The electrophysiologist, working with your surgeon, may combine ablation (the use of high-energy electrical energy to "disconnect" abnormal electrical pathways within the heart) with left ventricular reconstruction surgery (surgical removal of the infarcted or dead area of heart tissue). Educate Your Family Members: If you are at risk for SCD, talk to your family members so they understand your condition and the importance of seeking immediate care in the event of an emergency. Family members and friends of those at risk for SCD should know how to perform CPR. Classes to teach this are available in most communities. Can Sudden Cardiac Arrest Be Treated? Yes, sudden cardiac arrest can be treated and reversed, but emergency action must take place immediately. Survival can be as high as 90% if treatment is initiated within the first minutes after sudden cardiac arrest. The rate decreases by about 10% each minute longer it takes to initiate therapy. Those who survive have a better long-term outlook. What Should I Do if I Witness Sudden Cardiac Arrest? If you witness someone experiencing sudden cardiac arrest, dial 911 or your local emergency personnel immediately and initiate CPR. If done properly, CPR can save a person's life, as the procedure keeps blood and oxygen circulating through the body until help arrives. If there is an AED available, the best chance of rescuing the person includes defibrillation with that device. The shorter the time until defibrillation, the greater the chance the person will survive. It is CPR plus defibrillation that saves a person. After successful defibrillation, most people require hospital care to treat and prevent future cardiac problems. Sudden Cardiac Death and Athletes SCD occurs rarely in athletes, but when it does happen, it often affects us with shock and disbelief. Cause: Many cases of SCD are related to undetected heart disease. In the younger population, SCD is often caused by congenital heart defects, while in older athletes (ages 35 and older), the cause is more often related to coronary artery disease. Prevalence: In the younger population, most SCD occurs while playing team sports. It occurs in about one in 50,000 athletes, and more often in males. In older athletes (ages 35 and older), SCD occurs more often while running or jogging. Screening: The American Heart Association recommends cardiovascular screening for high school and collegiate athletes and should include a complete and careful evaluation of the athlete's personal and family history and a physical exam. Screening should be repeated every two years, with a history obtained every year..An electrocardiogram may detect asymptomatic heart disease in some young people. Men ages 40 and older and women ages 50 and older should also have a thorough examination and receive education about heart disease risk factors and symptoms. They may also need an exercise stress test based on their doctor’s evaluation. If heart problems are identified or suspected, the individual should be referred to a cardiologist for further evaluation and treatment guidelines before participating in sports. For More Information: Sudden Arrhythmia Death Syndromes Foundation 4527 S 2300 E, Suite 104 Salt Lake City, UT 84117-4448 Heart Rhythm Society 1325 G Street NW, Suite 400 Washington, DC 20005 CPR Information: For more information about CPR, please contact your local chapter of the American Red Cross or the American Heart Association (www.heart.org). Or ask your doctor for more information.	2	10	1	0	0	0.858579	1	2,620
Cystinosis Classification and external resources Chemical structure of cystine formed from L-cysteine (under biological conditions) ICD-10 E72.0 ICD-9 270.0 DiseasesDB 3382 eMedicine ped/538 MeSH D003554 Cystinosis is a lysosomal storage disease characterized by the abnormal accumulation of the amino acid cystine. It is a genetic disorder that typically follows an autosomal recessive inheritance pattern. Cystinosis is the most common cause of Fanconi syndrome in the pediatric age group. Fanconi syndrome occurs when the function of cells in renal tubules are impaired, leading to abnormal amounts of carbohydrates and amino acids in the urine, excessive urination, and low blood levels of potassium and phosphates. Cystinosis is a rare genetic disorder that causes an accumulation of the amino acid cystine within cells, forming crystals that can build up and damage the cells. These crystals negatively affect many systems in the body, especially the kidneys and eyes. The accumulation is caused by abnormal transport of cystine from lysosomes, resulting in a massive intra-lysosomal cystine accumulation in tissues. Via an as yet unknown mechanism, lysosomal cystine appears to amplify and alter apoptosis in such a way that cells die inappropriately, leading to loss of renal epithelial cells. This results in renal Fanconi syndrome, and similar loss in other tissues can account for the short stature, retinopathy, and other features of the disease. Definitive diagnosis and treatment monitoring are most often performed through measurement of white blood cell cystine level using tandem mass spectrometry. There are three distinct types of cystinosis each with slightly different symptoms: nephropathic cystinosis, intermediate cystinosis, and non-nephropathic or ocular cystinosis. Infants affected by nephropathic cystinosis initially exhibit poor growth and particular kidney problems (sometimes called renal Fanconi syndrome). The kidney problems lead to the loss of important minerals, salts, fluids, and other nutrients. The loss of nutrients not only impairs growth, but may result in soft, bowed bones (hypophosphatemic rickets), especially in the legs. The nutrient imbalances in the body lead to increased urination, thirst, dehydration, and abnormally acidic blood (acidosis). By about age two, cystine crystals may also be present in the cornea. The buildup of these crystals in the eye causes an increased sensitivity to light (photophobia). Without treatment, children with cystinosis are likely to experience complete kidney failure by about age ten. Other signs and symptoms that may occur in untreated patients include muscle deterioration, blindness, inability to swallow, diabetes, and thyroid and nervous system problems. The signs and symptoms of intermediate cystinosis are the same as nephropathic cystinosis, but they occur at a later age. Intermediate cystinosis typically begins to affect individuals around age twelve to fifteen. Malfunctioning kidneys and corneal crystals are the main initial features of this disorder. If intermediate cystinosis is left untreated, complete kidney failure will occur, but usually not until the late teens to mid twenties. People with non-nephropathic or ocular cystinosis do not usually experience growth impairment or kidney malfunction. The only symptom is photophobia due to cystine crystals in the cornea. It is currently being researched at UC San Diego, The University of Michigan, Tulane University School of Medicine, and at the National Institutes of Health in Bethesda, Maryland as well as at Robert Gordon University in Aberdeen and in Sunderland, UK as well as the Necker Hospital in Paris. Cystinosis occurs due to a mutation in the gene CTNS, located on chromosome 17, which codes for cystinosin, the lysosomal cystine transporter. Symptoms are first seen at about 3 to 18 months of age with profound polyuria (excessive urination), followed by poor growth, photophobia, and ultimately kidney failure by age 6 years in the nephropathic form. All forms of cystinosis (nephropathic, juvenile and ocular) are autosomal recessive, which means that the trait is located on an autosomal gene, and an individual who inherits two copies of the gene - one from both parents - will have the disorder. There is a 25% risk of having a child with the disorder, when both parents are carriers of an autosomal recessive trait. Cystinosis affects approximately 1 in 100,000 to 200,000 newborns. and there are only around 2,000 known individuals with cystinosis in the world. The incidence is higher in the province of Brittany, France, where the disorder affects 1 in 26,000 individuals. Cystinosis is normally treated with a drug called cysteamine (brand name Cystagon). The administration of cysteamine can reduce the intracellular cystine content. Cysteamine concentrates inside the lysosomes and reacts with cystine to form both cysteine and a cysteine-cysteamine complex, which are able to leave the lysosomes. When administered regularly, cysteamine decreases the amount of cystine stored in lysosomes and correlates with conservation of renal function and improved growth. Cysteamine eyedrops remove the cystine crystals in the cornea that can cause photophobia if left unchecked. Patients with cystinosis are also often given sodium citrate to treat the blood acidosis, as well as potassium and phosphorus supplements. If the kidneys become significantly impaired or fail, then treatment must be begun to ensure continued survival, up to and including renal transplantation. - Online 'Mendelian Inheritance in Man' (OMIM) 219800 - Infantile nephropathic - Online 'Mendelian Inheritance in Man' (OMIM) 219900 - Adolescent nephropathic - Online 'Mendelian Inheritance in Man' (OMIM) 219750 - Adult nonnephropathic - Hartnup disease - Fanconi syndrome - genetic disease - Cystinosis at NLM Genetics Home Reference - ^ a b A. Gahl, William; Jess G. Thoene and Jerry A. Schneider (2002). "Cystinosis". N Engl J Med 347 (2): 111–121. doi:10.1056/NEJMra020552. PMID 12110740. - ^ Cystinosis - ^ Howard G. WORTHEN, N; Robert A. GOOD (1958). "The de Toni-Fanconi Syndrome with Cystinosis". AMA J Dis Child. 95 (6): 653–688. PMID 1353216. - ^ "Cystinosis on Genetic home reference". http://ghr.nlm.nih.gov/condition=cystinosis. - ^ Kalatzis, V; Cherqui S, Jean G, Cordier B, Cochat P, Broyer M, Antignac C (October 2001). "Characterization of a putative founder mutation that accounts for the high incidence of cystinosis in Brittany". J Am Soc Nephrol 12 (10): 2170–2174. PMID 11562417. http://jasn.asnjournals.org/content/12/10/2170.long. Retrieved 31 March 2011. - ^ a b William A. Gahl, William A.; George F. Reed, Ph.D., Jess G. Thoene, M.D., Joseph D. Schulman, M.D., William B. Rizzo, M.D., Adam J. Jonas, M.D., Daniel W. Denman, M.A., James J. Schlesselman, Ph.D., Brian J. Corden, M.D., and Jerry A. Schneider, M.D. (1987). "Cysteamine Therapy for Children with Nephropathic Cystinosis". N Engl J Med 316 (16): 971–977. doi:10.1056/NEJM198704163161602. PMID 3550461. - Cystinosis Research Network - a non-profit organization advocating research, providing family assistance, and educating the public about cystinosis. - Cystinosis Patient Registry - contribute to research and be informed of available clinical trials and studies - GeneReviews/NCBI/NIH/UW entry on Cystinosis - Cystinosis - Cystinosis Research Foundation- an international research support and education foundation - BC Health Guide - Cystinosis Foundation UK - a UK Charity Supporting Families & Research - Hide and Seek Foundation For Lysosomal Disease Research Inborn error of amino acid metabolism (E70–E72, 270) K→acetyl-CoALysine/straight chainHypertryptophanemia GG→pyruvate→citrateG→glutamate→ IE of RTT Wikimedia Foundation. 2010. Look at other dictionaries: cystinosis — ▪ pathology inborn error of metabolism resulting in the deposition of crystals of the amino acid cystine in various body tissues. Tissues that are particularly affected include the bone marrow, liver, cornea (where the crystals can be seen) … Universalium cystinosis — noun A disorder caused by abnormal metabolism of cystine … Wiktionary cystinosis — A lysosomal storage disorder with various forms, all with autosomal recessive inheritance. The nephropathic form of early childhood is characterized by widespread deposits of cystine crystals throughout the body, including the bone … Medical dictionary cystinosis — cys·ti·no·sis … English syllables cystinosis — n. an inborn defect in the metabolism of amino acids, leading to abnormal accumulation of the amino acid cystine in the blood, kidneys, and lymphatic system. See also: Fanconi syndrome … The new mediacal dictionary cystinosis — … Useful english dictionary late onset juvenile cystinosis — cystinosis with onset in the second decade of life, characterized by photophobia, mild proximal tubulopathy, and slowly progressive glomerulopathy that may progress to chronic renal failure. Called also adolescent nephropathic c … Medical dictionary adult nonnephropathic cystinosis — benign nonnephropathic cystinosis cystinosis characterized by photophobia caused by deposition of cystine crystals in the cornea, without renal damage. Called also ocular nonnephropathic c … Medical dictionary infantile nephropathic cystinosis — the most common cause of Fanconi syndrome (def. 2), a type of cystinosis marked by vitamin Dâ€“resistant rickets, chronic acidosis, polyuria, and dehydration, all resulting from proximal renal tubular dysfunction, and by corneal opacities, growth … Medical dictionary nephropathic cystinosis — any of the types of cystinosis that involve kidney damage as well as ophthalmic symptoms; see early onset c. and late onset juvenile c … Medical dictionary	2	10	0	0	3	0.771758	3	2,418
What is a bone bruise? A bone bruise is a localized collection of blood within the bone caused by a bone contusion 1,6. - Most common in the knee and ankle - Joint pain, swelling - Not visible on X-ray; an MRI required for diagnosis - Treatment with splints and analgesics - Recovery time: several months What is a bone contusion? A bone contusion is any compression injury of the bone, which is usually associated with a bone bruise. What is subperiosteal hematoma? Subperiosteal hematoma is a collection of blood between the periosteum and the bone, which is also commonly referred to as bone bruise. What is bone marrow edema? Bone marrow edema is an area of changed density on the MR image that reflects either a traumatic bone bruise or a nontraumatic collection of the fluid within the bone. NOTE: Bone bruise, bone contusion and bone marrow edema are often used as synonyms 6,8,9,10. Types of Bone Bruise - A. Intraosseous bleeding - B. Subperiosteal hematoma A. INTRAOSSEOUS BLEEDING Intraosseous bleeding [intra = within; os = bone] is what is most commonly referred to as bone bruise and what is the main part of this article. Bone bruise is a localized collection of blood within a bone associated with a fracture of the inner, spongy layer, but not the outer cortical layer of the bone, caused by an acute trauma 9,10. Acute trauma due to: - The impact of the two bones in the joint or - Direct blow to the joint Bone bruises are common in football, soccer, basketball and hockey players, in those who practice martial arts, in runners who run on hard surfaces; other common causes are falls and car accidents 1,6. Symptoms and Signs - Swelling of the joint and, sometimes, one or more skin bruises, which do not result from a bone bruise but from injured ligaments, tendons, muscles and skin - Pain in the affected joint, which persists after the skin bruise ceases. - References 6,10 Picture 1. An MRI of a bone bruise in the knee See the white patch in the upper tibia (source: physio-pedia.com, Creative Commons License) - Causes and mechanism. Sudden stop of running (deceleration), hard landing on a foot with slightly bent knee or direct side blow to the knee can result in the impact of the thighbone (femur) and shinbone (tibia) in the knee, what can cause a bone bruise in the lower part of the thighbone (lateral femoral condyle) and/or in the upper part of the shinbone (tibial plateau). Such an injury is often associated with a rupture of the anterior cruciate ligament (ACL), or medial (MCL) or collateral ligament in an athlete’s knee 1,4,6. - Pain and swelling arise from an injury of the soft tissues in the knee joint and not from a bone bruise 6. - Healing time. Most bone bruises associated with the anterior cruciate ligament rupture heal in 60 days, but the healing time may be as long as 2 years 10,30,41. - Recovery time. Most athletes who suffer from anterior cruciate ligament injury return to full sport activities within 6 months 6. The presence of a bone bruise does not seem to affect the recovery time 6. Patella Dislocation and Bone Bruise Side (lateral) dislocation of the patella can cause a bone bruise in the thighbone (in the lateral femoral condyle) and at the bottom of the patella 6. A bone bruise in the ankle (in the lower part of tibia or/and in the talus bone) can occur after an ankle sprain (supination injury after landing on an outward rolled foot with the outer edge of the foot bearing weight) 1,4. Pain after an ankle sprain usually ceases after 4-6 weeks; the presence of the bone bruise usually does not add to pain and does not prolong the recovery time, which is about 3 months 28. In some individuals, a deep ankle pain during or after exercise may persist for some time. On an MR image, a bone bruise in the ankle can be sometimes seen even after 17 months, though 28. Picture 2. An MRI of a bone bruise in the ankle A white area in the back of the talus bone (source: physio-pedia.com, Creative Commons License) Other Common Sites - Heel bone (calcaneus) after landing on the heels; partial weightbearing for about 4 months may be required 32 - The ball of the foot 33 - Calf bone (fibula) in the part closer to the knee 18 - Hip (the femoral head) 5 - Pelvic bones: the ileal or pubic bone 34 - Collarbone (clavicle) 36 - Shoulder blade (scapula) 39 - Shoulder: the head of the long bone (humerus) in the arm 38 - Elbow 40 - Wrist bones (hamate) 37 - Spine (vertebra) 31 Types of Interosseous Bleeding Based on MRI Type 1: Reticular Bone Bruise Reticular bone bruise is limited to the medullary bone, is distant from the cortical bone and not connected to the joint surface; it is usually mild and scarce 25. Picture 3. Reticular bone bruise in the ankle a) An MRI of a reticular bone bruise in the front of the talus bone (arrow) b) Bone cracks in the medullary but not in cortical bone dark grey = medullary bone; light grey = cortical bone blue = cartilage; white = joint space (source: PubMed Central, Creative Commons licence) Type 2: Geographic Bone Bruise Geographic bone bruise is bigger and more dense than a reticular bruise and situated closer to the cortical bone; it can bulge into the joint space (see Picture 4) 25. Picture 4. Geographic bone bruise Dark grey = medullary bone; light grey = cortical bone blue = cartilage; white = joint space (source: PubMedCentral, Creative Commons Licence) Picture 5. An MRI of a large geographic bone bruise in the knee (the large white area in the lateral femoral condyle) (source: physio-pedia.com, Creative Commons license) Type 2a: Osteochondral Fracture When a geographic bone bruise communicates with a joint it is called osteochondral fracture 6. The damaged cartilage may need up to 1-2 years to heal 6. Type 3: Impaction Bone Bruise After an impact of the two bones in the joint, for example the tibia and femur in the knee, a depression of the articular surface and bone bruises on the both bones can form; this is called a “kissing contusion” 4,9. Picture 6. An MRI of a kissing contusion in the knee. The upper bone bruise is in the thighbone (femur) and the lower in the shinbone (tibia) (source: orthopaedicsone.com, Creative Commons Licence) - An X-ray can detect the real bone fracture but NOT an intraosseous bleeding (bone bruise within the bone) 25. - A CT also cannot detect intraosseous bleeding 25. Currently, only Magnetic Resonance Imaging (MRI) can detect bruises within the medullary bone: - T1-weighted MRI shows a bone bruise as an area of decreased intensity 10. - T2-weighted fat suppressed MRI or MRI with Short T1 Inversion Recovery [STIR] sequences shows the area of increased intensity 10. Bone bruise can be detected by an MRI as soon as 1-30 hours after an injury 41. Other conditions that can resemble a bone bruise: - Overuse or stress or insufficiency fracture due to repetitive microtrauma - Osteochondritis dissecans - Subchondral cyst - Periarticular bone infarction - Bone tumor/cancer, lymphoma, multiple myeloma - Bone inflammation (polyarthritis, reactive arthritis) or infection (bacterial arthritis, osteomyelitis) - Osteopenia: scarce bone in malnourished individuals or those with anorexia nervosa - Paget’s disease - Gaucher’s disease - Intraosseous ganglion cyst - Idiopathic transient bone marrow lesion syndrome - Post-operative lesion - Red marrow hyperplasia - Intraosseous hematoma in individuals with bleeding disorders 26 - References 6,10 - Elevate the affected limb - Put ice packs wrapped in the cloth over the affected joint for 5-10 minutes, few times a day for 1-2 days. - Reference 37 - Rest, avoiding bearing weight on the affected limb; use of crutches or a cane as long as walking causes pain - Splint (brace) - Over-the-counter (OTC) painkillers and remedies to reduce pain and swelling - Nonsteroidal antirheumatic drugs (NSAIDs), such as ibuprofen - Physical therapy: nonbearing exercises to maintain full motion and prevent stiffness of the joint - Avoiding smoking — nicotine delays wound healing 2 - Reference 6,10 There seems to be a lack of studies about the effectiveness of the following therapies on the bone bruise healing: - Microcurrent therapy - Kinesiology (kinesio) taping - Vitamin A, C, K, and bromelain supplements Healing and Recovering Time Healing time is the time in which an evidence of a bone bruise disappears from an MR image. The healing time for most bone bruises in the knee is about 2 months bat can be as long as 2 years 10,30,41 and for the bone bruises in the ankle about 12 months or more 28. Reticular bone bruises heal fastest, followed by geographic and impaction bruises 6,10,30. Healing time is longer in older individuals and those with the knee osteoarthritis 30. Picture 7. MRIs showing the healing of a bone bruise in the knee (A) A bone bruise in the tibia soon after the injury (B) After 3 weeks (C) Complete healing after 9 weeks (source: physio-pedia.com, Creative Commons Licence) Recovery time is the time in which an injured person can return to his or her usual activities. Recovery time can be shorter or longer than the bruise healing time and depends on the associated joint damage. The recovery time for most individuals with a bone bruise in the knee is shorter than 6 months and for those with a bruise in the ankle is about 3 months 19. Possible complications of intraosseous bleeding: - Stiffness of the affected joint 10 - Osteoarthritis, especially after a geographic bone bruise 4. - Avascular necrosis 10. B. SUBPERIOSTEAL HEMATOMA Subperiosteal hematoma is a collection of blood between the periost and the cortical bone 1,20. Subperiosteal Hematoma in the Shinbone (Bruised Shin) Subperiosteal edema in the shinbone usually results from a direct blow to the shins, commonly in those who practice martial arts and in football players. Symptoms include pain, bluish discoloration of the skin (from a skin bruise) and tender swelling, which usually start to diminish in 2-3 days, but can often persist for several months 47. Investigations are usually not needed; in doubtful cases diagnosis can be confirmed by an ultrasound, X-ray or CT 48. Bone bruise in the shinbone should not be confused with shin splints. Treatment includes rest, elevation of the leg above the level of the heart, avoiding bearing weight on the leg, ice packs for 10-15 minutes several times a day for 1-2 days, and painkillers 24,47. Subperiosteal hematoma can get calcified and the new bone tissue can form 46,49. The Eye Orbit Subperiosteal hematoma in the orbit (usually in the orbital roof) can appear days, weeks or even years after direct blunt trauma to the eye; other causes include weightlifting, violent vomiting, labor, sinusitis, panic attack or scuba diving 20,21. It most commonly occur in young males 20. Spontaneous hematoma can appear in individuals with hemophilia, leukemia or scurvy 20. Symptoms include protrusion of the eye and blurred vision that worsens over the days. Spontaneous healing is possible 29. Treatment may include intravenous antibiotics, steroids, aspiration or surgery 20. Subperiosteal hematoma in various skull bones can appear in newborns and rarely in older individuals with various bleeding disorders. Symptoms may include skin bruises anywhere in the body and a bulge on the scalp. Hematoma can resolve spontaneously, and if not, it can be punctured. If not treated within one month it may lead to ossification, which requires surgical removal 23. Other Sites for Subperiosteal Hematoma Pelvic bone (iliac or pubic bone): after a blunt or penetrating trauma 22. Tailbone (coccyx): pain can last for several weeks or, rarely, it can become chronic — in this case surgery can be considered. Sitting on doughnut cushions can help to prevent pain 43 Picture 8. Tailbone bruise (coccyx hematoma) (source: wikidot.com, Creative Commons licence) - Collarbone (clavicle) 35 - Ribs or breastbone (sternum); may be hard to distinguish from a rib fracture; hematoma can be detected by an ultrasound; pain may last for 2-4 weeks 44,45. - Forearm 37 What is a deep bone bruise? The term deep bone bruise may be used for a bruise within the medullary bone (intraosseous bleeding) as opposed to a subperiosteal hematoma, which is a superficial bone bruise. Bone Bruise vs Real, Stress and Occult Fracture - In a real bone fracture, both the cortical bone (the outer layer) and the medullary bone (the inner layer) are completely broken with the bone parts separated, what can be seen on an X-ray. - In a stress fracture due to repeated trauma, both the cortical and medullary bone are broken, but the bone parts on the both sides of the fracture do not split. Stress fracture can be sometimes detected by an X-ray, and if not, an MRI can be used 15. - In an occult bone fracture both the cortical and medullary bone are broken, but the fracture line is so thin that it is not detected by an X-ray 3. The occult bone fracture that involves the bone and the cartilage and makes a communication between a bone bruise and the joint is called osteochondral fracture 6. - In a bone bruise, only the medullary bone is broken and the cortical bone remains intact. A bone bruise cannot be detected by an X-ray or CT but only by an MRI 3. NONTRAUMATIC BONE MARROW EDEMA Bone marrow edema is a term used to describe nonspecific changes of the density on the MRI image of the bone, which can include bone bruise (blood collection), true edema (fluid collection), or localized inflammation. Nontraumatic bone marrow edema can be associated with various bone disorders: The Wrist and Hand - In rheumatoid arthritis, a bone marrow edema in the wrist is an early sign; it appears before rheumatoid factor 16 and is a bad prognostic sign 10,17. - Bone marrow edema-like syndrome (BMES) of the foot and ankle: - Younger patients with pain in the foot or ankle, without a known cause - Conservative treatment with splints may help. - Avascular necrosis of the femoral neck 10 - Transient osteoporosis of the hip (TOH) in women in the 3rd trimester of pregnancy or in middle-aged men 10,11 - Main symptom: severe, disabling pain in the lateral thigh, no tenderness - Can be treated solely with analgesics - Heals completely after delivery - In spondyloarthritis, a bone marrow edema can be the first finding on an MRI 10. Reactive Bone Marrow Edema Reactive bone marrow edema refers to changes in the MR image caused by a response of the bone tissue to inflammation, and may be caused by: - Benign and malign bone tumors - Osteoarthritis (edema is a bad prognostic sign) - Transient bone marrow edema syndrome - Ganglion cyst - Complex regional pain syndrome - Reference 14 ICD 9 and 10 Code The ICD 9 code for bone bruise in general (including interosseous bleeding and subperiosteal hematoma) is the same as for “contusion, unspecified,” which is 924.9, and the ICD 10 code is T14.9027. ICD codes by location of contusion: - Contusion of hip: ICD 9 = 924.01; ICD 10 = S70.00XA 42 - Contusion of knee: ICD 9 = 924.11; ICD 10 = S80.00XA 42 - Contusion of ankle: ICD 9 = 924.21; ICD 10 = S90.00XA 27 - Contusion of finger: ICD 9 code = 923.3; ICD 10 code = S60.00XA: ICD 10 code for contusion of thumb without nail damage = S60.019.A 50 - References + - PubMed (Bone bruise overview) - PubMed (Smoking and wound healing) - MRIcenter.com (MRI, CT and X-ray of bone bruise) - Sportsinjurybulletin (Bone bruise description) - PubMed (Bone bruise in the hip) - PubMed Central (Athlete’s knee) - American Journal of NeuroRadiology (Intraosseous hematoma) - Sagepub (Bone contusion) - BMJ (Kissing contusion in the knee) - Diagnosticimaging.com (Bone marrow edema diagnosis and prognosis) - PubMed Central (Transient osteoporosis or bone marrow edema of the hip) - PubMed (Bone marrow edema) - PubMed (Painful bone marrow edema syndrome) - Gentili.net (Reactive bone marrow edema) - Emedicine (Stress fracture) - PubMed (Bone marrow edema as an early sign of rheumatoid arthritis) - PubMed Central (Pathogenesis of rheumatoid arthritis) - PubMed Central (Bone bruise of the knee) - Natajournals (Ankle sprain) - PubMed Central (Subperiosteal hematoma in the orbit) - Informahealthcare (Subperiosteal hematoma in the orbit after an anxiety attack) - PubMed (Traumatic subperiosteal aneurysm) - PubMed (Subperiosteal hematoma in the skull bones in a newborn) - ACSM’s Primary Care Sports Medicine, y.2007 (Subperiosteal edema in the tibia) - PubMed Central (Types of bone bruises) - American Journal of Neuroradiology (Intraosseous hematoma in an infant with factor VII deficiency) - ICD9data.com (icd9 code) - Current Issues in Treatment of Osteochondral Defects, y.2013 (Osteochondral defect in the ankle) - PubMed Central (Subperiosteal hematoma) - PubMed (MRI of the knee in general practice) - Researchgate.net (Bone bruise in the spine) - PubMed (The heel bone (calcaneus)) - San Diego Running Institute (Metatarsalgia) - NBCsports.com (Pelvic bone bruise) - Netwellness.org (Bone bruise in the clavicle) - Dmi-uk.com (Bone bruise in the collarbone) - Chiro.org (Forearm and wrist bone bruises) - Healio.com (Bone bruise in the humeus head) - Aligatorarmy.com (The shoulder blade) - Sportsinjurybulletin (Common locations of bone bruises) - Webcir.org (Radiography of occult bone trauma) - ICD9data.com (ICD 9 code) - WebMD (Tailbone injury) - Researcgate (Subperiosteal hematoma in the ribs or sternum) - Sportsinjuryclinic.net (Bruised sternum) - Doctorslounge.com (Shin trauma not healing in 6 months) - Commonsportsinjuries.com (Shinbone bruise) - Ultrasoundcases.info (Ultrasonography of subperiosteal hematoma) - Medscape (Child abuse) - ICD9data.com (ICD 9 and 10 code for contusion of finger)	2	28	0	0	4	0.620054	4	4,723
distal biceps tendon rupture represents about 10% of biceps ruptures. Demographics. ruptures tend to occur in the dominant elbow (86%) of men (93%) in their 40s. Anatomic location. complete distal biceps avulsion. partial distal biceps avulsion. partial distal biceps tendon tears occur primarily on the radial side of the tuberosity footprint The diagnosis is often obvious for complete ruptures because of the deformity of the arm muscle (Popeye Muscle). A biceps tendon tear is made more obvious by contracting the muscle (Popeye Muscle). Partial ruptures are less obvious. To diagnose a partial tear, your doctor may ask you to bend your arm and tighten the biceps muscle Proximal and distal ruptures both involve the biceps brachii but have potential for very different outcomes. Biceps tendon ruptures tend to occur in middle-age men, although they can also occur in younger patients. Approximately 96% involve the long head, 3% the distal, and 1% the short head of the biceps.[1,2 Tenotomy of the LHBT can be associated with Popeye deformity and biceps cramping, which can result in poor satisfaction in young patients (Fig. 4).15,16,25,26Biceps tenodesis provides a new fixation point for the tenotomized tendonintheproximalhumerus,andthusmaintainsthelength-tensionrelationshipof the musculotendinous unit There is usually a bunching up of the muscle in the lower part of the upper arm resulting in a prominent lump called a ' popeye deformity '. The biceps will also be significantly weakened and considerable bruising over the bicep is normally noticed shortly after the injury. Other symptoms may include . This is often visibly different to the other biceps when contracting the muscle. Click for larger view of biceps rupture A biceps tendon rupture leads to weakness of the elbow and forearm if not repaired Clinically relevant anatomy [edit \| edit source]. The biceps brachii muscle consists of 2 parts: The long head and the short head. The long head originates at the supraglenoid tubercle and is attached to the dorsal aspect of the radial tuburosity. It runs intra-articularly over the humeral head and follows the bicipital groove distal to the glenohumeral joint tendon, which can result in cosmetic deformity including the Popeye sign (Fig. 1). The severity of cosmetic deformity after biceps tenotomy varies and patient percep-tion of the deformity is also variable. Elderly patients are less affected by the cosmetic outcome compared with younger patients.11,12 Cramping, soreness, or fatigue sensa • Popeye Deformity LHBT Rupture AC Joint • AC Joint Tenderness • Cross-Body Adduction • Obrien's Test** SLAP (Shoulder Exam, 2020) (Orthobullets, 2020) Fig. 4.1 Advanced OA of the R Hip with Subchondral Cystic Changes (Townsville Radiology Training, 2020) Hip Osteoarthritis The overall length of the proximal LHB have been well-studied in order to obtain the correct length-tension relationship and prevent a Popeye deformity. Once the screw is seated, the two limbs.. Biceps Tendon Tear at the Elbow. The biceps muscle is located in the front of your upper arm. It is attached to the bones of the shoulder and elbow by tendons — strong cords of fibrous tissue that attach muscles to bones. Tears of the biceps tendon at the elbow are uncommon. They are most often caused by a sudden injury and tend to result in. . The retracted muscle sags, giving it the appearance of a very prominent bulging biceps muscle. One must consider the possibility of a combined injury to the rotator cuff tendons with the biceps injury Orthobullets.com. T. RAUMATIC. I. NJURIES. Injury. History. Physical Exam. XR. MRI. Primary Anterior Dislocation. Fall or hit to abducted/ ER arm. Pain with ROM. Arm in ADD/ IR position. Not needed prior to reduction. Determine Popeye deformity Surgical release . D OC, M Y E LBOW Weakness may be due to pain or torn tendon. Full-thickness rotator cuff tears. Age usually a bit older than impingement. Pain rolling on shoulder in bed/night pain. Weakness. Lateral arm pain, near deltoid insertion, but does not radiate below elbow. Passive motion typically greater than active motion Bamboo spine is a pathognomonic radiographic feature seen in ankylosing spondylitis that occurs as a result of vertebral body fusion by marginal syndesmophytes. It is often accompanied by fusion of the posterior vertebral elements as well. A bamboo spine typically involves the thoracolumbar and/or lumbosacral junctions and predisposes to unstable vertebral fractures and Andersson lesions Shaishe's List: sports . from a posterior subluxed position at ~20° of flexion to a reduced position in full extension (reduction force from IT band transitioning from a flexor to an extensor of the knee Partial rupture of the distal biceps tendon exhibits features similar to that of complete disruption, including acute antecubital pain, weakness of elbow flexion, and forearm supination, and differs only in the fact that the biceps tendon is still palpable in the partial rupture. There are 2 etiolog Also, patients develop a cosmetic deformity of the biceps called a popeye sign. This happens when the muscle belly of the biceps drops down toward the elbow. Weakness is typically a result of pain, since the short head of biceps and the more powerful brachialis muscle preserve the elbow's flexion strength How You Can Avoid the Painful Popeye Deformity December 30, 2020 / Chronic Pain. December 30, 2020 / Chronic Pain. How Can I Deal With Rotator Cuff Injuries If I'm Over 45?. Olecranon bursitis is when the sac between your elbow bone and your skin gets swollen. This could result in a golf-ball sized lump on the tip of your elbow, which could look like cartoon Popeye. Cheerio sign (shoulder) The Cheerio sign has been described as a sign seen in a type III superior labral anterior posterior tear (SLAP lesion) of the glenoid labrum. In the Cheerio sign, a rounded core of soft tissue is surrounded by a rim of contrast material and gas. SLAP type III is the bucket handle tear of the superior labrum without an. Biceps tendonitis can be treated with rest, physical therapy, injections, or surgery depending on the severity and origin of the tendonitis. Surgery is performed when the tendonitis does not respond to nonoperative interventions and can involve simply cutting the tendon known as a tenotomy or cutting the tendon and inserting it into the upper part of the humerus . The muscle at the front of the upper arm is known as the biceps. The biceps originates from the front of the shoulder blade (attaching here via the short and long head of biceps) and inserts into the forearm via the distal. Shoulder conditions are among the most common musculoskeletal presentations seen in general practice 1 and up to 95% of people with shoulder pain are treated in the general practice setting. 2. There is some confusion and poor consensus surrounding the classification and naming of many shoulder conditions, 3 compounded by evidence indicating that clinical examination and investigations have. Department of Rehabilitation Services Physical Therapy Distal Bicep Tendon Repair- Rehabilitation Protocol The intent of this protocol is to provide the clinician with a guideline of the post Orthopedics and Sports Medicine. General orthopedics is a specialty dealing with the musculoskeletal system—the bones, joints, muscles, tendons, ligaments, cartilage and nerves. A 2016 study estimated that more than 126 million Americans—one out of every two adults—are affected by a musculoskeletal disorder A complete biceps tendon rupture at the shoulder also may result in a bulge in the upper arm between the elbow and shoulder—what is commonly referred to as a Popeye muscle or Popeye deformity. This happens because after the ruptured tendon retracts the muscle shortens and it bunches up in the arm A rotator cuff tear is an injury where one or more of the tendons or muscles of the rotator cuff of the shoulder get torn. Symptoms may include shoulder pain, which is often worse with movement, or weakness. This may limit people's ability to brush their hair or put on clothing. Clicking may also occur with movement of the arm The shoulder's biceps muscle has two attachments: the short head is outside of the shoulder joint and rarely causes shoulder problems, while the long head travels in front of the shoulder between the rotator cuff tendons and into the shoulder joint, attaching on the superior labrum, which is a ring of fibrocartilage around the edge of the shoulder socket that helps stabilize the. Detailed history and physical examination suggest the area of pain and deformity. The flexion of elbow and shoulder joint movement often shows abnormal bulge of uncoordinated biceps muscles. If there is a complete rupture of the Biceps Tendon then there will be a deformity of the arm, which will confirm the diagnosis PDF \| Background The classic injury mechanism of a distal biceps brachii tendon rupture (DBBTR) is eccentric loading to the flexed elbow when the... \| Find, read and cite all the research you need. Abstract. Imaging interpretation of the postoperative shoulder is a challenging and difficult task for both the radiologist and the orthopedic surgeon. The increasing number of shoulder rotator cuff, labrum, and biceps tendon repairs performed in the United States also makes this task a frequent occurrence You will likely hear a popping sound and feel instant pain when your elbow is hyperextended. Other potential symptoms include: dull to sharp pain when you move your elbow. pain when you. Biceps tenodesis is a surgical procedure used to reduce pain in the shoulder and surrounding area. It is an option when pain is caused by problems with the biceps tendon in the arm. In this. A 58 year old right hand dominant painter presents to the emergency department with right shoulder pain. The pain started after he returned a particularly forceful serve during a tennis match earlier that afternoon. He states that it has a similar quality to the shoulder pain he typically feels at night, but more intense and not improving with analgesia. He did not feel a pop or other. . AC Joint Separation •Type I Injuries: AC joint ligament is partially disrupted and the coracoclavicularligaments are intact Parsonage-Turner syndrome (PTS) is an uncommon neurological disorder characterized by rapid onset of severe pain in the shoulder and arm. This acute phase may last for a few hours to a few weeks and is followed by wasting and weakness of the muscles (amyotrophy) in the affected areas. PTS involves mainly the brachial plexus, the networks of. Among people with severe elbow arthritis and joint deformity, elbow joint replacement may provide the best opportunity for pain relief and restoration of joint function, according to the American Academy of Orthopaedic Surgeons 2 5. Related Articles. Chicken Comb for Knee Pain. Learn More Cubital tunnel syndrome and radial tunnel syndrome aren't as familiar as their better-known relative -- carpal tunnel syndrome -- but they also can cause severe pain, numbness, tingling, and. Shoulder examination frequently appears in OSCEs and you'll be expected to identify the relevant clinical signs using your examination skills. This shoulder examination OSCE guide provides a clear step-by-step approach to examining the shoulder, with an included video demonstration A swollen elbow happens when fluid builds up in the area. It can cause pain when bending or touching the elbow, redness, or warmth. Common causes include inflammation from arthritis, bursitis, or overuse injuries ICD-10-CM Codes › S00-T88 Injury, poisoning and certain other consequences of external causes ; S40-S49 Injuries to the shoulder and upper arm ; S46-Injury of muscle, fascia and tendon at shoulder and upper arm level 2021 ICD-10-CM Diagnosis Code S46.211 This is called tendonosis. Tendonosis of the biceps tendon can be painless or it can cause dull or sharp pain in the area of the tendon just past the front of the elbow in the forearm. In some cases, tendonosis can lead to partial tendon tears or complete tendon rupture. Biceps tendonosis is one of several possible causes of pain around the elbow Biceps tenodesis involves detaching the LHB from the superior labrum in the shoulder joint and reattaching it to the humerus. This procedure is more complex than a tenotomy, but avoids the risks of biceps deformity and weakness. Tenodesis is preferable for more active patients. Using the newest surgical techniques and implants . It is necessary to be able to recognize abuse signs,... \| Find, read and cite all the research. Elbow & Joint-range-of-motion-decreased Symptom Checker: Possible causes include Bursitis. Check the full list of possible causes and conditions now! Talk to our Chatbot to narrow down your search Average follow up was 13 months. Outcomes included Visual Analogue Pain Scale (0-10), ASES score, modified Constant score, pain at the tenodesis site, failure of fixation, cosmesis, deformity (popeye) and complications. Results: There were no failures of fixation in this study A deformity may be indicative of an pectoralis major muscle rupture. Popeye Sign present when there is a large bump in the area of the biceps muscle belly. Orthobullets. Carousel Previous Carousel Next. 2012 NCCAOM Herbal Exam Questions. Uploaded by. Elizabeth Durkee Neil. Anterior Compartment of Arm & Cubital Fossa A Popeye deformity occurred in 33% of tenodesis patients and 47% of tenotomy patients (P = .17). Tenotomy was performed with a shorter operative time (73 minutes vs 82 minutes, P = .03). Magnetic resonance imaging showed a recurrent rotator cuff tear in 20% of all cases The shoulder should also be examined for tenderness and deformity. though after surgery there can be a cosmetic 'popeye sign' visible in thin arms. In a small minority of cases where extensive arthritis has Orthobullets. Retrieved 5 November 2018. ^ Craig R, Holt T, Rees JL (December 2017). Acute rotator cuff tears.. Joint aspiration is a procedure whereby a sterile needle and syringe are used to drain synovial fluid from a patient's joint. Joint aspiration is typically performed by a doctor or ancillary health care provider as an office procedure or at the bedside of hospitalized patients The basic deformity is a subluxation at the talocalcaneonavicular joint. Several factors, including family history and intrauterine crowding, have been blamed as the causative factors. It is associated with meningomyelocele, arthrogryposis multiplex congenita, and tibial hemimelia scapula Adhesive capsulitis Rotator cuff tear Subacromial bursitis elbow Cubitus valgus Cubitus varus hand deformity Wrist drop Boutonniere deformity Swan neck deformity [en.wikipedia.org] See also Coxa vara Genu valgum Genu varum Musculoskeletal disorders : Acquired musculoskeletal deformities ( M20-M25, M95, 734-738 ) Upper limb shoulder. JSES Int 2021 Jul 20;5(4):821-826. Epub 2021 Apr 20. Department of Orthopaedic Surgery, Amphia Hospital, Breda, The Netherlands word clue lyon gangster movie nashville-davidson tn weather citiservi europe half metal half wood. Shortly softball bat stiri romaero 2014 bodyboard drop knee roll textview settext null pointer exception walgreens contacts 30 off unilocular cystic structure Shoulder Arthroplasty. Fealy et al. State-of-the art techniques in primary and secondary shoulder replacement surgery Complex Issues in the Primary and Revision Setting Shoulder Arthroplasty: Complex Issues in the Primary and Revision Setting assembles the clinical Stephen Fealy. Shoulder Arthroplasty knowledge of leading orthopaedic surgeons treating patients with arthritic shoulders In flexi rods on locs sparc-based alexandria city marina address charcot foot deformity treatment level one trauma centers in houston texas galleria morone 6 nicole richie golden globes dress lackierbox mieten stuttgart catalogo 11 oriflame 2013 mexico ball joint It bend laurie fallucca milwaukee download. Shortly subtitle. And get him to the. 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Shortly sign up photo ville porto portugal canada deficit per province heath ledger joker clothing recipient A manual of orthopaedic terminology.pdf - Free ebook download as PDF File (.pdf), Text File (.txt) or read book online for free And gavekort popeyes? How fried turkey atlanta type 99 nambu markings cultuur 19 utrecht 48 samsung smart tv series 5 d15b2 transmission. All fluid hydratight tensioner pump tallmantz phoenix p-1 crash everfound yan central police divisional hq contact birch wood house signs of jesus return Biceps Rupture: What Causes A Popeye's Muscle Deformity. Webmd.com DA: 13 PA: 48 MOZ Rank: 97. A biceps rupture occurs when you tear the tendon that runs from your shoulder to your elbow, called the distal biceps tendon; A tear may happen anywhere along the tendon, although tears are mos rhodes chicago schwegler poseidon greek mythology movie wp thumbnail crop klinova bouda comprobacion redundancia ciclica bombom hileleri indir gsu ruling urban outfitters logo fetih 1453 2 shoplifting dog video hidroboster para chevrolet lisbonne ou porto forum gelardi facebook upload ico images via verde plazaola alojamientos cyence cyber This book describes Shoulder Pain, Diagnosis and Treatment and Related Diseases Shoulder pain is the main symptom of many shoulder disorders. Movement of the shoulder joint can be extremely painful and may be extremely difficult. When something goes wrong with the shoulder, it hinders the ability to move freely and can produce a great deal of pain and discomfort. The shoulder is a ball-and. 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Erythema nodosum is presumed to be a hypersensitivity reaction. It is often a dermatological manifestation of infectious, or other, disease. The eruptive phase begins with fever, aching and arthralgia whilst a painful rash usually appears within a couple of days. Lesions begin as red, tender nodules. The borders are poorly defined and they are 2-6 cms in diameter. In the first week the lesions become tense, hard and painful. In the second week, they may become fluctuant, rather like an abscess but they do not suppurate or ulcerate. Individual lesions last around two weeks but occasionally, new lesions continue to appear for three to six weeks. Aching legs and swollen ankles may persist for many weeks. In the first week they are bright red but in the second week there is a blue or purple hue, even turning yellow like a resolving bruise before disappearing in a couple of weeks. They can occur anywhere but are usually on the anterior aspect of the lower leg. When the aetiology is an infection the lesions usually heal in six to eight weeks but 30% of idiopathic cases last six months. Arthralgia occurs in more than half of patients and begins either during the eruptive phase or two to four weeks before. Joints are red, swollen and tender, sometimes with effusions. Morning stiffness may occur. The ankles, knees and wrists are most often involved. Synovitis resolves in a few weeks but joint pain and stiffness may last up to six months. There are no destructive changes in the joint and synovial fluid is acellular and the rheumatoid factor is negative. - Erythema nodosum is often indicative of an underlying infectious disease but a cause is not always found. Some underlying causes are not infectious. - Streptococcal infection is the most common underlying cause and so it may be a feature of other diseases, including scarlet fever and rheumatic fever, although in the UK nowadays the former is uncommon and the latter rare. - Sarcoidosis is also commonly involved in adults, although it is not infectious in origin. - Tuberculosis must be considered. - Leprosy can produce a clinical picture of erythema nodosum, although the histological picture of the lesions is different. - Various forms of gastroenteritis - especially Yersinia enterocolitica, Salmonella spp. and Campylobacter spp. - can be associated. - Lymphogranuloma venereum may be a cause. - Mycoplasma pneumonia can be associated. - Fungal infections are less common in the UK but coccidioidomycosis is important in Southwest USA. It may occur in histoplasmosis and blastoplasmosis. - Sulfonamides are used less often nowadays but other drugs to be implicated include sulfonylureas, gold and oral contraceptives. - It may correlate with flare-up of Crohn's disease or ulcerative colitis. - It can precede the diagnosis of Hodgkin's lymphoma and non-Hodgkin's lymphoma by months and it can accompany Behçet's syndrome. - It may occur in pregnancy when it is usually in the second trimester. It is likely to recur in future pregnancies and may occur with oral contraceptives. - There are rare cases (<1 in 100) associated with Epstein-Barr virus, hepatitis B and hepatitis C and HIV. - In many cases no cause is found. Although in many cases it is idiopathic, it is important to exclude serious underlying disease: - A throat swab for streptococcus is the first test, although it may well be negative, even with streptococcal disease. - Anti-streptococcal O (ASO) titre may be more helpful, although a normal titre does not exclude infection. A rising titre may be more valuable. - Arrange an FBC and ESR. ESR is often very high regardless of the aetiology, and CRP may be more contributory. - Stool examination for Y. enterocolitica, Salmonella spp. and Campylobacter spp. may yield results, as may blood cultures - In sarcoidosis, calcium and angiotensin-converting enzyme (ACE) are often raised. - CXR may show bilateral hilar lymphadenopathy (BHL) in sarcoidosis, unilateral or asymmetrical adenopathy in malignancy, or evidence of pulmonary tuberculosis. - Intradermal skin tests may be required to exclude tuberculosis and coccidioidomycosis. - Excisional biopsy may be helpful where the diagnosis is in doubt. - Erythema induratum (modular vasculitis). - Insect bites. - Acute urticaria. - Familial Mediterranean fever. - Superficial thrombophlebitis (standard or superficial migratory thrombophlebitis). - Most cases are self-limiting and require only symptomatic relief. - If an infective aetiology has been discovered then appropriate therapy is in order but it should not be given blind. - A degree of relief can be obtained with cool compresses and bed rest with elevation of the foot of the bed. Bed rest has been advocated for many years and is anecdotally useful but the evidence base is lacking. - Non-steroidal anti-inflammatory drugs (NSAIDs) are useful and no other drugs are usually needed. Steroids are beneficial but should be used with caution and may be contra-indicated if infection has not been excluded. - In difficult cases, oral potassium iodide may be valuable, as may tetracycline and, in erythema nodosum of leprosy, thalidomide has seen a resurgence but further research is required[10, 11, 12]. The condition usually resolves within six weeks but it may be more protracted, especially if the underlying cause remains or when it is idiopathic. Serious complications are unusual unless part of the underlying disease. Chronic or recurrent disease is rare. Lesions heal without atrophy or scarring. Did you find this information useful? - Shimizu M, Hamaguchi Y, Matsushita T, et al; Sequentially appearing erythema nodosum, erythema multiforme and Henoch-Schonlein purpura in a patient with Mycoplasma pneumoniae infection: a case report. J Med Case Rep. 2012 Nov 23 6(1):398. doi: 10.1186/1752-1947-6-398. - Erythema Nodosum; Primary Care Dermatology Society - Whig J, Mahajan V, Kashyap A, et al; Erythema nodosum: Atypical presentation of common disease. Lung India. 2010 Jul 27(3):181-2. doi: 10.4103/0970-2113.68319. - Min MS, Fischer R, Fournier JB; Unilateral Erythema Nodosum following Norethindrone Acetate, Ethinyl Estradiol, and Ferrous Fumarate Combination Therapy. Case Rep Obstet Gynecol. 2016 2016:5726416. doi: 10.1155/2016/5726416. Epub 2016 Mar 27. - Mantadakis E, Arvanitidou V, Tsalkidis A, et al; Erythema nodosum associated with Salmonella enteritidis. Hippokratia. 2010 Jan 14(1):51-3. - Babamahmoodi F, Babamahmoodi A, Barani H, et al; Simultaneous occurrence of erythema nodosum in monozygotic twin sisters. Case Rep Med. 2012 2012:109427. doi: 10.1155/2012/109427. Epub 2012 Jun 5. - Schwartz RA, Nervi SJ; Erythema nodosum: a sign of systemic disease. Am Fam Physician. 2007 Mar 1 75(5):695-700. - Fowler A, Dargan P, Jones A; Puzzling hypercalcaemia: sarcoidosis without lung involvement. J R Soc Med. 2005 Feb 98(2):60-1. - Yi SW, Kim EH, Kang HY, et al; Erythema nodosum: clinicopathologic correlations and their use in differential diagnosis. Yonsei Med J. 2007 Aug 31 48(4):601-8. - Tabak F, Murtezaoglu A, Tabak O, et al; Clinical features and etiology of adult patients with Fever and rash. Ann Dermatol. 2012 Nov 24(4):420-5. doi: 10.5021/ad.2012.24.4.420. Epub 2012 Nov 8. - Passarini B, Infusino SD; Erythema nodosum. G Ital Dermatol Venereol. 2013 Aug 148(4):413-7. - Van Veen NH, Lockwood DN, van Brakel WH, et al; Interventions for erythema nodosum leprosum. Cochrane Database Syst Rev. 2009 Jul 8 (3):CD006949. doi: 10.1002/14651858.CD006949.pub2. - Gilchrist H, Patterson JW; Erythema nodosum and erythema induratum (nodular vasculitis): diagnosis and management. Dermatol Ther. 2010 Jul-Aug 23(4):320-7. - Wan P, Zhao X, Hunasehally RY, et al; Propylthiouracil-induced ANCA-positive erythema nodosum treated with thalidomide. Int J Dermatol. 2012 Mar 51(3):345-8. doi: 10.1111/j.1365-4632.2011.05135.x. Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. Patient Platform Limited has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.	2	9	2	0	0	0.589307	2	2,239
A working group evaluating sexual orientation-related disorders listed in the International Classification of Diseases (ICD), a publication of the World Health Organization (WHO), has recommended the disorders be deleted, a move that will make getting health care easier for gays and others who may identify with non-heterosexual orientations. The recommendation echoes policies of the leading U.S. psychiatry and psychology societies. “It is not justifiable from a clinical, public health, or research perspective for a diagnostic classification to be based on sexual orientation,” Susan D. Cochran, PhD, of the University of California Los Angeles, and other members of the working group wrote in the Bulletin of the World Health Organization. The WHO is the world body charged with deciding what is a disease and more than 170 countries, including the United States, follow their recommendations. The organization is currently revising the 10th edition of the ICD for release of the 11th edition in 2017. Cochran, a professor at the UCLA Fielding School of Public Health, said the recommendation, if adopted, resolves “a human rights issue.” “In California, gay people may have the right to marry, but in most of the world, being gay can be dangerous. There are at least six countries that criminalize homosexuality with a possible death sentence,” said Cochran, who is a clinical psychologist and epidemiologist. “This recommendation, to remove diagnoses that have no scientific basis, is a way of cleansing our public health apparatus of the social animus directed at a group of people for reasons that have no health justification.” The recommendation must survive several layers of approval, the final being a vote by the member countries. Earlier this month, the American Psychological Association wrote to the WHO with a similar recommendation. The Long Process of De-Pathologizing Human Sexuality In 1974, the American Psychiatric Association decreed that homosexuality would no longer be considered a mental illness, though it created a new disorder, ego-dystonic homosexuality, as a political compromise. That disorder was later dropped as a diagnosis, and the American Psychiatric Association’s fifth edition of its Diagnostic and Statistical Manual of Mental Disorders, released in May 2013, did away with all associations of sexual orientation with mental illness. In 1990, the ICD made the same declaration, but retained several purported disorders, Cochran said. Five diagnostic codes pertaining to sexual orientation appear in ICD-10, which is tentatively slated for adoption in the U.S. late next year after long delays. All carry the designation ‘F66.’ They include “sexual maturation disorder” (F66.0), described as anxiety or depression due to uncertainty over one’s sexual orientation or gender identity, and “ego-dystonic sexual orientation” (F66.1) for individuals who express unhappiness with their sexual preference and wish it were different. The ICD-10 codes also include F66.2, “sexual relationship disorder,” to describe “difficulties in forming or maintaining a relationship with a sexual partner” because of the person’s gender identity or sexual orientation. In a statement, Cochran said this last category could be used to apply a medical diagnosis to a married man who realizes that he is homosexual and, as a result, finds that this causes difficulties with his wife. Other categories could be also used to pathologize normal human sexuality. For example, if a teenager was unsure if they were gay, straight or bisexual and were distressed about that, that also is considered mental disorder. Or if a person were gay, and for whatever reason wished not to be, that also is considered a disorder. “It doesn’t make any sense. If a person were short and wished they weren’t, that is not a disorder. Or if someone was a lousy singer and wished they weren’t, that is not a disorder,” Cochran said. “In other words, the ICD takes content that is sexual orientation-related and attaches a diagnosis to it in ways that it does not do for other aspects of people.” ‘An end to the medicalization of homosexuality’ If the recommendation is adopted it will have an immediate and important impact on access to health care, she said. Every health care event and every doctor visit has an ICD code attached to it. These codes that are used for insurance billing, for public health surveillance and for medical records. Dropping the codes would mean “that gay people can feel free to seek care, to share their concerns, and not fear that they will diagnosed with a mental illness simply because the content is about homosexuality or gender atypicality,” Cochran said. “It would mean an end to the medicalization of homosexuality.” By removing these codes related to sexual orientation, the health care that gay people receive will be improved, Cochran said. For example, if a gay man is depressed and seeks care he is vulnerable to being mistreated by the health system. Currently, he could be diagnosed with ego-dystonic homosexuality if he says he is upset about how he is being treated as a gay man and wishes he were straight. There are discredited treatments, such as conversion therapy, that have been deemed unethical but sometimes are justified by this diagnosis. With the codes removed, it will be more likely that his complaints will result in a proper diagnosis of depression and treatments for that depression. An article published in the latest issue of the Bulletin of World Health Organization outlined the scientific basis for the recommendation to delete the sexual orientation-related disorders from the ICD. The group’s findings emerged from a review of literature published in recent decades that, in general, has indicated that sexual preferences are formed very early in life and that, while nonheterosexuals tend to report greater distress, it results from “greater experiences of social rejection and discrimination.” For example, studies have found a range of risk factors associated with parental disapproval or rejection of LGBT youth sexual orientation. A 2012 study published in the Journal of Homosexuality found that “parents who react non-supportively when their children disclose LGB sexual orientation may contribute to children’s increased odds of depression and hazardous substance use.” Other studies have found an increase in psychiatric disorders among LGB populations living in states that instituted bans on same-sex marriage, indicating that institutional forms of discrimination have significant deleterious effects on the mental health of LGB individuals. Additionally, the controversial and discredited conversion therapy has proven to be extremely harmful for those who undergo it. Though most of the country’s medical associations have opposed conversion therapy for years, some licensed therapists still practice it. Conversion therapy has already been banned in some states — including New Jersey and California — but it remains legal in most of the country, despite the consequences. A 1994 Journal of Consulting and Clinical Psychology article by Douglas Haldeman describes conversion therapy methods as including “electric shock, nausea-inducing drugs, hormone therapy, surgery,” and “visits to prostitutes and excessive bicycle riding.” In 1998, the American Psychiatric Association issued a decision on conversion therapy, stating that it opposes any psychiatric treatment based upon on the assumption that being gay is a mental disorder. The APA’s decision continued to state that such “reparative” therapies are ineffective and carry great risks, “including depression, anxiety, and self-destructive behavior, since therapist alignment with societal prejudices against homosexuality may reinforce self-hatred already experienced by the patient.” In the new recommendations, the ICD working group wrote, “retention of these categories may also be construed as supporting ineffective and unethical treatment that aims to encourage people with a same-sex orientation to adopt a heterosexual orientation or heterosexual behavior.” Cochran and colleagues said that removing sexual orientation disorders could help bring an end to the harmful practice.	2	3	0	0	6	0.492207	6	1,655
Don’t insert percutaneous feeding tubes in individuals with advanced dementia. Instead, offer oral assisted feedings. Strong evidence exists that artificial nutrition does not prolong life or improve quality of life in patients with advanced dementia. Substantial functional decline and recurrent or progressive medical illnesses may indicate that a patient who is not eating is unlikely to obtain any significant or long-term benefit from artificial nutrition. Feeding tubes are often placed after hospitalization, frequently with concerns for aspirations, and for those who are not eating. Contrary to what many people think, tube feeding does not ensure the patient’s comfort or reduce suffering; it may cause fluid overload, diarrhea, abdominal pain, local complications, less human interaction and may increase the risk of aspiration. Assistance with oral feeding is an evidence-based approach to provide nutrition for patients with advanced dementia and feeding problems. Don’t use sliding scale insulin (SSI) for long-term diabetes management for individuals residing in the nursing home. SSI is a reactive way of treating hyperglycemia after it has occurred rather than preventing it. Good evidence exists that SSI is neither effective in meeting the body’s physiologic insulin needs nor is it efficient in the long-term care (LTC) setting in medically stable individuals. Use of SSI is associated with more frequent glucose checks and insulin injections, leads to greater patient discomfort and increased nursing time and resources. With SSI regiments, patients may be at risk from wide glucose fluctuations or hypoglycemia when insulin is given when food intake is erratic. Don’t obtain urine tests until clinical criteria are met. Clinical uncertainty surrounding asymptomatic bacteriuria (ASB) and/or pyuria is the major driver for overtreatment of Urinary Tract Infections (UTI) in PALTC, (Nace). Colonization (a positive bacterial culture without signs or symptoms of a localized UTI) is a common problem in PALTC facilities that contributes to the over-use of antibiotic therapy in this setting, leading to an increased risk of diarrhea or other adverse drug events, resistant organisms, and infection due to Clostridioides difficile. An additional concern is that the finding of asymptomatic bacteriuria may lead to an erroneous assumption that a UTI is the cause of an acute change of status, hence failing to detect or delaying the timely detection of 5 signs and symptoms likely indicative of uncomplicated cystitis. These include dysuria, and one or more of the following: frequency, urgency, supra-pubic pain or gross hematuria. In the presence of dysuria and one or more sign/symptom, collection of a urine culture is indicated. Don’t prescribe antipsychotic medications for behavioral and psychological symptoms of dementia (BPSD) in individuals with dementia without an assessment for an underlying cause of the behavior. Careful differentiation of cause of the symptoms (physical or neurological versus psychiatric, psychological) may help better define appropriate treatment options. The therapeutic goal of the use of antipsychotic medications is to treat patients who present an imminent threat of harm to self or others, or are in extreme distress – not to treat nonspecific agitation or other forms of lesser distress. Treatment of BPSD in association with the likelihood of imminent harm to self or others includes assessing for and identifying and treating underlying causes (including pain; constipation; and environmental factors such as noise, being too cold or warm, etc.), ensuring safety, reducing distress and supporting the patient’s functioning. If treatment of other potential causes of the BPSD is unsuccessful, antipsychotic medications can be considered, taking into account their significant risks compared to potential benefits. When an antipsychotic is used for BPSD, it is advisable to obtain informed consent. Refer to F-758: Free from Unnecessary Psychotropic Medications/PRN Use. Don’t routinely prescribe lipid-lowering medications in individuals with a limited life expectancy. Hypercholesterolemia, or low HDL-C, is an important risk factor for all-cause mortality, coronary heart disease mortality, hospitalization for myocardial infarction or unstable angina in persons older than 70 years. In fact, studies show that elderly patients with the lowest cholesterol have the highest mortality after adjusting other risk factors. In addition, a less favorable risk-benefit ratio may be seen for patients older than 85, where benefits may be more diminished and risks from statin drugs more increased (cognitive impairment, falls, neuropathy and muscle damage). Don’t place an indwelling urinary catheter to manage urinary incontinence. The most common source of bacteremia in the post-acute and long-term care (PA/LTC) setting is the bladder when an indwelling urinary catheter is in use. The federal Healthcare Infection Control Practices Advisory Committee (HICPAC) recommends minimizing urinary catheter use and duration of use in all patients. Specifically, HICPAC recommends not using a catheter to manage urinary incontinence in the PA/LTC setting. Appropriate indications for indwelling urinary catheter placement include acute retention or outlet obstruction, to assist in healing of deep sacral or perineal wounds in patients with urinary incontinence, and to provide comfort at the end of life if needed. Don’t recommend screening for breast, colorectal or prostate cancer if life expectancy is estimated to be less than 10 years. Many patients residing in the LTC setting are elderly and frail, with multimorbidity and limited life expectancy. Although research evaluating the impact of screening for breast, colorectal and prostate cancer in older adults in general and LTC residents in particular is scant, available studies suggest that multimorbidity and advancing age significantly alter the risk-benefit ratio. Preventive cancer screenings have both immediate and longer term risks (e.g., procedural and psychological risks, false positives, identification of cancer that may be clinically insignificant, treatment-related morbidity and mortality). Benefits of cancer screening occur only after a lag time of 10 years (colorectal or breast cancer) or more (prostate cancer). Patients with a life expectancy shorter than this lag time are less likely to benefit from screening. Discussing the lag time (“When will it help?”) with patients is at least as important as discussing the magnitude of any benefit (“How much will it help?”). Prostate cancer screening by prostate-specific antigen testing is not recommended for asymptomatic patients because of a lack of life-expectancy benefit. One-time screening for colorectal cancer in older adults who have never been screened may be cost-effective; however, it should not be considered after age 85 and for most LTC patients older than 75 the burdens of screening likely outweigh any benefits. Don’t obtain a C. difficile toxin test to confirm “cure” if symptoms have resolved. Patients residing in PA/LTC facilities are particularly at risk for CDI because of advanced age, frequent hospitalizations and frequent antibiotic exposure. However, only symptomatic patients should be tested. Furthermore, studies have shown that C. difficile tests may remain positive for as long as 30 days after symptoms have resolved. False positive “test-of-cure” specimens may complicate clinical care and result in additional courses of inappropriate anti-C. difficile therapy. To limit the spread of C. difficile, care providers in the PA/LTC setting should concentrate on early detection of symptomatic patients and the consistent use of proper infection control practices, including hand washing with soap and water, contact precautions, and environmental cleaning with 1:10 dilution of sodium hypochlorite (bleach) prepared fresh daily. Don’t recommend aggressive or hospital-level care for a frail elder without a clear understanding of the individual’s goals of care and the possible benefits and burdens. Hospital-level care has known risks, including delirium, infections, side effects of medications and treatments, disturbance of sleep, and loss of mobility and function. These risks are often more significant for patients in the PA/LTC setting, who are more likely to be frail and to have multimorbidity, functional limitations and dementia. Therefore, for some frail elders, the balance of benefits and harms of hospital-level care may be unfavorable. To avoid unnecessary hospitalizations, care providers should engage in advance care planning by defining goals of care for the patient and discussing the risks and benefits of various interventions, including hospitalization, in the context of prognosis, preferences, indications, and the balance of risks and benefits. Advance directives such as the Physician Orders for Life Sustaining Treatment (POLST) paradigm form and Do Not Hospitalize (DNH) orders communicate a patient’s preferences about end-of-life care. Patients with DNH orders are less likely to be hospitalized than those who do not have these directives. Patients who opt for less-aggressive treatment options are less likely to be subjected to unnecessary, unpleasant and invasive interventions and the risks of hospitalization. Don’t initiate antihypertensive treatment in individuals ≥60 years of age for systolic blood pressure (SBP) <150 mm Hg or diastolic blood pressure (DBP) <90 mm Hg. There is strong evidence for the treatment of hypertension in older adults. Achieving a goal SBP of 150mm Hg reduces stroke incidence, all-cause mortality and heart failure. There is less consistent evidence that lower BP targets are beneficial for high-risk patients, especially frail patients in the post-acute and long-term care setting. Target SBP and DBP levels should be based on shared decision-making with the patient as there is data supporting benefit in treating more aggressively to a goal SBP of <140mm Hg in community-dwelling individuals ≥75 years of age with elevated cardiovascular risk. Using a reliable, representative method of taking blood pressures with special attention to orthostatic hypotension is important, as orthostatic hypotension has been associated with increased mortality and cardiovascular events. In addition, moderate or high-intensity treatment of hypertension has been associated with an increased risk of serious falls and injury in frail older adults. These items are provided solely for informational purposes and are not intended as a substitute for consultation with a medical professional. Patients with any specific questions about the items on this list or their individual situation should consult their physician. These items are provided solely for informational purposes and are not intended as a substitute for consultation with a medical professional. Patients with any specific questions about the items on this list or their individual situation should consult their physician. AMDA – The Society for Post-Acute and Long-Term Care Medicine is the only professional association representing medical directors, attending physicians and others practicing in the long term care continuum. AMDA is dedicated to excellence in patient care and provides education, advocacy, information and professional development to promote the delivery of quality long term care medicine. AMDA strives to provide cutting edge education, information and tools on clinical, management and technology topics that are specific to the evolving long term care setting. AMDA offers opportunities to learn about best practices and activities that can maximize the quality of care and quality of life for patients. 1–5: AMDA – The Society for Post -Acute and Long-Term Care Medicine convened a work group made up of members from the Clinical Practice Steering Committee (CPSC). Members of the CPSC include board certified geriatricians, certified medical directors, multi-facility medical directors, attending practitioners, physicians practicing in both office-based and nursing facility practice, physicians in rural, suburban and academic settings, those with university appointments, and more. It was important to AMDA that the workgroup chosen represent the core base of the AMDA membership. Ideas for the “five things” were solicited from the workgroup. Suggested elements were considered for appropriateness, relevance to the core of the specialty and opportunities to improve patient care. They were further refined to maximize impact and eliminate overlap, and then ranked in order of potential importance both for the specialty and for the public. A literature search was conducted to provide supporting evidence or refute the activities. The list was modified and a second round of selection of the refined list was sent to the workgroup for paring down to the final “top five” list. Finally, the work group chose its top five recommendations before submitting a final draft to the AMDA Executive Committee, which were then approved. 6–10: The AMDA Choosing Wisely® endeavor utilized a similar procedure as published in JAMA Intern Med. 2014;174(4):509-515 – A Top 5 List for Emergency Medicine for our five items. The AMDA Clinical Practice Committee acted as the Technical Expert Panel (TEP). Phase 1 – The Clinical Practice Steering Committee (CPSC) along with the Infection Advisory Committee clinicians brainstormed an initial list of low-value clinical decisions that are under control of PA/LTC physicians that were thought to have a potential for cost savings. Phase 2 – Each member of the CPSC selected five low-value tests considering the perceived contribution to cost (how commonly the item is ordered and the individual expense of the test/treatment/action), benefit of the item (scientific evidence to support use of the item in the literature or in guidelines); and highly actionable (use decided by PA/LTC clinicians only). Phase 3 – A survey was sent to all AMDA members. Statements were phrased as specific overuse statements by using the word “don’t,” thereby reflecting the action necessary to improve the value of care. Phase 4 – CPSC members reviewed survey results and chose the five items. For more information, visit www.paltc.org. Teno JM, Gozalo PL, Mitchell SL, Kuo S, Rhodes RL, Bynum JP, Mor V. Does feeding tube insertion and its timing improve survival? J Am Geriatr Soc. 2012 Oct;60(10):1918-21. Hanson LC, Ersek M, Gilliam R, Carey TS. Oral feeding options for people with dementia: a systematic review. J Am Geriatr Soc. 2011;59(3):463-72 Palecek EJ, Teno JM, Casarett DJ, Hanson LC, Rhodes RL, Mitchell SL. Comfort feeding only: a proposal to bring clarity to decision-making regarding difficulty with eating for persons with advanced dementia. J Am Geriatr Soc. 2010;58(3):580-4. Sorrell JM. Use of feeding tubes in patients with advanced dementia: are we doing harm? J Psychosoc Nurs Ment Health Serv. 2010 May;48(5):15-8. Sampson EL, Candy B, Jones L. Enteral tube feeding for older people with advanced dementia. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007209. Gillick MR, Volandes AE. The standard of caring: why do we still use feeding tubes in patients with advanced dementia? J Am Med Dir Assoc. 2008 Jun;9(5):364-7. Ganzini L. Artificial nutrition and hydration at the end of life: ethics and evidence. Palliat Support Care. 2006 Jun;4(2):135-43. Li I. Feeding tubes in patients with severe dementia. Am Fam Physician. 2002 Apr 15;65(8):1605-11. Finucane TE, Christmas C, Travis K. Tube feeding in patients with advanced dementia: a review of the evidence. JAMA. 1999 Oct 13;282(14):1365-70. Mitchell SL, Kiely DK, Lipsitz LA. The risk factors and impact on survival of feeding tube placement in nursing home residents with severe cognitive impairment. Arch Intern Med. 1997 Feb 10;157(3):327-32. Sue Kirkman M, Briscoe VJ, Clark N, Florez H, Haas LB, Halter JB, Huang ES, Korytkowski MT, Munshi MN, Odegard PS, Pratley RE, Swift CS. Consensus Development Conference on Diabetes and Older Adults. Diabetes in older adults: a consensus report. J Am Geriatr Soc. 2012 Dec;60(12):2342-56. American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2012 Apr;60(4):616-31. Haq J. Insulin sliding scare, does it exist in the nursing home. JAMDA. 2010 Mar;11(3):B14. Hirsch IB. Sliding scale insulin—time to stop sliding. JAMA. 2009;301(2):213-214. American Medical Directors Association. diabetes management in the long-term care setting clinical practice guideline. Columbia, MD:AMDA 2008, revised 2010. Pandya N, Thompson S, Sambamoorthi U. The prevalence and persistence of sliding scale insulin use among newly admitted elderly nursing home residents with diabetes mellitus. J Am Med Dir Assoc. 2008 Nov;9(9):663-9. Umpierrez GE, Palacio A, Smiley D. Sliding scale insulin use: myth or insanity? Am J Med. 2007;120(7):563-67. Golightly LK, Jones MA, Hamamura DH, Stolpman NM, McDermott MT. Management of diabetes mellitus in hospitalized patients: efficiency and effectiveness of sliding-scale insulin therapy. Pharmacotherapy. 2006;26(10):1421-32. Munshi et al. Management of Diabetes in Longterm Care and Skilled Nursing Facilities: A Position Statement of the American Diabetes Association. Diabetes Care 2016;39:308-318/DOI: 10.2337/dc15-2512. Queale WS, Seidler AJ, Brancati FL. Glycemic control and sliding scale insulin use in medical inpatients with diabetes mellitus. Arch Intern Med. 1997;157(5):545-52. Stone ND, Ashraf MS, Calder J, Crnich CJ, Crossley K, Drinka PJ, Gould CV, Juthani-Mehta M, Lautenbach E, Loeb M, MacCannell T, Malani TN, Mody L, Mylotte JM, Nicolle LE, Roghmann MC, Schweon SJ, Simor AE, Smith PW, Stevenson KB, Bradley SF. Surveillance definitions of infections in long-term care facilities: revisiting the McGeer Criteria. Infec Control Hosp Epidemiol. 2012;33(10):965-77. Drinka P. Treatment of bacteriuria without urinary signs, symptoms, or systemic infectious illness (S/S/S). J Am Med Dir Assoc. 2009 Oct;10(8):516-9. Arinzon Z, Peisakh A, Shuval I, Shabat S, Berner YN. Detection of urinary tract infection (UTI) in long-term care setting: is the multireagent strip an adequate diagnostic tool? Arch Gerontol Geriatr. 2009 Mar-Apr;48(2):227-31. High KP, Bradley SF, Gravenstein S, Mehr DR, Quagliarello VJ Richards C, Yoshikawa TT. Clinical practice guideline for the evaluation of fever and infection in older adult residents of long-term care facilities: 2008 update by the Infectious Diseases Society of America. J Am Geriatr Soc. 2009 Mar;57(3):375-94. Zabarsky TF, Sethi AK, Donskey CJ. Sustained reduction in inappropriate treatment of asymptomatic bacteriuria in a long-term care facility through an educational intervention. Am J Infect Control. 2008 Sep;36(7):476-80. Richards CL Jr. Infection control in long-term care facilities. J Am Med Dir Assoc. 2007 Mar;8(3 Suppl):S18-25. Ducharme J, Neilson S, Ginn JL. Can urine cultures and reagent test strips be used to diagnose urinary tract infection in elderly emergency department patients without focal urinary symptoms? CJEM. 2007 Mar;9(2):87-92. Loeb M, Brazil K, Lohfeld L, McGeer A, Simor A, Stevenson K, Zoutman D, Smith S, Liu X, Walter SD. Effect of a multifaceted intervention on number of antimicrobial prescriptions for suspected urinary tract infections in residents of nursing homes: cluster randomized controlled trial. BMJ. 2005 Sep 24;331(7518):669. Loeb M, Brazil K, Lohfeld L, McGeer A, Simor A, Stevenson K, Walter S, Zoutman D. Optimizing antibiotics in residents of nursing homes: protocol of a randomized trial. BMC Health Serv Res. 2002 Sep 3;2(1):17. Nace D, Perera S, Hanlon J, Saracco S, Anderson G, Schweon S, Klein-Fedyshin M, Wessel C, Mulligan M, Drinka P, Crnich C. J Am Med Dir Association. 2018(19) 765-769. Nicolle LE. Urinary tract infection in geriatric and institutionalized patients. Curr Opin Urol. 2002 Jan;12(1):51-5. Boscia JA, Kobasa WD, Abrutyn E, Levison ME, Kaplan AM, Kaye D. Lack of association between bacteriuria and symptoms in the elderly. Am J Med. 1986 Dec;81(6):979-82. Nicolle LE, Bentley D, Garibaldi R, Neuhaus E, Smith P. SHEA Long-Term Care Committee. Antimicrobial use in long-term-care facilities. Infect Control Hosp Epidemiol. 1996;17:119-28. High KP, Bradley SF, Gravenstein S, Mehr DR, Quagliarello VJ, Richards C, Yoshikawa TT. Clinical practice guideline for the evaluation of fever and infection in older adult residents of long-term care facilities: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis 2009;48: 149-71. American Medical Directors Association. Dementia in the long term care setting clinical practice guideline. Columbia, MD: AMDA 2012. Perkins, R. Evidence-based practice interventions for managing behavioral and psychological symptoms of dementia in NH residents. Ann LTC. 2012:20(12):20-4. Flaherty J, Gonzales J, Dong B. Antipsychotics in the treatment of delirium in older hospitalized adults: a systematic review. JAGS. 2011;59:S269-76. American Medical Directors Association. Delirium and acute problematic behavior clinical practice guideline. Columbia, MD: AMDA 2008. Ozbolt LB, Paniagua MA, Kaiser RM. Atypical antipsychotics for the treatment of delirious elders. J Am Med Dir Association. 2008;9:18–28. U.S. Food and Drug Administration. Information for healthcare professionals: antipsychotics. FDA Alert, [Internet]. 2008 Jun 16. [Cited 2008 Sep 23]. Available from: http://www.fda.gov/cder/drug/InfoSheets/HCP/antipsychotics_conventional.htm. U.S. Food and Drug Administration, U.S. Department of Health and Human Services. 2007 information for healthcare professionals: haloperidol (marketed as Haldol, Haldol decanoate, and Haldol lactate). [Internet]. 2007 Sep 17. [Cited 2013 Jul 23]. Available from http://www.fda.gov/cder/drug/InfoSheets/HCP/haloperidol.htm. Schneeweiss S, Setoguchi S, Brookhart A, Dormuth C, Wang PS. Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients. CMAJ 2007;176(5): 627–32. Gill SS, Bronskill SE, Normand SL, Anderson GM, Sykora K, Lam K, Bell CM, Lee PE, Fischer HD, Herrmann N, Gurwitz JH, Rochon PA. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med. 2007;146(11):775–86. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005;294(15):1934–1943. Schneider LS, Tariot PN, Dagerman KS. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med. 2006;355(15):1525–38. Sink KM, Holden KF, Yaffe K. Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. JAMA. 2005;293:596–608. U.S. Food and Drug Administration, U.S. Department of Health and Human Services. FDA public health advisory: deaths with antipsychotics in elderly patients with behavioral disturbances. [Internet]. 2005 Apr 11. [Cited 2013 Jul 23]. Available from http://www.fda.gov/cder/drug/advisory/antipsychotics.htm. Dalleur O, Spinewine A, Henrard S, Losseau C, Speybroeck N, Boland B. Inappropriate prescribing and related hospital admissions in frail older persons according to the STOPP and START criteria. Drugs Aging. 2012 Oct;29(10):829-37. Schiattarella GG, Perrino C, Magliulo F, Ilardi F, Serino F, Trimarco V, Izzo R, Amato B, Terranova C, Cardin F, Militello C, Leosco D, Trimarco B, Esposito G. Statins and the elderly: recent evidence and current indications. Aging Clin Exp Res. 2012 Jun;24(3 Suppl):47-55. Maraldi C, Lattanzio F, Onder G, Gallerani M, Bustacchini S, De Tommaso G, Volpato S. Variability in the prescription of cardiovascular medications in older patients: correlates and potential explanations. Drugs Aging. 2009 Dec;26 Suppl 1:41-51. Schatz IJ, Masaki K, Yano K, Chen R, Rodriguez BL, Curb JD. Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet. 2001 Aug 4;358(9279):351-5. Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM, Knook DL, Meinders AE, Westendorp RG. Total cholesterol and risk of mortality in the oldest old. Lancet. 1997 Oct 18;3 (9085):1119-23. Krumholz HM, Seeman TE, Merrill SS, Mendes de Leon CF, Vaccarino V, Silverman DI, Tsukahara R, Ostfeld AM, Berkman LF. Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. JAMA. 1994 Nov 2;272(17):1335-40. CMS Manual System Pub. 100-07 State Operations Provider Certification. Transmittal 8. Revision of Appendix PP–Section 483.25(d)–Urinary Incontinence, Tags F315 and F316. Centers for Medicare and Medicaid Services, U.S. Department of Health and Human Services; 2005 Jun 28 [cited 2014 Dec 31]. Available from: https://www.cms.gov/Regulations-and-Guidance/Guidance/Transmittals/downloads/r8som.pdf. Gould CV, Umscheid CA, Agarwal RK, Kuntz G, Pegues DA; Healthcare Infection Control Practices Advisory Committee. Guideline for prevention of catheter-associated urinary tract infections 2009. Infect Control Hosp Epidemiol. 2010 Apr;31(4):319-26. Hooton TM, Bradley SF, Cardenas DD, Colgan R, Geerlings SE, Rice JC, Saint S, Schaeffer AJ, Tambayh PA, Tenke P, Nicolle LE; Infectious Diseases Society of America. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010 Mar;50(5):625-63. Clarfield AM. Screening in frail older people: an ounce of prevention or a pound of trouble? J Am Geriatr Soc. 2010 Oct;58:2016-21. Gill TM. The central role of prognosis in clinical decision making. JAMA. 2012 Jan 11;307(2):199-200. Gross CP. Cancer screening in older persons: a new age of wonder. JAMA Intern Med. 2014 Oct;174(10):1565-7. Lee SJ, Leipzig RM, Walter LC. Incorporating lag time to benefit into prevention decision for older adults. JAMA. 2013 Dec (25);310(24):2609-10. Lonsdorp-Vogelaar I, Gulati R, Mariotto AB, Schechter CB, de Carvalho TM, Knudsen AB, van Ravesteyn NT, Heijnsdijk EA, Pabiniak C, van Ballegooijen M, Rutter CM, Kuntz KM, Feuer EJ, Etzioni R, de Koning HJ, Zauber AG, Mandelblatt JS. Personalizing age of cancer screening cessation based on comorbid conditions: model estimates of harms and benefits. Ann Intern Med. 2014 Jul 15;161(2):104-12. Moyer VA. Screening for prostate cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2012 Jul 17;157(2):120-34. Royce TJ, Hendrix LH, Stokes WA, Allen IM, Chen RC. Cancer screening rates in individuals with different life expectancies. JAMA Intern Med. 2014 Oct;174(10):1558-65. Spivack B, Cefalu C, Kamel H, et al. Health Maintenance in the Long Term Care Setting Clinical Practice Guideline. 2012. Columbia, MD: American Medical Directors Association. van Hees F, Habbema JD, Meester RG, Lansdorp-Vogelaar I, van Ballegooijen M, Zauber AG. Should colorectal cancer screening be considered in elderly persons without previous screening? A cost-effectiveness analysis. Ann Intern Med. 2014 Jun 3;160(11):750-9. Walter LC, Covinsky KE. Cancer screening in elderly patients: a framework for individualized decision making. JAMA. 2001 Jun 6;285(21):2750-6. Riggs MM, Sethi AK, Zabarsky TF, Eckstein EC, Jump RL, Donskey CJ. Asymptomatic carriers are a potential source for transmission of epidemic and nonepidemic Clostridium difficile strains among long-term care facility residents. Clin Infect Dis. 2007 Oct 15;45 (8):992. Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, McFarland LV, Mellow M, Zuckerbraun BS. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013 Apr;108(4):478–98. Creditor MC. Hazards of hospitalization of the elderly. Ann Intern Med. 1993 Feb 1;118(3):219. Deciding About Going to the Hospital. Interact v4.0 Tool. Florida Atlantic University; 2011 [cited 2015 Jan 2]. Available from: http://interact2.net/docs/INTERACT%20Version%204.0%20Tools/INTERACT%20V%204%20Deciding_About_Going_to_Hosptial%20Nov%2017%202014.pdf. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014 Mar 8;383(9920):911-22. Murray LM, Laditka SB. Care transitions in older adults from nursing homes to hospitals: implications for long-term care practice, geriatrics education, and research. J Am Med Dir Assoc. 2010 May;11(4):231-8. Tulsky JA. Beyond advance directives: importance of communication skills at the end of life. JAMA. 2005 Jul 20;294(3):359-65. Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, Stoyanovsky V, Antikainen RL, Nikitin Y, Anderson C, Belhani A, Forette F, Rajkumar C, Thijs L, Banya W, Bulpitt CJ; HYVET Study Group. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008 May 1; 358(18):1887-98. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC Jr, Svetkey LP, Taler SJ, Townsend RR, Wright JT Jr, Narva AS, Ortiz E. 2014 evidence-based guideline for the management of high blood pressure in adults. JAMA. 2014 Feb 5;311(5):507-20. Muntner P, Bowling CB, Shimbo D. Systolic blood pressure goals to reduce cardiovascular disease among older adults. Am J Med Sci. 2014 Aug;348(2):129-34. Tinetti ME, Han L, Lee DSH, McAvay GJ, Peduzzi P, Gross CP, Zhou B, Lin H. Antihypertensive medications and serious fall injuries in a nationally representative sample of older adults. JAMA Intern Med. 2014 Apr;174(4):588-95. Angelousi A, Girerd N, Benetos A, Frimat L, Gautier S, Weryha G, Boivin J-M. Association between orthostatic hypotension and cardiovascular risk, cerebrovascular risk, cognitive decline and falls as well as overall mortality: a systematic review and meta-analysis. Journal of Hypertension 2014, 32:1562–1571. Williamson JD, Supiano MA, Applegate WB, Berlowitz DR, Campbell RC, Chertow GM, Fine LJ, Haley WE, Hawfield AT, Ix JH, Kitzman DW, Kostis JB, Krousel-Wood MA, Launer LJ, Oparil S, Rodriguez CJ, Roumie CL, Shorr RI, Sink KM, Wadley VG, Whelton PK, Whittle J, Woolard NF, Wright JT Jr, Pajewski NM, SPRINT Research Group. Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged≥75 Years: A Randomized Clinical Trial. JAMA. 2016;315(24):2673.	2	25	0	0	2	0.870214	2	7,661
What is the ICD-10 code for throat culture? When do you use Z11 59? What is code Z20 828? What is R53 83? What is diagnosis code Z11 3? When do you use modifier 95? When do you use ICD-10 code Z20 822? When do you use U07 1? What is procedure code 87426? What is R53 81 diagnosis? What is R53 81? What is the diagnosis for ICD-10 code r50 9? What does “type 1 excludes” mean? A type 1 excludes note is for used for when two conditions cannot occur together, such as a congenital form versus an acquired form of the same condition. chronic sore throat (. What is exclude note? A type 1 excludes note is for used for when two conditions cannot occur together, such as a congenital form versus an acquired form of the same condition. A type 2 excludes note represents “not included here”. What is the ICd 10 code for naso pharyngitis? Ready for some good news? The common cold is still the common cold and has a simple, three-digit ICD-10 code: J00, “Acute naso-pharyngitis.” ICD-10 even includes “common cold” in the description. What is the ICD-10 code for emphysema? For these conditions, ICD-10 uses two base code catego-ries: J43 for emphysema and J44 for chronic obstructive pulmonary disease (COPD). All codes require a fourth digit. However, without additional testing, it is unlikely that a primary care physician can clearly differentiate emphysema from chronic bronchitis. Per the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health, “Most people who have COPD have both emphysema and chronic bronchitis. Thus, the general term ‘COPD’ is more accurate.”1 In What is the J00 code for rhinitis? Infective rhinitis defaults to the “Acute naso-pharyngitis” (common cold) J00 code, discussed earlier. However, chronic rhinitis gets its own code, J31.0. Vasomotor and allergic rhinitis also have their own code series (J30). (See “Rhinitis	4	4	1	0	18	0.514831	19	533
Sleep Apnea is a serious sleep disorder during which you stop breathing temporarily while sleeping repeatedly. Sleep Apnea Symptoms and Risks What is Sleep Apnea? In most cases, people aren’t aware that they have sleep apnea because they’re asleep at the time. However, if you’ve been told that you snore too much or if you’re tired even after a full night’s sleep, it’s extremely likely that you have sleep apnea icd 10. To know more about icd 10 code for sleep apnea, go through our article carefully. Types of Sleep Apnea There are basically three different types of sleep apnea. It’s important to identify which of them you may fall under in order to treat sleep apnea properly. - Obstructive Sleep Apnea: This is type of sleep apnea occurs most frequently. During this condition, your throat muscles relax and prevent you from taking in air.Do you know about obstructive sleep apnea icd 10? It is a reversible & recurrent obstruction of the pharyngeal airway when people are asleep. ICD-10 code for Obstructive sleep apnea (G47. 33) is classified medically under WHO under the diseases of the nervous system. - Central Sleep Apnea: This happens when there’s a disconnect between your brain and the breathing-related muscles. - Complex Sleep Apnea: This is a combination of both obstructive and central sleep apnea. Obstructive Sleep Apnea Causes As mentioned above, obstructive sleep apnea occurs when the muscles in your throat relax. These muscles generally support the tissue hanging from the uvula known as the soft palate. They also support the tonsils, tongue, and the sides of the throat. When these muscles relax, your airway constricts, which prevents you from breathing in effectively and you don’t get enough air. This causes your body to lose oxygen, which sends signals to your brain to briefly wake you up so you can resume breathing by opening up the airways. This pattern of relaxing the muscles, losing oxygen, waking up briefly and opening the airways may repeat 5 to 30 times every hour and all through the night. Even if you don’t remember waking up during these moments, your body remembers, and you suffer from hypersomnia the next day. Schedule an appointment with a local doctor to get a precise diagnosis and treatment for icd 10 obstructive sleep apnea. What Are The Symptoms Of Sleep Apnea? Even though there are three different types of sleep apnea, the signs and symptoms of obstructive sleep apnea and central sleep apnea are similar. As such, you can’t determine which type of sleep apnea you’re suffering from based on the sleep apnea symptoms alone. The following are the most common signs of sleep apnea: - Excessive snoring. - Another person reporting that you occasionally stop breathing in your sleep. - Gasping for air when you momentarily stop breathing in your sleep. - Dry mouth when you wake up. - Headaches early in the morning. - Insomnia or the inability to fall asleep at night. - Hypersomnia or the desire to sleep even during the day. - Lack of focus and inattentiveness. - Heightened irritation and frustration. Central Sleep Apnea Causes Central sleep apnea isn’t as common as obstructive sleep apnea, but its explanation is fairly simple. This is a condition in which your brain doesn’t transmit the necessary signals to your breathing muscles. As such, you stop breathing every once in a while. Once your oxygen level starts falling, you are quickly roused from sleep so you can resume breathing again. What are the Conditions Associated with Sleep Apnea? The following are some of the most common conditions associated with sleep apnea. - Hypersomnia: Long undisturbed sleep is necessary to function properly the next day. However, with sleep apnea, you keep waking up intermittently, even if you’re not aware of it. This leads to hypersomnia, which results in drowsiness, fatigue, and irritability all throughout the day. This, in turn, causes you to lose focus, become inattentive, and also get moody and depressed. - Insomnia: Some people also suffer from insomnia due to sleep apnea, especially those who are sensitive sleepers. After you wake up a few times because of your sleep apnea, you may not be able to go to sleep again. This, in turn, also leads to hypersomnia. - Snoring: People with sleep apnea also snore excessively and loudly. This makes sleep difficult for your partner as well and they may have to either go to another room or use earplugs to sleep. As such, sleep apnea also affects those around you. Losing sleep can negatively affect your life in many ways. What Are Effects of Long Term Sleep Apnea, If Left Undiagnosed? Sleep apnea is a serious medical condition. If you suffer from it, you need to seek immediate treatment. Failure to diagnose and treat sleep apnea in a timely manner can lead to a number of complications. The following are some of the effects of long term sleep apnea. - High Blood Pressure: When you suddenly lose oxygen while sleeping, your blood pressure increases, which places great stress on your cardiovascular system. Over time, this results in sustained high blood pressure. - Heart Issues: Continued fluctuations in the blood oxygen level and blood pressure can also lead to heart issues like abnormal heartbeats, heart attack, and strokes. Furthermore, a sustained irregular heartbeat can also be deathly. - Type 2 Diabetes: Sleep apnea makes it so that you develop a resistance to insulin, which can lead to type 2 diabetes. - Liver Problems: People suffering from sleep apnea often show signs of scarring and damage on their liver function tests. - Metabolic Syndrome: This is a condition that leads to high blood pressure, high sugar level, increased weight, and fluctuating cholesterol levels. All of these conditions can also increase the likelihood of heart conditions. Don’t let a lack of sleep affect your productivity. How to Cure Sleep Apnea? Once your sleep apnea doctors near me diagnose the sleep apnea, you may be referred to different sleep apnea treatment options and procedures. The following are the most effective sleep apnea treatment options. - Continuous Positive Airway Pressure (CPAP): CPAP machines are the most common sleep apnea devices. This device in which air pressure difference is used to keep your upper airway passages wide open and facilitate breathing through a mask when you sleep. Even though this is a popular sleep apnea treatment, it’s incredibly uncomfortable, and people often report that it prevents them from sleeping comfortably. - Auto CPAP: This airway pressure device moderates the pressure automatically when you sleep. - BPAP: This is yet another airway pressure device that provides more pressure upon inhaling and less upon exhaling. - Silent Nite for Sleep Apnea: If you’re looking for sleep apnea treatment options without CPAP, then Silent Nite may be your best choice. This anti-snoring sleep apnea device pushes the lower jaw forward to open your airways and facilitate breathing, thus treating sleep apnea. Sleep Apnea Treatment Near Me There are several different sleep apnea cures, but using a sleep apnea mouthpiece such as Silent Nite is more comfortable than most other options because it’s much more manageable. At URBN Dental, our expert dentists can treat your sleep apnea using the right set of Silent Nite mouthpieces. Please schedule an appointment at a highly recommended sleep apnea treatment center for further information on how to cure sleep apnea.	2	4	0	0	2	0.935473	2	1,651
Technical Appendix Introduction This appendix explains some of the sources and methods used by the National Safety Council (NSC) Statistics Department in preparing the estimates of deaths, injuries, and costs. Many of the estimates depend on death certificate data provided by the National Center for Health Statistics (NCHS). Here is a brief explanation of the certification and classification of deaths. Certification and classification The medical certification of death involves entering information on the death certificate about the disease or condition directly leading to death, antecedent causes, and other significant conditions. The death certificate is then registered with the appropriate authority, and a code is assigned for the underlying cause of death. The underlying cause is defined as “(a) the disease or injury which initiated the train of morbid events leading directly to death, or (b) the circumstances of the accident or violence which produced the fatal injury” (World Health Organization [WHO], 1992). Deaths are classified and coded on the basis of a WHO standard, the International Statistical Classification of Diseases and Related Health Problems, commonly known as the International Classification of Diseases or ICD (WHO, 1992). For deaths due to injury and poisoning, the ICD provides a system of “external cause” codes to which the underlying cause of death is assigned. Visit this page and click on “Data Table” for a condensed list of external cause codes. Comparability across ICD revisions The ICD is revised periodically, and these revisions can affect comparability from year to year. The sixth revision (1948) substantially expanded the list of external causes and provided for classifying the place of occurrence. Changes in the classification procedures for the sixth revision, as well as the seventh (1958) and eighth (1968) revisions, classified as diseases some deaths previously classified as injuries. The eighth revision also expanded and reorganized some external cause sections. The ninth revision (ICD-9,1979) provided more detail on the agency involved, the victims’ activity, and the place of occurrence. The tenth revision (ICD-10), which was adopted in the United States effective with 1999 data, completely revised the transportation-related categories. Specific external cause categories affected by the revisions are noted in the historical tables. This table lists the ICD-9 codes, the ICD-10 codes and a comparability ratio for each of the principal causes of unintentional-injury death. The comparability ratio represents the net effect of the new revision on statistics for the cause of death. The comparability ratio was obtained by classifying a sample of death certificates under both ICD-9 and ICD-10 and then dividing the number of deaths for a selected cause classified under ICD-10 by the number classified to the most nearly comparable ICD-9 cause. A comparability ratio of 1.00 indicates no net change due to the new classification scheme. A ratio less than 1.00 indicates fewer deaths assigned to a cause under ICD-10 than under ICD-9. A ratio greater than 1.00 indicates an increase in assignment of deaths to a cause under ICD-10 compared to ICD-9. The broad category of “accidents” or “unintentional injuries” under ICD-9 included complications and misadventures of surgical and medical care (E870-E879) and adverse effects of drugs in therapeutic use (E930-E949). These categories are not included in “accidents” or “unintentional injuries” under ICD-10. In 1998, deaths in these two categories numbered 3,228 and 276, respectively. Under ICD-9, the code range for falls (E880-E888) included a code for “fracture, cause unspecified” (E887). A similar code does not appear in ICD-10 (W00-W19), which probably accounts for the low comparability ratio (0.8409). In 1998, deaths in code E887 numbered 3,679. Beginning with 1970 data, tabulations published by NCHS no longer include deaths of nonresident aliens. In 2016, there were 1,045 such unintentional deaths, of which 324 were motor-vehicle related.	4	2	0	0	2	0.332961	2	874
December 17, 2012 Coding for Peripheral Neuropathy For The Record Vol. 24 No. 23 P. 25 Peripheral neuropathy involves damage to the peripheral nerves, which send information to and from the brain and spinal cord to other parts of the body. Damage to a peripheral nerve may affect communication between the brain and other body parts and may cause problems with muscle movement and sensation in the arms and legs. The condition can cause problems to a single peripheral nerve (mononeuropathy), multiple nerves in different areas (multiple mononeuropathy), or many nerves throughout the body (polyneuropathy). Additionally, it may affect sensory, motor, or autonomic nerves. Peripheral neuropathy may be the result of diabetes, traumatic injuries, infections, metabolic problems, and toxins, with diabetes being the most common cause. Symptoms of peripheral neuropathy vary depending on the type of nerve affected. Common signs and symptoms include numbness and tingling in feet or hands; burning pain in the arms and legs; sharp, jabbing, or electriclike pain; extreme sensitivity to touch; lack of coordination; muscle weakness or paralysis if motor nerves are affected; and bowel or bladder problems if autonomic nerves are affected. Mononeuropathy or mononeuritis is classified to ICD-9-CM categories 354 and 355. Additional digits will identify the specific nerve involved as follows: • 354.0, Carpal tunnel syndrome; • 354.1, Other lesion of median nerve; • 354.2, Lesion of ulnar nerve; • 354.3, Lesion of radial nerve; • 354.4, Causalgia of upper limb; • 354.5, Mononeuritis multiplex; • 354.8, Other mononeuritis of upper limb; • 354.9, Mononeuritis of upper limb, unspecified; • 355.0, Lesion of sciatic nerve; • 355.1, Meralgia paresthetica; • 355.2, Other lesion of femoral nerve; • 355.3, Lesion of lateral popliteal nerve; • 355.4, Lesion of medial popliteal nerve; • 355.5, Tarsal tunnel syndrome; • 355.6, Lesion of plantar nerve; • 355.71, Causalgia of lower limb; • 355.79, Other mononeuritis of lower limb; • 355.8, Mononeuritis of lower limb, unspecified; and • 355.9, Mononeuritis of unspecified site. Peripheral neuropathy that is not further specified as being caused by an underlying condition is assigned to code 356.9. Autonomic neuropathy not further specified is classified to code 337.9. If either peripheral or autonomic neuropathy is caused by diabetes, then a code from subcategory 250.6 will be sequenced first followed by code 357.2 for polyneuropathy in diabetes or code 337.1 for peripheral autonomic neuropathy. Diabetic peripheral neuropathy is one of the more serious complications of long-term diabetes. It typically affects patients with type 1 diabetes more frequently than those with type 2 and occurs more often in men. It’s thought to evolve from damage to capillaries in the extremities caused by the long-term effects of poorly controlled or uncontrolled blood glucose. This vascular damage injures the peripheral nerves. Patients describe the pain as burning, tingling, and occasionally stabbing. If a patient is admitted with a diabetic neuropathy or has neuropathy caused by diabetes, the diabetic code from category 250 must be sequenced as the principal diagnosis followed by the manifestations as secondary diagnoses. Conditions are coded in this manner even though the ICD-9-CM alphabetic index may not indicate dual coding (AHA Coding Clinic for ICD-9-CM, 1991, third quarter, page 8). In other words, the physician must state a cause-and-effect relationship between the manifestation and the diabetes before it can be coded as a diabetic condition. A patient with diabetes can develop neuropathy that is unrelated to the diabetes. If this is the case, the unspecified diabetes code will be assigned as well as the appropriate code for the neuropathy. Sequencing of the two conditions will depend on the circumstances of admission. However, if the physician establishes a link between the diabetes and the neuropathy, then it will be coded as a diabetic complication. According to Coding Clinic, if the physician documents “diabetes with neuropathy,” then a cause-and-effect relationship has been established, and it can be coded as a diabetic complication (250.6x + 357.2) (AHA Coding Clinic for ICD-9-CM, 2009, second quarter, page 15). It is not possible to cure neuropathy, but several medications have been found to help ease the pain. Among the most common medications are tricyclic antidepressants such as imipramine; serotonin and norepinephrine reuptake inhibitors, including duloxetine (Cymbalta); certain antiseizure medications, including pregabalin (Lyrica), gabapentin (Neurontin), and carbamazepine (Tegretol); lidocaine patches; and ointments such as ArthriCare and Zostrix (both of which are based on the chemical that gives peppers their heat). Finally, in extreme cases, powerful opioid analgesics such as OxyContin can be helpful, but the addictive aspect of these medications makes them a risky choice. For some patients with diabetic peripheral neuropathy, a physician might apply a transcutaneous electrical nerve stimulation unit or recommend therapies such as biofeedback, acupuncture, hypnosis, meditation, and yoga. Coding and sequencing for peripheral neuropathy are dependent on the physician documentation in the medical record and application of the Official Coding Guidelines for inpatient care. Also, use specific AHA Coding Clinic for ICD-9-CM and American Medical Association CPT Assistant references to ensure complete and accurate coding. — This information was prepared by Audrey Howard, RHIA, of 3M Consulting Services. 3M Consulting Services is a business of 3M Health Information Systems, a supplier of coding and classification systems to more than 5,000 healthcare providers. The company and its representatives do not assume any responsibility for reimbursement decisions or claims denials made by providers or payers as the result of the misuse of this coding information. More information about 3M Health Information Systems is available at www.3mhis.com or by calling 800-367-2447. ICD-10-CM Coding for Peripheral Neuropathy Coding neuropathy in ICD-10-CM is similar to coding it in ICD-9-CM. Upper-limb mononeuropathies are classified to category G56, and lower-limb mononeuropathies go to category G57, with the additional characters identifying the specific nerve and laterality. Polyneuropathy is classified to categories G60 to G65. If the neuropathy is caused by diabetes, then only one combination code is assigned to identify both the diabetes and the neuropathy. ICD-10-CM has combination codes in the diabetes section for the following types of diabetic neuropathy: mononeuropathy, polyneuropathy, autonomic (poly)neuropathy, and amyotrophy. For example, type 1 diabetes mellitus with diabetic polyneuropathy is classified to code E10.42, and type 1 diabetes mellitus with diabetic autonomic (poly)neuropathy is assigned to code E10.43.	4	8	0	0	5	0.841961	5	1,616
Clinical and Health Affairs What You Can Do Now to Prepare for ICD-10 By Patrice Kuppe ■ The United States is moving toward adoption of the 10th version of the World Health Organization’s International Classification of Diseases (ICD) codes. Because the change will have a significant impact on electronic health record and billing systems, ICD-10 is being rolled out in phases over the next couple of years. Physicians will need to begin using the new diagnosis codes starting in October 2013. This article describes the differences between ICD-9 and ICD-10 and the steps physicians and clinics can take now to prepare for the implementation. Big changes are underway in the realm of medical coding. Thanks to a mandate under the Health Insurance Portability and Accountability Act, hospitals, clinics, and health plans throughout the country are in the process of preparing for the implementation of the new International Classification of Diseases (ICD) 10 diagnosis and procedural codes for medical documentation and billing. The United States is one of the last countries in the world to adopt the 10th version of the codes, which was endorsed by the World Health Organization in 1990. Because the change will have an enormous impact on electronic health record (EHR) and billing systems and the people who use them, it will take place in phases over the next several years. Billing and information technology personnel are already working to meet a January 1, 2012, deadline for upgrading systems to meet new standards for electronic claims and other revenue cycle transactions. But for most physicians, October 1, 2013, is the deadline to pay attention to, as that is when they will have to begin using ICD-10-CM, the new diagnosis codes. (Physician services will continue to be coded using Current Procedural Terminology [CPT] codes.) By this same date, in addition to the ICD-10-CM codes, hospitals must start using ICD-10-PCS codes to report the resources and procedures used in inpatient cases (Table 1). There will be no grace period for implementation. The ICD-10 code set replaces ICD-9, which was adopted by the World Health Organization in 1975, the year Microsoft was founded and eight years before the virus that causes AIDS was identified. Obviously, much has changed with regard to computing and medicine since then. Not only does ICD-9 no longer accurately describe the practice of medicine, it is inadequate for meeting the demands of medical record-keeping in the 21st century, which include tracking quality measures, monitoring potential public health risks, and submitting utilization data. In some cases, ICD-9 simply has no code for a condition. For example, it initially had no code for severe acute respiratory syndrome (SARS); a special update had to be made in 2003 to add codes for SARS. In other cases, terminology is outdated and inconsistent with current Questions to Ask Your EHR and Billing System Vendors - How will their application, business processes, or systems address your needs during implemention of ICD-10? Will they maintain tables for each code set? How long will ICD-9 be available for use? Some will propose an embedded or proprietary solution, while others will delegate the responsibility to the user organization. - What is the migration strategy for making the change to ICD-10? Will multiple upgrades be required? This may be a concern for organizations that are not using the latest release of a vendor-supported application. - Will they ensure you have the right tools in place to help you select the more specific diagnosis codes? Will they provide specific provider templates for each specialty? medical practice. Asthma is one example where ICD-10-CM is much more precise and accurate than ICD-9-CM. With ICD-10-CM, asthma is classified as mild intermittent, mild persistent, moderate, or severe. Current guidelines base diagnosis and treatment of asthma according to these categories. But ICD-9-CM classifies asthma as intrinsic and extrinsic, which is no longer relevant for treatment. Thus, using ICD-9-CM codes to analyze treatment outcomes, prevalence of asthma in their patient population, and occurrences of acute episodes of asthma would not yield good data. ICD-9 has simply outlasted its usefulness. ICD-10-CM versus ICD-9-CM Physicians need to understand that the ICD-10-CM system is significantly different than the ICD-9-CM system. First, the number of codes will increase dramatically—from about 13,000 to 68,000. Second, the codes themselves are very different. The ICD-9-CM codes are only three to five characters long. The ICD-10-CM codes will be three to seven characters. In ICD-10-CM, the first character is alpha; characters 2 and 3 are numeric; characters 4 through 7 are alpha or numeric (Table 2). The increased number of codes and the change in code length, combined with considerably more code granularity, allows for much greater specificity. For example, under ICD-9-CM, there is one code for a patient with a traumatic closed fracture of the shaft of the radius and ulna (813.23). Under ICD-10-CM, there are multiple possibilities, as the fourth character of the code will identify the type of fracture (eg, greenstick or transverse), the fifth and sixth characters the location and condition (right or left side and in some cases whether the fracture was considered displaced or nondisplaced), and the final character if the encounter was initial, subsequent, or sequela. The resulting code might look like this: A52.131A—indicating displaced fracture of neck of right radius, initial encounter for closed fracture. Implementing the Change Given these differences, all provider organizations and health plans will need to engage in significant planning to make EHR and billing system modifications or upgrades. They also will need to provide training and ongoing support to staff. The key for successful migration to ICD-10 is to establish an environment in which new and old technology, along with like and unlike data sets, can co-exist and where information exchange can occur while the re-engineering of existing workflow and software takes place. Each provider organization will need to review all of its processes, systems, and reports and document where ICD-9 codes are currently used. In addition, each organization should conduct a financial impact analysis to determine if the new levels of specificity will change the reimbursements they receive from the government or commercial health plans. To navigate the challenges, the Center for Medicare and Medicaid Services is developing general equivalence mapping (GEM) tools to convert data from ICD-9-CM to ICD-10-CM and vice versa.1 The GEMs will be like dictionaries that will enable users to translate from one code set to the other. The mapping tools can be used to help you calculate reimbursement, format new provider-specific prompts, and update reports or forms. But the GEMs should be used with care for a number of reasons: - There are new concepts in ICD- 10-CM that are not present in ICD-9-CM; - In a few cases, the GEMs may have no matching codes; - There may be multiple ICD-9-CM codes for a single ICD-10-CM code; and - There may be multiple ICD-10-CM codes for a single ICD-9-CM code. Although these tools will aid during the transition period, organizations will still need to work with their EHR and billing-system vendors to ensure that the transition goes smoothly (see “Questions to Ask Your EHR and Billing System Vendors”). They will have to decide how long they will keep ICD-9 codes since the codes are attached to the date of service and not to the date the record or claim was created. And those organizations that do not use EHRs will need to update their charge sheets and make sure their billing system is ready. Finally, no tool will be a substitute for learning the ICD-10 codes. Thus, all health care providers, coders, and support and billing staff will need to be trained. Start Preparing Now Clearly, organizations should be getting ready for this change. A number of steps should be taken well before October 1, 2013: - Create a project team. Assign an executive to spearhead the work and to create awareness of the coming changes among both clinical and financial staff. - Conduct an assessment. List the places where codes are used and stored. - Talk to your software vendors about what the change could mean in terms of your systems. Successful conversion to ICD-10 will depend heavily on when your vendor has the upgrades completed and when they can be installed in your system. - Identify the changes that you need to make in your practice to convert to the ICD-10 code set. For example, your diagnosis coding tools, “super bills,” and public health reporting tools will need to be updated, and you will need to make it clear which code list to use based on the date of service. - Identify staff training needs and complete the necessary training. - Conduct internal testing to make sure you can generate transactions with the ICD-10 codes. - Conduct external testing with your clearinghouses and payers to make sure you can send and receive transactions with the ICD-10 codes. - Conduct a financial assessment. The transition from ICD-9 to ICD-10 presents health care providers with a number of financial opportunities and risks, both during the transition period and over the long term. You should identify how the change could affect your organization in terms of financial performance, availability of working capital, and financial reporting. We’ve handled changes in coding before. After an initial outcry over the conversion to the “new” CPT E/M code system in the early 1990s, we all adapted. In the end, the transition went relatively smoothly for those who took the time to plan and prepare. The move to ICD-10-CM will also be smooth if we start preparing now. MM Patrice Kuppe is director of administrative simplification for Allina Health System. 1. Centers for Medicare and Medicaid Services. ICD-10 Provider Resources. Available at: https://www.cms.gov/ICD10/05a_ProviderResources.asp#TopOfPage. Accessed: March 9, 2011. ICD-10 Summary 15-Minute Webinars *discount for MMA Members!	4	6	0	0	2	0.397866	2	2,211
- Osteotomy, or bone cutting, is a method in which a surgeon takes out a wedge of bone near a injured joint. In an osteotomy, the surgeon cuts the bone and then reorients it. — “Beverly Hills Medical Group, 57 Paseo de Roxas Street, Makati”, beverlyhills.ph - Synonyms and related keywords: varus derotational osteotomy, VDO, coxa vara, shepherd's crook deformity, femur deformity, nonunion, malunion, osteotomy, Ilizarov, internal fixation, femoral anteversion, fibrous dysplasia, developmental dysplasia. — “Femoral Osteotomy”, - An osteotomy is an elective surgical procedure, performed under general anesthesia, in which a bone is cut or There are several deformities that can be corrected by an osteotomy: among them hallux velux, a deformity of the big toe; coxa vera, a deformity of. — “What is Osteotomy?”, - Osteotomy: Definition. An osteotomy is a surgical operation whereby a bone is cut to shorten, lengthen, or change its alignment. It is sometimes performed on a hallux valgus, or to straighten a bone that has healed crookedly following a fracture. — “Osteotomy”, - Orthosports is a professional association of Orthopaedic surgeons in Sydney, Australia specialising in all Knee treatment including Knee Osteotomy at our Sydney Centre. — “Knee \| Osteotomy \| Osteotomy Operations \| Osteotomy”, .au - Overview: Proximal femoral osteotomy is currently commonly used for adults in the treatment of hip fracture nonunions and malunions and in cases of congenital and acquired hip deformities, as in the images below. — “Femoral Osteotomy: eMedicine Clinical Procedures”, - MDGuidelines is the most trusted source of disability guidelines, disability durations, and return to work information on osteotomy. — “Osteotomy - Medical Disability Guidelines”, - Definition of osteotomy in the Medical Dictionary. osteotomy explanation. Information about osteotomy in Free online English dictionary. What is osteotomy? Meaning of osteotomy medical term. What does osteotomy mean?. — “osteotomy - definition of osteotomy in the Medical dictionary”, medical- - a acetabular osteotomy salvage procedure which is indicated in patients without a concentrically reducible hip; distal fragment is displaced medially and upward as osteotomy hinges on the symphysis pubis;. — “Chiari Osteotomy - Wheeless' Textbook of Orthopaedics”, - Osteotomy. Knee Osteotomy. Knee osteotomy is surgery that removes a part of the bone of the joint of either the bottom of the femur (upper leg bone) or Osteotomy redistributes the weight-bearing force on the knee by. — “Osteotomy”, - Osteotomy (bone cutting) is a procedure in which a surgeon removes a wedge of bone near a damaged joint. — “Osteotomy (Tibiall, Femoral, & More): Surgery and Recovery”, - Tibial Osteotomy. Introduction. Knee osteoarthritis often affects only one side of the knee joint. When this occurs, realigning the angle made between the bones of the leg can shift your body weight so that the healthy side of the knee joint takes more of the stress. — “Tibial Osteotomy - Orthogate - Improving orthopedic care”, - There are several joint surgeries that can reduce pain and restore function in the affected joint. Osteotomy is one of the lesser-known joint procedures. Some patients may be candidates for osteotomy rather than a total joint replacement. — “What is Osteotomy? - What You Need to Know About Osteotomy”, - Knee osteotomy is surgery that removes a part of the bone of the joint of either the bottom of the femur (upper leg bone) or the top of the tibia (lower leg bone) to increase the stability of the knee. Osteotomy redistributes the weight-bearing. — “Knee Osteotomy Information on Healthline”, - Usually, the osteotomy is performed first and then, several months later if required, the ligament reconstruction is done. Only in select cases do we perform the osteotomy and knee ligament reconstruction together. — “Cincinnati Sportsmedicine Research and Education Foundation”, - osteotomy n. , pl. , -mies . Surgical division or sectioning of bone. osteotomist os ' teot ' omist Osteotomy is also used as an alternative treatment to total knee replacement in younger and active patients. — “osteotomy: Definition from ”, - The goal of osteotomy is to correct that collapse and thereby reduce the weight on that compartment. Osteotomy should therefore be considered before knee replacement for patients who are young, active, or heavy labourers. — “Knee Pain Info - Osteoarthritis and Osteotomy Surgery”, - Knee osteotomy — Comprehensive overview covers definition, risks, benefits of this alternative to knee replacement. — “Knee osteotomy - ”, - Osteotomy definition, the dividing of a bone, or the excision of part of it. See more. — “Osteotomy \| Define Osteotomy at ”, - A Patient's Guide to Tibial Osteotomy Introduction Knee osteoarthritis often affects only one side of the knee joint. When this occurs, realigning the angle made between the bones of the leg can shift your body weight so that the healthy. — “Tibial Osteotomy \| ”, - An osteotomy is a surgical procedure to cut a bone. The cut bone from the osteotomy can be removed or realigned as part of the surgical procedure. — “Osteotomy - Definition of Osteotomy”, - Osteotomy information including symptoms, causes, diseases, symptoms, treatments, and other medical and health issues. — “Osteotomy - ”, - An osteotomy is a surgical operation whereby a bone is cut to shorten, lengthen, or change its alignment. Osteotomy is one method to relieve pain in arthritis, especially of the hip and knee. — “Osteotomy - Wikipedia, the free encyclopedia”, - Encyclopedia: Osteotomy from Wikipedia. An osteotomy is a surgical operation whereby a bone is cut to shorten, lengthen, or change its alignment. It is sometimes performed to correct a hallux valgus, or to straighten a bone that has healed crookedly following a fracture. — “Osteotomy - Kosmix : Reference, Videos, Images, News”, related images for osteotomy - 11154n jpg - Fluoro before osteotomy png - 11135d jpg - 11154q jpg - 11154b jpg - 11135k jpg - Previous page - 11154a jpg - 11154h jpg - 11154p jpg - Figure 3 Peroperative photographs showing mandibular osteotomy - Previous page - Tibial osteotomy for Blounts disease - ChevronOsteotomy jpg - 11154o jpg - 11135j jpg - 11154c jpg - CLOSE WINDOW This severe vertical fracture line through the femoral neck is a high risk for nonunion with simple pinning fixation - CLOSE WINDOW Osteonecrosis localized to a small area of the weightbearing portion of the femoral head - 11154f jpg - CLOSE WINDOW Medial osteotomy being performed during rhinoplasty - 11154j jpg - 11154m jpg - 12319h jpg - 11135e jpg - Moving the chin bone is the simplest of all the cosmetic facial bone procedures Because the chin is easy to get to through the mouth and there is little in the way to get there cutting and - osteotomy jpg - 1133 0550x0475 jpg - 11135i jpg - 12319k jpg - Fluoro after osteotomy png - CLOSE WINDOW Final image showing a valgus producing osteotomy with improved orientation of the femoral neck fracture Intertrochanteric nonunion - CLOSE WINDOW Follow up radiographs demonstrate a well healed osteotomy with maintenance of the valgus positioning - 11154k jpg - Previous page Operative indications and cases to be wary of the lesser toes - 12319m jpg - Chevron Osteotomy - 11135m jpg - 447 0550x0475 jpg related videos for osteotomy - Metatarsal Osteotomy- Foot Treatment Metatarsal Osteotomy Exicision by MIS Technique Done by Dr.TVRaja (orthopedic & foot Surgeon) for more details visit www.footclinic.in - Calcaneal Osteotomy for TPD - Part 2 This is an osteotomy of the calcaneus for a flatfoot deformity to correct the hindfoot. This cutting of the heel bone allows the back half to be shifted back under the leg instead of being turned out. This is part one of two parts. - Scarf Osteotomy for Bunion Correction, Hallux Valgus Surgery \| Weil Foot & Ankle Institute Scarf osteotomy procedure at Weil4feet - osteotomy of bunions helps in correcting the deformed joint and retain normal joint movement. Please visit our site at www.weil4 - Peri-acetabular osteotomy PAO Marcus Bankes Clip from BBC1's City Hospital 2nd November 2005 - Lengthening over Nail, Gigli Saw osteotomy - Part 2 LON - Part 2, Lengthening over a nail for a case of tibial hemimelia, with a gigli saw osteotomy - Osteotomies around the Knee Osteotomy is a demanding and complex procedure for joint preserving knee surgery. This book is a comprehensive review of the subject. Recommended for experienced orthopedic surgeons who want a complete guide to osteotomies around the knee. Thieme Medical Publishers. - Osteotomy Description of a simple osteotomy below the knee joint - Post-Op Jaw Surgery Video #1 - Upper Jaw (Lefort One Osteotomy) & Genioplasty Day 12 Post Operation for jaw surgery and genioplasty. Visit my braces & jaw Surgery blog at perfectgrill.blogspot to see more of my daily diary of the recovery process from Day 1! Lots of photos!!! - Triple Innominate Osteotomy for DDH This video demonstrates Dr. Dennis Wenger's method for performing the triple innominate osteotomy for childhood hip dysplasia and other conditions such as Perthes disease. If you desire further information on surgical treatment of hip dysplasia or Perthes disease, please visit /ortho - Live Webcast of Osteotomy, Segment 3 - SMDC Health System Duluth Clinic pediatric orthopaedic surgeon David Gordon, MD, performs an osteotomy. Duluth Clinic orthopaedic surgeons Laura Trombino, MD, and Thomas Patnoe, MD, moderate. During the procedure, a wedge of bone is removed from the proximal femur and re-approximated to the hip using a fixation device. - Live Webcast of Osteotomy, Segment 5 - SMDC Health System Duluth Clinic pediatric orthopaedic surgeon David Gordon, MD, performs an osteotomy. Duluth Clinic orthopaedic surgeons Laura Trombino, MD, and Thomas Patnoe, MD, moderate. The team discusses various situations in which an osteotomy is appropriate. - HIGH TIBIAL OSTEOTOMY FOR OA KNEE - Nasal Hump Reduction with Powered Micro Saw Osteotomy Nasal Hump Reduction with Powered Micro Saw Osteotomy Op. Dr. Yakup Avşar - Osteotomia Le Fort I - Le Fort I Osteotomy step by step - Mikai PTA (Progressive Tibial Alignment) Osteotomy Live Surgery Mikai's PTA (Progressive Tibial Alignment) System for High Tibial Osteotomy. Come visit us at www.mikai.it. - Cranial Osteotomy - Gerontophile Sick Sodomy - Dr. Patrick DeHeer, DPM - 3rd Metatarsal Osteotomy This is a Weil osteotomy of the 3rd metatarsal with screw fixation for a plantarflexed, painful metatarsal joint of the right foot. The patient had prior foot surgery on the 1st and 2nd metatarsals and had a relative plantarflexed 3rd metatarsal because of this. Conservative care did not ease pain, therefore surgery was elected. A 3.0 cannulated screw from Synthes was used for fixation. - Procedure Cole Osteotomy (NO SOUND) Project Lead: Nicholas Giovinco Illustrated here is a Cole osteotomy, whereby a dorsiflexory wedge is removed from the midfoot to eliminate a high arched Cavus foot type. - Calcaneal Osteotomy for TPD - Part 1 This is an osteotomy of the calcaneus for a flatfoot deformity to correct the hindfoot. This cutting of the heel bone allows the back half to be shifted back under the leg instead of being turned out. This is part one of two parts. - Opening Base Wedge Osteotomy opening base wedge osteotomy, bunion surgery, foot surgery - PreopOnline part 4: Osteotomy THE MARKET S MOST PRECISE PLANNING TOOL Sectra Preop Online is based on proven surgical principles—with the added bonus of automatic calibration. EASY TO LEARN, EVEN EASIER TO USE Developed in close co-operation with our customers, Sectra Preop Online offers an intuitive user experience.¬¬¬¬ To make it even easier to get started, you can follow our webinar training sessions online. INSTANT ACCESS TO 50000 PROSTHESIS TEMPLATES FROM LEADING MANUFACTURERS With Sectra Preop Online, you have fingertip access to the worlds largest database of prosthesis templates. On those occasions when you need a special template, let us know and well simply add it to the database. ANY PACS, ANYWHERE Sectra Preop Online is PACS-independent. Which means it works seamlessly with your current system—regardless of vendor. Whats more, as this tool is web-based, you can access it wherever you happen to be working. FOR YOUR EYES ONLY All traffic between your workstation and the Sectra server is encrypted. This way, patient integrity is ensured at all times. A RISK-FREE INVESTMENT To get you started as soon as possible, we provide a start-up kit including a complete solution for efficient use of calibration markers in all digital images. You pay a modest fee for this kit—after that you only pay for each templated case. LEADING ORTHOPAEDIC SURGEONS AND CLINICS USE SECTRA With more than 500 installations worldwide, Sectra is at the forefront of digital pre-operative planning. Many leading practitioners ... - Live Webcast: Pediatric Osteotomy Surgery St. Mary's Medical Center in Duluth, MN, plans to broadcast a pediatric orthopaedic surgery, live on the Internet. The webcast is slated for Monday, April 30, 2007, at 12:00 pm CDT on OR- The public will be able to watch doctors perform a pediatric osteotomy surgery, which involves reshaping a child's leg or arm bones for improved form and function. - Weil Decompression Osteotomy for Hallux Rigidus \| Weil Foot & Ankle Institute Weil Decompression Osteotomy for Hallux Rigidus. The degnerative toe arthritis, Hallux Rigidus that limits bone movement can be treated with decompression osteotomy www.weil4 - Opening Base Wedge Osteotomy for Hallux Valgus Charles Morelli DPM This video demonstrates a technique for the correction of a bunion deformity (aka Hallux Valgus). This technique utilizes a medial approach as well as the Arthrex line of hardware, plates and screws to attain rigid internal fixation. - Live Webcast of Osteotomy, Segment 1 - SMDC Health System Duluth Clinic pediatric orthopaedic surgeon David Gordon, MD, performs an osteotomy of the hip. Duluth Clinic orthopaedic surgeons Laura Trombino, MD, and Thomas Patnoe, MD, moderate. During the procedure, a wedge of bone is removed from the proximal femur and re-approximated to the hip using a fixation device. - Osteotomy for Malunion Buttress Pin™ and Radial Pin Plate™ Fixation of Osteotomy for Malunion of the Distal Radius - Lengthening over Nail, Gigli Saw osteotomy - Part 3 LON Part 3 - Lengthening over a nail for a case of tibial hemimelia, with a gigli saw osteotomy - TraumaCad - High Tibial Osteotomy This measurement tool is used to measure the correction angle of a High Tibial Osteotomy (HTO), which is the angle between a line that is drawn from the center of the femur to the 62% coordinate of the knee, and a line from the 62% coordinate to the center of the tibiotalar joint.. - LEFORT I OSTEOTOMY FOR CORRECTION OF PSEUDO-PROGNATHISM LEFORT I OSTEOTOMY FOR CORRECTION OF PSEUDO-PROGNATHISM - Department of Defense 1976 - PIN 65136 - A BEFORE AND AFTER LOOK AT A YOUNG WOMAN WHOSE LOWER JAW PROJECTS ACUTELY BEYOND HER UPPER. - Live Webcast of Osteotomy, Segment 4 - SMDC Health System Duluth Clinic pediatric orthopaedic surgeon David Gordon, MD, performs an osteotomy. Duluth Clinic orthopaedic surgeons Laura Trombino, MD, and Thomas Patnoe, MD, moderate. During the procedure, a wedge of bone is removed from the proximal femur and re-approximated to the hip using a fixation device. - osteotomy of the first met OSTEOTOMIA DEL HALLUX VALGUS - Phil Osteotomy Surgery Part 1 - Pre-surgery Phil Osteotomy pre-surgery - Weil Metatarsal Osteotomy \| Weil Foot & Ankle Institute Weil Metatarsal Osteotomy. For more information, please visit our site at www.weil4 - Tibial Osteotomy and Medial Meniscus Allograft Replacement - Patient Experience Rory C. is a 62 year old avid runner who underwent a tibial osteotomy and medial meniscus allograft transplantation three years ago at The Stone Clinic. He is now running an hour per day and recently completed a 500 mile bicycle ride from San Francisco to San Diego. Visit for more information. - Fulkerson Osteotomy & Proximal Realignment Procedure - Dr. Tony Jabbour Successful Fulkerson Osteotomy & Proximal Realignment Procedure for patellar instability by Dr. Tony Jabbour. Check out for more info - Pediatric Surgery: Bilateral Pelvic Osteotomy, Bladder Extrophy Closure, and Rectal Prolapse Repair In this video from the Massachusetts General Hospital (MGH), surgeons Rafael Pieretti and Brian Grottkau perform a bladder extrophy closure and a bilateral pelvic osteotomy on an infant suffering from bladder extrophy, rectal prolapse and diastasis of the symphysis pubis. - Wrist Surgery Ulnar Shortening Osteotomy Dr. Jack Choueka performs an ulnar shortening for TFCC tear with ulna positive variance using Trimed plate - Lengthening over Nail, Gigli Saw osteotomy - Part 1 LON Part 1 - Lengthening over a nail for a case of tibial hemimelia, with a gigli saw osteotomy - Live Webcast of Osteotomy, Segment 2 - SMDC Health System Duluth Clinic pediatric orthopaedic surgeon David Gordon, MD, performs an osteotomy. Duluth Clinic orthopaedic surgeons Laura Trombino, MD, and Thomas Patnoe, MD, moderate. The team discusses situations in which hip osteotomies are appropriate, particularly in children. - Segmental Maxillary Osteotomy This tape demonstrates the surgical procedure for moving two central and one lateral maxillary incisor forward into proper occlusion. Orig. air date: FEB 3 76 twitter about osteotomy Blogs & Forum blogs and forums about osteotomy “For younger, more active patients, a procedure known as knee osteotomy is sometimes used to shift the patient's weight to the non Anti-inflammatory drugs, joint fluid therapy, and knee osteotomy are all options that patients should consider when attempting to reduce knee” — rooster juice " Medical Tourism Blog – Formosa Medical Travel, “Tibial plateau leveling osteotomy (TPLO) is a very commonly performed surgery to treat dog cruciate ligament injury. Cruciate ligament tears in dogs are by far the most common orthopedic injury that veterinarians see. There are many different” — TPLO – Tibial Plateau Leveling Osteotomy for the Treatment of, “The Clamshell Osteotomy: A New Technique to Correct Complex Diaphyseal Malunions. The Journal of Bone and Joint Surgery (American). 2009;91:314-324” — CLAMSHELL OSTEOTOMY \| , “There are several surgical options for hip dysplasia, depending on the size and age of the dog. In young dogs, with hips still in the development stage, a” — Triple Pelvic Osteotomy (TPO) \| Largest Pet Health and, my-pet- “The Weil Osteotomy. Filed under: Podiatry Issues — Tags: weil osteotomy — admin @ 3:55 am. The Weil Osteotomy is a commonly used a to be a large complication rate for the Weil Osteotomy and there is quite a bit of controversy surrounding” “Discuss your foot condition with certified foot and ankle consultants at the Foot Talk Forums of ! Nice to find a forum like this. The procedure is recommended for Hallux rigidus. (cheilectomy with first metatarsal shortening osteotomy and plantar flexor osteotomy of 1st MTP joint)As it” — recovery time first metatarsal shortening osteotomy - Foot, “INEC rolls out new election dates. How Lagos banker, Awosika, was Consensus: Many Lagos security trust fund rises to N6.2bn. Falcons get TomTomâ€ ̃s $1,” — The Punch - Blog:: Comments, “Canadian Orthopaedic Association - Association for orthopaedic surgeons and allied health professionals in Canada” — Forum - OA Knee - Opening Wedge High Tibial Osteotomy \| Issue, coa- “Supercoder Forum " Coding Specialties " Orthopedic Coding " oblique dorsal osteotomy? What CPT code should be used for an oblique dorsal osteotomy AKA Ludloff procedure, I've heard CPT 28296 should be used but then” — oblique dorsal osteotomy? " Supercoder Forum,	2	14	4	0	0	0.284804	4	5,141
Atherosclerosis Classification and external resources The progression of atherosclerosis (size exaggerated; see text) ICD-10 I70 ICD-9 440, 414.0 DiseasesDB 1039 MedlinePlus 000171 eMedicine med/182 MeSH D050197 Atherosclerosis (also known as arteriosclerotic vascular disease or ASVD) is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol. It is a syndrome affecting arterial blood vessels, a chronic inflammatory response in the walls of arteries, caused largely by the accumulation of macrophage white blood cells and promoted by low-density lipoproteins (plasma proteins that carry cholesterol and triglycerides) without adequate removal of fats and cholesterol from the macrophages by functional high density lipoproteins (HDL), (see apoA-1 Milano). It is commonly referred to as a hardening or furring of the arteries. It is caused by the formation of multiple plaques within the arteries. The atheromatous plaque is divided into three distinct components: - The atheroma ("lump of gruel," from ἀθήρα, athera, gruel in Greek), which is the nodular accumulation of a soft, flaky, yellowish material at the center of large plaques, composed of macrophages nearest the lumen of the artery - Underlying areas of cholesterol crystals - Calcification at the outer base of older/more advanced lesions. The following terms are similar, yet distinct, in both spelling and meaning, and can be easily confused: arteriosclerosis, arteriolosclerosis, and atherosclerosis. Arteriosclerosis is a general term describing any hardening (and loss of elasticity) of medium or large arteries (from the Greek arteria, meaning artery, and sclerosis, meaning hardening); arteriolosclerosis is any hardening (and loss of elasticity) of arterioles (small arteries); atherosclerosis is a hardening of an artery specifically due to an atheromatous plaque. The term atherogenic is used for substances or processes that cause atherosclerosis. Atherosclerosis is a chronic disease that remains asymptomatic for decades. Atherosclerotic lesions, or atherosclerotic plaques are separated into two broad categories: Stable and unstable (also called vulnerable). The pathobiology of atherosclerotic lesions is very complicated but generally, stable atherosclerotic plaques, which tend to be asymptomatic, are rich in extracellular matrix and smooth muscle cells, while, unstable plaques are rich in macrophages and foam cells and the extracellular matrix separating the lesion from the arterial lumen (also known as the fibrous cap) is usually weak and prone to rupture. Ruptures of the fibrous cap expose thrombogenic material, such as collagen to the circulation and eventually induce thrombus formation in the lumen. Upon formation, intraluminal thrombi can occlude arteries outright (i.e. coronary occlusion), but more often they detach, move into the circulation and eventually occlude smaller downstream branches causing thromboembolism (i.e. Stroke is often caused by thrombus formation in the carotid arteries). Apart from thromboembolism, chronically expanding atherosclerotic lesions can cause complete closure of the lumen. Interestingly, chronically expanding lesions are often asymptomatic until lumen stenosis is so severe that blood supply to downstream tissue(s) is insufficient resulting in ischemia. These complications of advanced atherosclerosis are chronic, slowly progressive and cumulative. Most commonly, soft plaque suddenly ruptures (see vulnerable plaque), causing the formation of a thrombus that will rapidly slow or stop blood flow, leading to death of the tissues fed by the artery in approximately 5 minutes. This catastrophic event is called an infarction. One of the most common recognized scenarios is called coronary thrombosis of a coronary artery, causing myocardial infarction (a heart attack). The same process in an artery to the brain is commonly called stroke. Another common scenario in very advanced disease is claudication from insufficient blood supply to the legs, typically caused by a combination of both stenosis and aneurysmal segments narrowed with clots. Atherosclerosis can occur body-wide, in the arteries to the brain, intestines, kidneys, legs, etc. with many infarctions involving only very small amounts of tissue. These are termed "clinically silent" because the person having the infarction does not notice the problem and does not seek medical help, or when they do, physicians do not recognize what has happened. - 1 Signs and symptoms - 2 Causes - 3 Pathophysiology - 4 Diagnosis - 5 Treatment - 6 Prognosis - 7 Controversy - 8 Research - 9 See also - 10 Footnotes - 11 External links Signs and symptoms Atherosclerosis typically begins in early adolescence, and is usually found in most major arteries, yet is asymptomatic and not detected by most diagnostic methods during life. Atheroma in arm, or more often in leg arteries, which produces decreased blood flow is called peripheral artery occlusive disease (PAOD). According to United States data for the year 2004, for about 65% of men and 47% of women, the first symptom of atherosclerotic cardiovascular disease is heart attack or sudden cardiac death (death within one hour of onset of the symptom). Most artery flow disrupting events occur at locations with less than 50% lumen narrowing (~20% stenosis is average). The illustration above, like most illustrations of arterial disease, overemphasizes lumen narrowing, as opposed to compensatory external diameter enlargement (at least within smaller arteries, e.g., heart arteries) typical of the atherosclerosis process as it progresses (see Glagov or the ASTEROID trial). The relative geometry error within the illustration is common to many older illustrations, an error slowly being more commonly recognized within the last decade. Cardiac stress testing, traditionally the most commonly performed non-invasive testing method for blood flow limitations, in general, detects only lumen narrowing of ~75% or greater, although some physicians claim that nuclear stress methods can detect as little as 50%. The main cause of atherosclerosis is yet unknown, but is hypothesized to fundamentally be initiated by inflammatory processes in the cell wall in response to retained low-density lipoprotein (LDL) molecules. Once inside the vessel wall, LDL molecules become susceptible to oxidation by free radicals, and become toxic to the cells. The damage caused by the oxidized LDL molecules triggers a cascade of immune responses which over time can produce an atheroma. The LDL molecule is globular shaped with a hollow core to carry cholesterol throughout the body. The body's immune system responds to the damage to the artery wall caused by oxidized LDL by sending specialized white blood cells (macrophages and T-lymphocytes) to absorb the oxidized-LDL forming specialized foam cells. These white blood cells are not able to process the oxidized-LDL, and ultimately grow then rupture, depositing a greater amount of oxidized cholesterol into the artery wall. This triggers more white blood cells, continuing the cycle. Eventually, the artery becomes inflamed. The cholesterol plaque causes the muscle cells to enlarge and form a hard cover over the affected area. This hard cover is what causes a narrowing of the artery, reduces the blood flow and increases blood pressure. Some researchers believe that atherosclerosis may be caused by an infection of the vascular smooth muscle cells; chickens, for example, develop atherosclerosis when infected with the Marek's disease herpesvirus. Herpesvirus infection of arterial smooth muscle cells has been shown to cause cholesteryl ester (CE) accumulation. Cholesteryl ester accumulation is associated with atherosclerosis. Linus Pauling's and Matthias Rath's extended theory states that deaths from scurvy in humans during the ice age, when vitamin C (an antioxidant) was scarce, selected for individuals who could repair arteries with a layer of cholesterol provided by lipoprotein(a), a lipoprotein found in vitamin C-deficient species (higher primates and guinea pigs). Pauling and Rath hypothesized that, although eventually harmful, lipoprotein deposition on artery walls was beneficial to the human species and a "surrogate for ascorbate" in that it kept individuals alive until access to vitamin C allowed arterial damage to be repaired. Atherosclerosis is thus a vitamin-C-deficiency disease. Various anatomic, physiological and behavioral risk factors for atherosclerosis are known. These can be divided into various categories: congenital vs acquired, modifiable or not, classical or non-classical. The points labelled '+' in the following list form the core components of metabolic syndrome. - Diabetes or Impaired glucose tolerance (IGT) + - Dyslipoproteinemia (unhealthy patterns of serum proteins carrying fats & cholesterol): + - High serum concentration of low-density lipoprotein (LDL, "bad if elevated concentrations and small"), and / or very low density lipoprotein (VLDL) particles, i.e., "lipoprotein subclass analysis" - Low serum concentration of functioning high density lipoprotein (HDL "protective if large and high enough" particles), i.e., "lipoprotein subclass analysis" - An LDL:HDL ratio greater than 3:1 - Tobacco smoking, increases risk by 200% after several pack years - Having hypertension +, on its own increasing risk by 60% - Elevated serum C-reactive protein concentrations - Vitamin B6 deficiency - Advanced age - Male sex - Having close relatives who have had some complication of atherosclerosis (e.g. coronary heart disease or stroke) - Genetic abnormalities, e.g. familial hypercholesterolemia - Lesser or uncertain The following factors are of relatively lesser importance, are uncertain or unquantified: - Obesity (in particular central obesity, also referred to as abdominal or male-type obesity) + - A sedentary lifestyle - Postmenopausal estrogen deficiency - High intake of saturated fat (may raise total and LDL cholesterol) - Intake of trans fat (may raise total and LDL cholesterol while lowering HDL cholesterol) - High carbohydrate intake - Elevated serum levels of triglycerides + - Elevated serum levels of homocysteine - Elevated serum levels of uric acid (also responsible for gout) - Elevated serum fibrinogen concentrations - Elevated serum lipoprotein(a) concentrations - Chronic systemic inflammation as reflected by upper normal WBC concentrations, elevated hs-CRP and many other blood chemistry markers, most only research level at present, not clinically done. - Stress or symptoms of clinical depression - Hyperthyroidism (an over-active thyroid) - Elevated serum insulin levels + - Short sleep duration - Chlamydia pneumoniae infection The relation between dietary fat and atherosclerosis is a contentious field. The USDA, in its food pyramid, promotes a low-fat diet, based largely on its view that fat in the diet is atherogenic. The American Heart Association, the American Diabetes Association and the National Cholesterol Education Program make similar recommendations. In contrast, Prof Walter Willett (Harvard School of Public Health, PI of the second Nurses' Health Study) recommends much higher levels, especially of monounsaturated and polyunsaturated fat. Writing in Science, Gary Taubes detailed that political considerations played into the recommendations of government bodies. These differing views reach a consensus, though, against consumption of trans fats. The role of dietary oxidized fats / lipid peroxidation (rancid fats) in humans is not clear. Laboratory animals fed rancid fats develop atherosclerosis. Rats fed DHA-containing oils experienced marked disruptions to their antioxidant systems, as well as accumulated significant amounts of phospholipid hydroperoxide in their blood, livers and kidneys. In another study, rabbits fed atherogenic diets containing various oils were found to undergo the greatest amount of oxidative susceptibility of LDL via polyunsaturated oils. In a study involving rabbits fed heated soybean oil, "grossly induced atherosclerosis and marked liver damage were histologically and clinically demonstrated." Rancid fats and oils taste very bad even in small amounts; people avoid eating them. It is very difficult to measure or estimate the actual human consumption of these substances. In addition, the majority of oils consumed in the United States are refined, bleached, deodorized and degummed by manufacturers. The resultant oils are colorless, odorless, tasteless and have a longer shelf life than their unrefined counterparts. This extensive processing serves to make peroxidated, rancid oils much more elusive to detection via the various human senses than the unprocessed alternatives. It is necessary to note that highly unsaturated omega-3 rich oil such as fish oil are being sold in pill form so that the taste of oxidized or rancid fat is not apparent. The health food industry dietary supplement are self regulated by the manufacture and outside of FDA regulations. To properly protect unsaturated fats from oxidation, it is best to keep them cool and in oxygen free environments. Atherogenesis is the developmental process of atheromatous plaques. It is characterized by a remodeling of arteries leading to subendothelial accumulation of fatty substances called plaques. The build up of an atheromatous plaque is a slow process, developed over a period of several years through a complex series of cellular events occurring within the arterial wall, and in response to a variety of local vascular circulating factors. One recent theory suggests that, for unknown reasons, leukocytes, such as monocytes or basophils, begin to attack the endothelium of the artery lumen in cardiac muscle. The ensuing inflammation leads to formation of atheromatous plaques in the arterial tunica intima, a region of the vessel wall located between the endothelium and the tunica media. The bulk of these lesions is made of excess fat, collagen, and elastin. At first, as the plaques grow, only wall thickening occurs without any narrowing. Stenosis is a late event, which may never occur and is often the result of repeated plaque rupture and healing responses, not just the atherosclerotic process by itself. Early atherogenesis is characterized by the adherence of blood circulating monocytes to the vascular bed lining, the endothelium, followed by their migration to the sub-endothelial space, and further activation into monocyte-derived macrophages. The primary documented driver of this process is oxidized Lipoprotein particles within the wall, beneath the endothelial cells, though upper normal or elevated concentrations of blood glucose also plays a major role and not all factors are fully understood. Fatty streaks may appear and disappear. Low Density Lipoprotein particles in blood plasma, when they invade the endothelium and become oxidized creates a risk for cardiovascular disease. A complex set of biochemical reactions regulates the oxidation of LDL, chiefly stimulated by presence of enzymes, e.g. Lp-LpA2 and free radicals in the endothelium or blood vessel lining. The initial damage to the blood vessel wall results in an inflammatory response. Monocytes (a type of white blood cell) enter the artery wall from the bloodstream, with platelets adhering to the area of insult. This may be promoted by redox signaling induction of factors such as VCAM-1, which recruit circulating monocytes. The monocytes differentiate into macrophages, which ingest oxidized LDL, slowly turning into large "foam cells" – so-described because of their changed appearance resulting from the numerous internal cytoplasmic vesicles and resulting high lipid content. Under the microscope, the lesion now appears as a fatty streak. Foam cells eventually die, and further propagate the inflammatory process. There is also smooth muscle proliferation and migration from tunica media to intima responding to cytokines secreted by damaged endothelial cells. This would cause the formation of a fibrous capsule covering the fatty streak. Calcification and lipids Intracellular microcalcifications form within vascular smooth muscle cells of the surrounding muscular layer, specifically in the muscle cells adjacent to the atheromas. In time, as cells die, this leads to extracellular calcium deposits between the muscular wall and outer portion of the atheromatous plaques. A similar form of an intramural calcification, presenting the picture of an early phase of arteriosclerosis, appears to be induced by a number of drugs that have an antiproliferative mechanism of action (Rainer Liedtke 2008). Cholesterol is delivered into the vessel wall by cholesterol-containing low-density lipoprotein (LDL) particles. To attract and stimulate macrophages, the cholesterol must be released from the LDL particles and oxidized, a key step in the ongoing inflammatory process. The process is worsened if there is insufficient high-density lipoprotein (HDL), the lipoprotein particle that removes cholesterol from tissues and carries it back to the liver. The foam cells and platelets encourage the migration and proliferation of smooth muscle cells, which in turn ingest lipids, become replaced by collagen and transform into foam cells themselves. A protective fibrous cap normally forms between the fatty deposits and the artery lining (the intima). These capped fatty deposits (now called 'atheromas') produce enzymes that cause the artery to enlarge over time. As long as the artery enlarges sufficiently to compensate for the extra thickness of the atheroma, then no narrowing ("stenosis") of the opening ("lumen") occurs. The artery becomes expanded with an egg-shaped cross-section, still with a circular opening. If the enlargement is beyond proportion to the atheroma thickness, then an aneurysm is created. Although arteries are not typically studied microscopically, two plaque types can be distinguished: - The fibro-lipid (fibro-fatty) plaque is characterized by an accumulation of lipid-laden cells underneath the intima of the arteries, typically without narrowing the lumen due to compensatory expansion of the bounding muscular layer of the artery wall. Beneath the endothelium there is a "fibrous cap" covering the atheromatous "core" of the plaque. The core consists of lipid-laden cells (macrophages and smooth muscle cells) with elevated tissue cholesterol and cholesterol ester content, fibrin, proteoglycans, collagen, elastin, and cellular debris. In advanced plaques, the central core of the plaque usually contains extracellular cholesterol deposits (released from dead cells), which form areas of cholesterol crystals with empty, needle-like clefts. At the periphery of the plaque are younger "foamy" cells and capillaries. These plaques usually produce the most damage to the individual when they rupture. - The fibrous plaque is also localized under the intima, within the wall of the artery resulting in thickening and expansion of the wall and, sometimes, spotty localized narrowing of the lumen with some atrophy of the muscular layer. The fibrous plaque contains collagen fibers (eosinophilic), precipitates of calcium (hematoxylinophilic) and, rarely, lipid-laden cells. In effect, the muscular portion of the artery wall forms small aneurysms just large enough to hold the atheroma that are present. The muscular portion of artery walls usually remain strong, even after they have remodeled to compensate for the atheromatous plaques. However, atheromas within the vessel wall are soft and fragile with little elasticity. Arteries constantly expand and contract with each heartbeat, i.e., the pulse. In addition, the calcification deposits between the outer portion of the atheroma and the muscular wall, as they progress, lead to a loss of elasticity and stiffening of the artery as a whole. The calcification deposits, after they have become sufficiently advanced, are partially visible on coronary artery computed tomography or electron beam tomography (EBT) as rings of increased radiographic density, forming halos around the outer edges of the atheromatous plaques, within the artery wall. On CT, >130 units on the Hounsfield scale (some argue for 90 units) has been the radiographic density usually accepted as clearly representing tissue calcification within arteries. These deposits demonstrate unequivocal evidence of the disease, relatively advanced, even though the lumen of the artery is often still normal by angiographic or intravascular ultrasound. In days gone by the lateral chest x-ray (demonstrating greater opacity in the aortic arch and descending aorta than the thoracic spine) gave an indication to the degree of calcified plaque burden a patient had. This has been known as Piper's sign and can often be seen in elderly persons particularly those with concomitant osteoporosis. Rupture and stenosis Although the disease process tends to be slowly progressive over decades, it usually remains asymptomatic until an atheroma ulcerates, which leads to immediate blood clotting at the site of atheroma ulcer. This triggers a cascade of events that leads to clot enlargement, which may quickly obstruct the flow of blood. A complete blockage leads to ischemia of the myocardial (heart) muscle and damage. This process is the myocardial infarction or "heart attack". If the heart attack is not fatal, fibrous organization of the clot within the lumen ensues, covering the rupture but also producing stenosis or closure of the lumen, or over time and after repeated ruptures, resulting in a persistent, usually localized stenosis or blockage of the artery lumen. Stenoses can be slowly progressive, whereas plaque ulceration is a sudden event that occurs specifically in atheromas with thinner/weaker fibrous caps that have become "unstable". Repeated plaque ruptures, ones not resulting in total lumen closure, combined with the clot patch over the rupture and healing response to stabilize the clot, is the process that produces most stenoses over time. The stenotic areas tend to become more stable, despite increased flow velocities at these narrowings. Most major blood-flow-stopping events occur at large plaques, which, prior to their rupture, produced very little if any stenosis. From clinical trials, 20% is the average stenosis at plaques that subsequently rupture with resulting complete artery closure. Most severe clinical events do not occur at plaques that produce high-grade stenosis. From clinical trials, only 14% of heart attacks occur from artery closure at plaques producing a 75% or greater stenosis prior to the vessel closing. If the fibrous cap separating a soft atheroma from the bloodstream within the artery ruptures, tissue fragments are exposed and released. These tissue fragments are very clot-promoting, containing collagen and tissue factor; they activate platelets and activate the system of coagulation. The result is the formation of a thrombus (blood clot) overlying the atheroma, which obstructs blood flow acutely. With the obstruction of blood flow, downstream tissues are starved of oxygen and nutrients. If this is the myocardium (heart muscle), angina (cardiac chest pain) or myocardial infarction (heart attack) develops. Areas of severe narrowing, stenosis, detectable by angiography, and to a lesser extent "stress testing" have long been the focus of human diagnostic techniques for cardiovascular disease, in general. However, these methods focus on detecting only severe narrowing, not the underlying atherosclerosis disease. As demonstrated by human clinical studies, most severe events occur in locations with heavy plaque, yet little or no lumen narrowing present before debilitating events suddenly occur. Plaque rupture can lead to artery lumen occlusion within seconds to minutes, and potential permanent debility and sometimes sudden death. Plaques that have ruptured are called complicated plaques. The extracellular matrix of the lesion breaks, usually at the shoulder of the fibrous cap that separates the lesion from the arterial lumen, exposing thrombogenic material, mainly collagen, and eventually causing thrombus formation. This thrombus will eventually grow and travel downstream until eventually occluding a narrow artery. Once the area is blocked, blood and oxygen will not be able to supply the vessels and will cause death of cells and lead to necrosis and poisoning. Serious complicated plaques can cause death of organ tissues, causing serious complications to that organ system. Greater than 75% lumen stenosis used to be considered by cardiologists as the hallmark of clinically significant disease because it is typically only at this severity of narrowing of the larger heart arteries that recurring episodes of angina and detectable abnormalities by stress testing methods are seen. However, clinical trials have shown that only about 14% of clinically debilitating events occur at locations with this, or greater severity of stenosis. The majority of events occur due to atheroma plaque rupture at areas without narrowing sufficient enough to produce any angina or stress test abnormalities. Thus, since the later-1990s, greater attention is being focused on the "vulnerable plaque." Though any artery in the body can be involved, usually only severe narrowing or obstruction of some arteries, those that supply more critically important organs are recognized. Obstruction of arteries supplying the heart muscle result in a heart attack. Obstruction of arteries supplying the brain result in a stroke. These events are life-changing, and often result in irreversible loss of function because lost heart muscle and brain cells do not grow back to any significant extent, typically less than 2%. Over the last couple of decades, methods other than angiography and stress-testing have been increasingly developed as ways to better detect atherosclerotic disease before it becomes symptomatic. These have included both (a) anatomic detection methods and (b) physiologic measurement methods. The example of the metabolic syndrome combines both anatomic (abdominal girth) and physiologic (blood pressure, elevated blood glucose) methods. Advantages of these two approaches: The anatomic methods directly measure some aspect of the actual atherosclerotic disease process itself, thus offer potential for earlier detection, including before symptoms start, disease staging and tracking of disease progression. The physiologic methods are often less expensive and safer and changing them for the better may slow disease progression, in some cases with marked improvement. Disadvantages of these two approaches: The anatomic methods are generally more expensive and several are invasive, such as IVUS. The physiologic methods do not quantify the current state of the disease or directly track progression. For both, clinicians and third party payers have been slow to accept the usefulness of these newer approaches. If atherosclerosis leads to symptoms, some symptoms such as angina pectoris can be treated. Non-pharmaceutical means are usually the first method of treatment, such as cessation of smoking and practicing regular exercise. If these methods do not work, medicines are usually the next step in treating cardiovascular diseases, and, with improvements, have increasingly become the most effective method over the long term. Most medicines for atherosclerosis are patented, allowing manufacturers to enjoy higher prices than non-patented medicines; and they may cause unwanted side-effects. In general, the group of medications referred to as statins has been the most popular and are widely prescribed for treating atherosclerosis. They have relatively few short-term or longer-term undesirable side-effects, and several clinical trials comparing statin treatment with placebo have fairly consistently shown strong effects in reducing atherosclerotic disease 'events' and generally ~25% comparative mortality reduction, although one study design, ALLHAT, was less strongly favorable. The newest statin, rosuvastatin, has been the first to demonstrate regression of atherosclerotic plaque within the coronary arteries by IVUS (intravascular ultrasound evaluation). The study was set up to demonstrate effect primarily on atherosclerosis volume within a 2 year time-frame in people with active/symptomatic disease (angina frequency also declined markedly) but not global clinical outcomes, which was expected to require longer trial time periods; these longer trials remain in progress. However, for most people, changing their physiologic behaviors[clarification needed], from the usual high risk to greatly reduced risk, requires a combination of several compounds, taken on a daily basis and indefinitely. More and more human treatment trials have been done and are ongoing that demonstrate improved outcome for those people using more-complex and effective treatment regimens that change physiologic behaviour patterns to more closely resemble those that humans exhibit in childhood at a time before fatty streaks begin forming. The success of statin drugs in clinical trials is based on some reductions in mortality rates, however by trial design biased toward men and middle-age, the data is as, as yet, less strongly clear for women and people over the age of 70. For example, in the Scandinavian Simvastatin Survival Study (4S), the first large placebo-controlled, randomized clinical trial of a statin in people with advanced disease who had already suffered a heart attack, the overall mortality rate reduction for those taking the statin, vs. placebo, was 30%. For the subgroup of people in the trial who had Diabetes Mellitus, the mortality rate reduction between statin and placebo was 54%. 4S was a 5.4-year trial that started in 1989 and was published in 1995 after completion. There were three more dead women at trial's end on statin than in the group on placebo; whether this was due to chance or some relation to the statin remains unclear. The ASTEROID trial has been the first to show actual disease volume regression (see page 8 of the paper, which shows cross-sectional areas of the total heart artery wall at start and 2 years of rosuvastatin 40 mg/day treatment); however, its design was not able to "prove" the mortality reduction issue since it did not include a placebo group: the individuals offered treatment within the trial had advanced disease, and treatment with placebo was judged to be unethical. Primary and secondary prevention Combinations of statins, niacin, intestinal cholesterol absorption-inhibiting supplements (ezetimibe and others, and to a much lesser extent fibrates) have been the most successful in changing common but sub-optimal lipoprotein patterns and group outcomes. In the many secondary prevention and several primary prevention trials, several classes of lipoprotein-expression-altering (less correctly termed "cholesterol-lowering") agents have consistently reduced not only heart attack, stroke and hospitalization but also all-cause mortality rates. The first of the large secondary prevention comparative statin/placebo treatment trials was the Scandinavian Simvastatin Survival Study (4S) with over fifteen more studies extending through to the more recent ASTEROID trial published in 2006. The first primary prevention comparative treatment trial was AFCAPS/TexCAPS with multiple later comparative statin/placebo treatment trials including EXCEL, ASCOT and SPARCL. While the statin trials have all been clearly favorable for improved human outcomes, only ASTEROID showed evidence of atherosclerotic regression (slight). Both human and animal trials that showed evidence of disease regression used more aggressive combination agent treatment strategies, which nearly always included niacin. Diet and dietary supplements Niacin (vitamin B3), in pharmacologic doses, (generally 1,000 to 3,000 mg/day, but starting with much lower doses increased over several weeks, to avoid side-effects) tends to improve (a) HDL levels, size and function, (b) shift LDL particle distribution to larger particle size and (c) lower lipoprotein(a), an atherosclerosis promoting genetic variant of LDL. Additionally, individual responses to daily niacin, while mostly evident after a month at effective doses, tends to continue to slowly improve further over time. (However, careful patient understanding of how to achieve this without nuisance symptoms is needed, though not often achieved.) Research work on increasing HDL particle concentration and function, beyond the usual niacin effect/response, even more important, is slowly advancing. Niacin is supplied in many OTC and prescription formulations; non-prescription formulations recommend much lower doses as they are sold as nutritional supplements, not regulated medications. Dietary changes to achieve benefit have been more controversial, generally far less effective and less widely adhered to with success. One key reason for this is that most cholesterol, typically 80-90%, within the body is created and controlled by internal production by all cells in the body (true of all animals), with typically slightly greater relative production by hepatic/liver cells. (Cell structure relies on fat membranes to separate and organize intracellular water, proteins and nucleic acids and cholesterol is one of the components of all animal cell membranes.) While the absolute production quantities vary with the individual, group averages for total human body content of cholesterol within the U.S. population commonly run about 35,000 mg (assuming lean build; varies with body weight and build) and about 1,000 mg/day ongoing production. Dietary intake plays a smaller role, 200–300 mg/day being common values; for pure vegetarians, essentially 0 mg/day, but this typically does not change the situation very much because internal production increases to largely compensate for the reduced intake. For many, especially those with greater than optimal body mass and increased glucose levels, reducing carbohydrate (especially simple forms) intake, not fats or cholesterol, is often more effective for improving lipoprotein expression patterns, weight and blood glucose values. For this reason, medical authorities much less frequently promote the low dietary fat concepts than was commonly the case prior to about year 2005. However, evidence has increased that processed, particularly industrial non-enzymatic hydrogenation produced trans fats, as opposed to the natural cis-configured fats, which living cells primarily produce, is a significant health hazard. Dietary supplements of Omega-3 oils, especially those from the muscle of some deep salt water living fish species, also have clinical evidence of significant protective effects as confirmed by 6 double blind placebo controlled human clinical trials. In animals Vitamin C deficiency has been confirmed as an important role in development of hypercholesterolemia and atherosclerosis, but due to ethical reasons placebo-controlled human studies are impossible to do. Vitamin C acts as an antioxidant in vessels and inhibits inflammatory process. It has therapeutic properties on high blood pressure and its fluctuation, and arterial stiffness in diabetes. Vitamin C is also a natural regulator of cholesterol and higher doses (over 150 mg/kg daily) may confer significant protection against atherosclerosis even in the situation of elevated cholesterol levels. The scale of vitamin C benefits on cardiovascular system led several authors to theorize that vitamin C deficiency is the primary cause of cardiovascular diseases. The theory was unified by twice Nobel prize winner Linus Pauling, and Matthias Rath (Rath's promotion of vitamins instead of effective medicines for treatment of serious diseases has been very strongly criticised by many reputable authorities, as discussed in detail elsewhere). They point out that vitamin C is produced by all mammals except mankind and the great apes. This is due to a genetic deficiency that arose with the common ancestor of human and apes. To survive humans and apes must eat sufficient vitamin C each day. Without vitamin C humans develop scurvy. Vitamin C is an essential element in insuring that the vascular system is strong and flexible. Pauling and Rath suggest that a deficiency causes weakness in the arterial system and the body compensates by trying to stiffen up the artery walls using other common blood elements. This causes the effect known as atherosclerosis. They suggest that clinical manifestations of cardiovascular diseases are merely overshoot of body defense mechanisms that are involved in stabilisation of vascular wall after it is weakened by the vitamin C deficiency and the subsequent collagen degradation. They discuss several metabolic and genetic predispositions (our inability to produce vitamin C at all being the main one) and their pathomechanism. The Unified Theory of Human Cardiovascular Disease suggests that atherosclerosis may be reversed and cured, but there has been no testing or trial of Pauling's vitamin C theory. Trials on Vitamin E have been made, and have generally not found a beneficial effect. It has been suggested that there may be a beneficial effect for some patients at high risk for atherosclerosis. A review of trials suggested that the lack of evidence for a beneficial effect may have been due to various specified shortcomings in the trial methodologies, such as testing vitamin E without concurrent use of vitamin C. Excess iron may be involved in the development of atherosclerosis, but one study found reducing body iron stores in patients with symptomatic peripheral artery disease through phlebotomy did not significantly decrease all-cause mortality or death plus nonfatal myocardial infarction and stroke. Further studies may be warranted. Changes in diet may help prevent the development of atherosclerosis. Researchers at the Agricultural Research Service have found that avenanthramides, chemical compounds found in oats, may help reduce the inflammation of the arterial wall, which contributes to the development of atherosclerosis. Avenanthramides have anti-inflammatory properties that are linked to activating proinflammatory cytokines. Cytokines are proteins that are released by the cell to protect and repair tissues. Researchers found that these compounds in oats have the ability to reduce inflammation and thereby help prevent atherosclerosis. Other physical treatments, helpful in the short term, include minimally invasive angioplasty procedures that may include stents to physically expand narrowed arteries and major invasive surgery, such as bypass surgery, to create additional blood supply connections that go around the more severely narrowed areas. Patients at risk for atherosclerosis-related diseases are increasingly being treated prophylactically with low-dose aspirin and a statin. The high incidence of cardiovascular disease led Wald and Law to propose a Polypill, a once-daily pill containing these two types of drugs in addition to an ACE inhibitor, diuretic, beta blocker, and folic acid. They maintain that high uptake by the general population by such a Polypill would reduce cardiovascular mortality by 80%. It must be emphasized however that this is purely theoretical, as the Polypill has never been tested in a clinical trial. Medical treatments often focus predominantly on the symptoms. However, over time, clinical trials have shown treatments that focus on decreasing the underlying atherosclerosis processes—as opposed to simply treating symptoms—more effective. In summary, the key to the more effective approaches has been better understanding of the widespread and insidious nature of the disease and to combine multiple different treatment strategies, not rely on just one or a few approaches. In addition, for those approaches, such as lipoprotein transport behaviors, which have been shown to produce the most success, adopting more aggressive combination treatment strategies has generally produced better results, both before and especially after people are symptomatic. Because many blood thinners, particularly warfarin and salicylates such as aspirin, thin the blood by interfering with Vitamin K, there is recent evidence that blood thinners that work by this mechanism can actually worsen arterial calcification in the long term even though they thin the blood in the short term. Lipoprotein imbalances, upper normal and especially elevated blood sugar, i.e., diabetes and high blood pressure are risk factors for atherosclerosis; homocysteine, stopping smoking, taking anticoagulants (anti-clotting agents), which target clotting factors, taking omega-3 oils from fatty fish or plant oils such as flax or canola oils, exercising and losing weight are the usual focus of treatments that have proven to be helpful in clinical trials. The target serum cholesterol level should ideally not exceed 4 mmol/L (160 mg/dL), and triglycerides should not exceed 2 mmol/L (180 mg/dL). Evidence has increased that diabetics, despite not having clinically detectable atherosclerotic disease, have more severe debility from atherosclerotic events over time than even non-diabetics who have already suffered atherosclerotic events. Thus diabetes has been upgraded to be viewed as an advanced atherosclerotic disease equivalent[clarification needed]. The belief that high fat and cholesterol consumption causes atherosclerosis has been questioned. Because fat and cholesterol are the substances of which plaque consists, they are both considered to be contributors to the cause of atherosclerosis, though this remains to be verified. Inflammation is considered to be a cause of atherosclerosis rather than fat and cholesterol. A team of scientists recently discovered the earliest known case of atherosclerosis in ancient Egyptian mummies. The findings could mean that some scientists may not understand heart disease as well as previously thought in regard to the conditions creating that condition. It may not be a modern disease at all and could have been common throughout human history. This team began by running mummies through a CT scanner. "Our hypothesis was that they wouldn't have heart disease, because they were active, their diet was much different, they didn't have tobacco," he says. But they were wrong. One of the mummies the team scanned was a princess in her 40s. "That she would have atherosclerosis," the researcher says, "I think we're missing a risk factor. Right now we know that high blood pressure, smoking, cholesterol, inactivity and other things cause atherosclerosis, but I think that we're less complete than we think." An indication of the role of HDL on atherosclerosis has been with the rare Apo-A1 Milano human genetic variant of this HDL protein. A small short-term trial using bacterial synthetized human Apo-A1 Milano HDL in people with unstable angina produced fairly dramatic reduction in measured coronary plaque volume in only 6 weeks vs. the usual increase in plaque volume in those randomized to placebo. The trial was published in JAMA in early 2006. Ongoing work starting in the 1990s may lead to human clinical trials—probably by about 2008. These may use synthesized Apo-A1 Milano HDL directly. Or they may use gene-transfer methods to pass the ability to synthesize the Apo-A1 Milano HDLipoprotein. Methods to increase high-density lipoprotein (HDL) particle concentrations, which in some animal studies largely reverses and remove atheromas, are being developed and researched. Niacin has HDL raising effects (by 10 - 30%) and showed clinical trial benefit in the Coronary Drug Project and is commonly used in combination with other lipoprotein agents to improve efficacy of changing lipoprotein for the better. However most individuals have nuisance symptoms with short term flushing reactions, especially initially, and so working with a physician with a history of successful experience with niacin implementation, careful selection of brand, dosing strategy, etc. are usually critical to success. However, increasing HDL by any means is not necessarily helpful. For example, the drug torcetrapib is the most effective agent currently known for raising HDL (by up to 60%). However, in clinical trials it also raised deaths by 60%. All studies regarding this drug were halted in December 2006. See CETP inhibitor for similar approaches. The ERASE trial is a newer trial of an HDL booster, which has shown promise. The ASTEROID trial used a high-dose of rosuvastatin—the statin with typically the most potent dose/response correlation track record (both for LDLipoproteins and HDLipoproteins.) It found plaque (intima + media volume) reduction. Several additional rosuvastatin treatment/placebo trials for evaluating other clinical outcomes are in progress. The actions of macrophages drive atherosclerotic plaque progression. Immunomodulation of atherosclerosis is the term for techniques that modulate immune system function to suppress this macrophage action. Immunomodulation has been pursued with considerable success in both mice and rabbits since about 2002. Plans for human trials, hoped for by about 2008, are in progress. Research on genetic expression and control mechanisms is progressing. Topics include - PPAR, known to be important in blood sugar and variants of lipoprotein production and function; - The multiple variants of the proteins that form the lipoprotein transport particles. Some controversial research has suggested a link between atherosclerosis and the presence of several different nanobacteria in the arteries, e.g., Chlamydophila pneumoniae, though trials of current antibiotic treatments known to be usually effective in suppressing growth or killing these bacteria have not been successful in improving outcomes. The immunomodulation approaches mentioned above, because they deal with innate responses of the host to promote atherosclerosis, have far greater prospects for success. - Arterial stiffness - Chelation therapy - Coronary circulation - Coronary catheterization - Fatty streaks - Monckeberg's arteriosclerosis - Intravascular ultrasound - ^ Maton, Anthea; Roshan L. Jean Hopkins, Charles William McLaughlin, Susan Johnson, Maryanna Quon Warner, David LaHart, Jill D. Wright (1993). Human Biology and Health. Englewood Cliffs, New Jersey, USA: Prentice Hall. ISBN 0-13-981176-1. OCLC 32308337. - ^ Ross R (April 1993). "The pathogenesis of atherosclerosis: a perspective for the 1990s". Nature 362 (6423): 801–9. doi:10.1038/362801a0. PMID 8479518. - ^ Ross R; Ross, Russell (January 1999). "Atherosclerosis — An Inflammatory Disease". New England Journal of Medicine 340 (2): 115–26. doi:10.1056/NEJM199901143400207. PMID 9887164. - ^ Finn AV, Nakano M, Narula J, Kolodgie FD, Virmani R. Concept of vulnerable/unstable plaque. Arterioscler Thromb Vasc Biol. 2010 Jul;30(7):1282-92. Review. PubMed PMID 20554950. - ^ Didangelos A, Simper D, Monaco C, Mayr M (May 2009). "Proteomics of acute coronary syndromes.". Current atherosclerosis reports 11 (3): 188–95. doi:10.1007/s11883-009-0030-x. PMID 19361350. http://www.springerlink.com/content/8qjl665766630k8p/fulltext.pdf. - ^ a b Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ (May 1987). "Compensatory enlargement of human atherosclerotic coronary arteries". N. Engl. J. Med. 316 (22): 1371–5. doi:10.1056/NEJM198705283162204. PMID 3574413. - ^ a b c d Nissen. "Effect of Very High-Intensity Statin Therapy on Regression of Coronary Atherosclerosis–The ASTEROID Trial". JAMA. http://jama.ama-assn.org/cgi/reprint/jama;295/13/1556.pdf?ijkey=Md42dlk7z9TzyL8&keytype=finite. - ^ Williams, KJ; Tabas, I (1995 May). "The response-to-retention hypothesis of early atherogenesis.". Arteriosclerosis, thrombosis, and vascular biology 15 (5): 551–61. PMID 7749869. - ^ Sparrow, CP; Olszewski, J (1993 Jul). "Cellular oxidation of low density lipoprotein is caused by thiol production in media containing transition metal ions.". Journal of lipid research 34 (7): 1219–28. PMID 8103788. - ^ Fabricant CG, Fabricant J (1999). "Atherosclerosis induced by infection with Marek's disease herpesvirus in chickens". Am Heart J 138 (5 Pt 2): S465–8. doi:10.1016/S0002-8703(99)70276-0. PMID 10539849. - ^ Hsu HY, Nicholson AC, Pomerantz KB, Kaner RJ, Hajjar DP (August 1995). "Altered cholesterol trafficking in herpesvirus-infected arterial cells. Evidence for viral protein kinase-mediated cholesterol accumulation". J Biol Chem 270 (33): 19630–7. doi:10.1074/jbc.270.33.19630. PMID 7642651. http://www.jbc.org/cgi/pmidlookup?view=long&pmid=7642651. - ^ Cheng J, Ke Q, Jin Z, Wang H, Kocher O, Morgan JP, Zhang J, Crumpacker CS (May 2009). Früh, Klaus. ed. "Cytomegalovirus Infection Causes an Increase of Arterial Blood Pressure". PLoS Pathog 5 (5): e1000427. doi:10.1371/journal.ppat.1000427. PMC 2673691. PMID 19436702. http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000427. - ^ Rath M, Pauling L (1992). "A unified theory of human cardiovascular disease leading the way to the abolition of this disease as a cause for human mortality". Journal of Orthomolecular Medicine 7 (1): 5–15. http://orthomolecular.org/library/jom/1992/pdf/1992-v07n01-p005.pdf. - ^ a b Blankenhorn DH, Hodis HN (August 1993). "Atherosclerosis--reversal with therapy". The Western journal of medicine 159 (2): 172–9. PMC 1022223. PMID 8212682. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1022223. - ^ a b c d e f g h i j k l m n o p q r s Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology: With STUDENT CONSULT Online Access. Philadelphia: Saunders. pp. 345. ISBN 1-4160-2973-7. 8th edition. - ^ Narain VS, Gupta N, Sethi R, Puri A, Dwivedi SK, Saran RK, Puri VK. Clinical correlation of multiple biomarkers for risk assessment in patients with acute coronary syndrome. Indian Heart J. 2008 Nov-Dec;60(6):536-42. - ^ Rinehart, J. F., and Greenberg, L. D. 1949. Arteriosclerotic lesions in pyridoxine-deficient monkeys. Amer. J. Path. 25:481-491. - ^ Rinehart, J. F., and Greenberg, L. D. 1956. Vitamin B6 deficiency in the Rhesus monkey with particular reference to the occurrence of atherosclerosis, dental caries, and hepatic cirrhosis. Amer. J. Clin. Nutr. 4:318-325. - ^ Gruberg, E. R., Raymond, S. A. 1981. Beyond Cholesterol: Vitamin B6, Arteriosclerosis, and Your Heart. 1st ed. New York: St. Martin's Press. - ^ Borissoff JI, Spronk HM, Heeneman S, ten Cate H. Is thrombin a key player in the 'coagulation-atherogenesis' maze? Cardiovasc Res. 2009;82(3):392-403. PMID19228706.http://cardiovascres.oxfordjournals.org/content/82/3/392.long - ^ Borissoff JI, Heeneman S, Kilinc E, Kassak P, Van Oerle R, Winckers K, Govers-Riemslag JW, Hamulyak K, Hackeng TM, Daemen MJ, ten Cate H, Spronk HM. Early atherosclerosis exhibits an enhanced procoagulant state. Circulation. 2010;122(8):821-830. PMID20697022. http://circ.ahajournals.org/cgi/content/full/122/8/821 - ^ Borissoff JI, Spronk HM, ten Cate H. The hemostatic system as a modulator of atherosclerosis. N Engl J Med. 2011;364(18):1746-1760. PMID21542745. http://www.nejm.org/doi/full/10.1056/NEJMra1011670 - ^ Food and nutrition board, institute of medicine of the national academies (2005). Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academies Press. pp. 481–484. http://www.nap.edu/openbook.php?record_id=10490&page=481. - ^ Food and nutrition board, institute of medicine of the national academies (2005). Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). National Academies Press. pp. 494–505. http://www.nap.edu/openbook.php?record_id=10490&page=494. - ^ Bhatt DL, Topol EJ (July 2002). "Need to test the arterial inflammation hypothesis". Circulation 106 (1): 136–40. doi:10.1161/01.CIR.0000021112.29409.A2. PMID 12093783. http://circ.ahajournals.org/cgi/content/full/circulationaha;106/1/136. - ^ Griffin M, Frazer A, Johnson A, Collins P, Owens D, Tomkin GH (1998). "Cellular cholesterol synthesis--the relationship to post-prandial glucose and insulin following weight loss". Atherosclerosis. 138 (2): 313–8. doi:10.1016/S0021-9150(98)00036-7. PMID 9690914. - ^ King, Cr; Knutson, Kl; Rathouz, Pj; Sidney, S; Liu, K; Lauderdale, Ds (December 2008). "Short sleep duration and incident coronary artery calcification". JAMA : the journal of the American Medical Association 300 (24): 2859–66. doi:10.1001/jama.2008.867. PMC 2661105. PMID 19109114. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2661105. - ^ "Food Pyramids: Nutrition Source, Harvard School of Public Health". http://www.hsph.harvard.edu/nutritionsource/pyramids.html. Retrieved 2007-11-25. - ^ Taubes G (March 2001). "Nutrition. The soft science of dietary fat". Science 291 (5513): 2536–45. doi:10.1126/science.291.5513.2536. PMID 11286266. http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=11286266. - ^ Song JH, Fujimoto K, Miyazawa T (2000). "Polyunsaturated (n-3) fatty acids susceptible to peroxidation are increased in plasma and tissue lipids of rats fed docosahexaenoic acid-containing oils". J. Nutr. 130 (12): 3028–33. PMID 11110863. - ^ Yap SC, Choo YM, Hew NF, et al. (1995). "Oxidative susceptibility of low density lipoprotein from rabbits fed atherogenic diets containing coconut, palm, or soybean oils". Lipids 30 (12): 1145–50. doi:10.1007/BF02536616. PMID 8614305. - ^ Greco AV, Mingrone G (1990). "Serum and biliary lipid pattern in rabbits feeding a diet enriched with unsaturated fatty acids". Exp Pathol 40 (1): 19–33. PMID 2279534. - ^ Mattes RD (2005). "Fat taste and lipid metabolism in humans". Physiol. Behav. 86 (5): 691–7. doi:10.1016/j.physbeh.2005.08.058. PMID 16249011. http://linkinghub.elsevier.com/retrieve/pii/S0031-9384(05)00397-5. "The rancid odor of an oxidized fat is readily detectable" - ^ Dobarganes C, Márquez-Ruiz G (2003). "Oxidized fats in foods". Curr Opin Clin Nutr Metab Care 6 (2): 157–63. doi:10.1097/00075197-200303000-00004. PMID 12589185. - ^ How Bad Are Cooking Oils? by Udo Erasmus, PhD - ^ supplements, FDA. "Dietary Supplements". http://www.fda.gov/Food/DietarySupplements/default.htm. - ^ Schwartz, CJ; Valente AJ, Sprague EA, Kelley JL, Cayatte AJ, Mowery J. (Dec 1992). "Atherosclerosis. Potential targets for stabilization and regression". Circulation 86 ((6 Suppl)): III117–123. PMID 1424045. - ^ "Coronary atherosclerosis - the fibrous plaque with calcification". www.pathologyatlas.ro. http://www.pathologyatlas.ro/coronary-atherosclerosis-fibrous-plaque.php. Retrieved 2010-03-25. - ^ Maseri A, Fuster V (2003). "Is there a vulnerable plaque?". Circulation 107 (16): 2068–71. doi:10.1161/01.CIR.0000070585.48035.D1. PMID 12719286. - ^ The Allhat Officers And Coordinators For The Allhat Collaborative Research Group, (2002). "Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT)". JAMA 288 (23if the ti is): 2998–3007. doi:10.1001/jama.288.23.2998. PMID 12479764. - ^ Vos E, Rose CP (November 2005). "Questioning the benefits of statins". CMAJ 173 (10): 1207; author reply 1210. doi:10.1503/cmaj.1050120. PMC 1277053. PMID 16275976. http://www.cmaj.ca/cgi/content/full/173/10/1207-a. - ^ T. E. Strandberg, S. Lehto, K. Pyörälä, A. Kesäniemi, H. Oksa (1997-01-11). "Cholesterol lowering after participation in the Scandinavian Simvastatin Survival Study (4S) in Finland". European Heart Journal 18 (18(11)): 1725–1727;. PMID 9402446. http://eurheartj.oxfordjournals.org/cgi/content/abstract/18/11/1725. Retrieved 2007-11-18. - ^ Nissen SE, Nicholls SJ, Sipahi I, et al. (2006). "Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial" (PDF). JAMA 295 (13): 1556–65. doi:10.1001/jama.295.13.jpc60002. PMID 16533939. http://jama.ama-assn.org/cgi/reprint/jama;295/13/1556.pdf?ijkey=Md42dlk7z9TzyL8&keytype=finite. - ^ Downs JR, Clearfield M, Weis S, et al. (May 1998). "Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study". JAMA : the journal of the American Medical Association 279 (20): 1615–22. doi:10.1001/jama.279.20.1615. PMID 9613910. http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=9613910. - ^ Bradford RH, Shear CL, Chremos AN, et al. (1991). "Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia". Arch. Intern. Med. 151 (1): 43–9. doi:10.1001/archinte.151.1.43. PMID 1985608. - ^ Sever PS, Poulter NR, Dahlöf B, et al. (2005). "Reduction in cardiovascular events with atorvastatin in 2,532 patients with type 2 diabetes: Anglo-Scandinavian Cardiac Outcomes Trial--lipid-lowering arm (ASCOT-LLA)". Diabetes Care 28 (5): 1151–7. doi:10.2337/diacare.28.5.1151. PMID 15855581. - ^ Linda Brookes, MSc. "SPARCL: Stroke Prevention by Aggressive Reduction in Cholesterol Levels". Medscape. http://www.medscape.com/viewarticle/536377. Retrieved 2007-11-19. - ^ Amarenco P, Bogousslavsky J, Callahan AS, et al. (2003). "Design and baseline characteristics of the stroke prevention by aggressive reduction in cholesterol levels (SPARCL) study". Cerebrovascular diseases 16 (4): 389–95. doi:10.1159/000072562. PMID 14584489. http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ProduktNr=224153&ArtikelNr=72562. - ^ a b Medtv: niacin dosage to b increased to 3,000mg/day over about 10 weeks to avoid side-effects - ^ Ginter E (2007). "Chronic vitamin C deficiency increases the risk of cardiovascular diseases". Bratisl Lek Listy 108 (9): 417–21. PMID 18225482. - ^ Böhm F, Settergren M, Pernow J (2007). "Vitamin C blocks vascular dysfunction and release of interleukin-6 induced by endothelin-1 in humans in vivo". Atherosclerosis 190 (2): 408–15. doi:10.1016/j.atherosclerosis.2006.02.018. PMID 16527283. - ^ Sato K, Dohi Y, Kojima M, Miyagawa K, Takase H, Katada E, Suzuki S. (2006). "Effects of ascorbic acid on ambulatory blood pressure in elderly patients with refractory hypertension". Arzneimittelforschung 56 (7): 535–40. PMID 16927536. - ^ Gladys Block, Christopher D Jensen, Edward P Norkus, Mark Hudes and Patricia B Crawford (2008). "Vitamin C in plasma is inversely related to blood pressure and change in blood pressure during the previous year in young Black and White women". Nutrition Journal 7 (35): 535–40. doi:10.1186/1475-2891-7-35. PMC 2621233. PMID 19091068. http://www.nutritionj.com/content/7/1/35. - ^ Brian A. Mullan; Ian S. Young; Howard Fee; David R. McCance (2002). "Ascorbic Acid Reduces Blood Pressure and Arterial Stiffness in Type 2 Diabetes". Hypertension 40 (6): 804–9. doi:10.1161/01.HYP.0000039961.13718.00. PMID 12468561. http://hyper.ahajournals.org/cgi/content/abstract/40/6/804. - ^ HJ Harwood Jr, YJ Greene and PW Stacpoole (June 5, 1986). "Inhibition of human leukocyte 3-hydroxy-3-methylglutaryl coenzyme A reductase activity by ascorbic acid. An effect mediated by the free radical monodehydroascorbate". J. Biol. Chem. 261 (16): 7127–7135. PMID 3711081. http://www.jbc.org/cgi/reprint/261/16/7127. - ^ Das S, Ray R, Snehlata, Das N, Srivastava LM (2006). "Effect of ascorbic acid on prevention of hypercholesterolemia induced atherosclerosis". Mol Cell Biochem 285 (1–2): 143–7. doi:10.1007/s11010-005-9070-x. PMID 16479321. - ^ Klenner F.R. (1974). "Significance of high daily intake of ascorbic acid in preventive medicine". J. Int. Acad. Prev. Med. 1: 45–49. http://www.seanet.com/%7Ealexs/ascorbate/197x/klenner-fr-j_int_assn_prev_med-1974-v1-n1-p45.htm. - ^ Stone, I. (1972). The Healing Factor: Vitamin C Against Disease. Grosset and Dunlap, New York/Perigee Books, published by The Putnam Publishing Group. ISBN 0-399-50764-7. http://www.roccomanzi.it/IMP-VITAMINERALI/SCIENZIATI/scienziati-docu/stone/HEALINGFACTVitaC-TUTTO-ING_file/HEALINGFACTVitaC-TUTTO-ING.htm. - ^ a b Rath M, Pauling L (1992). "A Unified Theory of Human Cardiovascular Disease Leading the Way to the Abolition of This Disease as a Cause for Human Mortality" (PDF). Journal of Orthomolecular Medicine 7 (1): 5–15. http://www.orthomolecular.org/library/jom/1992/pdf/1992-v07n01-p005.pdf. - ^ Robinson I, de Serna DG, Gutierrez A, Schade DS (2006). "Vitamin E in humans: an explanation of clinical trial failure". Endocr Pract 12 (5): 576–82. PMID 17002935. - ^ Geleijnse JM, Vermeer C, Grobbee DE, et al. (2004). "Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study". J. Nutr. 134 (11): 3100–5. PMID 15514282. - ^ Erkkilä AT, Booth SL (2008). "Vitamin K intake and atherosclerosis". Curr. Opin. Lipidol. 19 (1): 39–42. doi:10.1097/MOL.0b013e3282f1c57f. PMID 18196985. - ^ Wallin R, Schurgers L, Wajih N (2008). "Effects of the blood coagulation vitamin K as an inhibitor of arterial calcification". Thromb. Res. 122 (3): 411–7. doi:10.1016/j.thromres.2007.12.005. PMC 2529147. PMID 18234293. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2529147. - ^ Brewer GJ (2007). "Iron and copper toxicity in diseases of aging, particularly atherosclerosis and Alzheimer's disease". Exp. Biol. Med. (Maywood) 232 (2): 323–35. PMID 17259340. - ^ Sullivan JL, Mascitelli L (2007). "[Current status of the iron hypothesis of cardiovascular diseases]" (in Italian). Recenti Prog Med 98 (7–8): 373–7. PMID 17685184. - ^ Zacharski LR, Chow BK, Howes PS, et al. (2007). "Reduction of iron stores and cardiovascular outcomes in patients with peripheral arterial disease: a randomized controlled trial". JAMA 297 (6): 603–10. doi:10.1001/jama.297.6.603. PMID 17299195. - ^ Agricultural Research Service-funded research by Mohsen Meydani - ^ Nie, Wise, Peterson, and Meydani, Atherosclerosis journal: Avenanthramide, a polyphenol from oats, inhibits vascular smooth muscle cell proliferation and enhances nitric oxide production - ^ "Heart disease and stents". Cypher Stent. http://www.cypherusa.com/cypher-j2ee/cypherjsp/main_splash/stent.jsp. Retrieved 2008-04-01. - ^ Wald NJ, Law MR (June 2003). "A strategy to reduce cardiovascular disease by more than 80%". BMJ (Clinical research ed.) 326 (7404): 1419. doi:10.1136/bmj.326.7404.1419. PMC 162259. PMID 12829553. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=162259. - ^ Price PA, Faus SA, Williamson MK (February 2000). "Warfarin-induced artery calcification is accelerated by growth and vitamin D". Arteriosclerosis, thrombosis, and vascular biology 20 (2): 317–27. PMID 10669626. http://atvb.ahajournals.org/cgi/pmidlookup?view=long&pmid=10669626. - ^ Geleijnse JM, Vermeer C, Grobbee DE, et al. (November 2004). "Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study". J Nutr. 134 (11): 3100–5. PMID 15514282. http://jn.nutrition.org/cgi/content/full/134/11/3100. - ^ "Linus Pauling Institute at Oregon State University". lpi.oregonstate.edu. http://lpi.oregonstate.edu/infocenter/vitamins/vitaminK/. Retrieved 2010-03-25. - ^ "GlycoDocs.org". glycodocs.org. http://www.glycodocs.org/wellness/index.php. Retrieved 2010-03-25. - ^ http://circ.ahajournals.org/cgi/content/full/105/9/1135 - ^ http://www.npr.org/2011/04/09/135269340/egyptian-mummies-diagnosed-with-clogged-arteries?ft=1&f=1001 Retrieved April-10-11 - ^ Barter PJ, Caulfield M, Eriksson M, et al. (November 2007). "Effects of torcetrapib in patients at high risk for coronary events". N Engl J Med. 357 (21): 2109–22. doi:10.1056/NEJMoa0706628. PMID 17984165. http://content.nejm.org/cgi/content/full/NEJMoa0706628. - ^ Sue Hughes (March 26, 2007). "ERASE: New HDL mimetic shows promise". HeartWire. http://www.theheart.org/article/779839.do. - ^ Jan Nilsson; Göran K. Hansson; Prediman K. Shah (2005). "Immunomodulation of Atherosclerosis – Implications for Vaccine Development—ATVB In Focus". Arteriosclerosis, Thrombosis, and Vascular Biology 5 (1): 18–28. doi:10.1161/01.ATV.0000149142.42590.a2. PMID 15514204. http://atvb.ahajournals.org/cgi/content/abstract/atvbaha;25/1/18. - ^ M Stitzinger (2007). "Lipids, inflammation and atherosclerosis" (pdf). The digital repository of Leiden University. https://openaccess.leidenuniv.nl/dspace/bitstream/1887/9729/11/01.pdf. Retrieved 2007-11-02. "Results of clinical trials investigating anti-chlamydial antibiotics as an addition to standard therapy in patients with coronary artery disease have been inconsistent. Therefore, Andraws et al. conducted a meta- analysis of these clinical trials and found that evidence available to date does not demonstrate an overall benefit of antibiotic therapy in reducing mortality or cardiovascular events in patients with coronary artery disease." - Atherosclerosis at the Open Directory Project - A four-minute animation of the atherosclerosis process, entitled "Pathogenesis of Acute MI," commissioned by Paul M. Ridker, MD, MPH, FACC, FAHA, at the Harvard Medical School, can be viewed at pri-med.com. Cardiovascular disease: vascular disease · Circulatory system pathology (I70–I99, 440–456) Arteries, arterioles Veinsprimarily lower limb (Deep vein thrombosis)abdomen (Hepatic veno-occlusive disease, Budd–Chiari syndrome, May-Thurner syndrome, Portal vein thrombosis, Renal vein thrombosis)Other Arteries or veins Blood pressure Wikimedia Foundation. 2010.	2	55	14	3	3	0.753021	20	16,055
Capnography During Sedation The line of demarcation between conscious sedation and general anesthesia is sometimes very thin. It is possible during conscious sedation, intravenous sedatives and narcotics administered to allay apprehension can result in the loss of consciousness and respiratory obstruction. If this is not recognized immediately, the patient can become hypoxic. In the majority of cases, the respiratory obstruction occurs well before the onset of hypoxia. Therefore monitoring of respiratory status is essential to enable corrective measures before the occurrence of hypoxia. Following illustration explains reinforces this concept . Pulse oximetry is a monitor of oxygenation Supplemental oxygen can mask apnea or hypoventilation A Preponderance of evidence suggests that procedural sedation is associated with undetected apnea or hypoventilation that can result in oxygen desaturation. Hence it is obvious that some type of ventilation monitoring is required to safeguard against hypoxia during sedation procedures outside of the operating room. To detect apnea or hypoventilation during procedural sedation, a specific monitor of ventilation is required. The value of capnography is well appreciated during anesthesia as an airway and ventilation monitor so much so that it has become a standard of practice in the operating room. It is only a matter of time that capnography will find its way to becoming incorporated as a standard of practice for monitoring ventilation during sedation procedures. Capnography has evolved into a standard of monitoring during anesthesia because it has proven itself to be a valuable tool in recognizing ventilatory and circulatory events that could potentially lead to deleterious effects. Hypoxia is our primary concern during anesthesia, and therefore, by all means, any situation that results in hypoxia is avoided. One of the greatest assets of capnography is that it can identify situations that can potentially result in hypoxia. Capnography serves as a warning device by instantly drawing the anesthesiologist's attention to the events that could potentially lead to hypoxia, if uncorrected. Because of this, care- providers have been encouraged to extend the benefit of capnography to areas beyond the domain of anesthesiologists. Examples include the use of capnography in the EMT / ambulance services for monitoring ventilation, and emergency medical rooms for procedures and sedation. Presently, several procedures are being performed under sedation outside of the operating room. Although the aim of the conscious sedation nurse/personnel is to provide conscious sedation, the line between conscious sedation and sleep is very narrow and the patient drifts quite often into an unconscious state. During this state of sleep, airway obstruction or hypoventilation may occur that may not be detected until hypoxia occurs as is indicated by pulse oximetry. Occasionally endoscopies performed via the upper airway can also result in airway obstruction. The delayed identification of airway problems leads to a delayed intervention. It is not uncommon for anesthesiologists to be called in urgently to intervene under these circumstances. Capnography could provide early warning in identifying such respiratory or airway problems in advance so that corrective intervention can be undertaken before hypoxia ensues. Policymakers who understand the potential benefits and strides made in the operating room by capnography, logically recommend and extend its use to areas beyond the operating room to enhance the safety of patients undergoing sedation procedures. Capnography is routinely used in patients undergoing cardiac electrophysiology studies and ablation, ICD placement and testing at our institution. Others look for evidence to determine if capnography has truly any beneficial role to play in sedation procedures outside of the operating room. The value of capnography was recognized in the operating room settings prior to being adopted as standard of monitoring during anesthesia procedures. Similarly, several recent studies have shown the benefit of capnography in identifying events that can potentially lead to hypoxia during procedural sedation. This could be a precursor for capnography being accepted as standard of care during sedation procedures in the near future. Vargo et al studied forty-nine patients undergoing therapeutic therapeutic upper endoscopy, who were monitored with standard methods including pulse oximetry, automated blood pressure measurement, and visual assessment. In addition, graphic assessment of respiratory activity with side-stream capnography was performed in all patients. Endoscopy personnel were blinded to capnography data. Episodes of apnea (cessation of respiration for 30 or more seconds) or disordered respiration (45 second interval that contained at least 30 seconds of cumulative apneic activity) detected by capnography were documented and compared with the occurrences of hypoxemia, hypercapnea, hypotension, and the recognition of abnormal respiratory activity by endoscopy personnel. Capnography identified 54 events of apnea or disordered respiratory events during the endoscopic procedure, whereas, pulse oximetry picked up only 27 events (50%) where the respiratory events that were detected by capnography progressed to result in hypoxia (as defined by oxygen saturation below 90%). Hypoxemia occurred approximately 45.6 seconds (15-120 seconds) after the capnographic detection of respiratory events. Visual inspection of the patient by the care providers detected none of the 54 events detected by capnography. Capnography also detected hypoventilation as shown by a 25% increase from baseline end expiratory carbon dioxide values. Minor et al prospectively studied whether end-tidal carbon dioxide (ETCO2) monitors can detect respiratory depression (RD) and the level of sedation in emergency department (ED) patients undergoing procedural sedation. This was a prospective observational study conducted in an urban county hospital of adult patients undergoing procedural sedation. Patients were monitored for vital signs, depth of sedation per the physician by the Observer's Assessment of Alertness/Sedation scale (OAA/S), pulse oximetry, and nasal-sample ETCO2CO2 during procedural sedation. Respiratory depression was defined as an oxygen saturation <90%, an ETCO2 >50 mm Hg, or an absent ETCO2 waveform at any time during the procedure. The physician also determined whether protective airway reflexes were lost during the procedure and assisted ventilation was required, or whether there were any other complications. Seventy-four patients were enrolled in the study. Forty (54.1%) received methohexital, 21 (28.4%) received propofol, ten (13.5%) received fentanyl and midazolam, and three (4.1%) received etomidate. Respiratory depression was seen in 33 (44.6%) patients, including 47.5% of patients receiving methohexital, 19% receiving propofol (p = 0.008), 80% receiving fentanyl and midazolam, and 66.6% receiving etomidate. No correlation between OAA/S and ETCO2 was detected. Eleven (14.9%) patients required assisted ventilation at some point during the procedure, all of whom met the criteria for RD. Pulse oximetry detected 11 of the 33 patients with RD. Using the criteria of an ETCO2 >50 mm Hg, an absolute change >10 mm Hg, or an absent waveform may detect subclinical RD not detected by pulse oximetry alone. The authors concluded that the ETCO2 may add to the safety of procedural safety by quickly detecting hypoventilation during sedation in the Emergency department. McQuillen and steele described ETCO2 changes associated with different sedation strategies. This was a prospective, observational patient series in an urban pediatric emergency department (PED). Participants included 106 children with a mean age of 6.8 years. (range 1.2-16.6 years). Sedation/analgesia was given for fracture reduction (55%), laceration repair (37%), abscess incision and drainage (4%), and lumbar puncture (LP) (4%). Medications included fentanyl, morphine, ketamine, and midazolam. Continuous ETCO2 waveforms were recorded via a Capnogard ETCO2 Monitor. Oxygen saturation was recorded using a Nelcor N-200 pulse oximeter. Recording began prior to sedation and continued until the patient was awake or when it was necessary to remove the patient from the monitor for further medical care. Each record was analyzed for peak ETCO2 and averaged over five consecutive breaths, before and after the administration of medications. The main outcome measure was the change in ETCO2 levels. The mean increase in ETCO2 was 6.7 mmHg (P is included in, 0.00001; range: +0.16 to +22.3). ETCO2 increased by 3.2 mmHg (95% CI = 2.2-4.2) for midazolam alone, 5.4 mmHg (95% CI = 4.5-6.4) for midazolam and ketamine, and 8.8 mmHg (95% CI = 7.4-10.2) for midazolam and opiate. Two patients had transient SpO2 desaturations below 93%, which corrected with stimulation. The authors concluded that commonly used agents for pediatric sedation result in significant increases in ETCO2. ETCO2 is a useful adjunct in assessing ventilation and may serve as an objective research tool for assessing different sedation strategies. Tobias in his study used both end-tidal carbon dioxide (ETCO2) monitoring and pulse oximetry to evaluate the respiratory effects of revised midazolam and ketamine protocol. Fifty children who required sedation during invasive procedures formed the cohort for the study. During sedation, ETCO2 was sampled from nasal cannulae of spontaneously breathing patients and measured by a side-stream aspirating infrared device. During the procedure, O2 saturation decreased by 3% or more in three patients. Supplemental oxygen at 2 liters per minute was administered to these patients. The lowest oxygen saturation was 84%. During the total of 767 minutes of monitoring, there were 3068 ETCO2 values recorded. The high ETCO2 values ranged from 37 to 53 mmHg (40.5 +/- 3.3 mmHg). Ninety percent, or 2760, of the values were 40 mmHg or less, 7% or 214 were between 41 and 45 mmHg, 3% or 92 were between 46 and 49 mmHg, and 2 isolated values were greater than 50 mmHg. One episode of airway obstruction was identified by noting cessation of the ETCO2 waveform. This was relieved by repositioning the patient's airway. The three episodes of O2 desaturation, two ETCO2 values greater than 50 mmHg, and the episode of upper airway obstruction all occurred in three patients. Two of these patients had trisomy 21 with macroglossia, and the third had had a recent upper respiratory infection and a history of tonsillar hypertrophy. The incidence of adverse cardiorespiratory events associated with the current sedation regimen of midazolam-ketamine is lower than that reported with other commonly used regimens. The addition of ETCO2 monitoring provides an additional monitor to allow for early detection of airway obstruction or subclinical degrees of respiratory depression. Hart et al state that many studies have evaluated conscious sedation regimens commonly used in pediatric patients and recent advances in capnography equipment now enable physicians to assess respiratory parameters, specifically end-tidal CO2 (et-CO2), more accurately in spontaneously breathing sedated children than was possible in the earlier studies. They designed the study to: 1) compare the safety and efficacy of intravenous fentanyl, intravenous fentanyl combined with midazolam, and intramuscular meperidine-promethazine-chlorpromazine (MPC) compound when used for painful emergency department (ED) procedures: and 2) to determine whether the addition of et-CO2 monitoring enabled earlier identification of respiratory depression in this population. Forty-two children requiring analgesia and sedation for painful ED procedures were randomly assigned to receive either fentanyl, fentanyl-midazolam, or MPC compound. Vital signs, oxygen saturation, and et-CO2 were monitored continuously. Pain, anxiety, and sedation scores were recorded every five minutes. Respiratory depression (O2 saturation < or = 90% for over the minute or any et-CO2 > or = 50) occurred in 20% of fentanyl, 23% of fentanyl-midazolam, and 11% of MPC patients (P = NS). Of those patients manifesting respiratory depression, 6/8 were detected by increased et-CO2 only. MPC patients required significantly longer periods of time to meet discharge criteria than fentanyl and fentanyl-midazolam patients (P < 0.05). No differences were noted in peak pain, anxiety, or sedation scores. The authors concluded that Fentanyl, fentanyl-midazolam, and MPC produced a high incidence of subclinical respiratory depression. End-tidal CO2 monitoring provided an earlier indication of respiratory depression than pulse oximetry and respiratory rate alone. MPC administration resulted in a significantly delayed discharge from the ED. All the above studies are unanimous in that airway compromise and hypoventilation events do occur during procedural sedation and capnography identifies these events earlier than pulse oximetry. Thus, capnography serves as an early warning device of an impending hypoxia. If anesthesiologists are involved in laying out guidelines for non-operating-room locations, they are more likely to include capnography to monitor ventilation. This is probably because, by nature, anesthesiologists are trained to think about airway and ventilation at all times. This is also the reason why our cardiac electrophysiology/ablation rooms and minor Obstetric procedure rooms are provided with capnography as we oversee the sedation and anesthesia care here. The American Society of Anesthesiology in their document on "Practice Guidelines for Sedation and Analegesia by Non-Anesthesiologists" under the section 'Pulmonary ventilation' (http://www.asahq.org/publicationsAndServices/practiceparam.htm) states as follows: "It is the opinion of the Task Force that the primary causes of morbidity associated with sedation/analgesia are drug-induced respiratory depression and airway obstruction. For both moderate and deep sedation, the literature is insufficient to evaluate the benefit of monitoring ventilatory function by observation or auscultation. However, the consultants strongly agree that monitoring of ventilatory function by observation or auscultation reduces the risk of adverse outcomes associated with sedation/analgesia. The consultants were equivocal regarding the ability of capnography to decrease risks during moderate sedation, while agreeing that it may decrease risks during deep sedation. In circumstances where patients are physically separated from the caregiver, the Task Force believes that automated apnea monitoring (by detection of exhaled CO2 or other means) may decrease risks during both moderate and deep sedation, while cautioning practitioners that impedance plethysmography may fail to detect airway obstruction. The Task Force emphasizes that because ventilation and oxygenation are separate though related physiological processes, monitoring oxygenation by pulse oximetry is not a substitute for monitoring ventilation." Therefore, there are recommendations to monitor ventilation during procedural sedation 'particularly' if deep, but not a standard. Yet, it is up to the care-providers to decide how and what method is best for their practicing environment. Certainly capnography provides an early warning device to draw attention to abnormal ventilation. No doubt, capnography has limitations, particularly in nasal sampling. This limitation should be understood. However, there are devices to improve sampling of carbon dioxide in expired air and thus decrease artifacts. I generally get a baseline waveform and ETCO2 values, and focus attention to any changes from the baseline values. Thinking, always in my mind that any changes in ETCO2 from the baseline are due to depression of ventilation or airway obstruction until otherwise proven by close examination. In my opinion, a decrease in pulse oximetry is a late finding, and I would use other methods to identify events before they have had a chance to produce hypoxia. In conclusion, capnography seems to be a logical device to monitor ventilation during procedural sedation. This is because (a) The general consensus among anesthesiologists is that airway problems are primary causes of morbidity associated with sedation/analgesia are drug-induced respiratory depression and airway obstruction; (b) Available studies on procedural sedation confirm that respiratory events precede hypoxia, and capnography is a valuable monitoring device to detect respiratory events that could culminate in hypoxia; (c) Sedation procedures are being performed more often by non-anesthesiologists at remote locations from the 'OR' (operating room). They may not be as well experienced and adept as anesthesiologists in recognizing airway obstruction, apnea and hypoventilation; (d) Endoscopic physicians are preferring to use hypnotic agents such as propofol for quick recovery and discharge to reduce health care cost. These agents can result in respiratory depression and apnea. Just like the evolution of capnography in the operating room from a guideline status to the status of standard of practice, it is only a question of time that capnography will be accepted as a standard of care to enhance patient safety during procedural sedation. 1. Vargo JJ, Zuccaro G, Dumont JA, Conwell DL, Morrow JB, Shay SS. Automated graphic assessment of respiratory activity is superior to pulse oximetry and visual assessment of the detection of early respiratory depression during therapeutic upper endoscopy. Gastrointestinal Endoscopy 2002;55:826-31. 2. Miner JR, Heegaard W, Plummer D. End-tidal carbon dioxide monitoring during procedural sedation. Acad Emerg Med 2002;9:275-80. 3. McQuillen KK, Steele DW. Capnography during sedation/analgesia in the pediatric emergency department. Pediatr Emerg Care 2000;16:401-4. 4. Tobias JD. End-tidal carbon dioxide monitoring during sedation with a combination of midazolam and ketamine for children undergoing painful, invasive procedures. Pediatr Emerg Care 1999;15:173-5. 5. Hart LS, Berns SD, Houck CS, Boenning DA. The value of end-tidal CO2 monitoring when comparing three methods of conscious sedation for children undergoing painful procedures in the emergency department. Pediatr Emeg Care 1997;13:189-93. 6. Practice Guidelines For Sedation And Analgesia By Non-Anesthesiologists (Approved by the House of Delegates on October 25, 1995, and last amended on October 17, 2001).	2	19	1	0	0	0.827896	1	3,996
- Potter sequence Potter sequence Classification and external resources ICD-10 Q60.6 ICD-9 753.0, 658.0, 761.2 (for oligohydramnios) DiseasesDB 11252 MedlinePlus 001268 eMedicine ped/1878 Potter sequence (also known as Potter's syndrome, Potter's sequence or Oligohydramnios sequence) is the atypical physical appearance of a fetus or neonate due to oligohydramnios experienced in the womb. Oligohydramnios is the decrease in amniotic fluid volume sufficient to cause disruptions in morphogenesis of the fetus. Oligohydramnios is the causative agent of Potter sequence, but there are many things that can lead to oligohydramnios. It can be caused by renal diseases such as bilateral renal agenesis (BRA), atresia of the ureter or urethra causing obstruction of the urinary tract, polycystic or multicystic kidney diseases, renal hypoplasia, amniotic rupture, uteroplacental insufficiency from maternal hypertension or toxemia. Potter's sequence is known in the medical field as clubbed feet, pulmonary hypoplasia and cranial anomalies related to the oligohydramnios. The term Potter sequence was initially intended to only refer to cases caused by BRA, however, it has been mistakenly used by many clinicians and researchers to refer to any case that presents with oligohydramnios or anhydramnios regardless of the source of the loss of amniotic fluid. Up until this time the condition itself was considered to be extremely rare. However, in part to Potter's work it has come to light that the condition presents far more frequently than previously reported. Potter analyzed approximately 5000 autopsy cases performed on fetuses and newborn infants over a period of ten years and found that 20 of these infants presented with BRA, all of which had distinctive facial characteristics. These facial characteristics have subsequently be termed as being known as Potter facies. From her analysis she was able to deduce the sequence of events that leads to what is now known as Potter sequence. Potter went on to become a pioneer in the field of human renal development and her contributions are still employed and appreciated by clinicians and researchers to this day. Since its initial characterization, Potter sequence has been defined into five distinct subclassifications. There are those in the medical and research fields that use the term Potter sequence to specifically refer to only cases of BRA, while other groups use the term to loosely refer to all instances of oligohydramnios and anhydramnios regardless of the specific cause. The assignment of nomenclature to the various causes (types) were employed in order to help clarify these descrepancies, but, these subclassifications and nomenclature system have not caught on in the medical and research communities. Type OMIM Description Classic form n/a This term is traditionally used when the infant has bilateral renal agenesis (BRA), meaning that kidneys do not develop (malformation of the ureteric bud). True BRA also presents with bilateral agenesis of the ureters. After the creation of the nomenclature system for this sequence, BRA was recognized as possibly being an extreme variation of Potter sequence II. However, some clinicians and researchers still use the term classic Potter sequence so as to emphasize that they are specifically referring to cases of BRA and not another form. Type I 263200 Type I is due to autosomal recessive polycystic kidney disease (ARPKD), which occurs at a frequency of approximately one in 16,000 infants. The kidneys of the fetus/neonate will be enlarged, have many small cysts filled with fluid and will fail to produce an adequate volume of fetal urine. The liver and pancreas of the fetus may also show fibrosis and/or a cystic change. Type II 191830 Type II is usually due to renal agenesis, which can also fall under the category known as hereditary urogenital adysplasia or hereditary renal adysplasia (HRA). This is characterized by the complete agenesis or absence of one kidney and the remaining solitary kidney being small and malformed. Bilateral renal agenesis is believed to be the most extreme phenotypic variation of HRA. However, BRA is often referred to as classic Potter sequence, as it was this particular phenotype of neonates and fetuses that Potter originally reported in her 1946 manuscripts when characterizing this birth defect. Type III 173900 Type III is due to Autosomal dominant polycystic kidney disease (ADPKD) linked to mutations in the genes PKD1 and PKD2. While ADPKD is considered to be an adult-onset polycytic kidney disease, it can also present in the fetus and neonate in rare cases. Like ARPKD, ADPKD can also present with hepatic cysts and an enlarged spleen. An increased prevalence of vascular disease is also observed in these cases of ADPKD. Type IV n/a Type IV occurs when a longstanding obstruction in either the kidney or ureter leads to cystic kidneys or hydronephrosis. This can be due to chance, environment, or genetics. While these types of obstructions occur frequently in fetuses, they rarely tend to lead to fetal demise. Others 143400 Often cystic kidneys that do not fall under the classification of being polycystic will be termed as being multicystic renal dysplasia (MRD). Recently many cases of MRD have been linked to the mutations in the gene PUJO, however, this new possible genetic cause has not been assigned a Potter sequence nomenclature number. Another cause of Potter sequence (oligohydramnios or anhydramnios—little or no amniotic fluid) can be the rupturing of the amniotic sacs that contain the amniotic fluid of the fetus. This can happen spontaneously, by chance, environment, maternal trauma and in rare cases - maternal genetics. Terminology: syndrome versus sequence Potter syndrome is not technically a syndrome as it does not collectively present with the same telltale characteristics and symptoms in each and every case. It is more accurately described as a "sequence" or chain of events that may have different beginnings (absent kidneys, cystic kidneys, obstructed ureters or other causes), but which all end with the same conclusion (absent or reduced volume of amniotic fluid). This is why Potter syndrome is often called Potter sequence or oligohydramnios sequence by some clinicians and researchers. The term Potter syndrome is most frequently associated with the condition of oligohydramnios sequence regardless of the root cause of the absence or reduced volume of amniotic fluid. However, as noted in this article, the term Potter syndrome was initially coined in order to refer to fetuses and infants with BRA. It was not until later that the term became more encompassing as it was noted that other causes of failed fetal urine production also resulted in similar physical characteristics and prognoses of the fetuses and infants with BRA (that which Potter originally described in 1946). Since then, the term Potter syndrome has become a misnomer and experts have attempted not to eliminate the terminology, but to modify it in a way so as to be able to determine the different root causes by creating a nomenclature system. However, this classification system has not caught on in the clinical and research fields. Classic Potter sequence occurs when the developing fetus has bilateral renal agenesis, which also presents with agenesis of the ureters. BRA has been estimated to occur at a frequency of approximately 1:4000 to 1:8000 fetuses and neonates. However, recent analysis has estimated that the condition may occur at a much greater frequency. The condition has been reported to occur twice as common in males as in females, suggesting that certain genes of the Y chromosome may act as modifiers. However, no candidate genes on the Y chromosome have yet been identified. BRA appears to have a predominantly genetic etiology and many cases represent the most severe manifestation of an autosomal dominant condition with incomplete penetrance and variable expressivity. There are several genetic pathways that could result in this condition. To date, few of these pathways or candidate genes have been considered or analyzed regarding BRA. The majority of possible candidate genetic pathways are autosomal recessive in nature and do not coincide with the frequency or penetrance at which BRA occurs in the human population. Additionally, candidate genetic pathways would be expected to involve genes expressed in the developing urogenital system (UGS). Often, these same genes and/or pathways of interacting genes are also expressed in the developing UGS as well as the central nervous system (CNS), gut, lung, limbs, and eyes. Normal kidney development See kidney development. Importance of fetal urine Development of the mature kidney begins between weeks 5 and 7 of gestation. Fetal urine production begins in early gestation and comprises the majority of the amniotic fluid in the second and third trimesters of pregnancy. The fetus continuously swallows amniotic fluid, which is reabsorbed by the gastrointestinal tract and then reintroduced into the amniotic cavity by the kidneys via urination. Oligohydramnios occurs if the volume of amniotic fluid is less than normal for the corresponding period of gestation. The fetal urine is critical to the proper development of the lungs by aiding in the expansion of the airways - alveoli, by means of hydrodynamic pressure and by also supplying proline which is a critical amino acid for lung development. Alveoli are the small sacs in the lungs that exchange oxygen with the blood. If the alveoli, and thereby the lungs, are underdeveloped at the time of birth the infant will not be able to breathe air properly and will go into respiratory distress shortly after birth due to pulmonary hypoplasia (underdeveloped lungs). This is the primary cause of death to Potter sequence infants secondary to renal failure. The fetal urine also serves to cushion the fetus from being compressed by the mother's uterus as it grows. The failure of the metanephros to develop in cases of BRA and some cases involving unilateral renal agenesis (URA) is due primarily to the failure of the mesonephric duct to produce a ureteric bud capable of inducing the metanephric mesenchyme. The failed induction will thereby cause the subsequent degeneration of the metanephros by apoptosis and other mechanisms. The mesonephric duct(s) of the agenic kidney(s) will also degenerates and fail to connect with the bladder. Therefore, the means by which the fetus produces urine and transports it to the bladder for excretion into the amniotic sac has been severely compromised (in the cases of URA), or completely eliminated (in the cases of BRA). The decreased volume of amniotic fluid causes the growing fetus to become compressed by the mother's uterus. This compression can cause many physical deformities of the fetus, most common of which is Potter facies. Lower extremity anomalies are frequent in these cases, which often presents with clubbed feet and/or bowing of the legs. Sirenomelia, or "Mermaid syndrome" (which occurs approximately in 1:45,000 births) can also present. In fact, nearly all reported cases of sirenomelia also present with BRA. Other anomalies of the classic Potter sequence infant include a parrot beak nose, redundant skin, and the most common characteristic of infants with BRA which is a skin fold of tissue extending from the medial canthus across the cheek. The ears are slightly low and pressed against the head making them appear large. The adrenal glands often appear as small oval discs pressed against the posterior abdomen due to the absence of upward renal pressure. The bladder is often small, nondistensible and may be filled with a minute amount of fluid. In males the vas deferens and seminal vesicles may be absent, while in females the uterus and upper vagina may be absent. Other abnormalities include anal atresia, absence of the rectum and sigmoid colon, esophageal and duodenal atresia, and a single umbilical artery. Presence of a diaphragmatic hernia is also common in these fetuses/infants. Additionally, the alveolar sacs of the lungs fail to properly develop as a result of the reduced volume of amniotic fluid. Labor is often induced between 22 and 36 weeks of gestation (however, some of these pregnancies may go to term) and unaborted infants typically survive for only a few minutes to a few hours. These infants will eventually expire as either a result of pulmonary hypoplasia or renal failure. In recorded medical and research history BRA has proved to be 100% lethal in all cases of singleton births. Various other forms of the sequence are, or are near, 100% lethal. While genetic research has linked certain genetic mutations to be the cause of ARPKD, ADPKD and possibly MRD, to date no genetic mutation or chromosomal anomaly has been linked to be the cause of BRA. Chromosomal anomalies have been associated with BRA in certain cases (chromosomes 1, 2, 5 and 21), but these anomalies were not inherited and have not been observed in subsequent cases. Additionally, neither extreme substance abuse or environmental factors (high power line, mercury, etc.) have been reported to be linked to an increased incidence of BRA or other cause of Potter sequence. BRA and other causes of oligohydramnios sequence have been linked to a number of other problems, to include Down syndrome, Kallmann syndrome, branchio-oto-renal syndrome and others. The high-risk obstetrician or genetic counselor may ask for a blood sample from the fetus or will perform an amniocentesis. These samples are used to perform several tests, one of which may be to check for the proper number of chromosomes, called a karyotype, of the fetus. Some birth defects are known to be associated with missing a chromosome, having an extra chromosome, such as in Down syndrome, as well as by having a part of one chromosome break off and relocate to a portion of another chromosome (called a translocation). However, on each of the 23 pairs of chromosomes are thousands of different genes. While chromosomes are easy to visualize under a microscope and count, the genes on them are not. Genes are very small pieces of DNA when compared to the chromosomes they reside on. A gene contains a code for a protein and if the gene is mutated (different from normal) the protein that is made from it may not function properly - if at all. Unfortunately, genetic abnormalities could still exist despite having normal chromosomes. The only way to determine genetically inherited mutations in the infant is to perform a genome scan of the mother, father, affected infant and any unaffected siblings of the affected fetus. These analyses will reveal what genetic mutations are present in the affected infant, and by comparing these results to the surviving siblings and parents, it can be determined which mutations were inherited or were not. - ^ "oligohydramnios sequence" at Dorland's Medical Dictionary - ^ Liatsikos EN, Perimenis P, Dandinis K, Kaladelfou E, Barbalias GA (1999). "Mermaid and Potter's syndrome occurring simultaneously". Int Urol Nephrol 31 (3): 277–81. doi:10.1023/A:1007149414339. PMID 10672944. http://www.kluweronline.com/art.pdf?issn=0301-1623&volume=31&page=277. - ^ Potter EL. Bilateral Renal Agenesis. J Pediatr. 1946; 29:68.; Potter EL. Facial characteristics in infants with bilateral renal agenesis. Am J Obstet Gynecol. 1946; 51:885. - ^ WELCH RG (May 1958). "The Potter syndrome of renal agenesis". Br Med J 1 (5079): 1102–3. doi:10.1136/bmj.1.5079.1102. PMC 2028705. PMID 13536430. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2028705. - ^ Buchta RM, Viseskul C, Gilbert EF, Sarto GE, Opitz JM (August 1973). "Familial bilateral renal agenesis and hereditary renal adysplasia". Z Kinderheilkd 115 (2): 111–29. doi:10.1007/BF00440537. PMID 4744207. - ^ Banerjee A, 2003; Indian J Pediatr - ^ Siegel MJ, 2000; J Peri. - University of Iowa Potter Syndrome Research Group - Potterssyndrome.org, support website - Potter syndrome forums - 00350 at CHORUS - Giant Hero A book by Angie and Cecil Bellephant of Kankakee, Il. who lost their son, Titus, to Potter's sequence in 2003. The book, Giant Hero, is filled with information on Potter's resources, explanations and inspiration. Also see their book at Infinity Publishing, www.bbotw.com. The book, released in September 2008, is written by Tracy Ahrens and funded by the University of Iowa Potter's Sequence Research Group. Congenital malformations and deformations of urinary system (Q60–Q64, 753) AbdominalKidney Pelvic Vestigial Wikimedia Foundation. 2010. Look at other dictionaries: Potter syndrome — DiseaseDisorder infobox Name = Potter syndrome ICD10 = ICD10\|Q\|60\|6\|q\|60 ICD9 = ICD9\|753.0, ICD9\|658.0, ICD9\|761.2 (for oligohydramnios) ICDO = Caption = OMIM = MedlinePlus = 001268 eMedicineSubj = ped eMedicineTopic = 1878 DiseasesDB = 11252… … Wikipedia Séquence de Potter — La séquence (ou le syndrome) de Potter est une série de malformations caractéristiques du nouveau né suite à un oligo hydramnios. Caractéristiques Elle se caractérise par une agénésie rénale (qui cause l’oligo hydramnios), un faciès typique et… … Wikipédia en Français Potter facies syndrome — Pot·ter facies, syndrome (potґər) [Edith Louise Potter, American physician, 1901â€“1993] see under facies and see oligohydramnios sequence, under sequence … Medical dictionary Potter syndrome — a congenital condition characterized by absence of kidneys, resulting in decreased amniotic fluid (see oligohydramnios) and compression of the fetus. Babies have poorly developed lungs, a characteristic wrinkled and flattened facial appearance,… … Medical dictionary Potter facies — the characteristic facial appearance seen with oligohydramnios sequence (see under sequence), consisting of a flattened nose, receding chin, wide interpupillary space, large low set ears, and sometimes other anomalies … Medical dictionary Doege-Potter syndrome — Not to be confused with Potter sequence. Doege Potter syndrome Classification and external resources The structure of IGF 2, responsible for the hypoglycemia associated with Doege Potter syndrome Doege Potter syndrome (DPS) is a … Wikipedia Harry Potter and the Goblet of Fire (film) — Infobox Film name = Harry Potter and the Goblet of Fire caption = Promotional poster of the film director = Mike Newell producer = David Heyman writer = Novel: J. K. Rowling Screenplay: Steve Kloves starring = Daniel Radcliffe Rupert Grint Emma… … Wikipedia Scott–Potter set theory — An approach to the foundations of mathematics that is of relatively recent origin, Scott–Potter set theory is a collection of nested axiomatic set theories set out by the philosopher Michael Potter, building on earlier work by the mathematician… … Wikipedia Harry Potter and the Deathly Hallows — Part 1 Theatrical poster Directed by David Yates Produced by … Wikipedia Harry Potter influences and analogues — Writer J. K. Rowling cites several writers as influences in her creation of her bestselling Harry Potter series. Writers, journalists and critics have noted that the books also have a number of analogues; a wide range of literature, both… … Wikipedia	2	12	5	0	3	0.587147	8	4,336
Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Gender Dysphoria article more useful, or one of our other health articles. Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below. Synonym: gender identity disorder Gender dysphoria is the distress associated with the experience of one's personal gender identity being inconsistent with the phenotype or the gender role typically associated with that phenotype. Gender identity disorder is an outdated term as it erroneously suggests that being transgender is pathological. The role of health professionals in helping those who are transsexual or transgender is not to treat a disease, but to promote health and well-being in this group of people. This involves multidisciplinary care across a wide scope of health professionals. The World Professional Association for Transgender Health (WPATH) leads many groups in urging the de-psychopathologisation of gender nonconformity worldwide. The WPATH standards of care state that being transsexual, transgender, or gender-nonconforming is a matter of diversity not pathology. Gender dysphoria is the term used to describe the distress experienced by an individual about their assigned gender which is in conflict with their internal gender identity. For a DSM 5th edition (DSM-5) diagnosis, there must be a marked difference between the individual's expressed/experienced gender and the gender others would assign him or her, and it must continue for at least six months. Gender dysphoria is manifested in a variety of ways, including strong desires to be treated as the other gender or to be rid of one's sex characteristics, or a strong conviction that one has feelings and reactions typical of the other gender. Although there is wide support for a move to declassify gender identity issues as pathological, there remains a need for a diagnosis which will allow these individuals to access medical help and treatment which they may need to improve the quality of their lives. The term gender dysphoria therefore relates to the problems caused by the difference in experienced and assigned gender. The WPATH standards of care state: "The designation of gender identity disorders as mental disorders is not a license for stigmatization, or for the deprivation of gender patients' civil rights. The use of a formal diagnosis is often important in offering relief, providing health insurance coverage, and guiding research to provide more effective future treatments." In the words of Department of Health policy: "It cannot be overemphasised that being trans is not a mental illness." Trans or gender variant individuals are not necessarily dysphoric. Gender identity disorder Gender identity disorder remains a diagnosis under the ICD-10 classification. WPATH is involved in the forthcoming revision of this for ICD 11. Currently ICD-10 categorises being transsexual as a mental health illness. It defines gender identity disorder as: "A desire to live and be accepted as a member of the opposite sex, usually accompanied by the wish to make one's body as congruent as possible with one's preferred sex through surgery and hormonal treatment." Presence of the transsexual identity must be present for at least two years persistently and not be a symptom of another mental disorder. A person who feels a consistent and overwhelming desire to effect a transition and fulfil their life as a member of the opposite gender. Many transsexual people actively desire and complete gender reassignment surgery. Transgender, or trans An umbrella term for a number of different gender experiences, often used to include transsexual people, transvestites and cross-dressers. Trans woman/trans man Trans woman refers to an individual who has been assigned as a male at birth, but who later identifies as a woman. A trans man is an individual who has been assigned as a female at birth, but later identifies as a male. These are terms used to describe this person prior to having any surgery or obtaining a Gender Recognition Certificate (see below), as after either of these events, they would normally refer to themselves as a woman or a man respectively. Definitions are evolving, and may vary between users and cause some confusion. The Gender Recognition Act of 2004 in the UK allows transsexual people to change their legal gender. In the UK, individuals may apply to the Gender Recognition Panel for a Gender Recognition Certificate. Those applying under this process have to demonstrate that they have had a diagnosis of gender dysphoria and that they have lived in the changed gender role for at least two years. Once a Gender Regulation Certificate has been issued, that person should be identified as a man or a woman and not a 'trans man' or 'trans woman'. Once individuals have changed their name and formal style of address (ie Mr, Mrs, Miss, etc), their NHS records should be changed accordingly. A formal certificate should not be needed for this change to be affected. A review of this process is underway in the UK, with a move to streamline it and de-medicalise it. The Equality Act of 2010 in the UK protects all individuals against discrimination. This includes gender or gender reassignment along with other characteristics such as age, disability, race and religion. Prevalence figures vary and depend on methodology in studies attempting to establish data. A survey by the Equality and Human Rights Commission in 2012 of 10,000 people found 1% had some degree of gender variance. This was partly conducted to investigate the most appropriate ways and wording to collect data, and cannot necessarily be assumed representative of the population as a whole. A Gender Identity Research and Education Society (GIRES) publication in 2011, funded by the Home Office, estimates that prevalence is increasing. Its original report had estimated prevalence in the UK in 2007 as 20 per 100,000 people having sought medical help for gender variance. This represented 10,000 people of whom 6,000 had undergone gender transition. Of these, 80% were birth-assigned males choosing to become females, although this percentage is noted to be dropping. By 2010, 12,500 had presented for treatment. It was estimated that the number presenting for treatment is doubling every 6.5 years. The mean age of those presenting for treatment is 42. Those presenting for medical treatment are believed to be a tiny fraction of those affected by gender dysphoria. The GIRES report states currently around 100 children and adolescents are referred each year to the UK's single specialised gender identity service for this age. The number of referrals for this age group, however, is said to have been rising by 32% per year in recent years. The Gender Recognition Panel in the UK publishes statistics. In the July-September 2014 period, 76 applications for Gender Recognition Certificates were made and 54 were processed. Of these, 80% were granted a Gender Recognition Certificate. In this period of time it was noted there was the highest ever percentage of requests from those registered female at birth (47%). Overall the numbers of applications have been stable over a period of five years. There is likely to be a balance of a number of genetic, hormonal and environmental factors involved in gender dysphoria, but the cause is essentially unknown. Twin studies indicate genetic factors have at least some role. Individuals may present to a GP at various stages. They may have been living as a trans for some time and want help in accessing medical or surgical treatment. They may present with the symptoms of the stress associated with suppressing feelings, or with lack of acceptance/understanding displayed by friends and family. Depression, self-harm and suicide may be more common in transsexual individuals[12, 13]. This individual will need their GP to have an understanding, non-judgemental, confidential and supportive attitude in keeping with the duties laid down in the GMC Good Medical Practice guidance. The role of the GP is pivotal, not only in accessing specialist service but in providing ongoing support, endocrine treatment and monitoring. Some of the issues which it may be appropriate to explore include: - The timescale of the gender identity issue and any change over time. - The effect on relationships, job, family and social life. - The effect on health and well-being. Symptoms of associated depression. - Future ambitions and plans. - Any steps taken to live in the identified gender - cross-dressing, hormonal medication, changes to appearance. Specifically ask if there has been self-medication as there can be risks in taking medication without appropriate monitoring or medical advice. - Sexuality and relationships. - Perceptions and reactions of others, attitudes of significant others. - Feelings towards own gender-specific features such as genitals, breasts and body hair. - Support network. However, the presentation will differ in every individual, as will the relationship between that person and their GP, and the GP's own experience. It may be appropriate for some of these issues to be explored in secondary or tertiary services rather than in primary care. Children presenting with gender dysphoria may: - Prefer dressing in clothes usually worn by the opposite gender. - Prefer the type of play usually enjoyed more by the opposite gender. - Have more friends of the opposite gender. - State that they are a gender opposite to that which was assigned to them at birth. - Express a desire to be rid of their genitals, and find pubertal changes distressing. - Have experienced bullying at school. - Find it persists as they enter adolescence, or there may be remission - sometimes going on to homosexuality or bisexuality. Referral[4, 6, 15] Prior to referral a GP would normally be expected to: - Take a detailed history. - Assess whether any self medication is taking place and if so, screen for any side-effects or harms. - Perform a basic physical examination, including measurements of weight, height and blood pressure, as this may be relevant for endocrine treatment. - Assess mental health. Consider a concurrent psychiatric referral if the wait for a gender identity clinic is likely to be a long one and there are significant mental health problems. - Provide information on support groups such as tranzwiki. Referral of adults Swift referral to specialist gender services is the ideal. A number of NHS and private specialist services exist in the UK. GPs can refer directly to a gender identity clinic (GIC) in most of the UK. In England, prior approval from the clinical commissioning group (CCG) is not required. Specialist gender services consist of a multidisciplinary team, which may include psychiatrists, psychologists, psychotherapists, counsellors, surgeons of a number of specialities, endocrinologists, speech and language therapists, dermatologists, occupational therapists, nurses and social workers. Guidelines differ on advice for GPs about bridging prescriptions while the GIC appointment is awaited. The Royal College of Psychiatrists (RCPsych) guidelines advise that GPs consider prescribing of 'bridging' hormonal treatments to alleviate distress, but the British Association of Gender Identity Specialists advises against this, pointing out that GPs are unlikely to have the necessary confidence with prescribing and it is difficult for a GIC to advise before they have seen the person. The GMC advises that in occasional circumstances it may be necessary, such as when the person is already self-medicating and that involvement by the GP may protect from harmful side-effects or the risk of serious mental ill health. In this situation, the GP would be expected to screen for risks and arrange blood tests, and take advice from a GIC. Following assessment and treatment from a GIC, it may be that GPs will be asked to take on prescribing and monitoring of hormonal medication on a long-term basis. Referral of children and adolescents Young people under the age of 18 years should in the first place be referred to the local Child and Adolescent Mental Health Service (CAMHS). This is for assessment, diagnosis and support with associated psychological difficulties. Where appropriate, CAMHS may consider referral to the UK's only specialist gender service for children and adolescents, based in London (the Tavistock and Portman NHS Foundation Trust). Management[1, 4, 6, 17] In the UK, good practice guidelines for the assessment and treatment of gender dysphoria are laid down by the RCPsych, and endorsed by a host of organisations involved in management. These guidelines are informed by the Standards of Care set by the WPATH. Note that it is important to address users of gender services as they would wish to be addressed. Ask which they would prefer, discreetly, as soon as possible. Mistakes in gender address can cause offence and distress. Management is multidisciplinary and may involve any number of the following: - Psychotherapeutic support. - Endocrine treatment - see below for specific details. - Surgery. 12-18 months of endocrine therapy is usually required prior to surgical intervention. Surgical treatments include: - Chest surgery - breast augmentation or mastectomy. - Genital surgery - for those becoming male: vaginectomy, hysterectomy, salpingo-oophorectomy, phalloplasty, metoidioplasty, testicular prosthesis, scrotoplasty. - Genital surgery - for those becoming female: penectomy, orchidectomy, vaginoplasty, cliteroplasty, labioplasty. - Facial surgery - particularly feminisation surgery. - Vocal surgery - to change pitch of voice. - Speech and language therapy - help with developing gender-appropriate voice and communication skills. - Hair treatments - including hair transplantation, hair removal, hairpieces. - Exploration of fertility implications of treatment, and gamete storage. As with any hormonal treatment, risk factors must be assessed, and risks and benefits explained before treatment. Baseline and ongoing monitoring is required. Treatment, once initiated, is often lifelong. Some hormonal treatments are discontinued four weeks prior to gender surgery, and restarted four weeks afterwards. Endocrine treatment should be initiated and overseen by a specialist in this field. However, GPs will be involved in ongoing prescribing and monitoring, and therefore should be familiar with risks, contra-indications, etc, of individual preparations. For trans women, or for women following genital change surgery, the goal is to suppress androgens and provide oestrogen therapy. Traditionally cyproterone acetate or spironolactone have been used, but as these have been associated with risks and side-effects, increasingly depot injections of gonadotrophin-releasing hormone (GnRH) analogues are used. These include goserelin and leuprorelin. Typical doses would be goserelin 3.6 mg every four weeks, or 10.8 mg every three months. This would be stopped if gonads were removed surgically. Oestrogen supplementation can be delivered orally (1-6 mg per day) or subcutaneously (50-150 microgram patches every three days or in gel) with an optimum dose achieved by monitoring of plasma levels. Lipids, liver function and blood pressure should also be monitored. Contra-indications and cautions for oestrogen use should be considered (thromboembolic disease, migraine, cerebrovascular disease, coronary heart disease, etc). For trans men, or men following genital change surgery, the goal is to suppress oestrogens and provide testosterone therapy. Long-acting GnRH analogues as above are used to suppress ovarian function, and stopped if ovaries are removed. Testosterone replacement may be given in the form of depo injections (eg, Nebido® 1 g every three months, or Sustenon® 250 mg every 2-3 weeks) or by transdermal gel (5 g per day). Contra-indications and cautions should be considered (eg, breast cancer, uterine cancer, severe liver disease). Haemoglobin and haematocrit levels should be monitored as polycythaemia may occur. Hormone treatments in transsexual individuals are considered to be relatively safe, and although mortality is higher than in the general population, this is not thought to be related to hormone treatment. Routine screening in the transgender population Routine screening may be missed or appointments for inappropriate screening tests received in the transgender population due to current logistics. The NHS cervical screening programme, for example, cannot recall males. A trans man who still has a cervix should be offered routine cervical screening, and the GP will need to inform the cytology services that the sample does need to be checked. Women who were assigned to the male gender at birth do not need breast screening as their risk of breast cancer is very low. They would however be missed in the routine screening for aortic aneurysm but should be offered screening. A GP should be involved in setting up individualised reminders for appropriate screening and alerting the relevant services. Children and adolescents[16, 19] Multidisciplinary care is crucial. Most children and adolescents seen at the national specialist Gender and Identity Development Service are referred by CAMHS. Psychotherapy, counselling, and family therapy are integral aspects. The option of deferring puberty with the use of GnRH analogues is increasingly used to allow more time for the individual to be comfortable with their gender identity before undertaking any irreversible treatment. Gender dysphoria in children does not necessarily persist into adulthood; indeed, studies suggest it only does so in 6-23%. If gender dysphoria persists then hormone treatment may be considered from the age of 16 years. Seamless transition to adult care services at the age of 18 years should be the norm if this is the case. Outcome of the various treatments used has been difficult to establish but is generally considered to be good and continuing to improve. Generally assessments of outcome from genital surgery show benefit to well-being, cosmetic result and sexual function[20, 21]. Outcome of hormonal treatment has also been shown to improve well-being and quality of life. Few report regret following treatment. Studies have reported higher mortality rates in transsexual individuals, as well as higher rates of suicide and psychiatric morbidity[23, 24]. These rates are higher irrespective of whether gender-related surgery has taken place. Mostly mortality was not related to hormone treatment, although those treated with oestrogen may have a slightly higher mortality related to cardiovascular causes. Surgical complications may include necrosis, fistulae, stenosis, urinary problems, anorgasmia and poor cosmetic result. Side-effects of hormonal treatment may be a problem; minimisation of risks by lifelong monitoring is required. HIV disproportionately affects trans women, with an estimated prevalence of 19% in this population worldwide. Peer support and family support are conducive to good outcomes. Further reading and references O'Neill T, Wakefield J; Fifteen-minute consultation in the normal child: Challenges relating to sexuality and gender identity in children and young people. Arch Dis Child Educ Pract Ed. 2017 Dec102(6):298-303. doi: 10.1136/archdischild-2016-311449. Epub 2017 May 11. The Gender Recognition Act; Press for Change Hembree WC; Management of juvenile gender dysphoria. Curr Opin Endocrinol Diabetes Obes. 2013 Dec20(6):559-64. doi: 10.1097/01.med.0000436193.33470.1f. Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, version 7 2012; World Professional Association for Transgender Health (WPATH) What is Gender Dysphoria?; American Psychiatric Association. February 2016 Trans - a practical guide for the NHS; Dept of Health, October 2008 NHS England Interim Gender Dysphoria Protocol and Service Guideline 2013/14; Approved by the Clinical Priorities Advisory Group (CPAG) on 12 July 2013 The ICD-10 Classification of Mental and Behavioural Disorders; World Health Organization Good practice guidelines for the assessment and treatment of adults with gender dysphoria; Royal College of Psychiatrists (2013) Action to promote LGBT equality; GOV.UK. News story, July 2017 Technical Note - Measuring gender identity; Equality and Human Rights Commission survey, 2012 The Number of Gender Variant People in the UK - Update 2011; Gender Identity Research and Education Society Heylens G, De Cuypere G, Zucker KJ, et al; Gender identity disorder in twins: a review of the case report literature. J Sex Med. 2012 Mar9(3):751-7. doi: 10.1111/j.1743-6109.2011.02567.x. Epub 2011 Dec 6. Guidelines for the Care of Trans Patients in Primary Care; The Royal College of General Practitioners NI (RCGPNI) Barrett J; Gender dysphoria: assessment and management for non-specialists. BMJ. 2017 Jun 30357:j2866. Good Medical Practice - 2013; General Medical Council (last updated 2019). Trans healthcare; General Medical Council Gender Identity and Development Service (GIDS); Tavistock and Portman NHS Foundation Trust Hembree WC, Cohen-Kettenis PT, Gooren L, et al; Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017 Nov 1102(11):3869-3903. doi: 10.1210/jc.2017-01658. Meriggiola MC, Berra M; Safety of hormonal treatment in transgenders. Curr Opin Endocrinol Diabetes Obes. 2013 Dec20(6):565-9. doi: 10.1097/01.med.0000436187.95351.a9. Shumer DE, Nokoff NJ, Spack NP; Advances in the Care of Transgender Children and Adolescents. Adv Pediatr. 2016 Aug63(1):79-102. doi: 10.1016/j.yapd.2016.04.018. Epub 2016 Jun 3. Garaffa G, Christopher NA, Ralph DJ; Total phallic reconstruction in female-to-male transsexuals. Eur Urol. 2010 Apr57(4):715-22. doi: 10.1016/j.eururo.2009.05.018. Epub 2009 May 19. Klein C, Gorzalka BB; Sexual functioning in transsexuals following hormone therapy and genital surgery: a review. J Sex Med. 2009 Nov6(11):2922-39 Murad MH, Elamin MB, Garcia MZ, et al; Hormonal therapy and sex reassignment: a systematic review and meta-analysis of quality of life and psychosocial outcomes. Clin Endocrinol (Oxf). 2010 Feb72(2):214-31. doi: 10.1111/j.1365-2265.2009.03625.x. Epub 2009 May 16. Asscheman H, Giltay EJ, Megens JA, et al; A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2011 Apr164(4):635-42. doi: 10.1530/EJE-10-1038. Epub 2011 Jan 25. Dhejne C, Lichtenstein P, Boman M, et al; Long-term follow-up of transsexual persons undergoing sex reassignment surgery: cohort study in Sweden. PLoS One. 2011 Feb 226(2):e16885. doi: 10.1371/journal.pone.0016885. Radix A, Sevelius J, Deutsch MB; Transgender women, hormonal therapy and HIV treatment: a comprehensive review of the literature and recommendations for best practices. J Int AIDS Soc. 2016 Jul 1719(3 Suppl 2):20810. eCollection 2016.	2	19	7	0	0	0.976175	7	5,052
Recommendations of the Secretary of Health and Human Services, pursuant to section 264 of the Health Insurance Portability and Accountability Act of 1996 The Committee on Labor and Human Resources and the Committee on Finance of the Senate The Committee on Commerce and the Committee on Ways and Means of the House of Representatives Every day, our private health care information is being collected, shared, analyzed and stored with few legal safeguards. There was a time when our health care privacy was protected by our family doctors -- who kept hand-written records about us sealed away in big file cabinets. Today, revolutions in our health care delivery system mean that we have to place our trust in entire networks of insurers and health care professionals. The computer revolution means that our family secrets travel quickly from doctors to hospitals to insurance companies -- and cannot be protected by simply locking up the office doors each night. And, revolutions in biology mean that a whole new world of genetic tests have the potential to help either prevent disease or reveal our most personal secrets. Right now, the way we currently protect the privacy of our medical records is erratic at best -- dangerous at worst. It is time for our nation to enact federal legislation to protect the age-old right to privacy in this new world of progress. This report recommends that Congress enact national standards that provide fundamental privacy rights for patients and define responsibilities for those who serve them. Specifically, a federal privacy law should: - impose new restrictions on those who pay and provide for care, as well as those who receive information from them. It should prohibit disclosure of patient-identifiable infor mation except as authorized by the patient or as explicitly permitted by the legislation. Disclosures of identifiable information should be limited to the minimum necessary to accomplish the purpose of the disclosure, and should be used within an organization only for the purposes for which the information was collected. - provide consumers with significant new rights to be informed about how their health information will be used and who has seen that information. Providers and payers should be required to advise patients in writing of their information practices. Patients should be able to see and get copies of their records, and propose corrections. A history of disclosures should be maintained by providers and payers, and be made accessible to patients. - provide for punishment for those who misuse personal health information and redress for people who are harmed by its misuse. There should be criminal penalties for obtaining health information under false pretenses, and for knowingly disclosing or using medical information in violation of the Federal privacy law. Individuals whose rights under the law have been violated should be permitted to bring an action for damages and equitable relief. We are at a decision point. Depending on what we do, revolutions in health care, biotechnology, and communications can hold great promise or great peril. We must ask ourselves: Will we harness these revolutions to improve, not impede, health care? Will we strengthen, not strain, the very lifeblood of our health care system -- the bond of trust between a patient and a doctor. When all is said and done, will our health care records be used to heal us or reveal us? Without safeguards to assure that obtaining health care will not endanger our privacy, public distrust could turn back the clock on progress in our entire health care system. Instead, we must keep our eye on the future, and act today. The American people expect, and are entitled to, confidential, fair, and respectful treatment of health information about themselves. This report recommends that the Congress enact legislation requiring that treatment. The need for such legislation is found in the rapid changes in the ways that health care is provided, documented, and paid for in the United States. These changes pose a challenge to American values that are both complementary and competing. On the one hand, patients have a legitimate need for assurance of the confidentiality that permits them to be frank with their physicians about their health conditions and behavior. That assurance is fundamental to effective diagnosis, treatment and healing, and to the privacy that we in the United States cherish as essential to personal freedom and well-being. On the other hand, participants in the health care system -- insurers, governments at all levels, managed care organizations -- have legitimate needs for access to health records in performing their roles in the system. Furthermore, those pursuing broad social purposes -- medical researchers, public health workers, governmental policy makers seeking to contain health care costs -- rely on the availability of data arising from these private transactions. Local public health agencies use health records to identify outbreaks of infectious disease, and to trace the source of infections like the recent e. coli infections. Researchers have used health records to help us fight childhood leukemia and uncover the link between DES and reproductive cancers. Until comparatively recently, any tension between these needs for confidentiality and access was resolved directly between patients and their physicians. They conducted an essentially one-on- one relationship, in examination, treatment and payment, and, with some exceptions, could limit access to information about the patient. The paper records once kept under the control of physicians are giving way to computerized information which is increasingly stored far from its source -- the patient and the physician -- in forms and even locations of which they may have only imperfect understanding. Even physicians may be frustrated in their traditional role as patient advocates by the complexity of the systems that process their patients' information. Moreover, patients may have little if any contact with some of the doctors and payers involved in their care. The result has been a weakening of the traditional, if often informal, controls that patients and physicians previously exercised to protect patient information. The President spoke to the importance of these concerns in his commencement address at Morgan State University on May 18, 1997. He said that "technology should not be used to break down the wall of privacy and autonomy free citizens are guaranteed in a free society". He acknowledged the special concerns surrounding health records in his call for enhanced protections for privacy in the face of new technological reality, when we are facing "the frightening prospect that private information -- even medical records -- could be made instantly available to the world." Our Nation's participation in the Global Information Infrastructure (GII) has sharpened the issues, and our plans for that participation include attention to privacy protection. The statement of the President and Vice-President, A Framework for Global Electronic Commerce reflects this concern and commitment: Americans treasure privacy, linking it to our concept of personal freedom and well-being. Unfortunately, the GII's great promise -- that it facilitates the collection, re-use, and instantaneous transmission of information -- can, if not managed carefully, diminish personal privacy. It is essential, therefore, to assure personal privacy in the networked environment if people are to feel comfortable doing business. The concern about confidentiality of health information appears against a backdrop of more general concern about privacy, well expressed by Alan Greenspan, the Chairman of the Federal Reserve Board: The fears of invasion of privacy, as a consequence of inexorable forces seemingly out of the control of the average American, has risen to a major public policy issue. (Speech, Conference, "Privacy in the Information Age", Salt Lake City, Utah, March 7, 1997) These concerns are not confined to the United States. The European Union (EU) has addressed the issue, and the EU data protection directive requires member States to "protect the fundamental rights and freedoms of natural persons, and in particular their right to privacy with respect to processing of personal data".(1) B. Why Federal Legislation is Needed The existing legal structure does not effectively control information about individuals' health. Federal legislation, establishing a basic national standard of confidentiality, is necessary to provide rights for patients and define responsibilities for record keepers. Today, patients often sign blanket authorizations allowing use of their medical information in order to obtain treatment or payment for care. These authorizations may not really protect us, in part because they do not provide useful information about how our health records will be used, who will see them, or how we can get access to them. Such authorizations are not always voluntary -- if we do not sign the blanket authorization, we may sacrifice the ability to receive care or insurance benefits. In addition, as the health care system becomes more integrated and more computerized, it is becoming difficult to determine the appropriate person or place where our health information can be accessed or controlled. For these reasons, we are recommending that Congress replace the ineffective use of authorizations with a system of Federal legislative controls on the use of health information collected by health care payers and providers. As described below, Federal legislation should authorize sharing information for health care treatment and payment, and prohibit use of that information for most other purposes. Such legislation should also provide consumers with specific rights to know how their information will be used, to get access to that information, to request correction of errors, and to know who has seen their medical information. Before turning to the details of our recommendations, however, it is important to describe the current situation, and the general consensus that Federal action is needed. Current Protections are Inadequate. Today the legal control of health information is, in general, a matter of State law. Limited Federal law covers specialized classes of information such as information about substance-abuse patients and information gathered in some Federally funded programs. The Privacy Act of 1974 provides some procedures and protections for records, including health records, held by Federal agencies. All States have legal controls on the use and disclosure of health information, including a few comprehensive acts similar in broad outline to the Federal legislation we recommend here. Two States have enacted the Uniform Health-Care Information Act recommended by the National Conference of Commissioners on Uniform State Laws in 1985.(2) Many State laws protect special classes of health information, about HIV infection and AIDS patients and about mental health patients, for example. Some State case law imposes confidentiality duties. These State laws vary greatly in scope and strength, and the situation has been described as "a morass of erratic law, both statutory and judicial, defining the confidentiality of health informa tion."(3) The Health Care Information System Is Increasingly Interstate. The health care system, particularly its information component, is very much an interstate activity, and will continue to develop in that direction. Computerization and telecommunications render the concept of "location" of information nearly meaningless. Patients receive care in more than one State, infor mation about them is moved electronically across State borders to obtain payment (often through and to places remote from the patient and the provider), and providers operate across many States. In its administrative simplification requirements, the Health Insurance Portability and Accountability Act of 1996 calls for uniform standards for electronic transactions in health administration precisely because separate standards developed at other than the national level are not workable. There is continuing movement toward a computer-based patient medical record, with national standards for content and format, and the possibility of ready interstate transmission as needed for patient care. A major impetus toward adopting this type of record was a report of the Institute of Medicine in 1991 that recommended adoption of the computer-based patient record as the standard for all patient care records.(4) Likewise, increasing use of telemedicine means that patient information will often cross State lines, sometimes in real-time delivery of care. This promising development is an important facet of the National Information Infrastructure because of its potential to provide greater access to quality health care for all Americans, especially those living in rural and remote areas. The Problems Are Urgent. The need for Federal protection is not theoretical; it is real and it is urgent. In a major American city, a local newspaper published medical record information about a Congressional candidate's attempted suicide. But it is not just public figures such as the Congressional candidate or Arthur Ashe (whose HIV status was published in a newspaper without his permission) who are at risk: - The director of a work site health clinic operated by a large manufacturing company testified before the National Committee on Vital and Health Statistics that he was frequently pressured to provide personal health information about his patients to their supervisors. - Until recently, at a Boston-based HMO clinic, all employees could tap into patients' mental health treatment records in the clinic's computer. In Colorado, a medical student copied health records at night and sold them to medical malpractice attorneys. - Medical records were dumped in a parking lot after a psychiatric clinic in Louisiana was sold. Inappropriate disclosure of personal medical information is not the only problem we are facing. Errors in health information, errors that can have profound financial effects, are often too difficult to correct. Such inappropriate handling of medical information can and should be prevented. Calls for Federal Legislation. Numerous analyses over several years by government, industry, and professional groups have identified serious gaps in protections for health information, especially in the unregulated exchange of data, and have recommended Federal legislation to close them. There also has been significant Congressional action toward this goal, including several comprehensive health privacy bills introduced by Senators Bennett and Leahy, Representative McDermott, and Representative Condit. The fact that Congress, in the Health Insurance Portability and Accountability Act, mandated that the Department of Health and Human Services produce these recommendations is further evidence that the Congress understands that the time has come for action. - Earlier this year, the National Committee on Vital and Health Statistics held hearings and advised on this issue. After six days of hearing witnesses from the full spectrum of public and private constituencies concerned with privacy, consumer interests, and operation of the health care system, the Committee strongly recommended that the 105th Congress enact a health privacy law.(5) - The Office of Technology Assessment, in a study of privacy and medical information, noted that lack of legislation "allows for a proliferation of private sector computer databases and data exchanges without regulation, statutory guidance, or recourse for persons wronged by abuse of data."(6) - A study of regional health data networks by the Institute of Medicine recommended Federal privacy legislation.(7) C. Recommendation for Establishing Federal Privacy Standards We thus conclude that Federal legislation, establishing a basic national standard of confidentiality, is necessary to provide rights for patients and define responsibilities for record keepers. Such legislation should provide clear guidance and significant incentives for the confidential, fair, and respectful treatment of personal information that the public expects. It should encourage administrative, technological, and management choices in design of health information systems to these ends. And it should provide redress to those adversely affected by misuse of information. We are aware that our recommendations come at a time of continuing, rapid change in the health care system and its information components. The standards for administrative simplification that the Department will soon publish, under the Health Insurance Portability and Accountability Act of 1996, will in themselves lead to new developments in the transfer and use of information. In addition, the boundaries between health information and other information are blurring. Marketing uses of health information and health uses of marketing information may ultimately make this activity a subject for legislation. New technologies and new uses, unthought of before now, will present new issues and new concerns. These possibilities may well warrant legislative attention in the future, and bear careful watching. Aware of these contingencies, and of the need they may present for further legislative attention, we nevertheless recommend that the Congress enact legislation now, based on what we know now. Today, we should move forward with legislation that protects the heart of the health care system -- those who provide and pay for health care, and those who get information from them. Delay will leave the public unprotected as more information flows to more places. Our recommendations are founded on five key principles: Boundaries. An individual's health care information should be used for health purposes and only those purposes, subject to a few carefully defined exceptions. It should be easy to use information for those defined purposes, and very difficult to use it for other purposes. Federal health record confidentiality legislation should impose a legal duty of confidentiality on those who provide and pay for health care, and on other entities that receive health information from them. Security. Organizations to which we entrust health information ought to protect it against deliberate or inadvertent misuse or disclosure. Federal law should require such security measures. Consumer Control. Patients should be able to see what is in their records, get a copy, correct errors, and find out who else has seen them. Our recommendations significantly strengthen the ability of consumers to understand and control what happens to their health care information. Accountability. Those who misuse personal health information should be punished, and those who are harmed by its misuse should have legal recourse. Federal law should provide new sanctions and new avenues for redress for consumers whose privacy rights have been violated. Public Responsibility. Individuals' claims to privacy must be balanced by their public responsibility to contribute to the common good, through use of their information for important, socially useful purposes, with the understanding that their information will be used with respect and care and will be legally protected. Federal law should identify those limited arenas in which our public responsibilities warrant authorization of access to our medical information, and should sharply limit the uses and disclosure of information in those contexts. Federal privacy legislation should not require any disclosure of information, except to patients who ask to see their own records. The recommended allowable disclosures are just that -- allowable. Thus, for disclosures that are not compelled by other law, providers and payers should be free to disclose or not, according to their own policies and ethical principles. We offer these recommendations as a basic set of legal controls. But ethics and professional practice will in many cases dictate more guarded disclosure policies. Similarly, where our recommendations would permit disclosure, they are not intended to create any new legal basis for refusing to disclose if such disclosure is required by other law. Finally, our recommended standards are not intended to preempt or supersede other laws -- State or Federal -- that are more protective of individual privacy. The effect of implementing our recommendations would be that some current uses of informa tion could not continue without patient authorization. Some organizations that get information with ease now may not be able to get information without patient authorization, or without meeting new requirements. We have designed the requirements to serve patients. These recommendations must steer a course between two extreme convictions: that privacy is already so compromised that attempts to control health information are futile, and that privacy is so weighty a value that we must reverse our efforts to use information effectively. Legislation must, therefore, strike a balance that permits socially important uses of information while protecting the privacy of people who seek care and healing. We believe our recommendations find that balance. The remainder of this Introduction is a summary of the scope and content of what we believe a Federal health information privacy law should provide. A more detailed description of our specific recommendations for the rights of patients and the obligations of those who hold health information follows. Our recommendations are framed as expressions of basic policy for the major choices in designing such legislation. We appreciate the difficult choices and complex accommodations required to make Federal health privacy legislation a reality. We look forward to working closely with the Congress in developing such legislation. E. Boundaries -- Recommended Scope of A Federal Privacy Law There are four situations in which health information is collected, disclosed, or used, and that we recommend be addressed by Federal health privacy legislation: Provision of and Payment for Health Care. A Federal health privacy law should focus on health care payers and providers and the information they create and receive for the provision and payment of health care, and on those who receive information from those payers and providers. Providers and payers are the foundation of the health care system, and the primary creators and collectors of health information. The provisions of a Federal privacy law generally should apply to information about a patient collected in the provision of health care services or in the payment for health care services. A Federal privacy law should apply uniformly, regardless of the setting in which health care is provided. A person seeking treatment should be able to discuss his or her medical condition freely, with confidence that the information will be protected, whether treatment is sought from a private physician or hospital, a company doctor, or a community health center. Similarly, the law should apply uniformly to all such information, whether the information is oral or written, on paper or in a computer. A Federal health privacy law should limit the ways providers and payers can use identifiable health information. However, it need not cover information that individuals voluntarily provide about themselves directly to parties other than providers or payers, such as retailers or marketers. Health care research that includes the delivery of health care should be included in Federal privacy protections. Information obtained in this context should be protected by a Federal privacy law. Research that does not involve care, but which is based on medical records obtained from providers and payers, should also be protected, since the information is obtained directly from the health care system. Employers that render on-site health care for their employees, or provide health benefits through a self-funded health plan, are acting as providers and payers, and in this context should be covered by a health privacy law. They should be able to collect and use identifiable health information for health care and directly related purposes, but should not use the information they collect a providers and payers for other purposes, such as hiring and firing, placement and promotions. Health information often is obtained from individuals for purposes other than the provision of or payment for health care, and we recommend that these situations be addressed by other legisla tion. Thus, these recommendations do not extend to the results of a fitness-for-duty examination. Nor do our recommendations address the need for protection of genetic information in Federal and State DNA banks and DNA data banks for casualty identification or criminal investigation, or of information generated in workplace drug-testing programs. Some existing uses of health information should not be affected at all, such as reporting of birth and death and reporting of abuse such as child abuse. The confidentiality risks of these collections of information should be (and often are) addressed by legislation specific to them. We recognize that distinctions among the various holders of health information are not always clear. We are particularly concerned about automobile and similar types of insurance that include a health coverage component. While these insurers may not be labeled "health insurers," as a practical matter they obtain the same information in the same ways, and serve the same functions, as health insurers. Similarly, there may be some grey areas regarding when an employer is functioning as a provider (and thus covered by a Federal privacy law) and when not. These are areas that would benefit from public debate and additional fact-finding. We continue to review specific instances, and may ultimately find that some information not now recommended for protection can and should be included in a Federal privacy law. Similarly, we recognize that the collection, development, and use of information about health matters by entities other than providers and payers can present serious privacy hazards. It may well be appropriate to impose confidentiality restrictions in those contexts. While we now recommend a Federal health privacy law limited to health information held by providers and payers (and those receiving such information from them), we also believe that the Administration and Congress must continue to examine the hazards to privacy when health information is held in other settings, and consider ways of controlling those hazards. Service Organizations. Providers and payers do not act alone. They engage other organizations to assist in processing health information. These "service organizations" may be claims processors, pharmacy benefits managers that provide information to pharmacists about coverage and drug interactions, or similar organizations that process information to help make the health care system work better. These organizations should be bound by the same restrictions that apply to the providers and payers from which they obtain the health information. Service organizations have access to patients' health information as an integral part of the provision of and payment for heath care, and should be bound by a Federal health privacy law. Limited Disclosures for National Priorities. Federal health privacy legislation should also allow certain uses of identifiable health information needed to support national priority activities. In exchange for this access to information, legislation also should place strict boundaries around the use and redisclosure of that information to ensure that it is used for the identified priority purpose only. The major national priorities which we recommend for this treatment are public health, oversight of the health care system, research, and law enforcement. For these activities, it is not always possible to obtain permission and, in many cases, doing so would create significant obstacles in our efforts to fight crime, protect public health, or understand disease. However, along with access should come the duty to use that information only subject to legislative restrictions on how the information may be used and disclosed, tailored to the particular situations. Disclosure with Authorization. Sometimes a patient will authorize a provider or payer to disclose information to a third person not directly subject to the Federal health confidentiality legislation that we recommend. In these cases, the patient should be able to enforce an agreement with that third person about how the information will be used. Federal law should impose an enforceable obligation on the recipient to use the information only in accord with the agreement made with the patient at the time of the authorization. For example, if a potential employer requires health information as part of a background check for security purposes, the applicant can authorize his or her health care providers to disclose the information. But the employer's use of the information should be governed by the employer's statement of how it will use the information, and that agreement should be enforceable. We recommend that a Federal health privacy law impose new restrictions on health care payers and providers who create and receive health information, and on those who receive information from those payers and providers. Specifically: - Patient-identifiable information should not be disclosed except as authorized by the patient or as explicitly permitted by the legislation. - Those holding such information should be required to implement security measures to protect the information against reasonably anticipated threats. - All disclosures of identifiable information should be limited to the minimum necessary to accomplish the purpose of the disclosure. - Patient information should be used within an organization only for purposes reasonably related to the purposes for which the information was collected. - A patient's authorization to disclose information should have to meet specific requirements. - A provider or payer should not be allowed to condition treatment, payment, or coverage on a patient's agreement to disclose health information unless the information is needed for treatment, coverage, or payment purposes. - Those receiving information through a patient's authorization should be required to abide by the terms of the authorization agreement, or face civil liability. The attached recommendations provide the details for how such restrictions might operate. Many of these recommended rules would simply codify sound professional practices. For example, a provider should be able to use identifiable health information for mailing reminders to patients to schedule appointments. It should not be able -- absent patient consent -- to make available its patient list to a health company for use in a direct mailing announcing a new product or service (even if that product or service might benefit the patient). Providers and payers should be limited in their internal use of information, so that, for example, employers who obtain health information through their operation of self-insured health plans (i.e. as payers) should be prohibited from using that information for personnel decisions. G. Consumer Control Americans should know what rules protect their health records, how those records will be used and shared, how they can obtain their records and, if necessary, how they can correct errors in their records. We recommend that Federal law provide consumers with significant new rights to be informed about how their health information will be used and who has seen that information. Specifically: - Providers and payers should be required to advise patients in writing of their information practices. This notice should state clearly how the information will be used, and should also explain the patient's rights to limit disclosures. - Patients should be able to see and get copies of their records, and propose corrections. - A history of disclosures should be maintained by providers and payers, and be made accessible to patients. Our intent is to incorporate basic fair information practices into the health care setting. The attached recommendations provide details for how to make these consumer controls real. The requirement to safeguard information must be supported by real and severe penalties for violations. Federal legislation should include punishment for those who misuse personal health information and redress for people who are harmed by its misuse. Specifically: - There should be criminal penalties (including fines and imprisonment) for obtaining health information under false pretenses, and for knowingly disclosing or using medical information in violation of the Federal privacy law. - Penalties should be higher when violations are for monetary gain. - When there is a pattern or practice of unauthorized disclosure or other violations, there should be civil monetary penalties. - Any individual whose rights under the law have been violated, whether negligently or knowingly, should be permitted to bring an action for actual damages and equitable relief. For knowing violation attorney's fees and punitive damages also should be available. Only if we put the force of law behind our rhetoric can we expect people to have confidence that their health information is protected, and ensure that those holding health information will take their responsibilities seriously. I. Public Responsibility A Federal health privacy law should permit limited disclosures of health information without patient consent for specifically identified national priority activities. We have carefully examined the many uses that the health professions, related industries, and the government make of health information, and we are aware of the concerns of privacy and consumer advocates about these uses. The allowable disclosures and corresponding restrictions we recommend reflect a balancing of privacy and other social values. Specifically, in addition to disclosure for health care and payment purposes discussed above, we recommend that Federal legislation authorize disclosure of health information without explicit patient consent for four national priority activities. Recipients of information under such a legislative authorization should also be bound by restrictions on use and further disclosure of the information, tailored to their particular circumstances. Oversight of the Health Care System (including audit, investigation, quality assurance, and licensure). Combating fraud, abuse, and waste in health care and related payment programs is a major national priority. In addition, we have both legal and ethical duties to improve the quality of health care and records review is essential to this important task. We recommend that the legislation not add additional restrictions to access to health information for these purposes. No new judicial or administrative procedure should be required before oversight agencies can see health records, or use them against patients, providers, and others for wrongdoing in health or related programs. At the same time, existing legal constraints that govern access to or use of such information by oversight organizations should remain in place. We are also recommending criminal penalties for obtaining health information under false pretenses. For Public Health, and in Emergencies Affecting Life or Safety. The importance of public health and emergency medical activities to our health and safety cannot be overstated. Health information is necessary for tracing the source of rapidly spreading infectious diseases, finding links between diseases and their causes, and rendering appropriate medical care to victims in emergencies. We recommend that there be no new procedural burdens in the way of these priority, often urgent, activities. At the same time, public health workers should be prohibited from redisclosing that information for any other purpose. For Health Research. Research is essential to our health care. Federal law should permit use of information for research without consent under carefully-defined circumstances, and should also include safeguards, including restrictions on redisclosure, to ensure that individual subjects are not harmed. Federal requirements should include a determination by an institutional review board that the research does not involve more than minimal risk, that the absence of consent will not harm the participants, and that the research would be impracticable if consent were required. We also propose accommodating the special needs of clinical trials. Generally, patients should have access to their own records. For clinical trials, however, we recommend a limited exception to permit agreements that research subjects typically make, such as to forego access to their trial- related records for the duration of their participation in the trial, as long as they are consistent with Federal rules for the protection of research subjects. Pursuant to Other Laws or Court Orders, such as: to Law Enforcement Authorities, to State Health Data Systems, and in Court Proceedings. Law enforcement agencies need access to health information for many purposes. We recommend that this Federal health privacy law not alter current practices; that is, it should neither expand nor contract current laws governing disclosure of health information to law enforcement authorities. In many instances, law enforcement authorities today can obtain, share, and use health information without patient consent and without legal process. We are not recommending changes to these practices. Similarly, existing legal constraints on law enforcement access to and use of medical information should remain in place. We recognize that new issues are raised by the search capabilities of computerized records, and that there are arguments in favor of new restrictions to address these possibilities. However, until more experience is gained with the uses of computerization of these records, and the types and frequency of requested searches, it is premature to change existing law in this area. J. How Federal Privacy Legislation Should Relate to Other Laws Any Federal legislation controlling health information must be understood in the context of other State and Federal laws that also address, either incidentally or directly, the confidentiality of health information. In short, we recommend that existing confidentiality laws at both State and Federal level which provide more protection remain in force. A new Federal privacy law should provide a basic level of protection for everyone -- a "floor" of protection -- without reducing other protections. State Law. As noted above, there exists today a patchwork of State health privacy laws. While some are comprehensive and strong, the array of protections we recommend here would, in general, be stronger than most existing State law. We recommend that Federal health privacy legislation supersede State law that is less protective than the Federal law. If either the Federal or State law forbids a disclosure, the disclosure should not be made. Thus, the confidentiality protections should be cumulative, and the Federal legisla tion should provide "floor preemption." We make this recommendation with the recognition that a single national standard may be preferable from the administrative simplification perspective, and that some privacy interests might also be better served thereby. However, at this time, the freedom of States to protect their citizens' privacy through their own legislation is more important than the benefits of standardization that totally preemptive Federal legislation would confer. The attention several States have given to this issue should be respected. Many States have statutes to protect informa tion about HIV infection and AIDS patients, and about mental health patients, designed after wide public debate to suit local needs. In addition, the Federal government can clearly learn from the experiences of States as they respond to the complex task of protecting patient information in a rapidly changing environment. Other Federal statutes that afford protection to liberty, privacy, and consumers' rights generally do not displace stronger State laws. At present, the goals of this proposal argue that it not break that tradition. In addition, Congress expressed a preference for leaving stronger State laws in place in the Health Insurance Portability and Accountability Act of 1996. That Act calls for the Secretary of Health and Human Services to impose confidentiality controls on electronic transaction systems if Congress does not legislate on confidentiality by August 1999, and directs that any such controls not supersede State law with more stringent requirements.(8) Likewise, the standards for administrative simplification of health financial and administrative transactions, which that Act requires the Secretary of HHS to promulgate, may not supersede stronger State confidentiality laws.(9) Privacy needs, developments in health data systems, and the interests of nationwide administrative simplification for health transactions may ultimately justify preemptive Federal legislation. But, at least at present, as the National Committee on Vital and Health statistics noted, "this issue need not be treated as a single problem with a single solution."(10) If the Congress enacts Federal legislation leaving State controls in place, the impact of the respective laws on individual privacy rights and on effective use of health information bears careful watching. To the extent that dual regulation impairs health care or the operation of infor mation and payment systems, poses risks to confidentiality arising from misunderstanding of the applicability of multiple laws, or creates uncertainty in patients about rights and redress, consideration of additional action, such as developing a single national law or preempting State laws in particular areas, may be warranted. Federal Law. Similarly, we recommend that a Federal privacy law not limit or reduce other Federal legal protections that control how information about individuals is disclosed or used. As with State law, Federal privacy protections should be cumulative. For example, even where the recommended Federal privacy law would allow a disclosure without patient consent or judicial process, it should not obviate the need to comply with other Federal statutes that do require consent or judicial process. Nor should it diminish any rights, of patients or record holders, to challenge disclosures under other Federal law. If another Federal law requires legal process, or specific showings, prior to a disclosure, a record holder should remain obligated to observe those requirements. For Federal health records, the records management requirements and subject access provisions of the Privacy Act of 1974 should continue to apply. But we recommend that the Privacy Act's disclosure provisions be replaced by the general health information disclosure restrictions we recommend, to the extent that the latter are more stringent than the Privacy Act. K. Particular Classes of Information At present, we recommend that Federal health confidentiality law treat all types of health information alike. The intent is to provide a meaningful minimum floor of privacy protections in Federal law for all types of health information. We recognize, however, that there is a great deal of support for providing additional protection to certain types of health care information that people feel to be particularly sensitive. For example, Federal and State laws already provide stronger protections for certain information, (such as information about HIV status, substance abuse patient information, and mental health records), and we recommend that these standards remain in place. We further recognize that additional types of particularly sensitive information may be identified for special protection in the future, and look forward to working with the Congress in determining when such protections are appropriate. * * * * II. The Recommendations 1. PROVIDERS AND PAYERS, AND THOSE WHO RECEIVE INFORMATION FROM THEM We recommend that Federal health privacy legislation apply primarily to health care providers and payers. We recommend that persons receiving information under the provisions of such legislation without patient authorization for health oversight, public health, research, State data system purposes be subject to the requirements of the legislation. We recommend that health care providers be defined as persons who receive, create, use, or maintain, health information while providing health care in the ordinary course of business or practice of a profession, pursuant to license, certification, registration, or other legal authorization. We recommend that payers be defined to include persons who pay for health care through contracts of insurance or in connection with employment, and government programs that pay for care under a benefit plan. The legislation we recommend should apply in the first instance to providers of health care and payers for health care. They are at the heart of health care, and typically receive information directly from patients and generate health information. They are often one and the same. In turn, others who receive health information under the provisions of the legislation without patient authorization should be bound by its requirements. They are referred to as "those receiving health information under the provisions of the law without patient authorization." Providers are persons -- individual and institutional -- who receive, create, use, or maintain, health information while providing health care (including preventive health services) in the ordinary course of business or practice of a profession, pursuant to license, certification, registration, or other legal authorization. Health care payers pay for health care pursuant to advance agreements or statutory obligations -- the range of entities commonly described as "plans." They may include licensed insurance companies, hospital or medical service corporations, health maintenance organizations, or other entities licensed or certified by a State to provide health insurance or health benefits. They include employee welfare benefit plans and other arrangements that provide health benefits, whether or not funded through the purchase of insurance policies or contracts. They include public programs that pay for health care under a health benefit plan, such as Medicare, Medicaid, the health programs of the Veterans Health Service, and the Civilian Health and Medical Program of the Uniformed Services (CHAMPUS). The term should not be defined to include individuals and families who pay for their own care. The definition does not encompass liability insurers who receive health information, as needed, pursuant to claimants' authorization. Nor does it include life insurers, who receive information, with the patient's authorization, not as part of health care or payment, but to make underwriting decisions. We are making no recommendations with respect to including workers' compensation under Federal health privacy legislation at this time. Although workers' compensation carriers receive health care information in much the same manner as health plans, the need under workers' compensation systems to coordinate the health benefits provided with both the indemnity benefits (e.g., lost wages and disability payments) provided under the system and the determination of a worker's ability to return to work raises potential questions about the appropriateness of certain disclosures of medical information. We are continuing to review the need for federal privacy standards in this area and will inform Congress of any recommendations that we have in this area when we complete our review. We do not recommend that employers as such be controlled by the legislation, But they should be considered health care providers or payers when they actually perform those activities, and obliged to conduct themselves accordingly. (Controls on employers' use of health information so obtained for other purposes is discussed below in LIMITATIONS ON USE). 2. COVERED ACTIVITIES We recommend that health care be defined to include -- any preventive, diagnostic, therapeutic, rehabilitative, maintenance, or palliative care, counseling, service, or procedure with respect to the physical or mental condition, or functional status, of a patient or affecting the structure or function of the body; -- any sale or dispensing of a drug, device, equipment, or other item pursuant to a prescription; and -- procurement or banking of blood, sperm, organs, or any other tissue for administration to patients. 3. COVERED INFORMATION We recommend that health information include any information, oral or recorded, in any form or medium, including demographic information -- that relates to the past, present, or future physical or mental health or condition of a patient, the provision of health care to a patient, or the past, present, or future payment for the provision of health care to a patient; -- that is received, created, used, or maintained by a health care provider in the ordinary course of business or practice of a profession, or by a health care payer, or received by entities receiving informa tion under the provisions of the legislation without patient authorization; and -- that identifies the individual, or with respect to which there is a reasonable basis to believe that the information can be used to identify the patient. We recommend that the legislation cover any information about the patient held by providers and payers for their health care and payment activities. Thus, information that in other settings would not be health information -- name, identification number, employment status, address, financial data, family size, education, employment history -- should be covered by the protections of the legislation we recommend if held by a health care provider or payer for health care or payment purposes. The description of identifiability we recommend follows the text of the administrative simplification provisions of the Health Insurance Portability and Accountability Act of 1996 (Social Security Act § 1171(6)). We recommend that a legislative definition be no more specific at this time. A precise advance definition is difficult, and there is inadequate basis at this time for recommending one. The only effective formulation now is a test of reasonableness: Information is identifiable if there is a reasonable basis to believe that the information can be used to identify an individual. No single rule can define what constitutes readily identifiable data. Information is clearly identifiable if it includes a name, social security number or other generally known or readily available identification number, or photograph. Health information will normally be identifiable within providers and payers, and the identifiability question will typically have to be answered when information is to be disclosed outside a provider or payer. Reasonableness may depend on a judgment based on what other information is known to be available to a recipient, and the amount of effort and time that would be needed to achieve a positive identification. Other legal formulations are not more precise than the HIPAA formulation. The European Union data protection directive, a recent well-debated formulation of privacy rules, uses this test: an identifiable person is one who can be identified, directly or indirectly, in particular by reference to an identification number or to one or more factors specific to his physical, physiological, mental, economic, cultural or social identity; (Art. 2(a)) The Council of Europe's "Recommendations of the Committee of Ministers to Member States on the Protection of Medical Data" (No. R(97)5 (1997)) states a reasonableness test, but adds an "effort" standard: ....the expression "personal data" covers any information relating to an identified or identifiable individual. An individual shall not be regarded as "identifiable" if identification requires an unreasonable amount of time and manpower. (Appendix, Art 1.) The standard we recommend should not be read to mean that information is identifiable if there is a remote chance that somebody might possibly be able to identify a patient from a general description. The Panel on Confidentiality and Data Access of the Committee on National Statistics addressed this issue, and noted that zero-risk requirements for disclosure of statistical records were unrealistic. It recommended a standard that calls for a "reasonably low risk of disclosure of individually identifiable data." (George T. Duncan et al, eds., Private Lives and Public Policies: Confidentiality and Accessibility of Government Statistics 137 (1993)). The panel recommended that the Office of Management and Budget should continue to coordinate re search work on statistical disclosure analysis (at 155-157). This will be especially important as changes in the character and availability of technology alter the quantum of information constituting an identifier. Our recommendations include authority for issuance of guidelines for what levels and amounts of information constitute "identifiable" information, and guidelines for minimum allowable disclosures in particular situations (IMPLEMENTATION, below). Records disclosed in a form not intended to be individually identifiable should not be used intentionally to identify a person. A person who obtains such information with the intention of identifying individuals should be regarded as having obtained health information under false pretenses (CRIMINAL PENALTIES, below). Our recommendations do not distinguish among different types of health information based on presumed sensitivity, although we recommend leaving in place State and Federal laws that make that distinction. Our intent at this time is to recommend a meaningful minimum floor of privacy protections in Federal law for all types of health information. At the same time, we recognize that there are arguments for providing additional protection to certain types of health information that people view as particularly sensitive. We can learn from, and build on, States' experience with privacy laws that protect such information, and work with interest groups, privacy advocates, and others to assess how such information is best protected. Such information could be the subject of future Federal action; we look forward to working with the Congress in determining when such protections are appropriate. We recommend that research in which care is not delivered not be considered "health care," and thus not covered. There are some existing protections for information gathered solely for re search, which should continue to apply (RESEARCH, below). 4. SERVICE ORGANIZATIONS We recommend that providers and payers, and those receiving information under the provisions of the legislation without patient authorization, be permitted to engage other organizations, "service organizations," pursuant to contractual arrangements, to carry out functions for them that require use of health information. We recommend that providers and payers be required to advise their service organizations that their work is subject to the law, whereupon these organizations should become subject to the law. We recommend that service organizations be obliged to observe the use and disclosure restrictions, and to have a statement of information practices and to make it available upon request, but not be obliged to provide subject access and correction rights. Much health information obtained and used by the providers and payers is processed by service organizations engaged by contract. The patient does not have a direct relationship with these organizations and typically does not know of their role in the flow of information. Physicians and other providers engage companies to code, and to process bills and forward them to the appropriate payer. These companies may in turn deal with others engaged by payers. Between them, yet other companies may process health information by passing it from a provider's clearinghouse to a similar organization engaged by a payer. In some instances, these organizations make substantive or adjudicatory choices affecting the patient on behalf of their principals. In others, they do not, and may not retain the information in ways that permit easy retrieval. Often there are not clear distinctions among the functions these many processors are performing. As an agent of a payer, a pharmacy benefit management company adjudicates and pays claims, and may manage a formulary. It also provide health care, in conjunction with the pharmacist, in looking for drug interactions -- advising the pharmacist, physician, or patient that a prescribed drug taken in combination with one prescribed earlier may have adverse effects. A payer may engage a pharmacy benefit manager to operate a disease management program to assist patients in managing their illnesses, often chronic conditions such as asthma and diabetes, by education through direct mail and telephone communication to the patient, online communication with phy sicians and pharmacists, and video materials. We recommend that everyone in this chain of information handling be covered by the same rules. Patients must be assured that their privacy protections are not lessened when the providers or payers with which they have established relationships give information to outside service organizations for processing. Thus, service organizations, once advised of the nature of the in formation they are handling, should be independently bound by the confidentiality restrictions applicable to the principal which engaged them. They should not use or disclose patient information unless their principals explicitly permit, and the principals should be bound by the legislation in granting such permission. Thus, a service organization should not make independent use of this information unless the provider or payer permits such use, and then only if the legislation permits such use, i.e., with the authorization of the patient, or for a purpose for which the payer or provider could use it or disclose it. The complexity and multitude of these arrangements, and the typical lack of contact with the patient, make it impractical to impose on service organizations the obligation to provide access and correction rights (discussed below in PATIENT INSPECTION AND COPYING OF RECORDS and PATIENT CORRECTION OF RECORDS.) However, patients should be able to exercise these rights by contacting their providers or payers, and providers and payers may by contract require their processors to provide the necessary access and correction. Service organizations should not be required by law to offer patients a statement of the information practices, but they should be required to have such a statement and to make it available upon request. Processing of information by these organizations is a natural and understandable source of concern. There have been proposals that patients be permitted to forbid the computerization of their records, or otherwise to control directly the flow of information through the payment system. The National Committee on Vital and Health Statistics considered this possibility and had this observation: The Committee is not sympathetic to the notion that patients should have a choice in the technology used to create, store and transmit health information. This is not a choice that record subjects [have] for records maintained by other third party record keepers such as banks and employers. Requiring health record keepers -- who are spending vast sums on computerization -- to retain parallel paper systems is impractical and costly. It would deny the benefits and savings that the Congress has already determined will result from increased use of modern information technology. Computers are an inevitable part of modern health care and indeed are intrinsic to the actual delivery of hospital care today. Patients must accept this and move on to debate the proper protections for records in a computerized environment. (Health Privacy and Confidentiality Recommendations of the National Committee on Vital and Health Statistics, Approved on June 25, 1997) Control at this level of detail would be harmful to patients, since the effective and rapid processing of information, often for the benefit of the patient, depends on computerized systems. Our recommendation is for legislation that permits relationships necessary to operate the care and payment system, with common legal controls on all concerned to protect the patient informa tion. However, should it appear in the future that patient interests are being compromised by contractual arrangements that obscure choices about use and disclosure of information, or that thwart legitimate patient control over information, Congress might want to consider imposing obligations directly on these entities. In addition to engaging outside organizations to process information about patients, providers and payers will on occasion need to give identifiable information to attorneys, insurers, auditors, and similar special-purpose service organizations. These recipients should be subject to the same use and disclosure restrictions that apply to the information in the hands of the providers and payers. A similar mechanism, provision for a "qualified service organization," has long been in use under the Federal substance abuse confidentiality statute (Public Health Service Act § 543, 42 U.S.C. § 290dd-1). The regulation interpreting that statute permits substance abuse treatment providers to share patient information with outside organizations under agreements similar to the ones we propose here (42 C.F.R. §§ 2.11 (Qualified service organization) and 2.12(c)(4)). 5. SERVICE ORGANIZATIONS - GOVERNMENT AGENCIES We recommend that providers and payers which are Federal, State, or local government agencies be permitted to employ other government agencies, in accord with applicable law, to carry out functions for them that require identifiable health information. The other governmental organizations should be subject to the same disclosure and use restrictions as the covered entity. This is a governmental counterpart to the previous recommendation. Entities which provide or pay for health care, including government agencies, should be obliged to limit patient health in formation to the units or organizations actually performing those functions. However, government health providers or payers might on occasion use either outside private organizations (as discussed above) or other parts of their own departments or other departments of government for functions that involve personally-identifiable information, such as central data processing facilities. Likewise, State attorneys general's offices, and the Department of Justice, provide legal services to State and Federal health care facilities and may in the course of that work have access to health information. For such divisions of work within government, existing statutes may govern relationships, and the private contractual model is not directly useable. But the service agencies should be subject to the same use and disclosure restrictions as the covered entity, and thus should not use information about patients obtained in the course of this work for other purposes. B. Basic Requirements We recommend that there be a duty not to use or disclose health information except as authorized by the patient, or as explicitly permitted by the legislation. We recommend that there be no duty to disclose information (except to the patient), and that other laws providing greater protection for health informa tion, or rights for the patient, remain in effect. 1. LIMITATIONS ON USE We recommend that providers and payers and those receiving information under the provisions of the legislation without patient authorization be permitted to use the health information only for purposes compatible with and directly related to the purposes for which the information was collected or received, or for purposes for which they would be authorized to disclose the information. We recommend that legislation constrain the use of information within organizations. Organizations with many purposes and activities do on occasion create or collect information while acting as health care providers or payers. They may also receive information from providers or payers. The fact that an organizational entity holds information is not a proper basis for its uncontrolled use within the organization. Under the requirement we recommend, entities holding records should have to make distinct and explicit choices about which activities are sufficiently connected with their health activities to warrant the use of identifiable health information. Other uses could be made only with patient authorization, or under provisions of the legislation that permit disclosure without patient authorization. This requirement should not interfere with normal uses of information in the health care delivery or payment process, but should prevent uses extraneous to health, and may limit some existing uses of health information. We recommend that this be a somewhat more restrictive control than the Federal Privacy Act, which permits disclosure to officers and employees of the agency maintaining the record who have a need for the record in the performance of their duties (5 U.S.C. § 552a(b)(1)). It is not possible or desirable to set forth in legislation all appropriate internal uses for health information by providers and payers. A general statutory standard is required, and so our recommendation calls for limiting use of health information to purposes compatible with and directly related to the purpose for which the information was collected or received. For hospitals, for example, the use of health information to provide health care is obviously within the purpose of collection, and providing health care includes a wide variety of activities like management analysis, quality assurance and similar oversight activities, carrying out mandates of law, teaching, training, and research activities. Likewise, a provider or payer should be permitted to use information internally for a purpose for which it could make a disclosure. This limitation on how patient information is used is especially applicable to organizations that are not primarily health care providers or payers, but that perform those functions, such as employers. This proposal is not intended to cover employers as such. Existing laws (such as the Americans with Disabilities Act of 1990 § 102 (42 U.S.C. § 12112) and the Rehabilitation Act of 1973, (29 U.S.C. § 793) (with regulation at 41 C.F.R. § 60-741.23)) constrain the collection, use and disclosure of health information by employers and should not be disturbed. But we recommend that employers, when they function as providers or payers, be required to conduct themselves as such under the legislation. Workers have worried that employers get health information about them, and often their families, in the claims payment process, and may use it to discriminate against them. (Marilyn J. Field and Harold T. Shapiro, eds., Employment and Health Benefits: A Connection at Risk at 148 (1993)). This study by the Institute of Medicine recommends explicitly (at 246) that employer access to certain information collected in connection with health benefits be limited through controls similar to those in the Americans with Disabilities Act of 1990. We recommend just such controls, by regulating how an employer uses information received in the payment process, either as a self-insurer or by processing claims en route to an insurance company. Information should not be used outside of the payment activity. An employer could not use it, for example, to make decisions about promotions or job assignments. Even if employers have information in identifiable form for statistical and analytic operations related to payment, or for oversight of an outside payer, the legislation should forbid its use for anything but these payment-related purposes. Employers should be required to build impermeable barriers between activities that use health information and their other activities. The same considerations apply to health care delivered by an employer, or on the employer's premises, or by employee assistance programs. The information obtained in rendering these health services should not be used by the employer for purposes outside the purposes for which it was collected, except as authorized by the patient or otherwise allowed by the law. The examples here are from the employment context; the requirement should be applicable to all who have health information. 2. SAFEGUARDS AGAINST DISCLOSURE We recommend that providers and payers and those receiving information under the provisions of the legislation without patient authorization be required to maintain reasonable and appropriate administrative, technical, and physical safeguards -- to ensure the integrity and confidentiality of health information; and -- to protect against any reasonably anticipated threats or hazards to the security or integrity of the information and unauthorized uses or disclosures of the information. We recommend the statutory formulation of a basic obligation of all record holders -- to safeguard the information. No legislation can effectively specify how to do this, but it can require diligent and attentive choices of security measures. The technology is varied and dynamic, and different types of technology and information call for different types and degrees of security. We recommend that the legislation require providers and payers to take the appropriate levels and types of protective measures. The legislation should not create an obligation of absolute security. The key words are "reasonable," "appropriate," and "reasonably anticipated," to permit consideration of the degree of risk, the likely consequences of compromise, and the expenditure, financial and other, required to address the risk. The measures should especially include employee education, clear and certain punishment for misuse, and technical controls on access to information within an organization, since there is evidence that a substantial threat to information is careless or deliberate misuse by those who have authorized access to it in their normal work activities. A growing body of policy and technical material will help managers in formulating their plans in this regard. The Office of Management and Budget has promulgated policy establishing a minimum set of controls to be included in Federal automated information security programs (OMB Circular A- 130, Management of Federal Information Resources, Appendix III, (February 1996)). A recent study (commissioned by the National Library of Medicine of the National Institutes of Health and funded by the Library with additional support from the NIH Warren G. Magnuson Clinical Center and the Massachusetts Health Data Consortium), identifies best practices in social and technical mechanisms for protecting privacy and maintaining security that are currently used in information systems for health care. (National Research Council, Computer Science and Telecommunications Board, For the Record: Protecting Electronic Health Informa tion (1997)). The Health Insurance Portability and Accountability Act of 1996 requires the Secretary of Health and Human Services to develop standards for electronic transmission of financial and administrative information about health transactions, including security standards. Most of these standards will be published for initial comment this year. The Center for Democracy and Technology has produced Privacy and Health Information Systems: A Guide to Protecting Patient Confidentiality (1996), a guide to help designers of electronic health information systems to identify and deal with confidentiality issues. The Computer-based Patient Record Institute (CPRI) has produced a series of publications with guidance on security policies for computer-based patient records. (Guidelines for Establishing Information Security Policies at Organizations Using Computer-based Patient Records (January 1996), Guidelines for Information Security Education Programs (June 1995), Guidelines for Managing Information Security Programs (January 1996), Sample Confidentiality Statements and Agreements (May 1996), and Security Features for Computer-based Patient Record Systems (September 1996)). 3. MINIMUM DISCLOSURE We recommend that all uses and disclosures be restricted, to the extent practicable, to the minimum amount of information necessary to accomplish the purpose for which the information is used or disclosed. This recommendation is for an obligation to design systems to limit the amount of information that is disclosed to the minimum necessary for the intended purpose. Any judgment about what is practicable, and what is minimum, must take into account the technical capabilities of record systems and the costs of limiting uses and disclosures. It is likely to be easier to limit disclosure when disclosing computerized records than when providing access to paper records. Technological mechanisms to limit the amount of information available for a particular purpose, and make information available without identifiers, are an important contribution of computerization to personal privacy. For example, limited fields of information can be disclosed, and identifiers can be stripped. As a practical matter, sorting through paper records to ensure that only the minimum amount is disclosed will be expensive and time- consuming and can risk compromising the integrity of the record, and these factors relate to practicability. As technologies develop, it will become easier and cheaper to provide minimum information and to limit disclosure. We recommend that a Federal agency be authorized to issue guidelines for what levels and amounts of information constitute "identifiable" information, and guidelines for minimum allowable disclosures in particular situations. Recent studies have emphasized the value of privacy-enhancing technologies (PETS) in accomplishing necessary transactions with a minimum of identifying information. The Dutch Data Protection Authority and the Information and Privacy Commissioner for the Province of Ontario, Canada, both governmental privacy protection entities, recently collaborated in producing a report exploring privacy technologies that permit transactions to be conducted anonymously. (Information and Privacy Commissioner/Ontario, Canada, and Registratiekamer, the Netherlands, Privacy-Enhancing Technologies: The Path to Anonymity (1995)). The provision we recommend should not be a basis for automatic withholding of records in situations where the requester is best positioned to determine what information is necessary, such as oversight and public health investigations. C. Patient Awareness and Control We recommend that providers and payers, and those receiving information under the provisions of the legislation without patient authorization, be required to prepare a written notice to inform patients of their information practices and of the patients' rights regarding the health information. We recommend that the explanation be required to provide information on whatever rights the patient has with respect to information, including, if applicable -- the uses and disclosures of information authorized under the legislation and intended by the holder, as well the protections available; -- the right of the patient to prevent or limit disclosure in whatever circumstances that right exists; -- the right to inspect and copy information and to seek amendments; -- the procedures for authorizing disclosure of information and for revoking disclosure authorizations; -- the procedures for the exercise of rights under the legislation, and the procedures, if any, for complaint, redress, or appeal; and -- the fact that service organizations and those receiving information under the provisions of the legislation without patient authorization have explanations of information practices which are available upon request. We recommend that providers and payers be required to give patients this explanation, or at least advise patients affirmatively of its availability and provide a copy upon request. We recommend that service organizations and those receiving information under the provisions of the legislation without patient authorization be required to develop explanations of information practices meeting the same standards, and to provide a copy to patients upon request. An informed citizenry is essential to protection of privacy. The basic structures for protection of health information should include requirements that patients be told what is being done with in formation about them, and what their rights are. The Privacy Working Group of the President's Information Infrastructure Task Force formulated personal privacy principles (Principles for Providing and Using Personal Information (June 1995)), and three of them point to the centrality of public information and education: II.B. Notice Principle. Information users who collect personal information directly from the individual should provide adequate, relevant information about: - Why they are collecting the information; - What the information is expected to be used for; - What steps will be taken to protect its confidentiality, integrity, and quality; - The consequences of providing or withholding information; and - Any rights of redress. II.E. Education Principle. Information users should educate themselves and the public about how information privacy can be maintained. III.A. Awareness Principle. Individuals should obtain adequate, relevant information about: - Why the information is being collected; - What the information is expected to be used for; - What steps will be taken to protect its confidentiality, integrity, and quality; - The consequences of providing or withholding information; and - Any rights of redress. Likewise, the National Information Infrastructure Advisory Council (a public advisory committee to the President's Information Infrastructure Task Force) issued a statement, Common Ground: Fundamental Principles for the National Information Infrastructure (March 1995), which includes the following among its privacy and security principles: 10. Collectors and users of personally identifiable information on the NII should provide timely and effective notice of their privacy and related security practices. 11. Public education about the NII and its potential effect on individual privacy is critical to the success of the NII and should be provided. The reasoning behind these principles emphasized that the public should be aware of uses and transfer of information that may not be clear or obvious. Health information is transmitted and used by a large number of agencies and institutions, and patients should know at least in a general way where it is going, how they can make corrections, and how to find out more infor mation. The explanation is of special importance in view of our recommendation below (HEALTH CARE AND PAYMENT) that disclosures of health information for health care and for payment be permitted without patient authorization, but that patients be permitted to object to particular disclosures for these purposes. The explanation of the patient's right in this regard is an integral element (together with direct legal controls on use of information by providers and payers) of this more realistic and informed patient control of information that we offer to replace the consent processes under which patients now permit their records to be passed around. The Privacy Act of 1974 requires that Federal agencies advise the subjects of Federal records of their intended uses (5 U.S.C. § 552a(e)(3)). Cable television subscribers are entitled, under the Cable Communications Policy Act of 1984, to an annual notice of the cable company's informa tion practices (47 U.S.C. § 551(a)). The recommended requirement would bring these salutary practices to health information. All organizations should be required to have statements to inform patients, if they request it, of how they use health information, and what the rights of the patients are. The health care providers and payers, which have direct relationships with patients, should make this explanation available in an affirmative fashion, for example, at health care facilities, or with written material sent by mail to subscribers to health insurance plans. We recommend that the legislation require a written explanation that can be retained by the patient, so that patients can examine the policies and become aware of their rights at their leisure (when not under the anxiety sometimes attendant to receiving health care) and consult others as necessary. At the same time, we do not believe that it is desirable to prescribe in legislation the details of how the notice should be given. Federal agencies could incorporate in the explanation proposed here the notice of information practices required by the Privacy Act. Organizations that do not have direct contact with patients should also be required to prepare such an explanation and to make it available upon request. 2. PATIENT INSPECTION AND COPYING OF RECORDS We recommend that patients be allowed to inspect and copy health informa tion about them held by providers and payers. We recommend that patients be allowed to inspect and copy health information held by public health authorities, and by oversight agencies in any situation in which an oversight agency has made an adverse decision about the rights, benefits, or privileges of the patient. We recommend that those holding health information be permitted to deny patient inspection of particular information under any of these circumstances: -- the information is about another person (other than a health care provider) and the holder determines that patient inspection would cause sufficient harm to another individual to warrant withholding. -- inspection could be reasonably likely to endanger the life or physical safety of the patient or anyone else. -- the information includes information obtained under a promise of confidentiality (from someone other than a health care provider), and inspection could reasonably reveal the source. -- the information is held by an entity that has received it under the health oversight provisions of the legislation, and access by the patient could be reasonably likely to impede an ongoing oversight or law enforcement activity. -- the information is collected in the course of a clinical trial, the trial is in progress, an institutional review board has approved the denial of access, and the patient has agreed to the denial of access when consenting to participate. -- the information is compiled principally in anticipation of, or for use in, a legal proceeding. We recommend that providers and payers be permitted to deny inspection if the information is used solely for internal management purposes and is not used in treating the patient or making any administrative determination about the patient, or if it duplicates information available for inspection by the patient. We recommend, in instances where a patient is to be denied inspection, that the holder of the record be required to make available to the patient, to the maximum extent possible, any portion of the health information which is not allowed to be denied to the patient under the standards above. We recommend that providers and payers be permitted to charge a reasonable, cost-based fee for inspection and copying a record. We recommend that entities obliged to provide inspection rights be required to make a decision on patient inspection within 30 days of a request, and that if they deny inspection rights they be required to give the patient a written statement of the reason. We recommend that existing rights of subject access and correction under the Privacy Act of 1974 not be diminished. The ability to see one's own record is central to effective control of information and is a basic fair information practice. A patient's decision whether to disclose a record may depend on what the record says, and so access to the record is integral to making an informed choice to disclose in formation. The "Code of Fair Information Practice" recommended in 1973 by the Secretary's Advisory Committee on Automated Personal Data Systems includes as one of its five basic principles: There must be a way for an individual to find out what information about him is in a record and how it is used. (U.S. Department of Health and Human Services, Secretary's Advisory Committee on Automated Personal Data Systems, Records, Computers, and the Rights of Citizens 41 (1973)). The Privacy Protection Study Commission recommended that this right be available. (Personal Privacy in an Information Society 299 (1977)). A right to see one's record is available by law in 31 States (described in Public Citizen Health Research Group, Medical Records: Getting Yours (1995)), and has been a right (with very limited exceptions) in Federal health record systems since the Privacy Act of 1974 (5 U.S.C. § 552a(d)). The exceptions that we recommend provide for the limited situations in which, in the judgment of health professionals, access to the record by the patient would cause grave harm, or, in the case of oversight activities, would endanger the oversight activity, or in the case of clinical trials, would endanger a trial. There should be no obligation to employ the exceptions. In general, patients should be able to see and copy their records, but there should be a provision to permit health professionals to exercise their judgment to withhold information in the rare instances where that is appropriate. Further, the record holder should be able to deny access only to the portion of the record that falls within the stated exceptions. The record holder should redact the portions allowed to be denied, and should give the patient the rest of the information. There need be no obligation to let patients see information used solely for internal management purposes, which is a duplicate of the basic patient record (e.g., a back-up copy), or which is gathered for litigation. Some clinical trials will involve health care and thus will be covered by the law, and the usual right to see one's record raises a special issue in these cases. We believe that a right to see one's own record, properly managed, need not impair research. Subjects in clinical trials are often, by design of the research, unaware of the identity of the medication they are taking, or of other elements of their record. The research design precludes their seeing their own records and continuing in the trial. Further, patient access during the trial could endanger the entire trial. Thus, we recommend that it be clear that a patient can waive the normal right to inspect informa tion while the trial is in progress, regardless of the length of the trial. This waiver would be an element of the patient's consent to participate in the trial. The institutional review board should have to approve it, and the patient should be told clearly of this condition. The subject should have the usual right to see the record after the trial is completed. Some entities other than providers and payers should be obliged to provide patient access (and the related correction rights, described below). Public health agencies may be able to take actions to affect the lives of the patients. Some health oversight agencies can make operational choices that affect the patient, such as denial of payment, and it is essential that patients be able to see records held by these agencies, after a decision adverse to the patient is taken. Under current law, such disclosure is already required, and through adversary proceedings, patients can challenge incorrect information which served as the basis for the adverse decision. In other instances (e.g., an accreditation study of a hospital by the Joint Committee on Accreditation of Health Care Organizations) no individual patient interest is at stake in the oversight activity, and access is less significant. However, the right recommended here is not simply a right to fair procedure in an administrative transaction or criminal or civil legal action (which may be provided in any case by other law); it is a freestanding fair information practice right to see one's record at a time of one's choosing regardless of actual use in a proceeding or for decision making. It should be available unless there is a danger that patient access would impede the investigation. We recommend that any procedures established to implement these provisions not be unduly burdensome on law enforcement or oversight agencies. We do not recommend that researchers who receive information under the provisions of the legislation without patient authorization be obliged to permit patient access. In most instances, they have no direct contact with patients, and under our recommendations would be prohibited from using such information against a patient. The section on SERVICE ORGANIZATIONS, above, addresses the rights of patients to see in formation held by service organizations operating on behalf of entities that are obliged to give patients access to their records. 3. PATIENT CORRECTION OF RECORDS We recommend that patients be permitted to seek correction or amendment of health information about them held by any entity obliged to permit patients to inspect health information about them. We recommend that these conditions govern responses to such requests: -- if the entity makes the requested change, it must make reasonable efforts to inform others who have received the incorrect information about the change, who are identified by the patient; or who the entity knows have received the information, when it is reasonably foreseeable that the incorrect information may have an adverse impact on the recipient or patient. -- if the entity makes the requested change, it must make reasonable efforts to inform known sources of incorrect information. -- if an entity denies a request, it should inform the patient of the reasons for the denial and of any procedures for further review. The burden of proving that information needs to be amended or corrected should fall on the patient, and the legislation should not require a process for further review. -- if a patient's request is denied, the patient should have the right to file a concise statement with the requested correction and the patient's reasons for disagreeing with the refusal. This statement should be included in any subsequent disclosure of the disputed portion of the information about the patient. The holder may include a concise statement of its reasons for not making the requested change. This recommendation is intended to ensure basic fairness with respect to accuracy of informa tion. It follows the pattern established by the Privacy Act of 1974 for Federal agencies (5 U.S.C. § 552a(d)(2)). It is not intended to interfere with medical practice, or modify standard record- keeping practices. Reasonable attempts at notification of others should prevent the perpetuation and further transmission of erroneous information. The legislation should explicitly state a test of reasonableness in this regard, so that the vigor of the effort required is proportional to the importance of the information and the degree of hazard in disseminating incorrect information. We recommend that it be clear that this provision is not intended to provide a procedure for substantive review of decisions such as coverage determinations by payers. It is intended to deal with the content of records, not the underlying truth or correctness of the events recounted in them. Attempts under the Privacy Act of 1974 to use the Act's correction mechanism as a basis for collateral attacks on agency determinations have generally been rejected by the courts. We intend the result to be the same here. It is the standard practice of medical record keepers not to expunge any information in a treatment record. The usual procedure is to mark incorrect information and to add the correct information. Even if information is wrong, it is essential to the purpose of the medical record that the record reflect the information available when treatment decisions were made. We recommend no change in these practices, and there should be no requirement that information be erased or deleted. A record should be considered corrected or amended if incorrect information is marked as such, and the correct information added. 4. DISCLOSURE HISTORY We recommend that providers and payers, and those receiving information under the provisions of the legislation without patient authorization, be required to retain a history of all disclosures of health information made for treatment, payment, research, oversight, public health, emergencies, to State data systems, for law enforcement, in judicial proceedings, and with the authorization of the patient. We recommend that the record include the date and purpose of the disclosure; the name and address of the person to whom the disclosure was made or the location to which the disclosure was made; and where practicable, a description of the information disclosed. We recommend that patients be permitted to see this record, except in the case of disclosures to and by health oversight agencies and to law enforcement agencies where access by the patient could be reasonably likely to impede those activities. We recommend that the disclosure history be retained for the life of the record to which it relates. We recommend that there be no obligation on service organizations to retain a record of disclosures in the course of treatment and payment transactions. Patients ought to know who has seen information about them. This basic right was recommended by the Privacy Protection Study Commission (Personal Privacy in an Information Society 316 (1977), and is available, with limited exceptions, under the Privacy Act of 1974 (5 U.S.C. § 552a(c)). The ability to see who has seen one's record is a form of control on disclo sure. In a health facility where employees who receive care at the facility can easily check who has accessed their records, they often do check, and staff at the facility see this as an important confidentiality control (National Research Council, Computer Science and Telecommunications Board, For the Record: Protecting Electronic Health Information 98 (1977)). Our recommendation does not envision that the legislation specify any particular form for retention of this history, as long as the inquiring patient can find out where his or her information went. Health facilities may choose to keep the disclosure history in a patient file, in a separate log, or in any other way, as long as it is possible to identify or accurately reconstruct the disclo sures. Our recommendations call for an exception to the right of patient access when access could be reasonably likely to impede oversight or law enforcement activities. We recommend that any procedures to implement these provisions not be unduly burdensome on oversight or law enforcement agencies. No accounting should required for disclosures made under the next-of-kin and directory information provisions (described below). D. Disclosures Authorized by the Patient We recommend that providers and payers, and those receiving information under the provisions of the legislation without patient authorization, be permitted to disclose information pursuant to the authorization of a patient under the following conditions: -- the authorization is in writing, is dated, and is signed or otherwise authenticated; -- the authorization states an expiration date, or event, and is received by that date or event; -- the authorization specifies the information to be disclosed; -- the authorization specifies the entity or entities which are to disclose the information; -- the authorization specifies the person or persons to receive the infor mation; -- the authorization states that the patient has received a statement of the intended use of the information by the recipient; and -- the authorization is not on the same form on which a patient consents to health care, and states that treatment, coverage, and payment are not conditioned on the patient's authorization to disclose, unless the disclosure is necessary for treatment, coverage, or payment. We recommend that a person who requests a patient to authorize disclosure of health information be required to give the patient a copy of the authorization. We recommend that a patient be permitted to revoke an authorization to disclose information except to the extent that action has been taken in reliance on the authorization. We recommend that entities disclosing information pursuant to an authorization be required to retain a copy of the authorization, and a record of the disclosure. The ability to control use and disclosure of information is central to fair information practices, and we recommend requirements to ensure that the patient understands the nature of the disclo sure being authorized, and to ensure that there is adequate specificity to the patient's authorization, and to ensure that authorizations do not become general permissions for unrelated disclosures. The required signature may be an electronic authentication. To assist in preparing these authorizations, the Federal agencies should be authorized to publish model authorization forms and model statements of intended uses (see below, IMPLEMENTATION). 2. DISCLOSURE WITH PATIENT AUTHORIZATION: EXPLANATION, AGREEMENT, AND REMEDY We recommend that a person who requests a patient to authorize disclosure of health information be required to provide a statement for retention by the patient, not on the same form as the authorization, specifying the purposes for which the information is sought and the uses and disclosures to be made of it. We recommend that use or disclosure of the health information inconsistent with the statement be the basis for a civil action for damages. This recommendation is intended to provide patient control in the many situations in which patients authorize others to receive health information about themselves. It addresses informa tion that moves beyond the direct scope of the law we recommend. These disclosures are made for many reasons. Applicants for life or disability insurance authorize providers to disclose existing information about themselves, and are informed by the insurer how the information will be used, including, for example, for reports to the Medical In formation Bureau, a clearing house of information about life and disability insurance applicants to detect fraudulent applications. Claimants in liability situations authorize their providers to send information to liability insurers to show the extent of their injuries. In case which move to litigation, a plaintiff will typically authorize an attorney to receive medical records and transmit them to medical consultants for review, and then to the defendant's insurer, to show the extent of the plaintiff's injury. Patients may authorize disclosure of health information when receiving other services, such as social services. Disability determinations in the disability program under the Social Security Act are dependent on the patient's offering evidence of his or her health condition. People may authorize disclosure of their information for suitability investigations by government agencies, or for employment or assignment determinations. Legislation cannot address all the possible uses of health information by the great variety of persons and organizations that may receive it pursuant to patient authorization. Nonetheless, patients properly expect fair treatment of this information, and should be able to enforce that expectation. This information, obtained as it is from the health care setting, retains its sensitivity, and should be protected in a legally enforceable way. Collection of damages for use inconsistent with the stated purpose is the recommended enforcement mechanism. This recommendation provides that protection by permitting the patient to enforce the agreement the patient and the recipient make. The recipient may choose to promise essentially no confidential treatment, or may choose to specify, in general or in particular, how the information may be used. In some instances, other law will govern how the information may be further used (as in some collections of health infor mation by government agencies), and that law would define the recipient's promises to the patient. The patient may be able to take these promises into account in deciding whether to dis close information in a particular instance. To assist in developing such agreements, the Federal agencies should be authorized to prepare model authorization forms and model statements of intended uses (see below, IMPLEMENTATION). This recommendation would implement one of the Principles for Providing and Using Personal Information (discussed above in EXPLANATION OF INFORMATION PRACTICES), formulated by the Privacy Working Group of the President's Information Infrastructure Task Force: III.C. Redress Principle Individuals should, as appropriate, have a means of redress if harmed by an improper disclosure or use of personal information. The President's statement on the Global Information Infrastructure, A Framework for Global Electronic Commerce (June 1997), in its discussion of privacy, reiterates this point: Under these principles, consumers are entitled to redress if they are harmed by improper use or disclosure of personal information or if decisions are based on inaccurate, outdated, incomplete, or irrelevant personal information. 3. DISCLOSURE WITH PATIENT AUTHORIZATION: PROHIBITION ON REQUIREMENTS TO AUTHORIZE DISCLOSURE We recommend that providers be forbidden to condition treatment on the patient's authorization to disclose health information, unless the disclosure is necessary for a health care or payment purpose. We recommend that payers be forbidden to condition coverage or payment on the patient's authorization to disclose health information, unless the dis closure is necessary for a health care or payment purpose. We recommend that providers and payers be required, when requesting an authorization to disclose information for purposes other than health care or payment, to advise patients that treatment, coverage, and payment are not conditioned on the patient's authorization to disclose. We recommend this requirement so that providers and payers cannot require patients to authorize disclosure of health information as a condition of treatment, coverage, or payment unless the dis closure is actually necessary for those purposes. Such demands could nullify the legislation's controls on disclosure of information. If needed benefits or services are not available unless the patient consents to disclose information, patients could be unfairly compelled to permit disclo sures beyond those permitted by the legislation. A patient seeking care or payment should be informed that he or she can resist a request for an authorization. It is important that the authorization clearly state that the patient will receive the same treatment, coverage, or payment, whether or not the authorization is signed (DISCLOSURE WITH PATIENT AUTHORIZATION: AUTHORIZATION CONTENT, above). This requirement should not interfere with health care or the normal operation of the payment system. Patients may properly be required to make available information necessary to treat them, or for reimbursement. Likewise, where such requests are not forbidden by other law, patients could be asked to disclose information about past health history for underwriting purposes. Patients could be asked to authorize disclosure for purposes other than health care or payment, like marketing, as long as treatment, coverage or payment is available whether or not the patient authorizes the disclosure. This recommendation is not intended to prevent researchers from requiring subjects to agree to disclosures necessary for participation in a clinical trial. Research subjects are often asked to consent to disclosure of their past health history, as well as to permit information generated in the trial to be reviewed by sponsoring and oversight agencies. These disclosures are integral to the operation of clinical trials, and the legislation should permit such conditions. E. Other Disclosures We recommend that providers and payers and those receiving information under the provisions of the legislation without patient authorization be permitted to disclose health information without patient authorization to provide health care to any patient, and for payment, but that patients be permitted to restrict disclosures of particular information or disclosures to particular persons. We recommend that the traditional control on use and disclosure of information, the patient's written authorization, be replaced by comprehensive statutory controls on all who get health in formation for health care and payment purposes. The reality of the present authorization process is that the patient has little actual control of infor mation. The approach we recommend would replace the often ritualistic authorization with direct statutory controls and a realistic and effective opportunity for patient intervention in instances where the patient finds it truly necessary. Disclosures for health care are made routinely now. A requirement for a signed paper for a routine referral can impair care by delaying consultation and referral. For example, a physician may decide, from review of test results after the patient has left the office, to refer the patient for consultation; the patient should not have to journey to the office again to sign a form before the physician can discuss the case with the consulting specialist. The provider should not be constrained in deciding whom to consult unless the patient has specifically indicated a sensitivity to such consultations. Some existing State health confidentiality laws permit disclosures without consent to other health care providers treating the patient, and the Uniform Health-Care Information Act permits disclo sure "to a person who is providing health-care to the patient" (9 Part I, U.L.A. 475, § 2-104 (1988 and Supp. 1996)). For payment, existing authorizations are often forms that have little meaning to the patient, and that the patient must sign if reimbursement is to be obtained. This process should be replaced by one in which information flows easily and without unnecessary barriers when necessary for payment, while protected by direct legal obligations on providers and payers. Changes in insurance carriers, for example, should not require multiple authorizations. A failure to obtain an authorization should not prevent a health care provider from billing payers who might not be precisely identified when treatment is rendered. In addition, information moves from provider to payer through a chain of processing entities (see SERVICE ORGANIZATIONS, above) whose precise identity may not be known to the provider in contact with the patient. A true, fully enforced, authorization requirement for each of these transfers of information would bring the health care payment system to a halt. The traditional goals of the authorization process are important ones, and we must have strong and realistic ways of meeting those goals. It is our view that stringent statutory protections on information held by providers and payers, and an opportunity for patients to object to particular disclosures (an "opt-out"), can fulfill these goals more effectively than the authorization formula. The explanation of information practices that providers and payers would have to provide should specifically note the patient's opportunity to object to particular disclosures. The opportunity to object to a particular disclosure is a more realistic and effective form of control than routine signature of an authorization form, and exactly for that reason it may require attention from providers in responding to patient wishes. In turn, patients will have to exercise care and judgment in using it. In the treatment context, some elements of medical history are irrelevant to present treatment, and patients may reasonably want them concealed. A patient's sexually-transmitted disease at the age of 22 need not be announced to all who are treating an athletic injury when the patient is 44. But current medical history, especially medications, and some past medical history, are very much relevant to present treatment, and the patient cannot withhold this information from subsequent providers without grave risk. There are dangers in making treatment decisions based on incomplete information, and providers may properly decline to treat patients without full understanding of their medical history. Legislation should not prevent physicians from conditioning treatment on having that history. Thus, if the patient chooses to restrict disclosure for treatment, the patient and the concerned providers would have to negotiate the patient's actual control in light of the need for the history in treating the patient. Likewise, disclosure to a payer is necessary for reimbursement. To the extent that the patient does not want information disclosed to an insurer or other payer, the patient must address the financial aspects of treatment in some other way. We recommend that the legislation be written to allow physicians to use any patient's record, not just the record of the patient being treated, to accommodate the practice in which a physician who is treating a patient with a rare disease may examine the records of other hospital patients with the same disease. Likewise, physicians may consult the records of several people in the same family or living in the same household to assist in diagnosis of conditions that may be contagious or that may arise from a common environmental factor. 2. HEALTH OVERSIGHT We recommend that providers and payers and those receiving information for health oversight without patient authorization under the provisions of the legislation be permitted to disclose health information without patient authorization, if such disclosures are authorized by other law and any requirements of other law have been met, for oversight of the health care system, including -- any assessment, evaluation, determination, or investigation relating to the licensing, accreditation, or certification of health care providers; and -- any audit, assessment, evaluation, determination, or investigation relating to the effectiveness of, compliance with, or applicability of, legal, fiscal, medical, or scientific standards or aspects of performance related to health care or payment, including claims for benefits based on health status, claims of eligibility for programs that produce eligibility for health benefits, and claims for other benefits in programs conducted or funded by governments. We recommend that public agencies, as well as other entities acting on behalf of public agencies, acting pursuant to a requirement of a public agency, or carrying out activities under a State or Federal statute regulating assessment, evaluation, determination, or investigation with respect to health care, be eligible for this access. We recommend that standard-setting organizations with which a provider or payer has a contract providing for review of the covered entity's activities be eligible for this access. We recommend that those receiving information under the provisions of the legislation without patient authorization for research and public health be permitted to disclose health information for oversight of the particular re search or public health activity holding the information, and that no use of the information against the patient be permitted except for wrongdoing in connection with the research or public health activity. We recommend that public agencies receiving information under this provision be permitted to disclose health information in accord with applicable law. We recommend that other entities receiving information under this provision not be permitted to disclose health information except for oversight purposes. We recommend that these disclosures be permitted so that there can be effective oversight of health care activities. The types of oversight organizations and activities are many, and range from traditional law enforcement agencies, to government agencies investigating or paying for health care, to the professional licensure and discipline system, to regulators like insurance commissioners, and to accreditation, standard-setting, and quality review organizations and activities. These activities occur under a myriad of circumstances, including pursuant to complaints about criminal behavior, as part of professional disciplinary proceedings, and pursuant to contract by facilities which wish accreditation and engage organizations to review their activities. These activities may be performed by a public agency, or by another organization acting on behalf of a public agency, pursuant to a requirement of a public agency, or carrying out activities under a State or Federal statute requiring or otherwise providing for the assessment, evaluation, determination, or investigation. The standard-setting organizations perform their functions pursuant to contract with the institutions they are examining and accrediting. The common features among these activities are these: All, at some point in their operations, need access to individually-identifiable records. Their effectiveness depends on access being controlled by the oversight entity, not the holder of the information, whose behavior and activities are under examination. The oversight activity is required because of the large volume of fraud and abuse in the health care system. It necessitates a substantial enforcement apparatus, including conventional law enforcement agencies (such as the Federal Bureau of Investigation, and State and local police departments), and specialized agencies (such as the Inspectors General of the Department of Health and Human Services, the Office of Personnel Management, and the Department of Labor, and State Medicaid fraud control units.) The General Accounting Office has estimated health care losses due to fraud and abuse as approximately 10 percent of outlays. Some of the activities investigated by the Office of Inspector General of the Department of Health and Human Services display the scope of the issue, and suggest how records are needed in the investigation: -- Billing of Medicare and Medicaid by nursing homes for unnecessary services and services which were not provided at all (OIG Special Fraud Alert, "Fraud and Abuse in the Provision of Services in Nursing Facilities" (61 Fed. Reg. 30623-30625 (1996)), including: A physician billing $350,000 over a 2-year period for comprehensive physical examinations of residents without seeing a single resident, and falsifying medical records to indicate that the services were rendered. A psychotherapist manipulating Medicare billing codes to charge for 3 hours of therapy for nursing home residents when in fact he spent only a few minutes with each resident. A speech specialist preparing documentation overstating time spent on each session, claiming to spend 20 hours with residents every day, and submitting some claims for residents he had never seen, and some who were dead. -- Billing of Medicare and Medicaid for services by home health agencies that were not provided, or provided by untrained personnel, or otherwise in violation of the rules governing reimbursement of home health services (OIG Special Fraud Alert, "Home Health Fraud, and Fraud and Abuse in the Provision of Medical Supplies to Nursing Facilities (60 Fed. Reg. Reg. 40847-4085 (1995), including: Billing Medicare for 123 home health visits to a patient who never received a single visit, and submitting claims for beneficiaries who were in an acute care hospital during the period the agency claimed to have provided home visits. Billing for a home health aide provided to a beneficiary who was not housebound, and actually very mobile. Claiming nearly $26 million during one year in visits that were not made, visits to patients who were not homebound, and visits not authorized by a physician, all supported by forging beneficiary signatures on visit logs and physician signatures on plans of care. Review of patient records was essential to the inquiries that identified these abuses. Some oversight activities, such as audits and evaluations, are done without direct access to identifiable patient information, since these inquiries take the form of a statistical inquiry to determine, for example, the rate at which a certain procedure is performed in a hospital or to calculate the average cost of a particular procedure. Computerized techniques make this possible without direct access to identifiers, and it is the practice of oversight agencies to do as much inquiry as possible without identified information. But there are many instances in which identifiers are needed. Even in a statistical inquiry of the type just described, in a paper environment individual patient charts must be examined, and the patient's name would be disclosed because it would be on each page of the chart. Other inquiries require review of individual medical records, to identify individual instances of the anomalies in treatment or billing patterns detected in statistical analysis. Billing abuses of the type cataloged above are detected by cross-checking the records of individual patients, to see the medical documentation in support of a service. The oversight agency reviews identifiable records to verify that it is comparing the same treatment history. Once an offense is identified and is to be prosecuted, a complete and intact record is required for evidentiary purposes, and due process requires that persons subject to sanction or prosecution have access to the precise factual basis for those actions. This recommendation is meant to permit disclosure of health information for inquiries that may not be solely about the actual delivery of health care. The definition of health care and payment encompasses "claims for benefits based on health, and claims of eligibility for programs that produce eligibility for health benefits and claims for other benefits in programs conducted or funded by governments." Fraudulent schemes sometimes involve several government programs, such as public assistance, food stamps, and disability programs, as well as health payment programs like Medicaid. Law enforcement officials work in teams to examine the common patterns in these activities, and we intend to permit, for example, the use of information about Medicaid beneficiaries in such investigations. Programs such as workers' compensation also involve review of health records to determine whether program requirements have been met. Patient records are needed for other inquiries relating to quality of care, and the rights of patients. The Peer Review Organizations authorized under title XI, part B of the Social Security Act (42 U.S.C. §§ 1320c et seq.) review the quality of care provided to Medicare beneficiaries. The Protection and Advocacy for Mentally Ill Individuals Act of 1986 (42 U.S.C. § 10801 et seq.) authorizes grants for State programs to investigate abuse and neglect of individuals with mental illness, and authorizes access to patient records for this purpose (§ 105(a)(4), 42 U.S.C. § 10805(a)(4)). State insurance regulatory agencies examine the records of insurance companies. The Department of Labor reviews plans under the Employment Retirement Income Security Act of 1974 (ERISA) (29 U.S.C. § 1134). State professional licensure agencies examine the records of health professionals, and may use evidence in them in taking action against the professionals. In the case of research, Federal reviewers may examine records to evaluate compliance with the regulation for protection of research subjects (45 C.F.R. part 46, and 21 C.F.R. parts 50 and 56). The Nuclear Regulatory Commission reviews records to determine medical licensees' compliance with its regulations. This recommendation does not propose any new judicial process prior to disclosure. The legisla tion we recommend should permit access to records without compulsory process where that access is otherwise allowed. However, it should not abrogate or modify other statutory requirements for judicial determinations or other procedural safeguards, or permit disclosures forbidden by other law. It should not abrogate or modify other legal restrictions on redisclosure of information, such as the requirement for court review for disclosure for purposes unrelated to health care of information obtained under the Attorney General's investigative demand authority in section 3486 of title 18 of the U.S. Code, added by the Health Insurance Portability and Ac countability Act of 1996, § 248. We also recommend that the legislation make obtaining health information under false pretenses be a Federal felony. Many investigative agencies have and use compulsory process authority. Inspectors General have it under the Inspector General Act of 1978 (5 U.S.C. App. 3, § 6(a)(4) (1988)). The Attorney General has a new investigative demand authority, mentioned just above, providing authority to examine any medical records in investigating health fraud, with power to invoke the aid of any court in enforcing the demand. In these cases, the statutes under which investigative authorities operate determine the procedure surrounding the demand. Thus, even if compulsory process is used for an oversight investigation, we recommend that there be no requirement for judicial consideration of the type required in the civil litigation situations described below under JUDICIAL PROCEEDINGS AND ADMINISTRATIVE PROCEEDINGS: PATIENT AS PARTY and JUDICIAL PROCEEDINGS: OTHER. 3. PUBLIC HEALTH We recommend that providers and payers and those receiving information under the provisions of the legislation without patient authorization be permitted to disclose health information without patient authorization, for public health purposes to -- a legally constituted public health authority for disease or injury reporting, public health surveillance, or public health investigation or intervention; -- anyone authorized to receive the information to comply with requirements or direction of a public health authority; or -- an individual authorized by law to be notified in a public health intervention. We recommend that a public health authority be defined as an authority of the United States, a State, a political subdivision of a State, or an Indian tribe, that is formally responsible for public health matters as part of its official mandate. We recommend that further disclosure by a recipient be limited to health care, public health, research, and oversight of the particular public health activity, except that no restrictions should apply to an individual who is notified in a public health intervention. Numerous important public health activities use identifiable information about patients. Disclo sure and use of information for those purposes, under careful controls to protect the patients, contributes to an important social benefit. Traditional public health surveillance, investigation, and intervention with respect to communicable disease continues to be important. Infectious disease is still a serious threat to health. In a report on this topic the Centers for Disease Control and Prevention offer as a major objective the expansion and coordination of surveillance systems for the early detection, tracking, and evaluation of emerging infections in the United States. The report states that "[s]urveillance is the single most important tool for identifying infectious diseases that are emerging, are causing serious public health problems, or are diminishing in importance." (Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, Addressing Emerging Infectious Disease Threats: A Prevention Strategy for the United States 12 (1994)). These well-known activities have been supplemented by carefully-designed and valuable assessment activities to collect information about other health conditions and injuries. Assessment activities (e.g., assessing the health needs of the community) embody several core public health practices that all communities need to perform (Michael A. Stoto et al., eds., Healthy Communities: New Partnerships in the Future of Public Health (1996)). Disclosures to facilitate these activities, including both reporting requirements imposed by statute and other collections of data based on more general authority, should be allowed. In all States, certain conditions are required to be reported to public health authorities, but the recommendation permits disclosure without an explicit statutory command to report an item of information. (Terence L. Chorba, et al., Mandatory Reporting of Infectious Diseases by Clinicians, 262 JAMA 3018-3026 (1989) and Eugene Freund et al., Mandatory Reporting of Occupational Diseases by Clinicians 262 JAMA 3041-3044 (1989)). Many public health surveillance activities are conducted without identifiable information, but some do require identifiable information. In some instances, identifiers are needed, but the infor mation may be used only in aggregate form. This is the case with surveillance programs for certain diseases and conditions where identifiers are needed to ensure an accurate count when duplicate reports may come from different sources. But there may be no intervention, and aggregate results are produced without reference to any identified individual. Disease registries, such as cancer registries, operate this way. State-based cancer registries are funded by the Centers for Disease Control and Prevention through the National Program of Cancer Registries (Public Health Service Act §§ 399H-399L (42 U.S.C.A. §§280e-280e4)). The Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute, operated since 1973, collects and publishes cancer incidence and survival data from population-based cancer registries covering approximately 14 percent of the U.S. population. It is from reports by hospitals and laboratories to these registries that we have accurate information about cancer incidence, survival rates, and geographical variations in our Nation. Other activities important to public health and safety are conducted by bodies like the National Transportation Safety Board. It investigates airplane and train crashes, in an effort to reduce mortality and injury by making recommendations for safety improvements, and it uses medical records in its investigations. Similar inquiries are conducted by the military services. The Occupational Safety and Health Administration, the Mine Safety and Health Administration, and the National Institute for Occupational Safety and Health also conduct public health investigations related to occupational health and safety. The Nuclear Regulatory Commission and State agencies working with it investigate occupational worker or general public radiation injury, and misadministration of radioactive materials to patients; these inquiries often require access to individually-identifiable health information. All of these activities relate to the public health and safety, and the legislation should permit disclosure for them. Other programs, directed toward communicable disease such as sexually-transmitted disease, involve contact with the individual and provision of health care, and occasionally, enforcement actions to prevent transmission of disease. All States have authority to isolate and quarantine individuals who endanger public health. The emergence of multi-drug resistant tuberculosis has renewed attention to these powers of States. The issues are discussed in Lawrence O. Gostin, Controlling the Resurgent Tuberculosis Epidemic, 269 JAMA 255 (1993). Surveillance of the effect of drugs and medical devices also involves collection of information, sometimes in identifiable form. The tracking of medical devices (under section 519 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. § 360i)) require that physicians report infor mation (sometimes including patient identifiers) to device manufacturers, and these reports may in turn find their way to the Food and Drug Administration. The proposal envisions that disclosures will be made not only to government agencies, but also to private entities as required or permitted by law. In tracking medical devices, for instance, the initial disclosure is not to a government agency, but to a device manufacturer that collects infor mation under explicit legal authority, or at the direction of the Food and Drug Administration. The cancer registries mentioned above are often non-profit organizations such as universities which receive reports from physicians and laboratories pursuant to State statutory requirements to report. These activities should not be impaired. We recommend a provision for disclosure to "an individual authorized by law to receive the information in a public health intervention" so that physicians or health departments, in carrying out public health interventions authorized by law, can notify individuals who have been exposed to a communicable disease. That notification may implicitly reveal the identity of the patient, but should be permitted as a disclosure in the course of an authorized public health intervention. The recommendation does not include a confidentiality obligation on the individual notified. The provision we recommend should sharply constrain public health agencies and other institutional entities receiving information in how they further disclose it. Public health authorities have a long ethical tradition of complete confidentiality in the conduct of their investigations, and are subject to confidentiality obligations under State law. The use and control of information by health departments is discussed in Lawrence O. Gostin, et al., The Public Health Information Infrastructure, 275 JAMA 1921-1927 (1996)). The Federal legislation should bolster those ethical and legal obligations by additional safeguards. Information obtained under the public health provision should not be further disclosed except for public health purposes (which may include action against individuals, such as in quarantine situations to protect the public health, with whatever disclosure that involves), for research, or for audit or investigation of the particular public health entity holding the health information. It may also involve use and disclosure of patient information in enforcement proceedings against entities. We recommend that providers and payers and those receiving information under the provisions of the legislation without patient authorization be permitted to disclose health information without patient authorization for re search. We recommend that disclosures be permitted only under the following conditions: The research would be impracticable to conduct without the individually-identifiable health information; The research has been approved by an institutional review board organized and operated in a manner consistent with and in accord with the institutional review board requirements of Federal Policy for Protection of Human Re search Subjects; and The institutional review board has determined that disclosure is allowable without the informed consent of the subjects, and, in making that judgment, has determined that -- the research project is of sufficient importance so as to outweigh the intrusion into the privacy of the patient who is the subject of the infor mation that would result from the disclosure; -- the research is of minimal risk; -- not obtaining consent will not adversely affect the rights and welfare of the subjects; and -- the research could not practicably carried out if consent were required. We recommend that a researcher receiving information be required to remove or destroy personal identifiers, at the earliest opportunity consistent with the purposes of the research, unless an institutional review board has determined that there is a health or research justification for retention of identifiers and there is an adequate plan to protect the identifiers from improper use and disclosure. We recommend that the health information so obtained not be further disclosed except -- pursuant to a reasonable belief that the disclosure is necessary to prevent or lessen a serious and imminent threat to the health or safety of an individual or to the public health; -- for another research project that meets the same conditions set out in the legislation for initial research disclosure; or -- for oversight of the research project. We recommend that information so obtained not be used or disclosed in any administrative, civil, or criminal action or investigation directed against the patient. Health research is an integral and essential part of modern health care, and the source of much of the knowledge on which medical treatment is based. Much of that research is based on analysis of existing health records, and thus access to health records is vital to research. Research based on health and other records has been an important source of information about the health of the population, and about how to prevent and treat disease. This research differs from research where there is an interaction with the researcher, and where the individual must of course be aware of the research and give informed consent. The latter activity may be covered as a form of health care, but is different from the records-based research for which disclosure without patient authorization is recommended here under certain conditions. A wide variety of research activities use health records -- biomedical, epidemiological, and health services research, and statistical activities. Likewise research on behavioral, social, and economic factors affecting health, and the effect of health on other aspects of life, may use health records. Use of records in research and the privacy aspects of such research are discussed in a recent report published by the Department of Health and Human Services, Privacy and Health Research, a report to the U.S. Secretary of Health and Human Services by William W. Lowrance (1997). Researchers have an excellent record for maintaining confidentiality of information they get this way, and privacy has not been harmed as a result. The Privacy Protection Study Commission, in its recommendation about health-care records, recognized the research uses of health records, and supported disclosure without patient authorization under stringent conditions, which are reflected in the present recommendations (Personal Privacy in an Information Society 309 (1977)). Much important and helpful scientific knowledge has come from large-scale studies using existing records. They are discussed in Leon Gordis and Ellen Gold, Privacy, Confidentiality, and the Use of Medical Records in Research, 207 Science 153-156 (1980). Among examples of valuable research findings are these: When mothers took DES during pregnancy to prevent a miscarriage, female offspring of these pregnancies were at increased risk of developing a rare type of cancer of the vagina when they reached adolescence. Workers exposed to vinyl chloride are at high risk of liver cancer. This finding could only be made by reviewing the medical records of large groups of employees and linking the employees' records at the factory site with hospital records and death certificates if they existed. The cause of increased risk of a form of blindness called retrolental fibroplasia in low birth weight infants was identified through examination of records. It was caused by high oxygen concentrations administered to premature newborns. Since this finding, use of a lower level of oxygen has virtually wiped out this form of blindness in premature infants. The treatment of acute leukemia in children was greatly enhanced by studies of medical records that showed that new forms of therapy were effective. Beta-blocker therapy resulted in fewer re-hospitalizations and improved survival among elderly survivors of acute myocardial infarction. State Medicaid policies restricting the number of prescriptions per month to prevent fraud and abuse also produced large declines in use of effective medications, adverse impacts on health status, and increased utilization of more expensive health care services. With this information, several States discontinued policies that limit prescriptions per month. The need to provide these records without contacting the patients results from the scale and type of studies using records, and their scientific characteristics. It is often impracticable, or impossible, to seek authorization from everyone in a records-based study of this kind. Some involve hundreds of thousands, and occasionally millions, of people. If it were necessary to seek authorization, some people would refuse, and some could not be found. In these cases, the people not included might have unknown common characteristics that would skew the results -- a problem that can render the results useless, and a special problem in studying rare health conditions, where a usable count depends on finding every case. The results of these inquiries appear as statistics -- aggregate results, with analysis and conclusions -- and no one's actual identity is ever published. However, the research does depends on information about specific individuals, and in the course of the research identifiers are sometimes necessary -- to be sure that there are not duplicate reports, or to match health records with other records, like records of treatment in several health facilities or death records, to determine the long-term effects of a condition or a treatment. In other cases, the research may call for identifying patients through existing provider records, and then contacting them and with their consent obtaining further information. There are effective techniques for contacts of this kind -- often by the provider after the researcher has identified them -- without revealing information to individuals other than the patient. This can all be done, and is done now, without harming the patient. Thus, we recommend that the legislation include conditions closely modeled on the regulation that protects subjects in research funded by Federal agencies, the Federal Policy for the Protection of Human Subjects (the "Common Rule," first published at 56 Fed. Reg. 28002-28032 (1991) and codified for the Department of Health and Human Services at 46 C.F.R. part 46 and 20 C.F.R. parts 50 and 56). Under this regulation, an institutional review board may waive the normal requirement for informed consent of the subjects if the research is of minimal risk, if the waiver will not adversely affect the rights and welfare of the subjects, and if the research could not be practicably carried out without the waiver (45 C.F.R. § 46.116(d)). However, we recommend that such protection be imposed by statute, and that there be criminal penalities for obtaining health information under false pretenses and for wrongful disclosure. These conditions help ensure that records are disclosed only after careful consideration, by requiring, for example, that researchers show that patient identifiers are genuinely needed for the research and that the expected results are of sufficient importance to warrant the disclosure. The "impracticable" test does not mean, and should not mean, that it is impossible to conduct the research in any other way, nor does it require that patient authorization be obtained if at all possible. Institutional review boards appropriately weigh such factors as cost, time and other resources available for data collection, and the quality of results. The proposal should not oblige anyone to disclose records for research. Some providers may conclude that their records, or portions of them, are so sensitive that they should not be disclosed to outside researchers, even under the careful conditions that currently govern research and that we recommend. It is fundamental to the protection of individuals in research that they not be disadvantaged by the research except to the extent that they know the disadvantage and voluntarily choose to accept it. The strict restrictions on further disclosure that we recommend would ensure that end. They come from this principle (called "functional separation") enunciated by the Privacy Protection Study Commission: Information collected or maintained for a research or statistical purposes may be not be used in individually identifiable form to make any decision or take any action directly affecting the individual to whom the record pertains, except within the context of the re search plan or protocol. (Personal Privacy in an Information Society 572-574 (1977)) 5. EMERGENCY PURPOSES We recommend that providers and payers, and those receiving information under the provisions of the legislation without patient authorization, be permitted to disclose health information without the authorization of the patient pursuant to a reasonable belief that the disclosure is necessary to prevent or lessen a serious and imminent threat to the health or safety of an individual. We recommend that disclosure be permitted only to a person reasonably likely to be able to prevent or lessen the threat. We recommend that information so disclosed not be permitted to be used in any proceeding against the patient except for proceedings related to the reason for its disclosure, but that there be no other control on the use or dis closure of this information by the recipient, except to the extent that the recipient is otherwise covered by the law. This recommendation addresses situations where it is necessary to disclose information to prevent harm to individuals. For example, law enforcement authorities may need information from a psychiatric record to predict the behavior of a person who is threatening others. Providers may be under an ethical or legal duty to warn someone of potential harm by a patient. The latter circumstance has been addressed in court cases, and the provision we recommend permits disclosures in accord with cases which require disclosure, of which the leading case is Tarasoff v. Regents of the University of California (17 Cal. 2d 425 (1976)). In that case, a psychologist was told by a patient that the patient intended to kill a third person. The psychologist notified the police but did not warn the intended victim. The patient subsequently killed that person. The Supreme Court of California found that the therapist had an obligation to use reasonable care to protect the intended victim against danger, including warning the victim of the peril. Many States have adopted (judicially or legislatively) some type of Tarasoff duty to warn, but not all State have done so. The provision we recommend takes no substantive position on a health care provider's duty to warn, but permits the disclosure if required or allowed under applicable law. An emergency disclosure provision does present some risks of improper disclosure, through, for example, a fraudulent telephone request with a claim that cannot be verified that information is needed for life-saving purposes. There will be pressures and uncertainties when disclosures are requested under emergency circumstances, and decisions must often be made instantaneously and without the ability to seek authorization or to perform complete verification of the request. We believe that this risk is warranted, and that the law should not hold record holders liable if they make a reasonable judgment and disclose information in good faith, even if later events reveal that the judgment was in error. It is difficult to predict who might receive information under this provision, and so we recommend that the control on further use be formulated as a prohibition on using the informa tion against the patient outside the occasion for the disclosure. This provision should not otherwise control redisclosure, so that it would not, for example, burden a private individual who is notified of a threat by a patient with legal sanctions for discussing the incident. Some recipients will be health care providers, and would be obliged to comply with the legislation regardless of where the information came from. 6. STATE HEALTH DATA SYSTEMS We recommend that providers and payers be permitted to disclose health in formation without patient authorization, if required or explicitly authorized by State law or regulation, for health data programs that collect health data for analysis in support of policy, planning, regulatory, and management functions identified by State statute or regulation. We recommend that information so obtained not be further disclosed except under the same conditions and circumstances applicable to information disclosed for research purposes. This recommendation is in support of State programs that collect data to analyze health care outcomes, quality, costs and patterns of utilization, effects of public policies, changes in the health care delivery system, and related phenomena to engage in better policy making, planning, regulation, and management. These programs frequently require reporting of information for all patients treated or released by specified classes of providers within the State. The recipient may be a State agency, or may be a private organization working in collaboration wit the State. In some instances the information is reported without identifiers, but in other instances it includes some form of identifier that may make the information identifiable under the standards we propose. The information is used to analyze trends in health care services and the costs of care. This activity partakes of the character of research, oversight, public health, and payment, but does not fall neatly into any one category. It is a valuable activity that offers the possibility of improved understanding of clinical, administrative, and financial aspects of the health care system. These benefits can be achieved while protecting the privacy interests of the patients. Like research, these activities sometimes need identifiable information, but the identity of the individuals is irrelevant to the outcome, and the results appear only in the aggregate. For these disclosures we recommend that the data collection be required or explicitly authorized by State law or regulation. As in the case of research, the principle of functional separation formulated by the Privacy Protection Study Commission is applicable. Thus, we recommend that the restrictions on further use of this information be the same as the restrictions on further use of information disclosed for research purposes (RESEARCH, above) We recommend that health care professionals involved in the direct provision of patient care be permitted to disclose health information, in connection with the patient's current treatment, to family members of the patient and others with whom the patient has a close personal relationship -- if the patient has been notified of the right to object to such disclosure and has not objected; or -- in circumstances where such notification has not been given, if the disclosure is consistent with good health professional practice and ethics. Certain routine communications take place with a patient's family and friends in connection with illness and injury. A spouse or parent should surely be told about the condition of a patient who has been injured or suddenly taken ill. A helpful neighbor assisting an elderly person being discharged from the hospital should be informed of the person's limitations in mobility, or of a health problem that requires ongoing practical help. A roommate or friend may be dispatched to the drug store to pick up prescription medication. In general, patients should have a choice about these disclosures, and providers should notify patients of this right, and proceed only if the patient does not object. It is not envisioned that formal written authorization will be obtained. There may be instances where it is not feasible to notify patients, but where communication with the family is necessary. In these cases, health care professionals involved in the direct provision of patient care should have the option of using their judgment, and informing relatives as necessary, in accordance with health professional practice and ethics. As with all permitted disclosures, providers should be able to decline to disclose in this fashion without consulting the patient. Institutions may impose on their employees policies which are more restrictive. No further control on the use or disclosure of this information by the recipient is appropriate. 8. DIRECTORY INFORMATION We recommend that health care providers be permitted to disclose, without patient authorization, the fact of a person's presence in a facility, and the location, and to describe the patient's conditions in general terms that do not communicate specific medical information about the patient, if the patient has not affirmatively objected in advance to these disclosures. Hospitals and other inpatient facilities serve as temporary residences, and directory information of this type is regularly provided to verify that a person is a patient in the facility, to assist visitors to the patient, to permit mail communication, and to let persons beyond the patient's immediate circle know in a general way of the patient's condition (in terms like "good," "fair," "stable," "serious," or "critical"). Patients should be permitted to restrict such disclosures, but we do not recommend a legislative requirement for notice of this opportunity beyond the required explanation of information practices more generally (EXPLANATION OF INFORMATION PRACTICES, above). Any institution should be free to have more restrictive policies, and many might choose to ask patients explicitly whether they agree to making directory information available. In the case of institutions which of their nature identify the condition being treated, disclosure of directory information would communicate specific medical information, and should not be permitted. No further control on the use or disclosure of this information by the recipient is appropriate. 9. LAW ENFORCEMENT: INVESTIGATION OF PROVIDERS AND PAYERS We recommend that providers and payers be permitted to disclose health in formation without patient authorization -- for investigation or prosecution of a covered entity, or -- to determine whether a crime has been committed and the nature of any crime that may have been committed, other than a crime that may have been committed by the patient, if such disclosures are authorized by other law, and all requirement of other law have been met. Law enforcement agencies often inquire into activities of providers and payers, and review health records in that process, without having any interest in the patients. This may occur, for example, in inquiries about compliance with tax laws, where a review of patient records might assist in estimating a provider's income, or in inquiries about compliance with safety and health laws, where review of health information might assist investigators. The patients are not the focus of the investigation and do not have an interest that warrants independent judicial consideration of the disclosure of their information. We are not recommending any changes to existing legal constraints that govern access to or use of patient information by law enforcement agencies. In addition, our recommendations would make obtaining health information under false pretenses be a Federal felony. In other cases, health information about a victim of a crime may be needed to investigate the crime, or to allow prosecutors to determine the proper charge. For some crimes, the severity of the victim's injuries will determine what charge should be brought against a suspect. For medical information to be relevant, the crime will normally involve bodily injury to the patient. Here again, while the patient is involved, the focus of the investigation is not the patient, but someone else. While the patient certainly has a privacy interest in the use of his or her information in the investigative process and judicial proceedings, this approach leaves control of this information to the procedures of the criminal justice system. 10. LAW ENFORCEMENT We recommend that providers and payers and those receiving information under the provisions of the legislation without patient authorization for oversight purposes be permitted to disclose health information without patient authorization -- to investigate a crime against, or on the premises of, a health care provider or payer, -- to comply with State law that requires the reporting of specific items of health information to a law enforcement authority, -- to assist in the identification or location of a victim, witness, suspect, or fugitive in a law enforcement inquiry, in situations similar to those in which State law requires disclosure of specific items of health infor mation to a law enforcement authority, -- upon request of a law enforcement official who states that the health information is needed for a legitimate law enforcement inquiry, and that the request complies with all applicable law, or -- upon the request of an official of the U.S. Intelligence Community, as that term is defined in section 3 of the National Security Act, 50 U.S.C. §401a, who states that the information requested is needed for a lawful purpose, if such disclosures are authorized by other law, and all requirement of other law have been met. We recommend that the Intelligence Community and law enforcement agencies which receive information under this provision not be subject to restrictions on its further use or disclosure, except as provided by other law. The disclosures we recommend here are an exception to a basic principle of the protections we recommend, which is to limit the use of health information to purposes connected directly with health care and payment. It is an instance of balancing private interests and the principle of public responsibility when law enforcement agencies need access to health information. Thus, we recommend that the legislation maintain current practices by permitting disclosure of health information to law enforcement authorities and permitting them to use that information, subject to other applicable law. These disclosures are necessary to protect the health care system and the public, and they comport with certain well accepted realities of law enforcement and the criminal justice system. We are not recommending any changes to existing legal constraints that govern access to or use of patient information by law enforcement agencies. In addition, our recommendations would make obtaining health information under false pretenses be a Federal felony. In instances where a crime is committed on the premises of, or against, a health care provider it may be necessary to review records. The presence of a patient in a particular location in a facility, or the timing of an observation in a chart, may help in identifying a suspect or an offense, and may incidentally disclose health information to investigators. The information needed may be limited, but could well include health information covered by the law. State laws commonly require that health providers report gunshot wounds, injuries associated with arson, and other specific conditions. In the same vein, police typically make inquiries in emergency rooms in pursuing persons injured while committing crimes. Responses to these inquiries, even if not specifically required by law, are analogous to the reports required by law, and serve to prevent health care facilities from becoming sanctuaries for fleeing criminals. These inquiries are usually close in time to the offense and the appearance for treatment of the patient in a health care facility. In other instances law enforcement authorities now get health information without patient consent, pursuant to other law. We are not recommending any changes to existing legal constraints that govern access to or use of patient information by law enforcement agencies. In getting information, law enforcement officials should have to comply with whatever other law was applicable. Thus, if State law permitted disclosure only after compulsory process with court review, a provider or payer should not be allowed to disclose information unless the law enforcement authorities had complied with that requirement. We recognize that there are arguments in favor of new confidentiality restrictions to address, for example, the law enforcement possibilities in the search capabilities of computerized health records. Until more experience is gained with the nature and speed of computerization of these records, and the types and frequency of requested searches, it is premature to change existing law in this area. Existing constitutional and other legal constraints would of course remain in place. The provision we recommend here should not permit health care providers to disclose at their own instance information about patients that is evidence of a crime (apart from crimes connected with the health care facility). The basic obligation of nondisclosure which we propose precludes this. This provision should be permissive, and health care facilities may, as far as the protection we are recommending is concerned, choose to refuse to cooperate with requests from law enforcement authorities. However, there may be other statutes that compel cooperation of the covered entity, and the legislation should permit this cooperation. 11. JUDICIAL AND ADMINISTRATIVE PROCEEDINGS: PATIENT AS PARTY We recommend that providers and payers and health oversight agencies be permitted to disclose health information without patient authorization -- pursuant to the Federal Rules of Civil Procedure, the Federal Rules of Criminal Procedure, or comparable rules of other courts or administrative agencies in proceedings in which the patient is a party and has placed his or her physical or mental condition or functional status in issue; -- if directed by a court in connection with a court-ordered examination of an individual; or -- to petition a court for guardianship or protective services for the patient. We recommend that the party seeking the information be required to give written notice in advance to the patient or patient's attorney. We recommend that providers and payers and health oversight agencies be permitted to disclose information in these circumstances only after receiving written notification that the above conditions have been fulfilled. The controls we recommend here of necessity intersect with existing procedural laws and rules of Federal and State courts and administrative agencies. We recommend that the legislation impose procedural controls on disclosure of information in these circumstances, but leave substantive judgments about use of the health information to the law governing the proceeding. In this type of proceeding, the patient's privacy interest is necessarily more limited than one in which the patient is not already a party, and in addition the patient is in a position to seek appropriate restrictions from the court. This provision for disclosure is intended to apply to administrative proceedings, such as appeal processes in Federal benefit programs. Our recommended procedure is meant to provide assurance to providers and payers that disclo sure is proper, and to give notice to the patient. A person seeking health information should be required to notify the patient or the patient's attorney of the request, and to give the holding entity a signed document attesting to this notification, and to give sufficient time to permit the patient to challenge the request. In particular, such a provision would provide an opportunity to object to demands for informa tion where the patient may have a proper claim that the request for information is too sweeping, or that the information is irrelevant to the proceeding. Some litigation reasonably requires medical information, but the patient's entire past medical history may not be relevant to the issue at hand, and its disclosure may be an inappropriate invasion of privacy. This procedure would ensure notice to the patient, and an opportunity to object in a timely fashion under the rules applicable to the proceeding. The dispute about the need for the medical information or the scope of the request could then be resolved by the tribunal considering the matter. The general rule that disclosures must be limited to the minimum amount of information necessary to accomplish the purpose for which the information is to be used should be fully applicable, and this rule could thus be used by patients to contest the scope of discovery requests. 12. JUDICIAL PROCEEDINGS: OTHER We recommend that providers and payers be permitted to disclose health in formation in a judicial or administrative proceeding (other than a proceeding in which the patient is a party and has put his or her condition at issue), pursuant to an administrative or judicial subpoena if the patient has been notified in advance and has not objected in a timely manner. We recommend that if the patient has been notified in advance and does object in a timely manner, the official issuing the subpoena not order the in formation disclosed unless the person seeking the information has demonstrated that -- there are reasonable grounds to believe that the information will be relevant to the proceeding; and -- the need for the information outweighs the privacy interest of the patient. We recommend that in determining whether the need for the information outweighs the privacy interest of the patient, the court or agency consider -- the particular purpose for which the information was collected; -- the degree to which disclosure of the information will embarrass, injure, or invade the privacy of the patient; -- the effect of the disclosure on the patient's health care; -- the importance of the information to the lawsuit or proceeding; and -- any other factor deemed relevant by the court. We recommend that a covered entity be permitted to challenge a demand for health information on any grounds available under this or other law. This recommendation addresses the need for health information in proceedings other than proceedings in which the patient is a party. The procedure we recommend is basically the same as for those situations. The test for disclo sure is somewhat different, in light of the need to demand a higher degree of justification for seeking health information in proceedings that are not law enforcement proceedings, or in which the patient is not already before the court. 13. JUDICIAL PROCEEDINGS: INFORMATION OTHERWISE ALLOWED TO BE DISCLOSED We recommend that disclosure be permitted without notice to the patient, or judicial determination, if the health information could be disclosed under other provisions of the legislation not requiring notice or judicial determination, provided that the conditions in the other provisions are satisfied. The procedural safeguards attendant to disclosure of health information in judicial proceedings should not be required when the information could be disclosed under other provisions without judicial proceedings. In these instances, the requirements of the other sections authorizing the disclosure provide safeguards for the individuals. Notice to individuals simply because compulsory process was being used would serve no useful purpose and might wrongly convey the impression that the patient was somehow being investigated. Disclosures that we propose be permitted without patient authorization are sometimes in fact made pursuant to compulsory legal process required or authorized by other law. Health oversight agencies have this authority (discussed in the HEALTH OVERSIGHT section, above). State and local public health agencies have subpoena or warrant authority to obtain information. The Occupational Safety and Health Administration and the National Institute for Occupational Safety and Health have authority to compel disclosure of health records for their public health and safety investigations and occupational health and safety research (29 U.S.C. §§657, 669), and the Mine Safety and Health Administration (30 U.S.C. §813) has similar authority. Should agencies with that authority have to use it, they should not be required to comply with the notice and judicial determination requirements applicable in other proceedings using compulsory process. The legislation should also provide that, if disclosure is conditioned upon a requirement to dis close in State law, Federal agencies may make the disclosure despite the inapplicability of State law to their activities. F. Specialized Classes of Persons and Entities We recommend that patients be covered by the protections of the legislation for two years after death, and that the right to control the patient's health in formation within that time be held by an executor or administrator, or in the absence of such an officer, by next-of-kin, determined under State law, or in absence of both, by the holder of the health information. Whether to apply confidentiality legislation to information about deceased patients is a difficult issue, with good arguments in favor both of protecting and not protecting this information. In traditional privacy law, privacy interests, in the sense of the right to control disclosure of infor mation about oneself, cease at death. The underlying purpose of health record confidentiality -- to encourage a person seeking treatment to be frank in the interest of obtaining care -- may require, from the patient's perspective, confidential treatment of information even after death. However, the problem of ensuring confidentiality after death is complicated by the traditional method of managing affairs after death -- control by an executor or administrator, who is often a relative. The result may be that the very people the deceased may have hoped would not know of his or her health condition will control the information. At the same time, perpetual confidentiality has serious drawbacks. If information is needed for legitimate purposes, there should be someone legally authorized to disclose it, by analogy with authorization by a living person. A permanent bar to disclosure would serve privacy interests only rarely, and could interfere with important and acceptable uses of information, such as historical research. A two year period of confidential treatment, with provisions for authorization by specific persons, would preserve dignity and respect by preventing uncontrolled disclosure of information immediately after death but permitting disclosure for proper purposes during this period. It should be noted that providers may, apart from legally compelled disclosure, choose to keep in formation confidential for a longer period. 2. IDENTIFICATION OF DECEASED PERSONS We recommend that health information be permitted to be disclosed to identify a dead person, or to aid a medical examiner's or coroner's investigation. Information from health records is used to identify dead persons, and this recommendation permits providers and payers to disclose information for this purpose. In an instance where in formation so disclosed reveals information about a living person, that information should not be used for any purpose relating to the living individual. Medical records are used in investigation of causes of death, and should be permitted to be disclosed for that purpose. 3. CORRECTIONAL AND DETENTION FACILITIES We recommend that health information about patients who are inmates of correctional facilities, or incarcerated in detention facilities, be available to prison and detention officials responsible for the custody and care of the inmates and detainees, and that no further restrictions apply to the use and disclosure of this information. We recommend that the rights and obligations of the legislation not apply to inmates or detainees, or the officials or entities responsible for their care and custody. This recommendation acknowledges the special situation of persons in correctional facilities, whose health care is a fundamental responsibility of the officials of those facilities. We recommend that patients below the age of 18 who, acting alone, have the legal capacity to apply for and obtain health care and who have sought such care, should have all rights under the legislation with respect to information relating to such care. We recommend that in cases not covered by the preceding condition, and in which the patients is age 14, 15, 16, or 17, either the patient or the parents or legal guardians be authorized to exercise all rights under the law. We recommend that the rights of patients under 14 years of age be exercised by the parent or legal guardian of the patient. These recommendations recognize the special situation of minors. They take into account the responsibility and concern of parents for their children, and at the same time acknowledge the ability under many State laws of minors to consent to their own care for particular conditions named in statute. 5. POWERS OF ATTORNEY We recommend that persons authorized by law (other than on account of minority) to act for a patient, or authorized by an instrument recognized under law, to act as agent, attorney, proxy or other legal representative, exercise all rights of the patient to the extent authorized by the grant of authority. We recommend that persons authorized by law, or by an instrument recognized under law, to make decisions about a patient's health care exercise the rights of the patient to the extent necessary to effectuate the terms or purposes of the grant of authority. These recommendations address situations in which patients have formally authorized others to act for them, or are unable to act for themselves. They are necessary accommodations in situations where, for purposes beyond decisions about information, others are acting for patients. As it relates to persons authorized to make health care decisions for others, this recommendation recognizes the power, under the laws of most States, of individuals to designate others to make health care decisions on their behalf, in the form of durable powers of attorney or similar instruments. The definition of rights we recommend is similar to one offered by the National Conference of Commissioners on Uniform State Law, in the Uniform Health-Care Decisions Act (9 Part I U.L.A. 93 (Supp. 1994)) in this circumstance. 6. PATIENTS UNABLE TO MAKE CHOICES FOR THEMSELVES We recommend that if a patient is not capable of exercising his or her rights under the legislation but has not been legally adjudicated as incompetent or has not had a legal representative appointed, the patient's rights under the recommended Federal privacy act be exercised by a person who holds a health care power of attorney for the patient, or in the absence of such a person, by next of kin, or in the absence of such a person, the health care provider. We recommend that anyone exercising these rights be required to do so in the best interest of the patient. This is intended to deal with situations where a patient is unable to exercise the rights under the confidentiality law, and there is no formal legal arrangement for others to exercise those rights. 7. BANKING AND PAYMENT PROCESSES We recommend that providers and payers be permitted to disclose, in connection with payment by debit, credit, or other payment card or account number, or other electronic payment means, the minimum amount of health information necessary to complete the payment transaction. We recommend that a debit, credit, or other payment card issuer, or anyone otherwise directly involved in payment or billing transactions through such means, be permitted to use or disclose health information about a patient only for authorization, settlement, billing or collection, and for other purposes directly related to these financial operations. Financial organizations such as banks that issue credit cards now process payment for health care. In the course of making payment for health care, and billing customers, they may incidentally receive health information. When a patient pays a provider using a credit card, the transaction does not use health information as such, and the provider should not include health information in communicating with the bank to receive payment. However, some health information can be derived by ready inference from information that is included in the financial transaction. The specialty of a provider, which is easily determined, may indicate the type of health care being received. The amount or pattern of charges may suggest with some precision the gravity or character of a patient's condition. Any health information so disclosed should be used only for the immediate purposes of the transaction. Since entities performing these functions are typically regulated as financial or credit institutions, and transactions with health information are integrated into their more general operations, there is no value in identifying them as payers or service organizations and subjecting them to the range of obligations imposed on providers and payers and their service organizations. The legislation should prevent them from using identifiable patient information for purposes beyond the immediate transactions. In particular, they should not be allowed to use health infor mation for purposes like direct marketing by the processor or by others, for the development of consumer profiles, for prescreening, for credit evaluation, or for other purposes. The limitations we recommend should not interfere with use of patient information in audits, transfer of receivables or accounts, or the range of activities that surround the sale or transfer of receipts, or any legal or regulatory access to information that is common to the transactions of the processor more generally. The intent is to prevent the use of health information as such for any purpose beyond those narrowly connected with payment. 8. DISCLOSURES WITHIN THE DEPARTMENT OF VETERANS AFFAIRS We recommend that disclosures of health information within the Department of Veterans Affairs for the purposes of the benefit programs of that Department be permitted without explicit authorization. In the Department of Veterans Affairs health information about its beneficiaries currently flows as necessary from its medical facilities to its benefits payment elements, to permit benefit determinations based on health status. There is little value in requiring, for these information transfers within that agency, that veterans give the same authorization they would have to provide, for example, to permit disclosure of a private provider's records to a private insurance company. Simplicity and convenience for the veterans, and reduction of merely formalistic documentation, warrant this exception to the authorization requirements. The Privacy Act of 1974 provides a structured framework for the maintenance of the information, and existing confi dentiality statutes cover DVA information without distinguishing health information from other information (38 U.S.C. § 5701). 9. MILITARY SERVICES -- MEMBERS We recommend that the Secretaries of Departments including military services be authorized to promulgate regulations permitting disclosure without patient authorization of health information about members of the military services, by health care providers and payers that are part of the military services or operating on behalf of the military services. The purpose of the health care system of the military services differs in its basic character from that of the health care system of society generally, and the leadership of the military services has a special relationship with its members. The special situation of the military services is acknowledged by the Constitutional provision for separate lawmaking for them (U.S. Const. art. I, § 8, cl. 14), and in their separate criminal justice system, under the Uniform Code of Military Justice (10 U.S.C. §§ 801 et seq.) Officials of the military services are responsible for the health of the members, and use informa tion, including health information, to make operational choices about assignment of personnel and other matters relating to the national defense functions. Examples include the medical status of pilots, the reliability of nuclear weapons personnel, and compliance with controlled substance policies. The normal role of the patient in authorizing disclosure of health information would be inconsistent with these responsibilities and relationships, and thus we recommend that the military departments be permitted to modify the disclosure rules as necessary. Under this recommendation, the rules could be modified for providers and payers which are direct military activities, as well as for civilian facilities serving members of the military services pursuant to contract (such as TRICARE managed care support contractors). We recommend that the authority to modify the disclosure rules apply only to health information about members of the military services. The legislation should not permit promulgation of regulations to permit disclosure or use of in formation that is restricted or controlled by other law. This recommendation is applicable to the Department of Defense and the Department of Transportation. 10. MILITARY SERVICES -- CIVILIAN EMPLOYEES AND CONTRACTORS We recommend that the Secretaries of Departments including military services be authorized to promulgate regulations restricting the revocation of authorizations for disclosure of information by civilian employees and contractors' employees in instances where ongoing access to health informa tion is necessary for the conduct of national defense functions. This provision addresses the situation of civilian employees of the military services, and contractor personnel, who authorize use of their health records to evaluate their suitability for deployment and other defense-related activities. Information about their health is needed on a continuous basis, and revocation of the authorization would interfere with use of the information, possibly in situations where the lack of information could have serious operational consequences. G. Relationship to Other Law We recommend that the legislation not preempt, supersede, or modify the operation of -- any law that provides for the reporting of vital events such as birth and death; -- any law requiring the reporting of abuse or neglect of any individual; -- the provisions of the Public Health Service Act regarding notification of emergency response employees of possible exposure to infectious diseases (Public Health Service Act subpart II, part E, title XXVI (42 U.S.C. §§ 2681-2690); -- any law requiring or explicitly authorizing the reporting of injuries or illnesses in connection with a workers' compensation program; or -- any law that establishes a privilege for records used in health professional peer review activities. These activities are all subject to existing law, and we recommend that they not be affected at all by the legislation. This proposal is not simply that disclosures to comply with these laws be allowed: it is that these disclosures and activities under these should not be affected at all. The reporting of vital events like birth and death may include health information, but the reports are made pursuant to an existing body of law which controls use of the information so disclosed, and are for public purposes beyond health care. All States have laws in this area, many based in whole or in part on the model statute promulgated by the National Center for Health Statistics (Centers for Disease Control and Prevention, National Center for Health Statistics, Model State Vital Statistics Act and Regulations (1992)). The reporting of neglect or abuse is addressed by law in every State. In workers' compensation programs, State laws require employers to report injuries to State agencies or workers' compensation insurance carriers. While in many cases these reports will come from employers and will not include health information, there will be instances in which a health care provider will make the report. The legislation should not affect these reports. To the extent that health information is used in health professional peer review activities, control of its use and disclosure should be left to the specialized statutes governing those activities. 2. PRIVILEGE STATUTES We recommend that a patient's authorization for disclosure of health infor mation for health care or payment, or disclosure under the legislation for those purposes without patient authorization not diminish, waive, or otherwise impair any testimonial privilege. Existing privileges, which in some instances can be abrogated by disclosure of the information covered by the privilege, should be preserved. 3. THE PRIVACY ACT OF 1974 We recommend that providers and payers now subject to the Privacy Act of 1974 remain subject to that Act. We recommend that these providers and payers be obliged to observe the disclosure restrictions of federal privacy legislation as well as any disclosure restrictions of the Privacy Act that are more restrictive than such legislation. We recommend that Federal agencies be permitted to make disclosures now allowed by the Privacy Act to the National Archives and Records Administration. The Privacy Act of 1974 (5 U.S.C. § 552a) was a pioneering statute for the use and control of personal information, and continues to serve the public well as a control on the use and disclo sure of information by the Federal government. Its significant contribution to privacy interests are its requirements that agencies maintain only information necessary to the agencies' purposes; that individuals have the right to access and to request amendment of their records; and that agencies be open about the records they keep and their uses and disclosures. Written to cover the wide variety of records found in the entire Federal government in 1974, including many of minimal sensitivity, its use and disclosure provisions are not highly restrictive. The Act explicitly identifies many disclosures as allowable without individual consent. Information may be used by employees of an agency who have a need to know the information to perform their duties, and "agency" includes an entire cabinet Department. Infor mation may be disclosed pursuant to court order and pursuant to proper requests from law enforcement authorities, and to certain other Federal agencies. There are several other specified allowable disclosures. Beyond those set out in the text of the Act, agencies have discretion to make other disclosures through their administrative power under the Act to establish, by notice, comment, review by the Office of Management and Budget and Congress, a routine use -- a dis closure of information outside the agency "for a purpose which is compatible with the purpose for which it was collected." In devising their routine uses agencies have latitude in determining what is "compatible," although the courts have been looking more closely in recent years at agency choices. Many Federal agencies conduct activities that would be covered by the legislation we recommend, such as the provision of care by the Clinical Center of the National Institutes of Health, the hospitals and clinics of the Department of Veterans Affairs, the Department of Defense and the Indian Health Service, and the payment activities of Medicare and the Civilian Health and Medical Program of the Uniformed Services (CHAMPUS). We recommend that federal health record confidentiality legislation limit the latitude of these agencies to make the disclosures otherwise permitted by the Privacy Act. Federal agencies should be restricted in their intra-agency disclosures, and in promulgation of routine uses, to the purposes and uses set out in the health privacy legislation we recommend. This recommendation is based on these principles: Health information is a specialized class of information that deserves the more careful treatment, in terms of disclosure restrictions, that the legislation we now recommend would provide. Federal and other (private, State and local government) health care and payment activities ought, as much as possible, to be subject to the same confidentiality rules. A common set of rules for health records in all health programs is more important than a common set of rules for records whose only similar feature is their Federal maintenance. At present, existing confidentiality statutes are often overlaid on the Privacy Act, with the effect that the protections are cumulative. That is the result sought here, and it should be addressed explicitly in the law. There are strong reasons to encompass both Federal and other health records within a common protective scheme. There is increasing interaction among the Federal, private, and State government sectors in sharing of facilities, purchase of care, and the like. The work of all these facilities and their personnel would be simplified by a common set of rules. We recommend that the proposal leave in place the subject access and amendment provisions of the Privacy Act, and that it not diminish any protections against disclosure provided by that Act. Unforeseen circumstances can be accommodated under the administrative authority we recommend, below (discussed under AUTHORITY FOR LIMITED SUSPENSION). The archives provision deals with the special situation of Federal agencies whose records are subject to the Federal Records Act. 4. STATE LAW We recommend that the legislation preempt State laws only to the extent that those laws are less stringent or restrictive than the Federal law. We recommend that the Federal legislation supersede State law only when the State law is less protective than the Federal law. If either the Federal or State law forbids a disclosure, the disclo sure should not be permitted. Thus, the confidentiality protections would be cumulative, and the Federal legislation would provide "floor preemption." Generally, Federal statutes that provide rights to individuals with respect to privacy and liberty do not displace stronger State laws, and we believe that the legislation we recommend should follow that tradition. We are aware of the strong arguments, and repeated recommendations, that Federal law in this area should be totally preemptive, i.e., that it totally occupy the field of protection of health care information, so that no State could maintain or establish any law governing use and disclosure of health information. Those arguments are based on the increasing integration of the health care information system in this country, in which information passes easily from State to State, when information generated in one State may with ease be retrieved in another State, and when it is difficult even to identify the "location" of information to determine which State's law applies. Nevertheless, we have concluded that the careful attention States have given, and continue to give, to this issue, should be respected. Some States have comprehensive health confidentiality statutes analogous to the one recommended here, and others are considering them. Many have carefully designed statutes protecting specialized classes of information, particularly information about AIDS and HIV infection patients, and mental health patients. The Federal protection would ensure that everyone has an adequate level of privacy protection, and if the people of the several States wish more, or see special privacy needs which are not being met, they can retain or enact additional safeguards. 5. OTHER LAW GOVERNING HEALTH INFORMATION We recommend that the legislation not modify or supersede other Federal or State law that provides greater protection. Some health information subject to the legislation we recommend will also be subject to other law restricting its use and disclosure. The subjects of this information ought to have the benefit of all applicable law. This may be the case with information held by payers and providers, in States with more protective statutes for some elements of health information (as discussed above in STATE LAW), and will be the case with some information held by Federal agencies. It may also be the case with information disclosed by payers and providers under provisions of the legislation without patient authorization. In the latter instance, the information would, in its new setting, become subject to other statutes as well as the redisclosure provisions of the legislation we recommend. For example, informa tion disclosed for research may become subject to statutes governing certain statistical activities (Public Health Service Act § 308(d), 42 U.S.C. § 242m(d)), health services research activities of the Agency for Health Care Policy and Research and its grantees and contractors (Public Health Service Act § 903(c), 42 U.S.C. § 299a-1(c)), or research subject identity protection (Public Health Service Act § 301(d), 42 U.S.C. § 241(d)). In other instances, State law may also restrict the disclosure of this information. In the case of Peer Review Organizations, which review health information to ensure the quality of care for Medicare beneficiaries, health information is protected by its authorizing statute (Social Security Act § 1160, 42 U.S.C. § 1320c-9). The Americans with Disabilities Act prohibits discrimination on the basis of disability, and in regulating the assessment of applicants and employees, requires employers, among other things, to keep medical information "on separate forms and in separate medical files" and to treat this "as a confidential medical record." (§§ 102(c)(3) and (4), 42 U.S.C. §§ 12112(c)(3) and (4)). Section 503 of the Rehabilitation Act of 1973, 29 U.S.C. § 793, provides the same protections for Federal contractor employees and job applicants (regulation at 41 C.F.R. § 60-741.23). These laws should continue to apply. Information obtained by employers in providing health care or payment should be subject to the legislation we propose. Information subject to the Americans with Disabilities Act or Rehabilitation Act (whether or not obtained in treatment or payment) should continue to be covered by these laws. There should be no conflict between the requirements, since neither those laws nor the legislation we recommend requires any disclosure that violates the other law. In providing for the continuance of stronger State law, the legislation should not modify the scope of the Employment Retirement Income Security Act of 1974 (ERISA) (29 U.S.C. § 1134) preemption of State laws. We recommend new minimum federal standards that would apply to many different entities that hold health information, including ERISA plans. However, we are not recommending that States be given new authority to apply more protective privacy standards to ERISA plans. 6. FEDERAL SUBSTANCE ABUSE CONFIDENTIALITY STATUTE We recommend that the Secretary of Health and Human Services be authorized to determine, by regulation, which elements of the Federal substance abuse confidentiality statute ((Public Health Service Act § 543, 42 U.S.C. § 290dd-2) should continue to apply, so that the net effect of that statute and the one recommended will be at least as strong protection for the information concerned. We recommend that the Secretary of Veterans Affairs be similarly empowered with respect to the statute governing substance abuse, sickle cell disease, and HIV infection in the records of the Department of Veterans Affairs (38 U.S.C. § 7332). This recommendation will ensure that the strongest protections of the new legislation and the existing laws will both apply to covered information. The relevant Cabinet Secretaries would publish regulations to specify what rules apply. We recommend that any patient whose rights have been violated knowingly or negligently be permitted to bring an action, in a U.S. District Court or any court of competent jurisdiction for actual damages and for equitable relief. We recommend that actual damages encompass nonpecuniary losses such as physical and mental injury as well as pecuniary losses. We recommend that in the case of knowing violation, attorneys' fees and punitive damages should be available. We recommend that common law liability be eliminated for any disclosure that is permitted by the legislation we recommend and is not otherwise prohibited by State or Federal statute. We recommend that members of institutional review boards and their parent entities not be liable for a good faith determination of the propriety of a dis closure for research under the provisions allowing for such disclosure. We recommend that there be no liability for a disclosure based on good faith reliance on a certification by a government authority or other person that a requested disclosure is in accord with the law. The ability to seek redress for violations is an important element of confidentiality protection. There have been, and will continue to be, improper disclosures of health information, through negligence or deliberate choice. The victims of such disclosures should be able to seek civil redress. The Privacy Working Group of the President's Information Infrastructure Task Force identified this as a basic principle in its Principles for Providing and Using Personal Information: III.C. Redress Principle Individuals should, as appropriate, have a means of redress if harmed by an improper disclosure or use of personal information. The President's statement on the Global Information Infrastructure, A Framework for Global Electronic Commerce (June 1997) reiterates this point: Under these principles, consumers are entitled to redress if they are harmed by improper use or disclosure of personal information or if decisions are based on inaccurate, outdated, incomplete, or irrelevant personal information. Other statutes establishing confidentiality obligations provide a cause of action, such as the Fair Credit Reporting Act, which permits suits in the U.S. District Courts, or in any other court of competent jurisdiction, to enforce liabilities under that act (15 U.S.C. §§ 617-618). Cable television operators are forbidden to disclose subscriber information except under defined circumstances, and violations give rise to civil liability, with a cause of action in the U.S. District Court (47 U.S.C. § 551(f)). The wrongful disclosure of video tape rentals or sales information gives rise to a similar cause of action (18 U.S.C. § 2710(c)). New restrictions on disclosure of State motor vehicle information were imposed by the Violent Crime Control and Law Enforcement Act of 1994, and individuals have a cause of action in the U.S. District Court against persons who obtain or disclose information in violation of the restrictions (Pub. L. No. 103-322, § 300002, 108 Stat. 1796, 2101, 18 U.S.C. § 2724). We recommend that the legislation take a balanced approach that compensates, in the case of negligence, only for actual losses, although not only monetary losses. In the case of a knowing violation, punitive damages and attorneys' fees should also be available. Our recommended definition of actual damages envisages better recovery possibilities than the Privacy Act of 1974, whose damages provisions (subsections (g)(1)(D) and (g)(4))) have in some instances been read to mean only pecuniary damages, and whose standard for recovery is that the Federal agency acted intentionally or wilfully ((g)(4)). The Privacy Protection Study Commission, responding to a specific Congressional request to address this issue, recommended expansion of the Privacy Act recovery to both special and general damages (Personal Privacy in an Information Society 530-1 (1997)). The limitations of the Privacy Act in providing satisfactory remedies has been noted by various commentators, including Paul M. Schwartz and Joel R. Reidenberg, Data Privacy Law § 5-5(a)(1996). We recommend that the rights provided by the legislation be enforceable in any court of competent jurisdiction, as in the case of the Fair Credit Reporting Act, and we recommend that there be nothing to prevent States from providing other remedies in State law for violation of the Federal law. We recommend that recovery for the wrongful behavior of public employees acting in an official capacity be against their agencies, in accord with current law. Some current enforcement of privacy rights occurs through litigation under common law theories of a general public policy of medical confidentiality (derived from privilege and licensing statutes), contract, malpractice, and tortious invasion of privacy. Federal confidentiality legislation should bring certain and uniform standards to the redress and recovery process, and thus we recommend that there be no common law recovery for uses and disclosures of informa tion permitted by the Federal law and not otherwise prohibited. These recommendations are intended to protect record holders and those who assist in making determinations about disclosures against liability based on those disclosures if they act in good faith. Record holders should be able to, but should not have to, make their own inquiries into requests for allowable disclosures in the absence of a facial irregularity in the request. 2. CIVIL MONEY PENALTIES We recommend that there be authority to impose civil money penalties on any covered entity which has demonstrated a pattern or practice of failure to comply with the provisions of the law. We recommend this additional remedy for grave or continuing offenses. The procedural aspects of the penalties could be similar to those for wrongdoing in the Medicaid and Medicare programs, under section 1128A of the Social Security Act. 3. ALTERNATIVE DISPUTE RESOLUTION We recommend that the alternative dispute resolution procedures be available for disputes giving rise to civil liability under the law. 4. CRIMINAL PENALTIES We recommend criminal penalties (including fine and imprisonment) at the felony level for obtaining health information under false pretenses, for knowing and unlawful obtaining of health information, and for knowing and unlawful use or disclosure of health information. We recommend that the penalties be higher for any of these acts performed for profit or monetary gain. Activities that should violate the law would be requesting or obtaining health information under false pretenses from a covered entity; knowingly obtaining protected health information with the intent to sell, transfer, or use the information for profit or monetary gain; knowingly selling, transferring, or using health information for profit or monetary gain; or knowingly using or disclosing health information in violation of the law's requirements for nondisclosure. The penalties we recommend are modeled on the penalties provided in the Health Insurance Port ability and Accountability Act of 1996 for violation of disclosure restrictions in the administrative simplification provisions of that Act (Social Security Act § 1177, 42 U.S.C. § 1320d-6). We recommend that the legislation provide authority to issue regulations to implement the legislation. We recommend that there be authority to -- sponsor research relating to the privacy and security of health information; -- develop information and technical guidance for protection of health informa tion; and -- develop technology to implement standards regarding health information. We recommend that there be authority to promulgate -- model notices of information practices for use by entities subject to the legis lation; -- model authorizations for disclosure and model statements of intended use of health information by persons requesting that patients authorize disclosure of health information; -- guidelines for the administrative, technical, and physical safeguards required to protect health information; -- guidelines for what levels and amounts of information constitute "identifiable" information, and guidelines for minimum allowable disclosures in particular situations; -- guidelines for use within organizations of health information "only for purposes compatible with and directly related to the purposes for which the information was collected or received"; -- requirements for institutional review boards authorized to approve disclo sures for research; -- model notices to advise patients of efforts to obtain health information in legal proceedings; and -- standards for electronic and magnetic writings that would fulfill the requirements of the legislation. This recommendation recognizes the need for interpretation and application when new confiden tiality standards govern health information. An ongoing Federal authority is needed to preclude doubt and confusion, to provide certainty in applying the rules, and to be a point of public reference and recourse with respect to violations subject to civil money penalties. In addition, there should be authoritative sources for technical guidance for several matters that cannot be addressed in detail in legislation. Entities subject to the legislation should be assured that they are in compliance if they used model notices, security practices, and other forms and techniques promulgated centrally. In some areas, like restricting use of health information to the purposes for which it was collected, new organizational and administrative techniques could be promulgated to assist small businesses to comply. 2. AUTHORITY FOR LIMITED SUSPENSION We recommend that there be authority to suspend, by regulation, any provision of the legislation for a limited period in the event of an unforeseen significant threat to health or safety, significant threat to patient privacy, major economic disruption, or manifest unfairness. The design of precise controls on the use and disclosure of information is a complex task, and it is possible that the legislation would forbid a disclosure, or otherwise constrain behavior, in a way that causes unanticipated hardship. Authority to suspend a provision would ensure that situations like this could be addressed, on a temporary basis, pending Congressional consideration of amendments. Federal agencies are accustomed to the flexibility provided by the Privacy Act of 1974, whose routine use provision (5 U.S.C. § 552a(a)(7) and (b)(3)) permits agencies to make administrative choices to disclose information beyond the disclosures explicitly allowed in the statute. We do not recommend administrative authority as flexible as the routine use provision, which appears in a law covering all activities of all Federal agencies, and where a statutory catalog of all possible uses of information was not feasible. We recommend a provision to deal with extraordinary situations that may have not been foreseen, and then only for a limited time. 3. EFFECTIVE DATE We recommend that the obligations of the providers and payers become effective 9 months after the promulgation of implementing regulations. We recommend that there be authority to exempt records in existence on the date of enactment from compliance with specific provisions of the law, for time-limited periods. These recommendations are for an implementation schedule to ensure adequate time to apply the rules to health information in the hands of providers and payers. The requirements we recommend can be applied with minimal trouble to new transactions with patients and to records developed with the legislation as background and guidance. At the same time, to apply the legislation to existing records, including some that are in archival status, could present undue hardships, with little benefit to patients. It is not intended that patients whose records exist already should not get the protection of the law. The exemption provision should be available only for situations where there is no significant adverse privacy effect on the patient. Thomas Jefferson said: "Our laws and institutions must keep pace with the progress of the human mind." We believe that these recommendations should be the first -- not the last -- chapter in an on-going bipartisan process to safeguard our citizens' right to health care privacy in an ever-changing world. Ultimately, we must judge ourselves by whether we leave the next generation with real federal privacy standards grounded in fundamental principles. Will we have boundaries to ensure that, with very few exceptions, our health care information is used only for health care? Will we have assurances that our information is secure? Will we have knowledge about and control over what happens to our health care records? Will those who violate our privacy be held accountable -- and those who are violated be able to seek redress? Will we be able to safeguard our privacy rights while still protecting our core public responsibilities like research, public health , and law enforcement? In short, will we be able to harness these revolutions in biology, communications, and health care delivery to breath new life into the trust between our patients and their doctors, between our citizens and their government, between our past and our future. We can. And, if we work together and act quickly, we will. (1) The directive requires EU States to "protect the fundamental rights and freedoms of natural persons, and in particular their right to privacy with respect to processing of personal data". (Directive 95/46/EC of the European Parliament and of the Council of 24 Oct. 1995 on the protection of individuals with regard to the processing of personal data and on the free movement of such data, art. 25, ¶ 1 (Eur. O.J. 95/L281)). (2) 9 Part I, U.L.A. 475 (1988 and Supp. 1996) (3) Workgroup for Electronic Data Exchange, Report to the Secretary of U.S. Department of Health and Human Services Appendix 4, Confidentiality and Antitrust Issues 5 (1992). For other analyses of the State law situation see Robert M. Gellman, Prescribing Privacy: The Uncertain Role of the Physician in the Protection of Patient Privacy, 62 N.C. L. Rev. 255 (1984); Lawrence O. Gostin, Health Information Privacy, 80 Cornell L. Rev. 101 (1995); Paul M. Schwartz and Joel R. Reidenberg, Data Privacy Law § 7-3 (1996). (4) Richard S. Dick and Elaine B. Steen, eds., The Computer-Based Patient Record: An Essential Technology for Health Care (1991). A revised version of this report is expected in the autumn of 1997. (5) The National Committee on Vital and Health Statistics, an advisory committee to the Secretary of Health and Human Services, is established by the Public Health Service Act § 306(k), 42 U.S.C. § 242k(k), and its membership was expanded to include persons distinguished in "privacy and security of electronic information" by the Health Insurance Porta bility and Accountability Act of 1996. In the course of its consultation on these recommendations, its Subcommittee on Privacy and Confidentiality held six days of hearings on health privacy during the first two months of 1997. Witnesses included health care providers, researchers, public health authorities, Federal and State oversight agencies, accreditation organizations, insurers, claims processors, pharmaceutical manufacturers, Federal agencies, law enforcement agencies, and patient and privacy advocates. (Health Privacy and Confidentiality Recommendations of the National Committee on Vital and Health Statistics, Approved on June 25, 1997) (6) U.S. Congress, Office of Technology Assessment, Protecting Privacy in Computerized Medical Information 44 (1993). (7) Molla A. Donaldson and Kathleen N. Lohr, eds. Health Data in the Information Age: Use, Disclosure and Privacy 190 (1994). (8) Health Insurance Portability and Accountability Act of 1996, Pub. L. No. 104-191, § 264(c)(2), 110 Stat. 1936, 2033 (1996). Congress has provided for confidentiality protection for a limited class of information if legislation is not enacted. If Congress does not enact legislation on standards for privacy of health information transmitted in connection with financial and administrative transactions (i.e. the information subject to the standards to be developed under section 262) within 36 months, the Secretary of HHS must issue regulations with privacy standards for these transactions within 42 months of enactment (§ 264(c)(1)). This is timed to coincide with the effective date of the standards under section 262. (9) Social Security Act § 1178(a)(2)(B), added by section 262 of the Health Insurance Portability and Accountability Act of 1996.	2	56	7	0	0	0.667185	7	38,097
May 21, 2012 Coding for Seizures and Epilepsy For The Record Vol. 24 No. 10 P. 28 Seizures are episodes of abnormal electrical brain activity that cause changes in attention or behavior. The term “convulsions” may be used interchangeably with seizures, but during a convulsion, the body rapidly and uncontrollably shakes. Epilepsy is a brain disorder in which a person has repeated seizures. Also called a seizure disorder, epilepsy may be diagnosed when the patient has two or more unprovoked seizures. A seizure episode is classified to ICD-9-CM code 780.39, Other convulsions. This code also includes convulsive disorder not otherwise specified (NOS), fit NOS, and recurrent convulsions NOS. Basically, code 780.39 is for the single episode of a seizure. Subcategory 780.3, Convulsions, includes the following codes: • 780.31, Febrile convulsions (simple), unspecified; • 780.32, Complex febrile convulsions; and • 780.33, Posttraumatic seizures. Epilepsy and recurrent seizures are classified to category 345. Subcategory 345.9 includes the following diagnoses: • Epileptic convulsions, fits, or seizures NOS; • Seizure disorder NOS; and • Recurrent seizure disorder NOS. Types of Epilepsy There are two main categories of epilepsy: partial (also called local or focal) and generalized. Partial seizures occur in only one part of the brain. The following are two common types of partial epilepsy: • Simple focal seizure is a type of partial epilepsy where the awareness is retained and does not result in loss of consciousness. It may alter emotions or change the patient’s senses, such as taste or smell. This type of epilepsy is classified to subcategory 345.5, Localization-related (focal) (partial) epilepsy and epileptic syndromes with simple partial seizures. • Complex focal seizure (subcategory 345.4) alters consciousness resulting in staring or nonpurposeful movements such as hand rubbing, chewing, lip smacking, and walking in circles. Generalized seizures involve all parts of the brain. The following are the six types of generalized seizures: • Absence seizures (petit mal): characterized by blank staring and subtle body movements that begin and end abruptly. It may cause a brief loss of consciousness. • Tonic seizures: causes stiffening of the muscles and may cause the patient to fall to the ground. • Clonic seizures: characterized by rhythmic, jerking muscle contractions that affect both sides of the body at the same time. • Myoclonic seizures: associated with sudden brief jerks or twitches on both sides of the body. • Atonic seizures: causes patients to lose muscle tone, so they subsequently collapse. • Tonic-clonic seizures (grand mal): most intense type of epilepsy causing loss of consciousness, muscle rigidity, and convulsions. Subcategory 345.0, Generalized nonconvulsive epilepsy, includes atonic and typical absences, minor and pykino-epilepsy, petit mal, and akinetic and atonic seizures. Subcategory 345.1, Generalized convulsive epilepsy, includes clonic, myoclonic, tonic, and tonic-clonic epileptic seizures; grand mal; major and progressive myoclonic epilepsy; and Unverricht-Lundborg disease. Notice that petit mal is classified to subcategory 345.0, and grand mal is classified to subcategory 345.1. However, there are also codes available for petit mal status (345.2) and grand mal status (345.3). Status epilepticus indicates a state of continuous seizure activity lasting for a significant amount of time or having frequent recurrent seizures without regaining full consciousness in between them. This is a life-threatening condition because the brain cannot get enough oxygen to survive. Most of the codes in category 345 require a fifth digit subclassification to complete the code. Fifth digit 0 is for without mention of intractable epilepsy. Fifth digit 1 is with intractable epilepsy and includes the terms “pharmaco-resistant,” “poorly controlled,” “refractory,” or “treatment resistant.” Codes 345.2, Petit mal status, and 345.3, Grand mal status, do not require fifth digit subclassification. Seizures documented as the late effect of stroke are classified to code 438.89, Other late effects of cerebrovascular disease. An additional code may be assigned for the specific type of seizure/seizure disorder (code 780.39 or category 345) documented. Coding and sequencing for seizures and epilepsy are dependent on the physician documentation in the medical record and application of the Official Coding Guidelines for inpatient care. Also, use specific AHA Coding Clinic for ICD-9-CM and American Medical Association CPT Assistant references to ensure complete and accurate coding. — This information was prepared by Audrey Howard, RHIA, of 3M Consulting Services. 3M Consulting Services is a business of 3M Health Information Systems, a supplier of coding and classification systems to more than 5,000 healthcare providers. The company and its representatives do not assume any responsibility for reimbursement decisions or claims denials made by providers or payers as the result of the misuse of this coding information. More information about 3M Health Information Systems is available at www.3mhis.com or by calling 800-367-2447. ICD-10-CM Coding for Seizures and Epilepsy Coding for seizures and epilepsy in ICD-10-CM is similar to ICD-9-CM. ICD-10-CM category G40 is titled “Epilepsy and recurrent seizures.” The following are the fourth character subcategories for epilepsy: • G40.0, Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset; • G40.1, Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures; • G40.2, Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures; • G40.3, Generalized idiopathic epilepsy and epileptic syndromes; • G40.A, Absence epileptic syndrome; • G40.B, Juvenile myoclonic epilepsy [impulsive petit mal]; • G40.4, Other generalized epilepsy and epileptic syndromes; • G40.5, Epileptic seizures related to external causes; • G40.8, Other epilepsy and recurrent seizures; and • G40.9, Epilepsy, unspecified. Notice that the above subcategories are mainly separated by localized vs. generalized. In addition, there are separate codes if the epilepsy is idiopathic vs. symptomatic. The fifth and sixth characters will identify the presence or absence of status epilepticus and intractable epilepsy. Convulsions, not elsewhere classified are classified to category R56 and includes the following subcategories: • R56.0, Febrile convulsions; • R56.1, Posttraumatic seizures; and • R56.9, Unspecified convulsions (which includes seizures NOS).	4	7	0	0	5	0.793455	5	1,595
NORD gratefully acknowledges Andrew G. Engel, MD, Department of Neurology and Muscle Research Laboratory, Mayo Clinic, for the preparation of this report. The congenital myasthenic syndromes (CMS) are a diverse group of disorders that have an underlying defect in the transmission of signals from nerve cells to muscles. These disorders are characterized by muscle weakness, which is worsened upon exertion. The age of onset, severity of presenting symptoms, and distribution of muscle weakness can vary from one patient to another. A variety of additional symptoms affecting other organ systems can be present in specific subtypes. Severity can range from minor symptoms such as mild exercise intolerance to severe, disabling ones. Most CMS are transmitted by autosomal recessive inheritance; a few specific subtypes are transmitted by autosomal dominant inheritance. Genetic diagnosis these disorders is important because therapy that benefits one type CMS can worsen another type.Introduction The CMS involve the neuromuscular junction which is a synapse where signals from motor nerves are passed to muscle fibers and tell the muscles fibers when to contract. The normal neuromuscular junction consists of a presynaptic region, a synaptic space, and a postsynaptic region. The presynaptic region contains the end of a motor nerve cell called the motor nerve terminal. The motor nerve terminal overlies a specialized region of the muscle fiber called the postsynaptic region. The space between the motor nerve terminal and the postsynaptic region is called the synaptic space or synaptic cleft. The postsynaptic region displays multiple folds, known as junctional folds. The motor nerve terminal contains small vesicles that are filled by the neurotransmitter, acetylcholine, or ACh for short that acts as a chemical ‘messenger’ with instructions for the muscles to contract. The membrane covering the motor nerve terminal and facing the synaptic space is known as the presynaptic membrane. The membrane covering the postsynaptic region is known as the postsynaptic membrane.. The segment of the postsynaptic membrane that covers the tips of junctional folds is lined by molecules of the acetylcholine receptor, or AChR for short. The synaptic space is lined by a membrane known as the synaptic basement membrane. This membrane anchors molecules of acetylcholinesterase, or AChE for short, an enzyme that converts ACh to acetate and choline. The process of how the motor nerve endings communicate with the muscle fibers is a highly specialized process and a genetic defect that impairs that communication can result in a congenital myasthenic syndrome. Understanding this process helps to understand myasthenic disorders. When muscles are in the resting state, there is a randomly occurring release of acetylcholine from single synaptic vesicles in the motor nerve terminal. This release is known as exocytosis. The amount of ACh released from a single synaptic vesicle is referred to as a quantum of ACh. ACh released from a synaptic vesicle travels through the synaptic space and binds to the AChRs that are concentrated on the tips of the junctional folds. When this binding occurs, it causes a channel in the center of AChR to and allows positively charged sodium and lesser amounts of calcium ions to enter the muscle fiber. This process briefly changes the electric charge across the postsynaptic membrane from negative to positive (small postsynaptic depolarization) which is referred to as a miniature endplate potential (MEPP). When a person wants to perform a voluntary action, (e.g. raising one’s hand, dancing, kicking a ball, etc.), a series of successive nerve impulses are sent to the motor nerve terminal where they depolarize the presynaptic membrane, causing structures called voltage-gated calcium channels to open which allows calcium to enter the motor nerve terminal. This calcium influx results in a nearly synchronous release of the contents of several synaptic vesicles which results in a larger depolarization of the postsynaptic membrane, known as the endplate potential (EPP). When the EP reaches a certain threshold, it opens voltage-gated sodium channels found along the entire muscle fiber outside of the motor endplate area and this triggers a propagated muscle fiber action potential which causes the muscle fiber to contract. The difference between the endplate potential and the depolarization required to activate the voltage-gated sodium channels is known as the safety margin of neuromuscular transmission. In healthy individuals, the amplitude of the EPP is quite large. With continued activity the EPP begins to decrease but still remains large enough to trigger a muscle fiber action potential. After the muscle contracts, ACh is released from the AChRs into the synaptic space) where it is broken down (hydrolyzed) by AChE into two molecules, acetate and choline. Choline is transported back into the nerve terminal where it recombines with acetate under the influence of an enzyme known as choline acetyltransferase to be stored once again within the synaptic vesicles. The factors governing the safety margin of neuromuscular transmission fall into four major categories: (1) factors that affect the number of ACh molecules in the synaptic vesicle; (2) factors that affect quantal release mechanisms; (3) the density of AChE in the synaptic space; and (4) factors that affect the efficacy of individual quanta. The efficacy of individual quanta depends on the endplate geometry, the packing density of AChRs on the tips of the junctional folds, the affinity of these AChRs for ACh, and the kinetic properties of the AChR ion channel. Congenital myasthenic syndromes are caused when there is an alteration (mutation) in a specific gene. This results in an abnormal protein or even loss of a protein that impairs some part of the process described above. The abnormal protein (disease protein) can reside in the motor nerve terminal, or the synaptic space, or in the postsynaptic region that underlies the nerve terminal, but in some patients the disease protein is also present in others tissues or organs causing not only CMS but also a variety of other symptoms. The cardinal symptom of all myasthenic disorders is muscle weakness that is induced or worsened by exertion. This is referred to as fatigable weakness. In healthy people, physical activity causes a small decrease in the number of ACh quanta released from the nerve terminal that does not impair the safety margin of neuromuscular transmission, but it is incapacitating in myasthenic patients in whom the safety margin is already reduced. In some patients with CMS, the weakness is confined to muscles supplied (innervated) by the cranial nerves causing double vison, droopy eyelids (eyelid ptosis), facial weakness, hypernasal or slurred speech, and swallowing difficulties. In other patients, the above symptoms are combined with weakness of the limb and torso muscles causing generalized myasthenia. In still others, the weakness is limited to the limb and torso muscles causing ‘limb-girdle myasthenia’. The myasthenic disorders caused by defects in enzymes required for protein glycosylation can also be associated with development delay, seizures, intellectual disability, neuropathy, and metabolic abnormalities of different organs. Several different types of CMS have been identified.1 The currently identified types are: Synaptic basal lamina-associated Defects in the acetylcholine receptor Defects in proteins required for normal endplate development and maintenance Congenital defect of glycosylation Other myasthenic syndromes Each type can be subdivided into several subtypes that are discussed below. Endplate Choline Acetyltransferase (ChAT) Deficiency After acetylcholine is released from the nerve terminal, it binds to acetylcholine receptor for a brief period; when it is released from the receptor, it is rapidly broken down (hydrolyzed) by the enzyme acetylcholinesterase into choline and acetate. The released choline is transported to the nerve terminal where the enzyme choline acetyltransferase (ChAT) reforms (resynthesizes) acetylcholine. The resynthesized acetylcholine is then transported into the synaptic vesicles, where it becomes available to be released into the synaptic space as needed. Deleterious mutations in the CHAT gene, alone or in combination, alter the expression, catalytic efficiency, or stability of the ChAT protein.2,3 The defect in ChAT causes progressive decrease of the acetylcholine content of the synaptic vesicles during activity and hence reduces the amplitude of the EPP, which reduces the safety margin of neuromuscular transmission. Some patients present with hypotonia (low muscle tone), paralysis of cranial and limb muscles and apnea (failure to breathe) at birth. Others are normal at birth and develop attacks of apnea during infancy or childhood precipitated by infection, excitement, or no apparent cause.3-7 In some children an acute attack is followed by respiratory failure that lasts for weeks.8 A few patients are respirator-dependent and paralyzed since birth3 and some develop brain atrophy caused by lack of oxygen (hypoxia) during episodes of apnea.3,7 Others improve with age, but still have variable eyelid drooping (ptosis), impaired movement of the ocular muscles, fatigable weakness, and recurrent episodes of cyanosis, in which there is bluish discoloration of the skin due to impaired respiration and inadequate oxygenation of the blood. Some patients complain only of mild to moderately severe fatigable weakness. The weakness is worsened by exposure to cold because this further reduces the efficiency of the mutant enzyme.5 Treatment consists of preventive (prophylactic) therapy with pyridostigmine (Mestinon) which is a medication that inhibits the activity of acetylcholinesterase (which breaks down acetylcholine in the synaptic space). This prolongs the life time of acetylcholine in the synaptic space and, consequently, the number of acetylcholine receptors it can activate. Parents of affected infants should be provided an inflatable rescue bag and a fitted mask, and should be instructed in the intramuscular injection of neostigmine methylsulfate (another inhibitor of acetylcholinesterase), and are advised to install an apnea monitor in their home. A single patient reported to date had a severe CMS associated with an unusually exaggerated response to brain stimuli (cerebral cortical hyperexcitability), ataxia (lack of coordination), and intellectual disability.9 Genetic studies revealed a dominant single amino acid change in the gene SNAP25B, which produces an essential protein required by the synaptic vesicles to release acetylcholine (exocytosis). The endplates were structurally normal on examination by the electron microscope. Treatment with 3,4-diaminopyridine (3,4-DAP), which increases the number of quanta released by nerve impulse, improved the patient’s weakness but not her ataxia or intellectual disability. Synaptotagmin 2 Deficiency Synaptotagmin 2 is another presynaptic protein. It senses the calcium concentration in the nerve terminal; when this is increased, it acts on other proteins to initiate the release of acetylcholine into the synaptic space (exocytosis). In two kinships, mutations in this gene caused limb muscle weakness, loss of the tendon reflexes, and a reduced amplitude of the muscle fiber action potential that precedes muscle fiber contraction. This response as well as the weakness was transiently improved by exercise. The treatment of this condition has not been described.10 Paucity of Synaptic Vesicles and Impaired Quantal Release The clinical features resemble that of autoimmune myasthenic gravis, but the onset is at birth or in early infancy and tests for anti-acetylcholine receptor antibodies are negative. A specific diagnosis requires electron microscopy and electrophysiology studies of the motor endplate. A presynaptic defect is revealed by a severe decrease (to approximately 20% of normal) in quantal release of acetylcholine by nerve impulse accompanied by a proportionate decrease in the number of synaptic vesicles in the nerve terminal. This CMS responds to treatment with pyridostigmine.11 SYNAPTIC BASAL LAMINA-ASSOCIATED Endplate Acetylcholinesterase (AChE) Deficiency The endplate species of acetylcholinesterase (AChE) is composed of 12 catalytic subunits, which rapidly breaks down (hydrolyzes) acetylcholine, plus a collagenic subunit, called ColQ, which anchors the entire molecule to the basal lamina of the endplate. Subunits are single protein molecules that combine with other proteins to form a larger protein complex. The ColQ protein is composed of three identical strands each of which binds to 4 catalytic subunits. Histochemical and electron microscopy studies reveal absence of acetylcholinesterase from the endplate and smaller than normal nerve terminals. Severely affected patients present at birth with apnea and generalized weakness that persists throughout life. Less severely affected patients present later in childhood.12 The patients do not respond to, or are worsened by, pyridostigmine which acts by inhibiting acetylcholinesterase. Therapy is still unsatisfactory, but ephedrine13 and albuterol14 have a gradually developing beneficial effect. CMS Associated with β2-Laminin Deficiency β2-laminin is a component of the basal lamina of different tissues and is highly expressed in kidney, eye, and at the endplate where the protein is important for the appropriate alignment of the nerve terminal with the postsynaptic region. β2-laminin also contributes to the development and organization of the two regions. Mutations in β2-laminin result in Pierson syndrome, a rare disorder associated with malformations of the kidneys and eyes. A patient with Pierson syndrome had a myasthenic syndrome. The kidney defect was corrected by renal transplant at age 15 months. Quantal release by nerve impulse and the MEPP amplitude were both reduced. Electron microscopy revealed abnormally small nerve endings accounting for the decreased quantal release. The synaptic space was widened and the junctional folds were simplified, accounting for the decreased MEPP amplitude.15 DEFECTS IN ACETYLCHOLINE RECEPTOR (AChR) Primary AChR Deficiency The acetylcholine receptor is made up 5 subunits. Subunits are single protein molecules that combine with other proteins to form a larger protein complex; in this case, the acetylcholine receptor. Two of these subunits are called alpha (α) and the remaining 3 are called beta (β), delta (δ) and epsilon (ε) in adults. Before birth, the fetal subunit contains a gamma (γ) instead of a ε subunit. In primary AChR deficiency, the amount of AChR expressed at the endplate is reduced and the safety margin of neuromuscular transmission is impaired by the decreased amplitude of the EPP. The clinical deficits vary from mild to severe. Patients with recessive mutations in the ε subunit are generally less severely affected than those with mutations in other subunits because compensatory expression of the fetal γ subunit can partially substitute for the defective ε subunit. The sickest patients have severe ocular, bulbar and respiratory muscle weakness from birth and survive only with respiratory support and gavage feeding. Gavage feeding is the use of a small, narrow tube inserted through an infant’s nostrils and run down the throat to the stomach to directly supply nourishment to an affected infant. Infants may be weaned from a respirator and begin to tolerate oral feedings during the first year of life, but have bouts of aspiration pneumonia and may need intermittent respiratory support during childhood and adult life. Motor development is severely delayed; they seldom learn to take steps and can walk for only for a short distance. Older patients close their mouths by supporting their jaw with their hand and elevate their eyelids with their fingers. Facial deformities, protruding jaw, misalignment teeth (malocclusion), and abnormal curvature of the spine such as scoliosis or kyphoscoliosis become noticeable during the second decade. Muscle bulk is reduced. The tendon reflexes are normal or hypoactive. Less severely affected patients experience moderate physical handicaps from early childhood. Limited eye movements and ptosis of the lids become apparent during the first year of life. They fatigue easily, walk and negotiate stairs with difficulty, cannot keep up with their peers in sports, but can perform most activities of daily living. Mutations in the AChR α, β, and δ subunits that reduce or prevent the expression of AChR are either lethal in embryonic life or cause marked disability and high mortality after birth. In the least affected patients motor development is only slightly delayed; they only have mild eyelid ptosis and limitation of eye movements. They are often clumsy in sports, fatigue easily, and cannot run well, climb rope, or do pushups. In some patients, a myasthenic disorder is suspected only when they develop prolonged respiratory arrest on exposure to a neuromuscular blocking agent drug during a surgical procedure. Treatment consists of pyridostigmine an inhibitor of acetylcholinesterase. This medication increases the lifetime of acetylcholine in the synaptic space which allows each acetylcholine molecule to bind to different acetylcholine receptors repeatedly before it leaves the synaptic space by diffusion. Many patients derive additional benefit from the use of 3,4-diaminopyridine (3,4-DAP)16 which prolongs the depolarization of the presynaptic membrane by nerve impulse. This allows more calcium to enter the nerve terminal which increases the number of acetylcholine quanta released by each nerve impulse. Finally, some patients derive still additional benefit from albuterol. 17 Kinetic Defect in AChR: The Slow-Channel Syndrome This syndrome is caused by dominant mutations in the acetylcholine receptor (AChR) gene that leads to the abnormally slow closure of the AChR ion channel. The prolonged openings of the ion channel cause overloading of the postsynaptic region with positively charged ions, including calcium. The local increase in calcium concentration damages the junctional folds, and can damage the muscle fiber nuclei under the folds. The onset of symptoms ranges from infancy to early adult life. The disease causes selectively severe weakness and loss of bulk (atrophy) of the cervical, scapular, and of the wrist and finger extensor muscles.18 The safety margin of synaptic transmission is compromised by damage to the junctional folds with loss of acetylcholine receptors, and by the receptors becoming desensitized (unresponsive) during physiologic activity due to prolonged exposure to acetylcholine. This syndrome does not respond to, or is worsened by, pyridostigmine but is improved by relatively high doses of fluoxetine (Prozac) which blocks (plugs) the acetylcholine receptor ion channel and thereby reduces the length of channel openings.19 Kinetic Defect in AChR: The Fast-Channel Syndrome This syndrome is transmitted by recessive inheritance and is the physiologic and anatomic opposite of the slow-channel syndrome.18 The length of the AChR channel openings is decreased because the mutations reduce the ability of AChR to bind acetylcholine, or because they hinder the opening of the AChR ion channel, or because they cause the ion channel to become intermittently unstable. The structural integrity of the endplate is unaffected. This syndrome becomes manifest only if the second copy of the AChR subunit gene is not expressed, or if both copies of the gene harbor the same mutation, so that the fast- channel mutation dictates the clinical consequences. The safety margin of neuromuscular transmission is reduced because the mutant gene reduces the probability and length of channel openings, which reduce the amplitude and duration of EPP. The clinical consequences vary from mild to severe. Most patients respond to combined treatment with pyridostigmine and 3,4-DAP. Prenatal CMS Caused by Mutations in AChR Subunits and Other Specific Proteins The first identified prenatal myasthenic syndrome was traced to mutations in the fetal AChR γ subunit. In humans, AChR harboring the fetal subunit appears on developing muscle fibers around the ninth week of gestation and becomes concentrated at early nerve-muscle junctions around the sixteenth week of gestation. Subsequently, the γ subunit is replaced by the adult ε subunit and is no longer present at fetal endplates after the thirty-first week of gestation. Thus harmful mutations of the γ-subunit reduce fetal movements (hypomotility) between the sixteenth and thirty-first week of gestation.20 The clinical consequences at birth are contractures of large joints, small muscle bulk, webbing around the neck, armpits, elbows, fingers, or behind the knees, flexion contractures of the fingers, rocker-bottom feet with prominent heels, and a characteristic facial appearance with mild eyelid ptosis and a small mouth with downturned corners. A contracture is a condition in which a joint becomes permanently fixed in a bent or straightened position, completely or partially restricting the movement of the affected joint. Myasthenic symptoms are absent after birth because by then the normal adult ε subunit is expressed at the endplates.21 Recent studies also identified lethal fetal akinesia syndromes arising from deleterious null mutations in both copies of the AChR α, β, and δ subunits as well as in other CMS disease genes. CMS CAUSED BY DEFECTS IN ENDPLATE DEVELOPMENT OR MAINTENANCE To date, mutations have been detected in genes for proteins that are essential for motor endplate development and maintenance. As with the communication of nerve signals from nerve cells to muscle fibers described above, the health and development of the motor endplate depends upon a sequence of interrelated, chemical reactions involving multiple genes and their protein products. These genes are MuSK, Agrin, LRP4, and DOK-7. Agrin is secreted into the synaptic space by the nerve terminal where it binds to the lipoprotein-related protein LRP4 in the postsynaptic membrane creating an agrin-LRP4 protein complex. The Agrin-LRP4 complex then binds to and activates MuSK. This enhances MuSK phosphorylation and leads to clustering of LRP4 and MuSK. Activated MuSK in concert with postsynaptic DOK-7 and other postsynaptic proteins acts on Rapsyn to concentrate AChR in the postsynaptic membrane, enhances synapse specific gene expression by postsynaptic nuclei, and promotes postsynaptic differentiation. Clustered LRP4, in turn, promotes differentiation of motor axons. The agrin-LRP4-MuSK-Dok-7 signaling system is also essential for maintaining the structure of the adult neuromuscular junction.22 Only a few patients with agrin-related CMS have been reported. The severity of the symptoms varies according to the location of the mutations in the agrin gene and whether or not the mutations affect agrin expression.23,24,25 The consequences are severe when a mutation that hinders attachment of agrin to LRP4 dominates the clinical picture. In such a patient the synaptic contacts were dispersed, the postsynaptic regions were poorly differentiated, the nerve terminals were small, and there were degenerative changes in the muscle fibers under the junctional folds.24 Another report describes three kinships in which the agrin mutations were associated with slowly progressive wasting of the distal leg and later of the upper arm muscles.25 Treatment of the agrin-related CMS is unsatisfactory, but one patient responded partially to ephedrine.24 There are only two reports of LRP4-related CMS. The first report described a 17-year-old girl with moderately severe fatigable limb-girdle weakness, irregularly shaped synaptic contacts, and mild endplate AChR deficiency. In a muscle located between the ribs (intercostal muscle) of this patient the MEPPs and EPPs were of normal amplitude indicating the identified mutations could spare neuromuscular transmission in some muscles.26 Subsequently, two sisters with moderately severe CMS and harboring a homozygous mutation that hinders LRP4 from activating MuSK were shown to have structurally and functionally abnormal endplates and endplate AChR deficiency.27 This disease presents at birth or in early life with eyelid ptosis or respiratory distress. Subsequently, it involves the ocular, facial and proximal limb muscles, and in some kinships the bulbar muscles as well.28,29,30,31,32 Introduction of the mutant gene in mice results in recurrent cycles of focal loss of nerve supply (denervation) and reestablishment of nerve supply (reinnervation) resulting in extensive remodeling of the endplates.33 Pyridostigmine therapy is ineffective or worsens the disease.31 A recent report indicates that therapy with albuterol has been highly effective in two brothers.34 No clear genotype-phenotype correlations (correlation between a given mutation and the clinical features) have been observed. DOK-7 is expressed within developing and mature muscle fibers. In developing muscle fibers it serves as an intrinsic activator of MuSK.35 In mature muscle, it is activated by MuSK to activate rapsyn to concentrate acetylcholine receptors on the junctional folds and to promote the development and maintenance of the endplate. This CMS can be mild or severe. The pathogenic mutations can curtail DOK-7 expression or prevent DOK-7 to activate, or be activated by, other intracellular proteins. There appears to be no consistent correlation between the identified mutations and the clinical features. All affected patients have limb-girdle weakness with lesser facial and neck muscle weakness but a few have severe bulbar weakness and few have significant limitation of the eye movements.36,37 The clinical course is mild to severe. Impaired maintenance of the endplates is evidenced by ongoing destruction and remodeling of the endplates. Neuromuscular transmission is compromised by the decreased quantal release from the nerve terminal by nerve impulse and by a reduced amplitude of the MEPP.37 Importantly, this CMS is rapidly worsened by pyridostigmine but responds well over a period of time to ephedrine38 or albuterol.37 Rapsyn concentrates and anchors acetylcholine receptors on the junctional folds39 and is required for development of the junctional folds.40 Most patients present in the first year of life.41 Joint contractures at birth and other congenital malformations occur in close to one-third.42 Intercurrent infections or fever can trigger respiratory crises that can cause brain damage due to lack of oxygen (anoxia). 43,44 The eye movements are intact in most patients.42 Multiple synaptic contacts appear on single muscle fibers. The endplate acetylcholine receptor deficiency is milder than in primary acetylcholine receptor deficiency42 and the junctional folds are not well differentiated. Most patients respond well to pyridostigmine; some derive additional benefit from ephedrine or albuterol43 and some are further improved by 3,4-DAP. Indo-Europeans harbor a common N88K mutation in the gene that produces rapsyn, which involves replacement of an asparagine molecule (N) by a lysine molecule (K) at codon 8845 (codon: a sequence of 3 adjacent nucleotides that constitutes a genetic code for a specific amino acid). Different mutations hinder self-association of rapsyn molecules, or their binding to acetylcholine receptors, or impede agrin-MuSK-LRP4-mediated clustering of these receptors, or decrease rapsyn expression.40,46 There are no genotype-phenotype correlations (correlation between a given mutation and the clinical features) except that Near-Eastern Jewish patients with a homozygous E-box mutation (E-box: a sequence before the coding region of a gene involved in regulating gene expression) have a milder course with eyelid ptosis, a large protruding jaw, severe weakness of the masticatory and facial muscle, and hypernasal speech.47 MYASTHENIC SYNDROMES ASSOCIATED WITH CONGENITAL DEFECTS OF GLYCOSYLATION Glycosylation is the process by which sugar ‘trees’ or residues (glycans) are created, altered and chemically attached to certain proteins or fats (lipids). When these sugar molecules are attached to proteins, they form glycoproteins; when they are attached to lipids, they form glycolipids. Glycoproteins and glycolipids have numerous important functions in all tissues and organs. Glycosylation involves many different genes, encoding many different proteins such as enzymes. A deficiency or lack of one of these enzymes can lead to a variety of symptoms potentially affecting multiple organ systems. Glycosylation to nascent peptides increases their solubility, folding, stability, assembly, and intracellular transport. Peptides are amino acid compounds and can perform a wide range of functions in the body. O-glycosylation involves addition of sugar residues to the amino acids serine and threonine; N-glycosylation occurs in sequential steps that decorate the amino group of the amino acid asparagine.48,49 To date, defects in four enzymes subserving N-glycosylation have been shown to cause a CMS: GFPT1,50,51 DPAGT1,52,53 ALG2, and ALG14.54 Accumulation of small tubules within the muscle fibers, referred to as tubular aggregates, are a clue to the diagnosis but are not seen in all patients. Because glycosylated proteins are present at all endplate sites, the safety margin of neuromuscular transmission is likely compromised by a combination of pre- and postsynaptic defects. GFPT1 controls the entry of glucose into the glycosylation pathway. A defect in GFPT1 predicts reduced glycosylation, and therefore defective function, of several endplate- associated proteins.50 The synaptic contacts are small and the postsynaptic regions are poorly developed .51 One patient whose mutations abolished expression of the muscle- specific exon of GFPT1 had severe facial, bulbar, and respiratory muscle weakness, and has been paralyzed since birth. She has a vacuolar myopathy, reduced quantal release evoked by nerve impulse, and low MEPP amplitude. A vacuolar myopathy is a muscle disease that is associated with the development of abnormal pockets or spaces called vacuoles within muscle tissue. DPAGT1 catalyzes the first committed step of N-linked protein glycosylation. DPAGT1 deficiency predicts impaired asparagine glycosylation of multiple proteins distributed throughout the organism, but in the first 5 patients harboring DPAGT1 gene mutations only neuromuscular transmission was adversely affected.52 A subsequent study of two siblings and of a third patient showed the DPAGT1 deficiency associated with intellectual disability.9 The siblings respond poorly to pyridostigmine and 3,4-DAP; the third patient was partially improved by pyridostigmine and albuterol. Intercostal muscle studies showed fiber type disproportion, small tubular aggregates in some muscle fibers, and autophagic vacuoles (vacuoles that degrade and digest subcellular structures). Evoked quantal release, the MEPP amplitude, and the endplate acetylcholine receptor content were all reduced to ~50% of normal. ALG2 AND ALG14 Deficiency ALG2 catalyzes the second and third committed steps of N-glycosylation. In one family, four affected siblings had a deleterious homozygous mutation, and a third patient was homozygous for a low-expressor mutation. ALG14 forms an enzyme complex with ALG13 and DPAGT1 and also contributes to the first committed step of N-glycosylation. In one family two affected siblings carried two different recessive mutations. Endplate ultrastructure and parameters of neuromuscular transmission were not investigated.54 OTHER CONGENITAL MYASTHENIC SYNDROMES PREPL Deletion Syndrome The hypotonia-cystinuria syndrome is caused by recessive deletions involving the SLC3A1 and PREPL genes at chromosome 2p21. The major clinical features are cystinuria, growth hormone deficiency, muscle weakness, eyelid ptosis, and feeding problems. Cystinuria is an inherited metabolic disorder characterized by the abnormal movement (transport) in the intestines and kidneys, of certain organic chemical compounds (amino acids). A patient with isolated PREPL deficiency had myasthenic symptoms since birth and growth hormone deficiency but no cystinuria, and responded transiently to pyridostigmine during infancy.55 She harbors a paternally inherited nonsense mutation in the PREPL gene and a maternally inherited deletion involving both PREPL and SLC3A1; therefore the PREPL deficiency determines the phenotype. PREPL expression was absent from the patient’s muscles and endplates. Endplate studies revealed decreased evoked quantal release and small MEPP amplitude despite robust endplate acetylcholine receptor expression.55 Because PREPL is an essential activator of the clathrin associated adaptor protein 1 (AP1),56 and AP1 is required by the vesicular acetylcholine transporter to fill the synaptic vesicles with acetylcholine,57 the small MEPP is attributed to a decreased vesicular content of acetylcholine. Two patients with this syndrome have been identified to date. The first patient had abrupt episodes of respiratory and facial weakness associated with weakness of muscles required for speaking and swallowing since birth lasting from 3 to 30 minutes typical of periodic paralysis as well as a myasthenic disorder. Studies of neuromuscular transmission revealed normal amplitude EPPs that frequently failed generate muscle action potentials pointing to voltage-gated sodium channels (SCN4A gene) as the culprit. The gene for voltage-gated sodium channels (SCN4A) harbored two recessive mutations which caused the sodium channel to become inactive soon after it was activated by the EPP.58 A second patient with similar clinical findings was recently identified. In this patient two different recessive mutations in voltage-gated sodium channel caused abnormal inactivation of the sodium (Na) channel by activity.59 CMS Caused by Plectin Deficiency Plectin, encoded by the PLEC gene, has different tissue-specific and organelle-specific forms (known as isoforms) that serve to link cytoskeletal filaments to target organelles.60-62 Organelles are a general term for any number of organized or specialized structures within a living cell. Plectin is concentrated at sites of mechanical stress. For example, in skeletal muscle it is present under the junctional folds of the endplates, under the surface membrane of the muscle fiber, at the Z-disks (thin protein bands that mark the boundaries of adjoining contractile units), and around nuclei and mitochondria, which are found by the hundreds within virtually every cell of the body and which generate most of the cellular energy. In skin, it is associated with hemidesmosomes (peg-like structures that link epithelial cells to the underlying basement membrane). Alone or in combination, mutations in plectin can result in a blistering skin disease known as epidermolysis bullosa simplex (EBS), in progressive muscular dystrophy, and sometimes in a myasthenic syndrome. The two patients investigated by the author had EBS, a myasthenic syndrome due to low amplitude MEPPs caused by degenerating junctional folds, as well as muscular dystrophy associated with dislocation of the muscle fiber nuclei, mitochondria and myofibrils (basic rod-like units of muscle cells) as well as defects in the muscle fiber surface membrane causing calcium overloading and degeneration of the muscle fibers.63 CMS Associated with Defects in the Mitochondrial Citrate Synthase Carrier SLC25A1 The SLC25A1 gene encodes a transporter protein that is responsible for the movement of citrate across the inner membranes of mitochondria. Mutations in the SLC25A1 gene interfere with brain, eye, and psychomotor development.64 Two siblings born to consanguineous parents had a CMS associated with intellectual disability and whole exome sequencing revealed they carried a homozygous mutation in SLC25A1. Subsequent studies showed that the mutation impairs the transport activity of the enzyme, and that knockdown of the gene equivalent to SLC25A1 in zebra fish hindered motor axons from innervating muscle fibers.65 A third patient who harbored two recessive mutations in SLC25A1 had myasthenic symptoms as well underdeveloped optical nerves, undeveloped corpus callosum (a structure connecting the two cerebral hemispheres), and excessive urinary excretion of 2-hydroxyglutaric acid.64 CMS Associated with Centronuclear Myopathies Eyelid ptosis, weakness of the external ocular and facial muscles, exercise intolerance, a decremental EMG study, and response to pyridostigmine have been documented in patients with centronuclear myopathies (CNM) caused by mutations in amphiphysin (BIN1),66 myotubularin (MTM1),67 and dynamin 2 (DNM2)68 as well as in other CNM patients with no identified mutations.69 Congenital myasthenic syndromes are caused by alterations (mutations) in specific genes. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body. Approximately 20 different genes are known to cause CMS. These genes contain instructions for proteins that are essential for the proper function or health of the neuromuscular junction and the motor endplate. Some of these proteins are found in other areas of the body and, in those subtypes, other areas of the body in addition to the neuromuscular junction can be affected. In some individuals with CMS, no altered gene has been found indicating that additional, as-yet-unidentified genes exist that can cause a congenital myasthenic syndrome. In most subtypes, CMS are inherited as autosomal recessive traits. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females. Specific CMS subtypes, specifically SNAP25, synaptotagmin 2, and the slow-channel-myasthenic syndrome are transmitted by autosomal dominant inheritance. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females. A generic diagnosis of a CMS can be made on clinical grounds from a history of fatigable weakness involving ocular muscles, bulbar muscles (muscles of the face, and muscles used for speaking and swallowing), and limb muscles since infancy or early childhood, a history of similarly affected relatives, and a variety of tests. Such tests include a decremental electromyographic (EMG) response, and negative tests for antibodies against the acetylcholine receptor (AChR) and the muscle specific receptor tyrosine kinase (MuSK). However, in many CMS patients the family history is negative; in others the onset is delayed, the EMG abnormalities are not present in all muscles or are present only intermittently, and the weakness has a restricted distribution. An electromyography or EMG test records electrical activity in skeletal (voluntary) muscles at rest and during muscle contraction. The decremental EMG response is measured by stimulation of a motor nerve to muscle at a rate of 2 to 3 times per second; the evoked electrical responses from muscle, known as compound muscle action potentials, or CMAPs, are recorded by electrodes placed on skin overlying the stimulated muscle. The response is abnormal if the fourth evoked CMAP is more than 10% smaller than the first evoked CMAP. Single fiber EMG is a more sensitive but less specific test for a myasthenic disorder. In this test, single intramuscular nerve fibers are stimulated repetitively and the evoked single fiber action potentials are recorded simultaneously from 2 to 4 muscle fibers at a time. An abnormally increased variability in the time-locked firing of individual action potentials is an early indicator of a defect in neuromuscular transmission.1 A specific diagnosis of a CMS depends on identifying the disease gene and the pathologic mutations in that gene. Commercially available studies can readily detect mutations in previously identified types of CMS. Mutations in previously unrecognized types of CMS can be detected by whole exome sequencing or whole genome sequencing but the bioinformatic analysis of the obtained result remains challenging. Genetic diagnosis of the CMS is important because therapy that benefits one type CMS can worsen another type. There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the CMS overall and that fact that certain subtypes have only been identified in a handful or fewer individuals, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with CMS. As stated above, it is critically important to identify the specific subtype in each individual as medications that prove effective for one type of CMS may be ineffective or even harmful in another. More detailed treatment information for specific subtypes of CMS is discussed in the “Signs and Symptoms” section above under each individual subtype listing. Current therapies for CMS include medications known as cholinergic agonists such as pyridostigmine or amifampridine, long-lived open channel blockers of acetylcholine receptor ion channel fluoxetine and quinidine, and adrenergic agonists such as salbutamol and ephedrine. Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site. For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office: Toll-free: (800) 411-1222 TTY: (866) 411-1010 For information about clinical trials sponsored by private sources, in the main, contact: For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/ Engel AG. Anatomy and molecular architecture of the neuromuscular junction. In: Engel AG, ed. Myasthenia Gravis and Myasthenic Disorders. 2nd Ed. New York: Oxford University Press; 2012 pp 1-36. Engel AG. Congenital myasthenic syndromes. In: Engel AG, ed. Myasthenia Gravis and Myasthenic Syndromes. 2nd Ed. New York: Oxford University Press; 2012, pp 173-230. Engel AG, Shen,X.M., Sine,S.M. Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment. Lancet Neurology. 2015;14:420-434. 1. Harper CM. Electrodiagnosis of myasthenic disorders. In: Engel AG, ed. Myasthenia Gravis and Myasthenic Disorders. 2nd ed. New York: Oxford; 2012: pp. 37-59. 2. Ohno K, Tsujino A, Shen XM, et al. Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. Proc Natl Acad Sci USA. 2001;98:2017-2022. 3.Shen XM, Crawford TO, Brengman J, et al. Functional consequences and structural interpretation of mutations in human choline acetyltransferase. Hum Mutat. 2011;32:1259-1267. 4. Byring RF, Pihko H, Shen XM, et al. Congenital myasthenic syndrome associated with episodic apnea and sudden infant death. Neuromuscul Disord. 2002;12:548-553. 5. Maselli RA, Chen D, Mo D, Bowe C, Fenton G, Wollman RL. Choline acetyltransferase mutations in myasthenic syndrome due to deficient acetylcholine resynthesis. Muscle Nerve. 2003;27:180-187. 6. Mallory LA, Shaw JG, Burgess SL, et al. Congenital myasthenic syndrome with episodic apnea. Pediatr Neurol. 2009;41:42-45. 7. Schara U, Christen HJ, Durmus H, et al. Long-term follow-up in patients with congenital myasthenic syndrome due to CHAT mutations. Eur J Paediatr Neurol. 2010;14:326-333. 8. Kraner S, Laufenberg I, Strassburg HM, Sieb JP, Steinlein OK. Congenital maysthenicsyndrome with episodic apnea in patients homozygous for a CHAT missense mutation. Arch Neurol. 2003;60:761-763. 9. Shen XM, Selcen D, Brengman J, Engel AG. Mutant SNAP25B causes myasthenia, cortical hyperexcitability, ataxia, and intellectual disability. Neurology. 2014;83:2247-2255. 10. Herrmann DN, Horvath R, Snowden JE, et al. Synaptotagmin 2 mutations cause an autosomal-dominant form of Lambert-Eaton myasthenic syndrome and nonprogressive motor neuropathy. Am J Hum Genet. 2014;95:332-339. 11. Walls TJ, Engel AG, Nagel AS, Harper CM, Trastek VF. Congenital myasthenic syndrome associated with paucity of synaptic vesicles and reduced quantal release. Ann NY Acad Sci. 1993;681:461-468. 12. Ohno K, Engel AG, Brengman JM, et al. The spectrum of mutations causing endplate acetylcholinesterase deficiency. Annals of Neurology. 2000;47:162-170. 13. Bestue-Cardiel M, de-Cabazon-Alvarez AS, Capablo-Liesa JL, et al. Congenital endplate acetylcholinesterase deficiency responsive to ephedrine. Neurology. 2005;65:144-146. 14. Liewluck T, Selcen D, Engel AG. Beneficial effects of albuterol in congenital endplate acetylcholinesterase deficiency and DOK-7 myasthenia. Muscle Nerve. 2011;44:789-794. 15. Maselli RA, Ng JJ, Andreson JA, et al. Mutations in LAMB2 causing a severe form of synaptic congenital myasthenic syndrome. J Med Genet. 2009;46:203-208. 16. Engel AG. The therapy of congenital myasthenic syndromes. Neurotherapeutics. 2007;4:252-257. 17. Sadeh M, Shen XM, Engel AG. Beneficial effect of albuterol in congenital myasthenic syndrome with ε subunit mutations. Muscle Nerve. 2011;44:289-291. 18. Engel AG, Ohno K, Sine SM. Sleuthing molecular targets for neurological diseases at the neuromuscular junction. Nature Rev Neurosci. 2003;4:339-352. 19. Harper CM, Fukudome T, Engel AG. Treatment of slow channel congenital myasthenic syndrome with fluoxetine. Neurology. 2003;60:170-173. 20. Hesselmans LFGM, Jennekens FGI, Vand Den Oord CJM, Veldman H, Vincent A. Development of innervation of skeletal muscle fibers in man: Relation to acetylcholine receptors. Anat Rec. 1993;236:553-562. 21. Morgan NV, Brueton LA, Cox P, et al. Mutations in the embryonal subunit of the acetylcholine receptor ( CHNRG ) cause lethal and Escobar variants of the multiple pterygium syndrome. Am J Hum Genet. 2006;79:390-395. 22. Burden SJ, Yumoto N, Zhang W. The role of MuSK in synapse formation and neuromuscular disease. Cold Spring Harb Perspect Biol. 2013;5:a009167-a009167. 23. Huze C, Bauche S, Richard P, et al. Identification of an agrin mutation that causes congenital myasthenia and affects synapse function. Am J Hum Genet. 2009;85:155-167. 24. Maselli RA, Fernandez JM, Arredondo J, et al. LG2 agrin mutation causing severe congenital myasthenic syndrome mimics functional characteristics of non-neural agrin (z-) agrin. Hum Genet (Berlin). 2012;131:1123-1135. 25. Nicole S, Chaouch A, Torbergsen T, et al. Agrin mutations lead to a congenital myasthenic syndrome with distal muscle weakness and atrophy. Brain. 2014;137:2429-2443. 26. Ohkawara B, Cabrera-Serrano M, Nakat T, et al. LRP4 third β-propeller domain mutations cause novel congenital myasthenic syndrome by compromising agrin-mediated MuSK signalling in a position-specific manner. Hum Mol Genet. 2014;23:1856-1868. 27. Selcen D, Ohkawara B, Shen, X.-M.,McEvoy, K., Ohno, K. Engel, A.G. Impaired development and maintenance of the neuromuscular junction in LRP4 myasthenia. JAMA Neurology. 2015;72. 28. Chevessier F, Faraut B, Ravel-Chapuis A, et al. MUSK, a new target for mutations causing congenital myasthenic syndrome. Hum Mol Genet. 2004;13 3229-3240. 29. Mihaylova V, Salih MA, Mukhtar MM, et al. Refinement of the clinical phenotype in MUSK -related congenital myasthenic syndromes. Neurology. 2009;73:1926-1928. 30. Maselli R, Arredondo J, Cagney O, et al. Mutations in MUSK causing congenital myasthenic syndrome impair MuSK-Dok-7 interaction. Hum Mol Genet. 2010;19:2370-2379. 31. Ben Ammar A, Soltanzadeh P, Bauchˆ S, et al. A mutation causes MuSK reduced sensitivity to agrin and congenital myasthenia. PLoS One. 2013;8:e53826. 32. Maggi L, Brugnoni R, Confalioneri P, et al. Marked phenotypic variability in two siblings affected by congenital myasthenic syndrome caused by mutations in MUSK J Neurol. 2013;Epub ahead of print:10/12/2013. 33. Chevessier F, Girard E, Molgo J, et al. A mouse model for congenital myasthenic syndrome due to MuSK mutations reveals defects in structure and function of neuromuscular junctions. Hum Mol Genet. 2008;17:3577-3595. 34. Gallenmuller C, Muller-Felber W, Dusl M, et al. Salbutamol-responsive limb-girdle congenital myasthenic syndrome due to a novel missese mutaion and heteroallelic deletion in MUSK. Neuromuscul Disord. 2014;24:31-35-2014. 35. Okada K, Inoue A, Okada M, et al. The muscle protein Dok-7 is essential for neuromuscular synaptogenesis. Science. 2006;312:1802-1805. 36. Beeson D, Higuchi O, Palace J, et al. Dok-7 mutations underlie a neuromuscular junction synaptopathy. Science. 2006;313:1975-1978. 37. Selcen D, Milone M, Shen XM, et al. Dok-7 myasthenia: phenotypic and molecular genetic studies in 16 patients. Ann Neurol. 2008;64:71-87. 38. Schara U, Barisic N, Deschauer M, et al. Ephedrine therapy in eight patients with congenital myasthenic syndrome due to DOK7 mutations. Neuromuscul Disord. 2010;19:828-832. 39. Ramarao MK, Cohen JB. Mechanism of nicotinic acetylcholine receptor cluster formation by rapsyn. Proc Natl Acad Sci USA. 1998;95:4007-4012. 40. Ohno K, Engel AG, Shen XM, et al. Rapsyn mutations in humans cause endplate acetylcholine receptor deficiency and myasthenic syndrome. Am J Hum Genet. 2002;70:875-885. 41. Burke G, Cossins J, Maxwell S, et al. Rapsyn mutations in hereditary myasthenia. Distinct early- and late-onset phenotypes. Neurology. 2003;61 826-828. 42. Milone M, Shen XM, Selcen D, et al. Myasthenic syndrome due to defects in rapsyn: Clinical and molecular findings in 39 patients. Neurology. 2009;73:228-235. 43. Banwell BL, Ohno K, Sieb JP, Engel AG. Novel truncating RAPSN mutation causing congenital myasthenic syndrome responsive to 3,4-diaminopyridine. Neuromuscul Disord. 2004;14:202-207. 44. Skeie GO, Aurlien H, Mller JS, Norgard G, Bindoff LA. Unusual features in a boy with rapsyn N88K mutation. Neurology. 2006;67:2262-2263. 45. Muller JS, Mildner G, Mller-Felber W, et al. Rapsyn N88K is a frequent cause of CMS in European patients. Neurology. 2003;60:1805-1811. 46. Cossins J, Burke G, Maxwell S, et al. Diverse molecular mechanisms involved in AChR deficiency due to rapsyn mutations. Brain. 2006;129:2773-2783. 47. Ohno K, Sadeh M, Blatt I, Brengman JM, Engel AG. E-box mutations in RAPSN promoter region in eight cases with congenital myasthenic syndrome. Hum Mol Genet. 2003;12:739-748. 48. Haeuptle MA, Hennet T. Congenital disorders of glycosylation: An update on defects affecting the biosynthesis of dolichol-linked oligosaccharides. Hum Mutat. 2009;30:1628-1641. 49. Freeze HH, Chong JX, Bamshad MJ, Ng BG. Solving glycosylation disorders: Fundamental approaches reveal complicated pathways. Am J Hum Genet. 2014;94:161-165. 50. Senderek J, Muller JS, Dusl M, et al. Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect. Am. J. Hum. Genet. 2011;88:162-172. 51. Selcen D, Shen XM, Milone M, et al. GFPT1-myasthenia: Clinical, structural, and electrophysiologic heterogeneity. Neurology. 2013;23:370-378. 52. Belaya K, Finlayson S, Slater C, et al. Mutations in DPAGT1 cause a limb-girdle congenital myasthenic syndrome with tubular aggregates. Am J Hum Genet. 2012;91:1-9. 53. Selcen D, Shen XM, Li Y, Stans AA, Wieben E, Engel AG. DPAGT1 myasthenia and myopathy. Genetic, phenotypic, and expression studies. Neurology. 2014;82:1822-1830. 54. Cossins J, Belaya K, Hicks D, et al. Congenital myasthenic syndromes due to mutations in ALG2 and ALG14. Brain. 2013;136:944-956. 55. Regal L, Shen XM, Selcen D, Verhille C, Meulemans S, Creemers JWM. PREPL deficiency with or without cystinuria causes a novel myasthenic syndrome. Neurology. 2014;82:1254-1260. 56. Radhakrishnan K, Baltes J, Creemers JWM, Schu P. Trans-Golgi network morphology and sorting is regulated by prolyl-oligopeptidase-like protein PREPL and AP-1 complex subunit æ1A. J Cell Sci. 2013;126:1155-1163. 57. Kim MH, Hersh LB. The vesicular acetylcholine transporter interacts with clathrin-associated adaptor complexes AP-1 and AP-2. J Biol Chem. 2004;279:12580-12587. 58. Tsujino A, Maertens C, Ohno K, et al. Myasthenic syndrome caused by mutation of the SCN4A sodium channel. Proc Natl Acad Sci USA. 2003;100:7377-7382. 59. Arnold WD, Feldman DH, Ramirez S, et al. Defective fast inactivation recovery of Nav 1.4 in congenital myasthenic syndrome. Ann Neurol. 2015;77:840-850. 60. Elliott CE, Becker B, Oehler S, Castanon MJ, Hauptmann R, Wiche G. Plectin transcript diversity: identification and tissue distribution of variants with distinct first coding exons and rodless isoforms. Genomics. 1997;42:115-125. 61. Fuchs P, Zorer M, Rezniczek GA, et al. Unusual 5′ transcript complexity of plectin isoforms: novel tissue- specific exons modulate actin binding activity. Hum Mol Genet. 1999;8:2461-2472. 62. Konieczny P, Wiche G. Muscular integrity – a matter of interlinking distinct structures via plectin. In: Laing NG, ed. The sarcomere and skeletal muscle disease: Springer; 2008:165-175. 63. Selcen D, Juel VC, Hobson-Webb LD, et al. Myasthenic syndrome caused by plectinopathy. Neurology. 2011;76:327-336. 64. Edvardson S, Porcelli V, Jalas C, et al. Agenesis of corpus callosum and optic nerve hypoplasia due to mutation in SLC25A1 encoding the mitochondrial citrate transporter. J Med Genet. 2013;50:240-245. 65. Chaouch A, Porcelli V, Cox DM, et al. Mutations in the mitochondrial citrate carrier SLC25A1 are associated with impaired neuromuscular transmission. J Neuromuscul Dis. 2014;1:75-90. 66. Claeys KG, Maisonobe T, Bohm J, et al. Phenotype of a patient with recessive centronuclear myopathy and a novel BIN1 mutation. Neurology. 2010;74:519-521. 67. Robb SA, Sewry CA, Dowling JJ, et al. Impaired neuromuscular transmission and response to aceylcholinesterase inhibitors in centronuclear myopathy. Neuromuscul Disord. 2011;21:379-386. 68. Gibbs EM, Clarke NF, Rose K, et al. Neuromuscular junction abnrormalities in DNM2-related centronuclear myopathy. J Mol Med (Berl). 2013;91:727-737. 69. Liewluck T, Shen XM, Milone M, Engel AG. Endplate structure and parameters of neuromuscular transmission in sporadic centronuclear myopathy associated with myasthenia. Neuromuscul Disord. 2011;21:387-395. 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Type 2 diabetes is a common metabolic condition that develops when the body fails to produce enough insulin or when. which is referred to as peripheral neuropathy. ★★ Diabetes Type 2 With Neuropathy Icd 10 Code ★★ ::The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days.[ DIABETES TYPE 2. Reviews and ratings for lantus when used in the treatment of diabetes, type 2. 18 reviews submitted. User Reviews for Lantus. Diabetic Peripheral Neuropathy; Apr 5, 2016. Perfect code for Diabetic peripheral neuropathy in ICD 10 CM is E11.42. not specified in the medical record, the default is DM type 2 (E11.-). Sep 16, 2017. The study, Prevalence and Risk Factors for Diabetic Peripheral Neuropathy in Youth with Type 1 and Type 2 Diabetes: SEARCH for Diabetes in. Abstract. We assessed serum uric acid (SUA) levels in patients with type 2 diabetes mellitus (T2DM) with or without peripheral neuropathy. (diagnosed by the. ★ Diabetes Type 2 With Neuropathy Icd 10 Code ★ :: Diabetic Symptons – The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days. Just Released: 2017 Report. Don’t try anything before you read. ★ What Is Diabetic Peripheral Neuropathy ★ :: Type 2 Diabetes Homeopathic Treatments – The 3 Step Trick that Reverses Diabetes Permanently in As Little. ★★ Risk Factors For Type 2 Diabetes ★★ ::The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days.[ RISK FACTORS FOR TYPE 2. Help Diabetic Neuropathy Pain Nerve damage or diabetic neuropathy resulting from chronically high blood glucose can be one of the most frustrating and debilitating complications of diabetes because of the pain, discomfort and disability it can Expert Information On Diabetes Symptoms, Treatment and More. Type 2 diabetes is a lifelong condition that causes a person’s blood sugar level to become too high. It mainly occurs in people aged over 40. Sep 1, 2016. Approximately half of all patients with type 2 diabetes develop peripheral neuropathy, which contributes to functional decline and significantly. WebMD offers a primer on type 2 diabetes. What causes this chronic condition, how do you know you have it, and what can you do about it? Aims/Hypothesis: The purpose of the study is to estimate the prevalence and risk factors for diabetic peripheral neuropathy (DPN) in type 2 diabetic outpatients. Read about peripheral neuropathy, a term for a group of conditions in which the. In the UK, diabetes (both type 1 and type 2) is the most common cause of. Jul 2, 2015. Without weight loss and moderate physical activity, 15% to 30% of these people will develop full-blown type 2 diabetes within 5 years.1. Type+2+Diabetes+ • Type&2&is. Type 2 diabetes mellitus, should be assigned. Code Z79.4, Long-term (current) use of insulin, should also be assigned Dec 9, 2011. Everyday Health Type 2 Diabetes. Peripheral neuropathy, the most common diabetic complication, can cause numbness or pain in the legs, ★ Non Diabetic Peripheral Neuropathy ★ :: Diabetes Irritability – The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days.[ NON. May 1, 2014. Aim We aimed to estimate the morbidity rate and associated factors for diabetic peripheral neuropathy (DPN) in a low-middle income country. Diabetes mellitus type 2 (also known as type 2 diabetes) is a long-term metabolic disorder that is characterized by high blood sugar, insulin resistance. Apr 8, 2014. Abstract. Objective : 1)To compare the visual evoked potentials in type-2 DM patients with that of healthy controls and to find out if any. Although weight loss in type 2 diabetes may be achieved in studies. Crane MG, Sample C. Regression of diabetic neuropathy with total vegetarian (vegan) diet. Alpha Lipoic Acid For Diabetic Neuropathy @ Alpha Lipoic Acid Diabetes ★★ Treatments For Diabetic Neuropathy In Feet The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days. Jun 22, 2015. Neuropathy is a What is Diabetes mellitus-Type 1 vs Type 2? Meaning of Diabetes mellitus-Type. com/Diabetes+mellitus-Type+1+vs+Type+2. peripheral neuropathy and. Nov 17, 2016. 2 Causes Of Diabetic Peripheral Neuropathy; 3 Treatments For. Type 2 diabetes is characterized by insulin sensitivity, wherein the body no. Diabetic angiopathy is a form of angiopathy. and almost always as a result of peripheral. also associated with diabetes mellitus; type 1 and 2. @ Diabetes Type 2 Effects On Body ★★ Peripheral Neuropathy Diabetes The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days. Diabetes mellitus type 2. Other symptoms that are commonly present at diagnosis include a history of blurred vision, itchiness, peripheral neuropathy, The aim of this study was to describe a case of type 2 diabetic patient with peripheral neuropathy treated with 6-week Whole-Body Vibration program training. Pathophysiology+of+Type+2+ Diabetes:. Peripheral Neuropathy Foot problems. type 2 diabetes by 3- to 10- fold, Diabetic neuropathy epidemiology, diagnosis, treatment options, and images at. in nerve pathology between type 1 and type 2 diabetes, small-fiber neuropathy. rates were 25% and 35% for diabetic peripheral neuropathy (DPN), and 29%. MRI is recruiting participants for a clinical research study in the management of Diabetic Peripheral Neuropathy (DPN) in people with Type 2 Diabetes. @ Treatment For Diabetic Peripheral Neuropathy ★★ Diabetes Type 2 Death The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days. Sensory and autonomic neuropathy in people with diabetes are. and autonomic and peripheral neuropathy. Diabetes is the. diabetes mellitus. Diabetes. Type 2 diabetes — Comprehensive overview covers symptoms, treatment, prevention of this often weight-related condition. Diabetic Neuropathy Treatment Diabetes Care ★★ Treatment For Diabetic Neuropathy In Legs ★★ ::The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days.[ TREATMENT FOR. @ What Is The Treatment For Diabetic Neuropathy Development of diabetic retinopathy in patients with type 2 diabetes was found to be related to both. Peripheral neuropathy in diabetes may manifest in. This collection features AFP content on type 2 diabetes and related issues, Alpha-Lipoic Acid for Treatment of Diabetic Peripheral Neuropathy. Dec 6, 2012. This multicenter, randomized, double-blind, placebo-controlled trial involved 214 patients with type 2 diabetes and neuropathy (baseline. Components of metabolic syndrome associated with peripheral neuropathy in prediabetic. with neurological changes in individuals at risk for type 2 diabetes. Foot Complications. Learn about neuropathy (which can cause numbness in the feet). Help change the conversation about type 2 diabetes. Best answer for best headache medicine for diabetics ★★ Diabetes Type 2 With Peripheral Neuropathy ★★ ::The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days.[ DIABETES TYPE 2. A patient with type 2 diabetes has sensory neuropathy of the feet and legs and. is prescribed for a diabetic patient with peripheral neuropathy who has. ★★ Diabetic Peripheral Neuropathy Symptoms ★★ ::The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days.[ DIABETIC PERIPHERAL. Diabetic peripheral sensory neuropathy was defined as at least two of:. Anthropometric, metabolic, and sensory testing data in type 2 diabetic and comparison. Neuropathy is a nerve disorder which can affect type 1 and type 2 diabetics. The term peripheral neuropathy may also be used and the term simply refers to. More Neuropathy Articles ... - Diabetic Peripheral Neuropathy Reversible: She complained of feeling bloated and unable to eat and had symptoms of acute painful peripheral neuropathy, that is burning sensation with pins and needles in. All health care professionals should be persuaded that autonomic neuropathy can be revers... - Biochemist Induced Peripheral Neuropathy: Folk Remedy Essentials. About Cayenne. Originally from South America, the cayenne plant has spread across the globe both as a food and as a medicine. B12 deficiency isn't a bizarre, mysterious disease. But recent research suggests it's far more commo... - Peripheral Neuropathy Treatment With Vitamin B12: Learn about peripheral neuropathy causes such as diabetes, alcohol, medication, shingles, vitamin deficiency, autoimmune diseases, and inherited diseases. Jun 8, 2016. Abstract. This is the protocol for a review and there is no abstract. The objectiv... - Ms Or Peripheral Neuropathy: ★★ Diabetic Peripheral Neuropathy Icd 9 Code ★★ ::The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days.[ DIABETIC PERIPHERAL. See More. MS Demyelination #MS Meme Education @MSMemesandmore # mseducation https://www. Neuropathy T... - Diabetic Neuropathy Anti Depressant: Oct 16, 2017. To examine the efficacy of duloxetine vs. pregabalin in the treatment for diabetic peripheral neuropathic pain (DPNP), comparing patient subgroups with and without concomitant antidepressant use. This post hoc analysis assessed data fro... - Diabetic Peripheral Neuropathy Pdf: diabetic peripheral neuropathy and the preliminary mechanism. Key words: Toona sinensis, diabetic peripheral neuropathy, oxidative stress, NGF-β, TNF-α. @ Reversing Diabetic Peripheral Neuropathy ★★ Diabetes Type 2 Journal The 3 Step Trick that Rever...	4	9	0	0	7	0.702406	7	2,185
Many patients have ‘allover’ pain that can sometimes be helped by exploring and trying some effective Certainly people have hurt all over for centuries. Most often, the more labor a person does the more pain they will develop. Repetitive motions in work, exercise, sports, and musical instrument practice nearly always produce long term pain symptoms. For many years, doctors disbelieved patients when they said they had pain in so many different places. If a condition was not accepted by mainstream medicine, it was hard to label it accurately, let alone formulate a treatment plan. Getting insurance to recognize the diagnosis and pay for it was difficult for many years. A diagnosis for multiple areas of muscle pain was not accepted until 1979. Not until 1979, did a diagnosis relating to fibromyalgia symptoms gain acceptance. “myalgia and myositis, unspecified (729.1)” icd9. The international classification of disease updated or changed in 2015 to ICD10 from the ICD 9 codes required in 1979. There are 68,000 codes in ICD 10 and there were 13000 codes in ICD 9. In the past insurers have often denied coverage for ‘fibromyalgia’ and related treatments arguing that the disease was not real or not officially recognized. Now the code, m79.7 identifies this diagnosis. There is a lot involved in a doctor determining a diagnosis, and it is important that fibromyalgia (FM) is officially recognized as a disease that insurance should be paying for. We know it exists and creates a lot of pain. Fibromyalgia means inflammation of the lining of muscles. Where does it come from? The medical explanation is “etiology unknown”. Or no one knows why it happens. Unfortunately, too common an explanation for conditions without adequate research. Unfortunately, many patients turned to addicting pain medications. Finally, in 2007, Pfizer was approved to launch Lyrica as a treatment for fibromyalgia. It is a structural derivative of the inhibitory neurotransmitter Gaba, gamma aminobutyric acid, originally for neuropathic pain. However, this medication was shown to have similar addicting components as benzodiazepines like valium and Xanax. The drug is classified in the controlled substance act in schedule 5, so is not the first drug of choice to prescribe for fibromyalgia. Fortunately, there are other non-addicting options. In 2008, the pharmaceutical company Eli Lilly was approved to release Cymbalta for fibromyalgia. It works at 2 brain neurotransmitters. This medicine is also approved to treat depression, generalized anxiety, diabetic peripheral neuropathy and musculoskeletal pain. Savella was approved by the FDA in 2009 for release by forest and cypress pharmaceuticals as the 3rd fibromyalgia medication. “Fibro” (as it is not affectionately called) does not involve joint pain nor is it the same as osteoarthritis pain. Early on, fibromyalgia mapping was promoted using a technique where the doctor feels for contracted ligaments and muscles by touching the patient with consistent pressure at 18 tender points. Mapping is subjective and almost all patients will have tenderness if pressure is applied when they don’t feel well. In the early 1990s Dr. Paul St Amand suggested an officially unapproved treatment, but it was harmless. His protocol involves 3 parts. Titrating the guaifenesin, avoiding salicylates, following a low carb diet if the patient is hypoglycemic (hypoglycemic means that a person needs to eat proteins or complex carbs in small amounts frequently like every 2-4 hours, or the blood sugar will begin to drop. It isn’t a disease, but some people don’t maintain a steady blood glucose unless they eat non sugar and nonfat foods regularly.) Dr. Amand formulated his phosphates theory. He speculated that some mutant gene may be interfering with urinary excretion of phosphates which could allow a retention of phosphates, which could allow a negative effect on the mitochondria, which are the energy producers of each cell. The theory then postulated that the cause of the fatigue would bring on the body wide malfunctions found in fibromyalgia. He proposed that guaifenesin would correct the problem. It is from the guaiac tree, native to the Caribbean and the north coast of South America. This natural product is an expectorant that loosens the mucous in the sinuses and lungs which is helpful for a cold, allergic rhinitis and a cough. It became available in 1952 as the brand Mucinex. Dr. Amand proposed that salicylates would block the Mucinex benefit. The salicylic derivatives are in a vast number of products in topical creams, lotions, hair care, cosmetics so the doctor’s book and web site provide a list of do not use products. The body mapping system was utilized to determine if the Mucinex was helping and possibly toa ‘measured’ subjective method. Many patients have been helped with this plan. It seems it works, or it doesn’t with individual response. Now that the plant product is generic and over the counter, no RX is required unless the extended release 200 and 300 mg doses are used. Using the theory that myalgias (muscle aches) and fatigue is usually present in Lyme disease, some patients with a positive lab antibody titre for Lyme disease have been treated with minocycline to see if it helped those 2 symptoms. Studies suggest that the empirical (treatment without enough research to prove the benefit) use of antibiotics in this case is not worth the risks and cost. Exception is the patient who has anxiety about an untreated lab finding. NON MEDICATION TREATMENTS Massage therapists that are trained in FM massage is good. Relaxation and biofeedback are helpful. Along with the pain of fibromyalgia, there is usually associated depression from pain and reduced activities, fatigue almost always accompanies the pain. Behavior therapy helps patients to learn better ways to deal with the problem and to focus on how to participate in improving their health. Stretching, herbal and nutritional supplements are often beneficial. DIAGNOSTIC TESTS AND CURES There is no lab test, x ray, or invasive procedure that provides a definitive diagnosis of fibromyalgia. It is not a terminal disease. Unfortunately, currently, there is no known cure. However, at miller health, many fibromyalgia patients have been treated and they have experienced improvement. FMS FIBROMYALGIA SYNDROME A syndrome is a group of symptoms that often occur together Ongoing pain in various muscles, sleep problems, feelings of weakness, memory difficulties, depression, diminished abilities to process stress issues, anxiety about the symptoms, inabilities to function normally, and fatigue.	2	9	2	0	0	0.918467	2	1,432
ICD-10-CM Code K12 Stomatitis and related lesions Non-Billable CodeNon-Billable means the code is not sufficient justification for admission to an acute care hospital when used a principal diagnosis. Use a child code to capture more detail. ICD Code K12 is a non-billable code. To code a diagnosis of this type, you must use one of the four child codes of K12 that describes the diagnosis 'stomatitis and related lesions' in more detail. - K12 Stomatitis and related lesions NON-BILLABLE - BILLABLE K12.0 - BILLABLE K12.1 - BILLABLE K12.2 and - K12.3 NON-BILLABLE - K12.30 Oral mucositis (ulcerative), unspecified BILLABLE - K12.31 Oral mucositis (ulcerative) due to antineoplastic therapy BILLABLE - K12.32 Oral mucositis (ulcerative) due to other drugs BILLABLE - K12.33 Oral mucositis (ulcerative) due to radiation BILLABLE - K12.39 Other oral mucositis (ulcerative) BILLABLE The ICD code K12 is used to code Mouth ulcer A mouth ulcer (also termed an oral ulcer, or a mucosal ulcer) is an ulcer that occurs on the mucous membrane of the oral cavity. Mouth ulcers are very common, occurring in association with many diseases and by many different mechanisms, but usually there is no serious underlying cause. \|ICD 9 Code:\|\|528.9\| A mouth ulcer (in this case associated with aphthous stomatitis) on the labial mucosa (lining of the lower lip). Coding Notes for K12 Info for medical coders on how to properly use this ICD-10 code Additional Code Note: Use Additional CodeUse Additional Code note means a second code must be used in conjunction with this code. Codes with this note are Etiology codes and must be followed by a Manifestation code or codes. - Code to identify: - Alcohol abuse and dependence See code F10.- - Exposure to environmental tobacco smoke See code Z77.22 - Exposure to tobacco smoke in the perinatal period See code P96.81 - History of tobacco use See code Z87.891 - Occupational exposure to environmental tobacco smoke See code Z57.31 - Tobacco dependence See code F17.- - Tobacco use See code Z72.0 Code Type-1 Excludes: Type-1 ExcludesType-1 Excludes mean the conditions excluded are mutually exclusive and should never be coded together. Excludes 1 means "do not code here." - Cancrum oris - instead, use code A69.0 - Cheilitis - instead, use code K13.0 - Gangrenous stomatitis - instead, use code A69.0 - Herpesviral [herpes simplex] gingivostomatitis - instead, use code B00.2 - Noma - instead, use code A69.0 ICD-10-CM Alphabetical Index References for 'K12 - Stomatitis and related lesions' The ICD-10-CM Alphabetical Index links the below-listed medical terms to the ICD code K12. Click on any term below to browse the alphabetical index.	4	2	0	0	13	0.344326	13	746
Textbook of Psychiatry/Somatoform Disorders - 1 Introduction - 2 Terminology - 3 Phenomenology - 4 Pathogenesis - 5 Treatment - 6 Final Considerations - 7 References The somatoform disorders have in common the "repeated presentation of physical symptoms, together with persistent requests for medical investigations, in spite of repeated negative findings and reassurances by doctors that the symptoms have no physical basis" (World Health Organization, 1992). Psychiatrists worldwide use either the ICD-10 or DSM-IV systems of classification when diagnosing mental illness. For most conditions there is little difference between the two systems, but for the somatoform disorders the conditions included differ slightly – see Table 1 for details. Table 1: Comparison of Somatoform Disorders: ICD-10 vs. DSM-IV Somatoform Disorders (F45) Somatoform Disorders (300) \|Somatization disorder\|\|Somatization disorder\| \|Undifferentiated somatoform disorder\|\|Undifferentiated somatoform disorder\| \|Hypochondriacal disorders (includes Body dysmorphic disorder)\|\|Hypochondriasis\| \|Body dysmorphic disorder\| \|Somatoform autonomic dysfunction\| \|Persistent somatoform pain disorder\|\|Pain disorder\| \|Other somatoform disorders\| \|Somatoform disorder, unspecified\|\|Somatoform disorder, not otherwise specified\| For the purposes of this chapter we take an inclusive view of disorders loosely grouped under the somatoform label and cover the following conditions: • Somatization Disorder • Hypochondriacal Disorder • Somatoform Pain Disorder and Chronic Pain • Conversion (Dissociative Motor) Disorder • Body Dysmorphic Disorder • Functional Somatic Syndromes (e.g., chronic fatigue syndrome/myalgic encephalomyelitis, fibromyalgia, chronic pelvic pain, multiple chemical sensitivity). The Somatoform Disorders are important to recognise because they are relatively common, costly and almost invariably present to doctors other than psychiatrists. In addition, many doctors find patients with these disorders difficult to understand and treat. The feature that all of these illnesses have in common is the patient’s experience of medically unexplained symptoms, which refers to physical (or somatic) symptoms that are disproportionate to identifiable physical disease. The terminology is confusing in this area, as many terms are used interchangeably. For example, although we often use the term medically unexplained symptoms in this chapter you may also encounter terms such as "somatization," "functional symptoms" or "hysterical symptoms" seemingly referring to the same thing. It is possible for one patient to fulfil diagnostic criteria for several somatoform disorders at one time (e.g., somatoform pain disorder and dissociative disorder) which has led to criticism of current diagnostic systems, and it is likely that future versions of ICD/DSM will change how such disorders are defined (Kroenke, Sharpe et al. 2007). To make matters worse, psychiatrists often use different diagnostic terminology to that used by their medical colleagues; these differences can hamper doctors’ ability to come to a shared understanding of a patient’s problems. Take, for example, a woman who suffers from a wide number and range of symptoms for which no adequate pathological cause has been found. These symptoms have been present for many years, have resulted in marked disability and, despite a long history of consultations with many different doctors, there has been no improvement. The woman’s medically unexplained symptoms include fatigue, dizziness, headache, subjective limb weakness and painful joints. A psychiatrist makes a diagnosis of "somatization disorder," whilst a rheumatologist diagnoses "fibromyalgia" and a neurologist "chronic fatigue syndrome/myalgic encephalomyelitis." The patient herself rejects all of these diagnoses and prefers to think of herself as having "multiple chemical sensitivity." In the field of the somatoform disorders, the labels often say more about the specialty of the person applying them than any underlying pathology. The lesson to learn here is that these diagnostic labels are descriptive, often overlapping and seldom uncontentious. Clinical Symptoms and Classification All somatoform disorders are highly co-morbid (i.e., co-exist) with each other and with anxiety and depression. Therefore screening for anxiety and depression, which are treatable, should be undertaken in any patient presenting with a medically unexplained syndrome. In the following section we go through the somatoform disorders in turn and highlight their diagnostic features. The diagnostic descriptions are based on ICD-10 criteria where possible. We emphasise from the outset that the classification of the so called somatoform disorders is a mess, which we hope (perhaps optimistically) will be improved in the current revisions of both ICD and DSM: i) Somatization Disorder The patient has a history of multiple and recurrent medically unexplained symptoms (>6 symptoms) starting in early adult life and lasting for at least 2 years. The symptoms cause distress and impairment and lead to repetitive consultations with medical personnel that are typically unhelpful. There is usually a history of unnecessary or unhelpful investigations or procedures and the patient may have a high level of disability. These patients commonly present to many different specialists and are high users of health care resources. ii) Hypochondriacal Disorder The patient is persistently preoccupied (for > 6 months) and distressed with the possibility of having one or more serious illnesses. This health anxiety persists despite repeated medical reassurance that they do not suffer from the feared illness(es). There is overlap with obsessive-compulsive disorder. iii) Somatoform Pain Disorder and Chronic Pain The patient has persistent (> 6 months), severe and distressing pain that is not fully explained by a physical disorder and they are pre-occupied by their pain symptoms. Chronic pain is also a common symptom in somatization disorder. iv) Conversion (or Dissociative Motor) Disorder The patient has motor or sensory symptoms (e.g., seizures, paralysis, loss of speech, blindness) for which there is inadequate physical explanation. There is usually considerable disability associated with the symptoms. The patient should not be intentionally feigning the symptoms. This disorder was of great interest to early neurologists and psychiatrists including Charcot, Janet and Freud, when it was known as hysteria. The term conversion disorder originally implied that psychological symptoms (or conflicts) were converted to motor symptoms, although this rather simplistic view is now outdated (Halligan, Bass et al. 2000). Nevertheless, in practice clinicians treating these patients expect to be able to determine psychological or emotional factors that are contributing to the patient’s presentation. v) Body Dysmorphic Disorder The patient has a persistent preoccupation that a part of the body is diseased or deformed, when to an objective observer it is not. The patient will often pursue surgical or other cosmetic treatments in order to correct the perceived deformity and therefore commonly present to dermatologists or cosmetic surgeons. In ICD-10 this disorder is classified within hypochondriacal disorder, but DSM-IV prefers to keep it as a distinct disorder. Many psychiatric researchers believe that body dysmorphic disorder would actually be better classified as an anxiety disorder because there is often considerable overlap with obsessive compulsive disorder. iv) Functional Somatic Syndromes The functional somatic syndromes refer to a number of related syndromes that have been characterised by the reporting of somatic symptoms and resultant disability rather than on the evidence of underlying conventional disease processes. Many such syndromes have been described. Some of these - such as irritable bowel syndrome - are well recognised within mainstream medicine but others - such as sick building syndrome - are not. All however share the feature of a disconnection between subjective symptomatology and objective biomedical pathology. Most medical specialities have at least one functional somatic syndrome – see Table 2 for examples. Table 2: Functional somatic syndromes by medical speciality \|Medical Specialty\|\|Functional Somatic Syndrome\| \|Gastroenterology\|\|Irritable bowel syndrome\| Repetitive strain injury \|Cardiology\|\|Non cardiac chest pain\| \|Infectious Disease\|\|Chronic fatigue syndrome/myalgic encephalomyelitis (sero-negative) Lyme Disease \|Respiratory Medicine\|\|Hyperventilation syndrome\| \|Dentistry\|\|Atypical facial pain Temporomandibular joint dysfunction \|Ear Nose & Throat\|\|Globus syndrome\| \|Non allied syndromes\|\|Gulf War syndrome Sick building syndrome Multiple chemical hypersensitivity Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), irritable bowel syndrome and fibromyalgia, have been more extensively researched than most other functional somatic syndromes, which has led to specific pathophysiological mechanisms being advanced for each and the development of widely accepted diagnostic criteria. Nevertheless, as yet no specific explanation is compelling and it remains the case that the similarities between the different syndromes are sufficiently striking for there to be a compelling case for considering them together (Barsky and Borus 1999; Wessely, Nimnuan et al. 1999). Commonly used diagnostic criteria for the three most well known functional somatic syndromes are outlined below: Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS) (Fukuda, Straus et al. 1994) - 6 months disabling fatigue - Substantially reduced activity - At least 4 of these symptoms: - Impaired memory or concentration - Sore throat - Tender glands - Aching/stiff muscles - Multiple joint pains - New Headaches - Unrefreshing sleep - Post-exertional fatigue Irritable bowel syndrome (Rome Foundation, 2006) - Recurrent abdominal pain or discomfort at least 3 days per month in the last 3 months associated with ≥2 of the following: - Improvement with defecation - Onset associated with a change in frequency of stool - Onset associated with a change in the form (appearance) or the stool Fibromyalgia (Wolfe, Smythe et al. 1990) - Widespread pain in combination with… - Tenderness at ≥11 of 18 specific tender point sites Somatic symptoms are common and are the main reason why people seek medical care. Around a third of somatic symptoms that are seen in primary care can be classified as medically unexplained (Kroenke, 2003), whilst the proportion is at least as high in secondary care clinics (Nimnuan, Hotopf et al. 2001; Reid, Wessely et al. 2001; Carson, Best et al. 2003). The prevalence (frequency) of the specific somatoform disorders varies depending on the setting and the diagnostic criteria used. For example the population prevalence of strictly defined somatisation disorder is around 0.5%, but rises to as much as 16.6% when abridged criteria are used (Creed and Barsky, 2004). Likewise the population prevalence of hypochondriacal disorder has been estimated at between 0.02% and 7.7%, with abridged criteria suggesting a prevalence as high as 10.7% (Creed and Barsky, 2004). Body dysmorphic disorder is believed to be present in approximately 1-2% of the general population (Mackley, 2005). Fewer studies have looked at the epidemiology of somatoform pain or conversion disorders, and once again differing diagnostic criteria and populations lead to difficulties in interpretation. Prevalence estimates for the commonest functional somatic syndromes are shown in Table 3. Most epidemiological research in the functional somatic syndromes has focussed on the prevalence of CFS/ME, fibromyalgia and irritable bowel syndrome - probably because operational criteria exist for these disorders. Table 3: Prevalence figures for a sample of functional somatic syndromes \|Functional Somatic Syndrome\|\|Estimated population prevalence\| \|Chronic fatigue syndrome\|\|0.007 – 0.56% (Ranjith, 2005)\| \|Irritable bowel syndrome\|\|3 – 20% (Brandt, Bjorkman et al. 2002)\| \|Fibromyalgia\|\|0.5 – 5% (Neumann and Buskila, 2003)\| \|Non cardiac chest pain\|\|25% (Fass and Dickman, 2006)\| \|Chronic pelvic pain\|\|15% women (Zondervan and Barlow, 2000)\| \|Tension-type headache\|\|38% (Jensen and Stovner, 2008)\| Most research shows that women suffer from somatoform disorders more frequently than men, with the probable exceptions of hypochondriacal disorder and body dysmorphic disorder. A low level of education is also a risk factor. Other aetiological factors are reviewed below under "Assessment." Allow adequate time Adequate time should be allowed for assessment of patients with medically unexplained symptoms. Although this can be difficult in the setting of a busy primary care clinic or medical outpatients, time spent engaging the patient and gaining a full history will pay dividends later. Patients with severe and enduring medically unexplained symptoms will often have had negative experiences of medical care in the past (Reid, Ewan et al. 1991) (Deale and Wessely, 2001) and it is important that the patient feels believed whenever they are seen by a new health care professional. Therefore good communication skills are important. Start with the symptoms A good place to start is by taking an exhaustive and full history of all current symptoms. This is not solely for (or even for the purposes of) making a diagnosis, but to demonstrate to the patient that they are being taken seriously and it gives an indication of the way that the patient relates to their symptoms. Duration, severity, exacerbating and relieving factors should be explored for the main symptoms. One of the most neglected questions is to ask the patient what their concerns are about their symptoms (e.g., are they worried that they have cancer?). As a general rule, the more symptoms someone has, the more likely they are to be medically unexplained. It is useful to understand how impaired someone is by their symptoms on a day to day basis and how their illness impacts on their life. When the opportunity arises, psychosocial difficulties should be explored; the easiest way to do this is to use the patient’s own terminology to ask about an area more fully (e.g., if a patient mentions they are "stressed," you can use this word to ask them what is difficult for them in their life). This can help you understand the patient’s illness behaviour better i.e., how does the patient behave when they are symptomatic? Do their symptoms enable them to avoid situations that are stressful? Understanding what the patient attributes their symptoms to can help you explain how unhelpful patterns may have emerged (e.g., a person with CFS/ME who believes their symptoms are due to work stress will behave and manage their symptoms very differently from someone who attributes identical symptoms to a persistent viral infection. Review previous notes It is preferable to have read previous notes and investigations before meeting the patient, although this is not always possible. It is essential to review old notes before ordering more investigations, as repeating old investigations for previously investigated symptoms can lead to iatrogenic harm (Page and Wessely, 2003). A notes review can add valuable information on previous symptoms or past diagnoses (including somatoform disorders). It also offers an important insight into how the patient interacts with doctors and other doctors’ opinions of the patients’ problems. Rule out anxiety and depression Patients with anxiety or depression commonly present with physical rather than emotional symptoms. Both anxiety and depression are often experienced physically (e.g., anxiety can present with difficulty swallowing, stomach unease, sweaty palms; depression can present with weight loss, poor appetite, low energy). However, most patients will talk about the emotional symptoms of anxiety and depression if the topic is approached sensitively. Because the terms "anxiety" and "depression" are not universally understood, it is useful to have some probing questions you can use that are suitable for the culture in which you are working. Some examples of questions that are suitable for use in the Western setting are shown in Table 4. Table 4: Example probe questions when screening for anxiety or depression \|Do you often feel tense? Do you find yourself worrying a lot? Do you ever feel panicky? Is it difficult for you to relax? Do you feel keyed-up most of the time? \|Do you feel low or down very much? Do you still enjoy things as much as you used to? Do you feel slowed down? Are you often aware of feeling sad or miserable? Do you feel hopeful about the future? Communication For patients with medically unexplained symptoms the first consultation with a new doctor is important. As mentioned above, these patients have often had negative experiences of medical consultations in the past, so an empathic manner and sensitively taken history can be therapeutic in itself. It is never a good idea to imply that you don’t find a patient’s symptoms credible or that there is "nothing wrong" because investigations have been negative. The patient’s symptoms are real and often uncomfortable, even if their patho-physiology is unclear. Many doctors dislike it if a patient expresses negative sentiments about their colleagues or other services. For the most part it is not necessary to enter into an argument with the patient about the rights and wrongs of their previous medical encounters, instead respond to the emotional content of what the patient is saying rather than the specifics (e.g., "that must have made you feel very angry"). One issue around all medically unexplained syndromes is when do they become medically explained? Everyone remembers genuine breakthroughs in our understanding of health and disease; one such example being the discovery that General Paresis of the Insane (GPI) (sufferers of which could be found in all the asylums of Europe at the end of the 19th century) was a manifestation of neurosyphilis. When, a generation later, penicillin was found to kill the causative agent, GPI largely disappeared. In our own time, generations of doctors had been taught that peptic ulcer was due to excessive acid secretion, itself the result of stress: that is until Helicobacter Pylori was identified. But we should also pause for thought. First, the traffic is not all one way. For every previously viewed unexplained or psychiatric illness whose "medical" cause is identified, there is an equal and opposite traffic, as previously viewed medical entities such as visceral proptosis, autointoxication, floating kidneys, chronic appendicitis and so on and so on make the opposite journey. Second, many of the mechanisms that we highlight in this contribution do not cease to be relevant once a causative organism or factor is identified – far from it. The same issues remain relevant, for example psychosocially informed treatments (e.g., Cognitive Behavioural Therapy) do not lose their effectiveness, which is not surprising given that they are of proven efficacy in improving outcome in conditions as diverse as cancer, rheumatoid arthritis, multiple sclerosis, HIV related illness and so on. Somatoform disorders are best thought of as multi-factorial in origin. It is rare than one mechanism (be it emotional or physical) is responsible for a patient’s symptoms. When thinking about why a patient is suffering from medically unexplained symptoms, the traditional psychiatric formulation is helpful i.e., what are the predisposing, precipitating and maintaining factors in this person’s symptoms? It can also be useful to think about how someone’s symptoms may have a physiological (as opposed to patho-physiological) explanation. Genetics There is evidence that the general tendency to experience symptoms has a partly heritable basis (Gillespie, Zhu et al. 2000). Furthermore the evidence for the role of genetics in specific somatoform disorders has also increased in recent years. For example twin studies have shown that CFS/ME is substantially heritable (Buchwald, Herrell et al. 2001) and there is also evidence that chronic pain states, including fibromyalgia, might have a genetic component (Buskila, 2007), as might irritable bowel syndrome (Talley, 2006). There may be some genetic liability for hypochondriacal disorder and somatisation disorder, but this has been less investigated (Kendler, Walters et al. 1995; Noyes, Holt et al. 1997). Neuroendocrine changes Changes within the neuroendocrine system offer an interesting explanation for some of the biological changes seen in the somatoform disorders, although the story is not totally coherent. Most intensive research in this field has been done in CFS/ME and fibromyalgia. There is some evidence of low circulating cortisol in CFS/ME, which is in contrast to the pattern seen in major depression (Parker, Wessely et al. 2001; Cleare 2003). In addition the serotonergic system may be overactive in CFS/ME (Parker, Wessely et al. 2001). A reduction in the responsivity of the hypothalamic-pituitary-adrenal (HPA) axis has also been shown in fibromyalgia (Parker, Wessely et al. 2001). Neuroendocrine changes in irritable bowel syndrome have been less examined, although there is some evidence of abnormal activity of the HPA axis and also that the gut may be over activated by corticotrophin releasing hormone in those with the condition (Fukudo, Nomura et al. 1998). It is likely that at least some of the neuroendocrine abnormalities that have been observed are secondary and these abnormalities are probably best viewed as maintaining factors. Infection or injury Injury and infection may play a precipitating role in some somatoform disorders and this idea has been most explored for conditions such as CFS/ME and fibromyalgia. In clinical practice patients often cite an injury as the precipitant to chronic pain conditions such as fibromyalgia and this has some limited support in the literature (Al-Allaf, Dunbar et al. 2002). It is generally accepted that there is no single infective agent involved in the pathogenesis of CFS/ME (Afari and Buchwald 2003) or irritable bowel syndrome (Talley and Spiller 2002). Prospective cohort studies - the only way to determine causality - have confirmed that exposure to Epstein-Barr virus (EBV) increases he risk of CFS/ME (White, Thomas et al. 1998), as have Q fever, Lyme Disease (Prins, van der Meer et al. 2006) and viral illnesses requiring hospitalisation (Hotopf, Noah et al. 1996). However, psychiatric morbidity, female gender and prolonged convalescence are still the most important predictors of developing CFS/ME following infection (Hotopf, Noah et al. 1996; Candy, Chalder et al. 2003). As we write the world’s media are reporting a great breakthrough in the struggle to identify the cause of CFS/ME; a new retrovirus (XMRV) has been identified in 67% of a large series of CFS/ME patients in the USA but only 3% of controls (Lombardi, Ruscetti et al. 2009) - an association that is stronger than that between smoking and lung cancer. The finding is contained in the journal Science, a peer reviewed journal of outstanding reputation. It is indeed genuinely exciting and if true will indeed represent perhaps the single most important change in our understanding of the illness so far. Clinical practice will indeed change, and in the not too distant future, new and novel treatments should emerge. Of course the findings may not stand up to scrutiny, and there have been other equally dramatic claims made in this field before, which have not stood the test of time and replication. But, assuming that this new breakthrough is indeed just that, does that mean that all previous knowledge about CFS is rendered obsolete? Not at all. Perhaps a new drug will abolish CFS, but that seems unlikely. There will remain a major role for the kind of understanding and interventions that are the focus of this chapter, just as they remain important in so many other illnesses and diseases. Deconditioning Physical deconditioning offers an appealing mechanism for the maintenance of symptoms in the somatoform disorders. There is some evidence for reduced physical fitness in fibromyalgia (Valim, Oliveira et al. 2002) and reduced exercise capacity in CFS/ME when compared to sedentary controls (Fulcher and White, 2000). For patients with chronic and severe somatoform disorders (such as somatisation disorder) the physical effects of years of reduced activity or the use of aids such as wheelchairs can be profound. Such patients present an enormous rehabilitation challenge. Central dysfunction Some preliminary neuroimaging studies have been conducted in conversion disorder, CFS/ME, irritable bowel syndrome and pain syndromes that suggest that central mechanisms may play a role in these disorders. For example several functional neuroimaging studies have suggested that inhibitory networks are abnormally activated in conversion disorder (Aybek, Kanaan et al. 2008). At present, the usefulness of neuroimaging research in somatoform disorders is limited, but taken as a whole probably does support the idea of aberrant patterns of brain activation in these conditions (particularly in response to relevant probes such as experimentally induced pain). It is not known whether these changes pre-exist the illness or have developed secondarily. Childhood experiences Experience in childhood appears to be relevant to the development of somatoform disorders later in life. Longitudinal studies show that children who experience parental ill health in childhood are more likely to develop medically unexplained symptoms as adults (Hotopf, Mayou et al. 1999). Whether childhood illness increases the likelihood of adult somatoform disorders is less clear – certainly childhood medically unexplained illness appears to do so (Hotopf, Wilson-Jones et al. 2000). Childhood sexual abuse increases the risks of adult somatoform disorders (Paras, Hassan Murad et al. 2009). Stressful events Stressful events can precipitate the onset of a somatoform disorder and are known to occur more frequently in the period leading up to the onset of medically unexplained symptoms (Craig, Drake et al. 1994). A similar picture has been shown for CFS/ME, with patients experiencing "dilemmas" in the months preceding onset (Hatcher and House, 2003). Chronic stress (or life events) has also been shown to be important in the onset and maintenance of symptoms in irritable bowel syndrome (Creed, Craig et al. 1988; Bennett, Tennant et al. 1998) and fibromyalgia (Anderberg, Marteinsdottir et al. 2000). Trauma such as sexual abuse (Paras, Hassan Murad et al. 2009) or involvement in a disaster (van den Bergh, Grievink et al. 2005) also appears to be a risk factor for the development of a range of somatoform disorders Personality It is often presumed that personality factors are an important predisposing and maintaining factor in somatoform disorders, although there is little supporting evidence. Emotional instability (or neuroticism) may prolong the course of hypochondriacal disorder (olde Hartman, Borghuis et al. 2009) and, along with introversion, has been found to be a risk factor for the development of CFS/ME (Kato, Sulllivan et al. 2006; Prins, van der Meer et al. 2006). Patients with non-epileptic seizures (a type of conversion disorder) have been found to have high rates of personality disorder (Bowman and Markand, 1996). Clinically, patients with co-morbid personality disorder can be very challenging to manage. Illness beliefs Illness beliefs are enormously important in the maintenance (and possibly precipitation) of somatoform disorders. Beliefs link bi-directly to both behaviours and emotions, which means that by altering one of these domains the other two are likely to be affected – see the diagram below. Patients with CFS/ME are more likely to make physical illness attributions for a selection of common symptoms compared to controls (Butler, Chalder et al. 2001); perhaps in consequence and are more likely to believe their illness will be chronic and have serious consequences when compared to patients with chronic medical conditions (Weinman, Petrie et al. 1996). Illness worry is related to disability in fibromyalgia, but not in rheumatoid arthritis (Robbins and Kirmayer, 1990). Likewise, those with irritable bowel syndrome score more highly on hypochondriacal and bodily preoccupation scales than control groups (Gomborone, Dewsnap et al. 1995). Making physical attributions for unexplained symptoms is natural – the problem is what these may imply for the person’s concepts of self efficacy, acceptable treatment and likely prognosis. Deale et al showed that for patients with CFS to recover, it was not necessary that their illness attributions changed (e.g., "the illness is physical and caused by a virus"), but instead improvement was linked to change in beliefs such as "doing too much makes me worse," "I need to rest to get better" and so on (Deale, Chalder et al. 1998). In other words, physical illness attributions can act as a confounder or marker for more unhelpful beliefs that are associated with maladapative coping responses. The term "symptom amplification" is used to describe the manner in which innocuous symptoms become incorrectly attributed and then incorporated into a patient’s understanding of their illness, which leads to further incorrect attribution of other symptoms as they arise (Barsky and Borus, 1999). These beliefs and attitudes about symptoms may act as a mechanism that then guides the patient to adopt avoidant behaviours, leading to limitation of activity, which in turn leads to the secondary deconditioning and neuroendocrine effects outlined above. Avoidance behaviours are invariably based on the patient’s understanding of their illness (e.g., "when I feel fatigued, I cause myself further harm if I exercise") and are often possible to work with during treatment (Deale, Chalder et al. 1998). Living Environment We have discussed above the possible importance of the early family environment in predisposing someone to suffer from medically unexplained symptoms (e.g., by experiencing the illness of a parent in early life), however the behaviour and attitude of close family and friends can also play a role in the maintenance of medically unexplained symptoms. For example partners of patients with CFS/ME are more likely to make physical attributions about their partner’s symptoms than the partners of fracture clinic patients (Butler, Chalder et al. 2001). Clinically it is often as relevant to understand the illness beliefs of close family as it is the patient’s – particularly when the family are providing high levels of care and support. Financial Reward The financial "reward" to be gained from disability payments or litigation has been argued to play a role in the maintenance of ill-health in those suffering from somatoform disorders (Malleson, 2002). For example, being in receipt of sickness benefit or certification has been shown to be a poor prognostic sign in CFS/ME (Cope, David et al. 1994; Bentall, Powell et al. 2002) and fibromyalgia (Wigers, 1996), whilst the whiplash syndrome does not appear to exist in countries without an insurance/compensation culture (Schrader, Obelieniene et al. 1996). Media Several functional somatic syndromes including CFS/ME, Gulf War syndrome and repetitive strain injury, have gained public credibility in spite of widespread medical scepticism as to their very existence. The role of the media in this process has often been highlighted (Shorter, 1995; Barsky and Borus, 1999; Hazemeijer and Rasker, 2003). The availability and explosion in internet sites has also meant that patients may inadvertently be exposed to information that is inaccurate or even harmful (Armstrong, 2000; Kisely, 2002). The assessment itself can be therapeutic, particularly if time is taken to provide a clear explanation for symptoms, which is not perceived by the patient to blame them. The doctor may need to avoid colluding with the patient, but also avoid denying the reality of the symptoms. Research has shown that "empowering" explanations are the most beneficial for patients with medically unexplained symptoms (i.e., explanations that provide a tangible mechanism, de-emphasise blame and provide the opportunity for self-management) (Salmon, Peters et al. 1999). The provision of clear information in different forms (i.e., verbal and written) is necessary. Patients with medically unexplained symptoms often appear to be seeking reassurance, but this can be difficult to deliver effectively. It is counter-productive to tell a patient that "there is nothing wrong," when their symptoms are proof that there is. On the other hand it is important to counter specific illness fears that the patient may hold (e.g., "My symptoms mean I’ve got cancer," "This rash shows that I have HIV," "If I do too much I will permanently damage my spine") if that is not the case. This is why it is important to have asked the patient what they believe is wrong. Patients with hypochondriacal disorder will often attempt to elicit repeated reassurance, which fails to provide reassure for any length of time (Deale, 2007). If there is evidence of anxiety or depression at first assessment, then this should be treated in the usual way. Doing so will often, although not always, lead to a significant improvement in the patient’s somatic symptoms. A doctor that sees a patient with medically unexplained symptoms for follow-up has an important role to play in managing that patient’s interaction with medical services. Even if the doctor does not perceive themselves to be providing active therapy, they can be aware of potentially iatrogenic interventions (i.e., harm caused by doctors) (Page and Wessely, 2003). They can also provide regular follow-up that is not contingent on the patient being symptomatic, thereby discouraging the need for the patient to complain of symptoms in order to elicit care. It is sometimes possible to agree beforehand that only a certain proportion of the session will be devoted to discussing symptoms, and leave it to the patient to decide the content of the second half of the interview. Overall cognitive behavioural therapy (CBT) is known to be an efficacious treatment for the range of the conditions loosely grouped under the somatoform disorders (Sumathipala, 2007). CBT and similar therapies have shown specific usefulness in the treatment of hypochondriacal disorder (Thomson and Page, 2007), CFS/ME (Chambers, Bagnall et al. 2006), irritable bowel syndrome (Brandt, Bjorkman et al. 2002), fibromyalgia (Rossy, Buckelew et al. 1999) and burning mouth syndrome (Zakrzewska, Glenny et al.). CBT can be adapted for use in any of these disorders, but like most medical treatments relies on the patient being sufficiently motivated to participate. One of the first goals in CBT is for the therapist and patient to come to a shared understanding of the patient’s problems using a CBT framework – the therapist often uses diagrams like the one on page 18 to illustrate this. Evidence is lacking for useful psychotherapeutic treatments for conversion disorder (Martlew, Baker et al. 2007), although preliminary studies have shown that, once again, CBT may be useful (Goldstein, Deale et al. 2004). Overall there is evidence that antidepressant medication is useful in the treatment of somatoform disorders (O'Malley, Jackson et al. 1999; Sumathipala, 2007), although it is not possible to generally recommend the use of one type of antidepressant over another. For the functional somatic syndromes there are some specific recommendations, for example tricyclic antidepressants are effective in treating fibromyalgia (Arnold, Keck et al. 2000), abdominal pain in irritable bowel syndrome (Brandt, Bjorkman et al. 2002) and premenstrual tension (Steiner, Steinberg et al. 1996). On the other hand antidepressants have not been found to be useful in CFS/ME without co-morbid depression (Whiting, Bagnall et al. 2001). In general the effectiveness of antidepressants in these disorders increases if the patient has evidence of co-morbid depression or anxiety, however medication is probably less effective than psychological approaches. It can be necessary to rationalise inappropriate medication, as some patients with somatoform disorders are prescribed medication that is unnecessary or even harmful. This needs to be done by (or in conjunction with) primary care and the rationale discussed with the patient in advance. In clinical practice it is common to combine a psychotherapeutic and pharmacological approach to management. The patient may have strong feelings about treatment and these should be taken into consideration. In developed countries treatment for somatoform disorders can sometimes be provided by specialists (e.g., consultation-liaison psychiatrists) attached to general hospitals, although provision is often patchy and as in developing countries much of the burden falls to primary care. Factitious disorder or Munchausen’s syndrome is listed separately (adjacent to the somatoform disorders) in DSM-IV classification, whilst ICD-10 classes it amongst the personality disorders. Malingering is not considered to be a psychiatric disorder by either system. However the distinction of factitious disorder or malingering from the somatoform disorders can be unclear, so for the sake of completeness we mention them here. Diagnostic features are outlined below. Factitious disorder is probably a rare condition about which little is known, although persons suffering from this disorder are likely to have significant personality disturbance and a background of neglect or abuse. Malingering is more common, although quite how common is unknown due to the nature of the behaviour. • Persistent faking of symptoms or self-infliction of wounds to produce symptoms • Persistent visits to hospital in order to gain care for these symptoms (may move from hospital to hospital to avoid detection) • No external gain (e.g., financial) is apparent, so the gain is viewed as being psychological • Deliberate falsification of a medical condition • The falsification (or exaggeration) is for financial or other obvious material gain Afari, N. and D. Buchwald (2003). "Chronic fatigue syndrome: a review." American Journal of Psychiatry 160: 221-236. Al-Allaf, A. W., K. L. Dunbar, et al. (2002). "A case-control study examining the role of physical trauma in the onset of fibromyalgia syndrome." Rheumatology 41(4): 450-3. Anderberg, U., I. Marteinsdottir, et al. (2000). "The impact of life events in female patients with fibromyalgia and in female healthy controls." European Psychiatry 15: 295-301. Armstrong, R. (2000). "Fibromylagia: is recovery impeded by the internet?" Archives Internal Medicine 160: 1039. Arnold, L. M., P. E. Keck, et al. (2000). "Antidepressant treatment of fibromyalgia. A meta-analysis and review." Psychosomatics 41: 104-113. Aybek, S., R. Kanaan, et al. (2008). "The neuropsychiatry of conversion disorder." Current Opinion Psychiatry 21: 275-280. Barsky, A. and J. Borus (1999). "Functional somatic syndromes." Annals of Internal Medicine 130: 910-921. Bennett, E., C. Tennant, et al. (1998). "Level of chronic life stress predicts clinical outcome in irritable bowel syndrome." Gut 43: 256-261. Bentall, R., P. Powell, et al. (2002). "Predictors of response to treatment for chronic fatigue syndrome." British Journal of Psychiatry 181: 248-252. Bowman, E. and O. Markand (1996). "Psychodynamics and psychiatric diagnoses of pseudoseizure subjects." American Journal of Psychiatry 153(1): 57-63. Brandt, L., D. Bjorkman, et al. (2002). "Systematic review on the management of irritable bowel syndrome in North America." American Journal of Gastroenterology 97(11): S7-S26. Buchwald, D., R. Herrell, et al. (2001). "A Twin study of chronic fatigue." Psychosomatic Medicine 63: 936-943. Buskila, D. (2007). "Genetics of chronic pain states." Best Practice & Research in Clinical Rheumatology 21(3): 535-547. Butler, J., T. Chalder, et al. (2001). "Causal attributions for somatic sensations in paitents with chronic fatigue syndrome and their partners." Psychological Medicine 31: 97-105. Butler, J., T. Chalder, et al. (2001). "Causal attributions for somatic sensations in patients with chronic fatigue syndrome and their partners." Psychological Medicine 31: 97-105. Candy, B., T. Chalder, et al. (2003). "Predictors of fatigue following the onset of infectious mononucleosis." Psychological Medicine 33: 847-855. Carson, A., S. Best, et al. (2003). "The outcome of neurology outpatients with medically unexplained symptoms: a prospective cohort study." Journal of Neurology Neurosurgery and Psychiatry 74: 897-900. Chambers, D., A.-M. Bagnall, et al. (2006). "Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome / myalgic encephalomyelitis: an updated systematic review." Journal of the Royal Society of Medicine 99: 506-520. Cleare, A. (2003). "The neuroendocrinology of chronic fatigue syndrome." Endocrine Reviews 24(2): 236-252. Cope, H., A. David, et al. (1994). "Predictors of chronic "postviral" fatigue." Lancet 344: 864-868. Craig, T., H. Drake, et al. (1994). "The South London somatisation study II: influence of stressful life events and secondary gain." British Journal of Psychiatry 165: 248-258. Creed, F. and A. Barsky (2004). "A systematic review of the epidemiology of somatisation disorder and hypochondriasis." Journal of Psychosomatic Research 56: 391-408. Creed, F., T. Craig, et al. (1988). "Functional abdominal pain, psychiatric illness and life events." Gut 29: 235-242. Deale, A. (2007). "Psychopathology and treatment of severe health anxiety." Psychiatry 6(6): 240-246. Deale, A., T. Chalder, et al. (1998). "Illness beliefs and treatment outcome in chronic fatigue syndrome." Journal of Psychosomatic Research 45: 77-83. Deale, A., T. Chalder, et al. (1998). "Illness beliefs and treatment outcome in chronic fatigue syndrome." Journal of Psychosomatic Research 45(1): 77-83. Deale, A. and S. Wessely (2001). "Patients' perceptions of medical care in chronic fatigue syndrome." Social Science & Medicine 52: 1859-1864. Fass, R. and R. Dickman (2006). "Non-cardiac chest pain: an update." Neurogastroenterology Motility 18: 408-417. Fukuda, K., S. Straus, et al. (1994). "The chronic fatigue syndrome: a comprehensive approach to its definition and study." Annals of Internal Medicine 121: 953-959. Fukudo, S., T. Nomura, et al. (1998). "Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome." Gut 42(6): 845-849. Fulcher, K. Y. and P. D. White (2000). "Strength and physiological response to exercise in patients with chronic fatigue syndrome." Journal of Neurology Neurosurgery and Psychiatry 69: 302-307. Gillespie, N., G. Zhu, et al. (2000). "The genetic aetiology of somatic distress." Psychological Medicine 30: 1051-1061. Goldstein, L., A. Deale, et al. (2004). "An evaluation of cognitive behavioral therapy as a treatment for dissociative seizures." Cognitive and Behavioral Neurology 17: 41-49. Gomborone, J., P. Dewsnap, et al. (1995). "Abnromal illness attitudes in patients with irritable bowel syndrome." Journal of Psychosomatic Research 39(2): 227-230. Halligan, P., C. Bass, et al. (2000). "New approaches to conversion hysteria." BMJ 320: 1488-1489. Harrison, S. (2002). Temporomandibular joint pain. Assessment and Management of Orofacial Pain. J. Zakrzewska and S. Harrison. Amsterdam, Elsevier Science BV: 191-208. Hatcher, S. and A. House (2003). "Life events, difficulties and dilemmas in the onset of chronic fatigue syndrome: a case-control study." Psychological Medicine 33: 1185-1192. Hazemeijer, I. and J. Rasker (2003). "Fibromyalgia and the therapeutic domain. A philosophical study on the origins of fibromyalgia in a specific social setting." Rheumatology 42: 507-515. Hotopf, M., R. Mayou, et al. (1999). "Childhood risk factors for adults with medically unexplained symptoms: results from a national birth cohort study." American Journal of Psychiatry 156(11): 1796-800. Hotopf, M., N. Noah, et al. (1996). "Chronic fatigue and minor psychiatric morbidity after viral meningitis: a controlled study." Journal of Neurology, Neurosurgery and Psychiatry 60(5): 504-509. Hotopf, M., C. Wilson-Jones, et al. (2000). "Childhood predictors of adult medically unexplained syndromes." British Journal of Psychiatry 176(3): 273-280. Jensen, R. and L. Stovner (2008). "Epidemiology and comorbidity of headache." Lancet Neurology 7: 354-361. Kato, K., P. Sulllivan, et al. (2006). "Premorbid predictors of chronic fatigue." Archives General Psychiatry 63: 1267-1272. Kendler, K., E. Walters, et al. (1995). "A twin-family study of self-report symptoms of panic-phobia and somatization." Behavior Genetics 25(6): 499-515. Kisely, S. R. (2002). "Treatments for chronic fatigue syndrome and the internet: a systematic survey of what your patients are reading." Australian and New Zealand Journal of Psychiatry 36: 240-245. Kroenke, K. (2003). "Patients presenting with somatic complaints: epidemiology, psychiatric co-morbidity and management." International Journal of Methods in Psychiatric Research 12(1): 34-43. Kroenke, K., M. Sharpe, et al. (2007). "Revising the classification of somatoform disorders: key questions and preliminary recommendations." Psychosomatics 48: 277-285. Lombardi, V., F. Ruscetti, et al. (2009). "Detection of an infectious retrovirus, XMRV, in blood cells of patients with Chronic Fatigue Syndrome." Science DOI 10.1126/science.1179052. Mackley, C. (2005). "Body dysmorphic disorder." Dermatologic Surgery 31: 553-558. Martlew, J., G. Baker, et al. (2007) "Behavioural treatments for non-epileptic attack disorder." Cochrane Database of Systematic Reviews DOI: 10.1002/14651858. Neumann, L. and D. Buskila (2003). "Epidemiology of fibromyalgia." Current Pain & Headache Reports 7: 362-368. Nimnuan, C., M. Hotopf, et al. (2001). "Medically unexplained symptoms: an epidemiological study in seven specialities." Journal of Psychosomatic Research 51: 361-367. Noyes, R., C. Holt, et al. (1997). "A family study of hypochondriasis." The Journal of Nervous and Mental Disease 185: 223-232. O'Malley, P., J. Jackson, et al. (1999). "Antidepressant therapy for unexplained symptoms and symptom syndromes." The Journal of Family Practice 48(12): 980-990. olde Hartman, T. C., M. S. Borghuis, et al. (2009). "Medically unexplained symptoms, somatisation disorder and hypochondriasis: Course and prognosis. A systematic review." Journal of Psychosomatic Research 66(5): 363-377. Page, L. and S. Wessely (2003). "Medically unexplained symptoms: exacerbating factors in the doctor-patient encounter." Journal of the Royal Society of Medicine 96: 223-227. Paras, M., M. Hassan Murad, et al. (2009). "Sexual abuse and lifetime diagnosis of somatic disorders." JAMA 302(5): 550-561. Parker, A., S. Wessely, et al. (2001). "The neuroendocrinology of chronic fatigue syndrome and fibromyalgia." Psychological M edicine 31: 1331-1345. Prins, J., J. van der Meer, et al. (2006). "Chronic fatigue syndrome." Lancet 367: 346-355. Ranjith, G. (2005). "Epidemiology of chronic fatigue syndrome." Occupational medicine 55: 13-19. Reid, J., C. Ewan, et al. (1991). "Pilgrimage of pain: the illness experiences of women with repetition strain injury and the search for credibility." Social Science and Medicine 32: 601-612. Reid, S., S. Wessely, et al. (2001). "Medically unexplained symptoms in frequent attenders of secondary health care: retrospective cohort study." BMJ 322: 767-769. Robbins, J. and L. Kirmayer (1990). "Illness worry and disability in fibromyalgia syndrome." International Journal of Psychiatry in Medicine 20: 49-63. Rome Foundation (2006) "Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders." http://www.romecriteria.org/assets/pdf/19_RomeIII_apA_885-898.pdf. Rossy, L., S. Buckelew, et al. (1999). "A meta-analysis of fibromyalgia treatment interventions." Annals of Behavioral Medicine 21(2): 180-191. Salmon, P., S. Peters, et al. (1999). "Patients' perceptions of medical explanations for somatisation disorders: Qualitative analysis." BMJ 318(7180): 372-376. Schrader, H., D. Obelieniene, et al. (1996). "Natural evolution of late whiplash syndrome outside the medicolegal context." Lancet 347: 1207-11. Shorter, E. (1995). "Sucker-punched again! Physicians meet the disease-of-the-month syndrome." Journal of Psychosomatic Research 39(2): 115-118. Steiner, M., S. Steinberg, et al. (1996). "Fluoxetine in the treatment of premenstrual dysphoria." New England Journal of Medicine 332: 1529-1534. Sumathipala, A. (2007). "What is the evidence for the efficacy of treatments for somatoform disorders? A critical review of previous intervention studies." Psychosomatic Medicine 69: 889-900. Talley, N. (2006). "Genes and environment in irritable bowel syndrome: one step forward." Gut 55: 1694-1696. Talley, N. and R. Spiller (2002). "Irritable bowel syndrome: a little understood organic bowel disease?" Lancet 360: 555-564. Thomson, A. and L. Page (2007) "Psychotherapies for hypochondriasis." Cochrane Database of Systematic Reviews DOI: 10.1002/14651858. Valim, V., L. Oliveira, et al. (2002). "Peak oxygen uptake and ventilatory anaerobic threshold in fibromyalgia." Journal of Rheumatology 29: 353-357. van den Bergh, B., L. Grievink, et al. (2005). "Medically unexplained physical symptoms in the aftermath of disasters." Epidemiologic Reviews 27(1): 92-106. Weinman, J., K. Petrie, et al. (1996). "The illness perception questionnaire: a new method for assessing the cognitive representation of illness." Psychology and Health 11: 431-445. Wessely, S., C. Nimnuan, et al. (1999). "Functional somatic syndromes: one or many?" Lancet 354: 936-939. White, P., J. Thomas, et al. (1998). "Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever." British Journal of Psychiatry 173: 475-481. Whiting, P., A. Bagnall, et al. (2001). "Interventions for the treatment and management of chronic fatigue syndrome: a systematic review." Journal of the American Medical Association 286: 1360-1368. Wigers, S. (1996). "Fibromyalgia outcome: the predictive values of symptom duration, physical activity, disability pension and critical life events - a 4.5 year prospective study." Journal of Psychosomatic Research 41(3): 235-243. Wolfe, F., H. Smythe, et al. (1990). "The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: report of the multicenter criteria committee." Arthritis and Rheumatism 33: 160-173. World Health Organization (1992). The ICD-10 Classification of Mental and Behavioural Disorders. Geneva. Zakrzewska, J., A. Glenny, et al. "Interventions for the treatment of burning mouth syndrome (Cochrane Review)." Cochrane Library 2. 2004. Zondervan, K. and D. Barlow (2000). "Epidemiology of chronic pelvic pain." Best Practice & Research in Clinical Obstetrics & Gynaecology 14(3): 403-414.	2	8	0	0	3	0.926717	3	11,766
Complex Regional Pain Syndrome Type 1 Complex Regional Pain Syndrome, often referred to as CRPS, is a medical condition whereby the affected individual experiences severe pain in one or more limb. Complex Regional Pain Syndrome pain is typically described as being more intense than what would be expected for the inciting injury or stimuli. To date, the pathophysiology of Complex Regional Pain Syndrome is not well understood although studies have managed to identify two forms of the medical condition. The first is called Complex Regional Pain Syndrome Type 1 which is the most common form of the medical condition reported in patients. The other is Complex Regional Pain Syndrome Type 2, a rarer form of the condition distinguished from the aforementioned by the presence of distinct nerve damage. Complex Regional Pain Syndrome Type 1 Complex Regional Pain Syndrome Type 1 and Type 2 can also be distinguished by the fact that the former normally occurs after an initial noxious event. Other than this and the nerve damage mentioned in association with the development of Complex Regional Pain Syndrome Type 2, there’s hardly any difference between Complex Regional Pain Syndrome Type 1 versus Type 2. Reflex Sympathetic Dystrophy (RSD) is an old term used for Complex Regional Pain Syndrome Type 1 and some literature may still refer to the medical condition as RSD. Doctors, health insurance companies, and public health agencies also define Complex Regional Pain Syndrome Type 1 by alpha-numeric codes under the International Statistical Classification of Diseases and Related Health Problems, or ICD for short. ICD-10 is the 10th revision of the list. ICD-10 codes can also give information regarding the body site where the medical condition occurs, severity of the problem, and cause of the injury—among other things. Complex Regional Pain Syndrome Type 1 ICD-10 codes specify which limb is affected. Some examples of Complex Regional Pain Syndrome Type 1 ICD-10 codes are G90.51 for Complex regional Pain Syndrome Type 1 occurring in the upper limb and G90.59 if the condition occurs in some other specified site. The latter code is usually reserved for those rare cases of Complex Regional Pain Syndrome where it develops in other parts of the body besides the limbs. What Causes Complex Regional Pain Syndrome Type 1? As previously mentioned, Complex Regional Pain Syndrome Type 1 usually develops following an initial noxious event resulting in varying degrees of tissue injury. Some examples of such events include infections, sprains, surgery, nerve pressure, stroke, heart attack, immobilisation, and radiation therapy. It may be difficult to determine the actual cause of Complex Regional Pain Syndrome Type 1 in some patients and sometimes, more than a single noxious event may lead to the development of the disorder. In fact, some individuals with the injuries mentioned above may not end up with the Complex Regional Pain Syndrome Type 1 disorder at all, and studies have not yet been able to determine why that is. To determine the occurrence of Complex Regional Pain Syndrome Type 1 in a patient, an examiner would have to take note of their signs and symptoms and use a diagnostic checklist to compare them with those expected in Complex Regional Pain Syndrome Type 1 patients. Other conditions which may present the same signs and symptoms will also have to be tested for and ruled out before a Complex Regional Pain Syndrome Type 1 diagnosis is given. Signs and Symptoms in Complex Regional Pain Syndrome Type 1 Patients The first thing that would point to the presence of Complex Pain Regional Syndrome Type 1 in a patient is severe pain that’s more intense than the inciting injury and lasts longer than what is considered normal for said injury. The criteria used to determine whether or not a patient has Complex Regional Pain Syndrome is called the Budapest Criteria which helps with making a clinical diagnosis of the disorder. The Budapest Criteria is basically a guideline in the form of a checklist with the common Complex Regional Pain Syndrome signs and symptoms listed under the categories sensory, vasomotor, sudomotor, and motor. The Budapest Criteria also stipulates that any medical conditions with similar signs and/or symptoms must be checked for and ruled out before a diagnosis is made. Even though there’s no established medical procedure for the diagnosis of Complex Regional Pain Syndrome Type 1; medical tests such as X-rays, MRI scans, thermography, and bone scans can help rule out other medical conditions. Once a Complex Regional Pain Syndrome Type 1 diagnosis has been made, early treatment is recommended for better management of the medical condition. How Is Complex Regional Pain Syndrome Type 1 Treated? In some patients, Complex Regional Pain Syndrome Type 1 has been said to disappear after two years from the time of onset. However, this is a long time and a great risk for someone to suffer through severe pain with the hope that it will someday stop on its own. The delay in treatment can also make it difficult to manage the condition, leaving the patient in the unrelenting pain. Even though there is currently no cure for Complex Regional Pain Syndrome Type 1, some patients have been seen to improve vastly through treatments that combine medications, physiotherapy, and psychotherapy. The medicinal treatments used involve the use of various types of drugs mostly targeted at offering relief from Complex Regional Pain Syndrome Type 1 pain. Physiotherapy works hand-in-hand with the medications to increase the patient’s pain threshold and improve functionality of the affected limb through the use of gentle exercises. Because of the severe pain that affected individuals experience and the resulting increased dependency on caregivers, Complex Regional Pain Syndrome Type 1 patients are often depressed and anxious. This is where psychotherapy comes in. Therapies such as cognitive behavioural therapy and occupational therapy help those diagnosed with Complex Regional Pain Syndrome Type 1 manage their pain and learn new ways to perform their daily tasks so that they are not too dependent on their caregivers. Neridronate Complex Regional Pain Syndrome Type 1 treatment Among the many types of medications used for Complex Regional Pain Syndrome Type 1 treatment, Neridronate shows better long-term benefits when it comes to pain reduction and functional recovery. It is—so far—the only treatment designed specifically for Complex Regional Pain Syndrome treatment; made and approved for use in Italy. Despite the slight difference between Complex Regional Pain Syndrome Type 1 and Type 2, they are usually treated in the same way and that also applies to the Neridronate treatment. Neridronate is a bisphosphonate, which is a class of molecules used for the treatment of bone cancer and osteoporosis. The efficacy of Neridronate in the treatment of Complex Regional Pain Syndrome was actually discovered when a patient was being treated for the above mentioned condition. The patient had also been suffering from Complex Regional Pain Syndrome and reported improved relief from the symptoms after the bisphosphonate treatment. This discovery led to years of further studies until Neridronate was created and patented for the treatment of rheumatic diseases, particularly the difficult to treat Complex Regional Pain Syndrome. It is worth noting that Doctor Adami made significant contributions towards the strides made in implementing Neridronate for Complex Regional Pain Syndrome treatment. The efficacy of Neridronate for Complex Regional Pain Syndrome Type 1 treatment is partially reliant on the duration of the medical condition. Early Neridronate treatment is recommended for the best results, so it is best for a doctor to prescribe this treatment as soon as a Complex Regional Pain Syndrome diagnosis is confirmed after the onset of the first signs and symptoms. Some doctors in Italy believe that this is not entirely the case, and as long as a patient is still showing symptoms of Complex Regional Pain Syndrome then the medical condition will still be active and treatable using Neridronate, though the results may differ a little. Bisphosphonates easily bond to calcium which is a major component of bones. As a result of the easy bondage between bisphosphonates and calcium, the former is easily incorporated by bones. Once the bisphosphonates bind to the surface of bones, they halt the breakdown of bones which is one of the common symptoms of Complex Regional Pain Syndrome Type 1. This mechanism gives a little insight into the workings of the Neridronate treatment. Complex Regional Pain Syndrome patients are first evaluated to determine if they are eligible for Neridronate treatment. This is achieved by checking the patient’s clinical history and information about the treatments they’ve received so far, as well as other medical records such as any major dental work done 6 months prior, as one of the side effects of the treatment is jaw necrosis. Knowing the medications and other treatments that the patient is currently receiving is also important as some treatments—medical or otherwise—may not be compatible with Neridronate and may need to be stopped before the new treatment begins. Once a patient is confirmed to be eligible and ready for Neridronate treatment, they are given 4 infusions of Neridronate in accordance with Dr. Adami’s original protocol. Neridronate can be administered intravenously or orally, although the oral method may lead to side effects such as jaw necrosis and irritation of the stomach and oesophagus. Physiotherapy to help with blood and circulation, as well as pain medications for pain relief are recommended along with Neridronate treatment during the 2 to 3 months it takes for the infusions to take full effect. Light Therapy, also known as Heliotherapy, is also recommended to complete the treatment. A 97% rate of total remission has been reported, especially in patients still in the early stages of the disease. People who have been suffering from Complex Regional Pain Syndrome Type 1 for some time may experience varying levels of pain relief as each individual case is unique. As mentioned before, a few side effects may come from the use of Neridronate such as light flu-like symptoms, dizziness, and lower calcium or Vitamin D levels in the blood. The Light Therapy suggested above actually helps to remedy the issue of Vitamin D deficiency in patients receiving the Neridronate treatment. Other medications used for Complex Regional Pain Syndrome Type 1 treatment The other commonly used drugs for Complex Regional Pain Syndrome Type 1 pain relief include: - Oral Muscle Relaxants The effectiveness of these drugs with respect to pain relief varies with each individual. Some may get the best results from using one or all of these, while other patients may experience worsening of their symptoms instead. This makes it difficult to treat the medical condition and it is best to evaluate the best treatment option for each patient on a case-by-case basis. Most of these offer short term relief, if any, and only Neridronate has been proven to give Complex Regional Pain Syndrome patients lasting relief from their symptoms. True to its name, Complex Regional Pain Syndrome Type 1 is a complex medical condition. Research efforts continue to be made into understanding it and finding the best way to treat it. So far, the interdisciplinary approach seems to work for most patients. It is important that the patient communicates whether their symptoms get worse or better with any particular treatment so that adjustments can be made. Besides the types of treatments mentioned above, there are other methods for treating Complex Regional Pain Syndrome Type 1 that have been discovered. Some are natural remedies such as Epsom salt baths and heliotherapy. Others are controversial and considered unethical by some. Examples of these include surgical sympathectomy and amputation which most believe will only make the condition worse instead of treating it effectively. Increasing awareness of Complex Regional Pain Syndrome Type 1 contributes greatly to the discovery of new and better treatment options. A Complex Regional Pain Syndrome can return to their everyday life by managing their pain with medications and pursuing physical exercises to help restore limb function.	2	5	0	0	2	0.734136	2	2,373
Looking for online definition of polyneuropathy in the Medical Dictionary? polyneuropathy explanation free. What is polyneuropathy? Meaning of. Oct 14, 2005. Peripheral neuropathy is a somewhat ambiguous term, implying a disorder of peripheral nerves. Clearly, a single focal compressive palsy (e.g. carpal tunnel syndrome) or a. polyneuropathy (a fairly nonspecific pattern usually due to a diffuse process), or whether there. neuropathies are sensorimotor. The diagnostic challenge of small fibre neuropathy: clinical presentations, evaluations, and causes Neurological examinations investigating sensory, motor and autonomic signs help to define the topography and nature of neuropathy. Demyelinating neuropathies may also have a length-dependent pattern of sensory evolution because in a diffuse process, longer fibers have a greater likelihood of being blocked. Feb 15, 1998. An algorithmic approach to the evaluation and differential diagnosis of a patient with peripheral neuropathy is presented, based on important elements of the clinical history and physical examination, the use of. Hereditary abnormalities of myelin are usually diffuse, with a slowly progressive course. Introduction [return to contents] Peripheral neuropathy usually presents with weakness and sensory loss or pain in the arms and legs. It is estimated that. Peripheral nerves are composed of sensory, motor, and autonomic elements. Diseases can affect the cell body of a neuron or its peripheral processes, namely the axons or the encasing myelin sheaths. Most peripheral nerves are mixed and contain sensory and motor as well as autonomic fibers. Nerves can be subdivided. Peripheral neuropathy (PN) is damage to or disease affecting nerves, which may impair sensation, movement, gland or organ function, or other aspects of health, depending on the type of nerve affected. Common causes include systemic diseases (such as diabetes or leprosy), vitamin deficiency, medication (e.g., A polyneuropathy is a diffuse peripheral nerve disorder that is not confined to the distribution of a single nerve or a single limb and typically is relatively symmetrical bilaterally. Electrodiagnostic tests should always be done to classify the nerve structures involved, distribution, and severity of the disorder and thus help identify. Fda Approved Drugs Diabetic Neuropathy ★★ Reverse Diabetic Neuropathy ★★ ::The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days.[ REVERSE DIABETIC NEUROPATHY ] The. Aug 14, 2013. The FDA is also advising Know Anesthesia billing claim guidelines and rules for getting payments. How to bill the anesthesia claim in the correct manner without time delay. Oct 13, 2017. Sensory – Negative or positive, diffuse or focal; usually insidious in onset and showing a stocking-and-glove distribution in the distal extremities. Motor – Distal, proximal, or more focal weakness, sometimes occurring along with sensory neuropathy (sensorimotor neuropathy). Autonomic – Neuropathy that. Jul 1, 2015. nostic testing in the evaluation of length-dependent sensorimotor peripheral neu- ropathies; and (3). efficiently and effectively screen (in less than 2 minutes) an asymptomatic patient for peripheral neuropathy when they have a disorder in. the process may begin to look more diffuse. Care- ful history and. diabetic neuropathy any of several clinical types of peripheral neuropathy ( sensory, motor, autonomic, and mixed) occurring with diabetes mellitus; the most common is a chronic, symmetrical sensory polyneuropathy affecting first the nerves of the lower limbs and often affecting autonomic nerves. entrapment neuropathy any. Progressive muscle weakness. Limb-girdle (proximal) weakness. Chronic. Drug/toxin-induced myopathy: The following drugs may give rise to myopathy. POEMS syndrome (Polyneuropathy,Organomegaly,Endocrinopathy,Monoclonal protein,Skin changes) is characterized by the presence of a monoclonal plasma cell. Box 1 Peripheral Neuropathy Syndromes; Acute-Subacute Generalized Polyneuropathies; Sensorimotor: Acute motor and sensory axonal neuropathy. The term peripheral neuropathy designates a disturbance in function of one or more peripheral nerves. Several types of peripheral neuropathy are distinguishable by the extent of involvement. Depending upon the underlying cause, there may be selective involvement of motor, sensory, or autonomic fibers or more diffuse. Evaluation of Peripheral Neuropathy. • ISCHEMIC PERIPHERAL NEUROPATHY. • Diabetes. • Collagen-vascular disorders (polyarteritis nodosa). • Diffuse sensorimotor neuropathy or a mononeuritis multiplex. • Lupus – can mimic AIDP, diffuse sensorimotor neuropathy or mononeuritis multiplex. • Vascular and immune. Along with its needed effects, lithium may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need. 151800 – lipomatosis, multiple symmetric; msl – lipomatosis, familial benign cervical;; lipodystrophy, cephalothoracic Chapter 8 – Reflex evaluation. Reflexes are the most objective part of the neurologic examination and they are very helpful in helping to determine the. These disorders are termed generalized sensorimotor polyneuropathies, and they represent the most common form of peripheral neuropathy. This review focuses primarily on this. More-diffuse involvement of an entire limb might be caused by involvement of the brachial or lumbosacral plexus. Alternatively, if generalized. The incidence of peripheral neuropathy is not known, but it is a common feature of many systemic diseases. Diabetes and alcoholism are the most common. Goransson et al. (2006) detected clinically significant peripheral neuropathy in 17 (27%) of 62 patients with primary Sjogren syndrome. Nerve conduction. Polyneuropathy (poly- + neuro- + -pathy) is damage or disease affecting peripheral nerves (peripheral neuropathy) in roughly the same areas on both sides of the body, featuring weakness, numbness, and burning pain. It usually begins in the hands and feet and may progress to the arms and legs; and sometimes to other. Doctors may use terms such as predominantly motor neuropathy, predominantly sensory neuropathy, sensory-motor neuropathy, or autonomic neuropathy to describe the types of. Peripheral neuropathies that involve more diffuse nerve damage, such as diabetic neuropathy, are not amenable to surgical intervention. top. Peripheral Neuropathy Center Weill Medical College Cornell University Fda Approved Drugs Diabetic Neuropathy ★★ Reverse Diabetic Neuropathy ★★ ::The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days.[ REVERSE DIABETIC NEUROPATHY ] The. Aug 14, 2013. Infiltrates primarily in spinal cord & CNS 1. Angiotropic large B-cell lymphoma (Malignant angioendotheliomatosis; Intravascular B-cell lymphoma) Neuropathies are classified according to cause (endocrine, metabolic, nutritional, toxic, etc) or clinical presentation (sensory, motor, autonomic, mixed sensory and motor, mononeuritis, mononeuritis multiplex, etc). Due to the diverse causes of neuropathy, laboratory testing is invariably required for diagnosis or etiologic. Early in the course of certain PNS disorders, sensory symptoms are prominent and signs of peripheral neuropathy may be subtle. Results of EDX testing for patients with CIDP indicate diffuse slowing of action potential conduction velocities, prolonged distal latencies, prolongation of F waves, and/or the presence of. Polyneuropathies and other disorders of the peripheral nervous system. Approximate Synonyms. Neuropathy (nerve damage), multifocal motor. ICD-10- CM G62.89 is grouped within Diagnostic Related Group(s) (MS-DRG v35.0):. 073 Cranial and peripheral nerve disorders with mcc; 074 Cranial and peripheral nerve. Number: 0675. Policy. Aetna considers bortezomib (Velcade) for intravenous or subcutaneous administration medically necessary for treatment of the. Number: 0485. Policy. Aetna considers autonomic testing such as quantitative sudomotor axon reflex test (QSART), silastic sweat imprint, and. Genetic types of PMP-22 gene mutations Duplication of one gene (3 total copies of PMP-22): Types Segmental duplication in gene area. Due to unequal. More Neuropathy Articles ... - Peripheral Neuropathy And Ssd: Settlements and Awards Settlements $130,000 settlement for 19 year old client from mid-coast area of Maine. Defendant driver lost control on snowy and icy. Premier Disability Services, LLC® is a nationwide Social Security Disability firm. We fil... - Peripheral Neuropathy In Lupus Patients: Celiac disease, or gluten sensitivity, is an autoimmune inflammatory disease that damages the villi - the small, finger-like projections that line the. The incidence of peripheral neuropathy is not known, but it is a common feature of many systemic d... - Neuropathy In Dogs With Diabetes: Peripheral Neuropathy (Polyneuropathies) in Dogs. Polyneuropathy is a nerve disorder that affects multiple peripheral nerves. Unlike the central nervous system , which has the vertebrae of the spine, and the bone of the skull to protect it, the perip... - Diabetic Neuropathy Ankle Pain: Results. A higher incidence of neuropathic pain in those over 60 years of age showed an ABI > 1.3. Neuropathic pain was related to an abnormal ABI in 144 patients (64.2%). A statistically significant value was obtained in type 2 diabetes patients ... - Peripheral Neuropathy Diffrential Diagnosis: So, a differential diagnosis is simply a specific determination of what is causing your peripheral neuropathy symptoms. If you can at least get a proper diagnosis, consider yourself lucky for that, even though you unfortunately are suffering from the... - Elavil For Peripheral Neuropathy: Cancer patients often experience significant pain. Sometimes this is a side effect of the treatment, and sometimes because of the cancer itself. Peripheral Neuropathy is a common neurologic condition, which affects the peripheral nerves. The most com...	2	12	0	0	2	0.538649	2	2,252
Body septic infection: What is sepsis? \| Sepsis Sepsis (Blood Infection): Symptoms, Causes & Treatments What Is Sepsis? Sepsis is when your body has an unusually severe response to an infection. It’s sometimes called septicemia. During sepsis, your immune system, which defends you from germs, releases a lot of chemicals into your blood. This triggers widespread inflammation that can lead to organ damage. Clots reduce blood flow to your limbs and internal organs, so they don’t get the nutrients and oxygen they need. In severe cases, sepsis causes a dangerous drop in blood pressure. Doctors call this “septic shock.” It can quickly lead to organ failure, such as your lungs, kidneys, and liver. This can be deadly. Sepsis Causes and Risk Factors Bacterial infections are most often to blame for sepsis. But it can also happen because of other infections. It can begin anywhere bacteria, parasites, fungi, or viruses enter your body, even something as small as a hangnail. An infection of the bone, called osteomyelitis, could lead to sepsis. In people who are hospitalized, bacteria may enter through IV lines, surgical wounds, urinary catheters, and bed sores. Sepsis is more common in people who: - Have weakened immune systems because of conditions like HIV or cancer or because they take drugs such as steroids or those that prevent rejection of transplanted organs - Are pregnant - Are very young - Are elderly, especially if they have other health problems - Were recently hospitalized or had major surgeries - Use catheters or breathing tubes - Have diabetes - Have a serious medical condition such as appendicitis, pneumonia, meningitis, cirrhosis, or a urinary tract infection Because it can begin in different parts of your body, sepsis can have many different symptoms. The first signs may include rapid breathing and confusion. Other common symptoms include: Your doctor will do a physical exam and run tests to look for things like: Your doctor will probably keep you in the hospital’s intensive care unit (ICU). Your medical team will try to stop the infection, keep your organs working, and manage your blood pressure. IV fluids and extra oxygen can help with this. Broad-spectrum antibiotics may fight infections caused by bacteria early on. Once your doctor knows what’s causing your sepsis, they can give you medicine that targets that specific germ. Often, doctors prescribe vasopressors (which make your blood vessels narrow) to improve blood pressure. You could also get corticosteroids to fight inflammation or insulin to keep control of your blood sugar. If your case is severe, you might need other types of treatment, like a breathing machine or kidney dialysis. Or you may need surgery to drain or clean out an infection. As sepsis gets worse, it causes more problems throughout your body. These may include: - Kidney failure - Dead tissue (gangrene) on fingers and toes, leading to amputation - Lung, brain, or heart damage - A higher risk of infections over time Sepsis can be deadly in between 25% and 40% of cases. Preventing infection is the best way to prevent sepsis. Take these steps: - Wash your hands often with soap and water for at least 20 seconds each time. - Keep up with recommended vaccines for things like flu and chickenpox. - Keep control of any chronic health conditions. - If you have an injury that’s broken your skin, clean it as soon as possible. Keep it clean and covered as it heals, and watch for signs of infection. - Treat any infections. Get medical care right away if they don’t get better or if they seem like they’re getting worse. What Is Sepsis \| Sepsis Alliance Sepsis is the body’s overwhelming and life-threatening response to infection that can lead to tissue damage, organ failure, and death. In other words, it’s your body’s overactive and toxic response to an infection. Like strokes or heart attacks, sepsis is a medical emergency that requires rapid diagnosis and treatment. Sepsis can lead to severe sepsis and septic shock. You may have heard the term “blood poisoning” used instead of sepsis. Blood poisoning is not an accurate description of sepsis. You can learn more about sepsis and blood poisoning here. Your immune system usually works to fight any germs (bacteria, viruses, fungi, or parasites) to prevent infection. If an infection does occur, your immune system will try to fight it, although you may need help with medication such as antibiotics, antivirals, antifungals, and antiparasitics. However, for reasons researchers don’t understand, sometimes the immune system stops fighting the “invaders,” and begins to turn on itself. This is the start of sepsis. Some people are at higher risk of developing sepsis because they are at higher risk of contracting an infection. These include the very young, the very old, those with chronic illnesses, and those with a weakened or impaired immune system. Patients are diagnosed with sepsis when they develop a set of signs and symptoms related to sepsis. Sepsis is not diagnosed based on an infection itself. If you have more than one of the symptoms of sepsis, especially if there are signs of an infection or you fall into one of the higher risk groups, your doctor will likely suspect sepsis. Sepsis progresses to severe sepsis when in addition to signs of sepsis, there are signs of organ dysfunction, such as difficulty breathing (problems with the lungs), low or no urine output (kidneys), abnormal liver tests (liver), and changes in mental status (brain). Nearly all patients with severe sepsis require treatment in an intensive care unit (ICU). Septic shock is the most severe level and is diagnosed when your blood pressure drops to dangerous levels. Sepsis is the number 1 cost of hospitalization in the U.S. Costs for acute sepsis hospitalization and skilled nursing are estimated to be $62 billion annually. This is only a portion of all sepsis-related costs, since there are substantial additional costs after discharge for many. The average cost per hospital stay for sepsis is double the average cost per stay across all other conditions. And, sepsis is the primary cause of readmission to the hospital, costing more than $3.5 billion each year. Studies investigating survival have reported slightly different numbers, but it appears that on average, approximately 30% of patients diagnosed with severe sepsis do not survive. Up to 50% of survivors suffer from post-sepsis syndrome. Until a cure for sepsis is found, early detection and treatment is essential for survival and limiting disability for survivors. Updated August 2, 2021. Sepsis and Septic Shock – Infections Culture of a blood sample Tests to find the source of infection (tests usually include chest x-rays and other imaging tests and cultures of fluid or tissue samples) Doctors usually suspect sepsis when a person who has an infection suddenly develops a very high or low temperature, a rapid heart rate or breathing rate, or low blood pressure. To confirm the diagnosis, doctors look for bacteria in the bloodstream (bacteremia), evidence of another infection that could be causing sepsis, and an abnormal number of white blood cells in a blood sample. Samples of blood are taken to try to grow (culture) the bacteria in the laboratory (a 1- to 3-day process). However, if people have been taking antibiotics for their initial infection, bacteria may be present but may not grow in the culture. Sometimes catheters are removed from the body, and the tips are cut off and sent for culture. Finding bacteria in a catheter that had contact with the blood indicates that bacteria are probably in the bloodstream. To check for other infections that may cause sepsis, doctors take samples of fluids or tissue, such as urine, cerebrospinal fluid, tissue from wounds, or sputum coughed up from the lungs. These samples are cultured and checked for bacteria. Other tests are done to look for signs of organ malfunction and other complications of sepsis. They may include the following: Blood tests to measure levels of lactic acid and other metabolic waste products, which may be high, and the number of platelets (cells that help the blood clot), which may be low Blood tests or a sensor placed on a finger (pulse oximetry) to measure oxygen levels in the blood and thus evaluate how well the lungs and blood vessels are functioning Electrocardiography (ECG) to look for abnormalities in heart rhythm and thus determine whether the blood supply to the heart is adequate Other tests to determine whether shock results from sepsis or another problem Sepsis Explained – Water Quality and Health Council By Barbara M. Soule, RN, MPA, CIC, FSHEA, and Ralph Morris, MD, MPH July 22, 2016 Sepsis is the body’s overwhelming and life-threatening response to infection. Sepsis causes inflammation throughout the body, which can lead to tissue damage, organ failure, and even death, according to the Centers for Disease Control and Prevention (CDC). Sepsis is a serious complication of septicemia, also known as bacteremia or blood poisoning. Septicemia occurs when a bacterial infection somewhere in the body (e.g., the skin, kidneys, urinary tract, abdominal area or lungs) spreads into the bloodstream. We recently wrote about human Vibrio infections from contaminated shellfish and coastal and especially brackish waters. Some Vibrio infections progress to sepsis, which is why we highlighted the Louisiana Department of Wildlife and Fisheries advisory that fishermen in saltwater carry with them “basic disinfectant (chlorine bleach mixed one part bleach to four parts fresh water1 or tincture of iodine, or antibiotic ointment) and use if skin is punctured while handling fishing tackle, bait or fish.” According to the Mayo Clinic website, sepsis is diagnosed when at least two of the following signs accompany a probable or confirmed infection: - Elevated body temperature of 101 degrees F (or greater) or a below normal body temperature of 8 degrees F (or less) - Heart rate higher than 90 beats per minute - Respiratory rate higher than 20 breaths per minute. Severe sepsis is diagnosed with at least one more of the following, which indicate an organ may be failing: - Significantly decreased urine output - Abrupt change in mental status - Decrease in platelet count - Difficulty breathing - Abnormal heart pumping function - Abdominal pain Toxins released into the bloodstream by some bacteria can cause extremely low blood pressure. Septic shock results when the patient does not respond to simple fluid replacement. Septic shock can lead to death. Whereas most people recover from mild sepsis, the Mayo Clinic website indicates a 50 percent mortality rate for septic shock. The image above, from the CDC Sepsis Fact Sheet, lists major strategies for preventing sepsis. Who is Vulnerable to Sepsis? Anyone can develop septicemia and sepsis, but according to the Mayo Clinic the most vulnerable include the very young and very old; patients taking immunosuppressive medications; cancer patients; long-term steroid users; people with long-standing diabetes, AIDS or cirrhosis; people with large burns or severe injuries; and people with infections, such as pneumonia, meningitis, cellulitis and urinary tract infections. Sepsis Requires Treatment! Sepsis is a medical emergency that requires treatment. There are more than one million cases of sepsis each year in the US. Sepsis can lead to septic shock and death; survivors of sepsis may suffer permanent organ damage and have to deal with life-changing health effects. The CDC recommends calling your doctor or going to the emergency room immediately if you have any signs or symptoms of an infection or sepsis. CDC urges that you state, “I AM CONCERNED ABOUT SEPSIS” to ensure timely evaluation and treatment, which may include antibiotics, oxygen and intravenous fluids. The image below from the CDC Sepsis Fact Sheet may be helpful in determining when to seek medical attention. Forewarned is forearmed! For more information on sepsis, please see www.cdc.gov/sepsis. Barbara M. Soule, R.N. MPA, CIC, FSHEA is an Infection Preventionist and a member of the Water Quality & Health Council. Ralph Morris, MD, MPH, is a Physician and Preventive Medicine and Public Health official. Click here to download this article. 1 Fishermen should prepare this solution daily, as bleach solutions weaken over time. Sepsis From Intravenous (IV) Drug Use While drug abuse of any kind can be dangerous, certain routes of administration can cause greater damage than others. Intravenous drug use, the act of injecting a water-soluble drug into one’s body, is one of the most invasive and dangerous ways an individual can administer a drug. Through continued use and repeated trauma to the injection site, IV drug abuse leads to many hazardous health effects, including sepsis. What Is Sepsis? While many people think sepsis is an infection itself, it’s actually a complication caused by an infection. As explained by Mayo Clinic, “sepsis occurs when chemicals are released into the bloodstream to fight the infection trigger inflammatory responses throughout the body.” The type of infection which can cause sepsis varies. Sepsis is most heavily linked to bacteria, though certain forms of fungus or viruses may also cause it. Sepsis is commonly referred to as “blood poisoning,” as the bacteria or toxins produced by them overtake the bloodstream. What Are The Stages Of Sepsis? Mayo Clinic explains that sepsis is typically broken down into three stages: Sepsis is diagnosed only when there is reasonable suspicion or verification of an infection, in addition to two of the following symptoms: - Body temperature above 101 F (38.3 C) or below 96.8 F (36 C) - Heart rate higher than 90 beats a minute - Respiratory rate higher than 20 breaths a minute Within this state, a person must have one or more of the following symptoms: - Improperly working heart - Respiratory (breathing) struggles - Pain in the abdomen - Platelet count begins falling - Rapidly altered mental states - Urine production drastically drops Any of these symptoms indicate potential organ failure. As a person’s condition advances to this state, they will display the above signs and symptoms. But, in order to qualify as septic shock, a person’s blood pressure must remain low despite attempts to increase it with fluid replacement. Sepsis becomes more dangerous as it progresses through these stages. To avoid the greatest danger, treatment should begin as early as possible. How Does IV Drug Use Cause Sepsis? Intravenous drug use can introduce numerous toxins and pathogens into a person’s veins and body at large, which pave the way for infection. Pathogens include bacteria, fungi, and viruses. Staphyloccus aureus, or MRSA as it’s better known to most of us, is the bacteria most frequently responsible for IV drug infections. Transmission of these pathogens often occurs due to improper and unhygienic handling of needles. As a person becomes addicted, the need to use becomes so intense that they disregard their health. Because of this, some users share needles. This behavior increases the risk that a pathogen will be transmitted by blood-to-blood contact. Even if you never share needles, you could still be at risk. Far too many drug abusers repeatedly use the same syringe. Doing so allows bacteria to grow on the needle, which could then be transmitted into your tissue and blood. Even with new needles, a person can still get an infection if they don’t properly clean the injection site. Research has found that bacteria from a person’s skin presents a greater risk than that which is present on shared needles. Intravenous injection requires a vein, which leaves drug abusers with only so many options. Because of this, many users will repeatedly inject at the same site. This can create abscesses, track marks, or ulcers, all of which can lead to serious infection. Sometimes, a user will actually miss the vein and inject the drug into their muscle or right under the skin, raising the risk of infection in these regions. Lastly, it’s suspected that using black tar heroin increases a user’s risk of infection. What Types Of IV Drug-Related Illness Or Disease Cause Sepsis? Intravenous drug abuse causes a range of infections, many of which can become deadly. One of the biggest reasons why these infections endanger a person’s life is because they cause sepsis. The following infections can lead to sepsis: - Cellulitis: This infection affects both the skin and underlying tissue, and can spread outwards across the limb. - Endocarditis: This occurs when bacteria, fungus, or viruses cause an infection within your heart’s inner lining and valves. - Necrotizing fasciitis: Often referred to as the “flesh-eating disease,” this rare but serious infection is extremely aggressive and causes your body’s soft tissues to die. Whether you inject sporadically or chronically, you’re exposing yourself to danger. While it’s true that prolonged and chronic use increases your risk over time, it is possible to contract an infection from even one use. What Are The Complications And Dangers Of Sepsis? Sepsis poisons your blood and body. The more time that passes without treatment, the greater the risk of complications and fatality. Sepsis can become so severe that your organs struggle to function properly. This can lead to organ damage and/or failure. Combined with the dangers of the infections themselves, these effects even further increase the risk of death. A person’s veins can become septic and develop blood clots, inflammation, and bacteria throughout. Injecting into the jugular or other central veins increases this risk. These states could develop into sepsis and septic emboli (bacteria and pus-filled embolisms), both of which can be life-threatening conditions. As outlined by the Sepsis Alliance, individuals who recover from sepsis often face serious long-term effects, such as: - Amputated limbs - Chronic pain - Chronic fatigue - Post-traumatic stress disorder (PTSD) - Organ dysfunction How Is Sepsis Treated? If you suspect you have or are developing sepsis, seek medical help immediately. Left untreated, sepsis can progress rapidly to the point of threatening your life. As soon as you seek treatment, medical staff will likely administer a broad-spectrum antibiotic. This medication can address various types of infection and the bacteria which cause them. Once tests determine the specific bacteria, a more focused antibiotic may be used. Through these stages, Mayo writes that other treatments may be initiated, such as: - Drugs to stabilize the immune system - Insulin (to stabilize blood sugar) - IV fluids - Painkillers (staff should proceed accordingly with opioid-addicted individuals) - Vasopressor medication to raise blood pressure Advanced stages of sepsis may require: - Breathing support - Kidney dialysis Mayo Clinic cautions that “people with severe sepsis require close monitoring and treatment in a hospital intensive care unit. If you have severe sepsis or septic shock, lifesaving measures may be needed to stabilize breathing and heart function.” While sepsis can be treated, we urge you to consider preventative measures to avoid this risk. Effective drug rehab can help you to overcome your IV drug addiction. Here you’ll encounter counseling, behavioral therapies, and if needed, medication-assisted treatment. Along with other dynamic modalities, these things can help you overcome your addiction. Don’t Let IV Drug Abuse Destroy Your Health Or Claim Your Life Contact Vertava Health today if your or a loved one is struggling with an addiction to drugs or alcohol. Our treatment specialists can help find a program that is tailored to your needs. If you suspect that yourself or a loved one may have sepsis or another serious infection as a result of intravenous drug use contact your doctor or go to a hospital immediately. Sepsis: The Common Cause of Death You’ve Never Heard Of Charles Summerour was traveling for business when he acquired an everyday infection that almost killed him. After initially ignoring the symptoms of what turned out to be a urinary tract infection (UTI), the 54-year-old journalist began to feel markedly worse as the day wore on. He sought medical attention from a doctor, who promptly sent him to the hospital. Within hours of being admitted, Summerour’s blood pressure had dropped to dangerous levels, his kidneys were failing and his body was slipping into a little-known but very deadly condition called septic shock. What Is Sepsis? Caused by the body’s exaggerated immune response to an infection, sepsis is the most common cause of death in hospitalized patients in the United States. This condition is also referred to as blood poisoning and septicemia. According to the Centers for Disease Control and Prevention (CDC), the number of people hospitalized with sepsis has more than doubled over an eight-year period. The human body is constantly bombarded with potentially infectious viruses and bacteria, and people with healthy immune systems are usually able to fight off these microbes with little effort. But, when an infection isn’t subdued quickly enough, the immune system can kick into a dangerous state of overdrive, causing the body to injure itself in an attempt to get rid of invaders. If left too long, sepsis can escalate into a fatal condition called septic shock, which is marked by extensive tissue damage and organ failure. Anyone can develop sepsis at any age. It can start off as practically anything, including a case of the flu, pneumonia, a sinus infection, a UTI, or an infected bug bite or cut. What is scary is that these seemingly minor ailments can develop into sepsis in a matter of mere hours. According to Martin Doerfler, MD, senior vice president of clinical strategy and development at Northwell Health’s Center for Learning and Innovation in New York, at least 50 percent of people who go into septic shock do not survive. Browse Our Free Senior Care Guides The Importance of Spreading Awareness Even though it kills between 150,000 and 300,000 people in the U. S. every year, only about one-third of Americans have ever heard of sepsis. Spreading awareness is crucial because it can develop and become life-threatening in such a short period of time. In fact, Summerour had no idea what it was that nearly ended his life until he got home from the hospital. “The doctors called it an infection. They said my immune system had become compromised, but they didn’t really put a name to it,” he recalls. One of the biggest challenges to diagnosis and treatment is the ambiguous nature of the condition. “Sepsis is a very nondescript problem, and it may not jump into a physician’s mind initially,” Dr. Doerfler admits. Some of the more common initial symptoms of sepsis include fever, elevated heart rate and rapid breathing. Early diagnosis and treatment are paramount, but the preliminary signs of sepsis are also common in many other medical conditions. Therefore, medical professionals can have a difficult time making a definitive diagnosis before a patient begins experiencing severe symptoms, such as confusion, difficulty breathing and a serious drop in blood pressure. Seniors Are at Greater Risk of Sepsis Seniors are more vulnerable to the damaging effects of sepsis due to reduced immune function that occurs with age. Older individuals are also more likely to have chronic medical conditions, such as diabetes, cancer, and liver or kidney disease, that can further affect immune responses. For example, diabetics are more susceptible because their condition causes them to develop sores and wounds that heal slowly and are prone to infection. Furthermore, seniors make more frequent visits to health care settings, where the risk of developing an infection is increased. “The more you encounter the health care system, the more exposure you have to infectious viruses and bacteria,” Dr. Doerfler points out. Any surgery, no matter how minor, increases a person’s risk for becoming septic, as does the insertion of medical devices like catheters, feeding tubes and IVs. Even if an elder survives a systematic attack, they are likely to live with lasting consequences. Summerour’s brush with sepsis left him with stage 3 kidney failure. Even though he says his experience caused a lot of changes in his life, he knows that many people do not fare as well. It is this knowledge that convinced him to become a speaker and advocate for the Sepsis Alliance, a nationwide charity dedicated to raising awareness of the disease. Organ failure and amputation are some of the more common effects of sepsis, but older adults may also suffer serious cognitive issues afterwards. A University of Michigan study shows that 60 percent of seniors who were hospitalized for severe sepsis experienced significant declines in physical and/or mental ability even after they recovered from their underlying infections. Study authors estimate that this finding translates into 20,000 new dementia cases in elderly Americans every year. How to Protect Loved Ones from Sepsis There are two key ways to protect your loved ones and yourself from sepsis. The first is using consistent preventative measures to avoid contracting and spreading illnesses and infections. This includes receiving all recommended vaccines, including a flu shot each year, adhering to excellent hand-washing and hygiene practices and leading a healthy lifestyle for a strong immune system. The second component of protection consists of education and advocacy. If you or a loved one falls ill, it is crucial to know what signs of sepsis to look for and not be afraid to speak up and seek immediate medical help. Every hour that a person with sepsis goes without treatment, their risk of death increases by eight percent. Dr. Doerfler says the symptoms of sepsis can be ambiguous, but if your loved one has signs of an infection and begins acting abnormally confused or tired, the safest bet is to go to the hospital. He stresses that a change in mental state is a clear indicator that a person needs immediate medical attention, whether it is due to sepsis or another medical issue. A confused senior may be more resistant to going to the hospital, but if sepsis is suspected, their objections should be overruled. The Sepsis Alliance offers the following acronym to help the public easily remember the telltale symptoms of sepsis: - Shivering due to a fever over 101° F or a body temperature below 98.6° F - Extreme pain or general discomfort - Pale or discolored skin - Sleepiness, confusion or changes in consciousness - “I feel like I might die” and other similar remarks from a patient - Shortness of breath If you notice a combination of any of these symptoms in a loved one, call 911 or seek immediate medical treatment at the nearest emergency room. Be sure to tell the triage nurse and other medical professionals that you suspect sepsis. Nurses and doctors aren’t likely to arrive at this conclusion initially, which is why both Dr. Doerfler and Summerour say it’s a good idea for caregivers to give hospital staff a nudge in that direction. “You need to advocate and speak up for seniors who can’t speak for themselves,” says Summerour. “Don’t be afraid to be a little bit pushy.” Source: Centers for Disease Control and Prevention (https://www.cdc.gov/sepsis/index.html) Sepsis in Infants & Children By: Sylvia Owusu-Ansah MD, MPH, FAAP Anyone can get an infection, and almost any infection can lead to sepsis—the body’s extreme response to an infection. Without timely treatment, sepsis (sometimes called septicaemia or septicemia) can rapidly lead to tissue damage, organ failure, and death. Sepsis can affect anyone at any time, but it does tend to strike the very old and the very young. Children, particularly newborns and young infants, can be more susceptible to developing sepsis. Those with underlying health problems are also at a higher risk. Each year in the U.S., more than 75,000 infants and children develop severe sepsis. Almost 7,000 of these children die—more deaths than children who die from cancer. Be Alert to the Signs & Symptoms of Sepsis: Detecting sepsis early and starting immediate treatment is often the difference between life and death. Parents and caregivers must seek immediate medical care if they suspect their child has an infection that is not improving or is getting worse. Sepsis may have been preceded by an infection such as a urinary tract infection, pneumonia, or a skin or bone infection. The signs and symptoms of sepsis can include a combination of any of the following: Fever or low temperature (newborns and infants may have low temperature) Fast heart rate Feeling cold/cold hands and feet Clammy and pale skin Confusion, dizziness or disorientation Shortness of breath Extreme pain or discomfort Nausea and vomiting Important Note: Many of these signs and symptoms alone are common in babies and children when they are sick. Most of the time, they do not have sepsis. However, when more than one of these signs and symptoms happen together, or when a baby or child just seems sicker than usual—you should seek medical help. If your baby or child’s skin is cold, pale, or has developed strange colors or markings; if your baby or child has become unresponsive or is struggling to breathe; or if your baby has dry diapers for more than 12 hours—you should take him or her to the emergency room without delay. How Is Sepsis Treated? Sepsis, or even suspected cases of sepsis, are treated in the hospital. Often, babies and children will need care in an intensive care unit (ICU). Fighting the infection is an emergency. Doctors and nurses will give IV antibiotics to fight the infection. Many other things may be needed to fight sepsis—IV fluids, special heart and/or blood pressure medications, and medications to keep children calm and comfortable. In some cases, children may need a ventilator to help with breathing. You might hear the term “sepsis work-up.” “Sepsis work-up” refers to the combination of tests used to diagnose the specific cause of a child’s infection. It is important to figure out what type of virus or bacteria is causing the infection. The sepsis work-up may include testing blood, urine, and spinal fluid; an x-ray or an ultrasound test may also be included. When a child develops sepsis within a few months of birth (up to 90 days), it is called neonatal sepsis. If the sepsis develops within the first hours or days after birth, it is called early onset sepsis. Sepsis that develops after the baby is 1 week old is called late-onset neonatal sepsis. Premature infants develop sepsis more often than infants who are born on time. Sepsis in Older Children: As children get older, their exposure to illness can increase as they attend child care, go to school, and participate in activities, such as sports. Children, like adults, can develop bacterial infections such as urinary tract infections, skin infections, pneumonia, appendicitis, and meningitis. Left untreated, these can all lead to sepsis. What to Expect in the Hospital: Most sepsis patients are admitted to the hospital. Babies and children who are extremely sick may be cared for in the hospital ICU. Babies and children will need to have IV’s placed to give fluid and medications. They will have needle sticks for blood tests. Depending on their age, a soft tube or a needle might be needed to get urine for testing. To test spinal fluid, the baby or child may also need a spinal tap. This involves placing a hollow needle in the back to take a small sample of spinal fluid—the fluid that surrounds the spinal cord and brain. Testing the spinal fluid is important to determine the baby or child has meningitis. On occasion, surgery may be required for those who have surgical infections leading to sepsis such as a severe skin or bone infection or appendicitis. Parents and Caregivers Can Help Stop This Medical Emergency in Its Tracks. Talk with your pediatrician about steps you can take to prevent infections. Some steps include taking good care of chronic health conditions and following recommended vaccination schedules. Practice good hygiene, such as handwashing, and keeping cuts clean until healed. Know the signs and symptoms of sepsis. ACT FAST. Get medical care IMMEDIATELY if you suspect your child has sepsis or an infection that’s not getting better or is getting worse. Additional Information & Resources: About Dr. Dr. Owusu-Ansah: Sylvia Owusu-Ansah MD, MPH, FAAP is a board-certified pediatrician and pediatric emergency medicine physician who is currently an attending in Pittsburgh at Children’s Hospital of Pittsburgh UPMC and Director of Prehospital and EMS. Within the American Academy of Pediatrics, Dr. Owusu-Ansah sits on the Committee on Pediatric Emergency Medicine and has worked with the D.C. office on federal, state, and community advocacy issues including the School Access to Emergency Epinephrine Act. Dr. Owusu-Ansah is married to a firefighter/paramedic and has two beautiful daughters. The information contained on this Web site should not be used as a substitute for the medical care and advice of your pediatrician. There may be variations in treatment that your pediatrician may recommend based on individual facts and circumstances. 90,000 Treatment of purulent-septic skin diseases – Medical Center Boils, carbuncles, abscesses, purulent diseases of the hand Furuncle (“boil”, “abscess”) – purulent inflammation of the hair follicle, sebaceous gland. The emergence of a boil is facilitated by pollution and microtraumas of the skin (a common cause in men – careless shaving of the face), increased sweating and sebum secretion, malnutrition and metabolism, decreased immunity, etc.p. Symptoms: the furuncle is characterized by the appearance on the skin of a painful follicular pustule against the background of erythema red with necrosis in the center (the so-called boil rod). After rejection of necrotic tissue, healing occurs by scarring. Most often, a boil occurs on the skin of the neck, back of the head, face, back, and thighs. The appearance of boils at different stages of development is called furunculosis, and purulent-necrotic inflammation of the skin and subcutaneous tissue around a group of hair follicles and sebaceous glands is called carbuncle .When a boil is found on the face, severe complications (purulent meningitis, sepsis) are possible. In the absence of positive dynamics of conservative (antibacterial therapy, ointment dressings) treatment – an increase in the size of the abscess, an increase in T body 37-38C, you should immediately consult a surgeon. Surgical treatment – opening, sanitation of the purulent cavity with antiseptics, the appointment of subsequent dressings with antibacterial and healing ointments. We strongly recommend that you consult a doctor on the first day of the disease to apply the correct treatment. Abscess – delimited purulent inflammation of tissues with the formation of a purulent cavity, can develop in the subcutaneous tissue, muscles, bones, in organs and between them. An abscess can occur both independently, most often as a result of a boil when the infection spreads deep into the tissues, and as a complication of another disease (pneumonia, trauma, etc.). In a patient with this disease, body temperature rises to 38C, chills occur, locally the area of the abscess is convex, with reddening of the skin, fluctuation over the abscess.Complication of an abscess: phlegmon (not delimited purulent-necrotic soft tissue disease), sepsis. If you suspect an abscess, you should immediately consult a surgeon. The treatment is complex: operative (opening, debridement, drainage of the purulent cavity with subsequent daily dressings), antibacterial therapy, physiotherapy. Publications in mass media Sepsis is a symptom complex due to the constant or periodic entry into the blood of microorganisms from the focus of purulent inflammation.The clinical picture is dominated by severe multiple organ disorders, while local inflammatory changes are weakly expressed. The formation of metastatic foci of purulent inflammation in various organs and tissues is characteristic. Classification • Epidemiological •• Nosocomial sepsis (postpartum, postoperative, postcatheterization, postinjection, after gynecological examinations, neonatal sepsis) •• Community-acquired sepsis (cryptogenic, tonsillogenic, intestinal, burn classification) • Clinical • Localization of the entrance gate of infection •• Duration ••• Fulminant sepsis – 1-3 days ••• Acute sepsis – up to 6 weeks ••• Subacute or protracted sepsis – more than 6 weeks ••• Chronic sepsis (typical for patients with immunodeficiency states , especially with AIDS) – more than 6 months •• Clinical form ••• Septicemia – a form of sepsis, not accompanied by the formation of metastatic foci of purulent infection ••• Septicopyemia – a form of sepsis characterized by the formation of metastatic foci of infection (incl.including heart attacks) ••• Septic (bacterial) endocarditis. Note. Septicemia can transform into septicopyemia, which gives grounds to consider these forms as stages of one process •• Leading clinical and pathophysiological syndromes ••• Thrombohemorrhagic syndrome (eg, DIC) ••• Septic (infectious-toxic) shock ••• Toxic-dystrophic state. Etiology and epidemiology • Opportunistic flora – staphylococcus, streptococcus, E. coli and Pseudomonas aeruginosa, Klebsiella, fungi of the genus Candida , less often protozoa, mixed infection • Patients with sepsis are usually not infectious • For some infectious diseases (salmonella; diseases caused by opportunistic gram-negative microflora; meningococcal infection) is characterized by the presence of so-called “septic forms” (symptoms of sepsis).However, the diagnosis of “sepsis” in these cases is not made, since from an epidemiological point of view, the patient is dangerous to others. In addition, the above diseases have, in contrast to sepsis, a specific morphological and clinical picture. Pathogenesis • For the development of sepsis, it is necessary to penetrate the opportunistic pathogen through the entrance gate (more often injured skin or mucous membrane) with the development of a local reaction (primary affect), reactive lymphadenitis (lymphangitis), purulent thrombophlebitis with subsequent bacteremia and toxemia.Damage to the vascular wall over a large extent, phlebitis lead to the formation of infected microthrombi, causing abscesses and infarctions of internal organs • The clinical picture does not depend on the etiology, there are no morphological signs indicating the specifics of the process • Deep metabolic disorder due to severe intoxication, the predominance of catabolic processes (hypoalbuminemia , dysproteinemia, hyperglycemia, essential fatty acid deficiency, hypovitaminosis, metabolic acidosis).Severe dystrophic changes additionally worsen the functions of organs, which, even in the absence of clinically pronounced metastases in them, leads to systemic multiple organ failure characteristic of late irreversible stages of sepsis. Clinical picture. The incubation period, the cyclical course characteristic of infectious diseases are absent. Pathognomonic signs do not exist • Intoxication syndrome •• Lethargy, anorexia, changes in psycho-emotional status to gross cerebral disorders (coma) •• Fever (temperature curve is most often of the wrong type).Suspicion of the presence of sepsis arises when the duration of fever is more than 5 days and the presence of unmotivated rises in body temperature to febrile values, followed by a drop to subfebrile •• Signs of dystrophy and malnutrition with the development of malnutrition and weight loss, decreased skin elasticity, soft tissue turgor • Gastrointestinal dysfunction , nausea, vomiting (including and due to intoxication) • Microcirculation disorders – pallor of the skin with an earthy tinge, hemorrhagic rash, shortness of breath, decreased urine output • Hepatolienal syndrome • Symptoms of organ and tissue damage, according to the localization of metastatic foci or entrance gates of infection. Laboratory signs • Leukocytosis or leukopenia (with the etiological role of gram-negative flora and AIDS), neutrophilia with a hyperregenerative shift to the left, progressive anemia, thrombocytopenia • Hypoproteinemia with dysproteinemia (decreased albumin / protein globulin ratio) • Phase changes , indicating the development of DIC • Leukocyturia, bacteriuria, cylindruria, erythrocyturia • Positive results of bacteriological examination of blood (detection of blood culture), feces, urine, cerebrospinal fluid.To obtain a positive result, a three-time blood sampling in a volume of 20-30 ml is required with an interval of 1 hour, if possible, prior to the start of antibiotic therapy. Diagnostic criteria for clinical forms of sepsis • Septicopyemia – detection of one or more foci of metastatic inflammation with identification of the causative agent • Septicemia – signs of intoxication syndrome prevail with severe disorders of microcirculation and central hemodynamics, an extensive clinical picture of thrombohemorrhagic syndrome. Septic (infectious toxic) shock is characteristic • Septic (bacterial) endocarditis (see Infectious endocarditis ). Features of the infectious process: the entrance gate is more often the mucous membrane of the pharynx, but the local focus (a source of constant entry of microorganisms into the systemic circulation) is the endocardium. Management tactics • Hospitalization • Etiotropic therapy. Before the results of bacteriological research are obtained, antibiotics are chosen empirically • Immunostimulating therapy • Detoxification therapy (its adequacy ultimately determines the prognosis), incl.h. according to indications extracorporeal detoxification: plasmapheresis, hemosorption, perfusion of blood through donor organs of animals (spleen, liver) • Symptomatic therapy • Treatment is of the nature of intensive therapy and additionally includes emergency correction of disorders of the functions of vital organs (infectious-toxic shock with septicemia, decompensated heart failure with bacterial endocarditis) • The severity of the local inflammatory process of any localization does not correlate with the severity of sepsis. It should be borne in mind that a distant focus of purulent inflammation can be both a consequence of sepsis (metastasis) and its cause, which is important in determining the treatment tactics. • Etiotropic therapy •• Until the results of bacteriological research are obtained, especially with unclear etiology, the most effective combination of gentamicin or tobramycin 3-5 mg / kg / day IV and an antibiotic from the group of cephalosporins or imipenem + cilastatin 500 mg IV every 6 h •• Antibiotics are prescribed at the maximum dosage, IV, for at least 2 weeks (despite the normalization of body temperature) •• The criteria for effectiveness are an obvious positive dynamics of the general condition and laboratory parameters. • Immunostimulating drugs •• Normal human immunoglobulin for intravenous administration, normal human immunoglobulin (IgG + IgA + IgM) for intravenous administration •• IFN preparations. • Detoxification therapy – intravenous administration of large amounts of fluid in combination with diuretics, such as furosemide (forced diuresis method) •• The amount of fluid injected should not exceed the volume of urine excreted (in the absence of signs of dehydration in the patient) •• Central hemodynamic parameters (blood pressure) should be monitored , CVP) and the content of electrolytes in serum and urine •• Additional vasodilators should be administered. • Symptomatic therapy •• For anemia and thrombocytopenia – transfusion of blood, erythrocyte and platelet masses •• Anti-inflammatory therapy: NSAIDs and GC (the immunosuppressive effect of GC should be taken into account) •• Rehydration and parenteral nutrition in severe gastrointestinal dysfunction and severe nutritional disorders • heart failure and arrhythmias •• Anti-shock measures for infectious-toxic shock (septicemia): GC, adrenomimetics, plasma-substituting drugs, such as polyglucin. Surgical treatment in the presence of a focus of purulent infection available for surgical intervention. Synonym. General purulent infection ICD-10 • O85 Postpartum sepsis • P36 Bacterial sepsis of the newborn • T80.2 Infections associated with infusion, transfusion and therapeutic injection 90,000 Yersiniosis: symptoms, treatment and prevention. Help The source of infections in nature is small rodents, as well as cows and small ruminants, which are acutely ill or excrete the pathogen. The main route of transmission is through food. At a temperature of +4 – + 8 ° C, microbes are able to persist and multiply for a long time on various food products. Yersiniosis is ill at any age, but more often children are 1-3 years old. The incubation period of the disease lasts from 1 to 6 days. Yersiniosis begins acutely. Chills, headache, malaise, weakness, pain in muscles and joints, insomnia, sore throat, loss of appetite appear. Body temperature sometimes rises to 38-40 ° C.Signs of gastrointestinal tract damage (abdominal pain, nausea, vomiting, diarrhea) often come to the fore. During the course of the disease, new symptoms may appear, indicating damage to certain organs. There are several clinical forms of yersiniosis: localized (gastroenterocolitic), in which mainly the gastrointestinal tract is affected, and generalized (icteric, exanthemic, arthralgic, septic) forms. Gastroenterocolitic form occurs more often than others. It accounts for about 70% of diseases. It begins acutely, the body temperature rises to 38-39 ° C. Headache, malaise, insomnia, anorexia, chills appear. Simultaneously with the intoxication syndrome, abdominal pain, diarrhea, and sometimes vomiting occur. The stool is liquid with a pungent unpleasant odor, occasionally mixed with mucus and blood. Stool frequency varies from 2 to 15 times per day. A severe course is rare. More often, the body temperature is subfebrile or normal, the syndrome of general intoxication is weak, stool 2-3 times per day, abdominal pain is insignificant.Such patients are actively detected in group diseases. This form can occur in the form of enteritis, enterocolitis and gastroenterocolitis. The duration of this form of yersiniosis is from 2 days to 2 weeks. Icteric form develops either simultaneously with gastroenterocolitis, or 2-3 days after intestinal dysfunction. With this form, the symptoms of liver damage come to the fore, toxic hepatitis develops. Complaints of heaviness and pain in the right hypochondrium, sometimes itching of the skin.Yellowness of the skin and sclera appears. The liver is enlarged, painful on palpation. Darkening of urine is noted, feces are discolored. The exanthemic form of is characterized by intoxication syndrome and exanthema. The rash appears on the 1-6th day of illness. It can be punctate, small or large-spotted without itching of the skin. The rash usually disappears without a trace after 2-5 days, at the site of the former rash there is pityriasis peeling. Arthralgic form proceeds with fever, intoxication and severe pain in the joints.The main complaint is joint pain. Arthralgias sometimes cause immobility and insomnia. The joints are not externally changed. These forms are distinguished according to the dominant syndrome; they may have other symptoms characteristic of yersiniosis, but they are poorly expressed. Septic form is rare. It is characterized by high fever, chills, enlarged liver, spleen, and damage to various organs. Endocarditis, pneumonia, nephritis with acute renal failure, meningitis, meningoencephalitis, hepatitis may develop. Complications occur more often at 2-3 weeks. These include allergic exanthema (urticaria, erythema nodosum), Quincke’s edema, arthritis (mainly of large joints), myocarditis, urethritis, conjunctivitis, appendicitis. Irsioniosis, in addition to the above symptoms, is diagnosed on the basis of bacteriological studies of blood, feces. Treatment. In cases of mild course of yersiniosis in the absence of concomitant diseases, patients can be treated at home by an infectious disease doctor.For the treatment of yersiniosis, one of the antibiotics is used: tetracycline 0.5 g 4 times a day, chloramphenicol 0.5 g 4 times a day. In the septic form of yersiniosis, cephalosporins and fluoroquinolones are prescribed. The course of treatment for yersiniosis depends on the form and severity of the disease; with mild course – 5-7 days, with moderate and severe – up to 14 days.	2	17	0	0	2	0.896553	2	10,926
This article needs additional citations for verification. (July 2022) Anesthesia or anaesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), amnesia (loss of memory), and unconsciousness. An individual under the effects of anesthetic drugs is referred to as being anesthetized. \|Pronunciation\|\|/ˌænɪsˈθiːziə, -siə, -ʒə/\| Anesthesia enables the painless performance of procedures that would otherwise cause severe or intolerable pain in a non-anesthetized individual, or would otherwise be technically unfeasible. Three broad categories of anesthesia exist: - General anesthesia suppresses central nervous system activity and results in unconsciousness and total lack of sensation, using either injected or inhaled drugs. - Sedation suppresses the central nervous system to a lesser degree, inhibiting both anxiety and creation of long-term memories without resulting in unconsciousness. - Regional and local anesthesia, which blocks transmission of nerve impulses from a specific part of the body. Depending on the situation, this may be used either on its own (in which case the individual remains fully conscious), or in combination with general anesthesia or sedation. - Local anesthesia is simple infiltration by the clinician directly onto the region of interest (e.g. numbing a tooth for dental work). - Peripheral nerve blocks use drugs targeted at peripheral nerves to anesthetize an isolated part of the body, such as an entire limb. - Neuraxial blockade , mainly epidural and spinal anesthesia, can be performed in the region of the central nervous system itself, suppressing all incoming sensation from nerves supplying the area of the block. In preparing for a medical or veterinary procedure, the clinician chooses one or more drugs to achieve the types and degree of anesthesia characteristics appropriate for the type of procedure and the particular patient. The types of drugs used include general anesthetics, local anesthetics, hypnotics, dissociatives, sedatives, adjuncts, neuromuscular-blocking drugs, narcotics, and analgesics. The risks of complications during or after anesthesia are often difficult to separate from those of the procedure for which anesthesia is being given, but in the main they are related to three factors: the health of the individual, the complexity and stress of the procedure itself, and the anaesthetic technique. Of these factors, the individual's health has the greatest impact. Major perioperative risks can include death, heart attack, and pulmonary embolism whereas minor risks can include postoperative nausea and vomiting and hospital readmission. Some conditions, like local anesthetic toxicity, airway trauma or malignant hyperthermia, can be more directly attributed to specific anesthetic drugs and techniques. The purpose of anesthesia can be distilled down to three basic goals or endpoints:: 236 - hypnosis (a temporary loss of consciousness and with it a loss of memory. In a pharmacological context, the word hypnosis usually has this technical meaning, in contrast to its more familiar lay or psychological meaning of an altered state of consciousness not necessarily caused by drugs—see hypnosis). - analgesia (lack of sensation which also blunts autonomic reflexes) - muscle relaxation Different types of anesthesia affect the endpoints differently. Regional anesthesia, for instance, affects analgesia; benzodiazepine-type sedatives (used for sedation, or "twilight anesthesia") favor amnesia; and general anesthetics can affect all of the endpoints. The goal of anesthesia is to achieve the endpoints required for the given surgical procedure with the least risk to the subject. To achieve the goals of anesthesia, drugs act on different but interconnected parts of the nervous system. Hypnosis, for instance, is generated through actions on the nuclei in the brain and is similar to the activation of sleep. The effect is to make people less aware and less reactive to noxious stimuli.: 245 Loss of memory (amnesia) is created by action of drugs on multiple (but specific) regions of the brain. Memories are created as either declarative or non-declarative memories in several stages (short-term, long-term, long-lasting) the strength of which is determined by the strength of connections between neurons termed synaptic plasticity.: 246 Each anesthetic produces amnesia through unique effects on memory formation at variable doses. Inhalational anesthetics will reliably produce amnesia through general suppression of the nuclei at doses below those required for loss of consciousness. Drugs like midazolam produce amnesia through different pathways by blocking the formation of long-term memories.: 249 Nevertheless, a person can have dreams during anesthetic or have consciousness of the procedure despite having no indication of it under anesthetic. It is estimated that 22% of people dream during general anesthesia and 1–2 cases per 1000 have some consciousness termed "awareness during general anesthesia".: 253 It is unknown whether non-human animals have dreams during general anesthesia. Anesthesia is unique in that it is not a direct means of treatment; rather, it allows the clinician to do things that may treat, diagnose, or cure an ailment which would otherwise be painful or complicated. The best anesthetic, therefore, is the one with the lowest risk to the patient that still achieves the endpoints required to complete the procedure. The first stage in anesthesia is the pre-operative risk assessment consisting of the medical history, physical examination and lab tests. Diagnosing an animal's pre-operative physical status allows the clinician to minimize anesthetic risks. A well completed medical history will arrive at the correct diagnosis 56% of the time which increases to 73% with a physical examination. Lab tests help in diagnosis but only in 3% of cases, underscoring the need for a full history and physical examination prior to anesthetics. Incorrect pre-operative assessments or preparations are the root cause of 11% of all adverse anesthetic events.: 1003 Safe anesthesia care depends greatly on well-functioning teams of highly trained healthcare workers. The medical specialty centred around anesthesia is called anesthesiology, and doctors specialised in the field are termed anesthesiologists. Additional healthcare professionals involved in anesthesia provision have varying titles and roles depending on the jurisdiction, and include anesthetic nurses, nurse anesthetists, anesthesiologist assistants, anaesthetic technicians, anaesthesia associates, operating department practitioners and anesthesia technologists. International standards for the safe practice of anesthesia, jointly endorsed by the World Health Organization and the World Federation of Societies of Anaesthesiologists, highly recommend that anesthesia should be provided, overseen or led by anesthesiologists, with the exception of minimal sedation or superficial procedures performed under local anesthesia. A trained, vigilant anesthesia provider should continually care for the patient; where the provider is not an anesthesiologist, they should be locally directed and supervised by an anesthesiologist, and in countries or settings where this is not feasible, care should be led by the most qualified local individual within a regional or national anesthesiologist-led framework. The same minimum standards for patient safety apply regardless of the provider, including continuous clinical and biometric monitoring of tissue oxygenation, perfusion and blood pressure; confirmation of correct placement of airway management devices by auscultation and carbon dioxide detection; use of the WHO Surgical Safety Checklist; and safe onward transfer of the patient's care following the procedure. \|ASA class\|\|Physical status\| \|ASA 1\|\|Healthy person\| \|ASA 2\|\|Mild systemic disease\| \|ASA 3\|\|Severe systemic disease\| \|ASA 4\|\|Severe systemic disease that is a constant threat to life\| \|ASA 5\|\|A moribund person who is not expected to survive without the operation\| \|ASA 6\|\|A declared brain-dead person whose organs are being removed for donor purposes\| \|E\|\|Suffix added for patients undergoing emergency procedure\| One part of the risk assessment is based on the patient's health. The American Society of Anesthesiologists has developed a six-tier scale that stratifies the patient's pre-operative physical state. It is called the ASA physical status classification. The scale assesses risk as the patient's general health relates to an anesthetic. The more detailed pre-operative medical history aims to discover genetic disorders (such as malignant hyperthermia or pseudocholinesterase deficiency), habits (tobacco, drug and alcohol use), physical attributes (such as obesity or a difficult airway) and any coexisting diseases (especially cardiac and respiratory diseases) that might impact the anesthetic. The physical examination helps quantify the impact of anything found in the medical history in addition to lab tests.: 1003–09 Aside from the generalities of the patient's health assessment, an evaluation of specific factors as they relate to the surgery also need to be considered for anesthesia. For instance, anesthesia during childbirth must consider not only the mother but the baby. Cancers and tumors that occupy the lungs or throat create special challenges to general anesthesia. After determining the health of the patient undergoing anesthesia and the endpoints that are required to complete the procedure, the type of anesthetic can be selected. Choice of surgical method and anesthetic technique aims to reduce risk of complications, shorten time needed for recovery and minimize the surgical stress response. Anesthesia is a combination of the endpoints (discussed above) that are reached by drugs acting on different but overlapping sites in the central nervous system. General anesthesia (as opposed to sedation or regional anesthesia) has three main goals: lack of movement (paralysis), unconsciousness, and blunting of the stress response. In the early days of anesthesia, anesthetics could reliably achieve the first two, allowing surgeons to perform necessary procedures, but many patients died because the extremes of blood pressure and pulse caused by the surgical insult were ultimately harmful. Eventually, the need for blunting of the surgical stress response was identified by Harvey Cushing, who injected local anesthetic prior to hernia repairs.: 30 This led to the development of other drugs that could blunt the response leading to lower surgical mortality rates. The most common approach to reach the endpoints of general anesthesia is through the use of inhaled general anesthetics. Each anesthetic has its own potency which is correlated to its solubility in oil. This relationship exists because the drugs bind directly to cavities in proteins of the central nervous system, although several theories of general anesthetic action have been described. Inhalational anesthetics are thought to exact their effects on different parts of the central nervous system. For instance, the immobilizing effect of inhaled anesthetics results from an effect on the spinal cord whereas sedation, hypnosis and amnesia involve sites in the brain.: 515 The potency of an inhalational anesthetic is quantified by its minimum alveolar concentration (MAC). The MAC is the percentage dose of anesthetic that will prevent a response to painful stimulus in 50% of subjects. The higher the MAC, generally, the less potent the anesthetic. The ideal anesthetic drug would provide hypnosis, amnesia, analgesia, and muscle relaxation without undesirable changes in blood pressure, pulse or breathing. In the 1930s, physicians started to augment inhaled general anesthetics with intravenous general anesthetics. The drugs used in combination offered a better risk profile to the subject under anesthesia and a quicker recovery. A combination of drugs was later shown to result in lower odds of dying in the first seven days after anesthetic. For instance, propofol (injection) might be used to start the anesthetic, fentanyl (injection) used to blunt the stress response, midazolam (injection) given to ensure amnesia and sevoflurane (inhaled) during the procedure to maintain the effects. More recently, several intravenous drugs have been developed which, if desired, allow inhaled general anesthetics to be avoided completely.: 720 The core instrument in an inhalational anesthetic delivery system is an anesthetic machine. It has vaporizers, ventilators, an anesthetic breathing circuit, waste gas scavenging system and pressure gauges. The purpose of the anesthetic machine is to provide anesthetic gas at a constant pressure, oxygen for breathing and to remove carbon dioxide or other waste anesthetic gases. Since inhalational anesthetics are flammable, various checklists have been developed to confirm that the machine is ready for use, that the safety features are active and the electrical hazards are removed. Intravenous anesthetic is delivered either by bolus doses or an infusion pump. There are also many smaller instruments used in airway management and monitoring the patient. The common thread to modern machinery in this field is the use of fail-safe systems that decrease the odds of catastrophic misuse of the machine. Patients under general anesthesia must undergo continuous physiological monitoring to ensure safety. In the US, the American Society of Anesthesiologists (ASA) has established minimum monitoring guidelines for patients receiving general anesthesia, regional anesthesia, or sedation. These include electrocardiography (ECG), heart rate, blood pressure, inspired and expired gases, oxygen saturation of the blood (pulse oximetry), and temperature. In the UK the Association of Anaesthetists (AAGBI) have set minimum monitoring guidelines for general and regional anesthesia. For minor surgery, this generally includes monitoring of heart rate, oxygen saturation, blood pressure, and inspired and expired concentrations for oxygen, carbon dioxide, and inhalational anesthetic agents. For more invasive surgery, monitoring may also include temperature, urine output, blood pressure, central venous pressure, pulmonary artery pressure and pulmonary artery occlusion pressure, cardiac output, cerebral activity, and neuromuscular function. In addition, the operating room environment must be monitored for ambient temperature and humidity, as well as for accumulation of exhaled inhalational anesthetic agents, which might be deleterious to the health of operating room personnel. Sedation (also referred to as dissociative anesthesia or twilight anesthesia) creates hypnotic, sedative, anxiolytic, amnesic, anticonvulsant, and centrally produced muscle-relaxing properties. From the perspective of the person giving the sedation, the patient appears sleepy, relaxed and forgetful, allowing unpleasant procedures to be more easily completed. Sedatives such as benzodiazepines are usually given with pain relievers (such as narcotics, or local anesthetics or both) because they do not, by themselves, provide significant pain relief. From the perspective of the subject receiving a sedative, the effect is a feeling of general relaxation, amnesia (loss of memory) and time passing quickly. Many drugs can produce a sedative effect including benzodiazepines, propofol, thiopental, ketamine and inhaled general anesthetics. The advantage of sedation over a general anesthetic is that it generally does not require support of the airway or breathing (no tracheal intubation or mechanical ventilation) and can have less of an effect on the cardiovascular system which may add to a greater margin of safety in some patients.: 736 When pain is blocked from a part of the body using local anesthetics, it is generally referred to as regional anesthesia. There are many types of regional anesthesia either by injecting into the tissue itself, a vein that feeds the area or around a nerve trunk that supplies sensation to the area. The latter are called nerve blocks and are divided into peripheral or central nerve blocks. The following are the types of regional anesthesia:: 926–31 - Infiltrative anesthesia: a small amount of local anesthetic is injected in a small area to stop any sensation (such as during the closure of a laceration, as a continuous infusion or "freezing" a tooth). The effect is almost immediate. - Peripheral nerve block: local anesthetic is injected near a nerve that provides sensation to particular portion of the body. There is significant variation in the speed of onset and duration of anesthesia depending on the potency of the drug (e.g. Mandibular block, Fascia Iliaca Compartment Block). - Intravenous regional anesthesia (also called a Bier block): dilute local anesthetic is infused to a limb through a vein with a tourniquet placed to prevent the drug from diffusing out of the limb. - Central nerve block: Local anesthetic is injected or infused in or around a portion of the central nervous system (discussed in more detail below in spinal, epidural and caudal anesthesia). - Topical anesthesia: local anesthetics that are specially formulated to diffuse through the mucous membranes or skin to give a thin layer of analgesia to an area (e.g. EMLA patches). - Tumescent anesthesia: a large amount of very dilute local anesthetics are injected into the subcutaneous tissues during liposuction. - Systemic local anesthetics: local anesthetics are given systemically (orally or intravenous) to relieve neuropathic pain. A 2018 Cochrane review found moderate quality evidence that regional anesthesia may reduce the frequency of persistent postoperative pain (PPP) from 3 to 18 months following thoracotomy and 3 to 12 months following caesarean. Low quality evidence was found 3 to 12 months following breast cancer surgery. This review acknowledges certain limitations that impact its applicability beyond the surgeries and regional anesthesia techniques reviewed. When local anesthetic is injected around a larger diameter nerve that transmits sensation from an entire region it is referred to as a nerve block or regional nerve blockade. Nerve blocks are commonly used in dentistry, when the mandibular nerve is blocked for procedures on the lower teeth. With larger diameter nerves (such as the interscalene block for upper limbs or psoas compartment block for lower limbs) the nerve and position of the needle is localized with ultrasound or electrical stimulation. Evidence supports the use of ultrasound guidance alone, or in combination with peripheral nerve stimulation, as superior for improved sensory and motor block, a reduction in the need for supplementation and fewer complications. Because of the large amount of local anesthetic required to affect the nerve, the maximum dose of local anesthetic has to be considered. Nerve blocks are also used as a continuous infusion, following major surgery such as knee, hip and shoulder replacement surgery, and may be associated with lower complications. Nerve blocks are also associated with a lower risk of neurologic complications compared to the more central epidural or spinal neuraxial blocks.: 1639–41 Spinal, epidural and caudal anesthesiaEdit Central neuraxial anesthesia is the injection of local anesthetic around the spinal cord to provide analgesia in the abdomen, pelvis or lower extremities. It is divided into either spinal (injection into the subarachnoid space), epidural (injection outside of the subarachnoid space into the epidural space) and caudal (injection into the cauda equina or tail end of the spinal cord). Spinal and epidural are the most commonly used forms of central neuraxial blockade. Spinal anesthesia is a "one-shot" injection that provides rapid onset and profound sensory anesthesia with lower doses of anesthetic, and is usually associated with neuromuscular blockade (loss of muscle control). Epidural anesthesia uses larger doses of anesthetic infused through an indwelling catheter which allows the anesthetic to be augmented should the effects begin to dissipate. Epidural anesthesia does not typically affect muscle control. Because central neuraxial blockade causes arterial and venous vasodilation, a drop in blood pressure is common. This drop is largely dictated by the venous side of the circulatory system which holds 75% of the circulating blood volume. The physiologic effects are much greater when the block is placed above the 5th thoracic vertebra. An ineffective block is most often due to inadequate anxiolysis or sedation rather than a failure of the block itself.: 1611 Acute pain managementEdit Nociception (pain sensation) is not hard-wired into the body. Instead, it is a dynamic process wherein persistent painful stimuli can sensitize the system and either make pain management difficult or promote the development of chronic pain. For this reason, preemptive acute pain management may reduce both acute and chronic pain and is tailored to the surgery, the environment in which it is given (in-patient/out-patient) and the individual.: 2757 Pain management is classified into either pre-emptive or on-demand. On-demand pain medications typically include either opioid or non-steroidal anti-inflammatory drugs but can also make use of novel approaches such as inhaled nitrous oxide or ketamine. On demand drugs can be administered by a clinician ("as needed drug orders") or by the patient using patient-controlled analgesia (PCA). PCA has been shown to provide slightly better pain control and increased patient satisfaction when compared with conventional methods. Common preemptive approaches include epidural neuraxial blockade or nerve blocks. One review which looked at pain control after abdominal aortic surgery found that epidural blockade provides better pain relief (especially during movement) in the period up to three postoperative days. It reduces the duration of postoperative tracheal intubation by roughly half. The occurrence of prolonged postoperative mechanical ventilation and myocardial infarction is also reduced by epidural analgesia. Risks and complicationsEdit Risks and complications as they relate to anesthesia are classified as either morbidity (a disease or disorder that results from anesthesia) or mortality (death that results from anesthesia). Quantifying how anesthesia contributes to morbidity and mortality can be difficult because an animal's health prior to surgery and the complexity of the surgical procedure can also contribute to the risks. Prior to the introduction of anesthesia in the early 19th century, the physiologic stress from surgery caused significant complications and many deaths from shock. The faster the surgery was, the lower the rate of complications (leading to reports of very quick amputations). The advent of anesthesia allowed more complicated and life-saving surgery to be completed, decreased the physiologic stress of the surgery, but added an element of risk. It was two years after the introduction of ether anesthetics that the first death directly related to the use of anesthesia was reported. Morbidity can be major (myocardial infarction, pneumonia, pulmonary embolism, kidney failure/chronic kidney disease, postoperative cognitive dysfunction and allergy) or minor (minor nausea, vomiting, readmission). There is usually overlap in the contributing factors that lead to morbidity and mortality between the health of the animals, the type of surgery being performed and the anesthetic. To understand the relative risk of each contributing factor, consider that the rate of deaths totally attributed to the patient's health is 1:870. Compare that to the rate of deaths totally attributed to surgical factors (1:2860) or anesthesia alone (1:185,056) illustrating that the single greatest factor in anesthetic mortality is the health of the patient. These statistics can also be compared to the first such study on mortality in anesthesia from 1954, which reported a rate of death from all causes at 1:75 and a rate attributed to anesthesia alone at 1:2680.: 993 Direct comparisons between mortality statistics cannot reliably be made over time and across countries because of differences in the stratification of risk factors, however, there is evidence that anesthetics have made a significant improvement in safety but to what degree is uncertain. Rather than stating a flat rate of morbidity or mortality, many factors are reported as contributing to the relative risk of the procedure and anesthetic combined. For instance, an operation on a person who is between the ages of 60–79 years old places the patient at 2.3 times greater risk than someone less than 60 years old. Having an ASA score of 3, 4 or 5 places the person at 10.7 times greater risk than someone with an ASA score of 1 or 2. Other variables include age greater than 80 (3.3 times risk compared to those under 60), gender (females have a lower risk of 0.8), urgency of the procedure (emergencies have a 4.4 times greater risk), experience of the person completing the procedure (less than 8 years experience and/or less than 600 cases have a 1.1 times greater risk) and the type of anesthetic (regional anesthetics are lower risk than general anesthetics).: 984 Obstetrical, the very young and the very old are all at greater risk of complication so extra precautions may need to be taken.: 969–86 On 14 December 2016, the Food and Drug Administration issued a Public Safety Communication warning that "repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women during their third trimester may affect the development of children's brains." The warning was criticized by the American College of Obstetricians and Gynecologists, which pointed out the absence of direct evidence regarding use in pregnant women and the possibility that "this warning could inappropriately dissuade providers from providing medically indicated care during pregnancy." Patient advocates noted that a randomized clinical trial would be unethical, that the mechanism of injury is well-established in animals, and that studies had shown exposure to multiple uses of anesthetic significantly increased the risk of developing learning disabilities in young children, with a hazard ratio of 2.12 (95% confidence interval, 1.26–3.54). The immediate time after anesthesia is called emergence. Emergence from general anesthesia or sedation requires careful monitoring because there is still a risk of complication. Nausea and vomiting are reported at 9.8% but will vary with the type of anesthetic and procedure. There is a need for airway support in 6.8%, there can be urinary retention (more common in those over 50 years of age) and hypotension in 2.7%. Hypothermia, shivering and confusion are also common in the immediate post-operative period because of the lack of muscle movement (and subsequent lack of heat production) during the procedure.: 2707 Furthermore, the rare manifestation in the post-anesthetic period may be the occurrence of functional neurological symptom disorder (FNSD). Postoperative cognitive dysfunction (also known as POCD and post-anesthetic confusion) is a disturbance in cognition after surgery. It may also be variably used to describe emergence delirium (immediate post-operative confusion) and early cognitive dysfunction (diminished cognitive function in the first post-operative week). Although the three entities (delirium, early POCD and long-term POCD) are separate, the presence of delirium post-operatively predicts the presence of early POCD. There does not appear to be an association between delirium or early POCD and long-term POCD. According to a recent study conducted at the David Geffen School of Medicine at UCLA, the brain navigates its way through a series of activity clusters, or "hubs" on its way back to consciousness. Dr. Andrew Hudson, an assistant professor in anesthesiology states, "Recovery from anesthesia is not simply the result of the anesthetic 'wearing off,' but also of the brain finding its way back through a maze of possible activity states to those that allow conscious experience. Put simply, the brain reboots itself." Long-term POCD is a subtle deterioration in cognitive function, that can last for weeks, months, or longer. Most commonly, relatives of the person report a lack of attention, memory and loss of interest in activities previously dear to the person (such as crosswords). In a similar way, people in the workforce may report an inability to complete tasks at the same speed they could previously. There is good evidence that POCD occurs after cardiac surgery and the major reason for its occurrence is the formation of microemboli. POCD also appears to occur in non-cardiac surgery. Its causes in non-cardiac surgery are less clear but older age is a risk factor for its occurrence.: 2805–16 The first attempts at general anesthesia were probably herbal remedies administered in prehistory. Alcohol is one of the oldest known sedatives and it was used in ancient Mesopotamia thousands of years ago. The Sumerians are said to have cultivated and harvested the opium poppy (Papaver somniferum) in lower Mesopotamia as early as 3400 BCE. The ancient Egyptians had some surgical instruments, as well as crude analgesics and sedatives, including possibly an extract prepared from the mandrake fruit. In China, Bian Que (Chinese: 扁鹊, Wade–Giles: Pien Ch'iao, c. 300 BCE) was a legendary Chinese internist and surgeon who reportedly used general anesthesia for surgical procedures. Despite this, it was the Chinese physician Hua Tuo whom historians considered the first verifiable historical figure to develop a type of mixture of anesthesia, though his recipe has yet to be fully discovered. Throughout Europe, Asia, and the Americas, a variety of Solanum species containing potent tropane alkaloids was used for anesthesia. In 13th-century Italy, Theodoric Borgognoni used similar mixtures along with opiates to induce unconsciousness, and treatment with the combined alkaloids proved a mainstay of anesthesia until the 19th century. Local anesthetics were used in Inca civilization where shamans chewed coca leaves and performed operations on the skull while spitting into the wounds they had inflicted to anesthetize. Cocaine was later isolated and became the first effective local anesthetic. It was first used in 1859 by Karl Koller, at the suggestion of Sigmund Freud, in eye surgery in 1884. German surgeon August Bier (1861–1949) was the first to use cocaine for intrathecal anesthesia in 1898. Romanian surgeon Nicolae Racoviceanu-Piteşti (1860–1942) was the first to use opioids for intrathecal analgesia; he presented his experience in Paris in 1901. The "soporific sponge" ("sleep sponge") used by Arabic physicians was introduced to Europe by the Salerno school of medicine in the late 12th century and by Ugo Borgognoni (1180–1258) in the 13th century. The sponge was promoted and described by Ugo's son and fellow surgeon, Theodoric Borgognoni (1205–1298). In this anesthetic method, a sponge was soaked in a dissolved solution of opium, mandragora, hemlock juice, and other substances. The sponge was then dried and stored; just before surgery the sponge was moistened and then held under the patient's nose. When all went well, the fumes rendered the individual unconscious. The most famous anesthetic, ether, may have been synthesized as early as the 8th century, but it took many centuries for its anesthetic importance to be appreciated, even though the 16th century physician and polymath Paracelsus noted that chickens made to breathe it not only fell asleep but also felt no pain. By the early 19th century, ether was being used by humans, but only as a recreational drug. Meanwhile, in 1772, English scientist Joseph Priestley discovered the gas nitrous oxide. Initially, people thought this gas to be lethal, even in small doses, like some other nitrogen oxides. However, in 1799, British chemist and inventor Humphry Davy decided to find out by experimenting on himself. To his astonishment he found that nitrous oxide made him laugh, so he nicknamed it "laughing gas". In 1800 Davy wrote about the potential anesthetic properties of nitrous oxide in relieving pain during surgery, but nobody at that time pursued the matter any further. On 14 November 1804, Hanaoka Seishū, a Japanese doctor, became the first person to successfully perform surgery using general anesthesia. Hanaoka learned traditional Japanese medicine as well as Dutch-imported European surgery and Chinese medicine. After years of research and experimentation, he finally developed a formula which he named tsūsensan (also known as mafutsu-san), which combined Korean morning glory and other herbs. Hanaoka's success in performing this painless operation soon became widely known, and patients began to arrive from all parts of Japan. Hanaoka went on to perform many operations using tsūsensan, including resection of malignant tumors, extraction of bladder stones, and extremity amputations. Before his death in 1835, Hanaoka performed more than 150 operations for breast cancer. However, this finding did not benefit the rest of the world until 1854 as the national isolation policy of the Tokugawa shogunate prevented Hanaoka's achievements from being publicized until after the isolation ended. Nearly forty years would pass before Crawford Long, who is titled as the inventor of modern anesthetics in the West, used general anesthesia in Jefferson, Georgia. Long noticed that his friends felt no pain when they injured themselves while staggering around under the influence of diethyl ether. He immediately thought of its potential in surgery. Conveniently, a participant in one of those "ether frolics", a student named James Venable, had two small tumors he wanted excised. But fearing the pain of surgery, Venable kept putting the operation off. Hence, Long suggested that he have his operation while under the influence of ether. Venable agreed, and on 30 March 1842 he underwent a painless operation. However, Long did not announce his discovery until 1849. Horace Wells conducted the first public demonstration of the inhalational anesthetic at the Massachusetts General Hospital in Boston in 1845. However, the nitrous oxide was improperly administered and the person cried out in pain. On 16 October 1846, Boston dentist William Thomas Green Morton gave a successful demonstration using diethyl ether to medical students at the same venue. Morton, who was unaware of Long's previous work, was invited to the Massachusetts General Hospital to demonstrate his new technique for painless surgery. After Morton had induced anesthesia, surgeon John Collins Warren removed a tumor from the neck of Edward Gilbert Abbott. This occurred in the surgical amphitheater now called the Ether Dome. The previously skeptical Warren was impressed and stated, "Gentlemen, this is no humbug." In a letter to Morton shortly thereafter, physician and writer Oliver Wendell Holmes, Sr. proposed naming the state produced "anesthesia", and the procedure an "anesthetic". Morton at first attempted to hide the actual nature of his anesthetic substance, referring to it as Letheon. He received a US patent for his substance, but news of the successful anesthetic spread quickly by late 1846. Respected surgeons in Europe including Liston, Dieffenbach, Pirogov, and Syme quickly undertook numerous operations with ether. An American-born physician, Boott, encouraged London dentist James Robinson to perform a dental procedure on a Miss Lonsdale. This was the first case of an operator-anesthetist. On the same day, 19 December 1846, in Dumfries Royal Infirmary, Scotland, a Dr. Scott used ether for a surgical procedure. The first use of anesthesia in the Southern Hemisphere took place in Launceston, Tasmania, that same year. Drawbacks with ether such as excessive vomiting and its explosive flammability led to its replacement in England with chloroform. Discovered in 1831 by an American physician Samuel Guthrie (1782–1848), and independently a few months later by Frenchman Eugène Soubeiran (1797–1859) and Justus von Liebig (1803–1873) in Germany, chloroform was named and chemically characterized in 1834 by Jean-Baptiste Dumas (1800–1884). In 1842, Dr Robert Mortimer Glover in London discovered the anaesthetic qualities of chloroform on laboratory animals. In 1847, Scottish obstetrician James Young Simpson was the first to demonstrate the anesthetic properties of chloroform on humans and helped to popularize the drug for use in medicine. This first supply came from local pharmacists, James Duncan and William Flockhart, and its use spread quickly, with 750,000 doses weekly in Britain by 1895. Simpson arranged for Flockhart to supply Florence Nightingale. Chloroform gained royal approval in 1853 when John Snow administered it to Queen Victoria when she was in labor with Prince Leopold. For the experience of child birth itself, chloroform met all the Queen's expectations; she stated it was "delightful beyond measure". Chloroform was not without fault though. The first fatality directly attributed to chloroform administration was recorded on 28 January 1848 after the death of Hannah Greener. This was the first of many deaths to follow from the untrained handling of chloroform. Surgeons began to appreciate the need for a trained anesthetist. The need, as Thatcher writes, was for an anesthetist to "(1)Be satisfied with the subordinate role that the work would require, (2) Make anesthesia their one absorbing interest, (3) not look at the situation of anesthetist as one that put them in a position to watch and learn from the surgeons technique (4) accept the comparatively low pay and (5) have the natural aptitude and intelligence to develop a high level of skill in providing the smooth anesthesia and relaxation that the surgeon demanded" These qualities of an anesthetist were often found in submissive medical students and even members of the public. More often, surgeons sought out nurses to provide anesthesia. By the time of the Civil War, many nurses had been professionally trained with the support of surgeons. John Snow of London published articles from May 1848 onwards "On Narcotism by the Inhalation of Vapours" in the London Medical Gazette. Snow also involved himself in the production of equipment needed for the administration of inhalational anesthetics, the forerunner of today's anesthesia machines. Alice Magaw, born in November 1860, is often referred to as "The Mother of Anesthesia". Her renown as the personal anesthesia provider for William and Charles Mayo was solidified by Mayo's own words in his 1905 article in which he described his satisfaction with and reliance on nurse anesthetists: "The question of anaesthesia is a most important one. We have regular anaesthetists [on] whom we can depend so that I can devote my entire attention to the surgical work." Magaw kept thorough records of her cases and recorded these anesthetics. In her publication reviewing more than 14,000 surgical anesthetics, Magaw indicates she successfully provided anesthesia without an anesthetic-related death. Magaw describes in another article, "We have administered an anesthetic 1,092 times; ether alone 674 times; chloroform 245 times; ether and chloroform combined 173 times. I can report that out of this number, 1,092 cases, we have not had an accident". Magaw's records and outcomes created a legacy defining that the delivery of anesthesia by nurses would serve the surgical community without increasing the risks to patients. In fact, Magaw's outcomes would eclipse those of practitioners today. The first comprehensive medical textbook on the subject, Anesthesia, was authored in 1914 by anesthesiologist Dr. James Tayloe Gwathmey and the chemist Dr. Charles Baskerville. This book served as the standard reference for the specialty for decades and included details on the history of anesthesia as well as the physiology and techniques of inhalation, rectal, intravenous, and spinal anesthesia. Of these first famous anesthetics, only nitrous oxide is still widely used today, with chloroform and ether having been replaced by safer but sometimes more expensive general anesthetics, and cocaine by more effective local anesthetics with less abuse potential. Society and cultureEdit Almost all healthcare providers use anesthetic drugs to some degree, but most health professions have their own field of specialists in the field including medicine, nursing and dentistry. Doctors specializing in anaesthesiology, including perioperative care, development of an anesthetic plan, and the administration of anesthetics are known in the US as anesthesiologists and in the UK, Canada, Australia, and NZ as anaesthetists or anaesthesiologists. All anesthetics in the UK, Australia, New Zealand, Hong Kong and Japan are administered by doctors. Nurse anesthetists also administer anesthesia in 109 nations. In the US, 35% of anesthetics are provided by physicians in solo practice, about 55% are provided by anesthesia care teams (ACTs) with anesthesiologists medically directing certified registered nurse anesthetists (CRNAs) or anesthesiologist assistants, and about 10% are provided by CRNAs in solo practice. There can also be anesthesiologist assistants (US) or physicians' assistants (anaesthesia) (UK) who assist with anesthesia. There are many circumstances when anesthesia needs to be altered for special circumstances due to the procedure (such as in cardiac surgery, cardiothoracic anesthesiology or neurosurgery), the patient (such as in pediatric anesthesia, geriatric, bariatric or obstetrical anesthesia) or special circumstances (such as in trauma, prehospital care, robotic surgery or extreme environments). - Fluorescence image-guided surgery - Jet ventilation - List of surgical procedures - Surgical drain - Wooden chest – a post opioid anesthesia condition - Cardiac surgery - ^ "anaesthesia". Oxford English Dictionary (Online ed.). Oxford University Press. (Subscription or participating institution membership required.) - ^ a b c d e f g h i j k l m n o p q r s t Miller RD (2010). Erikson LI, Fleisher LA, Wiener-Kronish JP, Young WL (eds.). Miller's Anesthesia (Seventh ed.). US: Churchill Livingstone Elsevier. ISBN 978-0-443-06959-8. - ^ a b c d Gelb AW, Morriss WW, Johnson W, Merry AF, Abayadeera A, Belîi N, et al. (June 2018). "World Health Organization-World Federation of Societies of Anaesthesiologists (WHO-WFSA) International Standards for a Safe Practice of Anesthesia". Anesthesia and Analgesia. 126 (6): 2047–55. doi:10.1213/ANE.0000000000002927. PMID 29734240. S2CID 13688396. - ^ a b Fitz-Henry J (April 2011). "The ASA classification and peri-operative risk". Annals of the Royal College of Surgeons of England. 93 (3): 185–87. doi:10.1308/rcsann.2011.93.3.185a. PMC 3348554. PMID 21477427. - ^ Goneppanavar U, Prabhu M (September 2013). "Anaesthesia machine: checklist, hazards, scavenging". Indian Journal of Anaesthesia. 57 (5): 533–40. doi:10.4103/0019-5049.120151. PMC 3821271. PMID 24249887. - ^ Subrahmanyam M, Mohan S (September 2013). "Safety features in anaesthesia machine". Indian Journal of Anaesthesia. 57 (5): 472–80. doi:10.4103/0019-5049.120143. PMC 3821264. PMID 24249880. - ^ Standards for Basic Anesthetic Monitoring. Committee of Origin: Standards and Practice Parameters (Approved by the ASA House of Delegates on 21 October 1986, amended 20 October 2010 with an effective date of 1 July 2011) - ^ Birks RJS, ed. (March 2007). Recommendations for Standards of Monitoring During Anaesthesia and Recovery 4th Edition (PDF). Association of Anaesthetists of Great Britain and Ireland. Archived from the original (PDF) on 13 May 2015. Retrieved 21 February 2014. - ^ Reddy S, Patt RB (November 1994). "The benzodiazepines as adjuvant analgesics". Journal of Pain and Symptom Management. 9 (8): 510–14. doi:10.1016/0885-3924(94)90112-0. PMID 7531735. - ^ Mallinson T (2019). "Fascia iliaca compartment block: a short how-to guide". Journal of Paramedic Practice. 11 (4): 154–55. doi:10.12968/jpar.2019.11.4.154. ISSN 1759-1376. S2CID 145859649. - ^ a b c Weinstein EJ, Levene JL, Cohen MS, Andreae DA, Chao JY, Johnson M, Hall CB, Andreae MH (20 June 2018). "Local anaesthetics and regional anaesthesia versus conventional analgesia for preventing persistent postoperative pain in adults and children". Cochrane Database Syst Rev. 6 (2): CD007105. doi:10.1002/14651858.CD007105.pub4. PMC 6377212. PMID 29926477. - ^ Lewis, Sharon R.; Price, Anastasia; Walker, Kevin J.; McGrattan, Ken; Smith, Andrew F. (11 September 2015). "Ultrasound guidance for upper and lower limb blocks". The Cochrane Database of Systematic Reviews. 2015 (9): CD006459. doi:10.1002/14651858.CD006459.pub3. ISSN 1469-493X. PMC 6465072. PMID 26361135. - ^ Ullah H, Samad K, Khan FA (February 2014). "Continuous interscalene brachial plexus block versus parenteral analgesia for postoperative pain relief after major shoulder surgery". The Cochrane Database of Systematic Reviews. 2014 (2): CD007080. doi:10.1002/14651858.CD007080.pub2. PMC 7182311. PMID 24492959. - ^ a b Klomp T, van Poppel M, Jones L, Lazet J, Di Nisio M, Lagro-Janssen AL (September 2012). "Inhaled analgesia for pain management in labour". The Cochrane Database of Systematic Reviews. 12 (9): CD009351. doi:10.1002/14651858.CD009351.pub2. hdl:1871/48559. PMID 22972140. - ^ Radvansky BM, Shah K, Parikh A, Sifonios AN, Le V, Eloy JD (1 October 2015). "Role of ketamine in acute postoperative pain management: a narrative review". BioMed Research International. 2015: 749837. doi:10.1155/2015/749837. PMC 4606413. PMID 26495312. - ^ McNicol ED, Ferguson MC, Hudcova J (June 2015). "Patient controlled opioid analgesia versus non-patient controlled opioid analgesia for postoperative pain". The Cochrane Database of Systematic Reviews. 2020 (6): CD003348. doi:10.1002/14651858.CD003348.pub3. PMC 7387354. PMID 26035341. - ^ Jones L, Othman M, Dowswell T, Alfirevic Z, Gates S, Newburn M, et al. (March 2012). "Pain management for women in labour: an overview of systematic reviews". The Cochrane Database of Systematic Reviews. 3 (3): CD009234. doi:10.1002/14651858.CD009234.pub2. PMC 7132546. PMID 22419342. - ^ Guay J, Kopp S (January 2016). "Epidural pain relief versus systemic opioid-based pain relief for abdominal aortic surgery". The Cochrane Database of Systematic Reviews. 2017 (1): CD005059. doi:10.1002/14651858.CD005059.pub4. PMC 6464571. PMID 26731032. - ^ a b Lagasse RS (December 2002). "Anesthesia safety: model or myth? A review of the published literature and analysis of current original data". Anesthesiology. 97 (6): 1609–17. doi:10.1097/00000542-200212000-00038. PMID 12459692. S2CID 32903609. - ^ Chaloner EJ, Flora HS, Ham RJ (August 2001). "Amputations at the London Hospital 1852–1857". Journal of the Royal Society of Medicine. 94 (8): 409–12. doi:10.1177/014107680109400812. PMC 1281639. PMID 11461989. - ^ Braz LG, Braz DG, Cruz DS, Fernandes LA, Módolo NS, Braz JR (October 2009). "Mortality in anesthesia: a systematic review". Clinics. 64 (10): 999–1006. doi:10.1590/S1807-59322009001000011. PMC 2763076. PMID 19841708. - ^ Food and Drug Administration "FDA Drug Safety Communication: FDA review results in new warnings about using general anesthetics and sedation drugs in young children and pregnant women", FDA Website, 14 December 2016. Retrieved on 3 January 2017. - ^ American College of Obstetricians and Gynecologists "Practice Advisory: FDA Warnings Regarding Use of General Anesthetics and Sedation Drugs in Young Children and Pregnant Women", ACOG Website, 21 December 2016. Retrieved on 3 January 2017. - ^ Kennerly Loutey "Anesthesia in Pregnant Women And Young Children: The FDA Versus ACOG", Website, Retrieved on 3 January 2017. - ^ Whitaker Chair DK, Booth H, Clyburn P, Harrop-Griffiths W, Hosie H, Kilvington B, et al. (March 2013). "Immediate post-anaesthesia recovery 2013: Association of Anaesthetists of Great Britain and Ireland". Anaesthesia. 68 (3): 288–97. doi:10.1111/anae.12146. PMID 23384257. S2CID 9519895. - ^ D'Souza RS, Vogt MN, Rho EH. "Post-operative functional neurological symptom disorder after anesthesia". Bosn J of Basic Med Sci. 2020Aug.3;20(3):381–88. PMID 32070267 PMC 7416177 doi:10.17305/bjbms.2020.4646 - ^ Rudolph JL, Marcantonio ER, Culley DJ, Silverstein JH, Rasmussen LS, Crosby GJ, Inouye SK (September 2008). "Delirium is associated with early postoperative cognitive dysfunction". Anaesthesia. 63 (9): 941–47. doi:10.1111/j.1365-2044.2008.05523.x. PMC 2562627. PMID 18547292. - ^ How brain 'reboots' itself to consciousness after anesthesia. Science Daily (18 June 2014) - ^ Deiner S, Silverstein JH (December 2009). "Postoperative delirium and cognitive dysfunction". British Journal of Anaesthesia. 103 (Suppl 1): i41–46. doi:10.1093/bja/aep291. PMC 2791855. PMID 20007989. - ^ Powell MA (1996). "Chapter 9: Wine and the vine in ancient Mesopotamia: the cuneiform evidence". In McGovern PE, Fleming SJ, Katz SH (eds.). The origins and ancient history of wine (Food and nutrition in history and anthropology). Vol. 11 (1 ed.). Amsterdam: Gordon and Breach Publishers. pp. 96–124. ISBN 978-90-5699-552-2. - ^ Evans TC (1928). "The opium question, with special reference to Persia (book review)". Transactions of the Royal Society of Tropical Medicine and Hygiene. 21 (4): 339–40. doi:10.1016/S0035-9203(28)90031-0. The earliest known mention of the poppy is in the language of the Sumerians, a non-Semitic people who descended from the uplands of Central Asia into Southern Mesopotamia ... - ^ Booth M (1996). "The discovery of dreams". Opium: A History. London: Simon & Schuster, Ltd. p. 15. ISBN 978-0-312-20667-3. - ^ Stern LC (1889). Ebers G (ed.). Papyrus Ebers (in German). Vol. 2 (1 ed.). Leipzig: Bei S. Hirzel. OCLC 14785083. Retrieved 18 September 2010. - ^ Pahor AL (August 1992). "Ear, nose and throat in ancient Egypt". The Journal of Laryngology and Otology. 106 (8): 677–87. doi:10.1017/S0022215100120560. PMID 1402355. S2CID 35712860. - ^ Sullivan R (August 1996). "The identity and work of the ancient Egyptian surgeon". Journal of the Royal Society of Medicine. 89 (8): 467–73. doi:10.1177/014107689608900813. PMC 1295891. PMID 8795503. - ^ Mair, Victor H. (1994). "The Biography of Hua-t'o from the "History of the Three Kingdoms"". In Victor H. Mair (ed.). The Columbia Anthology of Traditional Chinese Literature. Columbia University Press. pp. 688–96. - ^ Ruetsch YA, Böni T, Borgeat A (August 2001). "From cocaine to ropivacaine: the history of local anesthetic drugs". Current Topics in Medicinal Chemistry. 1 (3): 175–82. doi:10.2174/1568026013395335. PMID 11895133. - ^ Koller K (1884). "Über die verwendung des kokains zur anästhesierung am auge" [On the use of cocaine for anesthesia on the eye]. Wiener Medizinische Wochenschrift (in German). 34: 1276–309. - ^ Bier A (1899). "Versuche über cocainisirung des rückenmarkes" [Experiments on the cocainization of the spinal cord]. Deutsche Zeitschrift für Chirurgie (in German). 51 (3–4): 361–69. doi:10.1007/BF02792160. S2CID 41966814. - ^ Brill S, Gurman GM, Fisher A (September 2003). "A history of neuraxial administration of local analgesics and opioids". European Journal of Anaesthesiology. 20 (9): 682–89. doi:10.1017/S026502150300111X. PMID 12974588. S2CID 46735940. - ^ Juvin, Phillippe; Desmonts, Jean-Marie (July 2000). "The Ancestors of Inhalational Anesthesia: The Soporific Sponges (XIth–XVIIth Centuries): How a Universally Recommended Medical Technique Was Abruptly Discarded". Anesthesiology. 93 (1): 265–269. doi:10.1097/00000542-200007000-00037. PMID 10861170. S2CID 4867308. Retrieved 15 January 2023. - ^ Toski JA, Bacon DR, Calverley RK (2001). "The history of Anesthesiology". In Barash PG, Cullen BF, Stoelting RK (eds.). Clinical Anesthesia (4th ed.). Lippincott Williams & Wilkins. p. 3. ISBN 978-0-7817-2268-1. - ^ Hademenos GJ, Murphree S, Zahler K, Warner JM (2008). McGraw-Hill's PCAT. McGraw-Hill. p. 39. ISBN 978-0-07-160045-3. - ^ a b Fenster JM (2001). "Power Struggle". Ether Day: The Strange Tale of America's Greatest Medical Discovery and the Haunted Men Who Made It. New York: HarperCollins. pp. 106–16. ISBN 978-0-06-019523-6. - ^ a b Hardman JG (2017). Oxford Textbook of Anaesthesia. Oxford University Press. p. 529. - ^ Izuo, Masaru (1 November 2004). "Medical history: Seishu hanaoka and his success in breast cancer surgery under general anesthesia two hundred years ago". Breast Cancer. 11 (4): 319–24. doi:10.1007/BF02968037. ISSN 1880-4233. PMID 15604985. S2CID 43428862. - ^ Ogata, Tomio (1973). "Seishu Hanaoka and his anaesthesiology and surgery*". Anaesthesia. 28 (6): 645–52. doi:10.1111/j.1365-2044.1973.tb00549.x. ISSN 1365-2044. PMID 4586362. S2CID 31352880. - ^ Hyodo, M.; Oyama, T.; Oyama, Tsutomu; Swerdlow, Mark (1992). The Pain Clinic IV: Proceedings of the Fourth International Symposium, Kyoto, Japan, 18-21 November 1990. VSP. ISBN 978-90-6764-147-0. - ^ Toby, Ronald P. (1977). "Reopening the Question of Sakoku: Diplomacy in the Legitimation of the Tokugawa Bakufu". Journal of Japanese Studies. 3 (2): 323–63. doi:10.2307/132115. ISSN 0095-6848. JSTOR 132115. - ^ "An Account of the First Use of Sulphuric Ether by... : Survey of Anesthesiology". LWW. Retrieved 22 February 2021. - ^ Long CW (1849). "An account of the first use of Sulphuric Ether by Inhalation as an Anesthetic in Surgical Operations". Southern Medical and Surgical Journal. 5: 705–13. - ^ "Miniature Portrait of Horace Wells". National Museum of American History, Smithsonian Institution. Retrieved 30 June 2008. - ^ Morkel H (16 October 2013). "The painful story behind modern anesthesia". pbs.org. - ^ Baillie TW (December 1965). "The first European trial of anaesthetic ether: the Dumfries claim". British Journal of Anaesthesia. 37 (12): 952–57. doi:10.1093/bja/37.12.952. PMID 5323141. - ^ Defalque RJ, Wright AJ (April 2004). "The short, tragic life of Robert M. Glover" (PDF). Anaesthesia. 59 (4): 394–400. doi:10.1111/j.1365-2044.2004.03671.x. PMID 15023112. S2CID 46428403. - ^ "Sir James Young Simpson". Encyclopædia Britannica. Retrieved 23 August 2013. - ^ Worlin, P. M. (1998). "Duncan and Flockhart: the Story of Two Men and a Pharmacy". Pharmaceutical Historian. 28 (2): 28–33. PMID 11620310. - ^ "Queen Victoria uses chloroform in childbirth, 1853". Financial Times. 28 November 2017. Archived from the original on 10 December 2022. - ^ Wawersik J (1 January 1997). "[History of chloroform anesthesia]". Anaesthesiologie und Reanimation. 22 (6): 144–52. PMID 9487785. - ^ Nagelhout J (2018). Nurse Anesthesia. St. Louis Missouri: Elsevier. pp. 2–4. ISBN 978-0323443920. - ^ Zorab J (June 1992). "On Narcotism by the Inhalation of Vapours by John Snow MD". Journal of the Royal Society of Medicine. 85 (6): 371. PMC 1293529. - ^ "Anesthesia LAND". patinaa.blogfa.com. Archived from the original on 3 December 2016. Retrieved 2 December 2016. - ^ Goode, Victoria (February 2015). "Alice Magaw: A Model for Evidence-Based Practice" (PDF). AANA Journal. 83 (1): 50–55. PMID 25842634. - ^ a b Cope DK (March 1993). "James Tayloe Gwathmey: seeds of a developing specialty". Anesthesia and Analgesia. 76 (3): 642–47. doi:10.1213/00000539-199303000-00035. PMID 8452281. S2CID 7574462. - ^ "Celebrating 75 years of Anaesthesia: our past, present and future \| Association of Anaesthetists". anaesthetists.org. Retrieved 17 October 2022. - ^ a b McAuliffe MS, Henry B (2010). "Nurse anesthesia worldwide: practice, education and regulation" (PDF). Downloads. Silver Spring, Maryland: International Federation of Nurse Anesthetists. Retrieved 13 June 2012. - ^ Abenstein JP, Long KH, McGlinch BP, Dietz NM (March 2004). "Is physician anesthesia cost-effective?". Anesthesia and Analgesia. 98 (3): 750–57, table of contents. doi:10.1213/01.ANE.0000100945.56081.AC. PMID 14980932. S2CID 7907307. - ^ Rosenbach ML, Cromwell J (May 1989). "When do anesthesiologists delegate?". Medical Care. 27 (5): 453–65. doi:10.1097/00005650-198905000-00002. PMID 2725080. S2CID 26298329. - ^ "Five facts about AAs". American Academy of Anesthesiologist Assistants. Archived from the original on 26 September 2006. Retrieved 25 November 2010.	2	76	15	2	0	0.369448	17	13,262
Myelinated retinal nerve fiber layer \|Myelinated Retinal Nerve Fiber Layer\| \|Classification and external resources\| Fundus photo of a 7 yo girl with myelinated RNFL, 20/20 vision, and mild hyperopia Myelinated Retinal Nerve Fiber Layer Myelinated retinal nerve fiber layer (RNFL) is often an incidental finding on ophthalmoscopic exam. It can vary in size and location and presents as well-demarcated patch of myelinated retinal ganglion cell axons. While a benign finding, it can be associated with anisometropia, strabismus, and amblyopia. Ophthalmic imaging can help differentiate myelinated RNFL from other mimicking ocular conditions (Table 2). International Classification of Disease ICD-9 377.49 Other disorders of optic nerve ICD-10 H35.89 Defect, defective retinal nerve bundle fibers Virchow was the first to describe myelinated retinal nerve fibers as “chalk-white spots” around the optic disc 1856. However, his observation was predated by over a century of neuronal study. In 1717, Leeuwenhoek described seeing a subset of nerves covered with “fatty parts.” Ehrenberg described “cylindrical tubes” in the myelinated nerve fibers in 1833. German embryologist and neurologist Remak postulated that the cylinders originate from neuronal ganglion cells in 1838. Schwann stated that the white substance around the nerve fiber is a sheath in 1839. In 1858, Virchow described that the “medullary sheath is not an absolutely necessary constituent of the nerve, but that it confines electricity within the nerve itself and allows discharge to take place only at the non-medullated extremities of the fibers.” Cajal recognized that the axis cylinder is the axonal process and that the myelin sheath is external and secreted by the axon in 1909. In 1918, Gradle stated: “The cause of sporadic medullation of retinal nerve fibers falls among still unexplored phases of ophthalmology…” Myelinated retinal nerve fiber layers (RNFLs), also known as medullated retinal nerve fibers, are white or grey-white well-demarcated patches on the outermost surface of the retina that obscure the underlying retinal vessels. The frayed feathered borders correspond to retinal ganglion cell axons. In a retrospective study reviewing the fundus photos of 5,789 patients, the prevalence of myelination of the RNFL was found to be 0.57%.The incidence of myelination of the RNFL in an autopsy series of 7,936 eyes was 0.98% of cases and 0.54% of eyes. Myelinated RNFLs are bilateral in 7.7% of cases.While myelinated RNFLs were found more often in females in one study, this finding was not replicated in another study. Clinically, myelinated RNFL patches most often appear in the superior sector of the optic nerve head and appear to be continuous with the optic nerve. They are often described as distributed around or contiguous with the optic disc and vascular arcades. Pathologic studies, however, show that myelinated RNFL patches are continuous with the optic nerve in only 33% of cases and discontinuous with the optic nerve head in 66% of affected eyes. Multiple distinct lesions were found in 12% of specimens. While generally sporadic, familial cases (see Genetics) of myelinated RNFL patches have been reported both in isolation and in combination with ocular (see Table 2) and systemic syndromes (see Table 3). Myelinated RNFLs are most often asymptomatic and have a variable effect on visual function, influenced by location, extent of myelination, and coexisting visual pathology. The most common ocular associations of myelinated RNFLs are axial myopia, amblyopia, and strabismus., (see Table 2). Myelinated RNFLs are most often congenital and non-progressive, but few cases of acquired progressive lesions in childhood and adulthood have been reported (see Table 4). They have also been reported to disappear after surgery and insults to the optic nerve (see Table 5). Myelination of the human central nervous system (CNS) generally originates proximally at the cell soma and progresses distally along the axon. Myelination of retinal ganglion cells differs because it proceeds from the optic tract toward the globe. Glial ensheathment of axons in the optic tract commences at five months of gestation. Oligodendocyte progenitor cells (OPC) originate from neuroepithelial cells in the ventral ventricular zone of the embryonic spinal cord and possibly the forebrain. Neurosignaling influences the migration of OPCs laterally and dorsally to all parts of the developing CNS. Progenitor cell fate is determined by master regulatory genes (including Olig1 and Yy1), chemoattractants and repellants, and specific regional transcription factors. OPC migration patterns can be influenced by extracellular signals (including netrin-1 and CXCL1 ). A specific combination of transcription factors program the OPC to terminally differentiate into a myelinating oligodendrocyte which ensheaths its terminal axons. By eight months of gestation, myelination has generally advanced beyond the chiasm to the optic nerve. Myelination continues distally until it reaches the lamina cribrosa, where it usually ceases. The lamina cribrosa is thought to be a physical barrier to myelination by blocking the migration of OPCs. This theory is supported by the facts that rabbits, which lack a lamina cribrosa, have naturally myelinated retinal nerve fibers, and retinas transplanted outside of the lamina cribrosa become myelinated. It has been shown that myelination continues in the human optic nerve during postnatal visual development after full-term gestation. The current theory is that ectopic OPCs lead to myelinated retinal nerve fibers. Rather than being a random process, axons may influence and even recruit nearby oligodendocytes in the myelination process. Several cases of human myelinated RNFLs have been extensively analyzed. Retina adjacent to a myelinated retinal nerve fiber layer patch is normal. The histopathology of the retina involving the myelinated retinal nerve fiber layer is abnormal. The tissue within the myelinated retinal patch has no microscopic signs of inflammation and few cell nuclei. There is a reduced retinal ganglion cell population in the patch compared to adjacent areas. The myelinated RNFLs compresses the underlying retinal layers, reducing the width and altering the conformation of the inner and outer plexiform layers. The border between the inner nuclear layer and outer nuclear layer in this area is also indistinct. Despite proximity to the retinal vessels, association with the vascular supply is rarely seen. Myelinated fibers are not confined to a patch or fascicle, and single myelinated fibers could be found in between fascicles of unmyelinated fibers. The axonal diameters of myelinated and unmyelinated fibers within the myelinated patch are larger than the axons outside the myelinated patch. Additionally, myelinated fibers in the patch are larger than any optic nerve and retinal fibers in the same eye. Myelin is less condensed in these large fibers and can show degenerative signs of myelinolysis. Myelination is more frequently discontinuous with the optic nerve than continuous. No abnormalities of the cribriform plate have been reported in eyes with myelinated RNFL. Associated with other disorders Recently, an autosomal recessive syndrome of growth retardation, alopecia, pseudoanodontia, optic atrophy (GAPO syndrome) was associated with hypertelorism, severe end-stage glaucoma and myelinated retinal nerve fiber layer. A syndrome of vitreoretinal degeneration, posterior subcapsular cataract, and skeletal abnormalities (missing digits) was also described. Goltz-Gorlin (multiple basal cell nevus) syndrome has also been reported to be associated with acquired myelination of the RNFL. A patient with Albright hereditary osteodystrophy was also found to have a focal area of myelination of the RNFL (unreported, seen at UCSD) (see Table 1). Table 1. Systemic syndromes associated with myelination of the RNFL \| GAPO Syndrome with congenital glaucoma \| \|Vitreoretinopathy and skeletal malformations\| \| Goltz-Gorlin syndrome (multiple basal cell nevus syndrome) \| \| Turner syndrome \| \| Epilepsy \| \| Dolichocephaly \| \| Craniosynostosis \| \| Downs Syndrome\| \| Albright hereditary osteodystrophy\| \| Von Recklinhausen’s disease \| \| Arnold-Chiari malformation and hydrocephalus\| Most cases of myelination of the RNFL are diagnosed incidentally in asymptomatic healthy children or adults by ophthalmoscopy. The clinical appearance of fan-shaped peri-papillary white striated patches in the distribution of the retinal nerve fiber layer is distinct (see Figure 1). The size of the lesions can vary from small (approximately one disc diameter in size) to involving large areas of the retina. Figure 1. Myelination of the RNFL in a 7 year old boy associated with anisomyopia and amblyopia. Ophthalmic Imaging Characteristics The imaging characteristics of myelination of the RNFL have been reviewed recently, and the results are summarized here. In addition to fundus photography, MultiColor imaging may be useful in determining fine anatomic details with excellent contrast (Figure 2a) On optical coherence tomography (OCT), myelinated RNFL is easily identified (red arrow). With dense myelination, there can be focal compression of the inner retina (Figure 2b). On infrared (Figure 2b) and red-free (Figure 2c) imaging, the RNFL appears white because of the high lipid content. Myelination of the RNFL appears dark on fundus autofluorescence (Figure 2d) also causes blockage on fluorescein angiography (FA) (Figure 2e). a. MultiColor imaging of the posterior pole in a patient with myelinated retinal nerve fiber layer. b. Infrared image and Spectralis® OCT of myelinated RNFL c. Red free image of myelinated RNFL d. Fundus autofluorescence of myelinated RNFL e. Fluorescein angiography appearance of myelinated RNFL Current clinically used ophthalmic imaging techniques can help differentiate myelination of the RNFL from other potentially serious conditions, including a cotton wool spot, BRAO, and retinal infiltration (Table 2). Table 2. Features differentiating myelination of the RNFL from other potentially mimicking retinal processes \| Differential Diagnosis\|\| Differentiating features using ophthalmic imaging\| \| Cotton wool spot (CWS):\| local infarction of the RNFL with a localized backup of axoplasmic flow \| OCT: focally elevated RNFL area with compression of the underlying retinal levels down to the photoreceptor layer; acutely, thickness map will show retinal thickening; follow-up OCT will show an area of retinal thinning; The vitreous may appear elevated over the CWS ; lesion will fade in 2 months\| \| Branch retinal artery occlusion (BRAO)\|\| FA: a branch of the central retinal artery will have an acute drop off in arterial flow into one of its branches ± an intra-arterial embolus \| OCT: hyperreflectivity and thickness (edema) of the nerve fiber and inner retinal layers in the ischemic retina compared to normal retina in the acute phase; if present, a cholesterol embolus may result in shadowing \| Peripapillary epiretinal membrane (ERM)\|\| OCT: The epiretinal membrane will be visible as a hyperreflective layer above the inner limiting membrane with or without vitreoretinal traction, increased retinal thickness, disruption of the foveal contour, intraretinal fluid, and disruption of the IS/OS.\| \| Serous retinal pigment epithelium detachment (SPED)\|\| OCT: subretinal fluid, highly reflective substances beneath the retinal pigment epithelium with detachment of the sensory retina\| FA: focal areas of pooling or a smokestack pattern of leakage in the area of the retinal pigment epithelial detachment ICG: focal hyperfluorescence in areas of choroidal neovascularization \| Retinal infiltrates \| (infectious, inflammatory, or neoplastic) \| Imaging varies based on the etiology\| OCT: vitritis (if infectious or inflammatory), subretinal or intraretinal hyperreflective deposits and serous macular detachments (neoplastic) FA: retinal vascular leakage or late staining, leakage from the disc, macular edema, capillary dropout, and neovascularization in Behcet’s disease; ± CRVO and retinal hemorrhages in leukemia \| Retinoblastoma\|\| OCT: larger isodense intraretinal lesions confined to the inner retinal layers with preservation of the overlying inner retina in early tumors\| \| Retinal necrosis\|\| FA: blockage of background choroidal fluorescence by the opacified necrotic retina in a wedge shape, cystoid macular edema in late recirculation; occlusive arteritis with periarteritic infiltrates, venous distention & tortuosity \| OCT: vitritis, inner retinal hyperreflectivity with outer retinal edema acutely, progressing to outer retinal disorganization with persistent inner retinal hyperreflectivity; with resolution of the retinal opacity: atrophic changes will be present, including a schisis cavity, RPE irregularity, and retinal atrophy Ocular conditions associated with myelination of the RNFL Myelination of the RNFL is often associated with anisometropia, strabismus, amblyopia and many other ocular conditions. In one review, strabismus (exotropia and esotropia) was found in 66% of patients with myelination of the RNFL. If a sufficient number of myelinated nerve fibers are present, a visual field deficit smaller than the size of the myelination can be present. If the myelination of the RNFL involves the optic nerve, blind spot enlargement may result. Similarly, myelinated RNFL patches surrounding the macula may result in ring scotomas. Isolated peripheral scotomas corresponding to the location of the myelinated nerve fiber patch may also be seen. Visual acuity and prognosis is variable and depends on the severity of the ocular complications (see Table 2). Treatment is geared toward the complications or associated syndromes (see Management). Table 3. Ocular associations with myelination of the RNFL \| Anterior segment:\| Prominent Schwalbe’s line Congenital cataracts Anterior segment mesenchymal dysgenesis Tilt of the crystalline lens \| Refractive and Sensorimotor: \| Decreased visual acuity \| Optic nerve associated: \| Afferent pupillary deficit Visual field deficits Optic nerve hypoplasia and dysplasia Optic nerve head drusen \| Uveal and Retinal: \| Persistence of the hyaloid artery Uveal coloboma Retinal break in an area of the myelinated RNFL Vitreomacular traction syndrome Epiretinal membrane Extreme photophobia with macular myelination Chroiditis and uveitis Retinal detachment Macular pigment dispersion Macular thickening Retinal vascular complications a. Telangectasias b. Branched retinal artery occlusion c. Branch vein occlusion d. Neovascularization e. Recurrent vitreous hemorrhage There are a few case reports of acquired and progressive myelination in childhood, adolescence, and adulthood. In a young girl with an inoperable arterial venous malformation complicated by chronic papilledema, bilateral optic nerve sheath fenestrations were performed, and the child acquired myelination of the RNFL in the right eye five months after the surgery and in the left eye six years later. In two children with NF1 and ipsilateral optic nerve gliomas, myelinated RNFLs developed without a decrease in visual acuity. One 23 year old male developed striated whitening of the retinal nerve fiber layer after blunt trauma to the eye. A nine year old boy with an Arnold-Chiari malformation and hydrocephalus was described to have progressive retinal nerve fiber layer myelination.One 46 year old woman had decreased vision from progression of a perifoveal MRNFL that was complicated by telangectasias, microaneurysms, and macular thickening that did not respond to argon laser photocoagulation. Table 4. Conditions associated with acquired and progressive myelination of the RNFL \| Blunt trauma \| \|Optic nerve sheath fenestration for chronic papilledema \| \| Optic nerve drusen \| \| Family history of optic nerve hypoplasia (unaffected child)\| \| Arnold-Chiari malformation associated with hydrocephalus\| \| Von Recklinhausen’s disease\| The disappearance of MRNFL has also been reported and associated with multiple neurologic and retinal diseases (see Table 5). Table 5. Conditions associated with loss of myelination of the RNFL \| Neurologic disease\| Optic neuritis Acute optic neuropathy Primary open angle glaucoma \| Inflammatory disease\| Bechet’s disease after recurrent papillitis and vitritis Plaque radiotherapy for choroidal melanoma \| Retinal disease\| Diabetic retinopathy Pars plana vitrectomy for epiretinal membrane When making the initial diagnosis, it is very important to differentiate this typically benign condition from a neoplastic infiltrate. A complete blood count is helpful in making this distinction. Differentiating myelination of the RNFL from an embolic phenomenon can be done with ophthalmoscopy and fluorescein angiography. The management of myelination of the RNFL is focused on following the patient over time and assessing for and treating associated complications. Myopia should be treated fully with glasses. Full correction with glasses will not cause aniseikonia, as dictated by the Knapp rule. If there is significant anisometropia, correction with contact lenses may not be tolerated secondary to aniseikonia. When diagnosed in children, amblyopia must be treated aggressively to optimize visual outcomes. Strabismus should be treated following the usual management protocols, and patients often respond well to surgical realignment. If gross visual defects are noted, formal visual field testing should be done to rule out a concomitant neuro-ophthalmologic issue, as visual field deficits are usually mild. If retinal vascular complications are noted, including neovascularization and vitreous hemorrhage, argon photocoagulation may be required. While typically benign condition, the above mentioned associated conditions and complications require ongoing ophthalmologic care to ensure the best visual and ocular outcomes for patients with myelination of the RNFL. - ↑ Virchow VR. Zur pathologischen anatomic der netzaut und des scherven. Virchows Arch Pathol Anat. 1856;10:170–193. - ↑ Gradle HS. The Blind Spot: III. The Relation of the Blind Spot to Medullated Nerve Fibers in the Retina. Journal of the American Medical Association. 1921;77(19):1483–7. - ↑ 3.0 3.1 Kodama T, Hayasaka S, Setogawa T. Myelinated retinal nerve fibers: prevalence, location and effect on visual acuity. Ophthalmologica. Journal international d’ophtalmologie. International journal of ophthalmology. Zeitschrift für Augenheilkunde. 1990;200(2):77–83. Available at: http://www.ncbi.nlm.nih.gov/pubmed/2338989. - ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 Straatsma BR, Foos RY, Heckenlively JR, Taylor GN. Myelinated retinal nerve fibers. American journal of ophthalmology. 1981;91(1):25–38. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7234927. - ↑ 5.0 5.1 Funnell CL, George NDL, Pai V. Familial myelinated retinal nerve fibres. Eye (London, England). 2003;17(1):96–7. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12579180. - ↑ Naghib J. Triad of myelinated retinal nerve fibers, axial myopia and amblyopia. Journal of ophthalmic & vision research. 2010;5(4):284–5. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3381089&tool=pmcentrez&rendertype=abstract. - ↑ 7.0 7.1 7.2 7.3 7.4 Straatsma BR, Heckenlively JR, Foos RY, Shahinian JK. Myelinated retinal nerve fibers associated with ipsilateral myopia, amblyopia, and strabismus. American journal of ophthalmology. 1979;88(3 Pt 1):506–10. Available at: http://www.ncbi.nlm.nih.gov/pubmed/484678. - ↑ 8.0 8.1 8.2 8.3 Magoon EH, Robb RM. Development of Myelin in Human Optic Nerve and Tract: A Light and Electron Microscopic Study. Archives of Ophthalmology. 1981;99(4):655–659. Available at: http://archopht.jamanetwork.com/article.aspx?articleid=633760. - ↑ 9.0 9.1 9.2 9.3 9.4 9.5 FitzGibbon T, Nestorovski Z. Morphological consequences of myelination in the human retina. Experimental eye research. 1997;65(6):809–19. Available at: http://www.ncbi.nlm.nih.gov/pubmed/9441705. - ↑ 10.0 10.1 Richardson WD, Kessaris N, Pringle N. Oligodendrocyte wars. Nature reviews. Neuroscience. 2006;7(1):11–8. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16371946. - ↑ Tsai H-H. Netrin 1 mediates spinal cord oligodendrocyte precursor dispersal. Development. 2003; 130(10):29095-2105. - ↑ Tsai H-H, Frost E, To V, et al. The chemokine receptor CSCr2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. Cell. 2002; 110(3):373-83. - ↑ 13.0 13.1 Wegner M. A matter of identity: transcriptional control in oligodendrocytes. Journal of molecular neuroscience : MN. 2008;35(1):3–12. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18401762. - ↑ 14.0 14.1 Berliner ML. Cytologic studies on the retina. Normal coexistence of oligodendroglia and myelinated nerve fibres. Arch. Ophthalmol. 1931;(6):740. - ↑ 15.0 15.1 Perry VH, Lund RD. Evidence that the lamina cribrosa prevents intraretinal myelination of retinal ganglion cell axons. Journal of neurocytology. 1990;19(2):265–72. Available at: http://www.ncbi.nlm.nih.gov/pubmed/2358833. - ↑ Vaney DI. A quantitative comparison between the ganglion cell populations and axonal outflows of the visual streak and periphery of the rabbit retina. The Journal of comparative neurology. 1980;189(2):215–33. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7364963. - ↑ Butt AM, Ransom BR. Morphology of astrocytes and oligodendrocytes during development in the intact rat optic nerve. The Journal of comparative neurology. 1993;338(1):141–58. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8300897. - ↑ Howng SYB, Avila RL, Emery B, et al. ZFP191 is required by oligodendrocytes for CNS myelination. Genes & development. 2010;24(3):301–11. Available at: http://genesdev.cshlp.org/content/24/3/301.long. - ↑ Francois J. Myelinated nerve fibres. In: Heredity in Ophthalmology. St Louis, MO: Mosby; 1961:494–496. - ↑ 20.0 20.1 Bozkurt B, Yildirim MS, Okka M, Bitirgen G. GAPO syndrome: four new patients with congenital glaucoma and myelinated retinal nerve fiber layer. American journal of medical genetics. Part A. 2013;161(4):829–34. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23494824. - ↑ 21.0 21.1 21.2 Traboulsi EI, Lim JI, Pyeritz R, Goldberg HK, Haller JA. A new syndrome of myelinated nerve fibers, vitreoretinopathy, and skeletal malformations. Archives of ophthalmology. 1993;111(11):1543–5. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8240111. - ↑ 22.0 22.1 22.2 De Jong PT, Bistervels B, Cosgrove J, de Grip G, Leys A, Goffin M. Medullated nerve fibers. A sign of multiple basal cell nevi (Gorlin’s) syndrome. Archives of ophthalmology. 1985;103(12):1833–6. Available at: http://www.ncbi.nlm.nih.gov/pubmed/4074174. - ↑ 23.0 23.1 23.2 Aaby AA, Kushner BJ. Acquired and progressive myelinated nerve fibers. Archives of ophthalmology. 1985;103:542–544 - ↑ 24.0 24.1 24.2 24.3 24.4 24.5 Kiso K. Beitrage zur Kenntis von der Vererbung der markhaltigen Sehnervenfasern der netzhaut. Graefes Arch Clin Exp Ophthalmol. 1928;120:154–174. - ↑ Schaffer D. Congenital abnormalities of retina. In: Tasman W, ed. Duane’s Ophthalmology. Philadelphia: Lippincott Raven; 1995:5–6. - ↑ 26.0 26.1 Parulekar M V, Elston JS. Acquired retinal myelination in neurofibromatosis 1. Archives of ophthalmology. 2002;120(5):659–5. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12003622. - ↑ 27.0 27.1 27.2 27.3 27.4 Ali BH, Logani S, Kozlov KL, Arnold AC, Bateman B. Progression of retinal nerve fiber myelination in childhood. American Journal of Ophthalmology. 1994;118:515–517. - ↑ Shelton JB, Digre KB, Gilman J, Warner JEA, Katz BJ. Characteristics of myelinated retinal nerve fiber layer in ophthalmic imaging: findings on autofluorescence, fluorescein angiographic, infrared, optical coherence tomographic, and red-free images. JAMA ophthalmology. 2013;131(1):107–9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23307221. - ↑ Ioannides A, Georgakarakos ND, Elaroud I, Andreou P. Isolated cotton-wool spots of unknown etiology: management and sequential spectral domain optical coherence tomography documentation. Clinical ophthalmology (Auckland, N.Z.). 2011;5:1431–3. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3198419&tool=pmcentrez&rendertype=abstract. - ↑ Shah VA, Wallace B, Sabates NR. Spectral domain optical coherence tomography findings of acute branch retinal artery occlusion from calcific embolus. Indian J Ophthalmol. 2010 Nov-Dec; 58(6): 523–524. PMCID: PMC2993984 - ↑ Legarreta JE, Gregori G, Knighton RW, Punjabi OS, Lalwani GA, Puliafito CA. Three-dimensional spectral-domain optical coherence tomography images of the retina in the presence of epiretinal membranes. American journal of ophthalmology. 2008;145(6):1023–1030. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18342830. - ↑ Shinojima A, Yuzawa M. Morphological Changes of Retinal Pigment Epithelial Detachment in Central Serous Chorioretinopathy. In: Liu DG, ed. Selected Topics in Optical Coherence Tomography. InTech; 2012. Available at: ht tp://www.intechopen.com/books/selected-topics-in- optical-coherence-tomography/morphological-changes- of-retinal-pigment-epithelial-detachment-in-central - serous-chorioretinopathy. - ↑ Parodi MB, Saviano S, Bondel E, et al. Hyperfluorescence associated with serous retinal pigment epithelial detachment on indocyanine green angiography. Acta Ophthalmologica Scandinavica. 2000;78(4):443–447. Available at: http://www.blackwell-synergy.com/links/doi/10.1034/j.1600-0420.2000.078004443.x. - ↑ Ortiz JM, Ruiz-Moreno JM, Pozo-Martos P, Montero JA. Visual acuity loss and OCT changes as initial signs of leukaemia. International journal of ophthalmology. 2010;3(3):281–2. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3340619&tool=pmcentrez&rendertype=abstract. - ↑ Rootman DB, Gonzalez E, Mallipatna A, et al. Hand-held high-resolution spectral domain optical coherence tomography in retinoblastoma: clinical and morphologic considerations. The British journal of ophthalmology. 2013;97(1):59–65. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23104902. - ↑ Yeh S, Wong WT, Weichel ED, Lew JC, Chew EY, Nussenblatt RB. Fundus Autofluorescence and OCT in the Management of Progressive Outer Retinal Necrosis. Ophthalmic surgery, lasers & imaging: the official journal of the International Society for Imaging in the Eye. 2010:1–4. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3265678&tool=pmcentrez&rendertype=abstract. - ↑ 37.0 37.1 37.2 Miller NR. Clinical neuro-ophthalmology. 4th ed. (Wilkins W and, ed.). Baltimore; 1982:367–9. - ↑ 38.0 38.1 38.2 Williams TD. Medullated retinal nerve fibers: speculations on their cause and presentation of cases. American journal of optometry and physiological optics. 1986;63(2):142–51. Available at: http://www.ncbi.nlm.nih.gov/pubmed/3953757. - ↑ 39.0 39.1 Duke-Elder S. Congenital deformities. In: Duke-Elder S, ed. St. Louis: Mosby, CV; 1963:646–651. - ↑ Hittner HM, Kretzer FL, Antoszyk JH, Ferrell RE, Mehta RS. Variable expressivity of autosomal dominant anterior segment mesenchymal dysgenesis in six generations. American journal of ophthalmology. 1982;93(1):57–70. Available at: http://www.ncbi.nlm.nih.gov/pubmed/6801987. - ↑ Schmidt D, Meyer JH, Brandi-Dohrn J. Wide-spread myelinated nerve fibers of the optic disc: do they influence the development of myopia? International ophthalmology. 20(5):263–8. Available at: http://www.ncbi.nlm.nih.gov/pubmed/9112197. - ↑ 42.0 42.1 Ellis GS, Frey T, Gouterman RZ. Myelinated nerve fivers, axial myopia, and refractory amblyopia: an organic disease. Journal of pediatric ophthalmology and strabismus. 24(3):111-9. - ↑ Cockburn DM. Tilted disc and medullated nerve fibres. American journal of optometry and physiological optics. 1982;59(9):760–1. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7137318. - ↑ Merritt JC. Myelinated nerve fibers associated with afferent pupillary defect and amblyopia. Journal of pediatric ophthalmology. 14(3):139–40. Available at: http://www.ncbi.nlm.nih.gov/pubmed/915641. - ↑ 45.0 45.1 45.2 Jean-Louis G, Katz BJ, Digre KB, Warner JE, Creger DD. Acquired and progressive retinal nerve fiber layer myelination in an adolescent. American journal of ophthalmology. 2000;130(3):361–2. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11020421. - ↑ Eide N. Retinal break in an area with medullated nerve fibres. Acta ophthalmologica. 1986;64(3):271–3. Available at: http://www.ncbi.nlm.nih.gov/pubmed/3751515. - ↑ Hubbard GB, Thomas MA, Grossniklaus HE. Vitreomacular traction syndrome with extensively myelinated nerve fibers. Archives of ophthalmology. 2002;120(5):670–1. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12003629. - ↑ Karadimas P, Kapetanios A, Panayotidhou E, Bouzas EA. Epiretinal membrane occurring with myelinated retinal nerve fibers and vascular abnormalities. Retina (Philadelphia, Pa.). 2003;23(6):880–1. Available at: http://www.ncbi.nlm.nih.gov/pubmed/14707848. - ↑ Kreidl KO, Lin DY, Egbert JE. Myelination of the macula associated with disabling photophobia. Archives of ophthalmology. 2003;121(8):1204–5. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12912705. - ↑ 50.0 50.1 BERLINER ML. MEDULLATED NERVE FIBERS ASSOCIATED WITH CHOROIDITIS: REPORT OF A CASE WITH PRELIMINARY STUDIES ON THE CAUSE OF THE APPEARANCE OF MEDULLATED NERVE FIBERS IN THE RETINA. Archives of Ophthalmology. 1931;6(3):404–413. Available at: http://archopht.jamanetwork.com/article.aspx?articleid=609280. - ↑ Jackson E. Uveitis with opaque optic nerve fibers. Am. J. Ophthal. 1918;1(448). - ↑ 52.0 52.1 Rosen B, Barry C, Constable IJ. Progression of myelinated retinal nerve fibers. American Journal of Ophthalmology. 1999;127(4):471–473. Available at: http://dx.doi.org/10.1016/S0002-9394(98)00377-8. - ↑ Mehta JS, Raman J, Gupta N, Sinha A. Retinal vascular anomalies in acquired myelinated nerve fibres. Acta ophthalmologica Scandinavica. 2003;81(3):311–2. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12780415. - ↑ 54.0 54.1 54.2 Leys AM, Leys MJ, Hooymans JM, et al. Myelinated nerve fibers and retinal vascular abnormalities. Retina (Philadelphia, Pa.). 1996;16(2):89–96. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8724950. - ↑ 55.0 55.1 Silvestri G, Sehmi K, Hamilton P. Retinal vascular abnormalities. A rare complication of myelinated nerve fibers? Retina (Philadelphia, Pa.). 1996;16(3):214–8. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8789859. - ↑ 56.0 56.1 Kushner BJ. Optic nerve decompression. Arch Ophthalmol. 1979;97:1459–1461. - ↑ 57.0 57.1 Baarsma GS. Acquired medullated nerve fibres. The British journal of ophthalmology. 1980;64(9):651. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1043786&tool=pmcentrez&rendertype=abstract. - ↑ A. S. Schwund Markhaltiger Nervenfasern in der Netzhaut bei intzundlicher Atrophie des Sehnervern in Folges eines Tumor oerebri. Z. Augenheilkd. 1905;13:739–50. - ↑ Gupta A, Khandalavala B, Bansal RK, Jain IS, Grewal SP. Atrophy of myelinated nerve fibers in pituitary adenoma. Journal of clinical neuro-ophthalmology. 1990;10(2):100–2. Available at: http://www.ncbi.nlm.nih.gov/pubmed/2141848. - ↑ Sharpe JA, Sanders MD. Atrophy of myelinated nerve fibres in the retina in optic neuritis. The British journal of ophthalmology. 1975;59(4):229–32. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1042599&tool=pmcentrez&rendertype=abstract. - ↑ Schachat AP, Miller NR. Atrophy of myelinated retinal nerve fibers after acute optic neuropathy. American journal of ophthalmology. 1981;92(6):854–6. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7315937. - ↑ Katz SE, Weber PA. Photographic documentation of the loss of medullated nerve fibers of the retina in uncontrolled primary open angle glaucoma. Journal of glaucoma. 1996;5(6):406–9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8946297. - ↑ Chavis PS, Tabbara KF. Demyelination of retinal myelinated nerve fibers in Behcet’s disease. Documenta ophthalmologica. Advances in ophthalmology. 1998;95(2):157–64. Available at: http://www.ncbi.nlm.nih.gov/pubmed/10431799. - ↑ Mashayekhi A, Shields CL, Shields JA. Disappearance of retinal myelinated nerve fibers after plaque radiotherapy for choroidal melanoma. Retina (Philadelphia, Pa.). 2003;23(4):572–3. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12972781. - ↑ Teich SA. Disappearance of myelinated retinal nerve fibers after a branch retinal artery occlusion. American journal of ophthalmology. 1987;103(6):835–7. Available at: http://www.ncbi.nlm.nih.gov/pubmed/3591888. - ↑ R. B. Schwund markhaltiger Nervenfasern in der Netzhaut nach Embolie der Art. Centralies retinae. Albrecht von Graefes Arch. Ophthalmol. 1922;107(10). - ↑ Gentile RC, Torqueti-Costa L, Bertolucci A. Loss of myelinated retinal nerve fibres in diabetic retinopathy. The British journal of ophthalmology. 2002;86(12):1447. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1771408&tool=pmcentrez&rendertype=abstract. - ↑ Williams AJ, Fekrat S. Disappearance of myelinated retinal nerve fibers after pars plana vitrectomy. American journal of ophthalmology. 2006;142(3):521–3. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16935613. The authors thank Penny Coppernoll-Blach and the UCSD Library staff for their help in facilitating the literature review necessary for this paper. Special thanks to Giulio Barteselli and Gabriel Balea for the ophthalmic photography presented here.	2	6	2	1	2	0.436427	5	9,546
\|Synonyms\|\|Tumor, tumour, carcinocytes\| \|Colectomy specimen containing a malignant neoplasm, namely an invasive colorectal cancer (the crater-like, reddish, irregularly shaped tumor)\| ICD-10 classifies neoplasms into four main groups: benign neoplasms, in situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior. Malignant neoplasms are also simply known as cancers and are the focus of oncology. Prior to the abnormal growth of tissue, as neoplasia, cells often undergo an abnormal pattern of growth, such as metaplasia or dysplasia. However, metaplasia or dysplasia does not always progress to neoplasia. The word is from Ancient Greek νέος- neo "new" and πλάσμα plasma "formation, creation". \|-plasia and -trophy\| - Benign tumors include uterine fibroids and melanocytic nevi (skin moles). They are circumscribed and localized and do not transform into cancer. - Potentially-malignant neoplasms include carcinoma in situ. They are localised, do not invade and destroy but in time, may transform into a cancer. - Malignant neoplasms are commonly called cancer. They invade and destroy the surrounding tissue, may form metastases and, if untreated or unresponsive to treatment, will prove fatal. - Secondary neoplasm refers to any of a class of cancerous tumor that is either a metastatic offshoot of a primary tumor, or an apparently unrelated tumor that increases in frequency following certain cancer treatments such as chemotherapy or radiotherapy. - Rarely there can be a metastatic neoplasm with no known site of the primary cancer and this is classed as a cancer of unknown primary origin Neoplastic tumors are often heterogeneous and contain more than one type of cell, but their initiation and continued growth is usually dependent on a single population of neoplastic cells. These cells are presumed to be clonal – that is, they are derived from the same cell, and all carry the same genetic or epigenetic anomaly – evident of clonality. For lymphoid neoplasms, e.g. lymphoma and leukemia, clonality is proven by the amplification of a single rearrangement of their immunoglobulin gene (for B cell lesions) or T cell receptor gene (for T cell lesions). The demonstration of clonality is now considered to be necessary to identify a lymphoid cell proliferation as neoplastic. It is tempting to define neoplasms as clonal cellular proliferations but the demonstration of clonality is not always possible. Therefore, clonality is not required in the definition of neoplasia. Neoplasia vs. tumor Tumor (American English) or tumour (British English), Latin for swelling, one of the cardinal signs of inflammation, originally meant any form of swelling, neoplastic or not. Current English, however, both medical and non-medical, uses tumor as a synonym for a neoplasm (a solid or fluid-filled cystic lesion that may or may not be formed by an abnormal growth of neoplastic cells) that appears enlarged in size. Some neoplasms do not form a tumor; these include leukemia and most forms of carcinoma in situ. Tumor is also not synonymous with cancer. While cancer is by definition malignant, a tumor can be benign, precancerous, or malignant. The terms mass and nodule are often used synonymously with tumor. Generally speaking, however, the term tumor is used generically, without reference to the physical size of the lesion. More specifically, the term mass is often used when the lesion has a maximal diameter of at least 20 millimeters (mm) in greatest direction, while the term nodule is usually used when the size of the lesion is less than 20 mm in its greatest dimension (25.4 mm = 1 inch). A neoplasm can be caused by an abnormal proliferation of tissues, which can be caused by genetic mutations. Not all types of neoplasms cause a tumorous overgrowth of tissue, however (such as leukemia or carcinoma in situ). Recently, tumor growth has been studied using mathematics and continuum mechanics. Vascular tumors (formed from blood vessels) are thus looked at as being amalgams of a solid skeleton formed by sticky cells and an organic liquid filling the spaces in which cells can grow. Under this type of model, mechanical stresses and strains can be dealt with and their influence on the growth of the tumor and the surrounding tissue and vasculature elucidated. Recent findings from experiments that use this model show that active growth of the tumor is restricted to the outer edges of the tumor, and that stiffening of the underlying normal tissue inhibits tumor growth as well. Benign conditions that are not associated with an abnormal proliferation of tissue (such as sebaceous cysts) can also present as tumors, however, but have no malignant potential. Breast cysts (as occur commonly during pregnancy and at other times) are another example, as are other encapsulated glandular swellings (thyroid, adrenal gland, pancreas). Encapsulated hematomas, encapsulated necrotic tissue (from an insect bite, foreign body, or other noxious mechanism), keloids (discrete overgrowths of scar tissue) and granulomas may also present as tumors. Discrete localized enlargements of normal structures (ureters, blood vessels, intrahepatic or extrahepatic biliary ducts, pulmonary inclusions, or gastrointestinal duplications) due to outflow obstructions or narrowings, or abnormal connections, may also present as a tumor. Examples are arteriovenous fistulae or aneurysms (with or without thrombosis), biliary fistulae or aneurysms, sclerosing cholangitis, cysticercosis or hydatid cysts, intestinal duplications, and pulmonary inclusions as seen with cystic fibrosis. It can be dangerous to biopsy a number of types of tumor in which the leakage of their contents would potentially be catastrophic. When such types of tumors are encountered, diagnostic modalities such as ultrasound, CT scans, MRI, angiograms, and nuclear medicine scans are employed prior to (or during) biopsy or surgical exploration/excision in an attempt to avoid such severe complications. DNA damage is considered to be the primary underlying cause of malignant neoplasms known as cancers. Its central role in progression to cancer is illustrated in the figure in this section, in the box near the top. (The central features of DNA damage, epigenetic alterations and deficient DNA repair in progression to cancer are shown in red.) DNA damage is very common. Naturally occurring DNA damages (mostly due to cellular metabolism and the properties of DNA in water at body temperatures) occur at a rate of more than 60,000 new damages, on average, per human cell, per day [also see article DNA damage (naturally occurring) ]. Additional DNA damages can arise from exposure to exogenous agents. Tobacco smoke causes increased exogenous DNA damage, and these DNA damages are the likely cause of lung cancer due to smoking. UV light from solar radiation causes DNA damage that is important in melanoma. Helicobacter pylori infection produces high levels of reactive oxygen species that damage DNA and contributes to gastric cancer. Bile acids, at high levels in the colons of humans eating a high fat diet, also cause DNA damage and contribute to colon cancer. Katsurano et al. indicated that macrophages and neutrophils in an inflamed colonic epithelium are the source of reactive oxygen species causing the DNA damages that initiate colonic tumorigenesis. Some sources of DNA damage are indicated in the boxes at the top of the figure in this section. Individuals with a germ line mutation causing deficiency in any of 34 DNA repair genes (see article DNA repair-deficiency disorder) are at increased risk of cancer. Some germ line mutations in DNA repair genes cause up to 100% lifetime chance of cancer (e.g., p53 mutations). These germ line mutations are indicated in a box at the left of the figure with an arrow indicating their contribution to DNA repair deficiency. About 70% of malignant neoplasms have no hereditary component and are called "sporadic cancers". Only a minority of sporadic cancers have a deficiency in DNA repair due to mutation in a DNA repair gene. However, a majority of sporadic cancers have deficiency in DNA repair due to epigenetic alterations that reduce or silence DNA repair gene expression. For example, of 113 sequential colorectal cancers, only four had a missense mutation in the DNA repair gene MGMT, while the majority had reduced MGMT expression due to methylation of the MGMT promoter region (an epigenetic alteration). Five reports present evidence that between 40% and 90% of colorectal cancers have reduced MGMT expression due to methylation of the MGMT promoter region. Similarly, out of 119 cases of mismatch repair-deficient colorectal cancers that lacked DNA repair gene PMS2 expression, PMS2 was deficient in 6 due to mutations in the PMS2 gene, while in 103 cases PMS2 expression was deficient because its pairing partner MLH1 was repressed due to promoter methylation (PMS2 protein is unstable in the absence of MLH1). In the other 10 cases, loss of PMS2 expression was likely due to epigenetic overexpression of the microRNA, miR-155, which down-regulates MLH1. In further examples, epigenetic defects were found at frequencies of between 13%-100% for the DNA repair genes BRCA1, WRN, FANCB, FANCF, MGMT, MLH1, MSH2, MSH4, ERCC1, XPF, NEIL1 and ATM. These epigenetic defects occurred in various cancers (e.g. breast, ovarian, colorectal and head and neck). Two or three deficiencies in expression of ERCC1, XPF or PMS2 occur simultaneously in the majority of the 49 colon cancers evaluated by Facista et al. Epigenetic alterations causing reduced expression of DNA repair genes is shown in a central box at the third level from the top of the figure in this section, and the consequent DNA repair deficiency is shown at the fourth level. When expression of DNA repair genes is reduced, DNA damages accumulate in cells at a higher than normal level, and these excess damages cause increased frequencies of mutation or epimutation. Mutation rates strongly increase in cells defective in DNA mismatch repair or in homologous recombinational repair (HRR). During repair of DNA double strand breaks, or repair of other DNA damages, incompletely cleared sites of repair can cause epigenetic gene silencing. DNA repair deficiencies (level 4 in the figure) cause increased DNA damages (level 5 in the figure) which result in increased somatic mutations and epigenetic alterations (level 6 in the figure). Field defects, normal appearing tissue with multiple alterations (and discussed in the section below), are common precursors to development of the disordered and improperly proliferating clone of tissue in a malignant neoplasm. Such field defects (second level from bottom of figure) may have multiple mutations and epigenetic alterations. Once a cancer is formed, it usually has genome instability. This instability is likely due to reduced DNA repair or excessive DNA damage. Because of such instability, the cancer continues to evolve and to produce sub clones. For example, a renal cancer, sampled in 9 areas, had 40 ubiquitous mutations, demonstrating tumour heterogeneity (i.e. present in all areas of the cancer), 59 mutations shared by some (but not all areas), and 29 “private” mutations only present in one of the areas of the cancer. Various other terms have been used to describe this phenomenon, including "field effect", "field cancerization", and "field carcinogenesis". The term “field cancerization” was first used in 1953 to describe an area or “field” of epithelium that has been preconditioned by (at that time) largely unknown processes so as to predispose it towards development of cancer. Since then, the terms “field cancerization” and “field defect” have been used to describe pre-malignant tissue in which new cancers are likely to arise. Field defects are important in progression to cancer. However, in most cancer research, as pointed out by Rubin “The vast majority of studies in cancer research has been done on well-defined tumors in vivo, or on discrete neoplastic foci in vitro. Yet there is evidence that more than 80% of the somatic mutations found in mutator phenotype human colorectal tumors occur before the onset of terminal clonal expansion. Similarly, Vogelstein et al. point out that more than half of somatic mutations identified in tumors occurred in a pre-neoplastic phase (in a field defect), during growth of apparently normal cells. Likewise, epigenetic alterations present in tumors may have occurred in pre-neoplastic field defects. An expanded view of field effect has been termed "etiologic field effect", which encompasses not only molecular and pathologic changes in pre-neoplastic cells but also influences of exogenous environmental factors and molecular changes in the local microenvironment on neoplastic evolution from tumor initiation to patient death. In the colon, a field defect probably arises by natural selection of a mutant or epigenetically altered cell among the stem cells at the base of one of the intestinal crypts on the inside surface of the colon. A mutant or epigenetically altered stem cell may replace the other nearby stem cells by natural selection. Thus, a patch of abnormal tissue may arise. The figure in this section includes a photo of a freshly resected and lengthwise-opened segment of the colon showing a colon cancer and four polyps. Below the photo there is a schematic diagram of how a large patch of mutant or epigenetically altered cells may have formed, shown by the large area in yellow in the diagram. Within this first large patch in the diagram (a large clone of cells), a second such mutation or epigenetic alteration may occur so that a given stem cell acquires an advantage compared to other stem cells within the patch, and this altered stem cell may expand clonally forming a secondary patch, or sub-clone, within the original patch. This is indicated in the diagram by four smaller patches of different colors within the large yellow original area. Within these new patches (sub-clones), the process may be repeated multiple times, indicated by the still smaller patches within the four secondary patches (with still different colors in the diagram) which clonally expand, until stem cells arise that generate either small polyps or else a malignant neoplasm (cancer). In the photo, an apparent field defect in this segment of a colon has generated four polyps (labeled with the size of the polyps, 6mm, 5mm, and two of 3mm, and a cancer about 3 cm across in its longest dimension). These neoplasms are also indicated, in the diagram below the photo, by 4 small tan circles (polyps) and a larger red area (cancer). The cancer in the photo occurred in the cecal area of the colon, where the colon joins the small intestine (labeled) and where the appendix occurs (labeled). The fat in the photo is external to the outer wall of the colon. In the segment of colon shown here, the colon was cut open lengthwise to expose the inner surface of the colon and to display the cancer and polyps occurring within the inner epithelial lining of the colon. If the general process by which sporadic colon cancers arise is the formation of a pre-neoplastic clone that spreads by natural selection, followed by formation of internal sub-clones within the initial clone, and sub-sub-clones inside those, then colon cancers generally should be associated with, and be preceded by, fields of increasing abnormality reflecting the succession of premalignant events. The most extensive region of abnormality (the outermost yellow irregular area in the diagram) would reflect the earliest event in formation of a malignant neoplasm. In experimental evaluation of specific DNA repair deficiencies in cancers, many specific DNA repair deficiencies were also shown to occur in the field defects surrounding those cancers. The Table, below, gives examples for which the DNA repair deficiency in a cancer was shown to be caused by an epigenetic alteration, and the somewhat lower frequencies with which the same epigenetically caused DNA repair deficiency was found in the surrounding field defect. \|Cancer\|\|Gene\|\|Frequency in Cancer\|\|Frequency in Field Defect\|\|Ref.\| \|Head and Neck\|\|MGMT\|\|54%\|\|38%\|\|\| \|Head and Neck\|\|MLH1\|\|33%\|\|25%\|\|\| \|Head and Neck\|\|MLH1\|\|31%\|\|20%\|\|\| Some of the small polyps in the field defect shown in the photo of the opened colon segment may be relatively benign neoplasms. Of polyps less than 10mm in size, found during colonoscopy and followed with repeat colonoscopies for 3 years, 25% were unchanged in size, 35% regressed or shrank in size while 40% grew in size. Cancers are known to exhibit genome instability or a mutator phenotype. The protein-coding DNA within the nucleus is about 1.5% of the total genomic DNA. Within this protein-coding DNA (called the exome), an average cancer of the breast or colon can have about 60 to 70 protein altering mutations, of which about 3 or 4 may be “driver” mutations, and the remaining ones may be “passenger” mutations However, the average number of DNA sequence mutations in the entire genome (including non-protein-coding regions) within a breast cancer tissue sample is about 20,000. In an average melanoma tissue sample (where melanomas have a higher exome mutation frequency) the total number of DNA sequence mutations is about 80,000. This compares to the very low mutation frequency of about 70 new mutations in the entire genome between generations (parent to child) in humans. The high frequencies of mutations in the total nucleotide sequences within cancers suggest that often an early alteration in the field defects giving rise to a cancer (e.g. yellow area in the diagram in this section) is a deficiency in DNA repair. The large field defects surrounding colon cancers (extending to at about 10 cm on each side of a cancer) were shown by Facista et al. to frequently have epigenetic defects in 2 or 3 DNA repair proteins (ERCC1, XPF or PMS2) in the entire area of the field defect. Deficiencies in DNA repair cause increased mutation rates. A deficiency in DNA repair, itself, can allow DNA damages to accumulate, and error-prone translesion synthesis past some of those damages may give rise to mutations. In addition, faulty repair of these accumulated DNA damages may give rise to epimutations. These new mutations or epimutations may provide a proliferative advantage, generating a field defect. Although the mutations/epimutations in DNA repair genes do not, themselves, confer a selective advantage, they may be carried along as passengers in cells when the cells acquire additional mutations/epimutations that do provide a proliferative advantage. The term tumor is derived from the Latin noun tumor "a swelling" ultimately from the verb tumēre "to swell". In the Commonwealth the spelling "tumour" is commonly used, whereas in the U.S. it is usually spelled "tumor". In its medical sense it has traditionally meant an abnormal swelling of the flesh. The Roman medical encyclopedist Celsus (ca 30 BC–38 AD) described the four cardinal signs of acute inflammation as tumor, dolor, calor, and rubor (swelling, pain, increased heat, and redness). His treatise, De Medicina, was the first medical book printed in 1478 following the invention of the movable-type printing press. In contemporary English, the word tumor is often used as a synonym for a cystic (liquid-filled) growth or solid neoplasm (cancerous or non-cancerous), with other forms of swelling often referred to as swellings. Related terms are common in the medical literature, where the nouns tumefaction and tumescence (derived from the adjective tumefied), are current medical terms for non-neoplastic swelling. This type of swelling is most often caused by inflammation caused by trauma, infection, and other factors. Tumors may be caused by conditions other than an overgrowth of neoplastic cells, however. Cysts (such as sebaceous cysts) are also referred to as tumors, even though they have no neoplastic cells. This is standard in medical billing terminology (especially when billing for a growth whose pathology has yet to be determined). - Birbrair A, Zhang T, Wang ZM, Messi ML, Olson JD, Mintz A, Delbono O (Jul 2014). "Type-2 pericytes participate in normal and tumoral angiogenesis". American Journal of Physiology. Cell Physiology. 307 (1): C25–38. PMC . PMID 24788248. doi:10.1152/ajpcell.00084.2014. - Cooper GM (1992). Elements of human cancer. Boston: Jones and Bartlett Publishers. p. 16. ISBN 978-0-86720-191-8. - Taylor, Elizabeth J. (2000). Dorland's Illustrated medical dictionary. (29th ed.). Philadelphia: Saunders. p. 1184. ISBN 0721662544. - Stedman's medical dictionary (28th ed.). Philadelphia: Lippincott Williams & Wilkins. 2006. p. Neoplasm. ISBN 0781733901. - "II Neoplasms". World Health Organization. Retrieved 19 June 2014. - Abrams, Gerald. "Neoplasia I". Retrieved 23 January 2012. - "Cancer - Activity 1 - Glossary, page 4 of 5". Retrieved 2008-01-08. - Clone definition - Medical Dictionary definitions of popular medical terms easily defined on MedTerms - Lee ES, Locker J, Nalesnik M, Reyes J, Jaffe R, Alashari M, Nour B, Tzakis A, Dickman PS (January 1995). "The association of Epstein-Barr virus with smooth-muscle tumors occurring after organ transplantation". N. Engl. J. Med. 332 (1): 19–25. PMID 7990861. doi:10.1056/NEJM199501053320104. - "Pancreas Cancer: Glossary of Terms". Retrieved 2008-01-08. - "Tumor". Dorland's Illustrated Medical Dictionary (31st ed.). Saunders. 2007. ISBN 978-1-84972-348-0. - Birbrair A, Zhang T, Wang ZM, Messi ML, Olson JD, Mintz A, Delbono O (Jul 2014). "Type-2 pericytes participate in normal and tumoral angiogenesis". American Journal of Physiology. Cell Physiology. 307 (1): C25–38. PMC . PMID 24788248. doi:10.1152/ajpcell.00084.2014. - Ambrosi D, Mollica F (2002). "On the mechanics of a growing tumor". International Journal of Engineering Science. 40 (12): 1297–316. doi:10.1016/S0020-7225(02)00014-9. - Volokh KY (September 2006). "Stresses in growing soft tissues". Acta Biomater. 2 (5): 493–504. PMID 16793355. doi:10.1016/j.actbio.2006.04.002. - Bernstein C, Prasad AR, Nfonsam V, Bernstei H (2013). "DNA Damage, DNA Repair and Cancer". New Research Directions in DNA Repair. pp. 413–65. ISBN 978-953-51-1114-6. doi:10.5772/53919. - Kastan MB (2008). "DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture". Mol. Cancer Res. 6 (4): 517–24. PMID 18403632. doi:10.1158/1541-7786.MCR-08-0020. - Cunningham FH, Fiebelkorn S, Johnson M, Meredith C (November 2011). "A novel application of the Margin of Exposure approach: segregation of tobacco smoke toxicants". Food Chem. Toxicol. 49 (11): 2921–33. PMID 21802474. doi:10.1016/j.fct.2011.07.019. - Kanavy HE, Gerstenblith MR (December 2011). "Ultraviolet radiation and melanoma". Semin Cutan Med Surg. 30 (4): 222–8. PMID 22123420. doi:10.1016/j.sder.2011.08.003. - Handa O, Naito Y, Yoshikawa T (2011). "Redox biology and gastric carcinogenesis: the role of Helicobacter pylori". Redox Rep. 16 (1): 1–7. PMID 21605492. doi:10.1179/174329211X12968219310756. - Bernstein C, Holubec H, Bhattacharyya AK, Nguyen H, Payne CM, Zaitlin B, Bernstein H (August 2011). "Carcinogenicity of deoxycholate, a secondary bile acid". Arch. Toxicol. 85 (8): 863–71. PMC . PMID 21267546. doi:10.1007/s00204-011-0648-7. - Katsurano M, Niwa T, Yasui Y, Shigematsu Y, Yamashita S, Takeshima H, Lee MS, Kim YJ, Tanaka T, Ushijima T (January 2012). "Early-stage formation of an epigenetic field defect in a mouse colitis model, and non-essential roles of T- and B-cells in DNA methylation induction". Oncogene. 31 (3): 342–51. PMID 21685942. doi:10.1038/onc.2011.241. - Malkin D (April 2011). "Li-fraumeni syndrome". Genes Cancer. 2 (4): 475–84. PMC . PMID 21779515. doi:10.1177/1947601911413466. - Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K (July 2000). "Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland". N. Engl. J. Med. 343 (2): 78–85. PMID 10891514. doi:10.1056/NEJM200007133430201. - Halford S, Rowan A, Sawyer E, Talbot I, Tomlinson I (June 2005). "O(6)-methylguanine methyltransferase in colorectal cancers: detection of mutations, loss of expression, and weak association with G:C>A:T transitions". Gut. 54 (6): 797–802. PMC . PMID 15888787. doi:10.1136/gut.2004.059535. - Shen L, Kondo Y, Rosner GL, Xiao L, Hernandez NS, Vilaythong J, Houlihan PS, Krouse RS, Prasad AR, Einspahr JG, Buckmeier J, Alberts DS, Hamilton SR, Issa JP (September 2005). "MGMT promoter methylation and field defect in sporadic colorectal cancer". J. Natl. Cancer Inst. 97 (18): 1330–8. PMID 16174854. doi:10.1093/jnci/dji275. - Psofaki V, Kalogera C, Tzambouras N, Stephanou D, Tsianos E, Seferiadis K, Kolios G (July 2010). "Promoter methylation status of hMLH1, MGMT, and CDKN2A/p16 in colorectal adenomas". World J. Gastroenterol. 16 (28): 3553–60. PMC . PMID 20653064. doi:10.3748/wjg.v16.i28.3553. - Lee KH, Lee JS, Nam JH, Choi C, Lee MC, Park CS, Juhng SW, Lee JH (October 2011). "Promoter methylation status of hMLH1, hMSH2, and MGMT genes in colorectal cancer associated with adenoma-carcinoma sequence". Langenbecks Arch Surg. 396 (7): 1017–26. PMID 21706233. doi:10.1007/s00423-011-0812-9. - Amatu A, Sartore-Bianchi A, Moutinho C, Belotti A, Bencardino K, Chirico G, Cassingena A, Rusconi F, Esposito A, Nichelatti M, Esteller M, Siena S (April 2013). "Promoter CpG island hypermethylation of the DNA repair enzyme MGMT predicts clinical response to dacarbazine in a phase II study for metastatic colorectal cancer". Clin. Cancer Res. 19 (8): 2265–72. PMID 23422094. doi:10.1158/1078-0432.CCR-12-3518. - Mokarram P, Zamani M, Kavousipour S, Naghibalhossaini F, Irajie C, Moradi Sarabi M, Hosseini SV (May 2013). "Different patterns of DNA methylation of the two distinct O6-methylguanine-DNA methyltransferase (O6-MGMT) promoter regions in colorectal cancer". Mol. Biol. Rep. 40 (5): 3851–7. PMID 23271133. doi:10.1007/s11033-012-2465-3. - Truninger K, Menigatti M, Luz J, Russell A, Haider R, Gebbers JO, Bannwart F, Yurtsever H, Neuweiler J, Riehle HM, Cattaruzza MS, Heinimann K, Schär P, Jiricny J, Marra G (May 2005). "Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer". Gastroenterology. 128 (5): 1160–71. PMID 15887099. doi:10.1053/j.gastro.2005.01.056. - Valeri N, Gasparini P, Fabbri M, Braconi C, Veronese A, Lovat F, Adair B, Vannini I, Fanini F, Bottoni A, Costinean S, Sandhu SK, Nuovo GJ, Alder H, Gafa R, Calore F, Ferracin M, Lanza G, Volinia S, Negrini M, McIlhatton MA, Amadori D, Fishel R, Croce CM (April 2010). "Modulation of mismatch repair and genomic stability by miR-155". Proc. Natl. Acad. Sci. U.S.A. 107 (15): 6982–7. PMC . PMID 20351277. doi:10.1073/pnas.1002472107. - Facista A, Nguyen H, Lewis C, Prasad AR, Ramsey L, Zaitlin B, Nfonsam V, Krouse RS, Bernstein H, Payne CM, Stern S, Oatman N, Banerjee B, Bernstein C (2012). "Deficient expression of DNA repair enzymes in early progression to sporadic colon cancer". Genome Integr. 3 (1): 3. PMC . PMID 22494821. doi:10.1186/2041-9414-3-3. - Narayanan L, Fritzell JA, Baker SM, Liskay RM, Glazer PM (April 1997). "Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair gene Pms2". Proc. Natl. Acad. Sci. U.S.A. 94 (7): 3122–7. PMC . PMID 9096356. doi:10.1073/pnas.94.7.3122. - Hegan DC, Narayanan L, Jirik FR, Edelmann W, Liskay RM, Glazer PM (December 2006). "Differing patterns of genetic instability in mice deficient in the mismatch repair genes Pms2, Mlh1, Msh2, Msh3 and Msh6". Carcinogenesis. 27 (12): 2402–8. PMC . PMID 16728433. doi:10.1093/carcin/bgl079. - Tutt AN, van Oostrom CT, Ross GM, van Steeg H, Ashworth A (March 2002). "Disruption of Brca2 increases the spontaneous mutation rate in vivo: synergism with ionizing radiation". EMBO Rep. 3 (3): 255–60. PMC . PMID 11850397. doi:10.1093/embo-reports/kvf037. - O'Hagan HM, Mohammad HP, Baylin SB (2008). Lee JT, ed. "Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island". PLoS Genet. 4 (8): e1000155. PMC . PMID 18704159. doi:10.1371/journal.pgen.1000155. - Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Di Pardo A, Messina S, Iuliano R, Fusco A, Santillo MR, Muller MT, Chiariotti L, Gottesman ME, Avvedimento EV (July 2007). "DNA damage, homology-directed repair, and DNA methylation". PLoS Genet. 3 (7): e110. PMC . PMID 17616978. doi:10.1371/journal.pgen.0030110. - Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C (March 2012). "Intratumor heterogeneity and branched evolution revealed by multiregion sequencing". N. Engl. J. Med. 366 (10): 883–92. PMC . PMID 22397650. doi:10.1056/NEJMoa1113205. - Slaughter DP, Southwick HW, Smejkal W (September 1953). "Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin". Cancer. 6 (5): 963–8. PMID 13094644. doi:10.1002/1097-0142(195309)6:5<963::AID-CNCR2820060515>3.0.CO;2-Q. - Bernstein C, Bernstein H, Payne CM, Dvorak K, Garewal H (February 2008). "Field defects in progression to gastrointestinal tract cancers". Cancer Lett. 260 (1–2): 1–10. PMC . PMID 18164807. doi:10.1016/j.canlet.2007.11.027. - Nguyen H, Loustaunau C, Facista A, Ramsey L, Hassounah N, Taylor H, Krouse R, Payne CM, Tsikitis VL, Goldschmid S, Banerjee B, Perini RF, Bernstein C (2010). "Deficient Pms2, ERCC1, Ku86, CcOI in field defects during progression to colon cancer". J Vis Exp (41): 1931. PMC . PMID 20689513. doi:10.3791/1931. - Rubin H (March 2011). "Fields and field cancerization: the preneoplastic origins of cancer: asymptomatic hyperplastic fields are precursors of neoplasia, and their progression to tumors can be tracked by saturation density in culture". BioEssays. 33 (3): 224–31. PMID 21254148. doi:10.1002/bies.201000067. - Tsao JL, Yatabe Y, Salovaara R, Järvinen HJ, Mecklin JP, Aaltonen LA, Tavaré S, Shibata D (February 2000). "Genetic reconstruction of individual colorectal tumor histories". Proc. Natl. Acad. Sci. U.S.A. 97 (3): 1236–41. PMC . PMID 10655514. doi:10.1073/pnas.97.3.1236. - Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW (March 2013). "Cancer genome landscapes". Science. 339 (6127): 1546–58. PMC . PMID 23539594. doi:10.1126/science.1235122. - Lochhead P, Chan AT, Nishihara R, Fuchs CS, Beck AH, Giovannucci E, Ogino S (2014). "Etiologic field effect: reappraisal of the field effect concept in cancer predisposition and progression". Mod Pathol. 28: 14–29. PMC . PMID 24925058. doi:10.1038/modpathol.2014.81. - Svrcek M, Buhard O, Colas C, Coulet F, Dumont S, Massaoudi I, Lamri A, Hamelin R, Cosnes J, Oliveira C, Seruca R, Gaub MP, Legrain M, Collura A, Lascols O, Tiret E, Fléjou JF, Duval A (November 2010). "Methylation tolerance due to an O6-methylguanine DNA methyltransferase (MGMT) field defect in the colonic mucosa: an initiating step in the development of mismatch repair-deficient colorectal cancers". Gut. 59 (11): 1516–26. PMID 20947886. doi:10.1136/gut.2009.194787. - Paluszczak J, Misiak P, Wierzbicka M, Woźniak A, Baer-Dubowska W (February 2011). "Frequent hypermethylation of DAPK, RARbeta, MGMT, RASSF1A and FHIT in laryngeal squamous cell carcinomas and adjacent normal mucosa". Oral Oncol. 47 (2): 104–7. PMID 21147548. doi:10.1016/j.oraloncology.2010.11.006. - Zuo C, Zhang H, Spencer HJ, Vural E, Suen JY, Schichman SA, Smoller BR, Kokoska MS, Fan CY (October 2009). "Increased microsatellite instability and epigenetic inactivation of the hMLH1 gene in head and neck squamous cell carcinoma". Otolaryngol Head Neck Surg. 141 (4): 484–90. PMID 19786217. doi:10.1016/j.otohns.2009.07.007. - Tawfik HM, El-Maqsoud NM, Hak BH, El-Sherbiny YM (2011). "Head and neck squamous cell carcinoma: mismatch repair immunohistochemistry and promoter hypermethylation of hMLH1 gene". Am J Otolaryngol. 32 (6): 528–36. PMID 21353335. doi:10.1016/j.amjoto.2010.11.005. - Zou XP, Zhang B, Zhang XQ, Chen M, Cao J, Liu WJ (November 2009). "Promoter hypermethylation of multiple genes in early gastric adenocarcinoma and precancerous lesions". Hum. Pathol. 40 (11): 1534–42. PMID 19695681. doi:10.1016/j.humpath.2009.01.029. - Wani M, Afroze D, Makhdoomi M, Hamid I, Wani B, Bhat G, Wani R, Wani K (2012). "Promoter methylation status of DNA repair gene (hMLH1) in gastric carcinoma patients of the Kashmir valley". Asian Pac. J. Cancer Prev. 13 (8): 4177–81. PMID 23098428. doi:10.7314/APJCP.2012.13.8.4177. - Agarwal A, Polineni R, Hussein Z, Vigoda I, Bhagat TD, Bhattacharyya S, Maitra A, Verma A (2012). "Role of epigenetic alterations in the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma". Int J Clin Exp Pathol. 5 (5): 382–96. PMC . PMID 22808291. - Hofstad B, Vatn MH, Andersen SN, Huitfeldt HS, Rognum T, Larsen S, Osnes M (September 1996). "Growth of colorectal polyps: redetection and evaluation of unresected polyps for a period of three years". Gut. 39 (3): 449–56. PMC . PMID 8949653. doi:10.1136/gut.39.3.449. - Schmitt MW, Prindle MJ, Loeb LA (September 2012). "Implications of genetic heterogeneity in cancer". Ann. N. Y. Acad. Sci. 1267: 110–6. PMC . PMID 22954224. doi:10.1111/j.1749-6632.2012.06590.x. - Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, et al. (February 2001). "Initial sequencing and analysis of the human genome". Nature. 409 (6822): 860–921. PMID 11237011. doi:10.1038/35057062. - Yost SE, Smith EN, Schwab RB, Bao L, Jung H, Wang X, Voest E, Pierce JP, Messer K, Parker BA, Harismendy O, Frazer KA (August 2012). "Identification of high-confidence somatic mutations in whole genome sequence of formalin-fixed breast cancer specimens". Nucleic Acids Res. 40 (14): e107. PMC . PMID 22492626. doi:10.1093/nar/gks299. - Berger MF, Hodis E, Heffernan TP, Deribe YL, Lawrence MS, Protopopov A, Ivanova E, Watson IR, Nickerson E, Ghosh P, Zhang H, Zeid R, Ren X, Cibulskis K, Sivachenko AY, Wagle N, Sucker A, Sougnez C, Onofrio R, Ambrogio L, Auclair D, Fennell T, Carter SL, Drier Y, Stojanov P, Singer MA, Voet D, Jing R, Saksena G, Barretina J, Ramos AH, Pugh TJ, Stransky N, Parkin M, Winckler W, Mahan S, Ardlie K, Baldwin J, Wargo J, Schadendorf D, Meyerson M, Gabriel SB, Golub TR, Wagner SN, Lander ES, Getz G, Chin L, Garraway LA (May 2012). "Melanoma genome sequencing reveals frequent PREX2 mutations". Nature. 485 (7399): 502–6. PMC . PMID 22622578. doi:10.1038/nature11071. - Roach JC, Glusman G, Smit AF et al. (April 2010). "Analysis of genetic inheritance in a family quartet by whole-genome sequencing". Science. 328 (5978): 636–9. PMC . PMID 20220176. doi:10.1126/science.1186802. - Campbell CD, Chong JX, Malig M et al. (November 2012). "Estimating the human mutation rate using autozygosity in a founder population". Nat. Genet. 44 (11): 1277–81. PMC . PMID 23001126. doi:10.1038/ng.2418. - Tumor in Medical Encyclopedia - "Swelling". MedlinePlus Medical Encyclopedia. October 14, 2012.	2	51	7	1	2	0.327844	10	9,909
411 - Post-COVID Conditions (“Long COVID”), Peds COVID Vaccine PS Take 3 – Practical Practice Pointers© From the CDC and the Literature 1) “Long Covid” – Caring for Persons with Post-COVID Conditions As of June 30, 2021, 33.5 million persons in the United States had received a diagnosis of COVID-19. This does not include the numerous others who never received a diagnosis. Although it appears most patients infected with SARS-CoV-2 recover within a few weeks, some experience ongoing post–COVID-19 symptoms. In June, the CDC issued a set of clinical guidelines addressing treatment of post-COVID conditions, often referred to colloquially as “Long COVID,” which they define as "new, recurring, or ongoing symptoms more than 4 weeks after infection, sometimes after initial symptom recovery" and includes a wide range of physical and mental health concerns. These consequences include both general complications of prolonged illness as well as hospitalization and post-acute sequelae of SARS-CoV-2 infection (PASC), which are more specific to effects of SARS-CoV-2 infection. At present, robust longitudinal surveillance data on post-COVID conditions are lacking and the prevalence is challenging to estimate, ranging from 5% to 80%. It has been challenging to create a single universal case definition for post-COVID conditions because studies differ in terms of the symptoms or conditions investigated, the temporal criteria used (three weeks up to many months following infection), the study settings included (outpatient vs. inpatient), and how symptoms and conditions are assessed (e.g., self-report vs. electronic health record database). Post-COVID conditions are associated with a spectrum of physical, social, and psychological consequences, as well as functional limitations that can present substantial challenges to patient wellness and quality of life. Multiple possible onset patterns for post-COVID conditions have been identified that further exemplify their heterogeneity, including, but not limited to: (A) persistent symptoms and conditions that begin at the time of acute COVID-19 illness; (B) new-onset late sequelae following asymptomatic disease or a period of acute symptom relief or remission; (C) an evolution of symptoms and conditions that include some persistent symptoms (e.g., shortness of breath) with the addition of new symptoms or conditions over time (e.g., cognitive difficulties); and/or (D) exacerbations or new manifestations of conditions that predated the COVID-19 illness. Some presentations may share similarities with other post-viral syndromes, such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), dysautonomia (e.g., postural orthostatic tachycardia syndrome [POTS]), or mast cell activation syndrome (MCAS). More common longer-term symptoms after COVID infection include: tiredness or fatigue, cognition and/or concentration concerns, headache, loss of taste or smell, palpitations, shortness of breath and/or dyspnea on exertion, chest pain, chronic cough, joint or muscle pains, insomnia, depression and/or anxiety, and low grade fever. It is important to recognize that some symptoms or combination of symptoms may be unusual or not make apparent physiological or anatomical sense, such as post-exertional malaise (PEM), where symptoms worsen following even minor physical or mental exertion for 12-48 hours after activity and often last days or even weeks. At this time, no laboratory test can definitively distinguish post-COVID conditions from other etiologies, in part due to the heterogeneity of them. Before ordering laboratory testing, the goals of testing should be clear to the healthcare professional and to the patient. Any laboratory testing should be guided by the patient history, physical examination, and clinical findings. More specialized testing may not be needed; however, expanded testing should be considered if symptoms persist for 12 weeks or longer. The guideline notes that more evidence is needed to support the utility of specific imaging tests for evaluation of post-COVID conditions. The absence of laboratory-confirmed abnormalities or the decision to forgo extensive laboratory testing should not lead to dismissing the possible impact of a patient’s symptoms on their daily function. For most patients, the goal of medical management is to optimize function and quality of life. Where clinically indicated, symptom management and a comprehensive rehabilitation plan based on their patients’ presenting symptoms, underlying medical and psychiatric conditions, personal and social situations, and their treatment goals can be initiated simultaneously with laboratory testing for most patients. Transparency is important for the process of goal setting; healthcare professionals should advise patients that post-COVID conditions are not yet well understood and assure them that regular follow-up and support will continue to be provided as new information emerges. There are no specific medications presently recommended for the management of patients with post-COVID conditions, and all treatment should be patient-specific based on their symptoms and clinical findings. Though some have used corticosteroids or other anti-inflammatory medications in patient management, their utility is unclear and potential side-effects are well-known. Some data has indicated that receiving a vaccine post-infection has helped alleviate certain symptoms, and this is recommended for all patients who have had COVID-19. As an ICD-10 code for post-COVID conditions does not yet exist, the CDC recommends documenting these conditions using B94.8 (sequelae of other specified infectious and parasitic diseases). The CDC concludes: - The term “Post-COVID Conditions” is an umbrella term for the wide range of physical and mental health consequences experienced by some patients that are present four or more weeks after SARS-CoV-2 infection, including by patients who had initial mild or asymptomatic acute infection. - Based on current information, many post-COVID conditions can be managed by primary care providers, with the incorporation of patient-centered approaches to optimize the quality of life and function in affected patients. - Objective laboratory or imaging findings should not be used as the only measure or assessment of a patient’s well-being; lack of laboratory or imaging abnormalities does not invalidate the existence, severity, or importance of a patient’s symptoms or conditions. - Healthcare professionals and patients are encouraged to set achievable goals through shared decision-making and to approach treatment by focusing on specific symptoms (e.g., headache) or conditions (e.g., dysautonomia); a comprehensive management plan focusing on improving physical, mental, and social wellbeing may be helpful for some patients. - Understanding of post-COVID conditions remains incomplete and guidance for healthcare professionals will likely change over time as the evidence evolves. We know already that the aftereffects of COVID-19 will forever scar some affected individuals, families, and communities, and we’re only beginning to appreciate the impact. The potential number of people who could experience this is staggering, with estimates of well over 3 million, and the health, social, and economic implications are immense. This is certainly a condition that we who practice primary care medicine are uniquely positioned to treat, as it will require a comprehensive biopsychosocialspiritual approach. Note that the “Assessment and Testing” section in the CDC guideline has some nice Tables for possible laboratory or other diagnostic testing as well as other survey instruments that can be used for assessment. - CDC - Evaluating and Caring for Patients with Post-COVID Conditions: Interim Guidance. Updated 14 June, 2021. Link to Table of Contents - Rogers-Brown JS, et al. Outcomes Among Patients Referred to Outpatient Rehabilitation Clinics After COVID-19 Diagnosis – US, January 2020-March 2021. MMWR Morb Mortal Wkly Rep 9 July 2021;70. Link Question from a Colleague 2) COVID vaccine guidelines and evidence We received the following (very paraphrased) questions from a colleague about my review of COVID vaccines and the new indications for the Pfizer vaccine for adolescents (Link): Question: I do not think vaccines should get an “easy pass” from a clinical trial and evidence-based medicine standpoint… While I agree that vaccinating this age group will help us with the overall pandemic and from a social and public health standpoint, I do not think the data on 12- to 15-year-old adolescents is robust from an EBM standpoint or from an individual benefit/risk standpoint. While I do hope (and have some confidence) the COVID vaccines will prove to be safe and effective in these younger age groups, I want to suggest some caution in how we utilize children for the greater good of adults and older folks. Answer: This colleague detailed their concern about small numbers of patients in the trials, the need to look at children specifically, not just as “little adults,” the concern about lack of “patient-oriented” data on hospitalization, respiratory failure, and deaths in adolescents. I think these points raise an important discussion about the use of the evidence to make guidelines and recommendations. An evidence-based guideline uses the best available evidence to arrive at a recommendation. In guideline development for any organization (ACIP, USPSTF, etc.), the evidence cannot or does not describe the correct path of action given all the potential contexts in which that guideline would be applied. It is a data-driven, but ultimately very human, process to work in a group to extrapolate evidence in a way that makes sense for the broader problems. The USPSTF, for example, has extrapolated all sorts of evidence (using both consensus methods and statistical modeling) to arrive at recommendations. The key is being explicit about the process of extrapolation. The ACIP is very explicit about their process. They use the GRADE framework to assess the evidence in front of them, and then use an Evidence-to-Recommendations (EtR) framework to arrive at a recommendation from that evidence. This framework asks specific questions about context and asks the guideline makers to weigh the potential benefits and potential harms considering that context. The ACIP posts all their EtRs here. The EtR is not yet posted for the Pfizer age change recommendation but should be soon. In the case of an ongoing pandemic, where vaccine hesitancy is causing a significant problem, schools and states are rejecting masking recommendations, and a variant is causing new chaos, the ACIP took the evidence available and made a decision with very direct appeal to what would result in the “greater good.” First, let me say, hooray! Our colleague’s question is exactly the sort of critical analysis and questioning we need more of in Family Medicine – this is how we best advocate for our patients – focusing on the right types of studies that look at the important outcomes. In our current pandemic context, yes, vaccines get a little bit of a “pass” because it’s an emergency. I’m personally OK with that, and it also makes me a little uneasy, but we don’t have the luxury of waiting for the evidence we’d want. I’m very comfortable with the multiple ways vaccine safety is monitored by the CDC, which have been increased for COVID vaccines, and that helps me feel a little better. Mark and John Carilion Clinic Department of Family and Community Medicine Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.	2	6	0	0	2	0.811846	2	2,411
Medical Coding BooksThe term "medical coding books" generally describes the three coding books that medical coders use; the CPT, ICD-9-CM, and HCPCS. These coding books are used to translate a written medical record into number sets prior to insurance submission. Number sets, also called medical codes, each represent a unique descriptor found in one of the three books. CPT, ICD-9-CM, & HCPCSThree Medical Coding Books: Codes can be selected from one, two, or all three medical coding books when coding a single medical record. Each book is distinct from the other, carrying it's own set of unique codes, descriptors, and guidelines. The CPT book was founded by the American Medical Association (AMA) in 1966 and is updated annually with changes effective January 1st of each year. Current Procedural Terminology (CPT) The Current Procedural Terminology book contains medical codes that are often called CPT codes or National Level I codes. These CPT codes depict procedures and services that can be performed by physicians, surgeons, specialists, and ancillary staff. In professional coding CPT codes are what insurance companies base their reimbursement on. All CPT medical codes are completely numeric and they are always five digits in length. Each five digit number set is unique and is not repeated in any other medical coding book. Each medical code also has a unique detailed descriptor attached to it. CPT Examples26740 - Closed treatment of articular fracture, involving metacarpophalangeal or interphalangeal joint; without manipulation, each 76813 - Ultrasound, pregnant uterus, real time with image documentation, first trimester fetal nuchal translucency measurement, transabdominal or transvaginal approach; single or first gestation 13121 - Repair, complex, scalp, arms, and/or legs; 2.6cm - 7.5cm ~ Codes for surgical procedures performed on the following organ systems: Integumentary, Musculoskeletal, Respiratory, Cardiovascular, Hemic and Lymphatic, Mediastinum, Digestive, Urinary, Male and Female Genitalia (includes maternity procedures), Nervous, Ocular, and Auditory. ~ E/M codes are listed next, followed by Anesthesia, Surgery (by organ system), Pathology, Radiology, and Medicine codes. ~ Category II and III codes are listed next. These unique codes are use for quality control measures and new technology. ~ Appendicies A - M are located near the end. ~ The alphabetic Index makes up the final portion of the CPT book and is used to look up codes by procedure name or anatomical locaiton. International Classification of Diseases, 9th Edition, Classification Modification (ICD-9-CM) This medical coding book was first published in 1948 and is updated every year with changes effective October 1st of each year. The ICD-9-CM (also known as the ICD-9) is divided into three volumes. Volume I is known as the Tabular Index, Volume II is known as the Alphabetic Index, and Volume III is known as either the Operative Index or the Procedure Index. Volumes I and II are used in both the professional and facility settings and Volume III is reserved for facility settings only. Volumes I and II contain medical codes that depict a diagnosis. These "diagnosis" codes are used to describe accidents, illnesses, injuries, and conditions. Codes from this medical coding book are three to five digits in length, have a decimal point following any third digit, and can be numeric or alpha-numeric in nature. Volume III contains medical codes for procedures performed in a facility setting. These medical codes are numeric, three to four digits in length, and have a decimal point following any second digit. Volume III also has a separate alphabetic index for locating its codes. ICD-9-CM ExamplesVolume I & II 881.00 - Open wound of elbow, forearm, 448.1 - Influenza due to identified novel H1N1 influenza virus (2009 Swine) 643.03 - Excessive vomiting in pregnancy, mild hyperemesis gravidarum, antepartum condition or complication. V03.7 - Need for prophylactic vaccination and inoculation against bacterial diseases; Tetanus toxoid alone 57.94 - Insertion of indwelling urinary catheter. 06.12 - Open biopsy of thyroid gland. ~ 3-4 digit numeric codes that describe in patient procedures (vol. III) ~ V codes; 3-5 digit codes that begin with a V and decribe circumstances for healthcare encounters. ~ "E" Codes; 3-5 digit codes that begin with an E and describe how an accident or injury occured. ~ Volume II (Alphabetic Index) is located next. This lists all accidents, injuries, diseases, and conditions alphabetical by name and includes three tables; Table of Hypertension, Table of Neoplasms, & Table of Chemicals and Drugs. ~ External cause index (E code index) is used specifically to reference E codes. This index is located between Volumes I and II. ~ Volume I (Tabular Index) makes up the center portion of the book. This contains all codes with their full descriptions, conventions, and notaitons. ~ Appendicies A-E ~ Alphabetic index for Volume III. This lists all in patient procedures in Volume III alphabetically for reference. ~ Tabular index for Volume III. This index contains all Volume III codes with their full descriptions, conventions, and notations. Healthcare Common Procedural Coding System (HCPCS) HCPCS codes are also know as National Level II codes. These codes are used to depict non-physician services, Durable Medical Equipment (DME), supplies, and drugs that are not covered by CPT national level I codes. HCPCS codes are five digits in length with no decimal holders and are alphanumeric in nature. Each codes begins with a letter and is followed by four numbers. The HCPCS book structured very similar to the CPT book. HCPCS Code ExamplesK0011 - Standard-weight frame motorized power wheelchair with programmable control parameters for speed adjustment, tremor dampening, acceleration control and braking A5120 - Skin barrier, wipes or swabs, each Q4011 - Cast supplies, short arm cast, pediatric (0-10 years), plaster. ~ The Table of Drugs with drugs listed alphabeticaly is next. ~ HCPCS modifiers listed with their full description is located between the Table of Drugs and the Tabula index. ~ The Tabular index lists all codes with their full description, conventions, and notations and is located in the center of the book. ~ Appendix A which is for Internet Only Manuals makes up the remainder of the book. Book NotationsSome certification exams allow high lighting and hand written notes in your medical coding books. Making tabs on the side of your books for easy referencing is also helpful. Also, consider using a pencil eraser or rubber thumb to aid in quick page turning. Exam TipsCertification exams do not require memorization, just an extensive knowledge of your medical coding books. The answer to almost every question is located in one of the medical coding books, you just need to know how to find it. Be sure to check out what medical coding books are approved and which ones are not prior to sitting for your certification exam. ICD-10Out of the three medical coding books the ICD-9-CM is the oldest. Decades of updates and revisions has created a decrease in code detail as well as a lack of room to expand with technology. The solution? The ICD-10-CM and ICD-10-PCS. The ICD-10-CM will replace Volumes I and II in the ICD-9 and the ICD-10-PCS will replace Volume III. With well over 100,000 additional codes these books will be in effect October 1, 2013......(more) Enjoy This Site? Then why not use the button below and add us to your favorite bookmarking service?	4	4	2	2	2	0.448655	6	1,756
\|Classification and external resources\| Tic disorders is defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM) based on type (motor or phonic) and duration of tics (sudden, rapid, nonrhythmic movements). Tic disorders are defined similarly by the World Health Organization (ICD-10 codes). \|Video clips of tics\| - F95.0 Transient tic disorder - F95.1 Chronic motor or vocal tic disorder - F95.2 Combined vocal and multiple motor tic disorder [Gilles de la Tourette] - F95.8 Other tic disorders - F95.9 Tic disorder, unspecified - Transient tic disorder consisted of multiple motor and/or phonic tics with duration of at least 4 weeks, but less than 12 months. - Chronic tic disorder was either single or multiple motor or phonic tics, but not both, which were present for more than a year. - Tourette syndrome was diagnosed when both motor and phonic tics were present for more than a year. - Tic disorder NOS was diagnosed when tics were present, but did not meet the criteria for any specific tic disorder. From DSM-IV-TR to DSM-5 - The word stereotyped was removed from tic definition: stereotypies and stereotypic movement disorder are frequently misdiagnosed as tics or Tourette syndrome. The definition of tic was made consistent for all tic disorders, and the word stereotyped was removed to help distinguish between stereotypies (common in autism spectrum disorders) and tic disorders. - Provisional tic disorder replaced transient tic disorder: because initially presenting tics may eventually be diagnosed as chronic tic disorder or Tourette's, transient can only be defined in retrospect and is not very useful to the clinician. The term provisional "satisfies experts with a more systematic epidemiological approach to disorders", but should not imply that treatment might not be called for. - Differentiation of chronic motor or vocal tic disorder: DSM-5 added a specifier to distinguish between vocal and motor tics that are chronic. This distinction was added because higher rates of comorbid diagnoses are present with vocal tics relative to motor tics. - Stimulant use as a cause removed: there is no evidence that the use of stimulants causes tic disorders. - New categories, Other specified and Unspecified: for tic disorders that result in significant impairment to the individual yet do not meet the full criteria for other tic disorders. The new categories account for tics with onset in adulthood, or tics triggered by other medical conditions or illicit drug use. The fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), published in May 2013, classifies Tourette's and tic disorders as motor disorders listed in the neurodevelopmental disorder category. Tic disorders, in order of severity, are: - 307.20 Other specified tic disorder (specify reason) - 307.20 Unspecified tic disorder - 307.21 Provisional tic disorder - 307.22 Persistent (chronic) motor or vocal tic disorder (specify motor or vocal) - 307.23 Tourette's disorder Education, and a "watch and wait" strategy, are the only treatment needed for many, and the majority of individuals with tics do not seek treatment; treatment of tic disorders is similar to treatment of Tourette syndrome. \|\|This article or section appears to contradict itself on the amount of people who've experienced tic disorders (1 to over 19%). (January 2017)\| Tic disorders are more common among males than females. A large, community-based study suggested that over 19% of school-age children have tic disorders; the children with tic disorders in that study were usually undiagnosed. As many as 1 in 100 people may experience some form of tic disorder, usually before the onset of puberty. Tourette syndrome is the more severe expression of a spectrum of tic disorders, which are thought to be due to the same genetic vulnerability. Nevertheless, most cases of Tourette syndrome are not severe. Although a significant amount of investigative work indicates genetic linkage of the various tic disorders, further study is needed to confirm the relationship. - American Psychiatric Association (2000). DSM-IV-TR: Tourette's Disorder. Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision (DSM-IV-TR), ISBN 0-89042-025-4. Available at BehaveNet.com Retrieved on August 10, 2009. - Swain JE, Scahill L, Lombroso PJ, King RA, Leckman JF. "Tourette syndrome and tic disorders: a decade of progress". J Am Acad Child Adolesc Psychiatry. 2007 Aug;46(8):947–68 doi:10.1097/chi.0b013e318068fbcc PMID 17667475 - ICD Version 2006. World Health Organization. Retrieved on 2007-05-24. - Evidente VG. "Is it a tic or Tourette's? Clues for differentiating simple from more complex tic disorders". Postgraduate medicine. 108 (5): 175-6, 179-82. PMID 11043089 Retrieved on 2007-05-24 - American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (Fifth ed.). Arlington, VA: American Psychiatric Publishing. pp. 81–85. ISBN 978-0-89042-555-8. - Neurodevelopmental disorders. American Psychiatric Association. Retrieved on December 29, 2011. - Moran, M. "DSM-5 provides new take on neurodevelopment disorders". Psychiatric News. January 18, 2013;48(2):6–23. doi:10.1176/appi.pn.2013.1b11 - "Highlights of changes from DSM-IV-TR to DSM-5" (PDF). American Psychiatric Association. 2013. Retrieved on June 5, 2013. - Ellis CR, Pataki C. "Background: Childhood Habit Behaviors and Stereotypic Movement Disorder". Medscape. Retrieved October 6, 2013. - Plessen KJ. Tic disorders and Tourette's syndrome. Eur Child Adolesc Psychiatry. 2013 Feb;22 Suppl 1:S55–60. PMID 23224240 doi:10.1007/s00787-012-0362-x - Roessner V1, Plessen KJ, Rothenberger A, et al. "European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment". Eur Child Adolesc Psychiatry. 2011 Apr;20(4):173-96. PMID 21445724. - Kurlan R, McDermott MP, Deeley C, et al. "Prevalence of tics in schoolchildren and association with placement in special education". Neurology 57 (8): 1383-8. PMID 11673576 - Tourette Syndrome Fact Sheet. National Institutes of Health (NIH). Retrieved on 2005-03-23. - Swerdlow NR. "Tourette syndrome: current controversies and the battlefield landscape". Current neurology and neuroscience reports. 5 (5): 329-31. doi:10.1007/s11910-005-0054-8 PMID 16131414 - The Tourette Syndrome Classification Study Group. "Definitions and classification of tic disorders". Arch Neurol. 1993 Oct;50(10):1013-6. PMID 8215958. Retrieved on 2005-03-22 - Walkup JT, Ferrão Y, Leckman JF, Stein DJ, Singer H. Tic disorders: some key issues for DSM-V (PDF). Depress Anxiety. 2010 Jun;27(6):600–10. PMID 20533370 doi:10.1002/da.20711	3	12	3	0	3	0.727407	6	1,700
- Potter syndrome Name = Potter syndrome ICD10 = ICD10\|Q\|60\|6\|q\|60 ICD9 = ICD9\|753.0, ICD9\|658.0, ICD9\|761.2 (for oligohydramnios) MedlinePlus = 001268 eMedicineSubj = ped eMedicineTopic = 1878 DiseasesDB = 11252 Potter syndrome is a congenital birth defect and is also known as Potter's syndrome, Potter's sequence or Oligohydramnios sequence. Specifically, Potter syndrome is a term used to describe the typical physical appearances of a fetus or neonate due to a dramatically decreased amniotic fluid volume oligohydramnios, or absent amniotic fluid anhydramnios, secondary to renal diseases such as bilateral renal agenesis(BRA). Other causes of Potter syndrome can be obstruction of the urinary tract, polycystic or multicystic kidney diseases, renal hypoplasia and rupture of the amniotic sac. The term "Potter syndrome" was initially intended to only refer to cases of BRA, however, it has been mistakenly used by many clinicians and researchers to refer to any case that presents with oligohydramniosor anhydramniosregardless of the source of the loss of amniotic fluid. renal agenesis(BRA) was first recognized as a defect of human fetaldevelopment in 1671by Wolfstrigel. However, it was not until 1946when Edith Potter (b.1901 - d.1993) extensively and painstakingly described the BRA phenotypeof the human fetus that the defect was fully appreciated. [Potter EL. Bilateral Renal Agenesis. J Pediatr. 1946; 29:68.; Potter EL. Facial characteristics in infants with bilateral renal agenesis. Am J Obstet Gynecol. 1946; 51:885.] Up until this time the condition itself was considered to be extremely rare. However, in part to Potter's work it has come to light that the condition presents far more frequently than previously reported. Potter analyzed approximately 5000 autopsycases performed on fetuses and newborn infants over a period of ten years and found that 20 of these infants presented with BRA, all of which had distinctive facial characteristics. These facial characteristics have subsequently be termed as being known as Potter facies. From her analysis she was able to deduce the sequence of events that leads to what is now known as Potter syndrome. Potter went on to become a pioneer in the field of human renal development and her contributions are still employed and appreciated by clinicians and researchers to this day. Since its initial characterization, Potter syndrome has been defined into five distinct subclassifications. There are those in the medical and research fields that use the term Potter syndrome to specifically refer to only cases of BRA, while other groups use the term to loosely refer to all instances of oligohydramniosand anhydramniosregardless of the specific cause. The assignment of nomenclature to the various causes (types) were employed in order to help clarify these descrepancies, but, these subclassifications and nomenclature system have not caught on in the medical and research communities. This term is traditionally used when the infant has bilateral renal agenesis (BRA). True BRA also presents with bilateral agenesis of the ureters. After the creation of the nomenclature system for this syndrome, BRA was recognized as possibly being an extreme variation of Potter syndrome II. However, some clinicians and researchers still use the term "classic Potter syndrome" so as to emphasize that they are specifically referring to cases of BRA and not another form. Type I is due to autosomal recessive polycystic kidney disease(ARPKD), which occurs at a frequency of approximately one in 16,000 infants. The kidneys of the fetus/neonate will be enlarged, have many small cysts filled with fluid and will fail to produce an adequate volume of fetal urine. The liver and pancreas of the fetus may also show fibrosisand/or a cystic change. Type II is usually due to renal agenesis(Buchta et al., 1973), which can also fall under the category known as "hereditary urogenital adysplasia" or "hereditary renal adysplasia" (HRA). This is characterized by the complete agenesis or absence of one kidney and the remaining solitary kidney being small and malformed. Bilateral renal agenesis is believed to be the most extreme phenotypic variation of HRA. However, BRA is often referred to as "classic Potter syndrome", as it was this particular phenotypeof neonates and fetuses that Potter originally reported in her 1946 manuscripts when characterizing this birth defect. Type III is due to autosomal dominant polycystic kidney disease(ADPKD) linked to mutations in the genes PKD1 and PKD2. While ADPKD is considered to be an adult-onset polycytic kidney disease, it can also present in the fetus and neonate in rare cases. Like ARPKD, ADPKD can also present with hepatic cysts and an enlarged spleen. An increased prevalence of vascular disease is also observed in these cases of ADPKD. Type IV occurs when a longstanding obstruction in either the kidney or ureterleads to cystic kidneys or hydronephrosis. This can be due to chance, environment, or genetics. While these types of obstructions occur frequently in fetuses, they rarely tend to lead to fetal demise. Often cystic kidneys that do not fall under the classification of being polycystic will be termed as being "multicystic renal dysplasia" (MRD). Recently many cases of MRD have been linked to the mutations in the gene PUJO, however, this new possible genetic cause has not been assigned a Potter syndrome nomenclature number. Another cause of Potter syndrome (oligohydramnios or anhydramnios) can be the rupturing of the amniotic sacs that contain the amniotic fluid of the fetus. This can happen spontaneously, by chance, environment, maternal trauma and in rare cases - maternal genetics. Terminology: Syndrome vs. Sequence Potter syndrome is not technically a syndromeas it does not collectively present with the same telltale characteristics and symptoms in each and every case. It is more accurately described as a "sequence" or chain of events that may have different beginnings (absent kidneys, cystic kidneys, obstructed uretersor other causes), but which all end with the same conclusion (absent or reduced volume of amniotic fluid). This is why Potter syndrome is often called "Potter sequence" or "oligohydramnios sequence" by some clinicians and researchers. The term "Potter syndrome" is most frequently associated with the condition of oligohydramniossequence regardless of the root cause of the absence or reduced volume of amniotic fluid. However, as noted in this article, the term "Potter syndrome" was initially coined in order to refer to fetuses and infants with BRA. It was not until later that the term became more encompassing as it was noted that other causes of failed fetal urine production also resulted in similar physical characteristics and prognoses of the fetuses and infants with BRA (that which Potter originally described in 1946). Since then, the term "Potter syndrome" has become a misnomer and experts have attempted to not eliminate the terminology, but to modify it in a way so as to be able to determine the different root causes by creating a nomenclature system. However, this classification system has not caught on in the clinical and research fields. Classic Potter syndrome occurs when the developing fetushas bilateral renal agenesis, which also presents with agenesis of the ureters. BRA has been estimated to occur at a frequency of approximately 1:4000 to 1:8000 fetuses and neonates. However, recent analysis has estimated that the condition may occur at a much greater frequency. The condition has been reported to occur twice as common in males as in females, suggesting that certain genes of the Y chromosomemay act as modifiers. However, no candidate genes on the Y chromosomehave yet been identified. BRA appears to have a predominantly genetic etiologyand many cases represent the most severe manifestation of an autosomal dominantcondition with incomplete penetrance and variable expressivity. There are several genetic pathways that could result in this condition. To date, few of these pathways or candidate genes have been considered or analyzed regarding BRA. The majority of possible candidate genetic pathways are autosomal recessivein nature and do not coincide with the frequency or penetrance at which BRA occurs in the human population. Additionally, candidate genetic pathways would be expected to involve genes expressed in the developing urogenitalsystem (UGS). Often, these same genes and/or pathways of interacting genes are also expressed in the developing UGS as well as the central nervous system(CNS), gut, lung, limbs, and eyes. Normal kidney development Importance of fetal urine Development of the mature kidneybegins between weeks 5 and 7 of gestation. Fetal urine production begins in early gestation and comprises the majority of the amniotic fluidin the second and third trimesters of pregnancy. The fetus continuously swallows amniotic fluid, which is reabsorbed by the gastrointestinal tract and then reintroduced into the amniotic cavity by the kidneys via urination. Oligohydramniosoccurs if the volume of amniotic fluid is less than normal for the corresponding period of gestation. The fetal urine is critical to the proper development of the lungs by aiding in the expansion of the airways - alveoli, by means of hydrodynamic pressure and by also supplying prolinewhich is a critical amino acidfor lung development. Alveoli are the small sacs in the lungs that exchange oxygen with the blood. If the alveoli, and thereby the lungs, are underdeveloped at the time of birth the infant will not be able to breathe air properly and will go into respiratory distress shortly after birth due to pulmonary hypoplasia(underdeveloped lungs). This is the primary cause of death to Potter syndrome infants secondary to renal failure. The fetal urine also serves to cushion the fetus from being compressed by the mother's uterusas it grows. The failure of the metanephros to develop in cases of BRA and some cases involving unilateral renal agenesis(URA) is due primarily to the failure of the nephric duct to produce a ureteric bud capable of inducing the metanephric mesenchyme. The failed induction will thereby cause the subsequent degeneration of the metanephros by apoptosisand other mechanisms. The nephric duct(s) of the agenic kidney(s) will also degenerate and fail to connect with the bladder. Therefore, the means by which the fetus produces urine and transports it to the bladder for excretion into the amniotic sac has been severely compromised (in the cases of URA), or completely eliminated (in the cases of BRA). The decreased volume of amniotic fluidcauses the growing fetusto become compressed by the mother's uterus. This compression can cause many physical deformities of the fetus, most common of which is Potter facies. Lower extremity anomalies are frequent in these cases, which often presents with clubbed feet and/or bowing of the legs. Sirenomelia, or "Mermaid syndrome" (which occurs approximately in 1:45,000 births) [Banerjee A, 2003; Indian J Pediatr] can also present. In fact, nearly all reported cases of sirenomeliaalso present with BRA. [ Siegel MJ, 2000; J Peri.] Other anomalies of the classic Potter syndrome infant include a parrot beak nose, redundant skin, and the most common characteristic of infants with BRA which is a skin foldof tissue extending from the medial canthusacross the cheek. The ears are slightly low and pressed against the head making them appear large. The adrenal glandsoften appear as small oval discs pressed against the posterior abdomendue to the absence of upward renal pressure. The bladder is often small, nondistensible and may be filled with a minute amount of fluid. In males the vas deferensand seminal vesiclesmay be absent, while in females the uterusand upper vaginamay be absent. Other abnormalities include anal atresia, absence of the rectumand sigmoid colon, esophagealand duodenalatresia, and a single umbilical artery. Presence of a diaphragmatic hernia is also common in these fetuses/infants. Additionally, the alveolar sacs of the lungs fail to properly develop as a result of the reduced volume of amniotic fluid. Labor is often induced between 22 and 36 weeks of gestation(however, some of these pregnancies may go to term) and unaborted infants typically survive for only a few minutes to a few hours. These infants will eventually expire as either a result of pulmonary hypoplasia or renal failure. In recorded medical and research history BRA has proved to be 100% lethal in all cases of singletonbirths. Various other forms of the syndrome are, or are near, 100% lethal. While genetic research has linked certain genetic mutations to be the cause of ARPKD, ADPKD and possibly MRD, to date no genetic mutation or chromosomal anomaly has been linked to be the cause of BRA. Chromosomal anomalies have been associated with BRA in certain cases (chromosomes 1, 2, 5 and 21), but these anomalies were not inherited and have not been observed in subsequent cases. Additionally, neither extreme substance abuse or environmental factors (high power line, mercury, etc.) have been reported to be linked to an increased incidence of BRA or other cause of Potter syndrome. BRA and other causes of oligohydramnios sequence have been linked to a number of other problems, to include Down syndrome, Kallmann syndrome, branchio-oto-renal syndromeand others. obstetricianor genetic counselormay ask for a blood sample from the fetus or will perform an amniocentesis. These samples are used to perform several tests, one of which may be to check for the proper number of chromosomes, called a karyotype, of the fetus. Some birth defects are known to be associated with missing a chromosome, having an extra chromosome, such as in Down syndrome, as well as by having a part of one chromosome break off and relocate to a portion of another chromosome (called a translocation). However, on each of the 23 pairs of chromosomes are thousands of different genes. While chromosomes are easy to visualize under a microscopeand count, the geneson them are not. Genes are very small pieces of DNA when compared to the chromosomes they reside on. A genecontains a code for a proteinand if the geneis mutated (different from normal) the proteinthat is made from it may not function properly - if at all. Unfortunately, genetic abnormalities could still exist despite having normal chromosomes. The only way to determine genetically inheritedmutations in the infant is to perform a genome scan of the mother, father, affected infant and any unaffected siblings of the affected fetus. These analyses will reveal what genetic mutations are present in the affected infant, and by comparing these results to the surviving siblings and parents, it can be determined which mutations were inheritedor were not. * [http://www.kidneygenes.com University of Iowa Potter Syndrome Research Group] * [http://www.potterssyndrome.org Potterssyndrome.org] , support website * [http://forums.delphiforums.com/potterssyndrome/start Potter syndrome] forums Wikimedia Foundation. 2010. Look at other dictionaries: Potter syndrome — a congenital condition characterized by absence of kidneys, resulting in decreased amniotic fluid (see oligohydramnios) and compression of the fetus. Babies have poorly developed lungs, a characteristic wrinkled and flattened facial appearance,… … Medical dictionary Potter syndrome — a congenital condition characterized by absence of kidneys, resulting in decreased amniotic fluid (see oligohydramnios) and compression of the fetus. Babies have poorly developed lungs, a characteristic wrinkled and flattened facial appearance,… … The new mediacal dictionary Doege-Potter syndrome — Not to be confused with Potter sequence. Doege Potter syndrome Classification and external resources The structure of IGF 2, responsible for the hypoglycemia associated with Doege Potter syndrome Doege Potter syndrome (DPS) is a … Wikipedia Синдром Поттера (Potter Syndrome) — врожденный дефект развития, характеризующийся отсутствием у человека почек в результате уменьшения количества околоплодных вод (см. Олигоамнион) и сдавления плода. У детей с этим синдромом обычно бывают плохо развиты легкие, лицо имеет типичное… … Медицинские термины Potter sequence — Not to be confused with Doege Potter syndrome or Pott s Disease. Potter sequence Classification and external resources ICD 10 Q60.6 ICD 9 … Wikipedia Potter — A potter is someone who makes pottery.Potter may also refer to:PeoplePotter, Alexandra (born 1970), British author Potter, Alfie (born 1989), English football player Potter, Allen (1818 ndash;1885), American politician Potter, Alonzo, Bishop… … Wikipedia Syndrome de Dodge-Potter — Le Syndrome de Dodge Potter est un syndrome paranéoplasique causé par une tumeur bénigne ou maligne. Sommaire 1 Fréquence 2 Cause 3 Conséquences 4 Traitement … Wikipédia en Français Syndrome de VACTERL — Le syndrome de VACTERL (ou Association VACTERL) est un ensemble d anomalies congénitales ou malformations, qui ne répondent à aucun critère précis de regroupement, mais qui n apparaissent pas non plus de manière aléatoire. C est une extension du… … Wikipédia en Français syndrome — The aggregate of symptoms and signs associated with any morbid process, and constituting together the picture of the disease. SEE ALSO: disease. [G. s., a running together, tumultuous concourse; (in med.) a concurrence of symptoms, fr. syn,… … Medical dictionary Potter facies syndrome — Pot·ter facies, syndrome (potґər) [Edith Louise Potter, American physician, 1901â€“1993] see under facies and see oligohydramnios sequence, under sequence … Medical dictionary	2	13	2	0	2	0.47366	4	4,222
The central nervous system includes the brain and spinal cord. Peripheral nerves are located outside the brain and spinal cord. They carry information. Results: A total of 772 Olmsted County residents aged 18 to 91 years were diagnosed with IBD. After 12,476 person-years, 9 patients developed neuropathy, providing an. What Makes the Functional Neurological and Functional Medicine Approach Unique in treating patients with Peripheral Neuropathy? The Functional 01.10.2002 · WebMD’s guide to the causes and types of peripheral neuropathy. Peripheral neuropathy affects the peripheral nervous system, which transmits messages between the central nervous system and other parts of the body. Causes And Symptoms Of Peripheral Neuropathy Aug 9, 2017. Peripheral neuropathy — Comprehensive overview covers diagnosis, causes and treatment of this often painful disorder. Peripheral neuropathy (PN). The effect of this is to cause symptoms in more than Those with bowel disease were also more than six times more likely to also have a disorder called sensorimotor polyneuropathy, a nerve disease that can cause weakness, pain, and numbness. These diseases were more common in women with bowel disease than men. “Inflammatory bowel disease patients commonly. Background. Small fiber neuropathy (SFN) is caused by damage to the small, unmyelinated fibers in the peripheral nerves that innervate the skin and. The Intestinal Microbiome and Inflammatory Bowel Disease. The intestinal microbiome consists of the microorganisms that inhabit the gut. The intraluminal. Peripheral neuropathy (PN) is one of the most frequently reported neurologic complications of IBD.– In addition to nutritional (e.g., B12 deficiency) and iatrogenic (e.g., metronidazole neurotoxicity) causes, patients with IBD may experience severe immune-mediated neuropathies as extraintestinal manifestations throughout. had higher rates of peripheral neuropathy than. symptoms in patients with celiac disease?. celiac disease and inflammatory bowel disease and I. In recent years, there has been an increasing incidence of inflammatory bowel disease in children and adolescents. Neurologic involvement. Teles BC, Brasil EF, Peripheral neuropathy and neurological disorders in an unselected Brazilian population based cohort of IBD patients. Inflamm Bowel Dis. 2008;14: 389–395. Peripheral neuropathy (PN) is one of the most frequently reported neurological complications in IBD patients. Several different PN phenotypes have been described in these patients. Paraesthesias due to small fibre involvement ( autonomic or sensory) and increased threshold for temperature detection (or axonal sensory. Neurologic Manifestations of Inflammatory Bowel Disease. treatments for IBD? JF Yes. Peripheral neuropathy, in patients with inflammatory bowel disease:. Nerve Report: 2017 Release. Don’t try anything before you read. Peripheral neuropathy in IBD patients remains unrecognized. • Heightened awareness is necessary for successful treatment. • Exact prevalence of peripheral nerve. Neuropathic Bowel Disease. By. minute.People with inflammatory bowel disease or ibd experience. pittsburgh pa 15237 peripheral neuropathy is a. Abstract. Peripheral neuropathy (PN) in inflammatory bowel disease (IBD) patients has been reported as individual cases or small series; however, its clinical @ Icd 9 Code Diabetic Peripheral Neuropathy ★★ Diabetes Type 1 Type 2 Difference The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11. Sep 19, 2009. Of the 102 IBD patients, 8.8% (n=9) had evidence of peripheral neuropathy ( Table I). Three patients had mononeuropathies: Two had carpal tunnel syndrome and one had fibular nerve entrapment due to rapid weight loss and to immobilization after abdominal surgery. All other patients with the exception of. Clinical and Electrodiagnostic Findings in Patients with Peripheral Neuropathy and Inflammatory Bowel Disease. Gondim, Francisco de A. A. MD, PhD *,†; de Oliveira. Gondim FAA, Brannagan TH, Sander H, Chin RL, Latov N. Peripheral neuropathy in patients with inflammatory bowel disease. Brain 2005; 128: 867-79. The aim of this. Crohn's Disease Initially Accompanied by Deep Vein Thrombosis and Ulnar. Neuropathy without Metronidazole Exposure. Peripheral neuropathy without drug exposure is known to be associated with CD activity. ent peripheral neuropathy have been described in IBD patients.12. Medical treatment with metronidazole or. Peripheral neuropathy in patients with inﬂammatory bowel disease. between IBD and peripheral neuropathy has. UC patients with peripheral neuropathy Peripheral neuropathy incidence in inflammatory bowel disease. Clinicians should consider other etiologies of neuropathy in patients with IBD. neurologic disorders in patients with CD (7, 8). Peripheral neuropathy is one of the most frequently reported neurologic complications of CD (3, 11). In one study, 30% of 33 pa- tients suffering from neuropathy associated with inflamma- tory bowel disease had demyelinating forms of neuropa- thy (4). Only six cases of CIDP. Alternative Medicine Approaches to Disease This section was compiled by Frank M. Painter, D.C. Make comments or suggestions to [email protected] Classification. Vertigo is classified into either peripheral or central depending on the location of the dysfunction of the vestibular pathway, although it. Diabetic Neuropathy And Postural Hypotension Even healthy older adults usually have less secure balance than they had when they were younger. Older adults may be taking many medications or are coping. Eighteen diabetics with autonomic neuropathy, nine Lyme is often Misdiagnosed as other Disease and Disorders Many found their "misdiagnosed" disease or syndrome disappeared after receiving treatment for. Apr 1, 2005. Abstract. Peripheral neuropathy (PN) in inflammatory bowel disease (IBD) patients has been reported as individual cases or small series; however, its clinical and electrodiagnostic features have not been well characterized. We conducted a retrospective review of patients with PN and either Crohn's. Dec 30, 2015. This study is aimed at studying the prevalence and characteristics of different types of headaches in patients with Crohn's disease. Materials and Methods. The peripheral and central nervous system complications such as CD and ulcerative colitis (UC) may arise in IBD. However, exact prevalence of. Objective: Our aim was to determine the incidence of peripheral neuropathy in a population-based inflammatory bowel disease (IBD) cohort from Olmsted County, Minnesota. Jul 21, 2014. Core tip: Extraintestinal manifestations occur in about one-third of patients with inflammatory bowel disease (IBD) and may precede the onset of gastrointestinal symptoms by many years. Electrodiagnostic studies reveal progressive acquired demyelinating sensory and motor peripheral polyneuropathy. Chronic Inflammatory Demyelinating Polyneuropathy Following. CIDP is an acquired peripheral neuropathy, patients with inflammatory bowel disease. Aug 14, 2017. An inflammatory bowel disease, Crohn disease may have mental effects due to its troublesome symptoms that include abdominal pain, diarrhea that can be. Peripheral neuropathy is characterized by damage to the peripheral nerves that connect the brain to the rest of the body, resulting in symptoms like. Demyelinating sensorimotor peripheral neuropathy. Peripheral neuropathy in patients with the. Peripheral neuropathy in patients with inflammatory bowel disease. Dec 8, 2005. However, an axonal motor polyneuropathy in UC as found in the present case was described in a few adult patients. In a retrospective study conducted by Larrode et al. (5), a peripheral sensorimotor ne- uropathy developed in four patients with a paral- lel course to IBD. One case was secondary to vita-. Patients with peripheral neuropathy may. whether from the disease or. it is referred to as idiopathic peripheral neuropathy. Sometimes, peripheral nerve. The primary outcomes were induction of remission or response for active IBD or relapse rate for patients in remis-. (32%) and peripheral neuropathy (20%). Conclusions. One high quality RCT. Figure 1 \| Thalidomide proposed mechanism of action in inflammatory bowel disease. TNF- tumour necrosis factor; TH – T. Guillain-Barré syndrome, tuberculosis and inflammatory. Latov N: Peripheral neuropathy in patients with. in inflammatory bowel disease patients:. Diabetic Neuropathy natural treatment using vitamins supplements herbs, alternative therapy and remedy and the role of diet and food June 15 2017 by Ray. Peripheral neuropathy has a variety of systemic, metabolic, and toxic causes. The most common treatable causes include diabetes mellitus, hypothyroidism. Inflammatory Bowel Disease Linked. including carpal tunnel syndrome and small fiber neuropathy, "Inflammatory bowel disease patients commonly suffer. 5.00 Digestive System. A. What kinds of disorders do we consider in the digestive system? Disorders of the digestive system include gastrointestinal. Patients with IBD have an approximately 3-fold higher risk of venous cerebral thrombosis compared with the general population. Peripheral neuropathy, the most common neurologic issue stemming from IBD, can occur as a side effect to anti–tumor necrosis factor-α (anti-TNF) therapy or treatment with the antibiotic. Crohns Disease, a chronic inflammatory bowel disease condition, within 10 years of onset it is common for patients to develop peripheral neuropathy, •Peripheral neuropathy in IBD patients remains unrecognized. •Heightened awareness is necessary for successful treatment. •Exact prevalence of peripheral nerve damage in IBD is unknown. •Peripheral nerve damage is associated with drugs used in IBD. •Micronutrient deficiency must be discarded before initiating. Diarrhea, also spelled diarrhoea, is the condition of having at least three loose or liquid bowel movements each day. It often lasts for a few days and can. Chronic inflammatory demyelinating polyneuropathy. Peripheral neuropathy. Filali A, Hentati F. Peripheral neuropathy in inflammatory bowel disease patients:. Jan 18, 2014. Studies show Crohn's disease can lead to a variety of nervous system disorders. The good news is that it doesn't happen often. Peripheral neuropathy that causes nerve damage, tingling and pain in the extremities is one example. A condition known a polyneuropathy can lead to nerve degeneration and. This article reviews the wide range of cancers associated with inflammatory bowel disease and the drugs used to manage them. Surveillance recommendations. More Neuropathy Articles ... - Peripheral Neuropathy And Postural Hypotension: The Peripheral Neuropathy of Vitamin. neuropathy, the postural hypotension resolved rapidly and. peripheral neuropathy responded well to therapy because. Feb 15, 2014. Orthostatic hypotension is defined as the reduction in systolic blood pressure. an... - Painful Peripheral Neuropathy Emedicine: Management of Painful Peripheral Diabetic Neuropathy. of duloxetine as a first-line treatment for painful diabetic peripheral neuropathy in. May 1, 2017. A widely accepted definition of diabetic peripheral neuropathy. Pain actually may be under-repor... - Medicine For Peripheral Neuropathy: Numbness & Tinging (Peripheral Neuropathy) chemotherapy side effect, causes, and when to contact your healthcare provider during cancer treatment. Peripheral neuropathy is a type of damage to your peripheral nervous system. Find in-depth informat... - Dyck Pj Peripheral Neuropathy: Peripheral Neuropathy: A Practical Approach to Diagnosis and Symptom. P.C., Dyck, P.J. Prevalence of monoclonal protein in peripheral neuropathy. forms of peripheral neuropathy and to evaluate. Wees et al27 and Dyck et al,28 when intramural. 761-80. ... - Can Acupuncture Help Diabetic Neuropathy: @ Diabetes Type 2 With Peripheral Neuropathy ★★ Acupuncture Diabetes The 3 Step Trick that. medical centers indicate yoga can help steady the. types of peripheral neuropathy. Neuropathy comes from the Latin neuro (relating to the nerves) and pathos (... - B12 Treatment For Peripheral Neuropathy: Read user ratings and reviews for VITAMIN B12 on WebMD including side effects and interactions, treatment effectiveness, ease of use, safety and satisfaction. Advanced Biological Antiaging Protocols and Therapies. Peripheral neuropathy (PN) is damage...	2	10	2	0	2	0.716386	4	2,769
The abbreviation ICD stands for “International Statistical Classification of Diseases and Related Health Problems”. The ICD catalogue is compiled by the World Health Organisation (WHO). It is internationally recognised and the most important classification system for medical diagnoses. The ICD catalogue is used to code medical diagnoses and is used in a wide range of countries, especially in the inpatient sector, but also in the outpatient sector. The latest, 11th version of the WHO catalogue, ICD-11, has been in force since 1 January 2022. The previous version, ICD-10, has been in use since 1994 and was last updated in 2019. Use of the ICD catalogue in Switzerland Since 2011, it has been mandatory for all hospitals and clinics in Switzerland to use the German Modification version (ICD-10-GM), which differs from the WHO version, for coding medical diagnoses. The ICD-10-GM is published by the Federal Institute for Drugs and Medical Devices (BfArM) and updated annually. In Switzerland, the new version is usually adopted every two years. Accordingly, the ICD-10-GM version 2022, for example, was, or will be, used in both 2022 and 2023. The Federal Statistical Office (FSO) announces the valid version of the classifications in each case. For use in the Swiss health system, the ICD-10-GM is also translated into French and Italian by the Federal Statistical Office (FSO). An essential goal of the use of the ICD classification is the uniform coding of diagnoses to enable the statistical analysis of data. In addition, the coding of diagnoses by ICD codes is used in particular in the tariff system in Switzerland. In all three inpatient tariff systems, ICD codes are used to group cases. From 2025 onwards, diagnoses will probably also be coded in the outpatient sector, within the framework of outpatient flat rates, using the ICD classification. Structure of the CIM catalogue The codes in the ICD-10-GM classification catalogue have an alphanumeric structure consisting of a letter in the first position followed by two digits, a dot and one or two decimal places (e.g. I21.0 “Acute transmural myocardial infarction of anterior wall” or I25.11 “Atherosclerotic heart disease: Single-vessel coronary artery disease”). The classification catalogue consists of two parts, the Tabular List and the Alphabetic Index. The Tabular List is divided into 22 chapters, with the first 17 chapters in particular describing diseases in the stricter sense. Each of the 22 chapters is divided into individual disease groups, e.g. E10-E14 “Diabetes mellitus”. A group contains different three-digit disease classes (also called categories). As an example, the disease class E10.- “Insulin-dependent diabetes mellitus” can be mentioned here. The categories are usually further subdivided into four-digit subcategories. This subcategorisation allows coding of localisation, varieties or specific diseases if the category includes a group of affections. To stay with the example above: E10.1 “Insulin-dependent diabetes mellitus: With ketoacidosis” forms a subcategory. Sometimes there is further refinement and thus five-digit codes (e.g. M23.21 “Derangement of meniscus due to old tear or injury: Anterior horn of medial meniscus”). Important for coding: Only terminal codes are valid, i.e. only codes for which no further subdivision exists. These can be three-digit, four-digit or five-digit codes of the ICD-10-GM. For correct coding, it is recommended that the first step is to search for the leading term for the diagnosis in the Alphabetic Index and the second step is to use the Tabular List to check the accuracy of the code found and to determine whether further specification is necessary. The ICD-10 Alphabetic Index supports the search for the correct ICD code. The Alphabetic Index contains search terms for diseases, syndromes, traumas and symptoms. However, the Tabular List is always decisive for coding. Thus, if the Alphabetic Index leads to a non-specific code, it must always be checked with the Tabular List whether a more specific coding is possible. Our free online search MedCodeSearch can also help you find the right code. In addition to the ICD catalogue, you can search other catalogues such as the CHOP catalogue or various tariff systems such as SwissDRG or TARMED. The intelligent search function we have implemented makes finding the right code child’s play.	4	4	0	0	6	0.182072	6	988
I'm a provider You will be redirected to myBlue. Would you like to continue? Please wait while you are redirected. DESCRIPTIONEndobronchial valves are synthetic devices that are deployed with bronchoscopy into ventilatory airways of the lung for the purpose of controlling airflow. They have been investigated for use in patients who have prolonged broncho-pleural air leaks, as well as an alternative to lung volume reduction surgery (LVRS) in patients with lobar hyperinflation from severe emphysema. Proper lung functioning is dependent upon a separation between the air-containing parts of the lung and the small vacuum-containing space around the lung called the pleural space. When air leaks into the pleural space the lung is unable to inflate resulting in hypoventilation and hypoxemia; this condition is known as a pneumothorax. A pneumothorax can result from a variety of processes including trauma, high airway pressures induced during mechanical ventilation, lung surgery, and rupture of lung blebs or bullae which may be congenital or a result of chronic obstructive pulmonary disease (COPD). Although an air leak from the lung into the pleural space may seal spontaneously, it often requires intervention. Techniques currently employed to attempt air leak closure include the following: An endobronchial valve is a device that permits one-way air movement. During inhalation the valve is closed preventing air flow to the diseased area of the lung. The valve opens during exhalation to allow air to escape from the diseased area of the lung. When used to treat persistent air leak from the lung into the pleural space, the endobronchial valve theoretically permits less air flow across the diseased portion of the lung during inhalation aiding in air leak closure. The valve may be placed, and subsequently removed, by bronchoscopy. Endobronchial valves have also been investigated for use in severe emphysematous COPD. In emphysematous COPD peripheral lung tissue may form bullae. These diseased portions of the lung ventilate poorly, cause air trapping, and hyperinflate, compressing relatively normal lung tissue. They also may rupture, causing a pneumothorax. Use of an endobronchial valve is thought to prevent hyperinflation of these bullae. Consideration for the use of endobronchial valves in COPD is based on the improvement observed in patients who have undergone lung volume reduction surgery (LVRS). LVRS involves excision of In October 2008, the “IBV® Valve System” (Spiration, Inc, Redmond, WA) was approved by the FDA under the Humanitarian Device Exemption for use in controlling prolonged air leaks of the lung or significant air leaks that are likely to become prolonged air leaks following lobectomy, segmentectomy, or lung volume reduction surgery (LVRS). An air leak present on postoperative day 7 is considered prolonged unless present only during forced exhalation or cough. An air leak present on day 5 should be considered for treatment if it is: 1) continuous, 2) present during normal inhalation phase of inspiration, or 3) present upon normal expiration and accompanied by subcutaneous emphysema or respiratory compromise. IBV Valve System use is limited to 6 weeks per prolonged air leak. In December 2008, the “Zephyr Endobronchial Valve” (formerly Emphasys, now Pulmonx, Redwood City, CA) was considered by the Anesthesiology and Respiratory Therapy Device Panel for use as a permanent implant intended to improve forced air expiratory volume in one second (FEV1) and 6-minute walk test distance in patients with severe, heterogeneous emphysema who have received optimal medical management. The panel declined to recommend the device for FDA approval. Also, see the related medical policy, Lung Volume Reduction Surgery for Severe Emphysema. POLICYEndobronchial valves are considered investigational as a treatment of prolonged air leaks. Endobronchial valves are considered investigational as a treatment for patients with COPD or emphysema. POLICY EXCEPTIONSFederal Employee Program (FEP) may dictate that all FDA-approved devices, drugs or biologics may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity. POLICY GUIDELINESInvestigative service is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized by certifying boards and/or approving or licensing agencies or published peer review criteria as standard, effective medical practice for the treatment of the condition being treated and as such therefore is not considered medically necessary. The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language. POLICY HISTORY03/31/2011: Approved by Medical Policy Advisory Committee. 03/27/2012: Policy reviewed; no changes. 12/21/2012: Added the following new 2013 CPT codes to the Code Reference section: 31647, 31648, 31649 and 31651. 03/17/2014: Policy reviewed; no changes to policy statement. Removed deleted CPT codes 0250T, 0251T, and 0252T from the Code Reference section. SOURCE(S)Blue Cross Blue Shield Association policy # 7.01.128 This may not be a comprehensive list of procedure codes applicable to this policy.	2	6	2	0	0	0.776678	2	1,165
- Color blindness Color blindness or color deficiency Classification and external resources An 1895 illustration of normal vision and various kinds of color blindness ICD-10 H53.5 ICD-9 368.5 DiseasesDB 2999 MeSH D003117 Color blindness or color vision deficiency is the inability or decreased ability to see color, or perceive color differences, under lighting conditions when color vision is not normally impaired. "Color blind" is a term of art; there is no actual blindness but there is a fault in the development of either or both sets of retinal cones that perceive color in light and transmit that information to the optic nerve. The gene that causes color blindness is carried on the X chromosome, making the handicap more common among men (who have just one X chromosome) than among women (who have two, so must inherit the gene from both parents). The symptoms of color blindness also can be produced by physical or chemical damage to the eye, optic nerve, or the brain generally. These are not true color blindness, however, but they represent conditions of limited actual blindness. Similarly, a person with achromatopsia, although unable to see colors, is not "color blind" per se but they suffer from a completely different disorder, of which an atypical color deficiency is only one manifestation. The English chemist John Dalton published the first scientific paper on this subject in 1798, "Extraordinary facts relating to the vision of colours", after the realization of his own color blindness. Because of Dalton's work, the condition was often called daltonism, although this term is now used for a single type of color blindness, called deuteranopia. Color blindness is usually classed as a mild disability but there are situations where color blind individuals can have an advantage over those with normal color vision. Some studies conclude that color blind individuals are better at penetrating certain color camouflages; this may be an evolutionary explanation for the surprisingly high frequency of congenital red–green color blindness. This article is about color blindness in humans; for other species, see color vision. - 1 Background - 2 Classification - 3 Causes - 4 Diagnosis - 5 Management - 6 Epidemiology - 7 Society and culture - 8 Problems and compensations - 9 See also - 10 Notes - 11 References - 12 Bibliography - 13 External links The typical human retina contains two kinds of light cells: the rod cells (active in low light) and the cone cells (active in normal daylight). Normally, there are three kinds of cones, each containing a different pigment, which are activated when the pigments absorb light. The spectral sensitivities of the cones differ; one is maximally sensitive to short wavelengths, one to medium wavelengths, and the third to long wavelengths, with their peak sensitivities in the blue, yellowish-green, and yellow regions of the spectrum, respectively. The absorption spectra of all three systems cover the visible spectrum. These receptors are often called S cones, M cones, and L cones, for short, medium, and long wavelength; but they are also often referred to as blue cones, green cones, and red cones, respectively. Although these receptors are often referred to as "blue, green, and red" receptors, this terminology is not very accurate, especially as the "red" receptor actually has its peak sensitivity in the yellow region. The sensitivity of normal color vision actually depends on the overlap between the absorption spectra of the three systems: different colors are recognized when the different types of cone are stimulated to different degrees. Red light, for example, stimulates the long wavelength cones much more than either of the others, and reducing the wavelength causes the other two cone systems to be increasingly stimulated, causing a gradual change in hue. Many of the genes involved in color vision are on the X chromosome, making color blindness more common in males than in females because males have only one X chromosome, while females have two. Because this is an X-linked trait about 1% of women have a 4th color cone and can be considered tetrachromats although it is not clear that this provides an advantage in color discrimination. - Inherited: There are three types of inherited or congenital color vision deficiencies: monochromacy, dichromacy, and anomalous trichromacy. - Monochromacy, also known as "total color blindness," is the lack of ability to distinguish colors; caused by cone defect or absence. Monochromacy occurs when two or all three of the cone pigments are missing and color and lightness vision is reduced to one dimension. - Rod monochromacy (achromatopsia) is an exceedingly rare, nonprogressive inability to distinguish any colors as a result of absent or nonfunctioning retinal cones. It is associated with light sensitivity (photophobia), involuntary eye oscillations (nystagmus), and poor vision. - Cone monochromacy is a rare total color blindness that is accompanied by relatively normal vision, electoretinogram, and electrooculogram. - Dichromacy is a moderately severe color vision defect in which one of the three basic color mechanisms is absent or not functioning. It is hereditary and, in the case of Protanopia or Deuteranopia, sex-linked, affecting predominantly males. Dichromacy occurs when one of the cone pigments is missing and color is reduced to two dimensions. - Protanopia is a severe type of color vision deficiency caused by the complete absence of red retinal photoreceptors. It is a form of dichromatism in which red appears dark. It is hereditary, sex-linked, and present in 1% of males. - Deuteranopia is a color vision deficiency in which the green retinal photoreceptors are absent, moderately affecting red–green hue discrimination. It is a form of dichromatism in which there are only two cone pigments present. It is likewise hereditary and sex-linked. - Tritanopia is a very rare color vision disturbance in which there are only two cone pigments present and a total absence of blue retinal receptors. - Anomalous trichromacy is a common type of inherited color vision deficiency, occurring when one of the three cone pigments is altered in its spectral sensitivity. This results in an impairment, rather than loss, of trichromacy (normal three-dimensional color vision). - Protanomaly is a mild color vision defect in which an altered spectral sensitivity of red retinal receptors (closer to green receptor response) results in poor red–green hue discrimination. It is hereditary, sex-linked, and present in 1% of males. - Deuteranomaly, caused by a similar shift in the green retinal receptors, is by far the most common type of color vision deficiency, mildly affecting red–green hue discrimination in 5% of males. It is hereditary and sex-linked. - Tritanomaly is a rare, hereditary color vision deficiency affecting blue–yellow hue discrimination. Unlike most other forms, it is not sex-linked. By clinical appearance Based on clinical appearance, color blindness may be described as total or partial. Total color blindness is much less common than partial color blindness. There are two major types of color blindness: those who have difficulty distinguishing between red and green, and who have difficulty distinguishing between blue and yellow. - Total color blindness - Partial color blindness - Dichromacy (protanopia and deuteranopia) - Anomalous trichromacy (protanomaly and deuteranomaly) - Dichromacy (tritanopia) - Anomalous trichromacy (tritanomaly) Any recessive genetic characteristic that persists at a level as high as 5% is generally regarded as possibly having some advantage over the long term, such as better discrimination of color camouflaged objects especially in low-light conditions. At one time the U.S. Army found that color blind people could spot "camouflage" colors that fooled those with normal color vision.[not in citation given] Humans have a higher percentage of color blindness than macaque monkeys according to recent research. Another possible advantage might result from the presence of a tetrachromic female. Owing to X-chromosome inactivation, females who are heterozygous for anomalous trichromacy ought to have at least four types of cone in their retinae. It is possible that this affords them an extra dimension of color vision, by analogy to New World monkeys where heterozygous females gain trichromacy in a basically dichromatic species. Color blindness can be inherited. It is most commonly inherited from mutations on the X chromosome but the mapping of the human genome has shown there are many causative mutations – mutations capable of causing color blindness originate from at least 19 different chromosomes and 56 different genes (as shown online at the Online Mendelian Inheritance in Man (OMIM) database at Johns Hopkins University). Some of the inherited diseases known to cause color blindness are: - cone dystrophy - cone-rod dystrophy - achromatopsia (aka rod monochromatism, aka stationary cone dystrophy, aka cone dysfunction syndrome) - blue cone monochromatism, - Leber's congenital amaurosis. - retinitis pigmentosa (initially affects rods but can later progress to cones and therefore color blindness) Inherited color blindness can be congenital (from birth), or it can commence in childhood or adulthood. Depending on the mutation, it can be stationary, that is, remain the same throughout a person's lifetime, or progressive. As progressive phenotypes involve deterioration of the retina and other parts of the eye, certain forms of color blindness can progress to legal blindness, i.e., an acuity of 6/60 or worse, and often leave a person with complete blindness. Color blindness always pertains to the cone photoreceptors in retinas, as the cones are capable of detecting the color frequencies of light. About 8 percent of males, but only 0.5 percent of females, are color blind in some way or another, whether it is one color, a color combination, or another mutation. The reason males are at a greater risk of inheriting an X linked mutation is that males only have one X chromosome (XY, with the Y chromosome carrying altogether different genes than the X chromosome), and females have two (XX); if a woman inherits a normal X chromosome in addition to the one that carries the mutation, she will not display the mutation. Men do not have a second X chromosome to override the chromosome that carries the mutation. If 5% of variants of a given gene are defective, the probability of a single copy being defective is 5%, but the probability that two copies are both defective is 0.05 × 0.05 = 0.0025, or just 0.25%. Other causes of color blindness include brain or retinal damage caused by shaken baby syndrome, accidents and other trauma which produce swelling of the brain in the occipital lobe, and damage to the retina caused by exposure to ultraviolet light. Most ultraviolet light damage is caused during childhood and this form of retinal degeneration is the leading cause of blindness in the world. Damage often presents itself later on in life. Color blindness may also present itself in the spectrum of degenerative diseases of the eye, such as age-related macular degeneration, and as part of the retinal damage caused by diabetes. There are many types of color blindness. The most common are red–green hereditary photoreceptor disorders, but it is also possible to acquire color blindness through damage to the retina, optic nerve, or higher brain areas. Higher brain areas implicated in color processing include the parvocellular pathway of the lateral geniculate nucleus of the thalamus, and visual area V4 of the visual cortex. Acquired color blindness is generally unlike the more typical genetic disorders. For example, it is possible to acquire color blindness only in a portion of the visual field but maintain normal color vision elsewhere. Some forms of acquired color blindness are reversible. Transient color blindness also occurs (very rarely) in the aura of some migraine sufferers. The different kinds of inherited color blindness result from partial or complete loss of function of one or more of the different cone systems. When one cone system is compromised, dichromacy results. The most frequent forms of human color blindness result from problems with either the middle or long wavelength sensitive cone systems, and involve difficulties in discriminating reds, yellows, and greens from one another. They are collectively referred to as "red–green color blindness", though the term is an over-simplification and is somewhat misleading. Other forms of color blindness are much more rare. They include problems in discriminating blues from yellows, and the rarest forms of all, complete color blindness or monochromacy, where one cannot distinguish any color from grey, as in a black-and-white movie or photograph. Congenital color vision deficiencies are subdivided based on the number of primary hues needed to match a given sample in the visible spectrum. Monochromacy is the condition of possessing only a single channel for conveying information about color. Monochromats possess a complete inability to distinguish any colors and perceive only variations in brightness. It occurs in two primary forms: - Rod monochromacy, frequently called achromatopsia, where the retina contains no cone cells, so that in addition to the absence of color discrimination, vision in lights of normal intensity is difficult. While normally rare, achromatopsia is very common on the island of Pingelap, a part of the Pohnpei state, Federated States of Micronesia, where it is called maskun: about 10% of the population there has it, and 30% are unaffected carriers. The island was devastated by a storm in the 18th century, and one of the few male survivors carried a gene for achromatopsia; the population is now several thousand. - Cone monochromacy is the condition of having both rods and cones, but only a single kind of cone. A cone monochromat can have good pattern vision at normal daylight levels, but will not be able to distinguish hues. Blue cone monochromacy (X chromosome) is caused by a complete absence of L and M cones (red and green). It is encoded at the same place as red–green color blindness on the X chromosome. Peak spectral sensitivities are in the blue region of the visible spectrum (near 440 nm). People with this condition generally show nystagmus ("jiggling eyes"), photophobia (light sensitivity), reduced visual acuity, and myopia (nearsightedness). Visual acuity usually falls to the 20/50 to 20/400 range. Protanopes, deuteranopes, and tritanopes are dichromats; that is, they can match any color they see with some mixture of just two spectral lights (whereas normally humans are trichromats and require three lights). These individuals normally know they have a color vision problem and it can affect their lives on a daily basis. Protanopes and deuteranopes see no perceptible difference between red, orange, yellow, and green. All these colors, that seem so different to the normal viewer, appear to be the same color for this two percent of the population. The terms protanopia, deuteranopia, and tritanopia come from Greek, and literally mean "inability to see (anopia) with the first (prot-), second (deuter-), or third (trit-) [cone]", respectively. - Protanopia (1% of males): Lacking the long-wavelength sensitive retinal cones, those with this condition are unable to distinguish between colors in the green–yellow–red section of the spectrum. They have a neutral point at a greenish wavelength around 492 nm – that is, they cannot discriminate light of this wavelength from white. For the protanope, the brightness of red, orange, and yellow are much reduced compared to normal. This dimming can be so pronounced that reds may be confused with black or dark gray, and red traffic lights may appear to be extinguished. They may learn to distinguish reds from yellows and from greens primarily on the basis of their apparent brightness or lightness, not on any perceptible hue difference. Violet, lavender, and purple are indistinguishable from various shades of blue because their reddish components are so dimmed as to be invisible. for example, pink flowers, reflecting both red light and blue light, may appear just blue to the protanope. Very few people have been found who have one normal eye and one protanopic eye. These unilateral dichromats report that with only their protanopic eye open, they see wavelengths below the neutral point as blue and those above it as yellow. This is a rare form of color blindness. - Deuteranopia (1% of males): Lacking the medium-wavelength cones, those affected are again unable to distinguish between colors in the green–yellow–red section of the spectrum. Their neutral point is at a slightly longer wavelength, 498 nm. The deuteranope suffers the same hue discrimination problems as the protanope, but without the abnormal dimming. Similarly, violet, lavender, purple, and blue all seem much the same to a deuteranope. This form of colorblindness is also known as Daltonism after John Dalton. (Dalton's diagnosis was confirmed as deuteranopia in 1995, some 150 years after his death, by DNA analysis of his preserved eyeball.) Deuteranopic unilateral dichromats report that with only their deuteranopic eye open, they see wavelengths below the neutral point as blue and those above it as yellow. - Tritanopia (less than 1% of males and females): Lacking the short-wavelength cones, those affected are unable to distinguish colors along the blue–yellow dimension. This form of color blindness is not sex-linked. Those with protanomaly, deuteranomaly, or tritanomaly are trichromats, but the color matches they make differ from the normal. They are called anomalous trichromats. In order to match a given spectral yellow light, protanomalous observers need more red light in a red/green mixture than a normal observer, and deuteranomalous observers need more green. From a practical standpoint though, many protanomalous and deuteranomalous people have very little difficulty carrying out tasks that require normal color vision. Some may not even be aware that their color perception is in any way different from normal. Protanomaly and deuteranomaly can be diagnosed using an instrument called an anomaloscope, which mixes spectral red and green lights in variable proportions, for comparison with a fixed spectral yellow. If this is done in front of a large audience of males, as the proportion of red is increased from a low value, first a small proportion of the audience will declare a match, while most will see the mixed light as greenish; these are the deuteranomalous observers. Next, as more red is added the majority will say that a match has been achieved. Finally, as yet more red is added, the remaining, protanomalous, observers will declare a match at a point where normal observers will see the mixed light as definitely reddish. - Protanomaly (1% of males, 0.01% of females): Having a mutated form of the long-wavelength (red) pigment, whose peak sensitivity is at a shorter wavelength than in the normal retina, protanomalous individuals are less sensitive to red light than normal. This means that they are less able to discriminate colors, and they do not see mixed lights as having the same colors as normal observers. They also suffer from a darkening of the red end of the spectrum. This causes reds to reduce in intensity to the point where they can be mistaken for black. Protanomaly is a fairly rare form of color blindness, making up about 1% of the male population. Both protanomaly and deuteranomaly are carried on the X chromosome. - Deuteranomaly (most common — 6% of males, 0.4% of females): These individuals have a mutated form of the medium-wavelength (green) pigment. The medium-wavelength pigment is shifted towards the red end of the spectrum resulting in a reduction in sensitivity to the green area of the spectrum. Unlike protanomaly the intensity of colors is unchanged. This is the most common form of color blindness, making up about 6% of the male population. The deuteranomalous person is considered "green weak". For example, in the evening, dark green cars appear to be black to Deuteranomalous people. Similar to the protanomates, deuteranomates are poor at discriminating small differences in hues in the red, orange, yellow, green region of the spectrum. They make errors in the naming of hues in this region because the hues appear somewhat shifted towards red. One very important difference between deuteranomalous individuals and protanomalous individuals is deuteranomalous individuals do not have the loss of "brightness" problem. - Tritanomaly (equally rare for males and females [0.01% for both]): Having a mutated form of the short-wavelength (blue) pigment. The short-wavelength pigment is shifted towards the green area of the spectrum. This is the rarest form of anomalous trichromacy color blindness. Unlike the other anomalous trichromacy color deficiencies, the mutation for this color blindness is carried on chromosome 7. Therefore it is equally prevalent in both male & female populations. The OMIM gene code for this mutation is 304000 "Colorblindness, Partial Tritanomaly". Total color blindness Achromatopsia is strictly defined as the inability to see color. Although the term may refer to acquired disorders such as color agnosia and cerebral achromatopsia, it typically refers to congenital color vision disorders (i.e. more frequently rod monochromacy and less frequently cone monochromacy). In color agnosia and cerebral achromatopsia, a person cannot perceive colors even though the eyes are capable of distinguishing them. Some sources do not consider these to be true color blindness, because the failure is of perception, not of vision. They are forms of visual agnosia. Red–green color blindness Those with protanopia, deuteranopia, protanomaly, and deuteranomaly have difficulty with discriminating red and green hues. It is sex-linked: genetic red–green color blindness affects males much more often than females, because the genes for the red and green color receptors are located on the X chromosome, of which males have only one and females have two. Females (46, XX) are red–green color blind only if both their X chromosomes are defective with a similar deficiency, whereas males (46, XY) are color blind if their single X chromosome is defective. The gene for red–green color blindness is transmitted from a color blind male to all his daughters who are heterozygote carriers and are usually unaffected. In turn, a carrier woman has a fifty percent chance of passing on a mutated X chromosome region to each of her male offspring. The sons of an affected male will not inherit the trait from him, since they receive his Y chromosome and not his (defective) X chromosome. Should an affected male have children with a carrier or colorblind woman, their daughters may be colorblind by inheriting an affected X chromosome from each parent. Because one X chromosome is inactivated at random in each cell during a woman's development, it is possible for her to have four different cone types, as when a carrier of protanomaly has a child with a deuteranomalic man. Denoting the normal vision alleles by P and D and the anomalous by p and d, the carrier is PD pD and the man is Pd. The daughter is either PD Pd or pD Pd. Suppose she is pD Pd. Each cell in her body expresses either her mother's chromosome pD or her father's Pd. Thus her red–green sensing will involve both the normal and the anomalous pigments for both colors. Such females are tetrachromats, since they require a mixture of four spectral lights to match an arbitrary light. Blue–yellow color blindness Those with tritanopia and tritanomaly have difficulty discriminating blueish versus yellowish hues. Color blindness involving the inactivation of the short-wavelength sensitive cone system (whose absorption spectrum peaks in the bluish-violet) is called tritanopia or, loosely, blue–yellow color blindness. The tritanopes neutral point occurs near a yellowish 570 nm; green is perceived at shorter wavelengths and red at longer wavelengths. Mutation of the short-wavelength sensitive cones is called tritanomaly. Tritanopia is equally distributed among males and females. Jeremy H. Nathans (with the Howard Hughes Medical Institute) proved that the gene coding for the blue receptor lies on chromosome 7, which is shared equally by males and females. Therefore it is not sex-linked. This gene does not have any neighbor whose DNA sequence is similar. Blue color blindness is caused by a simple mutation in this gene. The Ishihara color test, which consists of a series of pictures of colored spots, is the test most often used to diagnose red–green color deficiencies. A figure (usually one or more Arabic digits) is embedded in the picture as a number of spots in a slightly different color, and can be seen with normal color vision, but not with a particular color defect. The full set of tests has a variety of figure/background color combinations, and enable diagnosis of which particular visual defect is present. The anomaloscope, described above, is also used in diagnosing anomalous trichromacy. Because the Ishihara color test contains only numerals, it may not be useful in diagnosing young children, who have not yet learned to use numerals. In the interest of identifying these problems early on in life, alternative color vision tests were developed using only symbols (square, circle, car). Besides the Ishihara color test, the US Navy and US Army also allow testing with the Farnsworth Lantern Test. This test allows 30% of color deficient individuals, whose deficiency is not too severe, to pass. Most clinical tests are designed to be fast, simple, and effective at identifying broad categories of color blindness. In academic studies of color blindness, on the other hand, there is more interest in developing flexible tests to collect thorough datasets, identify copunctal points, and measure just noticeable differences. There is generally no treatment to cure color deficiencies. However, certain types of tinted filters and contact lenses may help an individual to better distinguish different colors. Optometrists can supply a singular red-tint contact lens to wear on the non-dominant eye. This may enable the wearer to pass some color blindness tests, but they have little practical use. The effect of wearing such a device is akin to wearing red/blue 3D glasses and can take some time getting used to as certain wavelengths can "jump" out and be overly represented. Additionally, computer software and cybernetic devices have been developed to assist those with visual color difficulties such as an eyeborg, a "cybernetic eye" that allows individuals with color blindness to hear sounds representing colors. The GNOME desktop environment provides colorblind accessibility using the gnome-mag and the libcolorblind software. Using a gnome applet, the user may switch a color filter on and off choosing from a set of possible color transformations that will displace the colors in order to disambiguate them. The software enables, for instance, a color blind person to see the numbers in the Ishihara test. In September 2009, the journal Nature reported that researchers at the University of Washington and University of Florida were able to give trichromatic vision to squirrel monkeys, which normally have only dichromatic vision, using gene therapy. Color blindness affects a significant number of people, although exact proportions vary among groups. In Australia, for example, it occurs in about 8 percent of males and only about 0.4 percent of females. Isolated communities with a restricted gene pool sometimes produce high proportions of color blindness, including the less usual types. Examples include rural Finland, Hungary, and some of the Scottish islands. In the United States, about 7 percent of the male population – or about 10.5 million men – and 0.4 percent of the female population either cannot distinguish red from green, or see red and green differently from how others do (Howard Hughes Medical Institute, 2006). It has been found that more than 95 percent of all variations in human color vision involve the red and green receptors in male eyes. It is very rare for males or females to be "blind" to the blue end of the spectrum. Prevalence of color blindness Males Females Total References Overall — — — Overall (United States) — — — Red–green (Overall) 7 to 10% — — Red–green (Caucasians) 8% — — Red–green (Asians) 5% — — Red–green (Africans) 4% — — Monochromacy — — — Rod monochromacy (dysfunctional, abnormally shaped or no cones) 0.00001% 0.00001% — Dichromacy 2.4% 0.03% 1.30% Protanopia (red deficient: L cone absent) 1% to 1.3% 0.02% — Deuteranopia (green deficient: M cone absent) 1% to 1.2% 0.01% — Tritanopia (blue deficient: S cone absent) 0.001% 0.03% — Anomalous Trichromacy 6.3% 0.37% — Protanomaly (red deficient: L cone defect) 1.3% 0.02% — Deuteranomaly (green deficient: M cone defect) 5.0% 0.35% — Tritanomaly (blue deficient: S cone defect) 0.01% 0.01% — Society and culture Design implications of color blindness Color codes present particular problems for those with color deficiencies as they are often difficult or impossible for them to perceive. Good graphic design avoids using color coding or using color contrasts alone to express information; this not only helps color blind people, but also aids understanding by normally sighted people. Designers need to take into account that color-blindness is highly sensitive to differences in material. For example, a red–green colorblind person who is incapable of distinguishing colors on a map printed on paper may have no such difficulty when viewing the map on a computer screen or television. In addition, some color blind people find it easier to distinguish problem colors on artificial materials, such as plastic or in acrylic paints, than on natural materials, such as paper or wood. Third, for some color blind people, color can only be distinguished if there is a sufficient "mass" of color: thin lines might appear black while a thicker line of the same color can be perceived as having color. Designers should also consider that no one is simply red-blue, green-blue, yellow-blue, or yellow-red colorblind. using these color combinations, instead of the ever popular red means bad and green means good system, can lead to a much higher ability to use color coding effectively. This will still cause problems for those with monochromatic color blindness, but it is still something worth considering. When the need to process visual information as rapidly as possible arises, for example in an emergency situation, the visual system may operate only in shades of gray, with the extra information load in adding color being dropped. This is an important possibility to consider when designing, for example, emergency brake handles or emergency phones. Color blindness may make it difficult or impossible for a person to engage in certain occupations. Persons with color blindness may be legally or practically barred from occupations in which color perception is an essential part of the job (e.g., mixing paint colors), or in which color perception is important for safety (e.g., operating vehicles in response to color-coded signals). This occupational safety principle originates from the Lagerlunda train crash of 1875 in Sweden. Following the crash, Professor Alarik Frithiof Holmgren, a physiologist, investigated and concluded that the color blindness of the engineer (who had died) had caused the crash. Professor Holmgren then created the first test using different-colored skeins to exclude people from jobs in the transportation industry on the basis of color blindness. Driving motor vehicles Some countries (for example, Romania) have refused to grant individuals with color blindness driving licenses. In Romania, there is an ongoing campaign to remove the legal restrictions that prohibit colorblind citizens from getting drivers' licenses. The usual justification for such restrictions is that drivers of motor vehicles must be able to recognize color-coded signals, such as traffic lights or warning lights. While many aspects of aviation depend on color coding, only a few of them are critical enough to be interfered with by some milder types of color blindness. Some examples include color-gun signaling of aircraft that have lost radio communication, color-coded glide-path indications on runways, and the like. Some jurisdictions restrict the issuance of pilot credentials to persons who suffer from color blindness for this reason. Restrictions may be partial, allowing color-blind persons to obtain certification but with restrictions, or total, in which case color-blind persons are not permitted to obtain piloting credentials at all. In the United States, the Federal Aviation Administration requires that pilots be tested for normal color vision as part of the medical certification that is prerequisite to obtaining a pilot's license. If testing reveals color blindness, the applicant may be issued a license with restrictions, such as no night flying and no flying by color signals—such a restriction effectively prevents a pilot from working for an airline. The government allows several types of tests, including medical standard tests (e.g., the Ishihara, Dvorine, and others) and specialized tests oriented specifically to the needs of aviation. If an applicant fails the standard tests, he or she will receive a restriction on their medical certificate that states- "Not valid for night flying or by color signal control." He/she may apply to the FAA to take a specialized test, administered by the FAA. Typically, this test is the "color vision light gun test." For this test an FAA inspector will meet the pilot at an airport with an operating control tower, and the color signal light gun will be shone at the pilot from the tower, and he or she must identify the color. If he passes, he may be issued a waiver, which states that the color vision test is no longer required during medical examinations. He will then receive a new medical certificate with the restriction removed. This was once a Statement of Demonstrated Ability (SODA), but the SODA was dropped, and converted to a simple waiver (letter) early in the 2000s. Research published in 2009 carried out by the City University of London's Applied Vision Research Centre, sponsored by the UK's Civil Aviation Authority and the US Federal Aviation Administration, has established a more accurate assessment of color deficiencies in pilot applicants' red–green and yellow–blue color range which could lead to a 35% reduction in the number of prospective pilots who fail to meet the minimum medical threshold. Inability to distinguish color does not necessarily preclude the ability to become a celebrated artist. The expressionist painter Clifton Pugh, three-time winner of Australia's Archibald Prize, on biographical, gene inheritance and other grounds has been identified as a protanope. 19th century French artist Charles Méryon became successful by concentrating on etching rather than painting after he was diagnosed as having a red–green deficiency. Problems and compensations Color blindness very rarely means complete monochromatism. In almost all cases, color blind people retain blue–yellow discrimination, and most color-blind individuals are anomalous trichromats rather than complete dichromats. In practice this means that they often retain a limited discrimination along the red–green axis of color space, although their ability to separate colors in this dimension is severely reduced. Dichromats often confuse red and green items. For example, they may find it difficult to distinguish a Braeburn apple from a Granny Smith and in some cases, the red and green of a traffic light without other clues (for example, shape or location). The vision of dichromats may also be compared to images produced by a color printer that has run out of the ink in one of its three color cartridges (for protanopes and deuteranopes, the magenta cartridge, and for tritanopes, the yellow cartridge). Dichromats tend to learn to use texture and shape clues and so are often able to penetrate camouflage that has been designed to deceive individuals with color-normal vision. Traffic light colors are confusing to some dichromats as there is insufficient apparent difference between the red/amber traffic lights, and that of sodium street lamps; also the green can be confused with a grubby white lamp. This is a risk factor on high-speed undulating roads where angular cues can't be used. British Rail color lamp signals use more easily identifiable colors: the red is blood red, the amber is yellow and the green is a bluish color. Most British road traffic lights are mounted vertically on a black rectangle with a white border (forming a "sighting board") and so dichromats simply look for the position of the light within the rectangle — top, middle or bottom. In the Eastern provinces of Canada horizontally-mounted traffic lights are generally differentiated by shape to facilitate identification for those with color blindness. - Articles with images not understandable by color blind users - Cerebral achromatopsia - Ishihara color test - Motion blindness - ^ a b c d Because of variations in computer displays, these illustrations may not be accurately rendered. - ^ Dalton J (1798). "Extraordinary facts relating to the vision of colours: with observations". Memoirs of the Literary and Philosophical Society of Manchester 5: 28–45. - ^ a b c Morgan MJ, Adam A, Mollon JD (June 1992). "Dichromats detect colour-camouflaged objects that are not detected by trichromats". Proc. Biol. Sci. 248 (1323): 291–5. doi:10.1098/rspb.1992.0074. PMID 1354367. http://rspb.royalsocietypublishing.org/cgi/pmidlookup?view=long&pmid=1354367. - ^ a b "Color Blindness." University of Illinois Eye Center, Department of Ophthalmology and Visual Sciences. Retrieved September 29, 2006. - ^ Kokotailo R, Kline D. "Congenital Colour Vision Deficiencies." University of Calgary, Department of Psychology, Vision & Aging Lab. Retrieved September 29, 2006. - ^ a b c d "Guidelines: Color Blindness." Tiresias.org. Retrieved April 2, 2011. - ^ a b c d e f g h i Cassin, B. and Solomon, S. Dictionary of Eye Terminology. Gainsville, Florida: Triad Publishing Company, 1990. - ^ Spring, Kenneth R.; Matthew J. Parry-Hill; Thomas J. Fellers; Michael W. Davidson. "Human Vision and Color Perception". Florida State University. http://micro.magnet.fsu.edu/primer/lightandcolor/humanvisionhome.html. Retrieved 2007-04-05. - ^ Paul S. Hoffman. "Accommodating Color Blindness" (PDF). http://www.digitalspaceart.com/articles/ColorBlindness.pdf. Retrieved 2009-07-01. - ^ Neitz, Maureen E., PhD. "Severity of Colorblindness Varies". Medical College of Wisconsin. http://healthlink.mcw.edu/article/999211295.html. Retrieved 2007-04-05. - ^ Saito, Atsuko; Akichika Mikami, Takayuki Hosokawa, Toshikazu Hasegawa (2006-02). "Advantage of Dichromats Over Trichromats in Discrimination of Color-Camouflaged Stimuli in Humans1,2". Perceptual and Motor Skills 102 (1): 3–12. doi:10.2466/pms.102.1.3-12. ISSN 0031-5125. http://www.amsciepub.com/doi/abs/10.2466/pms.102.1.3-12. Retrieved 2011-06-25. - ^ Waggoner, Terrace L.. "About Color Blindness (Color Vision Deficiency) :Clinical information about color blindness". Colors for the Color Blind. http://www.toledo-bend.com/colorblind/aboutcb.asp. Retrieved 2009-10-29. - ^ REIT, SEYMOUR. (1979). MASQUERADE: THE AMAZING CAMOUFLAGE DECEPTIONS OF WORLD WAR 2. - ^ Onishi A, Koike S, Ida M, et al. (November 1999). "Dichromatism in macaque monkeys". Nature 402 (6758): 139–40. doi:10.1038/45963. PMID 10647004. - ^ Jordan G, Mollon JD (July 1993). "A study of women heterozygous for colour deficiencies". Vision Res. 33 (11): 1495–508. doi:10.1016/0042-6989(93)90143-K. PMID 8351822. http://linkinghub.elsevier.com/retrieve/pii/0042-6989(93)90143-K. Jameson KA, Highnote SM, Wasserman LM (June 2001). "Richer color experience in observers with multiple photopigment opsin genes". Psychon Bull Rev 8 (2): 244–61. doi:10.3758/BF03196159. PMID 11495112. http://pbr.psychonomic-journals.org/cgi/pmidlookup?view=long&pmid=11495112. - ^ Sharpe, LT; Stockman A, Jägle H, Nathans J (1999). "Opsin genes, cone photopigments, color vision and color blindness". In Gegenfurtner KR, Sharpe LT. Color Vision: From Genes to Perception. Cambridge University Press. ISBN 9780521004398. http://books.google.com/?id=4zQMQLLVkFYC. - ^ colblindor.com - ^ a b Byrne A, Hilbert D. "A Glossary of Color Science." Originally published in Readings on Color, Volume 2: The Science of Color. (MIT Press, 1997). Retrieved November 7, 2006. - ^ [dead link] - ^ Weiss AH, Biersdorf WR (1989). "Blue cone monochromatism". J Pediatr Ophthalmol Strabismus 26 (5): 218–23. PMID 2795409. - ^ David L. MacAdam (ed.) and Deane B. Judd (1979). Contributions to color science. NBS. p. 584. http://books.google.com/books?id=jgz_iI8NAzYC&pg=PA584. - ^ a b c Kalloniatis, Michael and Luu, Charles. "Psychophysics of Vision: The Perception of Color". http://webvision.med.utah.edu/KallColor.html#deficiencies. Retrieved 2007-04-02. - ^ Montgomery, Ted M., O.D.. "The Macula". http://www.tedmontgomery.com/the_eye/macula.html#X-chrome. Retrieved 2007-04-02. - ^ "Disease-causing Mutations and protein structure". UCL Biochemistry BSM Group. http://www.biochem.ucl.ac.uk/bsm/humgen/chr__034.html#304000. Retrieved 2007-04-02. - ^ a b Jan Dirk Blom (2009). A Dictionary of Hallucinations. Springer. p. 4. ISBN 9781441912220. http://books.google.com/books?id=KJtQptBcZloC&pg=PA4. - ^ a b "Seeing, Hearing and Smelling the World, a Report for the Howard Hughes Medical Institute". Howard Hughes Medical Institute. http://www.hhmi.org/senses/b130.html. Retrieved 2010-02-18. - ^ Toufeeq A (October 2004). "Specifying colours for colour vision testing using computer graphics". Eye (Lond) 18 (10): 1001–5. doi:10.1038/sj.eye.6701378. PMID 15192692. - ^ Zeltzer,, Harry I. (March 1991). "Patent application for contact lens for correction of color blindness". freepatentsonline.com. FreePatentsOnline.com. http://www.freepatentsonline.com/4998817.html. Retrieved 2009-10-28. - ^ Anon (19 January 2005). "Seeing things in a different light". BBC Devon features. BBC. http://www.bbc.co.uk/devon/news_features/2005/eyeborg.shtml. Retrieved 2009-10-30. - ^ Dolgin E (2009-09-16). "Colour blindness corrected by gene therapy". Nature News. doi:10.1038/news.2009.921. http://www.nature.com/news/2009/090916/full/news.2009.921.html. - ^ "Colour blindness". Better Health Channel. http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Colour_blindness. Retrieved 2007-04-02. - ^ a b c d "Prevalence and Incidence of Color blindness". WrongDiagnosis.com. 2008-06-22. http://www.wrongdiagnosis.com/c/color_blindness/prevalence.htm. Retrieved 2008-07-10. - ^ "Color Blindness: More Prevalent Among Males". Hhmi.org. http://www.hhmi.org/senses/b130.html. Retrieved 2009-04-16. - ^ a b c Masataka Okabe, Kei Ito (2008-02-15). "Colorblind Barrier Free". J*Fly. http://jfly.iam.u-tokyo.ac.jp/color/. Retrieved 2008-07-10. - ^ a b c d e f g h i Archive.org - ^ Vingrys AJ, Cole BL (1986). "Origins of colour vision standards within the transport industry". Ophthalmic Physiol Opt 6 (4): 369–75. doi:10.1111/j.1475-1313.1986.tb01155.x. PMID 3306566. - ^ "Petition to European Union on Colorblind’s condition in Romania". http://discromat.wordpress.com/2007/08/15/time-out/. Retrieved 2007-08-21. - ^ "Aerospace Medical Dispositions — Color vision". http://www.faa.gov/about/office_org/headquarters_offices/avs/offices/aam/ame/guide/app_process/exam_tech/item52/amd/. Retrieved 2009-04-11. - ^ Warburton, Simon (29 May 2009). "Colour-blindness research could clear more pilots to fly: UK CAA". Air transport. Reed Business Information. http://www.flightglobal.com/articles/2009/05/29/327137/colour-blindness-research-could-clear-more-pilots-to-fly-uk.html. Retrieved 29 October 2009. - ^ Cole BL, Harris RW (September 2009). "Colour blindness does not preclude fame as an artist: celebrated Australian artist Clifton Pugh was a protanope". Clin Exp Optom 92 (5): 421–8. doi:10.1111/j.1444-0938.2009.00384.x. PMID 19515095. - ^ Anon. "Charles Meryon". Art Encyclopedia. The Concise Grove Dictionary of Art.. Oxford University Press. http://www.answers.com/topic/charles-m-ryon. Retrieved 7 January 2010. - Kaiser, Peter K.; Boynton, R.M. (1996). Human Color Vision (2nd ed.). Washington, DC: Optical Society of America. ISBN 1-55752-461-0. - McIntyre, Donald (2002). Colour Blindness: Causes and Effects. UK: Dalton Publishing. ISBN 0-9541886-0-8. - Shevell, Steven K. (2003). The Science of Color (2nd ed.). Oxford, UK: Optical Society of America. p. 350. ISBN 0-444-512-519. - Smal, James; Hilbert, D.S. (1997). Readings on Color, Volume 2: The Science of Color (2nd ed.). Cambridge, Massachusetts: MIT Press. ISBN 0-262-52231-4. - Wyszecki, Günther; Stiles, W.S. (2000). Color Science: Concepts and Methods, Quantitative Data and Formulae (2nd ed.). Wiley-Interscience. ISBN 0-471-39918-3. Physiology: Eye and ear physiology Vision Auditory system Color topics Color perception Color space Basic colors Related Wikimedia Foundation. 2010.	2	29	8	0	2	0.26306	10	10,633
I. Pulmonary Arterial Hypertension: What Every Physician Needs To Know. Pulmonary arterial hypertension (PAH) is a disorder specific to the pulmonary arteries, resulting in an increase in pulmonary artery pressure (PAP), and pulmonary vascular resistance (PVR), leading to right ventricular (RV) dysfunction, right heart failure, and death. Pulmonary hypertension (PH) refers to elevated pressure in the pulmonary vasculature that can result from a wide range of conditions. It is critical to go through the appropriate diagnostic tests to determine whether your patient has PAH versus PH related to other underlying systemic disorders since treatment approaches are vastly different. Right heart catheterization (RHC) is the only method of diagnosing PAH (see section II: Right Heart Catheterization: Necessary to Diagnose PAH). There are currently nine PAH-specific treatments approved by the U.S. Food and Drug Administration (FDA). It is imperative to note that these treatments are not approved or indicated for PH, and can be harmful when used inappropriately (see Management section). Pulmonary hypertension is defined as a resting mean pulmonary artery pressure (mPAP) greater than or equal to 25 mm Hg. Pulmonary arterial hypertension is defined as a resting mean pulmonary artery pressure (mPAP) greater than or equal to 25 mm Hg, and a pulmonary capillary wedge pressure (PCWP) less than or equal to 15 mm Hg. The American College of Cardiology Foundation and the American Heart Association definition of PAH also includes pulmonary vascular resistance greater than 3 Wood units. The current classification comes from the 4th World Symposium on Pulmonary Hypertension held in 2008 at Dana Point. PH is classified into five groups listed below. In essence, PAH includes the idiopathic PAH (IPAH) and associated conditions that affect pulmonary arteries, with similar presentations and responses to PAH-specific medical therapies. It should be noted that all clinical trials performed resulting in approval of therapies have been done on the Group I PAH population. Group 1: Pulmonary arterial hypertension (PAH) Drug- and toxin-induced PAH Connective tissue diseases Congenital heart diseases Chronic hemolytic anemia Persistent pulmonary hypertension of the newborn Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH) Group 2: Pulmonary hypertension owing to left heart disease Group 3: Pulmonary hypertension owing to lung diseases and/or hypoxia Chronic obstructive pulmonary disease Interstitial lung disease Other pulmonary diseases with a mixed restrictive and obstructive pattern Alveolar hypoventilation disorders Chronic exposure to high altitude Group 4: Chronic thromboembolic PH (CTEPH) Group 5: PH with unclear multifactorial mechanisms Hematologic disorders: myeloproliferative disorders, splenectomy Systemic disorders: sarcoidosis; pulmonary Langerhans cell histiocytosis: lymphangioleiomyomatosis, neurofibromatosis, vasculitis Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis 1. Primary pulmonary hypertension or “PPH”; this term is still frequently used in the clinical setting; officially no longer supported in literature. It has been replaced by the term idiopathic pulmonary arterial hypertension or IPAH. 2. Secondary pulmonary hypertension; similarly this term is no longer used in literature. It was used to denote PH of all types, except for PPH. 3. Precapillary PH; this is a hemodynamic terminology, referring to pulmonary arterial hypertension (elevated pulmonary pressure stemming from precapillary region [i.e., normal PCWP]). 4. Postcapillary PH; this is a hemodynamic term, referring to pulmonary venous hypertension (PVH) (elevated pulmonary pressure stemming from the postcapillary region; that is, elevated PCWP). PAH results from restriction of blood flow through pulmonary arteries that leads to increase in PVR and consequently resulting in right heart failure. The increase in PVR is related to various mechanisms including: vasoconstriction, obstructive remodeling of the pulmonary vessel wall, inflammation, and thrombosis. Though the process by which PAH is initiated and progresses is heterogeneous, it is thought that PAH is the result of an interaction of a predisposing state plus one or more stimuli, a concept termed “multiple-hit hypothesis.” It involves an individual rendered susceptible due to genetic abnormality or substrate. The second “hit” may be either a systemic disorder (i.e., collagen vascular disease or HIV), an environmental trigger (i.e., hypoxia or anorexigen), or additional genetic conditions (i.e., mutation or polymorphism). Since the absolute risk of PAH (or those with known risk factors) is generally low, it is believed that individual susceptibility or genetic predisposition likely plays a significant role in the disease initiation and progression. This is thought to be an early component of the pulmonary hypertensive process. Significant vasoconstriction has been linked to abnormal function or expression of potassium channels in the smooth muscle cells and to endothelial dysfunction. B. Endothelial Dysfunction Mediated Processes Currently Targeted for PAH Treatments The PA endothelium tightly regulates the production of vasodilators and vasoconstrictors to maintain a low-pressured state. In PAH, an imbalance of the mediators occur resulting in overproduction of vasoconstricting agents and diminished level of vasodilators (Figure 1). Prostacyclin and Thromboxane A2 – these are metabolites of arachidonic acid. Prostacyclin is a potent vasodilator, inhibitor of platelet activation, and exerts antiproliferative effects; thromboxane A2 is a potent vasoconstrictor and promotes platelet activation. In PAH, there is a decreased prostacyclin synthase and an increased production of thromboxane A2 leading to decreased prostacyclin. Nitric oxide (NO) – this produces vasodilatation, inhibits platelet activation and vascular smooth muscle cell proliferation. The effects of NO are mediated through its second messenger, cyclic guanosine monophosphate (cGMP), which is rapidly degraded by phosphodiesterase (PDE). NO in the pulmonary circulation is degraded by PDE-5 isoenzymes, which is present in abundance in the lung tissue. This is the basis of using PDE-5 inhibition in PAH. Endothelin-1 (ET-1) – this is a potent vasoconstrictor and stimulator of PA smooth muscle cell proliferation. The plasma level of ET-1 is increased in PAH and its level has been shown to be inversely proportional to the magnitude of the pulmonary blood flow and cardiac output. ET-1 exerts its effects through two receptors – ETA and ETB. Clearance of ET-1 in the pulmonary vasculature is reduced in PAH. The rationales of current therapeutic approaches are directed at correcting the imbalance of the mediators by: 1. Augmenting actions of prostacyclins and increasing NO-induced activity 2. Blocking the ET-1 mediated processes C. Additional mechanisms 1. Serotonin (5-hydroxytryptamine) – is a vasoconstrictor that promotes smooth muscle cell hypertrophy and hyperplasia. Elevated plasma serotonin and reduced content of serotonin in platelets have been reported in IPAH and PAH associated with ingestion of dexfenfluramine, which increases the release of serotonin from platelets and inhibits its reuptake. Furthermore, mutations in the serotonin transporter (5-HTT) and its receptor 5-HT2B have been described in PAH patients. However, it is not certain if elevated serotonin levels are implicated in PAH since selective serotonin-reuptake inhibitors (SSRI) are not associated with an increased incidence of PH and remains unclear (see below). 2. Potassium channels – Inhibition of voltage-dependent potassium channels (Kv) have been linked to factors which promote PAH, such as hypoxia and fenfluramine derivatives. 3. Abnormalities of the coagulant cascade – Including increased levels of von Willebrand factor, plasminogen activator inhibitor-1, and plasma fibrinopeptide have been reported in PAH patients. 4. Inflammatory factors – Proinflammatory cytokines and autoantibodies have been implicated in PAH. D. Genetic Substrates Mutations in the gene encoding bone morphogenetic protein receptor type 2 (BMPR2) have been found to be associated with heritable PAH. BMPR2 is a component of the heteromeric vascular smooth muscle cell BMPR receptor, a member of the transforming growth factor ß (TGFß) signaling pathway. These mutations result in cellular proliferation. Activin-like kinase (ALK1), a less common mutation also in the TGFß family, is associated with hereditary hemorrhagic telangiectasia and PAH. In PAH, it has been observed that there is a collection of abnormalities that favor a decreased apoptosis/proliferation ratio in PA smooth muscle cells. These abnormal factors include inappropriate activation of transcription factors HIF-1α and NFAT, decreased expression of certain K+ channels (i.e., Kv1.5 and Kv2.1) and de novo expression of the antiapoptotic proteins. Histologic changes include: 1. Medial hypertrophy – due to both hypertrophy and hyperplasia of smooth muscle fibers, as well as an increase in connective tissue matrix; results in increase in the cross-sectional area of the media 2. Intimal thickening – occurring either as concentric or eccentric patterns, immunohistochemical stains show features of fibroblasts, myofibroblasts, and smooth muscle cells. 3. Adventitial thickening – seen in most cases of PAH 4. Plexiform lesions – end-stage lesions formed by a focal proliferation of endothelial channels lined by myofibroblasts, smooth muscle cells, and connective tissue matrix. Arteritis may be associated with plexiform lesions. Although it is the pulmonary arterial vasculature where the pathologic processes take place in PAH, the factor which determines symptoms and survival rests on the ability of the RV to function under the increased pressure and resistance. The RV is a thin-walled, compliant, crescent-shaped structure, formed by the RV free wall and the interventricular septum. Due to the low resistance of the pulmonary vasculature, the compliant RV is designed to pump the same stroke volume as the LV with 1/6 of the work. The determinant factor rests on how well the RV adapts to the increased afterload in PAH. Normal RV is coupled to low pressure in the pulmonary vascular system. In pulmonary hypertension, RV becomes uncoupled, challenged with elevated afterload in the pulmonary vasculature. The RV demonstrates a heightened sensitivity to changes in afterload and the RV stroke volume decreases proportionately to acute increases in afterload. The initial response is usually RV hypertrophy, although early studies in postacute pulmonary embolus demonstrated that previously normal RV is incapable of acutely generating mPAP >40 mm Hg. This hypertrophic process can be followed by contractile dysfunction and/or RV dilatation for further compensatory maneuver in order to maintain cardiac output. Continued remodeling of the RV soon causes alterations in RV shape from crescent to concentric, which in turn flattens out the septum. Ventricular interdependence refers to the concept that the size, shape, and compliance of one ventricle may affect the same factors in the neighboring ventricle. In the presence of RV volume or pressure overload, the interventricular septum shifts toward the left and limits LV filling and output. The consequences of RV remodeling include: (1) Decreased coronary perfusion pressure in the setting of increased oxygen demand; (2) due to interventricular dependence, RV remodeling results in LV diastolic dysfunction and a decrease in LV end diastolic volume. These changes result in RV-PA uncoupling, a term coined to describe the inability of the RV to work in concert with the high afterload of the PA. The end result is further decline in stroke volume and deterioration of end organ perfusion. Interestingly, the development of RV failure due to PH is quite variable. It is unclear why some RVs can compensate maintaining adequate cardiac output for prolonged periods while others immediately dilate and progress into right heart failure. Several mechanisms have been proposed including: (1) Retention of the “fetal” genotype, which is believed to be a contributory factor resulting in favorable outcome for PAH associated with congenital heart disease (CHD); (2) polymorphisms in genes related to the renin-angiotensin-aldosterone system; (3) differences in the degree of ischemia and apoptosis. Although the past two decades have witnessed an explosion of knowledge in PAH, culminating in nine FDA therapies for this “orphan” disease, the reality is that there is still a considerable delay in the recognition and diagnosis of PAH. The ongoing Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) database is the largest collection of information dedicated to PAH patients with 54 centers participating in the U.S. One of the most revealing findings is the fact that despite our advances in PAH, there is still a significant delay between symptom onset to diagnosis, with the median time reported to be 13.6 months (34.1 +/- 1.2 months). When one compares this duration to the measurement assessed with the original NIH PPH Registry conducted in the 1980s when very limited information was known about this condition, it was 2.0 years. Thus there has been some improvement, but the delay is still significant. Why diagnosing PAH is challenging: Relative rarity of the disease (diagnosis not considered by most physicians). Nonspecific nature of the presenting symptoms, such as shortness of breath and fatigue. Common misdiagnoses include asthma, deconditioned or being “out of shape,” weight gain and obesity, and depression. Routine outpatient tests (labs, electrocardiography, chest radiograph) are not sensitive nor specific to detect until condition is advanced. No easily identifiable physical examination characteristics (see section IV: Physical Examination). In order to evaluate and manage a patient with PAH, the physician must: Recognize predisposing factors and comorbidities that place certain patients at risk. Acknowledge that a high degree of suspicion is necessary to proceed to screening for PAH with an echocardiogram due to the nonspecific nature of the presenting symptoms. Know the usefulness and pitfalls of echocardiography as a screening tool. Understand how to complete an evaluation for PAH to determine the type of PH. Know that right heart catheterization (RHC) is the only method of diagnosing PAH. Regarding acute vasoreactivity testing, know when it is indicated and how to interpret the data. Perform risk assessment to determine appropriate therapy. Know the pros and cons of each therapy. Know the goals of treatment. Know how to follow patients long-term to determine treatment response and efficacy. Know how to manage PAH crisis/right ventricular failure. Know what the indications are to refer for lung transplantation. II. Diagnostic Confirmation: are you sure your patient has Pulmonary Arterial Hypertension? If PH is suspected (based on history, risk factor assessment, and physical examination), an echocardiogram is the next step. The Doppler echocardiogram provides the following: Estimation of RV systolic pressure Done by using the modified Bernoulli equation 4v2 v is the velocity of the tricuspid regurgitation (TR) jet in m/s. Right ventricular systolic pressure (RVSP) is derived by adding the right atrial pressure (RAP) to the gradient (RVSP = 4v2 + RAP). The RAP is either a standardized value or an estimated value based on the echocardiographic characteristics of the inferior vena cava, or the vertical height of the jugular venous pulse on physical examination. Degree of correlation between RVSP derived from TR jet and hemodynamics from RHCs with marked various results from poor to significant correlations. Several factors attribute to the various results: Spectral Doppler profile of TR is too weak or insufficient to measure the RV to RA pressure gradient in about 10% to 25% patients referred for PH evaluation. The signal can be enhanced by intravenous bolus administration of a small amount of agitated saline contrast or with commercially available encapsulated microbubble contrast agents which are used to enhance imaging quality. Very small amounts are needed to define TR jet, but the encapsulated agents need to be used with caution in patients with significant pulmonary vascular disease/pulmonary disorder. Patients with comorbidities (obesity, pulmonary disorder) have demonstrated worse correlation, mostly related to difficulty in obtaining adequate acoustic windows. Thus it is important to note the technical quality of the study to determine how reliable the echo is to indicate possible presence of PAH. Lack of accuracy of RAP estimation can significantly influence the RVSP result, especially in “borderline” elevated pressure. Doppler echocardiography may underestimate RVSP in patients with severe PH due to inadequate jet visualization and overestimate in patients with near normal pressures usually as a result of inaccurate RAP estimation. Evaluation of RV size and function to assess functional and morphologic cardiac consequences due to PAH Size and function of the RV have been shown to be critical determinants in the outcome of patients with PAH. Presence of enlarged right atrium and RV, septal flattening, and reduced RV systolic function highly correlate with significant PH and are well recognized markers of poor prognosis. Methods of assessing quantitative measures of RV function: Visual estimation – most often used but highly subjective. RV fractional area change done in apical four chamber view. Though this method incorporates both longitudinal and transverse RV shortening into a single measurement, it can be limited by incomplete endocardial definition leading to high variability. TAPSE (tricuspid annular plane systolic excursion) – simple to perform and has shown to be reproducible in PAH. This measures the total longitudinal systolic displacement of the RV base toward the RV apex, performed using the 2-D echocardiography or M-mode. Normal TAPSE is 2.4-2.7 cm. Ranges of RV dysfunctions are: mild (1.9-2.2 cm), moderate (1.5-1.8 cm), and severe (<1.5 cm). Presence any pericardial effusion (even trivial) has been found to be associated with worse prognosis. To rule out left heart disease (LHD) as a cause of PH since diagnosis of PAH mandates the absence of clinically significant LHD. Assessment of LV size, structure and function is important to exclude significant LV systolic and diastolic dysfunction, enlargement, and hypertrophy. Close scrutiny for diastolic abnormalities is becoming more relevant since older patients with multiple cardiac risk factors are being diagnosed with elevated pulmonary pressure (see Competing Diagnoses That Can Mimic Pulmonary Hypertension section). Presence of left atrial enlargement, even in the absence of obvious LV dysfunction, should raise the suspicion of elevated left-sided pressure and a diagnosis of pulmonary venous hypertension (PVH) rather than PAH. In these patients, it is critical to obtain a reliable pulmonary capillary wedge pressure (PCWP) during right heart catheterization; if a satisfactory PCWP cannot be obtained, left heart catheterization may need to be performed to accurately measure the left ventricular end diastolic pressure to definitively rule out PVH. PAH-specific therapies can worsen PVH by precipitating pulmonary edema. It has been suggested that LA size can be viewed for PH as HgbA1c for DM. It is a marker of duration, chronicity, and severity of left-sided pressure elevation Assess for valvular abnormality and congenital heart disease, which can precede or coincide with the diagnosis of PH. An echocardiographic contrast (“bubble”) study using agitated saline solution can screen for presence of intracardiac shunting. Transesophageal echocardiography (TEE) can add more refined structural information in these cases and may better define atypically situated atrial septal defects of the sinus venosus type (Table 2). Right Heart Catheterization: Necessary To Diagnose PAH Right heart catheterization is needed in PAH to: Establish the diagnosis of PAH by confirming that pulmonary artery pressures are elevated with normal left sided filling pressure. Perform acute vasodilator testing for patients with a new diagnosis of PAH of idiopathic, hereditary, or anorexigen-associated conditions. Assess prognosis of PAH based on RAP and cardiac output measurements. Guide treatment of the patient The normal PAP is systolic 15-30 mm Hg, diastolic 4-12 mm Hg, and mean 9-18 mm Hg. The normal PA pulse pressure is approximately 15 mm Hg. The upstroke of the PAP waveform marks the onset of RV ejection followed by systolic peak and pressure decay. The dicrotic notch is due to pulmonic valve closure. The peak of the PAP wave occurs within the T wave of surface electrocardiography. A gradient should not exist between the RV and PA systolic measurements, unless there is pulmonary valvular or pulmonary artery stenosis (Table 3). PAP waveform is affected by respiratory changes similar to other right-sided pressure. The pressure changes upon cardiac chambers due to respiration are negligible under normal physiology. Important exceptions to this are seen for patients on mechanical ventilatory support, respiratory distress, marked pulmonary disease, or morbid obesity, where a significant variation in intrathoracic pressure can be seen resulting in marked differences in PAPs with the respiratory cycle. A reading at the end-expiration should be obtained since this is the phase where intrathoracic pressure is closest to zero. Pulmonary Artery Pressure Measurements in PAH The PA diastolic pressure is close (within 2-4 mm Hg) to both the mean PCWP and left ventricular end-diastolic pressure (LVEDP) in normal individuals (normal pulmonary vascular resistance and in the absence of mitral valve disease). The PA diastolic pressure does not correlate well with the mean PCWP in the presence of pulmonary vascular disease where the PA diastolic pressure overestimates the mean PCWP. The lack of correlation is also seen in mitral regurgitation with large v wave where the PA diastolic pressure underestimates the mean PCWP. The normal mean PCWP is 2-12 mm Hg. The PCWP is used as a measurement of left-sided filling pressure and under normal physiology, a close correlation exists between the PCWP, left atrial pressure, and LVEDP. Conditions where the PCWP does not correlate with LVEDP include in the presence of following conditions: Severe mitral regurgitation or aortic regurgitation Pulmonary venous obstruction Significant LV noncompliance Accurate measurement of left heart filling pressure is critical for the correct diagnosis of PAH: Definition of PAH requires both elevation of mPAP (≥ 25 mm Hg) and normal PCWP or LVEDP (≤ 15 mm Hg). The difference between these two measurements calculates the transpulmonary gradient (TPG = mPAP – PCWP in mm Hg). Accurate PCWP is critical in calculating PVR (PVR = TPG/CO in Wood units). Elevated PCWP is characteristic of PH in the setting of chronically elevated left-sided cardiac filling pressure, termed pulmonary venous hypertension (PVH), and is classified as WHO Group 2 PH (see Clinical Classification section). PVH usually results from systolic and/or diastolic cardiac dysfunction or valvular heart diseases. Therefore, therapeutic decisions can be significantly different based on the left-sided filling pressure measurement. PAH is characterized by elevated PAPs, normal PCWP, and elevated TPG. PVH is characterized by elevated PAPs, elevated PCWP, and normal TPG. Common Pitfalls in Obtaining Accurate PCWP: Underwedging or Hybrid Waveform “Underwedging” typically occurs with incomplete advancement of the PA catheter resulting in a hybrid tracing of PAP and PCWP. This usually results in a falsely elevated PCWP, leading to misdiagnosing a patient as PVH. If an operator is suspicious that the PCWP being measured is greater than expected based on clinical assessment, an oxygen saturation measurement can be done from the distal port with the catheter in the wedge position. It should be equal or close to the systemic arterial oxygen saturation (usually >90%) done by pulse oximetry. If lower, the catheter is most likely underwedged. Placing the catheter in the correct PCWP position can be very difficult in a patient with significantly elevated PAPs, especially if PA is markedly dilated. One helpful maneuver is deflating the balloon, allowing the catheter to migrate distally, and carefully reinflating the balloon following the pressure tracings closely. Usually with this approach, optimal placement is obtained with balloon partially inflated. An intraluminal guide wire can also aid in advancing the catheter to a more distal position. All these maneuvers must be performed very cautiously and under direct fluoroscopic visualization; it must be remembered that patients with PAH are at increased risk of PA rupture, a likely fatal event. Common Pitfalls in Obtaining Accurate PCWP: Overwedged Waveform “Overwedged” tracing occurs due to excessive inflation of the balloon relative to the size of the vessel. The result is a characteristic pressure tracing, which is usually easily detected. This should be avoided not only due to inaccurate pressure measurement but due to the increase in risk of vessel rupture. In bedside catheter measurements, the potential for PA catheter migration also needs to be kept in mind. The balloon should be slowly inflated at every measurement with close monitoring of the pressure tracings, with inflation stopped when a PCWP tracing is obtained. Common Pitfalls in Obtaining Accurate PCWP: The “V” Wave The v wave is a normal finding on the wedge tracing and normally higher than the a wave so as to what measurement constitutes a “large” v wave can be subjective. Common causes of a large v wave include mitral regurgitation (MR), though the height of the v wave is neither sensitive nor a specific indicator of the degree of MR. Other causes include any situations that increase the volume or flow into a noncompliant left atrium, such as ventricular septal defect, mitral stenosis, cardiomyopathy of any etiology, or postoperative surgical conditions. The presence of a large v wave distorts the correlation between the PA diastolic pressure and PCWP so PA diastolic pressure now underestimates the mean PCWP. A large v wave causes the PCWP to overestimate the LVEDP. The best point to estimate the LV filling pressure in the presence of a large v wave is to measure the wedge pressure at end diastole, which coincides with end of a wedge pressure a wave. In PAH where determination of an accurate wedge pressure is critical to guide therapy, if there is any question regarding accuracy or reliability of the measurement, obtaining LVEDP is recommended. Characteristics of a Physiologically Reliable PCWP Distinct a and v waves should be present. An exception is noted in atrial fibrillation where an a wave will be absent. Need to wait for steady state in PCWP tracing to occur (not immediately after the balloon is inflated) and record at end-expiratory phase. A distinct immediate rise in pressure when balloon is deflated out of the wedge position. Catheter tip should be stable in PA when viewed under fluoroscopy with the balloon inflated (not moving back and forth). An oxygen saturation measured in PCWP >90%. Multiple measurements of PCWP with similar results. If these maneuvers fail to obtain a reliable PCWP, a left heart catheterization should be performed to measure LVEDP. Normal cardiac output (CO) at rest is 5-8 L/min and the normal cardiac index is 2.6-4.2 L/min/m2 (see Table 3). Accurate cardiac output measurement is critical in calculating PVR and assessing prognosis in PAH. The total pulmonary resistance (TPR) calculates the relationship between the mPAP and CO: TPR = mPAP × 80/CO; the normal TRP is 100-300 dynes-sec-cm-5. The PVR measures the resistance to flow imposed by the pulmonary vasculature without the influence of the left-sided filling pressure: PVR = (mPAP – PCWP) × 80/CO or PVR = TPG × 80/CO; the normal PVR is 20-130 dynes-sec-cm-5 (PVR = TPG/CO in Wood units) CO assessment is a critical measure of RV performance in the presence of elevated PAPs and decreased cardiac index (<2.2 or 2.5 L/min/m2, pending sources) is a marker of poor prognosis. Fick Cardiac Output The Fick output equation is based upon the principle that in the absence of a significant intracardiac shunt, the pulmonary blood flow and the systemic blood flow are equal. CO = oxygen consumption/arteriovenous oxygen difference, or CO = oxygen consumption/(arterial saturation – mixed venous saturation) × (Hgb) × 13.6. The measurement of the arteriovenous oxygen (AV O2) difference provides an estimate of the cardiac output. The arterial oxygen saturation is the constant factor for most individuals. Thus changes in AV O2 difference reflect the increase or decrease in the mixed venous oxygen saturation. A decrease in the CO is compensated by an increase in tissue oxygen extraction, which results in the decrease in the mixed venous saturation. The correlation between cardiac output and changes in mixed venous oxygen saturation applies in the setting of constant hemoglobin, arterial oxygen saturation, and oxygen consumption. In most hemodynamic laboratories, due to the impracticality of obtaining the exact oxygen consumption which requires collecting the patient’s exhaled air over several minutes, “assumed Fick” is used, which is derived from oxygen consumption based on the patient’s age, gender, and body surface area. Potential sources of error include incorrect measurement of venous or arterial blood samples, presence of mitral or aortic regurgitation, and intracardiac shunting or peripheral shunting at the tissue level, such as in septic shock. Thermodilution Cardiac Output Thermodilution cardiac output is derived by injecting a 10-ml bolus of saline over 2-4 seconds into the RA via the proximal port. This is done with the distal catheter tip in a stable position in the PA and not in a “wedge” position. The cardiac output measurements are obtained in triplicates, and the variances between the measurements should be less than 10%. Thermodilution method can potentially overestimate CO in low flow states when compared with Fick method. The thermodilution method is known to be inaccurate in the presence of severe TR, intracardiac shunts, low output states, and marked respiratory variation. With significant TR, a portion of the indicator warms during its prolonged stay within the RA and RV, which produces a characteristic curve with a slow decay to baseline temperature. Although the Fick method is used often in the presence of TR, studies have demonstrated conflicting results regarding the accuracy of both techniques. Evaluation for Intracardiac Shunting Chronic left-to-right intracardiac shunting can produce PAH. Echocardiogram with agitated saline contrast can detect right-to-left shunt but can fail to detect left-to-right shunts. Multiple measurements of oxygen saturations from superior and inferior vena cava, right atrium, and PA can detect and quantify shunts. This step is a crucial part of right heart catheterization in a patient with clinical or echocardiographic suspicion of intracardiac shunting. The risks associated with RHC in PAH has been studied. A recent multicenter study, which included 15 PAH centers over a 5-year period with more than 7,000 procedures evaluated the safety and risks of performing RHC in the PAH population. The overall incidence of serious adverse events was 1.1%. The most frequent complications were related to obtaining venous access; others included arrhythmia and hypotension due to vagal reactions or pulmonary vasoreactivity testing. When performed in experienced centers, RHC in PAH patients are safe and associated with low morbidity rates. Maneuvers To Enhance Safety RHC can be performed via femoral or jugular approach and is often determined by operator’s preference. Accessing from an internal jugular approach allows use of an ultrasound device to visualize the size and depth of the vein, which can enhance safety. PAH patients often have dilated right-sided chambers, which can make maneuvering the catheter difficult, especially under high pressure systems and under significant tricuspid valvular regurgitation. Performing the procedure under fluoroscopy reduces the risks of catheter “coiling” and inducing arrhythmia. Direct visualization also assists in placing the catheter in the safe and optimal “wedge” position to avoid PA rupture, “overwedging” and migration of the catheter. Fluoroscopy is also necessary in patients with intracardiac devices. Obtaining peripheral IV access in patients prior to starting the procedure is recommended to promptly deliver treatment in the event of vagal episodes, which can lead to significant clinical deterioration in PAH patients. The purpose of evaluating PAH patients with a short-acting vasodilator is to determine the degree in which the pulmonary vasoconstriction is contributing to the elevated PAPs. Vasodilator responsiveness identifies patients with a better prognosis and those who are more likely to have a sustained beneficial response to calcium channel blockers (CCB). Before PAH-directed therapies were available, initial reports of improved outcome upon treatment with high doses of oral nifedipine or diltiazem led to a flurry of treatment with CCBs. However, only a small number of patients (approximately 6%) were found to be “responders” in large series retrospective analysis. For the majority of patients who are not responders, treatment with high dose CCBs can result in clinical deterioration (hypotension, arrhythmia, syncope, or death), which can be worsened by the long half-life of the agents. Reports of adverse outcomes associated with vasodilator testing with CCBs led to the use of short-acting agents to assess responsiveness to identify those patient who may be considered treating with CCBs. Intravenous epoprostenol and IV adenosine have both been studied as acute vasodilators. Both are short-acting, potent vasodilators and investigators have reported different degrees of responsiveness depending on the criteria used. However, because both agents have the potential to cause systemic hypotension and side effects, using inhaled nitric oxide (NO) has emerged as the vasodilator of choice due to its pulmonary selectivity, short half-life, and lack of systemic side effects. However, it is expensive and requires trained respiratory personnel to administer (Table 4). The definition of what constitutes acute vasodilator “responder” has undergone changes over the years. Initial studies used a composite decrease in mPAP and PVR of 20%-30% to define responsiveness. A recent analysis by the European group has demonstrated that the number of patients who remained stable long term (>1 year) on CCB monotherapy (initially placed using the previous definition of 20% reduction in PAP and PVR) was smaller than previously reported (6.8%). A comparison of the initial vasoreactivity hemodynamics between patients who remained stable on CCB alone versus those who decompensated on CCBs led the European Society of Cardiology to define a positive acute vasodilator responder in an IPAH patient as: A fall in mPAP of at least 10 mm Hg to less than or equal to 40 mm Hg and Increased or unchanged CO For the small number of patients who demonstrate significant hemodynamic response and meet the criteria, initiation of treatment with CCBs can be considered. Such treatment requires very close vigilant follow-up to monitor for both efficacy and safety. For patients who fail to improve by clinical and objective criteria (reach FC II symptoms, exercise, and hemodynamic parameters) within the initial 3 months, treatment with PAH-directed therapies need to be implemented. The majority of patients who fail to achieve this acute response are not likely to respond to CCBs. Contraindications for CCB treatment (and acute vasodilator testing) include patients with advanced disease defined as: Functional class IV symptoms Overt clinical right heart failure Hemodynamic markers of advanced process (high RAP and/or reduced CO, systemic hypotension) Patients with such an advanced state should not undergo acute vasodilator testing since these patients need prompt treatment with PAH-approved therapies. It needs to be emphasized that all the CCB testing and treatments were performed in IPAH patients. For patients with PAH associated with other underlying processes (i.e., scleroderma), the number of patients who had acute vasodilatory response is even less, and the net benefit of vasodilator testing is at best weak if used for the sole purpose of determining candidates for CCB therapies. The development of acute pulmonary edema during vasodilator testing should raise the suspicion of veno-occlusive disease or pulmonary capillary hemangiomatosis, in which therapy with pulmonary vasodilator is contraindicated. Assessment of Prognosis Since PAH is a disease manifested by an increase in afterload of pulmonary arteries leading to progressive right ventricular dysfunction and failure, hemodynamic markers are considered to be the gold standard for indicating prognosis. This was first demonstrated in the NIH PPH Registry in the 1980s where the investigators concluded that “mortality was most closely associated with right ventricular hemodynamic function and can be characterized by means of an equation using three variables: mean pulmonary artery pressure, mean right atrial pressure, and cardiac index.” Specifically, RAP greater than or equal to 20 mm Hg, mPAP greater than or equal to 85 mm Hg, and CI less than 2 L/min/m2 were shown to be associated with an increased risk of death. The data obtained were the basis of formulating the regression equation to calculate survival based on hemodynamics, which was validated in a prospective study. Subsequent studies have corroborated the importance of elevated RAP (>12 or 15 mm Hg, pending sources) and low cardiac index (<2.2 or 2.5 L/min/m2, pending sources) as determinants of poor outcome. The relevance of mPAP on prognosis has been variable. In the retrospective study among patients treated with epoprostenol, patients with lower mPAP correlated with poor outcome, which may indicate that mPAP per se is not a reliable surrogate for RV function but needs to be assessed as part of pulmonary vascular resistance. A. History Part 1: Pattern Recognition Diagnosing PAH can be challenging primarily due to the nonspecific nature of the presenting symptoms. Here is a list of common baseline demographics and presenting symptoms of PAH patients: From the REVEAL Registry, which reports current PAH patient population from U.S. centers, the mean age is reported to be 53 ± 14 years and majority (80%) to be females. From the NIH PPH Registry, the most common presenting symptoms were the following: Dyspnea (98%), fatigue (73%), chest pain (47%), near syncope (41%), syncope (36%), leg edema (37%), and palpitations (33%). The quality of dyspnea has been described as progressive and “relentless,” different from seasonal or allergic-related phenomena. Dyspnea is usually exacerbated by activity, particularly going up an incline or climbing steps are usually reported to be difficult. Other activities patients describe being problematic include bending down (to pick up objects off the floor), squatting (such as to tie shoes), vacuuming, carrying any weight up the stairs, and lifting any objects overhead. It is not uncommon for these activities to produce dizziness and/or chest pain; in patients with severe PAH, they can provoke syncope. The difficulties faced in performing these activities reflect hemodynamic changes that increase pulmonary vascular flow and/or resistance. Young patient presenting with syncope: need to at least consider PAH. Although PAH is a rare disorder, it should be considered in the differential for a young patient presenting with syncope associated with exertion (i.e., related to sports activity). PAH in a young patient can be difficult to recognize because young individuals can compensate well during initial stages of PAH and the condition can progress rapidly (especially if related to a genetic mutation). B. History Part 2: Prevalence: These are updated risk factors for PAH as outlined from the Dana Point World Symposium in 2008. Risk factors for PAH include “any factor or condition that is suspected to play a predisposing or facilitating role in the development of the disease.” Definite association – defined as an epidemic or from a large, multicenter epidemiologic study aminorex, fenfluramine, dexfenfluramine, toxic rapeseed oil Possible association – defined as drugs with similar mechanisms of action as those in the “definite” or “likely” categories but which have not been studied cocaine, phenylpropanolamine, St. John’s Wort, chemotherapeutic agents, SSRI Likely association – defined as a single-center, case-control study demonstrating an association or a multiple-case series amphetamines, L-tryptophan, methamphetamines Recent observational studies have reported methamphetamine abuse significantly increases the risk of developing PAH Unlikely association – defined as one in which a drug has been studied in epidemiologic studies and an association with PAH has not been demonstrated Oral contraceptives, estrogen, cigarette smoking A. Idiopathic PAH (IPAH) – corresponds to sporadic disease in which there is neither a family history of PAH nor an identified risk factor. Recent epidemiologic studies show that the prevalence for PAH is 15 cases per million; for IPAH, 5.9 cases per million. A trend for older age range of patients being diagnosed has shown to be increasing (patients >70 years of age). REVEAL registry has shown that the majority are females (80%). B. Heritable PAH – when PAH occurs with a family history. Mutations in the BMPR2 gene can be detected in approximately 70% of the cases that are transmitted in autosomal dominant pattern. U.S. Registries among PH centers report prevalence of PAH associated with positive family history ranging from 10% to 13%. Characteristics of genetic transmission include: Variable penetrance – there can be “skipped” generations as far as phenotypic manifestations. Genetic anticipation – the disease can manifest at an earlier age with more aggressive features in subsequent generations. Recent studies have suggested that patients with PAH associated with BMPR2 mutations most likely represent a subgroup of patients with more severe disease and are less likely to demonstrate vasoreactivity than those with IPAH without BMPR2 mutations. This stresses the need to understand the indications for performing acute vasoreactivity testing during right heart catheterization (see Right Heart Catheterization, Acute Vasodilator Testing). It should be noted that all patients with BMPR2 mutations have heritable disease, regardless of family history. BMPR2 mutations have been identified in 11% to 40% of IPAH patients with no family history. C. Drug and toxin-induced PAH – the most recent update of identified drugs and toxins associated with PAH are listed above in Risk Factors in PAH. A few recent findings include: Serotonin produces vasoconstriction, promotes PA smooth muscle cell hypertrophy and hyperplasia, and has been implicated in PAH. However, serotonin level alone per se is probably not likely a determinant of PAH since serotonin-reuptake inhibitors have not been associated with an increased incidence of PAH. However, a recent case control study that brought this line of thought into question regarding the use of selective serotonin reuptake inhibitors in pregnant women after 20 weeks of gestation was found to have a possible association with an increased risk in offspring developing persistent PH of the newborn. The role of serotonin with PAH in the setting of pregnancy needs further evaluation. A significant association between methamphetamine use, whether inhaled, smoked, taken orally or intravenously, and the development of IPAH has been reported. D. PAH associated with connective tissue disease (CTD) – among all CTDs, scleroderma patients represent the largest subset of patients at risk for developing PAH. The prevalence of PAH has been well studied only for the systemic sclerosis population. Recent studies using echocardiography as screening and RHC for confirmation found a prevalence of PAH between 7% and 12%. The most recent analysis from the REVEAL Registry demonstrates that patients with CTD-associated PAH had a worse overall outcome compared with IPAH patients (1-year survival rate and freedom from hospitalization, 85% for IPAH and 67% for CTD-associated PAH ). This is particularly true for patients with PAH associated with scleroderma. Thus CTD patients represent the largest group at risk and for those who develop PAH and the worst prognosis (even with PAH-specific therapies). It is recommended for scleroderma patients to have a baseline echocardiogram and PFTs [International and European guidelines recommend annual Doppler echocardiography]. Obtain a follow-up test with development of any symptoms. It is most challenging to detect if any pulmonary vascular disease is progressing since dyspnea and/or fatigue can occur due to the underlying disease or treatments. It is recommended that if patients have these symptoms, which cannot be explained by other reasons, PAH should be considered and an echocardiogram evaluated. With findings consistent with PAH, RHC needs to be performed. A recently published report suggests that improved outcome can be seen with patients diagnosed due to active screening, though the effects of lead time bias need to be considered. Patients with systemic sclerosis can have other processes that can cause elevated PAPs other than PAH, such as lung fibrosis, diastolic dysfunction, and primary cardiac involvement due to scleroderma. This stresses the critical importance of RHC to confirm the elevated PAPs and to classify its etiology, whether PAH or pulmonary venous hypertension, to determine appropriate therapy. E. PAH associated with HIV infection – shown to have clinical, hemodynamic, and histologic characteristics similar to those seen in IPAH Recent prevalence reported to be 0.46%. Mechanism remains unclear. Indirect action of the virus through secondary messengers (cytokines, growth factors, endothelin, and viral proteins) suspected. Small studies have shown a benefit of PAH-directed therapy in patients with HIV (bosentan, epoprostenol). Current recommendations include monitoring and optimal treatment with both antiretroviral and PAH-specific therapies. F. PAH associated with liver disease – portopulmonary hypertension is development of PAH in association with elevated pressure in the portal circulation. It is the presence of portal hypertension, rather than underlying liver disease, that is the main risk factor. All candidates for liver transplantation need to undergo echocardiography to screen for portopulmonary hypertension. If the echocardiogram shows elevated pulmonary pressure, RHC must be performed to confirm the diagnosis and assess risk/candidacy for liver transplant. Overall about 8% of candidates for liver transplantation have portopulmonary hypertension and are at risk of its complications. A recent study identified female sex and autoimmune hepatitis as risk factors for development of portopulmonary hypertension (hepatitis C associated with decreased risk in this study). Pathologic changes in the small arteries in patients with portopulmonary hypertension appear identical to those seen in IPAH. RHC is absolutely critical for diagnosis of portopulmonary hypertension because there are several other factors that can elevate PAPs with advanced liver disease, such as high CO associated with the hyperdynamic circulatory state and elevated PCWP due to fluid overload and/or diastolic dysfunction. G. PAH associated with congenital heart disease (CHD) – with the number of patients with adult CHD increasing, long-term complications, which include PH and right heart failure, pose serious risks for this group of patients. Patients with hemodynamically significant systemic-to-pulmonary shunts will develop PAH if left untreated. This can result in Eisenmenger syndrome, which is defined as CHD with an initial large systemic-to-pulmonary shunt that initiates and propagates pulmonary vascular changes due to the persistent presence of increased blood flow and pressure, which over time increases PVR that results in a reversal of the shunt and cyanosis. Eisenmenger syndrome represents the most advanced form of PAH associated with CHD. Prevalence of PAH associated with congenital systemic-to-pulmonary shunts in Europe and North America has been estimated to range between 1.6 and 12.5 cases per million adults; 25% to 50% of this population have been shown to be affected by Eisenmenger syndrome. H. PAH associated with schistosomiasis – most likely due to multifactorial mechanisms, including portopulmonary hypertension (which is a common complication of schistosomiasis) and vascular inflammation (as a result of impacted Schistosoma eggs). This entity has been shown to have a similar clinical presentation to IPAH and histologic findings, including plexiform lesions. It is estimated that more than 200 million people are infected with Schistosoma and that 4% to 8% will develop hepatosplenic disease. Recent hemodynamic data demonstrate prevalence of PAH to be 4.6% of those individuals with hepatosplenic disease. Pulmonary venous hypertension is also common (3%), which addresses the need for invasive hemodynamic studies. I. PAH associated with chronic hemolytic anemia – PH has been most well described in patients with sickle cell disease (SCD). Prevalence of PAH in SCD is not clearly established. The largest study reported 32% of patients had PH; however, PH was defined echocardiographically. There is very limited data with hemodynamic confirmation and a large proportion of patients with SCD have pulmonary venous hypertension. Furthermore, a hyperdynamic state leading to high CO can also result in moderate elevation of PAPs with normal PVR. The mechanism of PAH in SCD remains unclear. It has been proposed that chronic hemolysis results in high rates of nitric oxide consumption and produces a state of resistance of nitric oxide bioactivity. A. Patients with hereditary PAH – genetic mutations predisposing to PAH (i.e., BMPR2) identified Echocardiogram yearly; RHC if echo demonstrates evidence of PAH (high RVSP or right heart chamber enlargement) B. First degree relative of a patient with BMPR2 mutation (or within pedigree of two or more patients with a diagnosis of PAH) Genetic counseling regarding BMPR2 genotyping Echocardiogram yearly; RHC if echo demonstrates evidence of PAH (high RVSP or right heart chamber enlargement) C. Patients with systemic sclerosis Response to approved PAH treatment not as favorable compared to IPAH Early detection, accurate diagnosis, and appropriate therapy imperative Baseline echocardiogram and yearly thereafter; RHC if echo demonstrates evidence of PAH (high RVSP or right heart chamber enlargement) D. HIV infection Echocardiogram if symptoms or signs are suggestive of PAH; RHC if echo demonstrates evidence of PAH (high RVSP or right heart chamber enlargement) E. Patients with portal hypertension prior to liver transplantation All candidates for liver transplantation need to undergo echocardiogram RHC is necessary for full hemodynamic measurements; increased PAP associated with significant risk of perioperative mortality and contraindication to transplantation F. Prior appetite suppressant use Echocardiogram only if symptomatic G. Patients with congenital systemic to pulmonary shunts Echocardiogram and RHC at the time of diagnosis Consider repair of defect if significant L-R shunt present (need to consider RV function, degree of hypoxia, and PVR) High probability of PAH developing if unrepaired shunts (Eisenmenger syndrome) H. Recent acute pulmonary embolism VQ scan 3 months after event if symptomatic, and echocardiogram pending clinical course Pulmonary angiogram if results positive G. Sickle cell disease Echocardiogram yearly; RHC if echo demonstrates evidence of PAH C. History Part 3: Competing diagnoses that can mimic Pulmonary Arterial Hypertension Diastolic dysfunction leading to diastolic heart failure (DHF; aka HFpEF: heart failure with preserved ejection fraction) refers to a clinical syndrome in which patients present with heart failure symptoms with preserved left ventricular (LV) systolic function. Epidemiologic studies have shown high prevalence of DHF (approximately 40%-70%) among symptomatic patients and the risk factors have been well elucidated (age >65 years, hypertension, elevated pulse pressure, obesity, coronary artery disease, diabetes mellitus, and atrial fibrillation). The predominant underlying structural abnormalities in diastolic heart failure are concentric remodeling and hypertrophy of the LV caused by chronic pressure overload, usually due to systemic hypertension. These alterations produce abnormalities in both relaxation and filling, which can be a precursor to LV systolic dysfunction or the main structural abnormality, producing symptoms and signs of heart failure. Patients presenting with diastolic dysfunction and PH is a common clinical dilemma and can be very challenging to distinguish from PAH. Up to 70% of patients with LV diastolic dysfunction may develop PH, the presence of which is associated with a poor prognosis. The presentations are similar to PAH and include dyspnea, fatigue, and/or signs and symptoms of heart failure. An echocardiogram can be misleading, for at “first glance” it typically shows normal LV systolic function with some degree of elevated pulmonary pressure, which can be misinterpreted as a presentation representing pulmonary vascular disease. It is crucial to carefully scrutinize the echocardiogram to specifically focus on findings suggestive of LV diastolic dysfunction in all patients (left atrial enlargement, LV hypertrophy, and elevated LV filling pressure [grade II to IV diastolic dysfunction]), but especially those with risk factors for diastolic dysfunction. Conversely, it is imperative to have a reliable assessment of RV size and systolic function as well, because in a patient with hemodynamically significant PAH, the RV will be enlarged and/or dysfunctional, whereas in cases of DHF, RV usually demonstrates normal size and function (see Table 2). At this juncture, it is critical to perform RHC to measure the left-sided filling pressure and calculate the TPG and PVR. It needs to be emphasized that attention must be paid to the quality of the PCWP tracing in order for the correct diagnosis to be made. Misinterpretation of either “underwedged” or hybrid tracing as true PCWP (thereby misdiagnosing as diastolic dysfunction due to falsely elevated PCWP) or recorded measurements from improper placement of the catheter can lead to a wrong diagnosis (see Diagnostic Confirmation section) The hemodynamic assessment can possibly fall into one of the following three categories: 1. The PCWP is normal (<15 mm Hg) and the TPG and PVR are elevated (≥ 3 Wood units); the patient has PAH and treatment needs to be considered after full evaluation. The diagnosis cannot be fully dependent on the single measurement of PCWP alone, because if the patient has just undergone diuresis, the PCWP can be “normal.” If the patient has clinical risk factors and/or echo findings suggestive of diastolic dysfunction, additional hemodynamic maneuvers including fluid challenge or an exercise RHC may be needed to assess response as a measure of the LV compliance. Although there are no definite standardizations, the recently published ACCF/AHA Expert Consensus Document on Pulmonary Hypertension and reports from the 4th World Symposium on Pulmonary Hypertension outline consensus-based recommendations for evaluation of patients presenting with Group II PH. 2. The PCWP is elevated (>15 mm Hg), the PVR is less than 3 Wood Units, and the TPG is normal; the patient has diastolic dysfunction, and therapy should be aimed at optimizing volume status, heart rate, and systemic blood pressure. 3. The PCWP and the PVR are both elevated (the TPG can be normal or elevated); careful evaluation and intervention need to be made to determine if the elevated PVR is passive (due to elevated filling pressure and thus responsive to diuretics and/or a systemic vasodilator) or fixed (remains elevated despite normalizing the PCWP and systemic blood pressure). If the PCWP and PVR both decrease (TPG normal) with optimal heart failure therapy, then the patient needs to be treated aggressively with these regimens. If the PCWP is normalized but the PVR remains elevated (elevated TPG with variable CO), this may be indicative of pulmonary arteriopathy being the dominant disorder with structural changes in pulmonary vasculature along with diastolic dysfunction. No PAH-specific therapies have been shown to be beneficial in heart failure to date; recent small studies with phosphodiesterase-5 inhibitor (PDE-5 inhibitor) sildenafil have shown promise in a few small studies. Treatment with epoprostenol and endothelin receptor antagonists (ERAs) have failed to show beneficial effects, though these trials did not specifically target patients with heart failure and PH. Studies using sildenafil have shown improvement in LV systolic and diastolic function, as well as systemic vasoreactivity in animal models of heart failure. Recent short-term studies evaluating patients with chronic systolic heart failure and PH using sildenafil have demonstrated improvement in exercise capacity and quality of life. However, data from a well-designed trial studying long-term benefits is necessary before any recommendations can be made in regards to use of sildenafil in patients with heart failure and PH. D. Physical Examination Findings. Accentuated P2 – high pulmonary pressure increases the force of pulmonic valve closure; heard best at apex Left parasternal heave and right-sided S4 – presence of high right ventricular pressure and hypertrophy Holosystolic murmur increasing with inspiration and increased jugular v waves – tricuspid regurgitation Diastolic murmur – pulmonary regurgitation RV lift – due to enlargement and/or hypertrophy of RV Right ventricular S3 – right ventricular dysfunction Marked distended jugular veins, hepatojugular reflux, hepatomegaly, peripheral edema, and ascites – right ventricular dysfunction and tricuspid regurgitation Low blood pressure, diminished pulse pressure, and cool extremities – low CO due to right ventricular failure Central cyanosis – intrapulmonary shunt, hypoxemia, pulmonary to systemic shunt Clubbing – congenital heart disease Rales and decreased breath sounds – pulmonary congestion (left heart failure), effusion Fine rales or crackles, accessory muscle use, wheezing, and productive cough – pulmonary parenchymal disorder Sclerodactyly, arthritis, telangiectasia, Raynaud phenomenon, and rash – connective tissue disease Peripheral venous insufficiency or obstruction – venous thrombosis Splenomegaly, spider angiomata, palmar erythema, icterus, caput medusae, and ascites – portal hypertension E. What diagnostic tests should be performed? Diagnosing PAH and determining etiology of disease requires the following steps: 1. The recognition of predisposing conditions and genetic susceptibilities placing certain patients at greater risk (see History Part B: Prevalence – Risk Factors for PAH). 2. Knowing the nonspecific nature of clinical presentation and having a high index of suspicion to screen for PAH. 3. Understanding the usefulness and pitfalls of echocardiography as a screening modality. 4. Undergoing the complete evaluation to classify the type of PH. 5. Performing the invasive hemodynamic assessment and acute vasodilator challenge, when indicated, to confirm a PAH diagnosis. 6. Obtaining risk stratification to determine therapy, including assessment for exercise capacity. List of tests to perform to diagnose PAH (see Figure 2. ). 1. Screening evaluations – history and physical, CXR, ECG, and echocardiogram 2. Determine associated conditions for PAH – serologies (HIV, ANA [and other CTD labs, such as RF, Scl-70], and LFTs [hepatitis serologies]) 3. To evaluate for significant LHD pathology – echocardiogram (TEE and coronary angiography as indicated) 4. To evaluate for significant pulmonary pathology – PFTs and sleep study (CT of chest as indicated) 5. To evaluate for thromboembolic disease – VQ scan (CT angiography and/or pulmonary angiogram as indicated) 6. To assess exercise capacity/functional status – 6 MWT (CPET in some centers) 7. For diagnosis – right heart catheterization 1. What laboratory studies (if any) should be ordered to help establish the diagnosis? Diagnostic Tests A: Laboratory Evaluations in the Diagnosis for PAH There is no one laboratory marker of value that indicates presence of, or diagnostic for, PAH. The laboratory tests listed below are necessary to assess for presence of associated systemic diseases and to determine degree of right heart failure. Laboratory assessments to determine the etiology of PH Connective tissue disease evaluation ANA, rheumatoid factor Rheumatologist referral for further characterization of any positive CTD screening or high clinical suspicion of CTD Hepatitis B and C Other laboratory evaluations Routine comprehensive laboratory evaluations (CBC, BMP, LFTs) BNP (baseline and periodic evaluations with treatment recommended) TSH (as clinically indicated) The measurement of distance walked in 6 minutes has become the test most frequently used to assess baseline exercise capacity and response to therapy in PAH. Indeed, the difference in the 6-minute walk distance (6MWD) has been used as the primary objective for almost all clinical trials for PAH treatments. The advantage of 6MWD is that it is noninvasive, has been reasonably validated and standardized among patients with PAH, and is simple to perform, inexpensive, and well tolerated in most patients with PAH. The disadvantage of this modality includes a learning effect after repeated testing, comorbid conditions affecting test performance, and other activities of the day influencing results. Increases in 6MWD have been shown to correlate with hemodynamics, quality of life, and survival. While there is no “set” distance that determines outcome, most experts agree that 6MWD is a useful tool to follow patients on therapy. From risk standpoint, 380 m is considered one marker that has been shown to correlate with improved clinical outcome. In interpreting 6MWD, there is varied opinion as to which parameter is most indicative of RV function (i.e., absolute distance, % predicted based on age and gender, heart rate recovery, Borg score). Most consider that achieving 15%-20% improvement in 6MWD in the first 3-4 months of initiating a PAH-specific therapy should be a goal. 2. What imaging studies (if any) should be ordered to help establish the diagnosis? Diagnostic Tests B: Radiographic Studies for Evaluation of PAH Usually performed as initial evaluation for complaints of dyspnea. Findings on chest radiograph are neither sensitive nor specific for PAH (i.e., normal chest radiograph is a common finding) Findings indicative of PH (usually seen in advanced stages) include: Prominent hilar pulmonary arteries Peripheral hypovascularity (pruning) RV enlargement (seen in lateral view) Electrocardiograms are usually neither sensitive nor specific for PH in the initial nonadvanced stage Changes consistent with PAH (usually indicative of advanced PAH with right-sided chamber dilatation) include: Right axis deviation Right atrial enlargement Thorough pulmonary evaluation is needed to determine if PH is associated with a significant degree of parenchymal and/or airway related disorders. Full pulmonary function test (PFT) with diffusion capacity (DLCo) is required. Chest CT – to determine parenchymal lung disease Sleep study – as clinically indicated Full evaluation for chronic thromboembolic disease is essential. It has been reported that about 3%-4% of patients who survive acute pulmonary embolus (PE) do not fully resolve the thrombus burden despite anticoagulation and can develop chronic thromboembolic pulmonary hypertension (CTEPH). Furthermore, it can be present in the absence of a clear history of PE in up to 50% of the patients. CTEPH is associated with poor prognosis (30% probability of survival at 5 years with mPAP >40 mmHg). Screening using a ventilation perfusion (VQ) scan is the test of choice: A normal or very low probability scan essentially excludes CTEPH, whereas a high probability scan warrants further evaluation with a pulmonary angiogram. It is necessary to rule out CTEPH even in those patients with an identifiable underlying risk factor or cause of PAH, such as scleroderma, for therapeutic implications of the diagnosis is significant. Clinical judgment is required for those with nondiagnostic or intermediate scans; need to account for suspicion of underlying parenchymal lung disease. CT angiogram, while excellent for excluding acute PE, is less sensitive than the perfusion scan to exclude CTEPH. In patients with parenchymal lung disease where a perfusion scan may be difficult to interpret, a CT angiogram may be useful. Pulmonary angiography is the “gold standard” to fully assess location and extent of thrombus burden and to determine if a patient is a candidate for thromboendarterectomy Surgical intervention (thromboendarterectomy) can reverse pulmonary hypertension and potentially cure the patient. cMRI is being explored as a potential tool in PAH since RV function is the ultimate determinant regarding outcome and prognosis. Possible utilities of cMRI in PAH include: Anatomic evaluation (RV volume and mass) Noninvasive hemodynamics (curvature ratio, delayed contrast enhancement, and PA flow velocity and area) Marker of RV response and remodeling (prognostic information, response to treatment). Studies have shown that baseline cMRI RV size and function serve to predict long-term survival while conventional prognostic markers (FC and 6MWT) do not. Clinically, there are barriers in using cMRI in the PAH population which include: Test and interpretation not widely available Difficulty for unstable patients to tolerate the test (length of the study, need to lie supine, claustrophobia, need to time with respiratory cycle and breathholding, and/or the need for contrast agent) For patients on intravenous epoprostenol, need to arrange for long tubing (the cassette must be kept out of the cMRI area) Cost of the study and insurance coverage Significant advances in developing PAH targeted therapies have been accomplished in the past two decades. There are currently nine FDA approved treatments for PAH (Table 5). These treatments aim to restore the imbalances in the endothelial system that are present in PAH patients: augmenting prostacyclin and nitric oxide pathways and blocking the endothelin pathways (see Section I: Pulmonary Arterial Hypertension – Pathobiology). Clinical Research Highlights Intravenous epoprostenol, the first PAH-specific therapy to be approved by the FDA in 1995, was shown to improve functional class (FC), exercise capacity, hemodynamics, and survival in IPAH. The landmark pivotal trial enrolled 81 functional class III and IV IPAH patients in a 1:1 randomization comparing IV epoprostenol to a conventional treatment (diuretics, digoxin, warfarin, calcium channel blockers). There were eight deaths during the 12-week trial period, all which occurred among patients who were randomized to conventional therapy that resulted in a survival benefit (P = .003). This was soon followed by a clinical trial evaluating epoprostenol in PAH associated with connective tissue disease that demonstrated marked improvements in 6MWD and hemodynamics but no effect on mortality in a 12-week, open-label randomized trial. Two longer-term observational studies have confirmed the chronic benefits of IV epoprostenol in PAH patients, specifically improvements in survival compared with historical controls, FC, 6MWD, and hemodynamics. Intravenous epoprostenol is a challenging treatment to implement due to its short half-life (<6 min) and the need for continuous IV infusion via a tunneled catheter. Each patient must learn the techniques of sterile preparation of the medication, operation of the ambulatory infusion pump, and care of the central venous catheter. Incidences of sepsis and catheter-related infections are not negligible (0.1 to 0.6 case per patient-year) and can cause significant morbidity. Mastering the sterile techniques required to take care of the indwelling catheter is essential. Any interruption of the drug infusion can be potentially life threatening due to the short half-life of epoprostenol and potential for rebound pulmonary hypertension. Intravenous epoprostenol is commonly started in the hospital at a dose of 1-2 ng/kg/min and titrated on the basis of PAH symptoms and side effects. Most experts consider an optimal dose of chronic therapy to be between 25 to 40 ng/kg/min. Chronic overdose can lead to high CO failure and worsening of heart failure symptoms. Periodic follow-up RHC is recommended to obtain full hemodynamics, including CO measurements, for patients on chronic intravenous epoprostenol treatment. Common side effects include headache, jaw pain, diarrhea, nausea, flushing, rash, musculoskeletal pain, and thrombocytopenia. Jaw pain (usually with first bite) rarely completely resolves. Over-the-counter prophylaxes are used for diarrhea, which is usually a chronic problem. Nausea and flushing usually subsides and resolves after a period of time (usually days to weeks). A “Flolan” rash can appear in some people (on face, trunk, or limbs). Thrombocytopenia can occur with long-term use so there is a need to follow platelet counts. This can be dose dependent. Intravenous epoprostenol is also unstable at room temperature so the cassette needs to be kept cold (usually with ice packs). Recently, temperature-stable epoprostenol (Veletri®) has been approved by the FDA. Its properties are reported to be generally similar except for the difference in the temperature-related stability. A registry of patients being treated is being collected. Due to the complexity of administering this therapy, epoprostenol use should be limited to experienced centers. Authors’ Preferred Method of Treatment/Recommendation Intravenous epoprostenol is recommended as the therapy of choice for the following: Young patients presenting with IPAH/advanced and/or worrisome clinical features/possible family history of PAH Syncope, symptoms or signs indicating advanced disease/RV dysfunction Echocardiogram showing enlarged right-sided chambers, RV dysfunction, pericardial effusion Hemodynamics showing elevated RAP (>12 mm Hg) and/or decreased CI (<2.5 L/min) Patients progressing/not improving on other therapies (usually in combination treatments) As a “bridge” to lung transplant Generally recommended for patients who are rapidly progressing, advanced stage upon initial diagnosis, high risk markers Initiate on intravenous epoprostenol as lung transplant evaluation takes place If patient responds well and improves, listing for transplant can be delayed and patient followed on therapy For patients with portopulmonary hypertension Initiate therapy to assess response on intravenous epoprostenol as “bridge to candidacy” for liver transplant Epoprostenol is considered the “gold standard” in PAH-specific therapy and recommended for advanced PAH (especially patients presenting in FC IV) and PAH with right heart failure, cardiogenic shock from RV failure, and/or requiring rescue therapy. Clinical Research Highlights Treprostinil is a prostacyclin analogue with a half-life of 4 hours, which was studied as a continuous subcutaneous infusion in a 12-week, placebo-controlled, randomized trial of four hundred seventy patients with FC II, III, or IV PAH. There was a modest but statistically significant median increase of 16 meters in 6MWD; the improvement was dose related and patients in the highest dose quartile reported close to a 40-m improvement. However, the major obstacle of using subcutaneous treprostinil is the pain and erythema at the infusion site, which was reported by 85% of the patients, and curtailed titration of the infusion. It is now recognized that site pain is not dose related, and that for most patients the initial site pain diminishes after proper dose escalation, which helps them improve their PAH symptoms. Due to the limitations imposed by the subcutaneous route of delivery, IV treprostinil was studied in a 12-week open-label trial of 16 patients. It demonstrated improvements in 6MWD (82 m) and hemodynamics. In another open-label trial, 31 FC II and III PAH patients on IV epoprostenol were transitioned to IV treprostinil. Twenty-seven patients completed the transition, but four needed to be transitioned back to epoprostenol. 6MWD measurements were maintained among patients who completed the transition; however, there was a modest increase in mPAP and decrease in cardiac index. Noteworthy is that the dose of IV treprostinil at the end of the study period was more than twice the dose of epoprostenol at the start of the study. Pain at the site of administration (site pain) is the most commonly encountered difficulty in using subcutaneous (SC) treprostinil. Usually the pain is most troublesome at the beginning of the therapy. It is not dose related; rather, the discomfort tends to get less as the dose is increased and PAH symptoms improve. Most patients, with adequate support can tolerate this treatment and gain benefit. Patients need to be told what can be expected at the onset and be educated as to what can be done. Several remedies are available ranging from topical ointments, creams, antiinflammatory agents, or different techniques that can help with the site pain. The advantage is that patients can receive the benefit of continuous prostacyclin treatment without the risk of tunneled catheter. For those patients who cannot tolerate the site pain, treprostinil can be given intravenously. The need for a tunneled intravenous catheter and managing the pump for patients receiving intravenous treprostinil are the same as intravenous epoprostenol. The side effect profile is also similar. The major difference lies in that treprostinil’s longer half-life (4-5 minutes for epoprostenol versus 4-5 hours for treprostinil), potentially renders it “safer” in the event of line malfunction and/or therapy interruption. Transition from intravenous epoprostenol to intravenous treprostinil has been shown to be overall safe and well tolerated, though the dose of treprostinil is typically higher, ranging from 1.5 to 2x the original epoprostenol dose. Another major difference is regarding management of line-related infections. A Centers for Disease Control and Prevention report has raised concerns regarding possible increased incidence of blood stream infections, particularly with gram-negative organisms, in patients receiving intravenous treprostinil. It is unclear if the rates of infections are truly different, but the increased incidence of gram-negative organisms needs to be noted. If there is concern for line infection or bacteremia, initiate appropriate antibiotics to cover both gram-positive and gram-negative organisms after appropriate cultures have been drawn. Authors’ Preferred Method of Treatment/Recommendation For patients who understand the benefits of the SC method, starting with this approach is recommended. Intravenous treprostinil may be used instead of epoprostenol for added safety related to longer half-life and convenience (cassette change every other day instead of every day with epoprostenol; also room temperature stable). For patients with family support concerns, or for those who live at a farther distance from the PH center where accessing emergent treatment may be a concern, treprostinil provides a safer approach of providing intravenous prostacyclin infusion. Given the complexity of administering and following patients receiving these treatments, administration should be limited to centers with experience. Clinical Research Highlights and Clinical Considerations Iloprost is a stable prostacyclin analogue that is delivered via an aerosolized device for 6 to 9 treatments per day. It was studied in a 12-week, multicenter, placebo-controlled, randomized trial of 207 FC III and IV patients. The unique aspect of this study was that patients enrolled were comprised not only of PAH patients but also of patients with PH related to inoperable chronic thromboembolic disease. This study also used a novel composite end point (improvement in FC by at least 1 level and increase in 6MWD by at least 10% in the absence of clinical deterioration), which demonstrated treatment benefit (16.8% vs. 4.9%, treated vs. placebo, P = .007). It is available in a 2.5 mcg test dose followed by 5.0 mcg and 20 mcg doses. The average inhalation times on the 20 mcg dose ranges from 5-8 minutes per session. It is generally well tolerated with coughing, headache, and flushing occurring as the most common side effects. Assessing for compliance is important when prescribing inhaled iloprost. When combined with oral therapies, some prescribers have recommended four to five treatments a day. Clinical Research Highlights and Clinical Considerations Inhaled treprostinil was studied in a 12-week, placebo, randomized study in patients with PAH added to background therapies of bosentan or sildenafil as assessed by improvements in the 6WMT (median placebo-corrected treatment effect of 20 m). Treprostinil is taken four times a day via inhalation using a specialized nebulizer. The initial therapy is started with three breaths four times a day, with increased breaths as tolerated. The maximal dose is nine breaths four times a day. It is generally well tolerated with cough and hypotension as the most common side effects. The usual practice is to use as combination treatment with oral therapies. Clinical Research Highlights and Clinical Considerations Bosentan is a nonselective endothelin receptor blocker (ETA and ETB). It is the first orally available therapy approved for PAH. The pivotal study, named BREATHE-1, was conducted in a 12-week placebo-controlled study among 213 patients with group I PAH. Treatment with bosentan improved the primary end point of 6MWD by 36 m, whereas placebo patients deteriorated by 8 m (P = .0002). Bosentan also improved the composite end point of time to clinical worsening (defined as death, initiation of IV epoprostenol, hospitalization for worsening PAH, lung transplantation, or atrial septostomy). Long-term observational findings in survival of patients treated with bosentan as first line therapy have shown improved survival compared with expected outcome based on the NIH registry equation. Bosentan was shown to be effective in mildly symptomatic patients in a landmark trial called the EARLY study. This was a placebo controlled trial of 6 months duration that enrolled 168 FC II PAH patients. The baseline 6MWD of this cohort was 438 m, which is higher than all the other studies in PAH (approximately 330-350 m). The results demonstrated a significant decrease in PVR, which was the primary end point to evaluate treatment effects on vascular remodeling, and a significant delay in clinical worsening. Bosentan is available in 62.5 mg and 125 mg. It is recommended to be started with 62.5 mg twice a day for 4 weeks; if LFTs are stable, increase to 125 mg twice a day. Bosentan is mainly metabolized through the hepatic P450 enzymes, and an increase in hepatic transaminases greater than 3 times the upper limit of normal has been reported in 10%-12% of the clinical trial population. It is dose related and transaminase abnormalities resolve upon dose reduction or discontinuation of the treatment. Bosentan is teratogenic and may decrease the efficacy of hormonal contraception, so women of childbearing age must be counseled to use dual contraception for birth control. Other side effects include headache, flushing, lower-extremity edema, and anemia. Treatment with bosentan requires monitoring of liver function tests on a monthly basis, and pregnancy tests on women of childbearing potential on a monthly basis, and hemoglobin/hematocrit on a quarterly basis. Patients should be counseled regarding potential for lower extremity edema, especially in the initial weeks of therapy, and the possible need for diuretic adjustments. Glyburide and cyclosporine A are contraindicated with bosentan due to significant drug-drug interactions. Authors’ Preferred Method of Treatment/Recommendation Bosentan is most effective among PAH patients who are diagnosed early (as shown by the EARLY trial). PAH patients that are FC II or early III (IIIA), and those with CTD-associated PAH (ERAs demonstrate antifibrotic properties). Patients who respond to bosentan tend to do well and the efficacy tends to remain long term. Patients for whom bosentan would not be recommended include: patients who are diagnosed late in the course of disease (i.e., FC IV or right heart failure) and patients with hepatic dysfunction. It must be stressed that ERAs are not effective as rescue therapy. Special attention must be paid to those patients who present with overt right heart failure, because ERAs can make the heart failure worse. One approach is to diurese and stabilize the patient with other PAH-directed therapy and use bosentan after right heart failure has been fully treated. Clinical Research Highlights and Clinical Considerations Ambrisentan is a selective ETA receptor antagonist studied in two placebo-controlled, randomized, 12-week studies of WHO Group I patients (ARIES-1 and ARIES-2), which were conducted in the U.S. and Europe/South America, respectively, in approximately 400 patients. The treatment resulted in a significant improvement in 6MWD and delay in time to clinical worsening in all treatment groups. The 2-year open label extension results from the ARIES clinical studies was recently published, showing that improvements in exercise capacity and functional class were sustained with a low risk of clinical worsening. Ambrisentan is available in 5 mg and 10 mg oral tablets taken once a day. The incidence of hepatic transaminase elevation greater than 3 times the upper limit of normal was low at 0.8% in clinical trials. After reviewing the post marketing safety data, the FDA has removed the monthly LFT monitoring requirement. It is agreed upon by most experts that LFT monitoring is recommended on a scheduled periodic basis with other laboratory evaluations. Peripheral edema, a known side effect of the ERA-class, was reported as mild to moderate in the clinical trials. Reports of significant edema during post marketing use followed. Analysis of reported events showed clinically significant fluid retention to be most notable among elderly patients and has prompted the FDA to issue a warning to be placed in the package insert. Though the precise mechanisms behind the fluid retention is not clear, retention occurs most commonly in patients with clinical diastolic features (i.e., elderly, hypertensive, diabetic, obese, and those with echocardiographic findings to support diastolic dysfunction). Ambrisentan is also teratogenic, so a monthly pregnancy test is required for women of childbearing age. Ambrisentan also can decrease hemoglobin so periodic monitoring of laboratory checks are required. Authors’ Preferred Method of Treatment/Recommendation Ambrisentan is also best used for patients who are diagnosed early in the course of the disease (FC II and early III PAH), including CTD-associated PAH. It is best to not initiate in patients who are in right heart failure, FC IV, or with evidence of advanced disease. A special note for elderly patients who are diagnosed with PAH: if the patient has clinical evidence of right heart failure, peripheral edema, or echocardiogram findings of diastolic dysfunction (especially enlarged left atrium), it is recommended not to use ambrisentan (or at least ensure euvolemic state), for heart failure can significantly worsen. Clinical Research Highlights and Clinical Considerations Sildenafil was studied in a 12-week randomized placebo-controlled study of 278 symptomatic PAH patients. The primary end point of 6MWD improved by 45, 46, and 50 m in the 20, 40, and 80 mg groups, respectively (P <.001). There was no change in the time to clinical worsening at week 12. The result of 222 patients who completed 1 year of treatment demonstrated that the 6MWD improvement was maintained; however, nearly all patients were titrated up to a dose of 80 mg three times a day. Side effects included headache, flushing, dyspepsia, and epistaxis. Visual and hearing impairments have been reported; patients at risk (i.e., elderly or diabetics) should be counseled and evaluations performed as clinically indicated. Sildenafil is contraindicated with nitrates for risk of inducing hypotension. Authors’ Preferred Method of Treatment/Recommendation Considerable variation in the use of sildenafil exists regarding dose and type of patients. Some studies have shown a higher dose to be more effective (used as titration) and clinicians have advocated using higher doses off-label. However, obtaining financial approval can, for higher doses, can be difficult. Some patients have further improvement with a higher dose but this is not seen in all patients. Use of sildenafil for “secondary” PH (i.e., those with predominant PH but with some features of left heart disease and lung disease) has gained considerable interest. Among all PAH therapies available, sildenafil seems to be most well suited for this group of patients. However, it must be emphasized that consideration for treating these patients needs to be done with complete evaluation, including a RHC that demonstrates PAH (or PH “out of proportion” of the underlying condition). The primary underlying pathology must be in the pulmonary vascular component for this therapy to have a chance to be effective. To date, there are no large randomized trials, though one trial studying patients with diastolic dysfunction and PH is underway. Sildenafil is most likely the agent of choice for patients who are mildly symptomatic. Note, this treatment is not effective as a “rescue” per se, but can be used along with diuretics for moderately symptomatic patients and features of right heart failure. Hypotension can be an issue, so it needs to be monitored carefully. The benefit of sildenafil can be seen fairly quickly upon initiation of treatment; however, it can also “wane” with chronic use (patient variability). It is imperative to follow patients closely for maintenance of efficacy. Clinical Research Highlights and Clinical Considerations Tadalafil, a PDE-5 inhibitor with a longer half-life than sildenafil, was recently studied in a 16-week, double-blind, placebo-controlled trial among 405 PAH patients using 2.5, 10, 20, and 40 mg tablets once a day. The highest dose of tadalafil demonstrated a 41 m increase in 6MWD compared with 9 m for a placebo (P <.001). There was also a delay in the time to clinical worsening (defined as death, hospitalization, initiation of new PAH therapy, and worsening WHO FC). Side effects include headache, diarrhea, nausea, back pain, dizziness, dyspepsia, and flushing. Authors Preferred Method of Treatment/Recommendation The above comments regarding sildenafil also applies to tadalafil. The notable difference would be since tadalafil has a longer half-life, it may not be the agent of choice for unstable patients, for effects of hypotension can last longer. CCBs are recommended for patients who demonstrate responsiveness during an acute vasodilator testing (see Diagnostic Confirmation section). Patients with IPAH who meet the criteria may be considered for treatment with CCBs. Long-acting nifedipine, diltiazem, or amlodipine is suggested. Verapamil should be avoided due to its potential negative inotropic effects. Patients need to be followed closely for efficacy and safety on CCBs. If a patient does not improve to FC I or II with CCBs, the patient should not be considered a chronic responder and PAH-specific treatment should be initiated. Anticoagulation has been studied in two small uncontrolled trials in IPAH patients. Based on these studies, most experts recommend warfarin anticoagulation. The recommended targeted to international normalized ratio for PAH is 1.5-2.0. In patients with APAH, anticoagulation is controversial with few data to support its use. In CTD, CHD, and portopulmonary patients, the risk of gastrointestinal bleeding may be increased. Most experts recommend warfarin anticoagulation in APAH patients to be considered in patients with advanced disease on intravenous prostanoids after careful assessment for any contraindicating factors. Hypoxemia is a potent pulmonary vasoconstrictor and thus can contribute to the progression of PAH. It is recommended that patients with PAH maintain oxygen saturation greater than 90% at all times; the exception would be CHD patients and those with Eisenmenger physiology, which need to be assessed case by case. Diuretics are used to treat volume overload due to right heart failure. For diuretic naïve patients, slow initiation and monitoring of renal function are recommended with a goal of attaining near-normal intravascular volume. In acute decompensated right heart failure and/or in presence of diuretic resistance, IV diuretics are needed. Although digoxin has not been well studied in patients with PAH, it is used with careful monitoring in low doses in the setting of refractory right heart failure and/or atrial arrhythmia. With the approval of therapies targeting different pathways, combining treatments to attain improved outcome has been the natural progression in the treatment approach. The potential to increase efficacy by using combination therapy must be measured against possible toxicity and drug-drug interactions. Most studies are an add-on combination approach. One study used an upfront combination using bosentan versus a placebo in FC III or IV patients receiving intravenous epoprostenol (BREATHE-2). The study failed to show benefit, though the study was underpowered. Two studies evaluated adding inhaled iloprost to bosentan therapy in a randomized, double-blind, placebo-controlled design. The STEP study enrolled 67 patients in a 12 week study that demonstrated safety as well as improvement in 6MWD (26 m, placebo corrected, P = .051); the COMBI study, which evaluated 40 patients, failed to demonstrate benefit and the study was terminated. The largest completed combination trial in PAH to date is the PACES study, which added sildenafil as an add-on therapy to intravenous epoprostenol. This 16-week, multinational, double-blind, placebo-controlled study enrolled 267 patients who were stable on epoprostenol therapy. Patients were randomized to receive 20 mg three times a day, titrated to 40 mg and 80 mg tid, at 4-week intervals, or a corresponding placebo. At the end of 16 weeks, more than 80% of patients had reached the 80 mg tid dosing level. The primary endpoint was changed in 6MWD and there was a placebo-adjusted increase of 26 m in the subjects who received sildenafil. There were 7 deaths in the placebo group and none in patients receiving sildenafil. Clinical worsening events, defined as death, transplant, hospitalization, or an increase in epoprostenol dose, were significantly different in favor or the treated group. Several large studies are currently underway evaluating the effect of combining different classes of oral regimen, including the COMPASS-2 trial (Effects of combination of bosentan and sildenafil versus sildenafil monotherapy on morbidity and mortality in symptomatic patients with pulmonary arterial hypertension), which is the first morbidity/mortality driven trial focusing on combination therapy in PAH. Lung transplantation as a potential therapeutic option needs to be considered and discussed at the time of diagnosis. Optimal timing of referral can be challenging; local practices and organ availability need to be considered: Patients who are good candidates with suboptimal response/progression on treatment need to be referred without delay Note that under the current prioritizing system used by the United Network of Organ Sharing (UNOS), PAH patients may be assigned lung allocation score below that of patients with other common diagnosis (i.e., pulmonary fibrosis, COPD). The thoracic committee is working on the system and is reviewing exceptions based on hemodynamic criteria to elevate the score to be more consistent with the degree of the patients’ clinical status Although no “absolute” indications for lung transplant referral exists, it is recommended that for patients who are on optimal medical therapy (which usually includes a systemic prostacyclin) and have evidence of hemodynamic instability (elevated right atrial pressure and/or decreased cardiac output), proceeding with completing lung transplant evaluation needs to take place. With an increasing number of options available, the decision regarding when and how to use such treatments have become more complex. It is important to realize that head-to-head comparative trials of agents have not been performed. A useful tool to guide clinicians in making therapeutic decisions is outlined in the ACCF/AHA recommendations for PAH, which uses a list of clinically relevant parameters to make a risk assessment of patients (Table 6). Patients with more advanced and symptomatic diseases are recommended to receive continuous infusion prostacyclins (Figure 3). Additionally, for those patients who are assessed as functional class II or III, either class of oral drugs can be initiated, but frequent reassessment is critical (Table 1). (See section on Long-term Management.) A. Immediate management. Pulmonary arterial hypertension usually manifests itself as a gradual, progressive development of dyspnea, therefore generally an outpatient presentation and evaluation. There are cases in which PAH can present acutely: Young patients presenting with syncope: Although PAH is a rare disorder, it should be considered in the differential for a young patient presenting with syncope associated with exertion (i.e., related to sports activity, acute onset). PAH in a young patient can be difficult to recognize for they can compensate well during initial stages and the condition can progress rapidly (especially if related to a genetic disorder Patients with PAH (not diagnosed or on therapy): Presenting with systemic disorder (most common presentations include upper respiratory infection/pneumonia, atrial arrhythmias, dietary indiscretion leading to right heart failure) As discussed above, the consequences of pulmonary vascular remodeling are an increase in pulmonary vascular resistance (PVR) and impedance of flow. These changes cause RV strain that impairs filling and causes RV volume and pressure overload. The RV then either hypertrophies and/or dilates, encroaching on the LV. Due to ventricular interdependence (note that two ventricles share the same shared bundle of fibers and that they move in “series”), RV hypertrophy and dilatation results in decreasing LV preload, cardiac output, and coronary perfusion. Increased RV wall stress results in RV ischemia. Tricuspic regurgitation develops as a result of RV dilatation resulting in chronic elevation of central venous pressure (CVP), which increases renal vein pressure leading to renal dysfunction; peripheral edema; visceral organ edema, resulting in hepatic dysfunction; and gut edema, causing decreased absorption of medications and nutrients. Another consequence of RV failure is the opening of the foramen ovale and development of right to left shunting that can augment cardiac output at the expense of oxygenation, causing or worsening hypoxemia. Definition of RV Failure Essentially, it is the inability of the RV to maintain adequate circulation through the pulmonary vascular bed at normal central venous pressure Goals for Management of RV Failure 1. Optimize RV preload 2. Maintain systemic blood pressure (keep PVR less than SVR) to avoid RV ischemia 3. Augment cardiac output 4. Reduce PVR A. Optimal Preload Critical in RV Failure Within physiologic limits, RV preload does improve contractility (approximately CVP 12-15 mm Hg) Excessive RV preload has the potential to overdistend the RV and cause impaired LV filling and decrease cardiac output via ventricular interdependence. Essential to avoid fluid bolus without careful assessment Diuretic use in RV failure Consider effects of ineffective GI absorption in RV failure Intravenous diuretics are more effective to “unload” the gut edema and initiate diuresis process If inadequate response, consider continuous intravenous diuretic drip Use combination treatments with Spironolactone (relatively preserved renal function and electrolytes; effective in aiding treatment of ascites) Intravenous Diuril in conjunction with loop diuretics Ultrafiltration when diuretics are not sufficient to unload the RV B. Use of Pressors in the Management of Acute RV Failure Essential goal of treating decompensated RV failure is to maintain systemic blood pressure above pulmonary artery pressure to preserve right coronary blood flow Perfusion of RCA occurs throughout the cardiac cycle, dominating in systole. As PVR approaches SVR, coronary perfusion decreases. Judicious use of vasopressors can ameliorate RV ischemia. Need to balance with direct effects on pulmonary circulation (effect on PVR and HR) Key points regarding pressors (Table 7) Use of Pressors in Pulmonary Hypertension and Right Heart Failure Norepinephrine (Equipotent ß1 and α1 receptor agonist) Low doses decrease PVR/SVR ratio Probably the best first-line agent for PH/RHF with hypotension Improves RV function by improving SVR and increasing cardiac output Potential to increase PVR at higher doses Phenylephrine (Direct α1 agonist) Increases PAP and PVR, decreases cardiac output, and worsens RV function In PH and RVF, should be avoided Epinephrine (Potent ß1 and α1 agonists) Often agent of last resort Not much data in PH and RVF Isoproterenol (ß1 and ß2 adrenergic agonist) Use limited by tachyarrhythmia Arginine vasopressin (V1 receptor agonist) Decreases PVR/SVR ratio Less tachyarrhythmias than norepinephrine Useful in PH/RVF and hypotension refractory to/or as first-line agent Used as rescue therapy in PH crisis, RV failure with hypotension after cardiac surgery, sepsis with PH and RV failure C. Optimizing Cardiac Output Animal models of PH Doses up to 5 mcg/kg/min, reduce PVR while increasing CO Doses 5-10 mcg/kg/min, significant tachycardia without improving PVR Canine model of acute RVF Dobutamine superior to NE in promoting RV/PA coupling Clinical uses for both acute and chronic PH Doses should be maintained <5 mcg/kg/min Combine with pulmonary vasodilator when feasible May cause systemic hypotension due to peripheral -adrenergic effects and may need NE or vasopressin for BP support Animal models of PH Significantly reduce PVR and improve RV function In pediatric population, demonstrated additive pulmonary vasodilatation when combined with inhaled nitric oxide One comparison study with PDE-5 inhibitor demonstrated inferior pulmonary selectivity and more systemic hypotension Clinical use in PH patients Systemic hypotension is the most common limiting factor. In a patient with stable BP, milrinone can augment cardiac output and provide both arterial and venous dilatation . Low dose recommended and better tolerated (0.25-0.375 mcg/kg/min) Dose adjustment needed for renal impairment (relatively contraindicated for clinically relevant renal insufficiency) Unclear benefit due to tachyarrhythmia effects, which is commonly seen with dopamine. A major drawback since increase in heart rate can worsen demand ischemia. Increase in heart rate can be seen in low doses (so called “renal dose”). Shown to increase PVR/SVR ratio Levosimendan (available in Europe) Acts as a vasodilator and has been shown to improve diastolic function and myocardial contractility without increasing oxygen consumption. It has been shown to reduce PVR and improve PA-RV coupling in experimental acute RV failure D. Optimizing PVR – Pulmonary Vasodilators Pulmonary vasodilators in acute RVF setting – desirable characteristics Selective for pulmonary vascular bed with little or no systemic effects Administered via intravenous or inhaled route Easily titratable and short half-life No toxic metabolites/side effects Cost benefit ratio favorable Inhaled Nitric Oxide Highly selective for pulmonary vascular bed with no systemic BP effects, thus ideal agent for PH/RV crisis Can be given via facemask or endotracheal tubing for a ventilated patient Not widely available in all institutions; high cost associated with use Intravenous epoprostenol can be challenging to initiate in the setting of acute RVF due to systemic hypotensive effects Inhaled epoprostenol has been shown to decrease PAPs, and improve cardiac output without effect on systemic BP after CT surgery. Also shown to improve oxygenation. Significant cost savings reported compared with inhaled nitric oxide Refractory PAH to medical therapy is characterized by Progression of RV failure and end-organ damage Worsening hypoxia and oxygenation requirement Spectrum of mechanical circulatory support for the failing RV include the following Right ventricular assist device (RVAD), which can be surgically or percutaneously implanted For PAH patients, complications associated with increased PVR makes this not an ideal supportive device Extracorporeal Membrane Oxygenation (ECMO) ECMO – routinely used to completely bypass the failing heart and provide gas exchange VA ECMO (Veno-Arterial) – used when both circulatory and pulmonary support required, as in decompensated PAH VV ECMO (Veno-veno) – used for respiratory support Novalung – pumpless device serving as parallel circuit to the lung This can unload the RV by providing right to left shunt and provide oxygenation without centrifugal pump Most experiences reported from group in Toronto, as well as a few in Europe Patients presenting with line related problems with intravenous prostacyclin infusions For patients receiving intravenous prostacyclins (epoprostenol or treprostinil) with complaints of irritation/discomfort, drainage, fever, malaise, complications of line infection need to be managed immediately which include: Full evaluation including comprehensive laboratory evaluations, cultures Prompt initiation of intravenous antibiotics Gram-positive coverage (i.e., Vancomycin) for patients on epoprostenol Gram-positive and negative coverage (i.e., Vancomycin and Piperacillin) for patients on treprostinil Critical points to remember for emergent treatments: PROSTACYCLIN INFUSIONS CANNOT BE INTERRUPTED If the tunneled line cannot be used (purulent drains, dislodged, line malfunction, etc), epoprostenol and treprostinil can be given via peripheral catheter temporarily For epoprostenol, this diluent is not compatible with any other drugs/infusions. There must be a dedicated line solely for the epoprostenol infusion In the case of sepsis with hemodynamic instability (hypotension), a dose decrease may be necessary. This is best done with the PH specialist managing the patient. Vasopressor support may also be needed (see Immediate Management – Pressors in the Management of RV Failure) A. Physical Examination Tips to Guide Management. Signs of Refractory / Worsening RV Failure Blood pressure – decreasing/low blood pressure ominous sign for further progression of RV failure (see section: Immediate Management) Heart rate – maintaining optimal heart rate essential to optimize cardiac output (CO = SV × HR). Insufficient heart rate – with clinical evidence of low output state, may need to adjust therapies to assist achieving optimal rate. If patient is on AV nodal blocking medications or beta blockers, decrease the dose. If in context with systemic hypotension, initiation of vasopressors and/or inotropes would be of clinical benefit. Tachycardia – usually a sign of decompensated state and best not to slow it down pharmacologically but to treat underlying problem (i.e., optimize volume status and cardiac output). Atrial arrhythmia – atrial fibrillation uncommon in PAH. If present, should carefully scrutinize for evidence of LHD. Atrial flutter can be seen as well as atrial tachycardia. All these arrhythmias poorly tolerated in PAH. Need to assess to restore sinus rhythm whenever possible. Oxygenation – maintaining stable and adequate oxygenation is critical in the treatment of PAH for hypoxemia/acidosis further aggravates vasoconstriction and pulmonary vascular dysfunction. Support with appropriate modalities (facemask, BIPAP, CPAP, Vapotherm) need to be done as expediently as possible. Mechanical Ventilatory Support – patients with advanced PAH generally do not tolerate the measures associated with intubation well. The effects of anesthesia used for intubation can result in hemodynamic/circulatory compromise. Furthermore, weaning the patient off the ventilatory support usually becomes very difficult process. Due to high morbidity (as well as mortality) associated with mechanical ventilatory support in these patients, every effort should be placed to use pharmacologic and respiratory support, as well as treating underlying conditions (sepsis, pneumonia, acid/base imbalance). However, patients with PAH do not tolerate hypoxemia well either. These are very challenging patients to manage. A referral to a PAH center is highly advisable. Signs of volume overload due to RVF – increase in JVP, hepatomegaly, ascites, hepatojugular reflux, peripheral edema. Signs of inadequate perfusion – low systolic pressure, low pulse pressure, decreased mentation (especially in elderly), cool extremities, unintentional weight loss, loss of appetite, nausea with oral intake, presyncope, and syncope. B. Laboratory Tests to Monitor Response To, and Adjustments in, Management Renal function assessment BUN, creatinine, urine output – essential to follow renal function parameters and response to diuretic treatments. If there is an inadequate urine output response, then consider providing more inotropic support and/or intensify diuretic regimen. Ultrafiltration or renal replacement therapy (continuous versus intermittent) may need to be considered. Markers of RV Function / Perfusion Total bilirubin (T. bili) – elevated T. bili can be a marker of hepatic congestion due to RV failure. BNP – marker of cardiac “stretch and stress.” Useful to compare with a baseline (if available) to determine the extent and follow with treatment. C. Long-term management. It is critical to have scheduled close follow-up of PAH patients on treatment(s). Three major reasons include: Patients usually have variable responses to PAH treatments. It is imperative to reassess patients within 1-3 months (depending on severity/therapy used) to assess for clinical changes. The effects of therapy can wane and change over the course of time. Even patients who did well initially can have recurrence of symptoms and worsen precipitously Side effects of PAH medications are diverse and varied. Close follow-up of these parameters are needed to ensure safety and optimal care of patients. In order to assess patient’s prognosis and progress on treatment, several surrogate markers have been studied as discussed below. A risk based approach has been recommended to determine appropriate treatments (see Medical Treatment). A list of surrogate markers and associated risk parameters are listed in Table 6. On treatment goals for PAH patients are as follows: To reach functional Class I or II Achieve 6MWD greater than 380 m (there is considerable amount of debate and controversy regarding use of 6MWD in PAH. While the set distance “number” is not agreed upon, it is accepted that a walk distance of greater than 400 m is associated with a better outcome. To improve hemodynamics with normalization of cardiac index (>2.2 L/min/m2) and RAP (<8 mm Hg) On echo, to normalize RV size and function and absence of any pericardial effusion In following BNP as a surrogate for RV function, for BNP to decrease (studies have shown that a decrease in BNP by 33-50% in the initial 3 months of starting a therapy is associated with favorable 1-year survival) and normalize. Functional class (FC) assessment has proven to be a reliable indicator of severity of disease at baseline and as a marker to determine response to therapy. Functional assessment classification modified from New York Heart Association (NYHA) functional classification has been adopted for PAH (Table 8). The most notable difference between the two systems is in its definition of class IV, which included patients with signs of right heart failure and syncope, highlighting the importance of right ventricular dysfunction as a significant clinical marker of poor outcome. Extensive studies have explored correlation between FC at baseline and outcome. Patients with IPAH in the NIH study, the risk of death was higher for patients in NYHA-FC III or IV than among those in NYHA-FC I or II. For patients in NYHA-FC I or II, the median survival was almost 6 years, while it was 2.5 years for patients in NYHA-FC III and 6 months for NYHA-FC IV. Baseline functional assessment was also shown to be highly predictive of outcome among patients treated with long-term epoprostenol. In one large retrospective study among IPAH patients treated with epoprostenol, survival after 3 and 5 years was 81% and 70%, respectively, for those patients who were in NYHA-FC III at presentation whereas for patients who were in functional class IV at baseline, the survival rates at the same time points were 47% and 27%. These earlier studies highlighted the importance of initiating treatments early in the course of PAH. Assessments to determine correlation between FC on therapy and outcome have been done as well. In the same retrospective study as above among IPAH patients treated with epoprostenol, patients who improved to FC I or II by first follow-up period (17 ± 15 months) had 3- and 5-year survival rates of 89% and 73%, respectively, compared with 62% and 35% for patients who were FC III. Patients who were FC IV at the same time period suffered the worst outcome with 42% survival at 2 years and 0% at 3 years. Current recommendations states that FC assessment is recommended to be made early after initiation of therapy with the goal of attaining FC I to II. For patients who demonstrate clinical improvement achieving FC I or II within the initial months after therapy, they should be carefully followed. For patients who deteriorate or remain in functional class IV, evaluation for lung transplantation should be pursued. Six-Minute Walk Test The distance covered during a 6 minute hall walk test (6MWD) has been the primary end point for almost all the major pivotal clinical trials in PAH. However, significant debates and studies are ongoing that explore which parameter(s) best serves as a surrogate of RV function with activity in PAH patients (i.e., absolute distance covered, % predicted achieved, heart rate recovery, or combination of these factors). It is generally agreed that patients who can achieve greater than 400 m have a favorable clinical outcome. Right Heart Catheterization Follow-up RHC is necessary in patients who are on continuous systemic prostanoid therapy, who demonstrate clinical deterioration, or a suboptimal response to treatment(s). Specifically, RHC is needed to ensure that continuous prostanoid dose is optimal by adjusting based on the cardiac index rather than increasing as clinically, which can result in high CO failure. Repeat RHC is highly variable among PH centers. Echocardiographic changes have been noted following therapies. In the prospective randomized trial with epoprostenol, the 12-week infusion of prostacyclin had beneficial effects on right ventricular size, curvature of the interventricular septum, and maximal tricuspid regurgitant jet velocity. Similarly, comparison of patients receiving treatment with the nonselective endothelin-1 antagonist bosentan demonstrated significant differences in changes in ventricular morphology, the minimum diameter of the inferior vena cava, and Doppler measurements, including right ventricular ejection time and mitral valve peak velocity. The echocardiographic finding that tends to be the focus by most physicians when evaluating for PAH—the estimation of PA systolic pressure measurement—has not been found to be predictive of outcome. Furthermore, studies performed to assess correlation between echocardiographic assessment of PASP and right heart measurement have demonstrated variable findings, depending on the population studied, the time interval between the two measurements, and the method of estimating the right atrial pressure, among others. Biomarker: B-type Natriuretic Peptide Brain natriuretic peptide (BNP) is produced mainly in the ventricles in response to myocyte stretch and stress. Considering the effect PAH has on the right ventricle, measuring BNP level has biologic plausibility. BNP levels have been shown to correlate with hemodynamics and survival in following patients on therapy. Furthermore, follow-up measurements after 3 months of epoprostenol therapy indicated that changes in plasma BNP levels correlated closely with changes in hemodynamics and demonstrated to be an independent predictor of survival. NT-proBNP among PAH patients of various etiology demonstrated good correlation between plasma levels of NT-proBNP and hemodynamics and survival. Using plasma BNP measurements as surrogate markers appears attractive since it is relatively easy to obtain, and provides an objective data that lends to serial comparative evaluations over time. The weakness lies in its variability, both in defining a range for the disease state and intrasubject variability. Furthermore, the potential for comorbidities and concurrent therapies, which can affect BNP levels makes it difficult to interpret findings. However, it provides yet another way of assessing the state of the right ventricle and studies are being conducted to further elucidate potential use of BNP as a marker of disease severity in PAH. Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) is a U.S. database of over 3,000 patients used to assess outcomes in those receiving PAH-directed therapy. It is the largest database being collected for PAH. The clinical risk factors for mortality are as follows: PVR more than 32 Wood units PAH associated with portal hypertension Functional Class IV Men older than 60 years of age Family history of PAH Other factors predictive of mortality PAH associated with connective tissue disease Functional Class III Mean RAP more than 20 mm Hg Resting systolic BP less than 100 mm Hg and HR more than 92 bpm 6MWD less than 165 ms BNP greater than 180 pg/ml Percent predicted carbon monoxide diffusing capacity less than or equal to 32% Pericardial effusion on echocardiogram Functional Class I 6MWD more than or equal to 440 ms BNP less than 50 pg/ml Percent predicted carbon monoxide diffusion capacity more than or equal to 80% E. Common Pitfalls and Side-Effects of Management Patients on Intravenous Prostacyclins Tunneled catheter care Patient and at least one family member must be fully knowledgeable on the management of the catheter and the pump. Patient must be educated to call if any discomfort is felt around the line, drains, any elevation in temps, or alarms from the pump. Patient should have the number to their specialty pharmacy that provides the intravenous medications since they provide 24/7 nursing support. Patients are best advised to alert their local hospital ED department about their diagnosis, treatment, and potential need for emergency care. Patients on Endothelin receptor antagonists The development of edema and increasing symptoms can be seen. Patients must be counseled to monitor their weight and to call if they see increase in peripheral edema, weight gain, or worsening dyspnea. It is not unusual to need increase in diuretics during the initiation of ERA treatments. For most individuals, after the appropriate adjustment period, their symptoms improve and the need for diuretics resolve. If this period goes untreated, patients can present with marked exacerbation of right heart failure, hypoxia, and decline in renal function. Patients on PDE-5 Inhibitors Patients need to be followed closely to see if their clinical improvement is maintaining. Similar to other therapies in this class (i.e., nitrates), the initial efficacy can diminish. Patients need to be educated regarding contraindication with all forms of nitrates and to let their emergency health care providers know that they are on “Viagra” (Revatio not known to most physicians). IV. Management with Co-Morbidities Portopulmonary hypertension is one of several pulmonary complications of liver disease, where PAPs are due to increased resistance to blood flow in patients with portal hypertension. ALL candidates for liver transplantation must undergo echocardiography to screen for portopulmonary hypertension. If elevated PAPs are detected, RHC must be performed. The definition of portopulmonary hypertension by RHC is as follows (same as PAH hemodynamic definition): Elevated mPAP more than 25 mm Hg Increased PVR more than 240 dynes.s.cm-5 (>3 Wood units) Normal PCWP less than 15 mm Hg or an elevated transpulmonary gradient (TPG) (mPAP-PCWP; abnormal is >12 mm Hg) In portopulmonary hypertension, it is critical to determine what is causing the PAPs to be elevated: High CO state – in general, patients with liver disease have high CO, which can elevate PAPs Increased blood volume due to fluid shifts (elevated PCWP) In portopulmonary hypertension, the PAPs and PVR are elevated. Thus in a patient with mPAP of 45 mm Hg, PCWP 14 mm Hg (TPG = 31 mm Hg) and CO of 6 L/min, the PVR (TPG/CO) is 5.2 Wood units, this patient has portopulmonary hypertension. However, if the patient has mPAP of 45 mm Hg and PCWP 18 (TPG 27) and CO 6 L/min, though the PCWP is above the defined limit of 15 mm Hg the PVR is elevated at 4.5 Wood units so you would not exclude the diagnosis. If the same patient had CO 9 L/min, then the PVR would be 3 Wood units, which would suggest that elevated PAPs are due to a high output state. Acute vasodilator studies are not very helpful in portopulmonary hypertension. These patients generally do not tolerate calcium channel blockers since they can exacerbate edema and portal hypertension. Also a positive vasodilator response does not predict survival with or without liver transplantation. General recommendations regarding portopulmonary hypertension and liver transplantation: mPAP less than 35 mm Hg: usual risk; no treatment for PH needed mPAP 35-50 mm Hg: increased risk; consider PAH-directed therapy to determine response Risk during induction of anesthesia, during and after graft reperfusion, and in the immediate post op period Hemodynamic perturbations are due to an increase in blood flow following reperfusion or due to fluid boluses needed, which can exacerbate pulmonary hypertension and RV failure Mortality rates reported range from 36% to 92% for patients who underwent liver transplant with an mPAP greater than 35 mm Hg mPAP greater than 50 mm Hg: high risk; most likely not eligible for liver transplant; consider medical therapy Scleroderma population represents the largest group of patients potentially at risk for developing PAH The most at-risk are patients with limited scleroderma (especially after several years of diagnosis). Patients with scleroderma complicated by PAH do not respond well to PAH treatments compared to IPAH patients. Scleroderma, the diffuse form in particular, is associated with other organ involvements, which can cause significant complications: GI complications – this is common with scleroderma and can be problematic since many of the PAH therapies can exacerbate these problems (i.e., reflux and diarrhea). Other GI problems include difficulty swallowing, malabsorption, bleeding, and weight loss. Pulmonary disease – most common and deadly manifestation. The most often seen are pulmonary fibrosis or interstitial lung disease. V. Patient Safety and Quality Measures A. Appropriate Prophylaxis and Other Measures to Prevent Readmission. It needs to be stressed that the outcome of patients with PAH have improved significantly with advances in medical therapy. PAH has evolved from a fatal disease to a chronically managed condition. Prognosis is dependent on the following: Functional Class upon presentation – worse for those who present at FC IV Associated conditions – scleroderma-associated PAH have worse prognosis Demographics – male gender, older population Presence of other organ dysfunction – renal insufficiency Salt and Fluid Management Sodium restricted diet (<2,000 mg/day) is advised and is especially critical for patients with RV dysfunction in order to manage volume status. For advanced disease state with RV failure, fluid restriction (<2 L/day) is recommended. Monitoring daily weights should be encouraged. Yearly influenza vaccinations are advised, as well as being up to date with pneumococcal vaccinations. Hemodynamic fluctuations of pregnancy, labor, delivery, and postpartum period are poorly tolerated in PAH patients and can result with devastating consequences. Though not much data is present, some series report up to a 50% maternal mortality rate. Current guidelines recommend that pregnancy be avoided or terminated early in women with PAH. It is imperative to have discussions regarding methods of birth control with patients. There is a great deal of controversy as to what is the preferred method. Estrogen-containing contraceptives may increase the risk of venous thromboembolism; however, currently available lower-dose preparations with concurrent warfarin anticoagulation may be an option. Some have advocated surgical sterilization and barrier methods. Low-level graded aerobic exercise (i.e., walking) recommended as tolerated. A study among 30 PAH patients who were stable on PAH treatments demonstrated improvements in 6-minute walk distance (6MWD), quality of life, functional class, and peak oxygen consumption. It is best to avoid heavy physical exertion or isometric exercise (i.e., straining against a fixed resistance) as this can cause exertional syncope. Exposure to high altitudes may contribute to hypoxic pulmonary vasoconstriction and is not well tolerated. For air travel, it is recommended that for patients with preflight pulse oximetry less than 92% to receive supplemental oxygen. Sodium restricted diet (<2,000 mg/day) is advised and is especially critical for patients with RV dysfunction to manage volume status. For advanced disease state with RV failure, fluid restriction (<2 L/day) is recommended. Monitoring daily weights should be encouraged. Yearly influenza vaccinations are advised as well as being up to date with pneumococcal vaccinations. Hemodynamic fluctuations of pregnancy, labor, delivery and postpartum period are poorly tolerated in PAH patients and can result with devastating consequences. Though not much data is present, some series report up to 50% maternal mortality rate. Current guidelines recommend that pregnancy be avoided or terminated early in women with PAH. It is imperative to have discussions regarding methods of birth control with patients. There is a great deal of controversy as to what is the preferred method. Estrogen-containing contraceptives may increase risk of venous thromboembolism; however, currently available lower-dose preparations with concurrent warfarin anticoagulation may be an option. Some have advocated surgical sterilization and barrier methods. B. What's the Evidence for specific management and treatment recommendations? McLaughlin, VV, Archer, SL, Badesch, DB. “ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents”. J Am Coll Cardiol. vol. 53. 2009. pp. 1573-1619. (Comprehensive up-to-date recommendations on background, evaluation, and management of PAH.) D’Alonzo, GE, Barst, RJ, Ayres, SM. “Survival in patients with primary pulmonary hypertension: results from a national prospective registry”. Ann Intern Med. vol. 115. 1991. pp. 343-9. (Epidemiology and risk assessments from the first NIH PPH Registry data from 1980s, prior to PAH-specific treatments were available. Only publications with natural history and outcome of PAH.) Simonneau, G, Robbins, IM, Beghetti, M. “Updated clinical classification of pulmonary hypertension”. J Am Coll Cardiol. vol. 54. 2009. pp. S43-54. (Lists clinical classification for PH from the 5th Dana Point World Symposium Meeting) Barst, RJ, Gibbs, SR, Hossein, A. ” Updated evidence-based treatment algorithm in pulmonary arterial hypertension”. J Am Coll Cardiol. vol. 54. 2009. pp. S78-84. (Discusses updated treatment recommendations from the 5th Dana Point World Symposium Meeting) Badesch, DB, Champion, HC, Sanchez, MA. “Diagnosis and assessment of pulmonary arterial hypertension”. J Am Coll Cardiol. vol. 54. 2009. pp. S55-66. (Discusses the evaluation recommendations from the 5th Dana Point World Symposium Meeting) de Perrot, M. J Heart Lung Transplantation. vol. 30. 2011. pp. 997(Study demonstrating Novalung experience from the Toronto Group) C. DRG Codes and Expected Length of Stay. Despite changes in nomenclature in medical research and in published literature, billing codes still use the old terminologies “Primary Pulmonary Hypertension” (PPH) and “Secondary Pulmonary Hypertension” (SPH). Primary Pulmonary Hypertension (416.0) Secondary Pulmonary Hypertension (416.8) Other relevant DRGs Dyspnea/shortness of breath (786.05) Scleroderma (710.1, 701.0) Diastolic heart failure, unspecified (428.30) Diastolic heart failure, acute (428.31) Diastolic heart failure, chronic (428.32) Diastolic heart failure, acute on chronic (428.33) Right heart failure (428.0) Length of Stay (LOS) This varies depending on clinical situation 1. Initial admission for evaluation; full workup, including RHC; and possible initiation of treatment. LOS can vary mostly depending on how unstable patient is upon presentation. Key workups include echocardiogram (with bubble if not done), VQ scan, PFTs, 6MWT (if able), serologies, and RHC. 2. For patients with advanced PAH (FC IIIB or IV, or decompensated RHF) and require intravenous therapy, usually LOS 3-5 days. Recommend transfer to PH Center. 3. For decompensated right heart failure admission requiring intravenous diuretics with or without inotropes, usually 3-5 days but can vary pending other underlying comorbidities and conditions. 4. For central access-related admissions, 1-3 days (or longer) depending if related to malfunction or infectious or both. Copyright © 2017, 2013 Decision Support in Medicine, LLC. All rights reserved. No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC. The Licensed Content is the property of and copyrighted by DSM. - I. Pulmonary Arterial Hypertension: What Every Physician Needs To Know. - II. Diagnostic Confirmation: are you sure your patient has Pulmonary Arterial Hypertension? - A. History Part 1: Pattern Recognition - B. History Part 2: Prevalence: - C. History Part 3: Competing diagnoses that can mimic Pulmonary Arterial Hypertension - D. Physical Examination Findings. - E. What diagnostic tests should be performed? - 1. What laboratory studies (if any) should be ordered to help establish the diagnosis? - 2. What imaging studies (if any) should be ordered to help establish the diagnosis? - III. Management - A. Immediate management. - A. Physical Examination Tips to Guide Management. - B. Laboratory Tests to Monitor Response To, and Adjustments in, Management - C. Long-term management. - E. Common Pitfalls and Side-Effects of Management - IV. Management with Co-Morbidities - V. Patient Safety and Quality Measures A. Appropriate Prophylaxis and Other Measures to Prevent Readmission. - B. What's the Evidence for specific management and treatment recommendations? - C. DRG Codes and Expected Length of Stay.	2	53	0	0	3	0.985055	3	28,692
Welcome to the NORD Physician Guide to Nontuberculous Mycobacterial Lung Disease (NTM). The NORD Online Physician Guides are written for physicians by physicians with expertise on specific rare disorders. This guide was written by Leah Lande, MD, Division of Pulmonary and Critical Care Medicine, Lankenau Medical Center. (see acknowledgements for additional information). NORD is a nonprofit organization representing all patients and families affected by rare diseases. The information NORD provides to medical professionals is intended to facilitate timely diagnosis and treatment for patients. NTM are mycobacterial species that are ubiquitous in the environment, and are classified separately from Mycobacterium tuberculosis complex and Mycobacterium leprae. Most of the disease burden from NTM is due to chronic lung infections in immunocompetent individuals with or without underlying lung disease. NTM pulmonary infection can occur in patients with underlying lung disease such as COPD, bronchiectasis, cystic fibrosis, primary ciliary dyskinesia and alpha-1 antitrypsin deficiency, and can also occur in individuals without any prior underlying lung disease The American Thoracic Society and Infectious Disease Society of America have published joint guidelines outlining the diagnostic criteria for pulmonary NTM infection. Specific treatment decisions will vary considerably depending on individual patient factors and antimicrobial susceptibility of the organisms. What is Nontuberculous Mycobacterial Lung Disease (NTM)? NTM are mycobacterial species that are ubiquitous in the environment, and are classified separately from Mycobacterium tuberculosis complex and Mycobacterium leprae. There are over 140 species of NTM that have been identified thus far 1,2. NTM have been found in household water and soils, and are likely causing human infection through environmental exposure 3,4,5. Most of the disease burden from NTM is due to chronic lung infections in immunocompetent individuals with or without underlying lung disease. The most common species to cause chronic lung infections is M. avium complex (MAC) 6. Other species that can cause chronic lung infection include M. abscessus, M. kansasii, M. fortuitum, M. xenopi, M. malmoense, M. szulgai, and M. simiae. The relative prevalence of each of these species varies throughout different parts of the world 6. In addition to pulmonary infection, NTM can also cause superficial lymphadenitis, skin and soft tissue infections, and disseminated disease in immunocompromised patients 6,7. There are different predisposing factors for the different forms and species of NTM. Patients with cavitary MAC infection are often prior smokers with underlying COPD or patients with pre-existing structural lung disease. Patients with the nodular bronchiectatic form of MAC or with M. abscessus infection are often thin, middle aged or elderly females, and over half have no prior history of smoking or underlying lung disease. They may have other associated findings, including pectus excavatum, mitral valve prolapse, scoliosis, and heterozygous mutations in the cystic fibrosis transmemberane regulator gene 12,13,14. Individuals with cystic fibrosis (CF) and non-CF bronchiectasis are at increased risk for developing NTM infections, most commonly MAC or M. abscessus. M. kansasii is more common in males and in individuals with underlying COPD or immune suppression from medications, HIV infection or malignancy 15,16,17. Individuals with certain immune defects, including interferon gamma receptor deficiencies, auto-antibodies to interferon gamma, STAT-1 deficiency and GATA2 deficiency also have increased risk of developing NTM, including disseminated disease 18,29,20,21. Marfan’s syndrome, hyper-IgE syndrome, and congenital contractural arachnodactyly have also been associated with pulmonary NTM disease 22,23,24. NTM pulmonary infection can occur in patients with underlying lung disease such as COPD, bronchiectasis, cystic fibrosis, primary ciliary dyskinesia and alpha-1 antitrypsin deficiency, and can also occur in individuals without any prior underlying lung disease 8. It is not yet fully understood why only certain individuals who are exposed to NTM in the environment develop infection. In addition, the severity of infection and disease course is highly variable between individuals, and the reasons for this variability are also not well understood at this time. The symptoms of NTM lung infection may include any of the following: NTM most commonly cause two different clinical entities in the lung. The first is nodular bronchiectasis, usually a less severe form of disease, characterized by interstitial tree-in-bud infiltrates on chest CT scan, often involving the right middle lobe and lingula. The second is cavitary disease, often involving the upper lobes, and characterized by more progressive and severe disease. Less commonly, NTM can present as a solitary pulmonary nodule 9 or as a hypersensitivity pneumonitis in response to an intense inhalational exposure to MAC organisms, also known as “hot tub lung” 10,11. The American Thoracic Society and Infectious Disease Society of America have published joint guidelines outlining the diagnostic criteria for pulmonary NTM infection 6. These guidelines require that a patient meet clinical, radiographic, and microbiologic criteria to establish a diagnosis of NTM pulmonary disease: NTM have traditionally been classified into rapidly growing and slowly growing mycobacteria. M. abscessus, M. chelonae, and M. fortuitum are rapidly growing mycobacteria, and usually grow in culture within one week. The slowly growing mycobacteria, which include the most common species, MAC, typically take 10-14 days to grow in liquid media, and 2-4 weeks to grow in solid media. Once growth is evident, nucleic acid probes can be performed for rapid identification of M. tuberculosis, M. kansasii and MAC. [see figure 1] The decision regarding whether to treat a patient with NTM pulmonary infection can sometimes be difficult. The potential risks of adverse effects of treatment must be weighed against the patient’s symptoms and severity of disease. If the decision is made not to treat, the patient should be monitored closely for disease progression. Antimicrobial regimens for the most common species of NTM are outlined below. Specific treatment decisions will vary considerably depending on individual patient factors and antimicrobial susceptibility of the organisms. Treatment should be continued for 12 months following conversion of sputum cultures to negative. Treatment of MAC 2007 ATS/IDSA guidelines for treatment include use of all 3 of the following drugs, either 3 times per week or daily, depending on disease severity and presence of cavitary disease 6: For nodular bronchiectatic MAC pulmonary disease (3 times per week regimen): For cavitary or severe nodular bronchiectatic MAC disease (daily regimen): *The 2007 ATS/IDSA statement recommendations do suggest that macrolide susceptibility testing be performed on isolates from patients in whom therapy is indicated 6. Antibiotic susceptibility testing is reliable only for macrolides and amikacin, in which MICS have been shown to correlate with in vivo response 6,25. For patients with severe disease or with macrolide resistant isolates, consideration should be given to the addition of IV amikacin or IM streptomycin (10-15mg/kg 3x/week) for the first 8-12 weeks of therapy. Lower doses of 5-8mg/kg should be considered in patients older than 50 years old, whose weight is <50kg, or whose duration of injectable therapy is extended beyond 8-12 weeks. The use of inhaled amikacin can also be considered. For patients who are intolerant of any of the above medications or with macrolide resistant isolates, the addition of Clofazimine 50-100mg daily can be considered as a part of a multi-drug regimen for treatment of MAC. Clofazimine is generally well tolerated, but can result in skin discoloration in up to 60% of patients. Currently, clofazimine is available in the United States for the treatment of MAC disease only with an IND application to the FDA for each patient. Table 1 – Potential drug toxicities from the most commonly used medications for MAC infection Monitoring for drug toxicity should include appropriate bloodwork, and regular auditory testing and ophthalmologic exams. Treatment of M. kansasii Treatment of Rapid Growers/M. abscessus M. abscessus, M. chelonae and M. fortuitum are resistant to Isoniazid, Ethambutol and Rifampin, but are susceptible to various different antibiotics, including macrolides, amikacin, cefoxitin, imipenem, doxycycline, sulfonamides, and fluoroquinolones. Susceptibility testing must be performed on all clinically significant isolates, as antibiotic sensitivity patterns will vary between different isolates. M. fortuitum and M. abscessus subspecies abscessus contain an inducible macrolide resistance (erm) gene, which can result in acquired macrolide resistance in these organisms after they are exposed to a macrolide. In order to detect this resistance, the isolate needs to be incubated for 14 days with a macrolide prior to determining the MIC for the macrolide 26,27. Antimicrobial regimens should be based on drug susceptibility testing for individual isolates. Table 2 lists antibiotic options that may be considered. Table 2. Antibiotic Regimens for Treatment of Rapidly Growing NTM Non-pharmacologic treatment of pulmonary NTM disease Monitoring for drug toxicity should be performed based on the potential adverse effects of the treatment regimen which is chosen. This may include monitoring of renal function (aminoglycosides), hepatic panel (macrolides), complete blood count (cefoxitin, sulfonamides) and auditory or vestibular testing (aminoglycosides and macrolides). Patients with localized bronchiectasis, cavitary disease, or refractory hemoptysis may be considered for surgical resection of the involved area. In addition to medications, the following modalities are also essential to proper care of patients with NTM lung disease: Information on current clinical trials is posted at www.clinicaltrials.gov All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site. Insmed is conducting a randomized, phase III, open-label study to evaluate the effectiveness of liposomal Amikacin for inhalation (LAI) when added to multi-drug regimen in individuals with NTM lung infection caused by mycobacterium avium complex (MAC). The clinical study, being conducted in 31 locations, will evaluate the benefits of adding LAI to current treatment regimens and also help in understanding side effects LAI may cause in patients with MAC lung infection: For information about clinical trials sponsored by private sources, contact: www.centerwatch.com NORD does not endorse or recommend any particular studies. 2. Brown-Elliott BA, Griffith DE, Wallace RJ Jr. Newly described or emerging human species of nontuberculous mycobacteria. Infect Dis Clin North Am 2002; 16: 187. 3. Mullis SN, Falkinham JO 3rd. Adherence and biofilm formation of Mycobacterium avium, Mycobacterium intracellulare and Mycobacterium chimaera to household plumbing materials. J Appl Microbiol 2013; 115:908. 4. Wallace RJ, Iakhiaeva E, Williams MD, et al. Absence of Mycobacterium intracellulare and presence of Mycobacterium chimaera in household water and biofilm samples of patients in the United States with Myciobacterium avium comoplex respiratory disease. J Clin Microbiol 2013; 51: 1747. 5. Falkinham JO 3rd. Reducing human exposure to Mycobacterium avium. Ann Am Thorac Soc 2013;10:378. 6. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007; 175: 367. 7. Wolinsky E. Nontuberculous mycobacteria and associated diseases. Am Rev Respir Dis 1979; 119: 107. 8. Prince DS, Peterson DD, Steiner RM, et al. Infection with Mycobacteriunm avium complex in patients without predisposing conditions. N Engl J Med 1989; 321: 863. 9. Lim J, Lyu J, Choi CM, et al. Non-tuberculous mycobacterial diseases presenting as solitary pulmonary nodules. Int J Tuberc Lung Dis 2010; 14: 1635. 10. Rickman OB, Ryu JH, Fidler ME, Kalra S. Hypersensitivity pneumonitis associated with Mycobacterium avium complex and hot tub use. Mayo Clin Proc. 2002 Nov;77(11):1233-7 11. Khoor A, Leslie KO, Tazelaar HD, et al. Diffuse pulmonary disease caused by nontuberculous mycobacteria in immunocompetent people (hot tub lung). Am J Clin Pathol 2001; 115: 755. 12. Kim RD, Greenberg DE, Ehrmantraut ME, et al. Pulmonary nontuberculous mycobacterial disease: prospective study of a distinct preexisting syndrome. Am J Respir Crit Care Med 2008; 178: 1066. 13. Iseman MD, Buschman DL, Ackerson LM. Pectus excavatum and scoliosis. Thoacic anomalies associated with pulmonary disease caused by Mycobacterium avium complex. Am Rev Respir Dis 1991; 144: 914. 14. Kartalija M, Ovrutsky AR, Bryan CL, et al. Patients with nontuberculus mycobacterial lung disease exhibit unique body and immune phenotypes. Am J Respir Crit Care Med 2013; 187:197. 15. Lillo M, Orengo S, Cernoch P, Harris RL. Pulmonary and disseminated infection due to Mycobacterium kansasii: a decade of experience. Rev Infect Dis 1990; 12: 760. 16. Shitrit D, Maum GL, Priess R, et al. Pulmonary Mycobacterium kansasii infection in Israel, 1999-2004: clinical features, drug susceptibility and outcome. Chest 2006; 129: 771. 17. Bamberger DM, Driks MR, Gupta MR, et al. Mycobacterium kansasii among patients infected with human immunodeficiency virus in Kansas City. Kansas City AIDS Research Consortium. Clin Infect Dis 1994; 18: 395. 18. Newport MJ, Huxley CM, Huston S, et al. A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N Engl J Med 1996; 335: 1941. 19. Patel SY, Ding L, Brown MR et al. Anti-IFN-gamma autoantibodies in disseminated nontuberculous mycobacterial infections. J Immunol 2005; 175: 4769. 20. Dupuis S, Dargemont C, Fieschi C, et al. Impairment of mycobacterial but not b=viral immunity by a germline human STAT1 mutation. Science 2001; 293: 300. 21. Hsu AP, Sampaio EP, Khan J, et al. Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood 2011; 118: 2653. 22. Gelb BD. Marfan’s syndrome and related disorders—more tightly connected than we thought. N Engl J Med 2006; 355: 841. 23. Melia E, Freeman AF, Shea YR et al. Pulmonary nontuberculous mycobacterial infections in hyper-IgE syndrome. J Allergy Clin Immunol 2009; 124: 617. 24. Paulson ML, Olivier KN, Holland SM. Pulmonary non-tuberculous mycobacterial infection in congential contractural arachnodactyly. Int J Tuberc Lung Dis 2012; 16: 561. 25. NCCLS Susceptibility Testing of Mycobacteria, Nocardiae, and Other Aerobic Actinomycetes; Approved Standard (M24-A) 2003. 26. Nash KA, Brown-Elliott BA, Wallace RJ Jr. A novel gene, erm (41), confers inducible macrolide resistance to clinical isolates of Mycobacterium abscessus but is absent from Mycobacterium chelonae. Antimicrob Agents Chemother 2009; 53: 1367. 27. Nash KA, Zhang Y, Brown-Elliott BA, Wallace RJ Jr. Molecular basis of intrinsic macrolide resistance in clinical isolates of Mycobacterium fortuitum. J Antimicrob Chemother 2005; 55: 170. Leah Lande, MD NORD is grateful to Dr. Lande for her authoring of this Physician’s Guide. This NORD Physician Guide was made possible by an educational grant from Insmed. Copyright ©2015 NORD - National Organization for Rare Disorders, Inc. All rights reserved. NORD is a registered 501(c)(3) charity organization. Please note that NORD provides this information for the benefit of the rare disease community. NORD is not a medical provider or health care facility and thus can neither diagnose any disease or disorder nor endorse or recommend any specific medical treatments. Patients must rely on the personal and individualized medical advice of their qualified health care professionals before seeking any information related to their particular diagnosis, cure or treatment of a condition or disorder.	2	11	0	0	1	0.500843	1	3,929
The ICD-9-CM is divided into three volumes: Volume 1 (tabular list of diseases). Volume 2 (Index of Diseases). Volume 3 (index of procedures and tabular list of procedures). Similarly, one might ask how many ICD 9 volumes are there? ICD-9-CM Volume 3. ICD– 9-CM Volume 3 is a system of procedure codes used by health insurers to classify medical procedures for billing purposes. It is a subgroup of the International Statistical Classification of Diseases and Related Health Problems (ICD) 9-CM. Volumes 1 and 2 are used for diagnostic coding. Second, which volumes of ICD 9-CM are used for diagnostic coding? ICD-9-CM is divided into three volumes , The first two consist of diagnostic codes, while the third volume contains a list of available procedure codes. Inpatient medical coders and medical billers use Volume 3 to describe medically necessary services provided in the hospital setting. So how many chapters does ICD 9 CM have? ICD-10 -CM has 21 chapters in the tabular list, while ICD-9-CM had 17 plus two additional classifications (V codes and E codes). Comparison between ICD-9-CM and ICD-10-CM. \|ICD-9-CM Chapter\|\|ICD-10-CM Chapter\| \|16. Symptoms, Signs, and Undefined Conditions (780-799)\|\|16. Certain disorders originating in the perinatal period (P00-P96)\| What are the ICD 9 codes? - These are commonly referred to as diagnostic codes. - ICD-9 stands for International Classification of Disease, Ninth Revision. - Coding is a universal or standard system used for is for the purpose of identifying diseases. - These codes have three, four or five digits. What is the difference between ICD 9 and ICD 10 codes? ICD-9 codes can contain between three and five digits, but ICD-10 codes can contain between three and seven digits. This is done to create codes that are more specific, in addition to accounting for diseases and conditions not covered under ICD-9. What letter is considered a wildcard character in ICD 10 CM? What are the differences between ICD-9 codes and CPT codes? In short, ICD-9 is the code used to identify the state or to describe the disease treated, also called diagnosis. CPT is the code used to describe the treatment and diagnostic services provided for that diagnosis. How many ICD-10 codes are there? There are over 70,000 ICD-10 PCS procedure codes and over 69,000 ICD-10-CM diagnostic codes, compared to approximately 3,800 procedure codes and approximately 14,000 diagnostic codes found in the previous ICD-9-CM. In which countries is ICD 10-CM used? The Czech Republic, Denmark, Romania, Slovakia and Thailand adopted ICD-10 to code mortality in 1994, and since then 33 other countries have joined. The United States began using ICD-10 in January 1999 to encode and classify mortality data from death certificates. Is ICD 9 still used? The ICD-9 – Code structure has been in place for 30 years. The terms currently used in ICD-9 are outdated, obsolete and no longer compatible with current medical practice. In addition, the structure of ICD-9 limits the number of new codes that can be created, and many ICD-9 categories are full. What does ICD stand for? International Classification of Diseases Why is ICD 10 important? The ICD-10 code system provides accurate and up-to-date procedural codes to improve healthcare costs and ensure fair reimbursement policies. Specifically, the current Codes help healthcare providers identify patients in need of immediate disease management and tailor effective disease management programs. What does CPT mean in medical terms? Current Procedural Terminology What is a CM code? This US ICD-10 modification is called ICD-10-CM, where the CM part stands for clinical modification. In addition to ICD-10-CM for identifying diagnoses, the Centers for Medicare & Medicaid Services have developed ICD-10-PCS, a set of codes for identifying procedures used on hospitalized patients. How to find Do you have ICD 10 codes? ICD-10: How to find the right code in 5 steps - Order the lists today. Both can be downloaded from the CMS website (www.cms.gov/icd10). - Step 2: Check the tabular list. - Step 3: Read the code‘s instructions. - Step 5: For glaucoma, you may need to add a seventh character. How many ICD 10 codes can be billed? You can combine up to 12 diagnostic codes into one Record Application form, only four of these diagnostic codes can be associated with a particular CPT code. This is because the current 1500 form has room for up to four diagnostic notes per line, and this will not change with the transition to ICD-10. WHO ICD 9? The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) is based on the ninth revision of the World Health Organization’s International Classification of Diseases (ICD-9). What are ICDs 9 and 10 codes? The ICD-9-CM codes have three to five characters that are numeric except for the V-codes (factors affecting health care), E-codes (external Causes of Injury) and M-Codes (Morphology of Neoplasms) beginning with a single letter. The new ICD-10-CM codes have three to seven alphanumeric characters. How often are ICD codes updated? The ICD code set is usually updated every 10 years. The US was the last industrialized nation to adopt ICD-10 for reporting illnesses and injuries, although it has been used for mortality statistics since 1999. What coding systems does the United States use? Two common medical classification systems are used – the International Classification of Diseases (ICD) and Current Procedural Terminology (CPT). In what year was ICD 9 CM first introduced? In testifying before Congress in May 2002, Sue Prophet, AHIMA’s Director of Coding Policies and Compliance, testified that “AHIMA believes that the introduction of a replacement for the ICD-9-CM diagnostic codes is an absolute necessity, since ICD-9-CM is more than 20 years old (implemented in 1979) and obsolete and	4	14	0	0	2	0.23282	2	1,397
Last updated: November 22, 2014 Synonyms: Metabolic diseases of muscle, metabolic myopathies, statin-induced myopathy, drug-induced myopathy. ICD-9 Codes: Myopathy, 359.9; alcoholic, 359.4; amyloid, 359.6; toxic, 359.4; Tarui disease, 271.2; deficiency of carnitine, 277.81; carnitine palmityl transferase, 791.3 ICD-10 Codes: G71 – G72; M60 – M63 Definition: Myopathy is a generalized term applied to a heterogeneous group of disorders that affect muscle. Inflammatory muscle disease is considered elsewhere. The differential diagnosis of weakness and myopathy is expansive and includes inflammatory, infiltrative, metabolic and disorders born of inborn errors (Table). The metabolic myopathies include disorders of skeletal muscle caused by alterations in biochemical pathways and divided into disorders of glycogenolysis, lipid metabolism, and mitochondrial myopathies. \|Table. Causes of Myopathy\| Adenylate Deaminase Deficiency \| Muscular Dystrophy Etiology: Most of these disorders have a genetic basis and show an autosomal recessive pattern of inheritance. Hypokalemic periodic paralysis is an autosomal dominant disorder. Mitochondrial myopathies show a maternal pattern of transmission because all mitochondrial DNA is derived from the mother. A small number of cases are acquired and are attributable to other underlying disorders such as cirrhosis, renal failure, metabolic disorders, or drugs. Pathology: Light microscopic examination of the muscle biopsy specimen may demonstrate lipid deposition (shown on oil red O stain) in lipid storage myopathies. Mitochondrial abnormalities may also be seen on routine microscopic examination, and the presence of irregular, ragged red fibers suggests a mitochondrial disorder. On electron microscopic examination, increased collagen deposition may be observed in patients with glycogen storage diseases. However, biopsy specimens from some patients may appear normal. Demographics: Most primary inherited cases become apparent in children and adolescents but may occur later in life. Cardinal Findings: These disorders impair muscle function on demand and often manifest as fatigue, aches, cramps, and myalgia and may result in myoglobinuria, rhabdomyolysis, or fixed weakness in some. In most, symptoms only develop when muscular activity or nutritional defect unmasks the underlying defect. Most patients show muscle weakness. Some are able to perform normal daily activities without problems but become symptomatic at higher levels of exercise. Clinical assessment should exclude central nervous system disorders or peripheral (denervation) neuropathy as the cause of muscle weakness or complaint. DISORDERS OF GLYCOGENOLYSIS —McArdle’s disease: Caused by a myophosphorylase deficiency (see Mcardle’s disease) —Tarui’s disease: Caused by a phosphofructokinase deficiency, Tarui’s disease has features similar to those of McArdle’s disease, but there may also be nausea, vomiting, and a hemolytic anemia. Most patients are diagnosed as adults and may or may not recall exercise intolerance when younger. Patients with phosphofructokinase deficiency cannot utilize glucose, and thus high carbohydrate meals may exacerbate exercise intolerance. —Acid maltase deficiency: An autosomal recessive disease with three phenotypes. It may manifest before 2 years of age as Pompe’s disease with infantile weakness, hypotonia, heart failure, and early death. A second variety begins in early childhood with truncal, proximal, and respiratory muscle weakness. Last, a milder adult subset may begin in the third or fourth decade, with muscle weakness and a pattern indistinguishable from polymyositis or limb- girdle muscular dystrophy. Acid maltase deficiency causes a vacuolar myopathy, and biochemical studies are necessary to prove the diagnosis. —Others: Episodic myopathy may occur as a result of deficiency of lactate dehydrogenase, aldolase, B-enolase, phosphorylase b kinase, or phosphoglycerate mutase. Brancher enzyme deficiency causes chronic proximal myopathy in children or older adults. Debrancher enzyme deficiency causes distal, rather than proximal, myopathy in the third to fourth decade of life. —Myoadenylate deaminase deficiency: Myoadenylate deaminase is a muscle- specific isoenzyme and is involved in the purine nucleotide cycle production of fumarate. It is characterized by exercise-related cramps in children and rarely leads to myoglobinuria. May be associated with delayed motor and speech development, hypotonia, or cardiomyopathy. Muscle enzymes are normal or high, but there is a lack of myoadenylate deaminase activity on histochemical staining of muscle. On ischemic forearm exercise testing, these patients are unable to generated an increase in serum ammonia levels. DISORDERS OF LIPID METABOLISM —Carnitine deficiency: Deficient transfer of long-chain free fatty acids to the mitochondria results from carnitine deficiency. Muscle weakness begins in childhood and may be associated with myalgias, proximal weakness, respiratory muscle weakness, cardiomyopathy, myoglobinuria, increased creatine phosphokinase, hypoketotic hypoglycemia, and increased lipid in muscle. —Carnitine palmityltransferase deficiency: An autosomal recessive disorder, carnitine palmityltransferase deficiency typically affects males, with exercise intolerance, myalgias, cramps, stiffness, and myoglobinuria. Attacks are triggered by exercise or fasting. Creatine phosphokinase and ischemic exercise tests are usually normal. Diagnosis is based on biochemical analysis of enzyme activity in muscle. Some of these patients develop rhabdomyolysis and renal failure, which is reversible if appropriately treated. Mitochondrial myopathies include a variety of disorders that result in alterations of mitochondria structure, number, or size. These may arise in children as limb myopathy, with or without ophthalmoplegia. Patients exhibit exercise intolerance, proximal or extraocular muscle weakness, myoclonus, salt craving, ataxia, sensorineural hearing loss, or peripheral neuropathy. Mitochondrial myopathies may arise in the adult as exercise intolerance, generalized or proximal weakness, and with normal or elevated creatine phosphokinase levels. Some may be acquired after exposure to mitochondrial toxins such as zidovudine or clofibrate. Myopathy has been reported to occur with cerivastatin, lovastatin, and simvastatin much more commonly than with pravastatin or atorvastatin. Dose- dependent myotoxic effects (including myalgia, myositis, or rhabdomyolysis) of statins occurs in 1% to 7% of patients. A 2002 FDA review of statin safety suggested that the fatal rhabdomyolysis rate was 0.15 cases per every 106 prescriptions. Cerivastatin was removed from the market after 31 cases of fatal rhabdomyolysis and 52 deaths worldwide. Those at risk were on higher doses and took concomitant gemfibrozil. Other factors that may contribute to statin myopathy include age, renal insufficiency, biliary obstruction, preexisting myopathic disorders (e.g., hypothyroidism), and use of other myotoxic drugs or drugs that induce the cytochrome P-450 enzyme CYP3A4. Mechanisms are not fully delineated, but statins inhibit the formation of mevalonate and ultimately ubiquinone (coenzyme Q10). Ubiquinone deficiency may further inhibit mitochondrial adenosine 5′-triphosphate production and myocyte function. There is no evidence that ubiquinone supplementation will have any clinical benefit in these patients. Treatment hinges on early recognition and drug cessation when appropriate. Diagnostic Tests: Serum potassium, magnesium, and creatine kinase should be measured. Some, but not all, metabolic myopathies are associated with elevated creatine phosphokinase levels; normal values do not exclude these disorders. Defects in the glycogenolytic pathway such as myophosphorylase deficiency may be detected with the forearm ischemic exercise test (absence of the normal increase in postexercise serum lactate levels is diagnostic). Myoglobin should be measured in urine if rhabdomyolysis is suspected. Biopsy: A muscle biopsy may be required to establish the diagnosis. Some metabolic syndromes are associated with elevated levels of muscle enzymes, but many do not show any abnormality or have findings only during episodes of rhabdomyolysis; in these cases, measurement of enzymatic activities in the biopsy specimen is usually required. Special handling of tissues is necessary to achieve accurate enzymatic determinations, and consultation with the pathology laboratory that will perform the analysis is essential to ensure that the specimen is collected correctly. The amount of tissue required for enzymatic analysis necessitates an open, rather than a needle, biopsy. Keys to Diagnosis: Muscle biopsy and measurement of muscle enzyme levels are usually required to establish the diagnosis in a patient with episodic or exercise-induced weakness or rhabdomyolysis. Secondary cases might be detected by routine blood and urine testing for metabolic imbalances. Therapy: Specific treatments are not always required. However, because the patient may be advised to modify diet and exercise to minimize problems, establishing the diagnosis is very important. For example, patients with carnitine palmityltransferase deficiency should be advised to avoid fasting and strenuous exercise; carbohydrate loading before moderate exercise may be useful. Carnitine deficiency may be treated by dietary supplements (as much as 4 g/day of carnitine), and anecdotal reports suggest the utility of L-carnitine, coenzyme Q10, or menadione in patients with mitochondrial myopathies. Acute rhabdomyolysis, which may occur in some of these syndromes, constitutes a medical emergency, requiring aggressive hydration, mannitol (for urine dilution) and alkalinization of urine to avoid permanent renal damage. Prognosis: Most patients can pursue normal daily activities and do not develop progressive problems. Precautions regarding diet and exercise are an important component of a successful outcome. Martin A, Haller RG, Barohn R. Metabolic myopathies. Curr Opin Rheumatol 1994;6:552–558.PMID:7865373 Rosenson RS. Current overview of statin-induced myopathy. Am J Med 2004;116:408–416.PMID:15006590 Wortmann RL, DiMauro S. Differentiating idiopathic inflammatory myopathies from metabolic myopathies. Rheum Dis Clin North Am2002;28:759–778.PMID:12506771	2	7	0	0	4	0.91499	4	2,326
Socioculturalism and Health Throughout the ICDs that can be evaluated are those of a sociocultural nature. Any study of socioculturalism and disease is complex due to the subjectivity of how this field was initially developed and since then has been subsequently re-defined and re-adapted several times. One of the major outcomes of this controversy are questions regarding lack of objectivity. The development of DSM and ICD systems has been somewhat culturally-based. This has prevented these methods of coding diseases to be effective when it comes to relying upon ICD-9 codes to identify culturally-bound syndromes. Like the nosologies of medicine during the 19th century, the current taxonomy (a more detailed and binary logic-based nosology) has relied upon an ever changing flowchart to define each and every diagnosis. A physician familiar with this system for coding disease is familiar more with the global or western philosophy of disease, not always any true cause for certain diseases. For this reason, the new ICD-10 about to be implemented partially corrects for many of these failures produced by the ICD-9. As multiculturalism becomes more respected socially, so too does the need for better understanding any other cultural traditions and beliefs that make a disease develop. Some diseases are purely cultural in that they are psychosomatic in nature and a consequence of the belief system the patient has towards his/her disease. This may even result in new labels given to the disease, as well as new names, new expectations, and even new responsibilities. In one social setting, a child with Tourette’s Syndrome is considered to have some sort of age-link tic-related disorder, and yet in another considered to be chanelling with extracoporeal or past spirits, and in another a victim of loss of soul followed by replacement of a past soul. The old ICD-9 system has just a few ways to define this condition, noting it with neurological and psychiatric and perhaps psychological, psychosomatic ICDs. The newer system has a more detailed cultural definition for the original state and its various components or axes, ranging from direct to indirect physiological and non-physiological linkages to other conditions or behaviors. The newer ICD system manages to provide a way to identify certain cultural differences that exist in disease progression. But it doesn’t necessarily change the interpretation of disease at all. Instead, it provides us with a way to define why some ICDs which have been assigned to a medical condition fail to meet the age-gender distribution features of that particular psychiatric, mental, psychosomatic, or physical disease. This review of population pyramids demonstrates how the current ICD system still misses the boat often when it comes to exactness in details. The new ICD assignments for culturally bound syndromes still lack in demonstrating any direct age-gender link to the traditional ICD and the actual appearance of a particular medical condition. In addition, this new system still lacks some of the associations being made betwen particular conditions and the possible application of the terms “culturally-bound” to these Western Medicine, Developed Country related medical conditions or diseases. A disease like anorexia nervosa is in some ways just as culturally bound as a possession of soul believed in by Hmong parents with children who demonstrate a history of epilepsy. For this reason, we have to dissect “culturally-bound” diseases further. These sociocultural-linked diseases are of several forms. Some are completely physical in nature, meaning they are physical changes and manifestations of a health condition in the body that is due completely to heredity. There are also physical diseases that develop due to cultural behaviors, and are often related to morees and taboos such as restrictions in diet, restrictions in physical social engagements (sports, groups meeting behaviors, religious practices involving interperson contact and the like), restrictions in how we must behave in terms of selecting spouses and marriages. Thirdly, there are behavioral psychological and biopsychological (even biological and psychiatric related) conditions that at times have an important physical science component, for example schizophrenia is an inherited trait common to the German speaking Amish communities. Finally, there are those primarily sociocultural or simply socially defined diseases, which are behavioral and psychological problems defined as such by the traditional culture, such as the Amok suicidal problem experienced by South Asian communities, or the unique stress syndromes many cultures have due to moving to a new setting. Culturally-linked diseases excluded from this review are those with an ecological component to their social, regional or even ethnic history. Examples of conditions excluded from this review include some very biological sociocultural-linked conditions also common to Western Society, but with different incidence rates, such as - numerous zoonotic pathogens, for example - intestinal organisms like the African tapeworm (Taenia solis) , - the Mexican-borne version of Syphilis strain resulting in pinta - the unique occupational disease Chiclero’s Ear. - “Old World” versus “New World” STDs, due to the controversy over the true origins of certain STDs during the colonial era - Recreational or religious natural products use, including cocaine leaf chewing, the Kat of Somalia, Betel Leaf consumption, India’s Hashish, Island Community nutmeg- or salap-related consumption, etc. Those most interesting diseases, conditions, or states to review are those which have distinct cultural definitions. In many cases these are defined as “diseases” or maladies only due to the way in which the Western Physician making use of these ICD systems defines a lack of normality, and subsequently identifies someone as “not normal”. These conditions are atypical to Western Culture, and at times could be likened to someone claiming a pattient is sick due to some misbehaved chakra or acupuncture point, reasoning not at all different from the “hot spots” or sensitive points philosophy used to explain something as western medicine-defined as fibromyalgia. The result of this philosophical approach used in western medicine by way of certain portions of the ICD system is the creation of certain conditions or diseases that are assumed to be proper and in need of such identification. The most commonly known results of such subjectivity and individual beliefs in medicine are those ICDs used, once used, or considered for the explanation in such human conditions and behaviors as the “Psychosomatically-induced” Irritable Bowel Syndrome identified as such by the 1950s, or the reason an individual becomes a criminal, or engages in unique sexual acts. Each of these has past and present pathological definitions attached to them, some considered solely psychiatrc, others considered biological, still others behavioral and as a result of “social detachment.” Culturally-bound syndromes change in definition over time. Most of the currently accepted syndromes for this category have some unique traits that define them as not a consequence of what western culture defines to be illness-inducing conditions or behaviors. The first list of these syndromes which follows are for ICD defined states that are very much subjective in their representation, causology and health-related outcomes. A certain number of these ICD-defined states or conditions are cultural in nature due to the rarity of what they represent, and the decision made by the medical field in general to categorize these features to just a particular group. The ICD 10 or DSM-IV-TR recognizes the following examples of these syndromes which are most closely linked to the contemporary definition for a “culturally bound” syndrome. - Amok. Malaysia. Periods of “homicidal frenzy”, brooding, and finally somnolence and amnesia. Afflicts mostly young to middle-aged males living away from home (college students). Often ends in suicide. ICD 10 code = F68.8 Other personality disorders of adult personality and behavior. Associated with Lin-Keh-Ming and hwa-byung of Korea. Other similar culture bound syndromes are perhaps: colerina-Andes Bolivia, Columbia, Ecuador, Peru, iich’aa Southwestern US Indigena, berserkergang-Scandinavia (Saami), cafard-Polynesia, benzi mazarazura- south African Shona, and ahad idze be-New Guinea. - Ataque de Nervios. Puerto Ricans and certain other Latinos/as. Uncontrollable shouting, trembling, heart palpitations, sense of heat rushing to the head, fainting and seizure like activities, temporary loss of consciousness, purported amnesia. Afflicts socially disadvantages women > 45 yo with no high school education. See “Nerves.” - Brain Fag. West Africa. Sometimes equated with Chinese equivalent neurasthenia, Korean hwa-byung, or Latino susta. A form of depression, anxiety or somatoform condition. - Dhat. India, China. Also called dhatu, jiryan, shen k’uei, and shen-kui. Characterized by anxiety, fatigue, somatic pains, “loss of energy”. Philosophically felt to be linked to semen loss, and so due to excess semen loss, leading to imbalances in the body’s five elements/four humours, made worse by bad diet. According to Chinese medical philosophy, the traditional mechanism for developing this condition is excess coitus, with chi loss incurred and loss of the spiritual “energy” or parts involved with making chi. The shen is akin to the essence used to produce the ‘vital force’ of late 18th and early 19th century western medical philosophy. Shen is “the sign of life in someone’s eyes”; loss of shen preceding death results in a very dark appearance of the inner orbit as seen through the pupil. As the Chinese names imply, disturbance and removal of this shen ensues (shen-kui). ICD 10 assignment: F48.8 Other specific Neurotic Disorder, or F45.34 Somatoform autonomic dysfunction of the genitourinary system (this may include autonomic anxiety symptomatology). Western medical collquial terms identify this as a sexual neurosis. - Hwa-byung. Korea. “Firey illness”. Anger or rage manifesting with pressure on the chest, movement of heat about the body, indigestion, fatigue, headache, and a variety of mood changes. Women are perhaps afflicted more than men. Philosophically this syndrome blamed on the oppression of Korean culture. - Koro. Hainan island of China, India, Singapore, Thailand. From “koro” for turtle. Anxiety and panic resulting in or are caused by a fear that the penis is retracting (like a tortoise head) into the abdomen. For women, breasts and genitalia are thought to contract. Excess coitus, exposure to cold, illness induce the signs (related appearances). Devices are used to prevent the retraction. Cantonese refer to this as suk-yeong, Mandarins as suo-yang, Assams as jinjinia bamar, Thai as rok-joo, Eastern Indians as rabt. ICD 10 assignment: F48.8 Other specific Neurotic Disorder, or F45.34 Somatoform autonomic dysfunction of the genitourinary system (this may include autonomic anxiety symptomatology). ICD9 - any combination of: Psychosexual dysfunction (302.7), Impotence/Frigidity (302.72), Anorgasmia (302.73, 302.74) - Latah. Malays. Startle or fright reflex responses characterized by exageration, such as overesponse to stimuli (recall autonomics and the fight or flight responses in relation to fright). Echopraxia, echolalia, and command obedience behaviors can ensue. Patient seems trancelike or even dissociative. Most often associated with women of low economic status. Similar syndromes in other cultures include amurakh (Siberia), iekunii, ikota, okan, myriachit, menkeiti, Lapp panic (Lapps), bachtschhi (Thailand), imu (Ainu indigena of Japan), mali-mali (Philippines), silok, susto (Mexico), yuan (Myanmar, formerly Burma), jumping (French Canada). ICD 10 – F48.8 Other Specified Neurotic Disorders, F48.88 Other Specified Dissociative [Conversion] disorders. - “Nerves.” Nerfiza (Egypt), Nevra (Greece), nervios (Mexico, Central and South America), nerves (northern Europe). Sorrow or anxiety, leading to head and muscle pain, reactivity, nausea, appetite loss, insomnia, fatigue, agitation. Linked to stress and low self-esteem. Women experience this more than men. ICD 10 F32.11 Moderate Depressive Episode with somatic syndrome, F48.0 Neurasthenia, F 45.1 Undifferentiated Somatoform Disorder. Related syndromes include: anfechtung (Hutterites), brain fag (Nigeria), colerina, pension and bilis (Mexico, Central America, South America), hsieh-bing or xie -bing (China), hwa-byung (Korean peninsula), qissaatuq (Inuits in Arctic territories), narahati-e a sa or maraz-e a-sab (Islamic Republic of Iran). - Pa-leng. China, esp. Taiwan, parts of southeast Asia. A frigiphobia, or fear of the cold or winds, due to association of these natural features with fatigue, impotence and death. Belief in the humoral theory for illness is an important part of these cultures. Fear is accompanied by onset of anxiety and obsessiveness. ICD 10- F40.2 Specific Phobias. Mexico and Central and South America have the related disorders agua frio, aire frio and frio. - Pibloktoq. Arctic and Subarctic Inuit. Arctic hysteria. Primarily associated with women. Preceded by tiredness, lack of facial expression, social extreme quietness, confusions. Events begin as “extreme excitement”, followed by convulsions and pseudo-coma like states. Peak attacks demonstrate adrenalin-like effects including significant strength and abberant physical and verbal behaviors. Indicative actions include removal of clothing, fleeing, jumping in water, rolling in snow, mimetic acts, choreiform movement, glossolalia, and coprophagia. Events end with fatigue, sleep and return to typical states following reawakening (see ref1., ref2; ICD 10 possibly: 1) F44.7 Mixed Dissociative (Conversion) Disorder or 2) F44.88 Other specific dissociative (conversion) disorder. Related to amok (Indonesia, Malaysia), banga or misala (Congo, Malawi, formerly Nyasaland), ebenzi (southern Africa, esp., Shona and affiliates), grisi siknis (Miskito, Honduran Indigena), imu (Ainu, indigena of Japan), latah (Indonesia, Malaysia), mali-mali (Philippines), nangiarpok, kayak angst, quajimaillituq (Inuit), ufufuyane (southern Africa, esp. Bantu, Zulu and affilated groups). Blood and physiological biochemical findings have led to numerous theories, including Vitamin A overdose. Episodes last for several minutes, and may have some relation to hypocalcemia-induced tetany cases. Interpersonal anxieities and cultural stressors play an important role, along with the meaning and purpose of this event. - Shenjing Shuairuo. China. Sense of mental and physical exhaustion, memory loss, inability to concentrate, irritability, headaches, weakening of nervous activities or nervous system (“neurasthenia”). - Susto. Also called Espanto. Mexico, Central and South America. “Soul loss” induced by the supernatural. Chief emotional result is fright, with minimal traumatic events physically experienced. Symptoms include agitation, anorexia, insomnia, fever, diarrhea, mental confusion, apathy, depression, introversion. Hypoglycemic states related to some events. Anxiety due to social stressors is a major contributor. Related to grief-loss events in life. ICD 10 is F45.1 Undifferentiated somatoform disorders, or F48.8 Other Specified Neurotic Disorders. Related to lanti (Philippines), latah (Indonesia, Malaysia), malgri (Australian aborigines), mogo laya (New Guinea), narahati (Islamic Republic of Iran), and saladera (Amazonian region). - Taijin Kyofusho. Japan. Other names: shinkeishitshu, or anthropophobia (fear of people, people interactions, and contracting disease). Social phobia about how one appears of presents himself/herself, behaviorally and somatically. Avoidance of close contacts may result. Feelings of embarassment, blushing; concerns that appearance, facial expressions, smell, words stated, might cause social unrest. Mostly afflicts younger people. Perfectionism may be a behavioral feature that results, with cultural influences upon younger populations resulting in “over-socilization” accompanied by perfectionism and then followed by breakage of social bonds due to feelings of inferiority and anxiety about personal presentation. ICD 10 – F40 Social Phobias, or F40.8 Other Phobic Anxiety Disorders. Other conditions with similar presentation: anfechtung (Hutterites), and itiju (Nigeria). - Ufufuyane. South Africa, esp. Bantu, Zulu and allies, and Kenya. Also referred to as saka. Anxiety state attributed to magic potions administered by rejected lovers, or due to spirit possession. Akin to voodoo (voodu) beliefs in part. Shouting, sobbing, paralysis, convulsions, trance-like stupor and loss of consciouness is associated with these spells. Young unmarried women are most often afflicted. Can relate to nightmares and night horrors with sexual themes, somnambulism, temporary blindness. Attacks last from days to weeks, and have a psychosomatic onset triggered by the sight of certain men or foreigners. ICD 10 codes are F44.3 Trance and possession disorders, or F44.7 Mixed dissociative [conversion] disorders. Other syndromes related to this include aluro (Nigeria), phii pob (Thailand), and zar (Egypt, Ethiopia and Sudan). - Uqamairineq. Inuits in the Arctic region. Paralysis of sudden onset with borderline sleep states; anxiety, agitation and hallucinations are related. Prodromal indicators are noted such as transient sound or smell (taste as well?). Chronic disease, resulting in attacks that last for several minutes at a time. Syndrome is related to “soul loss” experiences, “soul wandering” or spiritual possession. Dissociative hysteria cases have been realted to this, along with narcolepsy-catalepsy syndromes. ICD 10 is F44.88 Other Specific Dissociative [Conversion] Disorders and G47.4 Narcolepsy and Catalepsy (including sleep paralysis). Related to aluro (Nigeria), old hag (Newfoundland), and phii pob (Thailand). - Windigo. Northeastern Indigena of North America. Traditionally considered a form of psychosis. Rare cases have cannibalistic obsession. Traditional beliefs blame this on possession, usually of males, turning them into “cannibal monsters.” Depression, homicidal or suicidal thinking, and delusions are common, The ‘wish to eat human flesh’ is an indicator. Typical of people ostracized by their immediate peers and/or society. Chronic food shortages and cultural myths support the belief system leading to these states. Some studies suggest this medical illness is a made up syndrome meant to ostracise or execute governmental changes. ICD 10 suggested is F68.8 Other Specific disorders of adult personality and behavior. Related to amok (Malaysia), hseih-ping (China, esp. Taiwan), and zar (Egypt, Ethiopia and Sudan). The new ICD 10s for the above states are from the WHO ICD-10 classification of mental and behavioural disorders (see also Hirsch and Weinberger’s (eds.) Schizophrenia (2003)); a partial list of possible ICD9s appear in brackets. These diagnoses are as follows. - F32.11 Moderate Depressive Episode with somatic syndrome [296.2-3?] – Ataque de Nervios, Nerves - F40 Social Phobias [300.23] – Taijin Kyofusho - F40.2 Specific Phobias [300.2] – Pa-leng - F40.8 Other Phobic Anxiety Disorders [300.2, 300.20] – Taijin Kyofusho - F44.3 Trance and possession disorders – Possession Disorder, Ufufuyane - F44.7 Mixed dissociative [conversion] disorders [ICD9 300.1, 300.11] – Pibloktoq, Possession Disorder, Ufufuyane - F48.8 Other specific Neurotic Disorder – Dhat, Koro - F44.88 Other specific dissociative (conversion) disorder [ICD9 300.1, 300.11] – Latah, Pibloktoq, Uqamairineq - F45.1 Undifferentiated somatoform disorders [308.?] – Nerves, Susto - F45.34 Somatoform autonomic dysfunction of the genitourinary system (this may include autonomic anxiety symptomatology) [306?] – Dhat, Koro - F48.0 Neurasthenia – Nerves - F48.8 Other Specified Neurotic Disorders – Susto - F68.8 Other Specific disorders of adult personality and behavior [301.5?, 301.50?] – Amok, Windigo - G47.4 Narcolepsy and Catalepsy (including sleep paralysis) [306.0] – Uqamairineq Some of the ICD graphs for these syndromes are as follows. Dissociative States, Bipolar Disorders, Delusional Behavior, Narcolepsy/Catalepsy, and Social Phobia are several ICDs related to Sociocultural Syndromes in recent decades. Mixed Cultural and Multicultural Perspectives Cultural bound syndromes represent a set of conditions in which socioculturalism and western medical philosophy come face to face as people and doctors, both traditional and modern, try to understand the cause for an “illness” and the most effective remedial process. “Modern” medicine also bears beliefs about diseases, some which are centered on its own culture. How people with specific illnesses are treated plays a very important role in their long term progress. In the early 1800s, people with specific conditions such as epilepsy were treated like criminals and housed in jails or prisons. A few decades into the 19th century these legal practices were diminished or ceased due to the work of various humanitarian groups. In spite of these successes, however, public and professional views about certain diseases continue to exist thereby influencing greatly the life and future of people with such diagnoses. When western medical thought prevails over alternative philosophies for a disease, and as a result reduces the quality of life for these people, we have to question sometimes the values of such practices. Western societies and western medicine for example treat elders much differently than many developing countries. - Epilepsy. Multicultural. For example “Spirit Captures you and you fall down” of the Hmong. (see 1997 book with same title). ICD 9 = 345.* - Schizophrenia. For example Amish. - Possession Disorder. Multicultural. Individual sense his/her body is taken over by another entity. Disturbance of consciousness, identity or memory, changes in voice patterns or speech, loss of awareness of surroundings, with a high tolerance for pain and other environmental stimuli. ICD 10 codes are F44.3 Trance and possession disorders, or F44.7 Mixed dissociative [conversion] disorders. Relates closely to fuufuyane or saka. “Modern” medicine isn’t exact. In fact it is filled with medical conditions and ailments that could more accurately be defined as the “best fit” for the present time. This inherent trait of disease classification systems begins with the premise that the individual who defines the diseases in such a way is correct, even if his philosophy differs from others in the field. Nosology of disease is a specialty that was developed in the late 18th century, modified in the first half of the 19th century, modified and slightly modernized following the discovery of the bacterium and pharmaceutical means for disposing of pathologies during the early 1900s, and finally developed into a system of classification much like that of today some time in the 1960s or 1970s. This late 20th century nosology is not at all “perfected”. Even with this method of classifying disease, we are left with the culturally accepted assumption that the bifurcating system used to produce this methodology is very approporiate and most correct, and that the links drawn are “correct”. This subjectivity of human classification methods is what adds ‘cultural bias errors’ back into the classification system each time we cannot define the complete and total reasons for a particular medical condition existing. Examples of how these types of self-created, self or ethno-centered ideologies played out in the past are demonstrated by the histories of past diseases, such as the following: - The “Divine Somnambulism” of 1800 - The “Mania” demonstrated by Jesus, a diagnosis published by French physicians ca. 1830-1840 - Agua frio, or Aire frio, an illness still experienced by some Mexican nationals today - Iich’aa (southwestern US) and the native American philosophy - Hypoglycemia and fasting, to MDs a concerning health condition, to others a religious experience and an important part of shamanics - Temporary Blindness - a reason for the miracle cure of blindness? - Nightmares/Night Horrors and “having visions” - Tics and Tourette’s Syndrome, in the past a manifestation of nerves and nervous energy; today the consequence of personal growth and psychology, or to some, adolescent/teenage neurochemicals One of the more interesting issues is cultural medicine today pertains to these “health practices”, reactions to stress and change, and “illnesses” experienced by patients of the United States medical care system. Equally interesting is the attraction we have to certain historical tales about these illnesses and very strange activities. Porphyrism for example was used to claims possible truths for and assign meaning to the 14th century story of vampires of Eastern Europe. Bread tainted with ergot is used to explain why towns might have had a history of being possessed by evil spirits. Epilepsy is used to define the signs of demonic possession. The following culturally bound syndromes or behaviors important to US culture are reviewed in detail. These are examples of physicians in the current US paradigm trying to make other culturally defined interpretations of illness fit into their perspectives on health, behavior and disease. African Infibulation [ICD9 729.2] Demonic Possession and the like Genetic Blood Dyscrasias African Infibulation [ICD9 729.2] Note: “Genetic” should read “Genitalic” When specific cultures migrate into the United States, there are medical beliefs and syndromes that accompany these migrations. In the case of in-migration of certain parts of the African tradition, a commonly accepted practice in parts of Africa is female genital surgical manipulation or change in the form of one or more of the following surgical procedures: clitorectomy, labiectomy, and infibulation. The end result is the removal of female genital parts and closure of the vaginal passage, symbolizing a young female’s passage into her menstruation stage in life. These surgeries, according to cultural beliefs, “prepare her” for later marriage in a virginal state; it symbolized her “promise” of not engaging in any premarital promiscuity. These cultural practices are not accepted as humane practices by most “Western” and United States practitioners. In recent years, this sensitive sociocultural rite of passage related “health care method” has undergone intense professional scrutiny, legally as well as medically. The procedure and end result of this surgical practice are a part of ICD9 classification system, enabling this review of age-gender patterns to be completed. The ICD9s for these processes are as follows: - 729.2 – all of the below combined - 729.20 – unspecified mutilation process - 729.21 – involving a clitorectomy only - 729.22 - clitoris and labia removal or modification - 729.23 - clitoris and labia modification along with an infibulation process - 729.29 – all others The surgical processes typical of certain African societies includes a clitorectomy, labial removal and closure process (infibulation). Different ICDs are provided based on the degree to which this surgical procedures completes all three of these tasks. Although infibulation and its precursors are extremely rare events, rarely noted in the medical records along with use of the appropriate ICDs, these processes are found in exceptionally large population studies (>50M). They therefore provide us with some insight into the very poorly studied age-specific sociocultural behavior problem. The above age-gender curves of two of these processes demonstrate the possibility of 3 age ranges of distribution for this diagnosis. These three peaks are defined as follows, based upon the history and location for the performance of this procedure: - a) 70-100 yo-primarily individual who immigrated into this country with a history of experiencing this procedure, - b) individuals between 25 and 50 years of age, with peaks at 25-30 and 40-50 yo, with the possibility that the older age group received this procedure in their native lands before immigrating to the United States, or as a result of social pressure after their arrival into this country, and - c) individuals < 15 years of age, who are most likely experiencing this process either just before a recent migration into this country, or who have received this process as a result of cultural pressure to perform this act while residing in the United States. The following symbol is a link to more on this topic. Psychiatric or Culturally-bound? Demons and Physicians Demonic possession, hyperreligiosity, group hysteria, and pibloktoq or arctic hysteria are all psychological changes in individuals and people which physicians have historically tried to associate with personality disorders, and sometimes even biochemical disorders. This “branding” behavior (“the scarlet letter”) in medicine is especially true with certain disease types. History has allowed us to imagine new diagnoses for people who never seemed to fit in. This is because society forms its definitions of medical conditions or psychological states and then tries to place that person in some sort of category that is assigned based opn the most socially accepted profiles of these individuals. During the Salem witchcraft trials for example, young women with schizophrenia, dissociative disorder, certain forms of epilepsy, tics or tourette’s syndrome, epilepsy, or even some sort of ergot poisoning had the potential of ending up in the next farm pond dead from total immersion in water. A half century later the same events recurring briefly in the Hudson Valley around 1720 led a local elderly women to be accused of practicing the same sort of dissociative behaviors accompanied due to her poor social practices and her non-traditional religious upbringing. Likewise several decades later, around the turn of the century, an old woman near North Salem was accused of many things due to her loner style of living along the mountain face facing New York; but because she attended church on a regular basis she never received the punishment that society could have given her had she been labelled a witch by the local children. In the lower part of the Hudson Valley another young girl was suffering from a unique form of mental illness, one that made her pseudo-hallucinate whilst laying in bed, as if she were asleep. During her “events” she would recite bible passages and appear to be communicating with spirits from above. This behavior was an offshoot of an increasingly popular behavior Emanuel Swedenborg demonstrate just a could of decades earlier–whilst talking with angles visiting each of his body parts. Swedenborg’s schizophrenia was socially defined to be a consequence of his skills as a seer, and was supported more as time passed due to peoples’ curiosities about the metaphysical world. What Swedenborg then introduced to the United States by the end of the 18th century, a spirit seeker like Rachel brought into the next stage of social behaviors with metaphysics. About the same time, when the spoons started flying in Thorn house down in Fishkill, the daughter of this family was considered to be communicating with another spirit floating about in the vicinity, someone whose spirit was later found to be locked within the Thorn’s home attack in the form of an old stone that was finally discarded much later, as the daughter’s demonic possession also decided to leave this home behind. Further north in New York State, we see this same story re-juvenated such a following when the daughters of a farming family began spirit rapping with past spirits, thus making popular once again the possibility of channeling with old time family members, making your own necessary personal connections with the matron or patron of several generations back. All of these practices require some sort of imagination and belief to become active and effective in influencing how society looked upon such conditions as diseases or disasters for someone’s spirit, mind and personality. Many of the illnesses of this form are mostly define by cultural means. It is the beliefs of people that define whether or not a particular practice is good or bad, or can be assigned some name indiciating it is a curse or a gift. Even today, culture defines not only the type of condition a person has–good or bad–by which ICDs are assigned to a particular behavior or condition, but modern medicine is also guilty of mislabelling and misclassifying some of these conditions. Medicine in general limits its ability to categorize someone along a certain pre-approved dischotomous path of diagnostics when various unique culturally defined syndromes have to be classified using the ICD system. It is possible that the majority of the diagnoses developed using this method might even be misdiagnoses, or conditions redefined and erroneously rewritten in other words in order to best fit the category the diagnostician wishes to place someone’s behavior in. How does a regular physician define a shaman for example? Is he simply a delusional very old man? a child who had hyperreligiosity brought about due to temporal lobe epilepsy? someone with so much grandiosity and incongruent argumentativeness that he must be a schizophrenic? Regular medicine cannot answer these questions effectively, in the past, now or even in the future. Cultural beliefs and practice such as those associated with “demons” and religion are not terms that easily found in ICD books. It is even much less possible to find mention of the words like shaman, pibloktoq, chi, vital force, or the like in the medical books. These terms help to define a set of conditions referred to colloquially in the anthropological writings as cultural syndromes. They require the culture that pays close attention to them, believe in them and support this philosophy by way on engaging in expected behavioral responses. When this “illness” is identified in accordance with sociocultural expectations, the individual experiencing these events might even have a better chance of recovery, assuming traditional treatments are properly applied. In Native American tradition, the individual going through a shamanic initiation process might be recommended to spend much of that fasting period under appropriate medical control, by a medically trained individual who is a member of that tribe or cultural group. It is typically the case that regular physicians spend little time trying to understand these socioculturally-defined prognostical medical conditions. Doctors assign very little value to the alternative views of the world and disease related to these syndromes, and almost always resort to their standards–the use of ICDs to document the social beliefs, practices, behaviors and medical outcomes that result. This suggests that physicians in the western world can be very ethnocentric at times when it comes to understanding people and health. When an individual belief system or faith becomes an offshoot of traditional philosophies, and their practices seem to work for inexplicable reasons, the western physician lacks the understanding and ability to understand what is taking place when a person changes or gets better. A regular physician might even have to resort to his/her unofficial fallbacks for explaining such events, such as spontaneous recovery, or mind-body effects, in turn falling upon whatever pseudo-scientific theory is out there for the time being used to explain the body-to-mind events and abilities (autonomics, psychosomatically induced hormonal change, prostaglandins effect, interferons and enkephalins “natural opiates” responses, psychoneuroimmunological or neuroendocrine causality, etc). The following are the ICDs closely linked to psychoneuroimmunological and self-induced psychobehavioral reactions to illnesses that otherwise a physician is unable to explain or define (see figure above). Takotsubo (ICD9 429.83) “Worrying or crying yourself to death”, or apical balooning of the ventricular walls in Takotsubo cardiomyopathy (ICD9=429.83). The primary theory proposed for this is weakening of the muscle wall due to: a) changes in arterial flow (left anterior descending coronary artery), b) vasospasms of this and/or other coronary arteries, and/or c) microvasculature failure within the cardiac tissue — any or all of these must be accompanied by a period of severe emotional stress resulting in autonomic effects upon the coronary arteries system. http://en.wikipedia.org/wiki/Takotsubo_cardiomyopathy; http://en.wikipedia.org/wiki/File:TakoTsubo_scheme.png. A major problem with this theory is that the age distribution of Takotsubo patients is nearly opposite of the the age gender features for traditional cardiomyopathy. Takotsubo is a condition associated primarily with Japanese culture, and has its greatest impacts on older populations, with female patients far outnumbering male patients (see population pyramids below). A similar psychosomatic like disorder does exist in the Western World/WHO ICD system — Factitious Disorder [300.16]. By definition and description Factitious disorder is of the 300 series and is therefore a pyschologically induced condition, which does not exactly match the ICD provided for Takutshobo [429.83]. The 400 series ICDs are typically assocaited with cardiological disturbances. It is interesting to note several similarities between these two ICDs in terms of Age-Gender distributions: Incidence Peaks at ages traditionally related to socially important “elders”, with ages > 65 or even 70 years of age. Female incidence for both ICDs for these older age patients is much greater than incidence/prevalence for males In the above images, the culturally-linked disease that is the focus of this query is on the left. Which of the other 3 best matches it’s form and distribution by both age and gender? There is a formula that can be used to quantify this overlap, but the picture makes it fairly clear which one it is in this case. Takotsubo ~ Factitious Disorder, in that both afflict older populations and are attached to some sort of emotional trigger that impacts women more than men in their older years. The anatomical-physiological theory often posed in the literature has a distribution that is the most equally distributed for the above, in terms of men versus women. Overall age-gender distributions for these first and last ICDs displayed are remarkable similar, suggesting there is either a psychoneurological-cardiological (hypothalmic-autonomic) feature involved in both processes, or that one system affect is somehow related to the other through a third mechanism, such as stress-induced (endocrine, neurtransmitter, releasing factor?) cardioelectric response for Takotsubo, with this cardiac reaction missing from non Japanese elders. For this reason, the proposed cardiomyopathy based theory does not quite fit in statistical distribution of this disease one the age-gender population pyramid. It is possible that the 439.83 pyramid is a result of late diagnosis, with early cases misidentified as other forms of myopathies. But the gender difference in takotshubo cannot be explained using this line of reasoning. More importantly, the more specific and unique forms of cardiomyopathy such as Obscure African Cardiomyopathy (425.2), Alcohol Cardiomyopathy (425.5), and Nutritional Cardiomyopathy (425.7) have male age peaks at either mid-life statge (45-55 yo) or the elderly stage (>70 yo). The other common cardiomyopathy–hypertrophic subaortic stenosis (425.1)–has a distribution mimicking the overall 425.* series. The same gender distribution is seen for the various cardiomyopathies, with male onset peaking in the 20-30 age group for both the Acute myocarditis (422.) and Acute Pericarditis (420.) series. The subacute endocarditis is not male gender weighted (421., this gender equality is also incidentally found for other endocarditis ICDs as well, in particualr valve-related disorders and therapeutic events). In sum, based on age distribution alone, cardiomyopathy cannot explain how and why takotshubo’s syndrome prevails primarily in older women. The similarity of form of the population pyramid with 300.16 Factitious Disorder suggests this is very much a pscyhologically based syndrome or condition manifesting itself (psychosomatically- and/or autonomically-induced?) with regards to the cardiac musculature and perhaps conduction system. This synopsis of course is based primarily on just the 1-year age-gender distribution pyramids (and therefore could be totally incorrect). One of the most classical lessons in biology classes focused on genetics is the Sickle Cell disease and the impact it has on the potential for malaria. Due to a genetic condition, hemoglobin becomes capable of sickle-shpaed (curved) or forming a chain like structure which in turn forces the red blood cell to change its morphology into an elongated, bent sickle-linke form. This in turn changes the 3-dimenstionality of the red blood cell and prevents it from passing through the narrow capillary beds. This failure to pass in turn results in reduced oxygenation and ultimately the death of many solid organ structures and tissues immediately surrounding richly vascularized capillary bed regions. The effects of malaria on blood include causing the red blood cell to sickle, thereby resulting in the destruction of cells that bear the organism responsible fo this disease. One result of this is the natural selection of sickle cell hybrids, people who carry but do not fully present with sickle cell sickling. These individuals have the chance to live longer lives in spite of the sickle cell gene, and so “select for” those who are hybrids with this condition or bear a version of the sickle cell trait that only partially presents itself. This sickle cell behavior is different from the living and survival biologies noted for thalassemia and hemophilia victims. Thalassemics live into later years of a normal life, due to lack of organ damage induced by sickling red blood cells. Hemophiliacs have a genetic condition influencing a completely different part of the metabolic path and result in survival curves not at all similar to the other two types of conditions. They bear the greatest longevity of these 3 conditions, four conditions if we separate sickle cell carriers from those actively presenting their sickle cell trait. We can constrast the Sickle Cell curves with those of Thalassemia and Hemophilia (all are above). There is an inveitably high mortality rate by the age of 65 years for people with Sickle Cell, be it in its active state or partially presenting itself within the bodies of carriers. The latter have a slightly longer longevity rate, and demonstrate male prevalence peaks earlier than female peaks, with females living longer and in greater numbers during their entire reproductive years period. The numerous reasons for socile cell mortality pertain to the effects of sickling cells on the microvasculature of solid organs, the splenomegaly these effects can result in at the organ systems level, and a variety of long term well localized anoxic states. Contrast these sickle cell disease and carrier curves with those of thalassemia and hemophilia. The latter two lack a demonstration of early mortality. Thalassemia is diagnosed very early on in life (beginning in the neonatal stage). Hemophilia tends to be diagnosed a few years later in life. Which is the above best represents SUNDS (Sudden Unexplained Nocturnal Death Syndrome) Cultural Shock and SUNDS After Saigon was attacked during the Vietnam War, a large number of Vietnamese upper class political leaders migrated to the United States. This migration was followed by requests for their assistance submitted by United States military leaders who assisted them in their need for asylum. The immigrants settled in just several parts of the country, usually in close association with the American military leaders who befriended them and made recommendations regarding places to settle. Following the immigration of these families was the migration of relatives and other immediate family friends and associates. By 1979, a number of Vietnamese, Cambodian and Laotian refugees communities were established, which have ever since remained their own unique sociocultural entities. Some of the more sizeable establishments were placed in unsuspected parts of the country such as Colorado, Iowa and Oregon. Immediately, the most important disease and public health issue during this time became tuberculosis. A number of the elders in these populations were found to be carriers. Another common malady experienced by this population was schizophrenia, a diagnosis which remains popular to this day within these southeast Asian American communities, possibly as a result of some familial genetic pattern common to this psychiatric condition. Several culturally-bound syndromes are also linked to this cultural group. The best known of these southeast asian syndromes is the suicidal state that acculturation and problematic adaptation processes often result in. Very young children are more capable of adapting than older children and young adults, with child bearing adults aged 35 and greater the most difficult group to provide assistance for. As these adults reach 55 years of age and greater, cultural traditions become a stumbling block for families trying to take advantage of government-based assistance. One of the chief problems these governmental programs had over the years was its ability to meet the needs of three or more cultural groups, all lumped into the same category for assistance. Aside from Laotian, versus Cambodian, versus Vietnamese, there were the Hmong emigrated from China who lived in the upper-eastern parts of this territory, a number of southeast asian cultural groups residing in wilderness settings, and the more urban adapted and often Christianized southeast asians residing close to and within the more urban settings of these countries. Such social diversity not only sets the stage for large amounts of political instability to ensue, but also makes it more likely that a number of psychological states and psychiatric and, in western society, criminal-related or developmental and academic related problems from developing in eacho of these populations. Cultural differences only add to these public health concers in that there are some basic statistics that may differ considereably between these groups. Education is found to be higher in social sociocultural groups than others. The likelihood of developing som familiarity with ESL standards is another, and even fertility rates are impacted by these southeast asian subpopulation differences. The Hmong for example have a fertility rate that greatly suprasses the same for nearly all other sociocultural groups in this country, save the Mennonites of the Pacific Northwest perhaps. This condition was typically experienced by the precollege and college age groups, and is characterized bywhat might first appear to be anxiety or fugue-like states or a sense of social detachment and panic; these occur immediately before a suicidal act like jumping through a window is engaged in. Recent studies tend to link the immigrant illness experience to well defined psychiatric and psychological states common to western society, such as agoraphobia, social phobia, depression, avoidant disorder, and anxiety. But like many studies of sociocultural disease, the Laotian-Cambodian-Vietnamese illness can have its own distinct causes and symptomatology. For this reason, one disease common to elders, manifesting itself primarily at night, was soon identified and linked to the oldest of the old immigrants, and given the name Sudden Unexected Nocturnal Death Syndrome (SUNDS, for which see http://www.deathreference.com/Sh-Sy/Sudden-Unexpected-Nocturnal-Death-Syndrome.html). SUNDS was identified by several authors focused on potential biological causes as a heart-realted death induced by mental anguish, mostly during the nighttime hours and during specific stages of the sleep cycle. Important contributors to the possiblity for SUNDS were sleeping during the dream state, with highly stressful behaviors acted out possibly due to the content of the nightmare or nigth horrors being experienced. These problems in turn resulted in cardia dysarhythmia according to the physicians researching this condition, thus resulting in nocturnally-induced cardiac dysarrhythmias and death. (See http://www.mja.com.au/public/issues/177_08_211002/mck10856_fm.html) Can SUNDS be detected within an ICD data pull process? The first problem with pulling SUNDS related conditions is the variability in potential ICD realtionships developed for this culturally-bound illness. To date, the following ICDs already assessed may have some relationship with how these cases get coded in the medical records. No SUNDS ICD exists for ICD9, although it is possible that ICD 446.7 Takotsubo’s disease is incredibly close to the Hmong-Laotian syndrome, including the cardiac physiological events related to Takotsubo’s disease. The strong tendency for Tak0tsubo’s syndrome to influence women over men suggests a sociocultural/psychological component, which if this is true may help to explain the apparent gender difference the other cultural groups with SUNDS may be demonstrate (lesser female, more male elder related events were noted clinically). - 290. Dementias - 300.* Anxiety states - 300.02 Generalized Anxiety Disorder - 300.1 Dissociative Disorders - 300.11 Conversion Disorder - 300.13 Fugue - 300.14 Identity - 300.16 Factitious Disorder - 300.21-.22 Agoraphobia - 300.23 Social Phobia (301.7 Antisocial) - 306.2 Acute Physiological Malfunctions of the Heart due to Mental Factors (306.8 bruxism, 306.6 endocrine) - 307 Sleep Disorders (307.45 Circadian, 307.46 Arousal) - 307.46 Sudden Affective Disorder (SAD) - 308 Acute Reaction to Stress - 309. 4 Emotion and Conduct Adjustment Disorders - 309.21 Separation Anxiety - 309.29 Culture Shock - 309.81 PTSD - 309.* Adjustment Disorders - 309.1 Prolonged Depression - 310.1 Personality Change due to . . . - 427.5 Cardiac Arrest - 446.7 Takotsubo’s Disease (see http://en.wikipedia.org/wiki/Takotsubo_cardiomyopathy) - 452.2 Obscure Cardiomyopathy of Africa - Brugada Syndrome or Asian Pseudo-RBBB (http://cvgenetics.med.nyu.edu/genetic-conditions/brugada-syndrome; http://www.cigna.com/customer_care/healthcare_professional/coverage_positions/medical/mm_0052_coveragepositioncriteria_genetic_testing.pdf) SUNDS is most often linked or related to the above 3 ICDs. This study (and my 2000-2003 field studies for a Quantitative/Qualitative Analysis Certification program) again demonstrate that, like Takotsubo, SUNDS has a tendency to behave most like Factitious Disorder, but with a more equally distributed gender-related pattern for elderly populations. There is a mindbody relationship in cardiomyopathy that is worth noting. The following schematic was produced by a researcher attempting to define the causology of cardiomyopathies. Barry J. Maron, MD, Chair; Jeffrey A. Towbin, MD, FAHA; Gaetano Thiene, MD; Charles Antzelevitch, PhD, FAHA; Domenico Corrado, MD, PhD; Donna Arnett, PhD, FAHA; Arthur J. Moss, MD, FAHA; Christine E. Seidman, MD, FAHA; James B. Young, MD, FAHA. AHA Scientific Statement. Contemporary Definitions and Classification of the Cardiomyopathies. An American Heart Association Scientific Statement From the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation. 2006; 113: 1807-1816. Even though some of the conclusions these authors present have already been questioned, their overall research methodology is worth noting due to its similarity with the Health Belief Model utilized by many health education/health promotion researchers and employees. The above flowchart for cardiomyopathies can be integrated with the Health Belief Model. For African cardiomyopathy(425.2) , the age-gender distribution most closely resembles nutritional deficiency cardiomyopathy (425.7). Given the age-gender distribution of Takatsubo versus cardiomyopathy, it appears tak0tsubo is primarily a psychosomatic condition induced primarily through personal perceptions, beliefs and knowledge, more so than a result of a biological phenomenon related mostly to some histological or cellular defect in cardiac tissue. There is no other way to explain why women within their older years manifest this condition so much more than men. [To be Continued]	4	15	0	0	35	0.551158	35	11,813
21st Century psoriazis Psoriasis is a long-lasting autoimmune disease which is characterized by patches of abnormal skin. They may vary in severity from 21st Century psoriazis and localized to complete body coverage. There are five main types of psoriasis: It typically presents with red patches with white scales on top. Areas of the body most commonly affected are the back of the forearms, shins, around the navel, and the scalp. Fingernails and toenails are affected in most people at some 21st Century psoriazis in time. This may include pits in the nails or changes in nail color. Psoriasis is generally thought to be a genetic disease which is triggered by environmental factors. Symptoms often 21st Century psoriazis during winter and with certain medications such as beta blockers or NSAIDs. The 21st Century psoriazis mechanism involves the immune system reacting to skin cells. Diagnosis is typically based on the signs and symptoms. There is no cure for psoriasis. However, various treatments can help control the symptoms. These 21st Century psoriazis are called plaques and are most commonly found on the elbows, knees, scalp, and back. It may be accompanied by severe itching, swelling, and pain. It is often the result of an exacerbation of unstable plaque psoriasis, particularly following 21st Century psoriazis abrupt 21st Century psoriazis of systemic glucocorticoids. They include pustular, inverse, napkin, guttate, oral, and seborrheic-like forms. Pustular psoriasis appears as raised bumps filled with noninfectious pus pustules. Inverse psoriasis also known as flexural psoriasis appears as smooth, inflamed patches of skin. The patches frequently affect skin foldsparticularly around the genitals between the thigh and grointhe armpitsin the skin folds of an overweight 21st Century psoriazis known as panniculusbetween the buttocks in the intergluteal cleft, and under the breasts in the inframammary fold. Heat, trauma, and infection are thought to play a role in the development of this atypical form of psoriasis. Napkin psoriasis is a subtype of psoriasis common in infants characterized by red papules with silver scale in the diaper area that may extend to the torso or limbs. Guttate psoriasis is characterized by numerous 21st Century psoriazis, scaly, red or pink, droplet-like lesions papules. These numerous spots of psoriasis appear over large areas of the body, primarily the trunk, but also the limbs and scalp. Guttate psoriasis is often triggered by a streptococcal infection, typically streptococcal pharyngitis. Psoriasis in the mouth is very rare, in contrast to lichen Lazarev Sergey Nikolaevich despre psoriazisanother common papulosquamous disorder that commonly involves both the skin and mouth. When psoriasis involves the oral mucosa the lining of the mouthit may be asymptomatic, but it may appear as white or grey-yellow plaques. The microscopic appearance of http://climateexchangeplc.com/psoriazis-de-curare-a-corpului.php mucosa affected by geographic tongue migratory stomatitis is very similar to the appearance of psoriasis. Seborrheic-like psoriasis is a common form of psoriasis with clinical aspects 21st Century psoriazis psoriasis and seborrheic dermatitisand may be difficult to http://climateexchangeplc.com/piele-de-tratament-psoriazis-1.php from the latter. This form of psoriasis typically manifests as red plaques with greasy scales in areas of higher sebum production such as the scalpforeheadskin folds next 21st Century psoriazis the noseskin surrounding the 21st Century psoriazis, skin on the chest above the sternumand in skin folds. Psoriatic arthritis is a form of chronic inflammatory arthritis that has a highly variable clinical presentation and frequently occurs in association with skin and nail psoriasis. This can result in a sausage-shaped swelling of the 21st Century psoriazis and toes known as dactylitis. Psoriasis can affect the nails and produces a variety of changes in the appearance of finger and toe nails. In addition to the appearance and distribution of the rash, specific medical signs may be used by medical practitioners to assist with diagnosis. These may include Auspitz's 21st Century psoriazis pinpoint bleeding when scale is removedKoebner phenomenon psoriatic skin lesions induced by trauma to the skin and itching and pain localized to papules and plaques. Around one-third of people with psoriasis report a family history of the disease, and researchers have identified genetic loci associated with the condition. These findings suggest both a genetic susceptibility and an environmental response in developing psoriasis. Psoriasis has a strong hereditary component, and many genes are associated with it, but it is unclear how those genes work together. Most of the identified genes relate to the immune system, particularly the major histocompatibility complex MHC and T cells. Genetic studies are valuable due to their ability to identify molecular mechanisms and pathways for further study and potential drug targets. Classic genome-wide linkage analysis 21st Century psoriazis identified nine loci on different chromosomes associated with psoriasis. They are called psoriasis susceptibility 1 through 9 PSORS1 through PSORS9. Within those loci are genes on pathways that lead to inflammation. Certain variations mutations of those genes are commonly found in psoriasis. Some of these genes express inflammatory 21st Century psoriazis proteins, 21st Century psoriazis affect cells in the immune system that are also involved in psoriasis. Some of these genes are also involved in other autoimmune diseases. PSORS1 is located on chromosome 6 in the major histocompatibility complex MHCwhich controls important immune functions. Three genes in the PSORS1 locus have a strong association with psoriasis vulgaris: HLA-C variant HLA-Cw6 which encodes a MHC class I protein; CCHCR1variant WWC, which encodes a coiled protein that is overexpressed in psoriatic epidermis; and CDSNvariant allele 5, which encodes corneodesmosina protein which is expressed in the granular and cornified layers of the epidermis and upregulated in psoriasis. Two major immune system genes under investigation are interleukin subunit beta IL12B on chromosome click to see morewhich expresses interleukinB; and IL23R on chromosome 1p, which expresses the interleukin receptor, and is involved in T cell differentiation. Interleukin receptor and 21st Century psoriazis have both been strongly linked with psoriasis. A rare mutation in the gene encoding for the CARD14 protein plus an environmental trigger was enough to cause plaque psoriasis the most common form of psoriasis. Conditions reported as worsening the disease include chronic infections, stress, and changes in season and climate. The rate of psoriasis in HIV-positive individuals is comparable to that of HIV-negative individuals, however, psoriasis tends to be more severe in people infected with HIV. Psoriasis has been described as occurring after strep throatand may be worsened by skin or gut colonization with Staphylococcus aureusMalasseziaand Candida albicans. Drug-induced psoriasis may occur with beta blockers 21st Century psoriazis, lithium antimalarial medications non-steroidal anti-inflammatory drugs terbinafinecalcium channel blockerscaptoprilglyburidegranulocyte colony-stimulating factor interleukinsinterferons lipid-lowering drugs: Psoriasis is characterized by an abnormally excessive and rapid growth of the epidermal layer of the skin. Gene mutations of proteins involved in the skin's ability to function as a barrier have been identified as markers of susceptibility for the development of psoriasis. DNA released from dying cells acts as an inflammatory stimulus in psoriasis and stimulates the receptors on certain dendritic cells, which in turn produce the cytokine interferon-α. Dendritic cells bridge Primele semne de psoriazis innate immune system and adaptive immune system. They are 21st Century psoriazis in psoriatic lesions and induce the proliferation of T cells and type 1 helper T cells Th1. A diagnosis of psoriasis is usually based on the appearance of 21st Century psoriazis skin. Skin characteristics typical 21st Century psoriazis psoriasis are scaly, erythematous plaques, papules, 21st Century psoriazis patches of skin that may be painful and itch. If the clinical diagnosis is uncertain, a skin biopsy or scraping may be performed to rule out other disorders and to confirm the diagnosis. Skin from a biopsy will show clubbed epidermal projections that interdigitate with dermis on microscopy. Epidermal thickening is another characteristic histologic finding of psoriasis lesions. Unlike their mature counterparts, these superficial cells keep their nucleus. Psoriasis is classified as a papulosquamous disorder and is most commonly subdivided into different categories 21st Century psoriazis on histological characteristics. Each form has a dedicated ICD code. Another classification scheme considers genetic and demographic 21st Century psoriazis. Type 1 21st Century psoriazis a positive family history, starts before the age of 40, and is associated with the human leukocyte antigenHLA-Cw6. Conversely, type 2 does not show a 21st Century psoriazis history, presents after age 40, and is not associated with HLA-Cw6. The classification of psoriasis as an autoimmune disease has sparked considerable debate. Researchers have proposed differing descriptions of psoriasis and psoriatic arthritis; some authors have classified them as autoimmune diseases while others have classified them as distinct from autoimmune diseases and referred to them as immune-mediated inflammatory diseases. There is no consensus about how click here classify the severity of psoriasis. The DLQI score ranges from 0 minimal impairment to 30 maximal impairment and is calculated with each answer being assigned 0—3 21st Century psoriazis with higher scores indicating greater social or occupational impairment. The psoriasis area severity index PASI is the most widely used measurement tool for psoriasis. PASI assesses the severity of lesions and the area affected and combines these two factors into a single score from 0 no disease to 72 maximal disease. While no cure is available for psoriasis, many treatment options exist. Topical agents are typically used for mild disease, phototherapy for moderate disease, and systemic agents for severe disease. Topical corticosteroid preparations are the most effective agents when used continuously for 8 weeks; retinoids and coal tar 21st Century psoriazis found to be of limited benefit and 21st Century psoriazis be no better than 21st Century psoriazis. Vitamin D analogues such as 21st Century psoriazis were found to be significantly superior to placebo. Combination therapy with vitamin D and a corticosteroid 21st Century psoriazis superior to either treatment alone and vitamin D was found 21st Century psoriazis be superior to coal tar for chronic plaque psoriasis. Moisturizers and emollients such as mineral oilpetroleum jellymore infoand decubal an oil-in-water emollient were found to increase 21st Century psoriazis clearance of psoriatic plaques. Emollients have been shown to be even more effective at clearing psoriatic plaques when combined with phototherapy. The emollient salicylic acid is structurally similar to para-aminobenzoic http://climateexchangeplc.com/experienta-cu-psoriazis.php PABAclick at this page found in sunscreen, and is known to interfere with phototherapy in psoriasis. Coconut oilwhen used as an emollient in psoriasis, has been found to decrease plaque clearance with phototherapy. Ointment and creams containing coal tardithranolcorticosteroids i. The use of the finger tip unit may be helpful in guiding how much topical treatment to use. Vitamin D analogues 21st Century psoriazis be useful with steroids; 21st Century psoriazis, alone have a higher rate of side effects. Another topical therapy used to treat psoriasis is a form of balneotherapywhich involves daily baths in the Dead Sea. This is usually done for four weeks with the benefit attributed to sun exposure and specifically UVB light. This is cost-effective and it has been 21st Century psoriazis as an effective way to treat psoriasis without medication. Phototherapy in the form of sunlight has long been used for psoriasis. The UVB lamps should have a timer that will turn off the lamp when the time ends. The amount of light used is determined by a person's skin type. One of the 21st Century psoriazis with clinical phototherapy is the difficulty many patients have gaining access to a facility. Indoor tanning resources are almost ubiquitous today and could be considered as a means for patients to get UV exposure when dermatologist provided phototherapy is not available. However, a concern with the use of commercial tanning is that tanning beds that primarily emit UVA might not effectively treat psoriasis. One study found that plaque psoriasis is responsive to erythemogenic doses of either UVA or Http://climateexchangeplc.com/crema-pentru-copii-pentru-psoriazis.php, as exposure to either can cause dissipation of psoriatic plaques. It does require more see more to reach erythemogenic dosing with UVA. UV light therapies all have risks; tanning beds are no exception, 21st Century psoriazis in the link between UV light and the increased chance article source skin cancer. There are increased risks of melanoma, squamous cell and basal cell carcinomas; younger psoriasis patients, particularly those under age 35, are at increased risk from melanoma from UV light treatment. The World Health Organization 21st Century psoriazis listed tanning beds as carcinogens. A review of studies recommends that people who are susceptible to skin cancers exercise caution when using UV light therapy as a treatment. A major mechanism of NBUVB is the induction of DNA damage in the form of pyrimidine dimers. This type of phototherapy is useful in the treatment of psoriasis because the formation of these dimers interferes with the cell cycle and stops it. The interruption of the cell cycle 21st Century psoriazis by NBUVB opposes the characteristic rapid division of skin cells seen in psoriasis. The most common short-term side effect of this form of phototherapy is redness of the skin; less common side 21st Century psoriazis of NBUVB phototherapy are itching and blistering of the treated skin, irritation of the eyes in the form of conjunctival inflammation or inflammation of the corneaor cold sores due to reactivation of the herpes simplex virus in the skin surrounding the lips. Eye protection is usually given during phototherapy treatments. Psoralen and ultraviolet A phototherapy PUVA combines the oral or topical administration of psoralen with exposure to ultraviolet A UVA light. The mechanism of action of PUVA is unknown, but probably involves activation of psoralen by UVA light, which inhibits 21st Century psoriazis abnormally rapid production of the cells in psoriatic skin. There are multiple mechanisms of action associated with PUVA, including effects on the skin's immune system. PUVA is associated with nauseaheadachefatigueburning, and itching. Long-term treatment is associated with squamous cell carcinoma but not with melanoma. Psoriasis resistant to topical treatment and phototherapy may be treated with systemic therapies including medications by mouth or injectable treatments. The majority 21st Century psoriazis people experience a recurrence of psoriasis after systemic treatment is discontinued. Non-biologic systemic treatments frequently used for psoriasis include methotrexateciclosporinhydroxycarbamidefumarates such as dimethyl fumarateand retinoids. These agents are also regarded 21st Century psoriazis first-line treatments for psoriatic erythroderma. Biologics are manufactured proteins that interrupt the immune process involved in psoriasis. Unlike generalised immunosuppressive drug therapies such as methotrexate, biologics target specific aspects of the immune system contributing to psoriasis. Guidelines regard biologics as third-line treatment for plaque psoriasis following inadequate response to topical treatment, phototherapy, and non-biologic systemic treatments. European guidelines recommend avoiding biologics if a 21st Century psoriazis is planned; anti-TNF therapies such as infliximab are not recommended for use in chronic carriers of the hepatitis B virus or individuals infected with HIV. Several monoclonal antibodies target cytokines, the molecules that cells use to send inflammatory signals to each other. TNF-α is one of the main executor inflammatory cytokines. Four monoclonal antibodies 21st Century psoriazis infliximabadalimumabgolimumaband certolizumab pegol and one recombinant TNF-α decoy receptoretanercepthave been developed to inhibit TNF-α signaling. Additional monoclonal antibodies, such as ixekizumab have been developed against pro-inflammatory cytokines and inhibit the inflammatory pathway at a different point than the anti-TNF-α antibodies. Two 21st Century psoriazis that target T cells are efalizumab and alefacept. Efalizumab is a monoclonal antibody that specifically targets the CD11a subunit of LFA Efalizumab was voluntarily withdrawn from the European market in February and from the US market in June by the manufacturer due to the medication's association with cases of progressive multifocal leukoencephalopathy. Individuals with 21st Century psoriazis may develop 21st Century psoriazis antibodies against Ursachen psoriazis pe fotografie coate off 21st Century psoriazis. Neutralization occurs when an antidrug antibody prevents a monoclonal antibody such as infliximab from binding antigen in a laboratory test. Specifically, neutralization occurs when the antidrug antibody binds to infliximab's antigen binding site instead of TNF-α. When infliximab no longer binds tumor necrosis factor alphait no longer decreases inflammation, and psoriasis may worsen. Neutralizing antibodies have not been 21st Century psoriazis against etanercept, a biologic drug that is 21st Century psoriazis fusion protein composed of two TNF-α receptors. The lack of neutralizing antibodies against etanercept is probably secondary to the innate presence of the TNF-α receptor, and the development of immune tolerance. Limited evidence suggests removal of the tonsils may benefit people with chronic plaque psoriasis, 21st Century psoriazis psoriasis, and palmoplantar pustulosis. Uncontrolled studies have suggested that individuals with psoriasis or psoriatic arthritis may benefit from a diet supplemented with fish oil rich in eicosapentaenoic acid EPA and docosahexaenoic acid DHA. The effect of consumption of caffeine including coffee, black tea, mate, and dark chocolate remains to be determined. There is a higher rate of celiac disease among people with psoriasis. Most people with psoriasis experience nothing more than mild skin lesions that can be treated effectively with topical therapies. Psoriasis is known to have a negative impact on the quality of life of both the affected 21st Century psoriazis and the individual's family members. Itching and pain can interfere with basic functions, such as self-care and sleep. Individuals with psoriasis may feel self-conscious about their appearance and have a poor self-image that stems from fear of public rejection and psychosexual concerns. Psoriasis has been associated with low self-esteem and depression 21st Century psoriazis more common among those with the condition. Clinical research has indicated individuals often experience a diminished quality of life. Several conditions are associated with psoriasis. These occur more frequently in older people. Nearly half of individuals click at this page psoriasis over the age of 65 have at least three comorbidities, and two-thirds have at least two comorbidities. Psoriasis has been associated with obesity and several other cardiovascular and metabolic disturbances. Cardiovascular disease risk appeared to be correlated with the severity of psoriasis and its duration. Click at this page is no strong evidence to suggest that 21st Century psoriazis is associated with an increased risk of death from cardiovascular events. Methotrexate may provide a degree of protection for the heart. The odds of having hypertension are 1. A similar association was noted in people who have psoriatic arthritis—the odds of having hypertension were found to be 2. The link between psoriasis and hypertension is not currently understood. Mechanisms hypothesized to be involved in this relationship include the following: Statin use in those with psoriasis and hyperlipidemia was associated with decreased levels of high-sensitivity C-reactive protein 21st Century psoriazis TNFα as well as decreased activity of the immune protein 21st Century psoriazis The rates of Crohn's disease and ulcerative colitis are increased when compared with the general population, by a factor of 3. Approximately one third of people with psoriasis report being diagnosed before age Psoriasis affects about 6. People with inflammatory bowel disease such as Crohn's disease or ulcerative colitis are at an go here risk of developing psoriasis. Scholars believe psoriasis to 21st Century psoriazis been included among the various skin conditions called tzaraath translated as leprosy in the Hebrew Biblea condition imposed as a punishment for slander. The patient was deemed "impure" see tumah and taharah during 21st Century psoriazis afflicted phase and is ultimately treated by the kohen. The Greeks used the term 21st Century psoriazis λεπρα for scaly skin conditions. They used the term psora to describe itchy skin conditions. Leprosythey said, is distinguished by the regular, circular form of patches, while psoriasis is always irregular. Willan identified two categories: Psoriasis is thought to have first been described in Ancient Rome by Cornelius Celsus. The disease was first classified by English physician Thomas Willan. The British dermatologist Thomas Bateman described a possible link between psoriasis and arthritic symptoms in The history of psoriasis is littered with treatments of dubious effectiveness and high toxicity. In the 18th and 19th centuries, Fowler's solutionwhich contains a poisonous and carcinogenic arsenic compound, was used by dermatologists as a treatment for psoriasis. The word psoriasis is from Greek ψωρίασις, meaning "itching condition" or "being itchy" from psora"itch" and -iasis"action, condition". The International Federation of Psoriasis Associations IFPA is the global umbrella organization for national and regional psoriasis patient associations and also gathers the leading experts in psoriasis and psoriatic arthritis research for scientific conferences every three years. Non-profit organizations the National Psoriasis Foundation in the United States, the Psoriasis Association in the 21st Century psoriazis Kingdom and Psoriasis Australia offer advocacy and education about psoriasis in their respective countries. Pharmacy costs are the main source of direct expense, with biologic therapy the most prevalent. These costs increase significantly when co-morbid conditions such as heart disease, hypertension, diabetes, lung disease and psychiatric disorders are factored in. The role of insulin resistance in the pathogenesis of psoriasis 21st Century psoriazis currently under investigation. Preliminary research has suggested that antioxidants such as polyphenols may 21st Century psoriazis beneficial effects on the inflammation characteristic of psoriasis. From Wikipedia, the free encyclopedia. List of human leukocyte antigen alleles associated with cutaneous conditions. Cambridge University Press, ISBN CS1 maint: Overview of psoriasis and guidelines of care for the 21st Century psoriazis of psoriasis with biologics". J Am Acad Dermatol. Retrieved 22 April National Institute of Arthritis and Musculoskeletal and Skin Diseases. Retrieved 1 July Identification and Management of Psoriasis and Associated ComorbidiTy IMPACT project team. Drug Des Devel Ther. Davidson's principles and practice of medicine. Retrieved 16 March Andrews' Diseases of the 21st Century psoriazis Clinical Dermatology 10th ed. From the Medical Board of the National Psoriasis Foundation". Fitzpatrick's Dermatology in General Medicine 8th ed. Am J Clin Dermatol. Greenberg, Michael Glick, Jonathan A. Burket's oral medicine 11th ed. N Engl J Med. Retrieved 8 October The American Journal of Human Genetics. J Eur Acad Dermatol Venereol. J Int AIDS Soc. A Review of T-cell Subsets and Cytokine 21st Century psoriazis. J Cutan Med Surg. Expert Rev Gastroenterol Hepatol. Clinical dermatology 4th ed. Cytokine Growth Factor 21st Century psoriazis. Br J Community Nurs. Skin Disease, Immune Response and Cytokines. Clin Rev Allerg Immunol. The International League of Dermatological Societies. Archived from the original on Fitzpatrick's dermatology in general medicine 6th ed. Http://climateexchangeplc.com/ayurveda-l-psoriazis.php Am Board Fam Med. Clin Cosmet Investig Dermatol. Br J Clin Dermatol. Arthritis Care Res Hoboken. Cochrane Database Syst Rev. Guidelines of care for the management and treatment of picurare prescrise pentru psoriazis with topical therapies". The Cochrane database of systematic reviews. International Journal of Dermatology. Indian J Dermatol Venereol Leprol. Psoriasis American Academy of Dermatology". A Review of Phase III Trials. The Point of View of the Nutritionist. Int J Environ Res Public Health Review. Clin Cosmet Investig Dermatol Review. Nat Rev Gastroenterol Hepatol Review. Health Qual Life Outcomes. Clinical dermatology a color guide to diagnosis and therapy 5th ed. Am J Med Sci. Ir J Med Sci Psoriatic and Reactive Arthritis: A Companion to Rheumatology 1st ed. The American Journal of Managed Care. L40 ICD - 9-CM: Diseases of the skin and appendages 21st Century psoriazis morphology. Freckles lentigo melasma nevus melanoma. Aphthous stomatitis oral candidiasis lichen planus leukoplakia pemphigus vulgaris mucous membrane pemphigoid cicatricial pemphigoid herpesvirus coxsackievirus syphilis systemic histoplasmosis squamous-cell carcinoma. Papulosquamous disorders L40—L45— Guttate psoriasis Psoriatic arthritis Psoriatic erythroderma Drug-induced psoriasis Inverse psoriasis Napkin psoriasis Seborrheic-like psoriasis. Pityriasis lichenoides Pityriasis lichenoides et varioliformis acutaPityriasis 21st Century psoriazis chronica Lymphomatoid papulosis Small plaque parapsoriasis Digitate dermatosisXanthoerythrodermia perstans Large plaque parapsoriasis Retiform parapsoriasis. Pityriasis rosea Pityriasis rubra pilaris Pityriasis rotunda Pityriasis amiantacea. Hepatitis-associated lichen planus Lichen planus pemphigoides. Lichen 21st Century psoriazis Lichen striatus Lichen ruber moniliformis Gianotti—Crosti syndrome Erythema dyschromicum perstans Idiopathic eruptive 21st Century psoriazis pigmentation Keratosis lichenoides chronica Kraurosis vulvae Lichen sclerosus Lichenoid dermatitis Lichenoid reaction of graft-versus-host disease. Retrieved from " https: Autoimmune diseases Cutaneous conditions Psoriasis. Uses editors parameter CS1 maint: Uses authors parameter Good articles Articles with DMOZ links Wikipedia articles with LCCN identifiers RTT. Navigation menu Personal tools Not logged in Talk Contributions Create account Log in. Views Read Edit View history. Navigation Main page Contents Featured content Current events Random article Donate to Wikipedia Wikipedia store. Interaction Help About Wikipedia Community portal Recent changes Contact page. Tools What links here Related changes Upload file Special pages Permanent link Page information Wikidata item Cite this page. Psoriazisul poate fi vindecat sau nu policy About Wikipedia Disclaimers Contact Wikipedia Developers Cookie statement Mobile view. Reditchy, scaly patches of skin . Genetic disease triggered by environmental factors . Based on symptoms . Steroid creamsvitamin D3 cream, ultraviolet lightimmune system suppressing medications such as methotrexate . Pustulosis palmaris et plantaris. Wikimedia Commons has media related to Psoriasis. Epidermal wart callus seborrheic keratosis acrochordon molluscum contagiosum actinic keratosis squamous-cell carcinoma 21st Century psoriazis carcinoma Merkel-cell carcinoma nevus sebaceous trichoepithelioma. With epidermal involvement Eczematous contact dermatitis atopic dermatitis seborrheic dermatitis stasis dermatitis lichen simplex 21st Century psoriazis Darier's disease glucagonoma syndrome langerhans cell histiocytosis lichen sclerosus pemphigus foliaceus Wiskott—Aldrich syndrome Zinc deficiency. Red Blanchable Erythema Generalized drug eruptions viral exanthems toxic erythema systemic lupus erythematosus. Lichen planus configuration Annular Linear morphology Hypertrophic Atrophic Bullous Ulcerative Actinic Pigmented site Mucosal Nails Peno-ginival Vulvovaginal 21st Century psoriazis synromes with lichen sclerosus with lupus erythematosis other: Contact the Department of Development at Mayo Clinic. Clearing psoriasis lesions is possible. Don't settle for less than satisfactory treatment results. It's a good thing you live in the 21st baie psoriazis, when psoriasis treatment options are plenty and 21st Century psoriazis. In the 19th century, psoriasis remedies included ingredients such as cat and dog feces, goose oil, onions with sea salt and urine, and toxic substances such as nitrate, 21st Century psoriazis, and mercury. These were not very effective solutions, and in fact, were harmful because of the toxic 21st Century psoriazis. Today, there are many treatment options available for psoriasis. Topical medicationssystemic treatmentand light therapy are all effective at improving psoriasis symptoms. Science has come a long way since the old days of using toxins to treat psoriasis. Now there are many treatments that will not only help improve symptoms, but can clear psoriasis lesions. You don't have to settle for less than satisfactory results. If you feel you are not seeing 21st Century psoriazis treatment results you want, use the treatment check-up tool to see if it's time to visit your doctor about http://climateexchangeplc.com/tratamentul-psoriazisului-la-coate-la-domiciliu.php psoriasis treatment and treatment expectations. Good communication with your doctor is key to managing your psoriasis. It's important to talk to your doctor about your psoriasis treatment if:. Get ready for your appointment to discuss treatment options by using the doctor discussion guide. All material copyright MediResource Inc. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a rostopască iarbă psoriazis pentru condition. We respect your privacy and will not share link personal information. It's important to talk to your doctor about your psoriasis treatment if: Multiple Sclerosis Treatment Check-Up Tool. Toenail Fungus Treatment Options Table. Binge Eating Disorder Fact vs Myth. Tylenol Fact vs Myth. A closer look at MS symptoms. Put Some Spring in Your Step. Cutting Your Cancer Risk. Get Active This Spring! In order to receive our newsletter, please check the box 21st Century psoriazis " I'm not a robot ". - activ seleniu și psoriazis Web site security monitoring and malware removal. /bolesti-zdravoslovni-problemi/ psoriazis / 21st - century -healthcare / 21st - century -pet-health. - Tratamentul inovator al psoriazisului Web site security monitoring and malware removal. /bolesti-zdravoslovni-problemi/ psoriazis / 21st - century -healthcare / 21st - century -pet-health. - Tratamentul Dr. Nona psoriazisului images of psoriasis on arms for most people living in the 21st century. images of psoriasis on arms Natural killer diagnosticului de psoriazis. - care va vindeca psoriazis 21st Century Health Care USA -. - tratamentul psoriazisului culoare Contact the Department of Development at Mayo Clinic.	2	12	0	0	3	0.48906	3	7,391
Next generation medical wearables are facilitating the shift to a value-based care system, moving the point of care to the patient’s home while allowing doctors to monitor the patient’s condition through continuous, real-time data. Today’s healthcare system is dominated by a curative approach to medicine that prioritizes an acute, hospital-oriented mindset over one that recognizes long-term, continuing sickness. And yet, chronic conditions now account for more than half of all deaths in the nation and take up more than 85 percent of annual healthcare expenditures, according to the Centers for Disease Control and Prevention. A report from the Rand Corporation found that patients who have chronic conditions generally have worse health outcomes, higher hospital readmission rates, and incur more healthcare expenses. These patients also require comprehensive and regular care to manage their chronic conditions. Palliation and prevention must take precedence over curative medicine, and a value-based healthcare system now mandates a decentralized delivery of care wherein patients with chronic diseases are cared for in an outpatient setting with improved outcomes, namely, the patient’s home. Reducing healthcare costs with medical wearables The primary objective of a value-based healthcare system is to reduce costs while enabling better health outcomes for patients, both in the diagnostic and post-diagnostic stages. Medical wearables that continually collect patient data in real-time offer better biometrics from which physicians can make diagnoses and prescribe a treatment of care compared to traditional office or hospital visits. Not only can the information that patients disclose during their visits be inaccurate, health data that is collected exclusively during office or hospital visits reflect certain moments in time and may not reveal the manifestation of a symptom or condition. Take abnormal heart rhythms, or arrhythmias, for instance. Arrhythmias can lead to serious heart and health complications, such as stroke or sudden cardiac arrest, if left untreated. Doctors often prescribe an ECG test as a first diagnostic step. However, an ECG test only lasts 10-30 seconds and will only uncover electrical issues with the heart that are permanent or occur during the test. Alternatively, doctors can prescribe a Holter or patch monitor, which continually records the heart’s electrical activity for up to two days, but these are only recording devices and must be returned and analyzed in order to identify any abnormalities. Mobile cardiac telemetry (MCT) devices are the optimal diagnostic tools for heart disease, as they can record all heart activity for up to 30 days and continuously detect and automatically transmit all patient-indicated or auto-detected heart abnormalities through a cellular transmission. In fact, continuous ECG monitoring that patients wear at home have been found to significantly increase detection of atrial fibrillation (AF), according to an industry-funded study in JAMA. MCT devices are now considered the next generation medical wearables for diagnosing heart disease, because they combine real-time, continuous monitoring with precise biometrics to offer best diagnostic yield. Earlier detection of chronic diseases drives costs savings and better health outcomes for patients because they can benefit from a course of treatment earlier, before a chronic disease has progressed to a debilitating stage. From the post-diagnostic perspective, medical wearables offer a significant return on investment (ROI) for both doctors and patients. When doctors can more easily manage a patients remotely, they can improve their in-facility workflows to allow them to spend more time with patients needing immediate attention. Patients’ health outcomes and finances benefit from reduced hospitalizations and increased adoption of healthy behavioral and lifestyle changes. For example, many people are aware that exercise helps decrease blood pressure but actually seeing proof of this change with data generated from a medical wearable can help reinforce this positive behavior. Patients also have the benefit of working directly with a doctor who can assess the data and subsequently customize a treatment plan for the patient. Making medical wearables a standard of care Several factors have to come together to bring next generation medical wearables into common practice. First, the data generated from medical wearables has to be presented to doctors in a meaningful way, through an interface that identifies data trends and pinpoints important information from which actionable insights can be gleaned. Second, medical-grade wearables require fast cellular connection in order to provide real-time data, which the fast emerging 5G network promises to deliver. Finally, medical wearables have to exist within a reimbursement system that makes it advantageous for healthcare providers, doctors, and patients to use. Earlier this year, the Centers for Medicare & Medicaid Services (CMS) proposed its landmark 2019 Medicare Physician Fee Schedule and Quality Payment Program, which includes several amendments designed to encourage remote patient monitoring and telehealth programs through improved reimbursements. Already effective as of January 1, 2018, CMS has unbundled CPT code 99091 to enable eligible practitioners to receive separate reimbursement for time spent collecting and interpreting remote patient health data that is digitally stored and transmitted to a provider. By recognizing remote patient monitoring services for separate payment, CMS has encouraged widespread implementation of medical-grade remote monitoring solutions for outpatient care. Today, chronic disease has overtaken acute illness, so the healthcare system must change its approach to fit this new pattern of disease. Patients with chronic conditions need extensive monitoring and around-the-clock care that a hospital or isolated office visit is not equipped to provide. With advanced biometrics, continuous real-time monitoring, and increased patient engagement, medical wearable devices are a small investment on a large return. Waqaas Al-Siddiq is founder and CEO of Biotricity, a biometric remote monitoring solutions company. He is a serial entrepreneur, a former investment advisor, and expert in wireless communication technology. He has vast experience through executive roles within start-ups, mid-sized companies, and non-profits. For more information visit https://www.biotricity.com	2	3	2	0	0	0.907147	2	1,198
What is Behcet’s Disease (Behcet’s syndrome) - 1 What is Behcet’s Disease (Behcet’s syndrome) - 2 Causes - 3 Risk Factors - 4 Signs and Symptoms - 5 Complications - 6 Diagnosis and Tests - 7 Differential Diagnosis - 8 Treatment and Management - 9 Alternative Methods of Management - 10 Diet to Follow with Behcet’s Syndrome - 11 Prognosis - 12 Incidence and Prevalence - 13 ICD-9-CM and ICD-10-CM Codes Behcet’s disease or Behcet’s (pronounced: beh-CHETS) syndrome, named after the Turkish dermatologist Hulusi Behcet, is a rare inflammatory disorder that can affect blood vessels throughout the body. The autoimmune disease may cause inflammation in the eyes, sores in the mouth, ulcers on the genitals, and skin rashes, although the effects usually vary from person-to-person. Behcet’s disease is not well understood, and more research is needed to establish its specific causes. However, some research works indicate that bacterial, viral, environmental, and genetic factors play a role in causing the immune system to attack its own healthy blood vessels and cells. Exposure to infectious agents like Staphylococcus, Escherichia coli, Streptococcus bacteria, and herpes simplex virus could possibly trigger its development in individuals who are genetically susceptible to the disease. - Gender: Men are more likely to get affected than women. - Age: Occurs usually in both young and middle-aged men and women (20-40 years old), although children and older people also can have Behcet’s syndrome. - Origin: It normally affects people from countries along the old Silk Road, stretching from the Far East to the Middle East, including Japan, China, Iran, Egypt, Israel, and Turkey. - Genes: People with the gene HLA-B51 or HLA-B5 are at risk of developing the disease. Signs and Symptoms Patients with Paget’s syndrome may experience episodes of the symptoms flaring up and getting better on their own (remission). Common symptoms include: - Painful genital and mouth sores. - Skin lesions such as acne-like spots or an abnormal growth. - Lymphadenopathy causing abnormal enlargement or swelling of lymph nodes. - Inflammation in the eye, called uveitis causes pain, redness, along with blurred vision. - Pain and swelling of joints, involving knees, elbows, ankles, or wrists. - Inflammation in veins and arteries causes pain, swelling, and redness in the arms and legs, which may result in the formation of blood clots. - Systemic vasculitis may cause extreme fatigue, limiting the ability to do any activity and impairing quality of life. - Abdominal pain, loss of appetite, indigestion, diarrhea, vomiting. - A headache, loss of balance, fever, seizures, or double vision caused by inflammation in the central nervous system (CNS). - Decreased or permanent loss of vision caused by severe uveitis. - Bloody stools due to the damage caused by inflammation of the internal intestinal lining. - Severe neurological disorders such as personality or behavioral changes, or partial paralysis due to CNS inflammation and brain stem lesions. - Cerebral venous thrombosis or a blood clot inside the veins and arteries of the brain, increasing the pressure and cutting the blood supply, resulting in stroke-like symptoms. - Aneurysms and blockage of blood vessels due to swelling in large arteries. - Rarely, organ dysfunction or internal bleeding. Diagnosis and Tests No specific tests can definitively reveal Behcet’s syndrome since it takes several months or years before the common symptoms appear. Diagnosis is based on a set of clinical guidelines associated with the occurrence of symptoms. The clinical criteria established for classification of Behcet’s disease states patients must have recurrent mouth ulcerations (thrice or more in a year) along with at least two of the following: - Recurrent genital sores - Retinal inflammation, uveitis, or other eye problems - Skin sores and rashes - Positive pathergy test - Radiographs, MRI, or CT scan of sacroiliac joint and peripheral joints may indicate inflammation and accumulation of synovial fluid in the cavity. - Brain MRI, CT scanning, or MRA to identify inflammation of blood vessels in the brain (cerebral vasculopathy) and places of restricted blood circulation (acute ischemia). SPECT scan (single-photon emission computed tomography) of the brain can indicate insufficient blood flow (cerebral hypoperfusion or ischemia). - Angiography for evaluating aneurysms. - Doppler ultrasonography to rule out other causes of venous blockage. The patient’s forearm is pricked with a small, sterile needle and the area is examined after 1-2 days. The test gives a positive result if a small red spot or bump appears under the skin, which means the patient’s immune system has overreacted to the minor injury. Bowel tests, lumbar puncture, and skin biopsy might be required for individual patients depending upon the symptoms for the diagnosis. - Antiphospholipid Syndrome - AA (Inflammatory) Amyloidosis - Granulomatosis with Polyangiitis - Paraneoplastic Syndromes - Inflammatory Bowel Disease - Systemic Lupus Erythematosus (SLE) - MAGIC or “mouth and genital ulcers with inflamed cartilage” syndrome - PFAPA or “periodic fever, aphthous-stomatitis, pharyngitis, adenitis” syndrome - Reactive arthritis, psoriatic arthritis, ankylosing spondylitis - Bacterial and viral infections - Nutritional/hematological deficiencies Treatment and Management There is no cure for Behcet’s syndrome, though a treatment plan involving a combination of medications can help in relieving symptoms. Depending on the severity of symptoms, patients may need to take temporary medication to control flare-ups in pain and inflammation. Alternatively, people with Behcet’s disease may require long-term treatment to stop the development of serious complications. - Corticosteroids like methylprednisolone, prednisone, and dexamethasone are given intravenously for arthritis, topically for ulceration or eye problems, and orally for systemic symptoms. Their long-term use may increase the risks of high blood pressure, heartburn, weight gain, and osteoporosis. - Immunosuppressants including azathioprine, cyclophosphamide, chlorambucil, cyclosporine, and methotrexate to reduce the immune response, and thus stop the inflammation process that triggers other symptoms of Behcet’s syndrome. While mild side effects include hair loss, abdominal pain, and weakness, chronic use of these medications may cause liver and kidney function impairment. Some of the immunosuppressants may cause miscarriage or birth defects and should be avoided during pregnancy. - Anti-inflammatory medication such as colchicine, triptans, and NSAIDs are used for lessening pain and headaches. - Biologics like TNF-α inhibitors that target the antibodies associated with the process of inflammation. Common anti-TNF drugs include infliximab, interferon alpha, etanercept, certolizumab, adalimumab, and golimumab. Surgical care is needed when eye, lung, heart, gastrointestinal, and neurological complications develop, including: - Abnormal narrowing (stenosis) in blood vessels of the intestine. - Fistula formation, severe bleeding, and perforation in GI tract. - Aneurysms and ischemic damage to the lungs, requiring surgical excision. - Obstruction of blood flow in coronary arteries or veins (coronary thrombosis), formation excess tissues in endocardium (endocardial fibrosis). - Sores and ulcers, not responding to medication. - Cataracts, retinal detachment, and glaucoma. - Aneurysms and clots in the central nervous system. Alternative Methods of Management - Activity level should be adjusted as tolerated by the patient. Some limitations are imposed if there are symptoms of arthritis present. - Essential oils derived from cinnamon leaf, ginger, juniper berries, cypress, and clary sage may be used as anti-inflammatory massage oil for lessening joint pain and muscle stiffness. Diet to Follow with Behcet’s Syndrome Patients with Behcet’s disease involving gastrointestinal complications are recommended to follow a similar diet recommended for people with inflammatory bowel disease. Special liquid food containing glucose, salts, vitamins, minerals, lipids, and amino acids may be given intravenously. Anyone with the Behcet’s syndrome should avoid milk, cheese, ice cream, and yogurt since a recent study has shown intake of dairy products may worsen autoimmune symptoms in some individuals. As medical therapy can relieve moderate symptoms and control flare-ups, patients with Behcet’s syndrome can lead a normal life. Deaths are occasionally reported in people exhibiting major vascular, gastrointestinal, or neurological complications, and frequent flare-ups. Incidence and Prevalence Data from recent studies in the US identified 0.12-0.33 cases of Behcet’s disease per 100,000 Americans. In Turkey, its prevalence is the highest being 420 per 100,000 population. It ranges from 13.5-22 per 100,000 inhabitants in Korea, Japan, China, Saudi Arabia, and Iran. In Europe and North America, only 1 case was reported per 15,000-50,000 inhabitants. ICD-9-CM and ICD-10-CM Codes The ICD-9-CM code for Behcet’s disease is 136.1, and the ICD-10 code is M35.2.	2	14	0	0	3	0.775444	3	2,201
What are ICD and OPS codes? ICD and OPS codes were created in order to give structure to medical diagnoses and treatments and to name these in a standardized way. The ICD code is a globally recognized system that is used to consistently label medical diagnoses. ICD stands for “International Statistical Classification of Diseases and Related Health Problems”. The new ICD-11 officially came into effect in January 2022, alongside version ICD-10, which continues to be valid. Both versions can be used for a transition period of 5 years. Codes continue to be used in accordance with ICD-10 until the introduction of ICD-11 in Germany. “OPS” is short for “Operationen- und Prozedurenschlüssel” – the operation and procedure classification system. It serves as a coding system for operations and treatments. Patients will find these codes in doctor’s letters and other medical documents. However, without an explanation, most people won’t understand what they mean, as the official diagnosis procedure classifications are written in medical terminology that is difficult to grasp for anyone who is not a healthcare professional. gesund.bund.de in cooperation with “Was hab’ ich” provides you with clear and simple explanations of the ICD and OPS codes. Click here to access the ICD and OPS code search. What do the letters and numbers stand for in ICD codes? An ICD code uses a defined structure in which every letter and number has a meaning. In ICD-10 codes, the letters at the start and the two digits that follow these indicate the main category of a diagnosis. For example, the letter “J” is used to classify diseases of the respiratory system. J40 to J47 stand for chronic diseases of the lower respiratory tract, while J45 indicates asthma. Additional numbers after a dot can be used to indicate a more precise diagnosis. For example, J45.0 indicates predominantly allergic asthma, while J45.1 indicates non-allergic asthma. The ICD code can be followed by additional indicators. These letters provide further information: - The additional indicators R (right), L (left) and B (both sides) represent the affected side of the body. This enables doctors to specify if the left knee, right knee or both knees are affected in the case of a torn cruciate ligament, for example. - The additional indicators A (excluded diagnosis), G (confirmed diagnosis), V (tentative diagnosis) and Z (condition after a confirmed diagnosis) indicate the diagnostic certainty. This enables doctors to specify, for example, whether a torn cruciate ligament has been reliably proven or – on the contrary – excluded. The new ICD-11 classification Since 2022, a new optional system of classifying diagnoses using codes has been available internationally. This is the ICD-11 – a revision of the classification system that has been updated to reflect modern healthcare standards. New chapters were created for improved classification of diseases. In addition, several codes can now be combined with one another to describe diagnoses in more precise terms. The logical structure is designed to make it easier than before to classify diagnoses more specifically using codes. ICD-11 codes have a minimum of four and a maximum of six characters, the second character of which is always a letter. For example, the code for allergic asthma is J45.0 according to ICD-10. In ICD-11, it is now coded as CA23.0 – CA represents respiratory diseases, 2 indicates the lower respiratory tract, and 3 denotes asthma. The numbers after the dot indicate whether the asthma is allergic asthma (.0), non-allergic asthma (.1), other forms of asthma (.2) or non-specified asthma (.3). There are no additional indicators for side of the body or diagnosis certainty anymore. Instead, these are indicated by code extensions that start with an “X” and are linked by means of an “&” with a primary code – for example, XK8G for left side of the body or XY7Z for a preliminary diagnosis. What do the numbers stand for in OPS codes? OPS (operation and procedure) codes are used to classify various tests and treatments. The codes are revised annually and are organized into the following chapters: - 1: Diagnostic measures - 3: Diagnostic imaging - 5: Operations - 6: Medications - 8: Non-operative therapeutic measures - 9: Supplementary measures Chapters 2, 4 and 7 were in an original version published by the WHO but are not used in the German healthcare system. An OPS code is always a maximum of six characters long. The additional indicators R (right), L (left) and B (both sides) may also be used. The code begins with the chapter number, followed by a hyphen. For example, desensitization (hyposensitization) for a person who is allergic to insect venom is classified using the code 8-030.0. Here, the number 8 indicates a non-operative therapeutic measure, 8-03 indicates immunotherapy, 8-030 denotes allergen-specific immunotherapy, and the extension .0 means that bee or wasp venom is used in the treatment. What are these codes used for? ICD and OPS codes provide an important basis for the billing of medical services provides, for the creation of statistics, and for quality reporting by hospitals. ICD codes allow conditions to be classified in a clear and unambiguous way worldwide. This means, for example, that internationally comparable health and cause-of-death statistics can be created. However, the codes are not only useful in terms of patient care. They are also used in research, for example, to provide insights into the transmission or prevention of diseases. Would you like to understand the ICD and OPS codes in your doctor’s letter or sick leave notice? “Click here to access the ICD and OPS code search” - Federal Institute for Drugs and Medical Devices (BfArM). Structure of ICD-11 MMS. Accessed on 10/27/2021. - Federal Institute for Drugs and Medical Devices (BfArM). Code system basics. Accessed on 10/27/2021. - German Institute for Medical Documentation and Information (DIMDI). ICD-10-GM. Accessed on 05/20/2020. - Jakob R. ICD-11 – Anpassung der ICD an das 21. Jahrhundert [ICD-11-Adapting ICD to the 21st century]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz [Federal Health Bulletin - Health Research - Health Protection] 2018 Jul;61(7):771-777. German. doi: 10.1007/s00103-018-2755-6. - World Health Organization. ICD-11 for Mortality and Morbidity Statistics. Accessed on 10/27/2021. - World Health Organization. ICD-10. Accessed on 05/20/2020. - German Institute for Medical Documentation and Information (DIMDI). What additional indicators are there in ICD-10-GM and OPS and how are they used? Accessed on 03/31/2021.	4	6	0	0	5	0.783056	5	1,543
Antisocial personality disorder \|Antisocial personality disorder\| \|Classification and external resources\| Antisocial (or dissocial) personality disorder is characterized by a pervasive pattern of disregard for, or violation of, the rights of others. There may be an impoverished moral sense or conscience and a history of crime, legal problems, and impulsive and aggressive behavior. Antisocial personality disorder (ASPD) is the name of the disorder as defined in the Diagnostic and Statistical Manual (DSM). Dissocial personality disorder is the name of a similar or equivalent concept defined in the International Statistical Classification of Diseases and Related Health Problems (ICD), where it states that the diagnosis includes antisocial personality disorder. Both manuals have similar but not identical criteria. Both have also stated that their diagnoses have been referred to, or include what is referred to, as psychopathy or sociopathy, though distinctions are sometimes made. - 1 Diagnosis - 2 Further considerations - 3 Causes and pathophysiology - 4 Treatment - 5 Prognosis - 6 Epidemiology - 7 History - 8 See also - 9 References - 10 Further reading - 11 External links The APA's Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV-TR), defines antisocial personality disorder (in Axis II Cluster B): - A) There is a pervasive pattern of disregard for and violation of the rights of others occurring since age 15 years, as indicated by three or more of the following: - failure to conform to social norms with respect to lawful behaviors as indicated by repeatedly performing acts that are grounds for arrest; - deception, as indicated by repeatedly lying, use of aliases, or conning others for personal profit or pleasure; - impulsivity or failure to plan ahead; - irritability and aggressiveness, as indicated by repeated physical fights or assaults; - reckless disregard for safety of self or others; - consistent irresponsibility, as indicated by repeated failure to sustain consistent work behavior or honor financial obligations; - lack of remorse, as indicated by being indifferent to or rationalizing having hurt, mistreated, or stolen from another; - B) The individual is at least age 18 years. - C) There is evidence of conduct disorder with onset before age 15 years. - D) The occurrence of antisocial behavior is not exclusively during the course of schizophrenia or a manic episode. ASPD falls under the dramatic/erratic cluster of personality disorders. In the DSM-5, the diagnosis antisocial personality disorder is kept, but it is no longer on another axis as the other mental disorders. - It is characterized by at least 3 of the following: - Callous unconcern for the feelings of others; - Gross and persistent attitude of irresponsibility and disregard for social norms, rules, and obligations; - Incapacity to maintain enduring relationships, though having no difficulty in establishing them; - Very low tolerance to frustration and a low threshold for discharge of aggression, including violence; - Incapacity to experience guilt or to profit from experience, particularly punishment; - Marked readiness to blame others or to offer plausible rationalizations for the behavior that has brought the person into conflict with society. The ICD states that this diagnosis includes "amoral, antisocial, asocial, psychopathic, and sociopathic personality". Although the disorder is not synonymous with conduct disorder, presence of conduct disorder during childhood or adolescence may further support the diagnosis of dissocial personality disorder. There may also be persistent irritability as an associated feature. Psychopathy is commonly defined as a personality disorder characterized partly by antisocial behavior, a diminished capacity for remorse, and poor behavioral controls. Psychopathic traits are assessed using various measurement tools, including Canadian researcher Robert D. Hare's Psychopathy Checklist, Revised (PCL-R). "Psychopathy" is not the official title of any diagnosis in the DSM or ICD. American psychiatrist Hervey Cleckley's work on psychopathy formed the basis of the diagnostic criteria for ASPD, and the DSM has stated that ASPD has also been referred to as psychopathy. However, critics have argued that ASPD is not synonymous with psychopathy as the diagnostic criteria are not exactly the same, since criteria relating to personality traits are emphasized relatively less in the former. These differences exist in part because it was believed that such traits were difficult to measure reliably and it was "easier to agree on the behaviors that typify a disorder than on the reasons why they occur". Although the diagnosis of ASPD covers two to three times as many prisoners as are rated as psychopaths, Robert Hare believes that the PCL-R is better able to predict future criminality, violence, and recidivism than a diagnosis of ASPD. He suggests that there are differences between PCL-R-diagnosed psychopaths and non-psychopaths on "processing and use of linguistic and emotional information", while such differences are potentially smaller between those diagnosed with ASPD and without. Additionally, Hare argued that confusion regarding how to diagnose ASPD, confusion regarding the difference between ASPD and psychopathy, as well as the differing future prognoses regarding recidivism and treatability, may have serious consequences in settings such as court cases where psychopathy is often seen as aggravating the crime. Nonetheless, psychopathy has been proposed as a specifier under an alternative model for ASPD. In the DSM-5, under "Alternative DSM-5 Model for Personality Disorders", ASPD with psychopathic features is described as characterized by "a lack of anxiety or fear and by a bold interpersonal style that may mask maladaptive behaviors (e.g., fraudulence)." Low levels of withdrawal and high levels of attention-seeking combined with low anxiety are associated with "social potency" and "stress immunity" in psychopathy.:765 Under the specifier, affective and interpersonal characteristics are comparatively emphasized over behavioral components. Theodore Millon's subtypes \|Nomadic (including schizoid and avoidant features)\|\|Feels jinxed, ill-fated, doomed, and cast aside; peripheral, drifters; gypsy-like roamers, vagrants; dropouts and misfits; itinerant vagabonds, tramps, wanderers; impulsively not benign.\| \|Malevolent (including sadistic and paranoid features)\|\|Belligerent, mordant, rancorous, vicious, malignant, brutal, resentful; anticipates betrayal and punishment; desires revenge; truculent, callous, fearless; guiltless.\| \|Covetous (variant of "pure" pattern)\|\|Feels intentionally denied and deprived; rapacious, begrudging, discontentedly yearning; envious, seeks retribution, and avariciously greedy; pleasure more in taking than in having.\| \|Risk-taking (including histrionic features)\|\|Dauntless, venturesome, intrepid, bold, audacious, daring; reckless, foolhardy, impulsive, heedless; unbalanced by hazard; pursues perilous ventures.\| \|Reputation-defending (including narcissistic features)\|\|Needs to be thought of as infallible, unbreakable, invincible, indomitable, formidable, inviolable; intransigent when status is questioned; over-reactive to slights.\| Elsewhere, Millon differentiates ten subtypes (partially overlapping with the above) – covetous, risk-taking, malevolent, tyrannical, malignant, unprincipled, disingenuous, spineless, explosive, and abrasive – but specifically stresses that "the number 10 is by no means special ... Taxonomies may be put forward at levels that are more coarse or more fine-grained." The following conditions commonly coexist with ASPD: Causes and pathophysiology Personality disorders seem to be caused by a combination of these genetic and environmental influences. Genetically, it is the temperament and the kind of personality a person is born with, and environmentally, it is the way in which a person grows up and the experiences they have had. Hormones and neurotransmitters Traumatic events can lead to a disruption of the standard development of the central nervous system, which can generate a release of hormones that can change normal patterns of development. Aggressiveness and impulsivity are among the possible symptoms of ASPD. Testosterone is a hormone that plays an important role in aggressiveness in the brain. For instance, criminals who have committed violent crimes have higher levels of testosterone. The effect of testosterone is counteracted by cortisol which facilitates the cognitive control on impulsive tendencies. One of the neurotransmitters that have been discussed in individuals with ASPD is serotonin. A meta-analysis of 20 studies found significantly lower 5-HIAA levels (indicating lower serotonin levels), especially in those who are younger than 30 years of age. J.F.W. Deakin of University of Manchester's Neuroscience and Psychiatry Unit has discussed additional evidence of 5HT's connection with ASPD. Deakin suggests that low cerebrospinal fluid concentrations of 5-HIAA, and hormone responses to 5HT, have displayed that the two main ascending 5HT pathways mediate adaptive responses to post and current conditions. He states that impairments in the posterior 5HT cells can lead to low mood functioning, as seen in patients with ASPD. It is important to note that the dysregulated serotonergic function may not be the sole feature that leads to ASPD but it is an aspect of a multifaceted relationship between biological and psychosocial factors. While it has been shown that lower levels of serotonin may be associated with ASPD, there has also been evidence that decreased serotonin function is highly correlated with impulsiveness and aggression across a number of different experimental paradigms. Impulsivity is not only linked with irregularities in 5HT metabolism but may be the most essential psychopathological aspect linked with such dysfunction. Correspondingly, the DSM classifies "impulsivity or failure to plan ahead" and "irritability and aggressiveness" as two of seven sub-criteria in category A of the diagnostic criteria of ASPD. Limbic neural maldevelopment Cavum septi pellucidi (CSP) is a marker for limbic neural maldevelopment. One study found that those with CSP had significantly higher levels of antisocial personality, psychopathy, arrests and convictions compared with controls. The Socio-cultural perspective of clinical psychology view disorders as being influenced by cultural aspects, since cultural norms differ significantly, mental disorders such as ASPD are viewed differently. Robert D. Hare has suggested that the rise in ASPD that has been reported in the United States may be linked to changes in cultural mores, the latter serving to validate the behavioral tendencies of many individuals with ASPD. While the rise reported may be in part merely a byproduct of the widening use (and abuse) of diagnostic techniques, given Eric Berne's division between individuals with active and latent ASPD – the latter keeping themselves in check by attachment to an external source of control like the law, traditional standards, or religion – it has been plausibly suggested that the erosion of collective standards may indeed serve to release the individual with latent ASPD from their previously prosocial behavior. There is also a continuous debate as to the extent to which the legal system should be involved in the identification and admittance of patients with preliminary symptoms of ASPD. Some studies suggest that the social and home environment has contributed to the development of antisocial behavior. The parents of these children have been shown to display antisocial behavior, which could be adopted by their children. Researchers have linked physical head injuries with antisocial behavior. Since the 1980s, scientists have associated traumatic brain injury, including damage to the prefrontal cortex, with an inability to make morally and socially acceptable decisions. Children with early damage in the prefrontal cortex may never fully develop social or moral reasoning and become "psychopathic individuals ... characterized by high levels of aggression and antisocial behavior performed without guilt or empathy for their victims." Additionally, damage to the amygdala may impair the ability of the prefrontal cortex to interpret feedback from the limbic system, which could result in uninhibited signals that manifest in violent and aggressive behavior. ASPD is considered to be among the most difficult personality disorders to treat.[verification needed] Because of their very low or absent capacity for remorse, individuals with ASPD often lack sufficient motivation and fail to see the costs associated with antisocial acts. They may only simulate remorse rather than truly commit to change: they can be seductively charming and dishonest, and may manipulate staff and fellow patients during treatment.[verification needed] Studies have shown that outpatient therapy is not likely to be successful, however the extent to which persons with ASPD are entirely unresponsive to treatment may have been exaggerated. Those with ASPD may stay in treatment only as required by an external source, such as a parole. Residential programs that provide a carefully controlled environment of structure and supervision along with peer confrontation have been recommended. There has been some research on the treatment of ASPD that indicated positive results for therapeutic interventions. Schema Therapy is also being investigated as a treatment for ASPD. A review by Charles M. Borduin features the strong influence of Multisystemic therapy (MST) that could potentially improve this imperative issue. However this treatment requires complete cooperation and participation of all family members. Some studies have found that the presence of ASPD does not significantly interfere with treatment for other disorders, such as substance abuse, although others have reported contradictory findings. Therapists of individuals with ASPD may have considerable negative feelings toward clients with extensive histories of aggressive, exploitative, and abusive behaviors. Rather than attempt to develop a sense of conscience in these individuals, therapeutic techniques should be focused on rational and utilitarian arguments against repeating past mistakes. These approaches would focus on the tangible, material value of prosocial behavior. No medications have been approved by the FDA to treat ASPD, although certain psychiatric medications may alleviate conditions sometimes associated with the disorder and with symptoms such as aggression, including antipsychotic, antidepressant or mood-stabilizing medications. According to Professor Emily Simonoff, Institute of Psychiatry, "childhood hyperactivity and conduct disorder showed equally strong prediction of antisocial personality disorder (ASPD) and criminality in early and mid-adult life. Lower IQ and reading problems were most prominent in their relationships with childhood and adolescent antisocial behaviour." ASPD is seen in 3% to 30% of psychiatric outpatients. The prevalence of the disorder is even higher in selected populations, like prisons, where there is a preponderance of violent offenders. A 2002 literature review of studies on mental disorders in prisoners stated that 47% of male prisoners and 21% of female prisoners had ASPD. Similarly, the prevalence of ASPD is higher among patients in alcohol or other drug (AOD) abuse treatment programs than in the general population (Hare 1983), suggesting a link between ASPD and AOD abuse and dependence. A University of Colorado Colorado Springs study comparing personality disorders and Myers-Briggs Type Indicator types found that the disorder had a significant correlation with the Intuitive (N), Thinking (T), and Perceiving (P) preferences. The first version of the DSM in 1952 listed sociopathic personality disturbance. Individuals to be placed in this category were said to be "...ill primarily in terms of society and of conformity with the prevailing milieu, and not only in terms of personal discomfort and relations with other individuals". There were four subtypes, referred to as "reactions"; antisocial, dyssocial, sexual and addiction. The antisocial reaction was said to include people who were "always in trouble" and not learning from it, maintaining "no loyalties", frequently callous and lacking responsibility, with an ability to "rationalize" their behavior. The category was described as more specific and limited than the existing concepts of "constitutional psychopathic state" or "psychopathic personality" which had had a very broad meaning; the narrower definition was in line with criteria advanced by Hervey M. Cleckley from 1941, while the term sociopathic had been advanced by George Partridge. The DSM-II in 1968 rearranged the categories and "antisocial personality" was now listed as one of ten personality disorders but still described similarly, to be applied to individuals who are: "basically unsocialized", in repeated conflicts with society, incapable of significant loyalty, selfish, irresponsible, unable to feel guilt or learn from prior experiences, and who tend to blame others and rationalise. The DSM-II warned that a history of legal or social offenses was not by itself enough to justify the diagnosis, and that a "group delinquent reaction" of childhood or adolescence or "social maladjustment without manifest psychiatric disorder" should be ruled out first. The dyssocial personality type was relegated in the DSM-II to "dyssocial behavior" for individuals who are predatory and follow more or less criminal pursuits, such as racketeers, dishonest gamblers, prostitutes, and dope peddlers. (DSM-I classified this condition as sociopathic personality disorder, dyssocial type). It would later resurface as the name of a diagnosis in the ICD manual produced by the WHO, later spelled dissocial personality disorder and considered approximately equivalent to the ASPD diagnosis. The DSM-III in 1980 included the full term antisocial personality disorder and, as with other disorders, there was now a full checklist of symptoms focused on observable behaviors to enhance consistency in diagnosis between different psychiatrists ('inter-rater reliability'). The ASPD symptom list was based on the Research Diagnostic Criteria developed from the so-called Feighner Criteria from 1972, and in turn largely credited to influential research by sociologist Lee Robins published in 1966 as "Deviant Children Grown Up". However, Robins has previously clarified that while the new criteria of prior childhood conduct problems came from her work, she and co-researcher psychiatrist Patricia O'Neal got the diagnostic criteria they used from Lee's husband the psychiatrist Eli Robins, one of the authors of the Feighner criteria who had been using them as part of diagnostic interviews. The DSM-IV maintained the trend for behavioral antisocial symptoms while noting "This pattern has also been referred to as psychopathy, sociopathy, or dyssocial personality disorder" and re-including in the 'Associated Features' text summary some of the underlying personality traits from the older diagnoses. The DSM-5 has the same diagnosis of antisocial personality disorder. The Pocket Guide to the DSM-5 Diagnostic Exam suggests that a person with ASPD may present "with psychopathic features" if he or she exhibits "a lack of anxiety or fear and a bold, efficacious interpersonal style". - David P. Farrington, Jeremy Coid (16 June 2003). Early Prevention of Adult Antisocial Behavior. Cambridge University Press. p. 82. ISBN 978-0-521-65194-3. Retrieved 12 January 2008. - Patrick, Christopher (2005). Handbook of Psychopathy. Guilford Press. ISBN 9781606238042. Retrieved 18 July 2013. - "Psychopathy and Antisocial Personality Disorder: A Case of Diagnostic Confusion". Robert D. Hare, PhD Psychiatric Times. Vol. 13 No. 2. 1 February 1996. - Hare, R.D., Hart, S.D., Harpur, T.J. Psychopathy and the DSM—IV Criteria for Antisocial Personality Disorder (PDF). - Semple, David (2005). The Oxford Handbook of Psychiatry. USA: Oxford University Press. pp. 448–449. ISBN 0-19-852783-7. - Skeem, J. L.; Polaschek, D. L. L.; Patrick, C. J.; Lilienfeld, S. O. (15 December 2011). "Psychopathic Personality: Bridging the Gap Between Scientific Evidence and Public Policy". Psychological Science in the Public Interest 12 (3): 95–162. doi:10.1177/1529100611426706. - American Psychiatric Association (2000). "Diagnostic criteria for 301.7 Antisocial Personality Disorder". BehaveNet. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Retrieved 8 July 2013. - Schacter, Daniel L., Daniel T. Gilbert, and Daniel M. Wegner. Psychology. Worth Publishers, 2010. Print. - "Personality Disorders". American Psychiatric Association. 2013. Retrieved 25 October 2013. - WHO (2010)ICD-10: Clinical descriptions and diagnostic guidelines: Disorders of adult personality and behavior - "F60.2 Dissocial personality disorder". World Health Organization. Retrieved 12 January 2008. - R. James R. Blair. "Neurobiological basis of psychopathy". Retrieved 15 May 2013. - Merriam-Webster Dictionary. "Definition of psychopathy". Retrieved 15 May 2013. - Encyclopedia of Mental Disorders. "Hare Psychopathy Checklist". Retrieved 15 May 2013. - Hare, R. D. (2003). Manual for the Revised Psychopathy Checklist (2nd ed.). Toronto, ON, Canada: Multi-Health Systems. - American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision - World Health Organization (1992). International Statistical Classification of Diseases and Related Health Problems-10th revision - Kupfer, David; Regier, Darrell, eds. (2013). Diagnostic and Statistical Manual of Mental Disorders (in English) (5th ed.). Washington, DC and London, England: American Psychiatric Publishing (accessed on Google Play). ISBN 0890425558. - Nussbaum, Abraham (2013). The Pocket Guide to the DSM-5 Diagnostic Exam. Arlington, VA: American Psychiatric Publishing. ISBN 978-1-58562-466-9. Retrieved 5 January 2014. - Millon, Theodore, Personality Disorders in Modern Life, 2004 - Millon, Theodore – Personality Subtypes. Millon.net. Retrieved on 7 December 2011. - Quoted in Martha Stout, The Sociopath Next Door (2005) p. 223 - Internet Mental Health – antisocial personality disorder. Mentalhealth.com. Retrieved on 7 December 2011. - Oscar-Berman M; Valmas M; Sawyer K; Kirkley S; Gansler D; Merritt D; Couture A (April 2009). "Frontal brain dysfunction in alcoholism with and without antisocial personality disorder". Neuropsychiatric Disease and Treatment 2009 (5): 309–326. doi:10.2147/NDT.S4882. PMC 2699656. PMID 19557141. - "Antisocial personality disorder". Mayo Foundation for Medical Education and Research. 13 July 2013. Retrieved 25 October 2013. - Black, D. "What Causes Antisocial Personality Disorder?". Psych Central. Retrieved 1 November 2011. - Menelaos L. Batrinos (2012). "Testosterone and Aggressive Behavior in Man". Int J Endocrinol Metab. 10 (3): 563–568. doi:10.5812/ijem.3661. PMC 3693622. PMID 23843821. - Moore TM, Scarpa A, Raine A. (2002). "A meta-analysis of serotonin metabolite 5-HIAA and antisocial behavior". Aggressive Behavior. 28 (4): 299–316. doi:10.1002/ab.90027. - Brown, Serena-Lynn; Botsis, Alexander; Van Praag; Herman M. (1994). "Serotonin and Aggression". Journal of Offender Rehabilitation. 3–4 21 (3): 27–39. doi:10.1300/J076v21n03_03. - Adrian Raine, Lydia Lee, Yaling Yang, Patrick Colletti (2010). "Neurodevelopmental marker for limbic maldevelopment in antisocial personality disorder and psychopathy". BJPsych. the British Journal of Psychiatry 197 (3): 186–192. doi:10.1192/bjp.bp.110.078485. - Lock, M. P. (2008). "Treatment of antisocial personality disorder". The British Journal of Psychiatry 193 (5): 426. doi:10.1192/bjp.193.5.426. - Martha Stout, The Sociopath Next Door (2005) p. 136 - Sutker, Patricia B., and Albert N. Allain, Jr. "Antisocial Personality Disorder." Comprehensive Handbook of Psychopathology. Vol. III. : Springer US, 2002. 445-90. Google Scholar. Web. 13 March 2013 - Eric Berne, A Layman's Guide to Psychiatry and Psychoanalysis (1976) p. 241–2 - Stout, p. 136–7 - David McCallum, Personality and Dangerousness (2001) p. 7 - in Psych Central - "Protect – Watch Your Head". The Franklin Institute Online. The Franklin Institute. 2004. Retrieved 10 July 2013. - Nature Neuroscience, November 1999 - Archives of General Psychiatry, 1 February 2000 - Gabbard, Glen O., Gunderson John G. (2000) Psychotherapy for Personality Disorders. First Edition. American Psychiatric Publishing. ISBN 978-0-88048-273-8. - Stone, Michael H. (1993) Abnormalities of Personality. Within and Beyond the Realm of Treatment. Norton. ISBN 978-0-393-70127-2 - Oldham, John M., Skodol, Andrew E., Bender, Donna S. (2005) The American Psychiatric Publishing Textbook of Personality Disorders. American Psychiatric Publishing. ISBN 978-1-58562-159-0. - Salekin, R. (2002). "Psychopathy and therapeutic pessimism: Clinical lore or clinical reality?". Clinical Psychology Review 22: 169–183. doi:10.1016/S0272-7358(01)00083-6. - Derefinko, Karen J.; Thomas A. Widiger (2008). "Antisocial Personality Disorder". The Medical Basis of Psychiatry: 213–226. doi:10.1007/978-1-59745-252-6_13. ISBN 978-1-58829-917-8. - Bernstein, David P.; Arntz, Arnoud; Vos, Marije de (2007). "Schema Focused Therapy in Forensic Settings: Theoretical Model and Recommendations for Best Clinical Practice". International Journal of Forensic Mental Health 6 (2): 169–183. doi:10.1080/14999013.2007.10471261. - Gatzke L.M, Raine A. (2000). Treatment and Prevention Implications of Antisocial Personality Disorder Current Science Inc. Department of Psychology, University of Southern California. 2:51–55 - Darke, S; Finlay-Jones, R; Kaye, S; Blatt, T (1996). "Anti-social personality disorder and response to methadone maintenance treatment". Drug and alcohol review 15 (3): 271–6. doi:10.1080/09595239600186011. PMID 16203382. - Alterman, AI; Rutherford, MJ; Cacciola, JS; McKay, JR; Boardman, CR (1998). "Prediction of 7 months methadone maintenance treatment response by four measures of antisociality". Drug and alcohol dependence 49 (3): 217–23. doi:10.1016/S0376-8716(98)00015-5. PMID 9571386. - Beck, Aaron T., Freeman, Arthur, Davis, Denise D. (2006) Cognitive Therapy of Personality Disorders. Second Edition. The Guilford Press. ISBN 978-1-59385-476-8. - Mayo Clinic staff (12 April 2013). "Antisocial personality disorder: Treatments and drugs". Mayo Clinic. Mayo Foundation for Medical Education and Research. Retrieved 17 December 2013. - Simonoff E, Elander J, Holmshaw J, Pickles A, Murray R, Rutter M (2004). "Predictors of antisocial personality Continuities from childhood to adult life". The British Journal of Psychiatry 200 (2): 118–127. doi:10.1192/bjp.184.2.118. PMID 14754823. - Hare 1983 - Fazel, Seena; Danesh, John (2002). "Serious mental disorder in 23 000 prisoners: A systematic review of 62 surveys". The Lancet 359 (9306): 545. doi:10.1016/S0140-6736(02)07740-1. - Moeller, F. Gerard; Dougherty, Donald M. (2006). "Antisocial Personality Disorder, Alcohol, and Aggression". Alcohol Research & Health. National Institute on Alcohol Abuse and Alcoholism. Retrieved 20 February 2007. - "An Empirical Investigation of Jung's Personality Types and Psychological Disorder Features". Journal of Psychological Type/University of Colorado Colorado Springs. 2001. Retrieved August 10, 2013. - International Handbook on Psychopathic Disorders and the Law, Volume 1, Alan Felthous, Henning Sass, 15 Apr 2008, e.g. Pgs 24 – 26 - The Development of the Feighner Criteria: A Historical Perspective Kenneth S. Kendler, M.D.; Rodrigo A. Muñoz, M.D.; George Murphy, M.D. Am J Psychiatry 2009;167:134–142. 10.1176/appi.ajp.2009.09081155 - The DSM-IV Personality Disorders W. John Livesley, Guilford Press, 1995, Page 135 - Millon, T.; Davis, R. (1998). "Ten Subtypes of Psychopathy". In Millon, T.; et al. Psychopathy: Antisocial, Criminal and Violent Behavior. New York. ISBN 1572303441. \|Look up antisocial in Wiktionary, the free dictionary.\| - "Into the Abyss." Article on street crime referencing the roots and consequences of sociopathic behavior - DSM-IV-TR Criteria for Antisocial personality disorder - Psychopathy and Antisocial Personality Disorder: A Case of Diagnostic Confusion - Recent Studies Implicate Slow Monoamine Oxidase Enzyme/High Circulating T3 in Antisocial Behavior/Aggression/Violence 2007	2	39	12	4	2	0.635352	18	6,411
Heart failure means that your heart muscle doesn't pump as much blood as your body needs. Failure doesn't mean that your heart has stopped. It means that your heart is not pumping as well as it should. Because your heart cannot pump well, your body tries to make up for it. To do this: Your body has an amazing ability to make up for heart failure. It may do such a good job that you don't know you have a disease. But at some point, your heart and body will no longer be able to keep up. Then fluid starts to build up in your body, and you have symptoms like feeling weak and out of breath. This fluid buildup is called congestion. It's why some doctors call the disease congestive heart failure. Heart failure usually gets worse over time. But treatment can slow the disease and help you feel better and live longer. Anything that damages your heart or affects how well it pumps can lead to heart failure. Common causes of heart failure are: Other conditions that can lead to heart failure include: Symptoms of heart failure start to happen when your heart cannot pump enough blood to the rest of your body. In the early stages, you may: As heart failure gets worse, fluid starts to build up in your lungs and other parts of your body. This may cause you to: If your symptoms suddenly get worse, you will need emergency care. Your doctor may diagnose heart failure based on your symptoms and a physical exam. But you will need tests to find the cause and type of heart failure so that you can get the right treatment. These tests may include: An echocardiogram is the best and simplest way to find out if you have heart failure, what type it is, and what is causing it. Your doctor can also use it to see if your heart failure is getting worse. This test can measure how much blood your heart pumps to your body. This measurement is called the ejection fraction. If your ejection fraction gets lower and you are having more symptoms, it means that your heart failure is getting worse. Most people with heart failure need to take several medicines. Your doctor may prescribe medicines to: It is very important to take your medicines exactly as your doctor tells you to. If you don't, your heart failure could get worse. You might need to have a pacemaker or a defibrillator (ICD) if you have a problem with your heart rhythm. A pacemaker can help your heart pump blood better. An ICD can prevent a dangerous heart-rhythm problem. Lifestyle changes are an important part of treatment. They can help slow down heart failure. They may also help control other diseases that make heart failure worse, such as high blood pressure, diabetes, and coronary artery disease. The best steps you can take are to: To stay as healthy as possible, work closely with your doctor. Have all your tests, and go to all your appointments. It is also important to: Medicines and lifestyle changes can slow or even reverse heart failure for some people. But heart failure often gets worse over time. Early on, your symptoms may not be too bad. As heart failure gets worse, you may need to limit your activities. Treatment can often help reduce symptoms, but it usually doesn't get rid of them. Heart failure can also lead to other health problems. These may include: Your doctor may be able to give you medicine or other treatment to prevent or treat these problems. Heart failure can get worse suddenly. If this happens, you will need emergency care. To prevent sudden heart failure, you need to avoid things that can trigger it. These include eating too much salt, missing a dose of your medicine, and exercising too hard. Knowing that your health may get worse can be hard. It is normal to sometimes feel sad or hopeless. But if these feelings last, talk to your doctor. Antidepressant medicines, counseling, or both may help you cope. Health Tools help you make wise health decisions or take action to improve your health. \|Decision Points focus on key medical care decisions that are important to many health problems.\| \|Heart Failure: Should I Get a Pacemaker (Cardiac Resynchronization Therapy)?\| \|Heart Failure: Should I Get an Implantable Cardioverter-Defibrillator (ICD)?\| \|Sleep Apnea: Should I Have a Sleep Study?\| \|Actionsets are designed to help people take an active role in managing a health condition.\| \|Anxiety: Stop Negative Thoughts\| \|Blood Thinners Other Than Warfarin: Taking Them Safely\| \|Depression: Stop Negative Thoughts\| \|Healthy Eating: Eating Less Sodium\| \|Heart Failure: Activity and Exercise\| \|Heart Failure: Avoiding Medicines That Make Symptoms Worse\| \|Heart Failure: Avoiding Triggers for Sudden Heart Failure\| \|Heart Failure: Checking Your Weight\| \|Heart Failure: Taking Medicines Properly\| \|Heart Failure: Watching Your Fluids\| \|Heart Problems: Living With a Pacemaker\| \|Heart Problems: Living With an ICD\| \|Insomnia: Improving Your Sleep\| \|Low-Salt Diets: Eating Out\| \|Oxygen Therapy: Using Oxygen at Home\| \|Stop Negative Thoughts: Getting Started\| \|Stress Management: Breathing Exercises for Relaxation\| \|Stress Management: Doing Guided Imagery to Relax\| \|Stress Management: Doing Meditation\| \|Stress Management: Doing Progressive Muscle Relaxation\| \|Stress Management: Managing Your Time\| \|Stress Management: Practicing Yoga to Relax\| \|Stress Management: Reducing Stress by Being Assertive\| \|Warfarin: Taking Your Medicine Safely\| Learning about heart failure: Living with heart failure: Heart failure can be caused by any problem that damages your heart or affects how well it works. Certain triggers, such as too much sodium or not taking medicines the right way, may suddenly make heart failure worse. This can sometimes cause deadly problems such as pulmonary edema or cardiogenic shock. At first you may not have any symptoms from heart failure. For a while, your heart and body can make up for heart failure. For example, your heart can pump faster and pump more blood with each beat. This is called compensation. But as your heart has more trouble pumping enough blood to your body, you will likely have symptoms. These symptoms may get worse or change if your heart failure gets worse. Symptoms of heart failure start to happen when your heart can't pump enough blood to the rest of your body. In the early stages, you may: As heart failure gets worse, fluid starts to build up in your lungs and other parts of your body. This may cause you to: Heart failure is grouped—or classified—according to symptoms. Your treatment is based partly on what class of symptoms you have. There's also another way to define heart failure. It's based on the stages you might go through as your heart failure gets worse. Your doctor also may make treatment choices based on your stage of heart failure. Sometimes your symptoms may get worse very quickly. This is called sudden heart failure. It causes fluid to build up in your lungs, causing congestion. (This is why the problem is often called congestive heart failure.) Symptoms may include: Sudden heart failure is an emergency. You need care right away. Your risk for having heart failure is higher if you have certain risk factors. A risk factor is anything that increases your chance of having a particular problem. Heart failure is usually caused by another health problem, often coronary artery disease or high blood pressure. So anything that increases your risk for one of those problems also increases your risk for heart failure. The risk of heart failure rises as a person gets older. Call 911 or other emergency services right away if you have: Call your doctor right away if you have a pacemaker or ICD and think you have an infection near the device. Signs of an infection include: Call your doctor soon if you have symptoms of heart failure, which include: Call your doctor soon if: Many different types of doctors and nurses can treat you for heart failure, including your family doctor. Heart failure is a complex problem. So you will likely have several different tests over time. These tests can: If you have symptoms that suggest heart failure, you may have: An echocardiogram is the best and simplest way to diagnose heart failure. It also can help guide treatment. Sometimes, because of a person's weight, breast size, or severe lung disease, an echocardiogram might not be accurate. If that happens, a cardiac blood pool scan may be done instead. It checks how well the left ventricle is pumping. But it's not as good at finding heart valve disease and a thick heart muscle. Tests also may be done to find areas of the heart that are not getting enough blood. These tests include: When you're taking medicine for heart failure, you may have regular blood tests to check how the medicine is working. Your treatment for heart failure depends on: In the early stages of heart failure, treatment can help your symptoms. It may also prevent more damage to your heart. Treatment may include: You might take part in a disease management program. These programs include a broad range of services, such as education, home health care, visiting nurses, and rehabilitation. A very small number of people may have other treatments, including: If you have other heart problems that may have led to heart failure, you might have treatment for those problems: Sometimes heart failure can be fixed if another problem can be corrected, such as by treating hyperthyroidism. Because heart failure tends to get worse over time, it's important to think about what kind of care you would like at the end of your life. It's also important that your doctor and family know what you want. An advance directive is a legal document that tells doctors how to care for you at the end of your life. To learn more, see End-of-Life Decisions. The best way to prevent heart failure is to have a healthy lifestyle and control existing health problems like high blood pressure and diabetes. To reduce your risk: You can feel better when you have heart failure by taking your medicines as directed, having a healthy lifestyle, and avoiding things that make heart failure worse. Know what things you can do every day to stay healthy, what symptoms to watch for, and when to call a doctor. Avoid triggers, such as too much salt (sodium) and certain medicines, that can cause sudden heart failure. One Man's Story: "I was having a lot of trouble getting enough sleep. I was snoring so bad that my wife was sleeping in another room. I'd wake up 7 times a night. Sometimes I'd wake up gasping for breath. The next day I'd be so tired that I'd fall asleep while doing my woodworking in the garage. And I was really fuzzy-headed. I couldn't remember anything. "I thought it might be my heart failure. So I decided to talk to my doctor about it, and he suggested a sleep study. I found out that I have sleep apnea. I haven't been getting enough oxygen because of it. He put me on a CPAP machine at night. I've used it for the past 4 months. "It took a little time to get used to sleeping with a mask. But I'm sleeping much better. Now if I wake up, it's only once, and I go right back to sleep. I feel so much better during the day."—Pete This story is based on information gathered from many people living with heart failure. Many people with heart failure have trouble sleeping. Your doctor may be able to find out what is causing your sleep problems and help you get a good night's sleep. Most people with heart failure can still have an active and safe sex life. Talk with your doctor if you have concerns about having sex. Unfortunately, sexual problems are common. Your interest may drop, or you may have shortness of breath or other symptoms that limit your ability to have sex. Men may have erection problems. Talk to your doctor. You can get help for erection problems or other sexual troubles. It can be rewarding to help a loved one with heart failure. But it's also a lot of work. And it can be hard emotionally. If you are taking care of a loved one, make sure that you also take care of yourself. This can mean taking breaks by getting help from family or friends. You also may be able to use respite care. These services provide someone who will stay with your loved one while you get out of the house for a few hours. Heart failure brings big changes to your life. You may struggle with sadness and worry. You may wonder if you'll still be able to enjoy your life. Coping with your feelings and seeking help when you need it can help you live better with heart failure. Heart failure can be hard on your emotions. You may feel depressed that you can't do some of the things you used to do. You may worry about your future. And symptoms of heart failure, such as shortness of breath, can make this anxiety worse. These feelings are common. Talk to your doctor if you have symptoms of depression or are worried a lot. Depression and anxiety can be treated with counseling and medicine. You also can help yourself feel better by changing your "self-talk." Those are the things you tell yourself about how you're coping. Negative thoughts can make you feel bad. Changing the way you think can change the way you feel. One Woman's Story: "I would sit at my kitchen table and feel I was in this cloud of dread. I didn't feel like me. I felt like, 'I'm never going to be me again.' "—Joan Read about how Joan got help for depression and anxiety. For more information, see: The challenges of living with heart failure can increase your stress. And stress can make living with heart failure even harder. Stress also can disturb your sleep and make depression and anxiety worse. Explore ways to relax and manage stress to help your body, mind, and spirit. Emotional support from friends and family can help you cope with the struggles of heart failure. You might want to think about joining a heart failure support group. Ask your doctor about the types of support that are available where you live. Meeting other people with the same problems can help you know you're not alone. If you're shy or aren't a joiner, you can look at an online support group. Even though people online aren't talking face-to-face, they're sharing their feelings and creating a community. You probably will need to take several medicines to treat heart failure, even if you don't have symptoms yet. Medicines don't cure heart failure. But they can help your heart work better and improve symptoms. It's very important to take your medicines exactly as your doctor says. If you don't, your heart failure may get worse or you may get sudden heart failure. The medicines you take will depend on the type of heart failure you have. Some of the medicines treat the heart's pumping problems (systolic heart failure), while others treat problems with filling (diastolic heart failure). The most commonly used medicines are listed below. You also may take other medicines for health problems that can cause heart failure or for problems caused by heart failure. Talk to your doctor before you take any over-the-counter medicines. Some of them might make your symptoms worse. Surgeries for heart failure include: Cardiac resynchronization therapy (CRT) uses a biventricular pacemaker, which makes the heart's lower chambers (ventricles) pump together. This can help your heart pump blood better. This type of pacemaker can help you feel better so you can be more active. It also can help keep you out of the hospital and help you live longer. If you get a pacemaker, you have to be careful not to get too close to some devices with strong magnetic or electrical fields. These include MRI machines, battery-powered cordless power tools, and CB or ham radios. But most everyday appliances are safe. A pacemaker may be used alone or along with an implantable cardioverter-defibrillator (ICD) for heart failure. One Woman's Story: Getting a pacemaker has "made all the difference in the world. I could work in my yard and walk my dog."—Joyce Read about how a pacemaker helped Joyce be more active. Implantable cardioverter-defibrillators (ICDs) can prevent sudden death from an abnormal heart rhythm and may help you live longer. An ICD checks the heart for very fast and deadly heart rhythms. If the heart goes into one of these rhythms, the ICD shocks it to stop the deadly rhythm and returns the heart to a normal rhythm. If you get an ICD, you have to be careful not to get too close to some devices with strong magnetic or electrical fields. These include MRI machines, battery-powered cordless power tools, and CB or ham radios. But most everyday appliances are safe. An ICD may be used alone or along with a pacemaker for heart failure. Ventricular assist devices (VADs), also known as heart pumps, may be placed into the chest to help the heart pump more blood. VADs can keep people alive until a donor heart is available for transplant. In some cases, VADs may also be used as an alternative to heart transplant for long-term treatment. VADs are used in people who have severe heart failure. You may still hear about supplements that might improve heart failure symptoms. But no supplement or vitamin has been shown definitely to relieve heart failure or help you live longer. Examples include coenzyme Q10, fish oil, and hawthorn. Talk to your doctor before you take any over-the-counter medicine or supplement. They are used along with medical treatments for heart failure, not instead of treatment. As your heart failure gets worse, you may want to think about palliative care. It's a kind of care for people who have illnesses that don't go away and often get worse over time. It's different than care to cure your illness. But some people combine both types of care. If you are interested in palliative care, talk to your doctor. He or she may be able to manage your care or refer you to a doctor who specializes in this type of care. For more information, see the topic Palliative Care. Heart failure tends to get worse over time. So you need to decide what kind of care you want at the end of your life. It can be hard to have talks with your doctor and family about the end of your life. But making these decisions now may bring you and your family peace of mind. Your family won't have to wonder what you want. And you can spend your time focusing on your relationships. You will need to decide if you want life-support measures if your health gets very bad. An advance directive is a legal document that tells doctors how to care for you at the end of your life. This care includes electronic devices that are used for heart failure, such as pacemakers. You also can say where you want to have care. And you can name someone who can make sure your wishes are followed. \|American Heart Association (AHA)\| \|7272 Greenville Avenue\| \|Dallas, TX 75231\| Visit the American Heart Association (AHA) website for information on physical activity, diet, and various heart-related conditions. You can search for information on heart disease and stroke, share information with friends and family, and use tools to help you make heart-healthy goals and plans. Contact the AHA to find your nearest local or state AHA group. The AHA provides brochures and information about support groups and community programs, including Mended Hearts, a nationwide organization whose members visit people with heart problems and provide information and support. CardioSmart is an online education and support program that can be your partner in heart health. This website engages, informs, and empowers people to take part in their own care and to work well with their health care teams. It has tools and resources to help you prevent, treat, and/or manage heart diseases. You can set health and wellness goals and track your progress with online tools. You can track your weight, waist measurement, blood pressure, and activity. You can use calculators to help you find your body mass index (BMI) and check your risk for heart problems. You can search for a cardiologist. And you can find medicine information and prepare for your next appointment. Also, you can join online communities to connect with peers and take heart-healthy challenges. CardioSmart was designed by cardiovascular professionals at the American College of Cardiology, a nonprofit medical society. Members include doctors, nurses, and surgeons. \|Heart Failure Society of America\| \|Court International, Suite 240 S\| \|2550 University Avenue West\| \|Saint Paul, Minnesota 55114\| The Heart Failure Society of America provides information and education for people with heart failure and their families. The Web site has education modules designed to help people with heart failure, their loved ones, and individuals at risk to work better with their doctors or nurses. \|Heart Rhythm Society\| \|1400 K Street NW\| \|Washington, DC 20005\| The Heart Rhythm Society provides information for patients and the public about heart rhythm problems. The website includes a section that focuses on patient information. This information includes causes, prevention, tests, treatment, and patient stories about heart rhythm problems. You can use the Find a Specialist section of the website to search for a heart rhythm specialist practicing in your area. \|National Heart, Lung, and Blood Institute (NHLBI)\| \|P.O. Box 30105\| \|Bethesda, MD 20824-0105\| The U.S. National Heart, Lung, and Blood Institute (NHLBI) information center offers information and publications about preventing and treating: \|National Institutes of Health Senior Health\| \|9000 Rockville Pike\| \|Bethesda, MD 20892\| \|Phone:\|\|1-800-222-2225 Aging Information Center\| This website for older adults offers aging-related health information. The website's senior-friendly features include large print, simple navigation, and short, easy-to-read segments of information. A visitor to this website can click special buttons to hear the text aloud, make the text larger, or turn on higher contrast for easier viewing. The site was developed by the National Institute on Aging and the National Library of Medicine, both part of the National Institutes of Health (NIH). NIHSeniorHealth features up-to-date health information from NIH. Also, the American Geriatrics Society provides independent review of some of the material found on this website. - U.S. Department of Health and Human Services (2008). 2008 Physical Activity Guidelines for Americans (ODPHP Publication No. U0036). Washington, DC: U.S. Government Printing Office. Available online: http://www.health.gov/paguidelines/guidelines/default.aspx. - Coenzyme Q10 (2006). Medical Letter on Drugs and Therapeutics, 48(1229): 19–20. Other Works Consulted - Allen LA, et al. (2012). Decision making in advanced heart failure: A scientific statement from the American Heart Association. Circulation, 125(15): 1928–1952. - Drugs for treatment of chronic heart failure (2009). Treatment Guidelines From The Medical Letter, 7(83): 53–56. - Hunt SA, et al. (2009). 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults. Circulation, 119(14): e391–e479. - Levine GN, et al. (2012). Sexual activity and cardiovascular disease: A scientific statement from the American Heart Association. Circulation, 125(8): 1058–1072. - McKelvie R (2011). Heart failure, search date August 2010. BMJ Clinical Evidence. Available online: http://www.clinicalevidence.com. - Pina IL, et al. (2003). Exercise and heart failure: A statement from the American Heart Association Committee on Exercise, Rehabilitation, and Prevention. Circulation, 107(8): 1210–1225. - Riegel B, et al. (2009). State of the science. Promoting self-care in patients with heart failure. A scientific statement from the American Heart Association. Circulation, 120(12): 1141–1163. - Schocken DD, et al. (2008). Prevention of heart failure: A scientific statement from the American Heart Association Councils on Epidemiology and Prevention, Clinical Cardiology, Cardiovascular Nursing, and High Blood Pressure Research; Quality of Care and Outcomes Research Interdisciplinary Working Group; and Functional Genomics and Translational Biology Interdisciplinary Working Group. - Smith SC, et al. (2011). AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: A guideline from the American Heart Association and American College of Cardiology Foundation. Circulation, 124(22): 2458–2473. Also available online: http://circ.ahajournals.org/content/124/22/2458.full. - Somers VK, et al. (2008). Sleep apnea and cardiovascular disease: An American Heart Association/American College of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing in collaboration with the National - Weintraub NL, et al. (2010). Acute heart failure syndromes: Emergency department presentation, treatment, and disposition: Current approaches and future aims. A scientific statement from the American Heart Association. Circulation, 122(19): 1975–1996. \|Primary Medical Reviewer\|\|Rakesh K. Pai, MD, FACC - Cardiology, Electrophysiology\| \|Specialist Medical Reviewer\|\|Stephen Fort, MD, MRCP, FRCPC - Interventional Cardiology\| \|Last Revised\|\|May 8, 2013\| Last Revised: May 8, 2013 To learn more visit Healthwise.org © 1995-2013 Healthwise, Incorporated. Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.	2	7	4	1	2	0.981502	7	5,639
Telemedicine, as defined by the World Health Organization, is “The delivery of healthcare services, where distance is a critical factor, by all healthcare professionals using information and communication technologies for the exchange of valid information for diagnosis, treatment and prevention of disease and injuries, research and evaluation, and for the continuing education of healthcare providers, all in the interests of advancing the health of individuals and their communities.”1 Telemedicine is not new; the military and space industries have used it since the 1960s.2 Alaska initiated its 1998 Telehealth Solutions program3 to improve access to care in a state with too few physicians and more than 600,000 square miles of territory. Medicare began its telehealth demonstration project in Alaska and Hawaii in the early 2000s. According to the Office of Inspector General, Medicare spending for telehealth increased from $61,302 in 2001 to $17,601,996 in 2015.4 Telemedicine has grown rapidly because it offers the benefits of increased access, cost effectiveness, improved quality, and convenience for patients.5 Within telemedicine, the term “originating site” refers to the location of the patient, while the term “distant site” refers to the location of the specialist or remote diagnostic testing facility with no physical contact with the patient. When telemedicine is applied to remote imaging of diabetic patients to assess diabetic retinopathy, the retinal camera is located at the “originating site” while the ophthalmologists or optometrist reading the digital images is at the “distant site.”6 Medicare will pay for telehealth services when an interactive telecommunications system is used and sometimes when a “store and forward” system is used, whereby images or video are taken, stored, and viewed later by a health care practitioner.4 In 2011, the AMA added 2 telemedicine codes, 92227 and 92228, to CPT to “… meet the needs of diabetic retinopathy screening programs which provide remote imaging and data submission to a centralized reading center.” The codes are similar but differ in important ways. Code 92227 is remote imaging for detection of retinal disease, such as retinopathy in a patient with diabetes, with analysis and report under physician supervision, unilateral or bilateral. Code 92228 is remote imaging for monitoring and management of active retinal disease, such as diabetic retinopathy, with physician review, interpretation, and report, unilateral or bilateral. In the first code, emphasis is on detection of retinal disease, while the second code emphasizes management of retinal disease. Code 92227 is screening, and 92228 is evaluation and management of chronic eye disease. Significantly, 92227 is performed under physician supervision but omits an interpretation, while 92228 requires “interpretation and report.” In 2019, CPT added 3 new procedure codes to report various aspects of remote physiologic monitoring: - 99453: Remote monitoring of physiologic parameter(s) (eg, weight, blood pressure, pulse oximetry, respiratory flow rate), initial; set-up and patient education on use of equipment. - 99454: Remote monitoring of physiologic parameter(s) (eg, weight, blood pressure, pulse oximetry, respiratory flow rate), initial; device(s) supply with daily recording(s) or programmed alert(s) transmission, each 30 days. - 99457: Remote physiologic monitoring treatment management services, 20 minutes or more of clinical staff/physician/other qualified health care professional time in a calendar month requiring interactive communication with the patient/caregiver during the month. Remote physiologic monitoring treatment management services are provided when clinical staff members, physicians, or other qualified health care professionals use the results of remote physiologic monitoring to manage a patient under a specific treatment plan. To report remote physiologic monitoring, the device used must be a medical device as defined by the FDA, and service must be ordered by a physician or other qualified health care professional. The addition of these CPT codes was hailed as a positive move that expands telehealth for the Medicare program.7 Medicare administrator Seema Verma said, “There has been a telehealth benefit mostly for rural providers, but access to care is not just a rural issue, it’s something that patients struggle with across the country.”8 CMS says, “Studies note that remote patient monitoring has a positive impact on patients as it allows patients to share more live-time data with their providers and caregivers, which will lead to more tailored care and better health outcomes.”8 CMS also says, “It would also allow greater ability for Medicare Advantage enrollees to receive telehealth from places including their homes, rather than requiring them to go to a health care facility to receive telehealth services.”8 Remote physiologic monitoring of intraocular pressure (IOP) has the potential to help ophthalmologists and optometrists manage glaucoma better through closer monitoring of high-risk patients and to alert them to inadequate treatment before extensive damage of the optic nerve occurs. For most patients, IOP measurements during periodic eye exams provide sparse data that may be misinterpreted by the physician due to diurnal variability and unreliable patient compliance with medications. More frequent IOP measurements taken by the patient at home and periodically transmitted to the physician fit squarely within the meaning of remote physiologic monitoring. A device intended for this purpose, and FDA cleared, is the Icare Home Tonometer (Figure 1). It is a handheld device that a trained and certified patient can use to safely and reliably measure IOP at home without local anesthesia. Compared with Goldmann applanation tonometry, Icare Home measurements are comparable.9 The favorable Medicare coverage and payment policy for remote physiologic monitoring offer a new avenue to provide better eye care to patients. GP - World Health Organization. Telemedicine opportunities and developments in member states. 2010. https://www.who.int/goe/publications/goe_telemedicine_2010.pdf . Accessed July 12, 2019. - Wicklund E. Is there a difference between telemedicine and telehealth? PHI in the news. June 3, 2016. https://www.phi.org/news-events/1021/is-there-a-difference-between-telemedicine-and-telehealth . Accessed July 12, 2019. - Schnatz J. Alaska’s Telehealth Solutions programme. October 9, 2018. https://www.centreforpublicimpact.org/case-study/alaskas-telehealth-solutions-programme/ . Accessed July 12, 2019. - Jarmon GL. CMS paid practitioners for telehealth services that did not meet Medicare requirements. April 2018. https://oig.hhs.gov/oas/reports/region5/51600058.pdf . Accessed July 12, 2019. - American Telemedicine Association. Telehealth basics. https://www.americantelemed.org/resource/why-telemedicine/ . Accessed July 12, 2019. - CMS Medicare Learning Network. Telehealth services. January 2019. https://www.cms.gov/outreach-and-education/medicare-learning-network-mln/mlnproducts/downloads/telehealth-services-text-only.pdf . Accessed July 12, 2019. - Centers for Medicare & Medicaid Services. CMS finalizes policies to bring innovative telehealth benefit to Medicare Advantage. Press release. April 5, 2019. https://www.cms.gov/newsroom/press-releases/cms-finalizes-policies-bring-innovative-telehealth-benefit-medicare-advantage . Accessed July 12, 2019. - Wicklund E. CMS to reimburse providers for remote patient monitoring services. mHealth Intelligence. November 2, 2018. https://mhealthintelligence.com/news/cms-to-reimburse-providers-for-remote-patient-monitoring-services . Accessed July 12, 2019. - Mudie LI, LaBarre S, Varadaraj V, et al. The Icare Home (TA022) study: performance of an intraocular pressure measuring device for self-tonometry by glaucoma patients. Ophthalmology. 2016;123:1675-1684.	3	8	12	0	0	0.396955	12	1,762
Dec 17, 2008. Neuropathy starts out with pain and tingling in your feet. It usually is present in both feet, which can help you distinguish it from. Talk to your doctor or diabetic educator about how to do this if you don't already know how. CURE FOR DIABETIC NEUROPATHY ]. other resources that may help you reverse diabetes. way lower limit! Cure For Diabetic Neuropathy A regarding fiber. Diabetic neuropathy is a complication of diabetes causing damage to the nerves. Learn the types of diabetic neuropathy and the pain it causes in the hips. @ Diabetic Proximal Neuropathy ★★ What Causes Diabetic Retinopathy The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days. Feb 27, 2015. Are you seeking treatment for diabetic neuropathy?. How Does Spinal Cord Stimulation Work to Relieve Chronic & Acute Neuropathy? Nov 22, 2016. Read here about the ayurvedic treatment for diabetic neuropathy. types of diabetic neuropathies and how you can diagnose and treat them. 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Counsellink insight vacations Oct 03, 2013 · How do you explain a deductible… in plain language? To add to the complexity, different cost-sharing arrangements may apply depending on different situations: Variable copays or coinsurance. The agent can explain co-insurance as well Flexible Spending Account (FSA) - This is a tax-advantaged account that allows you to pay for qualified medical expenses not covered by your bangladesh cricket team picture asia cup 2012 plan, such as copays, deductibles, coinsurance and certain services. Definition of copay under Obamacare. However, the ways in which they function are much deductibles and coinsurance explained synonym different. A copay after deductible is a flat fee arme anna quizlet anatomy you pay for medical service as part of a cost-sharing relationship in which you and your health insurance provider must pay for your medical expenses. Healthcare can be complicated, and extra costs can hide behind words like copays, coinsurance, and deductibles. But your plan might have its own deductible. Original Medicare Part A and Part B use deductibles and coinsurance rather than copayments to define the out-of-pocket amount, or cost-share that is the member’s responsibility. However, it doesn’t include insurance premiums. State Language Arts Tests For example, some patients will be required to copay $15 for a regular check up, whereas other patients might have a $20 (or a lower or higher) copay for deductibles and coinsurance explained synonym the same appointment; Deductible is the amount you must pay for a health care service before your health insurance plan begins. Take the word “deductible.” It’s not an intuitive word, and it’s specific to two of the least understandable subjects: taxes and. Before coinsurance kicks in, though, you have to meet your deductible. http://mashpeecommons.com/portionen-rechner-online Find descriptive alternatives for deductible Your deductible, coinsurance, and copay are considered out-of-pocket costs. Search. If these Medicare terms have you confused, here’s a primer, plus the Medicare costs for 2020. Another example of different deductibles on one policy trellis d armature definition is if you have an endorsement or rider on your policy. As you read about your insurance deductibles, co-pays, coinsurance and out-of-pocket maximums, you’ll want to know what each of these mean. Deductibles, coinsurance, copays and out-of-pocket maximums are the basic elements to any health care plan. Synonyms for deductibles in Free Thesaurus. What is a deductible? To sum up, you will have to pay a certain percentage of the bill every time. 39033 morningside dr Shoucheng Zhang Stanine and synonym explained deductibles coinsurance Dec 21, 2016 · Medicare Part D Prescription Drug Plans are also offered by private insurance companies approved by Medicare. Copay After Deductible: Everything You Need to Know. camogrlxiv GO. OOPM = Copayments + Deductible + Coinsurance. $1340 per spell of illness.. In other words, they are health care expenses that you are responsible for. High Deductible Health Plan vs PPO (HSA Explained). Mar 07, 2017 · What is the difference between a deductible, coinsurance, and copayment? For example, if your coinsurance is 20 percent, you pay 20 percent of the cost of your covered medical bills Synonyms for coinsurance in Free Thesaurus. deductibles and coinsurance explained synonym Health insurance can be complicated, but it doesn't have to be. a mechanism where the insurer agrees to give the insured a reduced rate IF the insurance carries a specific percentage of insurance to value of the property Deductible [glossary] (if your plan has one), deductibles and coinsurance explained synonym the amount you pay for each prescription is either: A Copayment. The agent can explain co-insurance as well But employees accustomed to thinking a doctor's visit costs a $15 co-payment are in for sticker shock once they start writing checks for deductibles.Harris Interactive conducted a 2005 telephone poll of 2,000 adults covered by employer-sponsored health care …. For 2016, it was $6,850 Synonyms for deductible at Thesaurus.com with free online thesaurus, antonyms, and definitions. top 10 best science project ideas miss paraply newsea hello glory series 13 leg	2	6	1	0	0	0.330081	1	965
If you’re experiencing left hip pain and searching for information about its specific ICD-10 code, you’ve come to the right place. In this article, I’ll provide a clear explanation of what an ICD-10 code is, how it can be used to identify and classify medical conditions, and the specific code associated with left hip pain. ICD-10 stands for International Classification of Diseases, 10th Revision. It is a coding system used by healthcare professionals worldwide to record diagnoses and medical procedures. Each condition or symptom has its own unique code in the ICD-10 system, which allows for standardized documentation and easier sharing of information between healthcare providers. When it comes to left hip pain, the corresponding ICD-10 code is M25.551. This code specifically refers to “Pain in the left hip.” By using this code, healthcare providers can accurately document your condition and ensure that it’s properly recorded in your medical records. Having a standardized coding system like ICD-10 helps streamline communication among healthcare professionals and ensures that accurate information is captured for billing purposes as well as research and statistical analysis. So let’s dive deeper into the specifics of left hip pain and how it can be identified using the ICD-10 coding system. Understanding ICD-10 Codes ICD-10 codes play a crucial role in the healthcare industry, providing a standardized system for classifying and coding medical diagnoses, procedures, and symptoms. These codes are used by healthcare providers, insurance companies, researchers, and policymakers to track diseases, analyze trends, and ensure accurate billing and reimbursement. What is ICD-10? ICD-10 stands for the International Classification of Diseases, Tenth Revision. It was developed by the World Health Organization (WHO) as a replacement for the previous version, ICD-9. The transition from ICD-9 to ICD-10 took place on October 1st, 2015. How do ICD-10 Codes Work? ICD-10 codes are alphanumeric codes that provide detailed information about a patient’s diagnosis or condition. Each code consists of up to seven characters and is organized into chapters based on specific body systems or conditions. - M25.551 – Pain in right hip - M25.552 – Pain in the left hip - M25.559 – Pain in the unspecified hip These codes not only describe the location of pain but also provide additional details such as laterality (right vs. left), severity, causal factors if known (e.g., traumatic injury), and more. Benefits of Using ICD-10 Codes The implementation of ICD-10 brought several benefits to the healthcare industry: - Increased Specificity: Compared to its predecessor, ICD-9, ICD-10 offers greater specificity in describing diagnoses and conditions. - Improved Data Analysis: The detailed nature of ICD-10 codes allows for better analysis of disease patterns and trends. - Enhanced Reimbursement Accuracy: Accurate coding helps ensure that healthcare providers receive proper reimbursement for their services. - International Standardization: Since it is used worldwide, ICD-10 facilitates consistent reporting and comparison of health data across countries. Icd 10 Code for Left Hip Pain While the benefits of ICD-10 are significant, there are also challenges associated with its implementation: - Training and Education: Healthcare professionals need to receive comprehensive training to understand the intricacies of ICD-10 coding. - Increased Code Complexity: The expanded code set in ICD-10 requires coders to navigate a larger number of codes, which can be time-consuming and prone to errors. - Transition Costs: Transitioning from ICD-9 to ICD-10 involves significant costs for healthcare organizations, including software updates and staff training. In conclusion, understanding ICD-10 codes is essential for healthcare professionals and stakeholders. These codes provide a standardized system for accurately documenting diagnoses and conditions, enabling efficient data analysis and reimbursement processes. Despite the challenges associated with their implementation, the benefits of using ICD-10 far outweigh the initial hurdles. Tech expert fresh from the Australian Coast. Been in the tech industry more than 9 years, as part of a Business Growth Group. His out of office days are 100% for freestyle surfing and waves chasing.	4	2	0	0	4	0.864853	4	897
Protein C deficiency is a disorder of blood related to a disturbance in the anticoagulation mechanism and can precipitate thrombotic complications such as deep vein thrombosis (DVT) and pulmonary embolism. Protein C deficiency can be either congenital or acquired. Unlike other disorders, protein C deficiency does not present itself clinically. The complications that follow the disorder can be identified by their typical signs and symptoms. Neonates with severe type I homozygous protein C deficiency typically present with neonatal purpura fulminans (NPF), a life-threatening condition characterized by appearance of purple skin lesions due to generalized microvascular thrombosis occurring shortly after birth . Heterozygous protein C deficiency is associated with VTE and warfarin-induced skin necrosis (WISN). WISN is a thrombotic complication characterized by tissue necrosis resulting from infarction of the tissue that is devoid of blood supply. It develops in patients after initial administration of warfarin to control thrombosis . DVT, a commonly developed complication in patients with protein C deficiency, accompanies symptoms such as pain, tenderness, swelling and discoloration of skin on the site where clots are present. If DVT invades circulation and enters the lungs, it can obstruct the pulmonary artery causing pulmonary embolism. Pulmonary embolism is a life-threatening complication that is characterized by shortness of breath (SOB), chest pain, chest tenderness, coughing, increased pulse, slight fever and dizziness. Other less common complications that might accompany protein C deficiency comprise thrombophlebitis, which is presented as redness on the site where the inflamed vein is present and cirrhosis. The classical clinical presentation of cirrhosis includes jaundice, ascites, edema, mental confusion and hematemesis. Entire Body System Protein C Deficiency by Drew Roby Purine nucleoside phosphorylas deficiency, adenosine deaminase deficiency, and protein C deficiency are genetic disorders that lead to the disabling of the immune system. [www-personal.umd.umich.edu] Individuals with Glut1 deficiency syndrome also develop varying degrees of cognitive impairment, which can range from mild learning disabilities to severe intellectual disability. [rarediseases.org] No intellectual disability or psychomotor developmental delay was demonstrated. The proband, the first child of nonconsanguineous parents, was born at 38 weeks and 4 days of gestation. [nature.com] Furthermore, their pregnancies may result in a live birth with multiple congenital malformations and/or mental disability secondary to an unbalanced chromosomal arrangement. [sjmms.net] - Congestive Heart Failure The risk factors include obesity, oral contraceptive use, varicose veins, infection, trauma, surgery, pregnancy, immobility, and congestive heart failure. [healthcentral.com] Risk Factors for DVT and PE Obesity Immobilization Surgery Hospitalization for medical illness Trauma Prolonged travel Cigarette smoking Advancing age (risk doubles for every decade of life) Pregnancy Chronic illnesses Congestive heart failure (CHF) Chronic [circ.ahajournals.org] Within a few hours the leg ecchymosis enlarged to a dark blue, painful hematoma. In the absence of clinical and laboratory signs of infection, a diagnosis of purpura fulminans—like syndrome was proposed. [nejm.org] Nausea during pregnancy Research published in the American Journal of Obstetrics and Gynecology concluded that pyridoxine can reduce the severity of nausea in early pregnancy. However, more high-quality studies are necessary to confirm this. [medicalnewstoday.com] He also suffered from nausea, vomiting and anorexia. The patient’s last defecation was in semi liquid jelly- like form. His past medical history was unremarkable and he had had no previous abdominal surgery. [ispub.com] One recurrent mutation and its relative risk for thrombosis in relatives were analyzed in 11 families. [ncbi.nlm.nih.gov] All cases of hereditary deficiency were asymptomatic with regard to thrombosis and none had a strong family history of thrombosis. [doi.org] Griffin, Activation-resistant homozygous protein C R229W mutation causing familial perinatal intracranial hemorrhage and delayed onset of thrombosis, Thrombosis Research, 143, (17), (2016). M. J. Manco-Johnson, L. Bomgaars, J. Palascak, A. [oadoi.org] Liver, Gall & Pancreas - Protein S Deficiency S Deficiencies, Protein S Deficiency, DEFIC PROTEIN S, PROTEIN S DEFIC, protein S deficiency, protein S deficiency (diagnosis), Protein S Deficiency [Disease/Finding], deficiency protein s, s protein deficiency, protein s deficiencies, protein s deficiency [fpnotebook.com] C deficiency disease Protein C deficiency disorder Protein C resistance Protein S deficiency disease Protein S deficiency disorder Prothrombin G20210A mutation Prothrombin gene mutation Resistance to activated protein C due to Factor V Leiden Thrombophilia [icd9data.com] My answer: Your physician may choose to double-check the diagnosis of protein C and protein S deficiency. [fritsmafactor.com] Hörnig- Franz, Neonatale Purpura fulminans Neonatal purpura fulminans, Monatsschrift Kinderheilkunde, 10.1007/s00112-009-2022-x, 157, 12, (1242-1245), (2009). [oadoi.org] Chan, Diagnosis and management of neonatal purpura fulminans, Seminars in Fetal and Neonatal Medicine, 16, 6, (318), (2011). [doi.org] References 1.Nalbandian R, Mader I, Barrett J, Pearce J, Rupp E: Petechiae, eccymoses and necrosis of skin induced by coumarin congeners, JAMA 192:107-112,1965 2. [jnma.com.np] It is characterized by thrombocytopenia, petechiae, and ecchymoses together with disseminated thrombosis of small vessels, resulting in tissue hypoperfusion, imminent peripheral gangrenes, and is associated with high incidence of amputations, skin grafts [signavitae.com] Radiotherapy-induced carotid stenosis is an exacerbating feature of stroke in patients with protein C deficiency. We suggest early carotid duplex sonography and survey of the coagulation profile to prevent a stroke in patients with NPC. [ncbi.nlm.nih.gov] Disorders of coagulation leading to thrombotic disorders are approximately 1% of all ischemic strokes and 4-8% of young strokes. [dx.doi.org] Most stroke cases do not require evaluation of coagulation, but hypercoagulability is a significant reason for unexplained strokes, especially for youth strokes. [omicsonline.org] Fecal transplant is used to treat gut infections and is now being studied as a treatment for obesity, urinary tract infections, irritable bowel syndrome and more. [nytimes.com] Diagnosis of protein C is based on identification of complications that follow the disorder, with the most important one being DVT. DVT is confirmed by complete medical history, clinical presentation and laboratory test results. The levels of D-dimer are determined while confirming DVT. D-dimer is a product formed by degradation of fibrin clot and its concentration in blood is directly related to DVT, with increased levels indicating DVT. Additional tests used to confirm DVT include venography and ultrasonography which further help in verify the presence of blood clots. In venography technique, detection of blood clots is achieved by injecting a dye in a large body vein and examining it under X-ray where the clot becomes visible . However, ultrasound is a preferred method as it is non-invasive. Computerized tomography (CT) and magnetic resonance imaging (MRI) may also be used to determine the presence and location of blood clots. Treatment is based on dissolving clots by anticoagulation therapy. Heparin and warfarin are commonly used anticoagulants to treat thrombosis that accompanies protein C deficiency . As described earlier, initial administration of warfarin may cause WISN. Neonatal purpura fulminans must be treated as emergency as it is a life threatening condition. It is typically attended by replacing protein C with normal plasma or purified concentrate and a anticoagulation therapy with heparin . The prognosis is largely affected by the presence of other thrombotic events. The risk of developing VTE in patients with protein C deficiency is increased by about 12.5 folds . In a recent case study, the recurrence rate of VTE was found to be approximately 60% . Furthermore, the risk of worsening VTE has also been documented in pregnant women following birth. Protein C is encoded by the PROC gene. Mutations in the PROC gene change the normal structure of protein C and disrupt its anticoagulant function causing protein C deficiency . However, certain non-genetic factors may also increase the risk of developing mild acquired protein C deficiency such as ageing, surgery, pregnancy and immobility particularly in patients with a family history of thrombosis. As described earlier, protein C in its active form (aPC) serves to regulate the blood clotting mechanism by exerting anticoagulant activity through a series of activation and inactivation cycles. Therefore, deficit of protein C in the blood leads to irregulated anticoagulation due to the disturbance in the balance among clotting factors. This results in impediment in blood circulation and thrombophilia. Abnormal blood clots formed this way can cause further complications. Deep vein thrombosis (DVT) is one such complication that arises from deficiency of protein C. DVT is a type of blood clot that is formed in the deep veins of the body such as those of arms and legs. A DVT carries the likelihood for traveling through the blood stream and blocking an artery in the lungs, causing a life threatening condition called pulmonary embolism. The genetic pathogenesis of protein C deficiency lies in mutations in genes of chromosome 2. On the basis of the genetic mutations, protein C deficiency has been classified as type I and type II. Phenotypically, the condition is referred to as homozygous if an identical pair of mutated genes responsible for controlling protein C synthesis is inherited in an individual. Alternatively, when only one mutated gene is inherited, the condition is termed as heterozygous. Most patients with severe congenital protein C deficiency carry a homozygous defective gene and present with clinical symptoms in the initial days of life. In patients displaying a heterozygous cause, symptoms often develop later in life . Type I protein C deficiency is characterized by reduced synthesis of protein C in the blood and serum levels of protein C are found to be lowered by half compared to those of normal patients. Type II protein C deficiency is thought to result from point mutations of the protein C gene and indicates normal levels of protein C with diminished functional activity. Type I is the most common type of deficiency between the two forms . In patients with a family history of protein C deficiency or thrombosis, appropriate preventive measures must be taken. To prevent the development of a thromboembolic disease in patients with heterozygous protein C deficiency, thromboprophylaxis must be performed before surgery, during trauma and air travel. If the patient is pregnant, estrogen-containing hormonal therapy may also be used. Prevention of WISN is not inevitable in individuals with protein C deficiency. WISN can be avoided by administering small doses of warfarin and by concomitant use of another parenteral anticoagulant for a minimum of 5 days. Protein C deficiency is a disorder characterized by insufficient levels of protein C in the blood, a vitamin K-dependent circulating blood glycoprotein involved in the regulation of blood coagulation. Normally, protein C is synthesized in the liver and released into the blood in its inactive zymogenic form. In the blood, protein C is converted to its active form called activated protein C (aPC) by thrombin. The activation occurs on the vessel endothelium and is catalyzed by a thrombin-thrombomodulin complex . Once activated, the aPC binds and forms a complex with protein S, another vitamin k-dependent protein. In the bound form, the activated protein C inactivates factors Va and VIIIa which further results in inactivation of clotting factor X. As a result, the enzyme thrombin, which is responsible for activating fibrin clot formation, remains inhibited and consequently the anticoagulation mechanism is balanced . Deficiency of protein C leads to unregulated anticoagulation resulting in thrombophilia and increased risk of deep vein thrombosis (DVP) as well as pulmonary embolism . aPC also provides cytoprotective and antiinflammatory functions through protein C receptor and protease-activated receptor-1 (PAR-1) found in the vascular endothelium . Different cases of protein C deficiency vary widely, from very mild to extremely severe. The majority of patients with mild protein C deficiency hardly develop abnormal blood clots and lead a normal life. Infants suffering from severe protein C deficiency develop purpura fulminans shortly after birth . Purpura fulminans is a fatal disorder of the blood clotting mechanism characterized by formation of blood clots inside blood vessels. The presence of numerous blood clots hinders the normal flow of blood through blood vessels and continuous blood clotting uses up all available blood clotting proteins. Consequently, abnormal bleeding ensues from different parts of the body which appears clinically on the skin in the form of purple lesions. Protein C deficiency can either be congenital or acquired. The congenital form can be categorized as type I protein C deficiency and type II protein C deficiency. In type I, mutations in the PROC gene result in reduced synthesis of protein C. Type I is the most common type of protein C deficiency. In type II protein C deficiency, mutations in the PROC gene cause formation of an abnormal protein C that is insufficient as a functional protein and fails to regulate blood clotting. Protein C deficiency does not present with definite clinical symptoms. However, the complications that ensue the disorder can be recognized and diagnosis can be made accordingly. The patient's disease history, family history and laboratory data analysis can aid in establishing accurate diagnosis and designing appropriate treatment regimen. Treatment is mostly aimed at dissolving clots with anticoagulant therapy. Protein C deficiency is a disorder characterized by irregulated blood anticoagulation due to deficiency of protein C or presence of abnormal, non-functional protein C in the blood. Protein C is normally found in the blood and plays a vital role in preventing the formation of abnormal blood clots and promoting a smooth blood flow through the blood vessels. Two types of the disorder have been recognized; congenital and acquired. Congenital protein C deficiency has been further classified as type I and type II. Type I protein C deficiency is characterized by reduced synthesis of protein C by the body which leads to abnormally low levels of protein C in the blood. Type II is associated with the presence of abnormal functional protein C. Acquired protein C deficiency occurs due to other diseases that include severe infection, disseminated intravascular coagulation, liver disease, vitamin K deficiency, warfarin therapy, chemotherapeutic drugs and hemopoietic stem cell transplantation. The disorder itself does not show specific symptoms. However, the complications arising from protein C deficiency are presented clinically. One such complication is purpura fulminans that occurs in neonates few hours after birth with severe congenital protein C deficiency. Purpura fulminans is a fatal condition in which clots are formed throughout the body and are visible as purple skin lesions on the skin. Other manifestations of the disease include deep vein thrombosis (DVT), which is the formation of blood clot in one of the deep veins of the body as well as pulmonary embolism, which is the obstruction of the lung artery caused by DVT. The disorder is diagnosed by evaluation of symptoms, medical history and assessment of protein C levels. Accurate diagnosis is highly important as treatment based on incorrect diagnosis can further complicate the illness. Venography, ultrasound, CT scan and MRI scan are commonly used to detect presence and location of blood clots. In individuals with a family history of thrombotic diseases, preventive treatment is recommended especially during surgery and in pregnant patients. Treatment of the disorder is based on replacement of protein C with fresh frozen plasma or plasma concentrate and anticoagulant therapy with heparin and warfarin. - Dahlback B. Advances in understanding pathogenic mechanisms of thrombophilic disorders. Blood. 2008;112(1):19-27. - Mosnier LO, Zlokovic BV, Griffin JH. The cytoprotective protein C pathway. Blood. 2007;109(8):3161-3172. - Heit JA. Predicting the risk of venous thromboembolism recurrence. Am J Hematol. 2012;87 Suppl 1:S63-S67. - Dreyfus M, Masterson M, David M, et al. Replacement Therapy with Monoclonal Antibody Purified Protein C Concentrate in Newborns with Severe Congenital Protein C Deficiency. Seminars in Thrombosis and Hemostasis. 1995;21(4):371-381. - Bertina RM, Koeleman C, Koster T, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature. 1994;369:64–67. - Khan S, Dickerman JD. Hereditary thrombophilia. Thromb J. 2006;12;4:15. - Tait RC, Walker ID, Reitsma PH, et al. Prevalence of protein C deficiency in the healthy population. Thromb Haemost. 1995;73(1):87-93. - Mateo J, Oliver A, Borrell M, Sala N, Fontcuberta J. Laboratory evaluation and clinical characteristics of 2,132 consecutive unselected patients with venous thromboembolism--results of the Spanish Multicentric Study on Thrombophilia (EMET-Study). Thromb Haemost. 1997;77(3):444-451. - Moritz B, Rogy S, Tonetta S, Schwarz HP, Ehrlich H and the CEPROTIN Study Group. Efficacy and Safety of a High Purity Protein C Concentrate in the Management of Patients with Severe Congenital Protein C Deficiency. In: Scharrer I, Schramm W, ed. 31st Hemophilia Symposium Hamburg 2000. Berlin Heidelburg: Springer-Verlag. 2002;101-109. - Marciniak E, Wilson HD, Marlar RA. Neonatal purpura fulminans: a genetic disorder related to the absence of protein C in blood. Blood. 1985;65(1):15-20. - Reitsma PH, Bernardi F, Doig RG, et al. Protein C deficiency: a database of mutations, 1995 update. Thromb Haemost. 1995;73(5):876-889. - Brouwer JL, Lijfering WM, Ten Kate MK, et al. High long-term absolute risk of recurrent venous thromboembolism in patients with hereditary deficiencies of protein S, protein C or antithrombin. Thromb Haemost. 2009;101(1):93-99. - Marciniak E, Wilson HD, Marlar RA, et al. Neonatal purpura fulminans: a genetic disorder related to the absence of protein C in blood. Blood. 1985; 65(1):15-20. - Faraci PA, Deterling RA Jr, Stein AM, et al. Warfarin induced necrosis of the skin. Surg Gynecol Obstet. 1978;146(5):695-700. - Michiels JJ, Hamulyak K. Laboratory diagnosis of hereditary thrombophilia. Semin Thromb Hemost. 1998;24(4):309-320. - Schramm W, Spannagl M, Bauer KA, et al. Treatment of coumarin-induced skin necrosis with a monoclonal antibody purified protein C concentrate. Arch Dermatol. 1993;129(6):753-756. - Dreyfus M, Magny JF, Bridey F, et al. Treatment of homozygous protein C deficiency and neonatal purpura fulminans with a purified protein C concentrate. N Engl J Med. 1991;325(22):1565-1568.	2	6	0	0	1	0.924802	1	4,544
Borrelia Species Pcr Results Borrelia species DNA may occasionally be detected in the blood by PCR, but a negative PCR test is of no value in excluding localised Lyme disease. The overall sensitivity of PCR on a skin biopsy of an EM or ACA rash is around 50% and is limited by the chance of a single biopsy hitting a site with a significant number of organisms. In neurological Lyme disease involving the CNS, up to 10% of cases may be PCR positive on a CSF sample a negative PCR result does not exclude the diagnosis. Synovial fluid may be positive by PCR in up to 50% of cases. A negative result does not exclude the diagnosis. Investigation Of Suspected Lyme Disease Erythema migrans is a clinical diagnosis and does not require confirmation by laboratory testing. Lyme disease is not a notifiable disease so there is no statutory requirement to notify clinically suspected cases to the local Health Protection Team. The 2018 NICE Lyme disease guideline provides detailed advice about when a diagnosis of Lyme disease should be suspected and about which tests to use and when. The NICE Lyme disease guideline also contains a useful summary diagram of the routine serological testing recommendations for Lyme disease. Getting Tested For Lyme Disease Lyme disease testing is usually ordered by a doctor and is used when there are signs or symptoms consistent with Lyme disease. A blood sample can be drawn in a doctors office or other medical setting. If a test of cerebrospinal fluid is needed, an outpatient procedure called a lumbar puncture can be done in a hospital. Samples are then analyzed in a credentialed laboratory. Read Also: How Fatal Is Lyme Disease Sample Types For Lyme Disease Testing For routine Lyme disease serological testing, you must send a serum sample . For testing for neurological Lyme disease, you must send paired CSF and serum samples taken on the same day. If possible, please provide CSF cell count and total albumin, IgG and IgM values. If albumin, IgG and IgM measurements are not available, RIPL will make arrangements for these measurements at additional cost. PCR testing is available. We recommend that specialists call RIPL to discuss appropriate sample types for PCR. These may include joint fluid, biopsy tissue, CSF and EDTA plasma. Please submit biopsies as fresh tissue in a sterile container, ideally with a drop of sterile saline to prevent the tissue drying out. T Cells B Cells And Your Immune System Your immune system is a complex network of cells, chemicals, and organs that work together to help fight off harmful microorganisms like viruses or bacteria, known as pathogens. Antigens are proteins that are found on the surface of pathogens. When your immune system doesnt recognize a certain substance, the antigens on the pathogen cause your immune system cells to produce antibodies to fight it off. This is called an immune response. The immune system is composed of two main types of Lymphocytes, or white blood cells: T cells and B cells. T cells and B cells work together to recognize antigens, or foreign substances. Together they are responsible for your adaptive immunity. B cells are responsible for making antibodies that can destroy foreign substances. There are two different types of T cells, however. Helper T-cells stimulate B-cells to make antibodies, and help develop the other types of T-cells Killer T-cells. These Killer T-cells kill cells that have been infected by a foreign pathogen. During an immune response to a foreign antigen, B cells begin to secrete antibodies. The first antibodies it secretes are called IgM . After more exposure to the antigen, B-cells then begin to produce IgG antibodies . Also Check: Is Lyme Disease A Disability Finding The Right Lyme Disease Test Symptoms of Lyme disease can mimic a wide range of illnesses, which can cause tick-borne infections to go misdiagnosed for long periods of time. Laboratory testing is vital for confirming a diagnosis so that people can get the treatment that they need. However, it can be difficult to find the testing and care you need after potential infection of Lyme disease. Not all Lyme testing is created equal. For example, the CDC-recommended two-tiered testing is notoriously unreliable, as many commercially available tests are not always sensitive enough to detect active infections. IGeneX tests, on the other hand, provide higher sensitivity testing to detect the bacteria that causes Lyme and other tick-borne diseases. IGeneX test panels contain tests designed to detect IgM or IgG antibodies, meaning they can detect disease at multiple stages. Serological Testing Of Csf For The Diagnosis Of Neurological Lyme Disease Serological testing for neurological Lyme disease is based on demonstrating intrathecal synthesis of Borrelia-specific antibodies in CSF. For laboratory testing for neurological Lyme disease, IgG ViraChip® serology assays are performed on CSF and paired serum and the results compared. CSF samples must be tested in parallel with a contemporaneous serum sample and albumin and total IgG levels compared between the 2 sample types to produce a meaningful result. For necessary sample types and volumes see Sample types for Lyme disease testing. Recommended Reading: How To Test Ticks For Lyme Disease Key Points To Remember - Most Lyme disease tests are designed to detect antibodies made by the body in response to infection. - Antibodies can take several weeks to develop, so patients may test negative if infected only recently. - Antibodies normally persist in the blood for months or even years after the infection is gone therefore, the test cannot be used to determine cure. - Infection with other diseases, including some tickborne diseases, or some viral, bacterial, or autoimmune diseases, can result in false positive test results. - Some tests give results for two types of antibody, IgM and IgG. Positive IgM results should be disregarded if the patient has been ill for more than 30 days. Molecular Testing For Detection Of Borrelia Species Bacterial Dna PCR is available for Borrelia species DNA detection but is of limited value in routine testing for Lyme disease because the organism is only present in blood during the early stages of the disease and is predominantly restricted to the affected tissues. Diagnostic molecular testing for Borrelia species DNA is available on request for relevant specimen types. Please call RIPL to discuss individual cases. You May Like: Medication To Prevent Lyme Disease What Does It Mean If Your Lyme Disease Ab Blot Result Is Too High Two types of antibodies are detected in the Western blot test. IgM antibodies reflect a relatively recent infection. IgG antibodies in contrast are a sign of an older infection. IgM antibodies usually disappear after eight weeks post-exposure. IgG remains in the serum for a very long time. In the Western blot test there are three bands for IgM and 10 bands for IgG. Here is the important part: – You need to have 2 out of 3 for the positive IgM result – Or you need to have 5 out of 10 for the positive IgG result. This marker is called Lyme Disease AB , Blot and is an aggregate marker for the three IgM results. So if this marker is positive you have at least 2 out of 3 of the IgM markers positive. Here is the 2nd important part when it comes to a diagnosis: If a person doesn’t have signs or symptoms of Lyme disease, then the person does not have Lyme disease as the definition of disease requires symptoms. What could some of those symptoms be? What are the symptoms of Lyme disease? Lyme disease symptoms are wide-ranging, with more than a hundred different symptoms recorded. Symptoms can also change over time, as the bacteria spreads throughout the body. To make things more confusing, Lyme disease symptoms will also vary from patient-to-patient. Lyme disease can mimic hundreds of other conditions since its symptoms mirror many medical problems such as multiple sclerosis, arthritis, chronic fatigue syndrome or lupus, and is sometimes known as The Great Imitator because of this. Access To Lyme Disease Testing Services This guidance on the laboratory diagnosis of Lyme disease is intended for healthcare professionals in the UK. Patients concerned about possible Lyme infection should consult an appropriate healthcare professional, for example their GP, in the first instance. Health professionals wishing to discuss a possible case or ascertain local arrangements for testing should contact a local Infection specialist . NHS testing for Lyme disease is available through local service providers and the Rare and Imported Pathogens Laboratory at UK Health Security Agency Porton where ISO15189 accredited confirmatory testing is also provided. RIPL also provides a testing service for neurological Lyme disease. RIPL provides medical and laboratory specialist services to the NHS and other healthcare providers, covering advice and diagnosis of a wide range of unusual bacterial and viral infections, including Lyme disease. RIPL continuously updates its methods and will make further information on Lyme disease diagnostic testing available as it arises. Recommended Reading: Eye Doctor East Lyme Ct Lyme Disease Antibody Test Procedure The Lyme disease antibody test requires no advance preparation. A lab technician will swab the inside of your elbow with an antiseptic before drawing your blood. Your blood will be drawn from a vein in your arm using a small needle. The blood draw should not be painful, though you might feel a slight prick when the needle is inserted into your vein. The blood sample will be collected in a vial. The puncture site will be bandaged, if needed, after the needle is removed. After the blood draw, you are free to go home. There are very few risks associated with the Lyme disease antibody test. Excessive bleeding is possible, but there may be an increased risk if you take blood thinning medications or certain anti-inflammatory drugs like: Management Of Individuals Without Symptoms Following A Tick Bite Diagnostic testing is not recommended for individuals who do not develop any symptoms suggestive of Lyme disease after a tick bite. Some commercial companies offer services to test removed ticks for the presence of the bacteria that cause Lyme disease. UKHSA does not provide such tick-testing services. The results of such tests should not be used to inform diagnosis or treatment. A positive result does not mean that the infected tick will have passed on the bacteria there are many factors that determine whether Lyme disease results from the bite of an infected tick. A negative result may not be technically valid and could give false assurance, as it does not exclude the possibility that another tick elsewhere on the body has been missed by the patient. UKHSA runs a tick surveillance scheme and is happy to receive ticks for species identification and to monitor tick distribution. Don’t Miss: Is There A Cure For Lyme Alternative Diagnostic Tests Not Available At Ripl Tests used by the NHS and UKHSA to identify Lyme disease are well characterised, standardised, and are highly reproducible between laboratories. They are the methods of choice recommended in the 2018 NICE Lyme disease guidelines, following an extensive review of the evidence and literature. International external quality assurance schemes are in place to ensure consistency between different centres offering these tests. Several private laboratories in Europe and the US offer an alternative type of test called an ELISpot to diagnose Lyme disease. This looks for different markers in blood samples compared to conventional validated Lyme disease serology tests. The laboratories using these tests in the diagnosis of Lyme disease do not publish their methods, and have not produced peer reviewed publications on their clinical value. This makes it very difficult to verify their results, especially as there are no national or international EQA schemes for Lyme disease ELISpot tests and therefore no independent verification of performance between laboratories. Without independent evidence it is impossible to determine the validity of results produced using these alternative tests. RIPL cannot interpret the results of alternative diagnostic tests. Investigation Of Suspected Neurological Lyme Disease The diagnosis of neurological Lyme disease can only be confirmed by examination of the CSF and a paired serum sample. A definite diagnosis is based on the presence of a pleocytosis in the CSF, demonstration of intrathecal synthesis of specific antibodies to Borrelia species in CSF by comparison to serum and the presence of neurological symptoms. It is not possible to confirm intrathecal synthesis and hence definite neurological Lyme disease without a paired serum . In 2018 RIPL introduced a service for the detection of intrathecal synthesis of Borrelia-specific antibodies which is summarised in this flow diagram. An accessible text version of this flowchart is available below. Clinicians may ask for guidance on laboratory testing of CSF from RIPL if required. Don’t Miss: Old Lyme Beach House Rentals What Is A Lyme Disease Blood Test A Lyme disease blood test is used to determine if you have contracted Borrelia burgdorferi , the bacterium that causes Lyme disease. Lyme disease tests are conducted with a routine blood draw. While there are other species of Borrelia that cause Lyme disease, B. burgdorferi is the most common cause in the United States. Most antibody tests in the United States only test for B. burgdorferi, but other species-specific tests are available depending on a persons travel history. Lyme disease is transmitted to humans through ticks that are infected with Borrelia. - shortness of breath Lyme disease can be difficult to diagnose. Ticks are very small, and the bites are not always noticeable. Symptoms of the disease can vary from person to person. Not everyone experiences the classic bulls-eye rash pattern around a tick bite. It should be noted that testing is not always required to make a diagnosis. For people with a classic bulls-eye rash living in a high risk area, testing is not recommended for diagnosis. Your doctor will use the results of a Lyme disease antibody test, along with the report of your symptoms, to confirm a diagnosis. Antibodies are proteins your body makes in response to foreign or harmful substances called antigens. Common antigens include: Your body produces antibodies if you have contracted B. burgdorferi. These Lyme disease-specific antibodies will be present in your blood, and your test will be positive if you have the bacterial infection. Lyme Disease Western Blot Test The Lyme Disease Western Blot test is typically used as a confirmatory test for people who have had positive results from previous Lyme Disease testing. The immunoblot test is also known as a Lyme Disease Line Blot test. This test looks for the presence of both IgG and IgM antigen bands to confirm both recent and previous exposure. The detection of multiple bands is required for a positive result. The CDC does not recommend the Western Blot test as a front-line screening as some conditions other than Lyme Disease may cause a false positive. Lyme Disease is caused by infection with the bacteria Borrelia burgdorferi. It is most commonly spread by the Deer Tick or Black Legged Tick and is the most common tick-borne illness in the United States and Europe. Lyme disease can be difficult to diagnose because the symptoms are often similar to other afflictions. While some people will display a distinctive “bulls-eye” rash around the site of the bite, others may experience common flu-like symptoms such as fever, chills, fatigue, and headache. The ticks which spread the disease are typically very small and many people do not even realize they have been bitten. If left untreated, Lyme Disease can cause joint pain, numbness in the arms and legs, facial paralysis, Meningitis, heart problems, or memory problems. Turnaround time for the Lyme Disease Immunoblot test is typically 1-5 business days. Also Check: Lyme Shot For Dogs Side Effects Lyme Disease Antibody W/ Reflex To Blot Test Code: 6646 CPT Code: 86618 Includes: If Lyme Disease Antibody Screen is Equivocal or Positive, Lyme Disease Antibodies , Immunoblot will be performed at an additional charge : 86617 x2). Clinical Significance: Lyme disease is caused by a bacterium borrelia burgdorferi and is transmitted by ticks. EIA is the screening test with high sensitivity for antibody detection. Immunoblot testing qualitatively examines with high specificity antibodies in a patient’s specimen. Immunoblot testing is appropriate for confirming a detected EIA test result. Alternative Name: Borrelia burgdorferi, Lyme Screening, Lyme Antibody Screen Igg Vs Igm Antibodies Getting accurate test results is the first step in getting treatment for Lyme disease. Still, it can be difficult to navigate the world of testing and understand how different tests work. Were here to help clear up some of the confusion, specifically when it comes to different types of cells and antibodies. Also Check: Lyme Disease Specialist San Francisco Bay Area Antibodies And Lyme Disease Testing Remember that IgM antibodies appear early on as a response to an infection, but levels typically decline over time. Because of this, tests that rely on the detection of IgM antibodies, like the Lyme IgM Antibody Serology, may only be positive for two to six weeks after exposure. Other tests like the Lyme Broad Coverage Ab Assay, Lyme ImmunoBlot, and Lyme Western Blot detect multiple types of antibodies and may able to detect Lyme disease in the case of later re-activation of infection. Tests that depend on the detection of antibodies, specifically IgM antibodies, are time sensitive, and typically only have a small window which they can be used after exposure to a tick. Luckily there are other tests available for people who are in the late stages or have Chronic Lyme disease. These tests include the Lyme Multiplex PCR, Lyme Western Blot IgM, and the Lyme Dot-Blot Assay . Serological Testing Of Serum For The Diagnosis Of Lyme Disease The most commonly used tests look for antibodies to the Borrelia species that cause Lyme disease in the UK and Europe, but they also detect infections from strains of Borrelia from the US. The antibody response takes several weeks to reach a detectable level, so antibody tests in the first few weeks of infection may be negative. If the first sample was taken within 4 weeks from the onset of symptoms and is negative and there is a clinical suspicion of Lyme disease, then retesting in 4 to 6 weeks may be useful. It is very rare for patients to have negative antibody tests in longstanding infections. Borrelia antibodies persist indefinitely in some patients and this does not indicate continuing disease or a need for re-treatment. Serological testing for Lyme disease in the UK and much of the world follows a two-step approach: Recommended Reading: Can Lyme Disease Cause Blood In Urine	2	10	2	0	0	0.375501	2	3,914
ANAHEIM, California — Better characterization and increasing understanding of geographic atrophy are giving researchers hope that there will soon be new therapies for the disease. "We've got a disease without a treatment," said Mark Dunbar, OD, from the Bascom Palmer Eye Institute in Miami. But we "are trying to generate awareness that there is hopefully a treatment coming down the pipe." Dr Dunbar presented a review of the literature on geographic atrophy here at the American Academy of Optometry 2016. The disease — the advanced stage of age-related macular degeneration — affects more than 5 million people around the world, he reported. The prevalence of geographic atrophy closely parallels that of neovascular — or wet — age-related macular degeneration, rising sharply in people 65 years and older. "Geographic atrophy might be more common than we thought it was," he explained. Outcomes for patients with neovascular age-related macular degeneration improved dramatically after the advent of anti-vascular endothelial growth-factor (VEGF) therapy. "It's been a breakthrough having a treatment for the wet form of the disease," said Dr Dunbar. Researchers are now gaining a better understanding of geographic atrophy and hope for similar progress. Already, coding for the condition was changed in the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) to allow for the better collection of data, Dr Dunbar told Medscape Medical News. Previous ICD codes did not specifically code for geographic atrophy, they only distinguished between exudative and nonexudative AMD, he explained. The new codes will allow better tracking of disease progression in electronic health records. Table 1. ICD-10 Classification \|H35.31X0\|\|Non-exudative (dry) AMD\| \|H35.31X1\|\|Early AMD\|\|Combination of multiple small drusen (≤63 µm), few intermediate drusen (>63–125 µm), few intermediate drusen (≥63 to ≤124 µm), or retinal pigment epithelium abnormalities\| \|H35.31X2\|\|Intermediate AMD\|\|Extensive intermediate drusen (>63 µm to ≤124 µm) or at least 1 large drusen (>125 µm)\| \|H35.31X3\|\|Advanced atrophic AMD without subfoveal involvement\|\|Geographic atrophy not involving the center of the fovea\| \|H35.31X4\|\|Advanced atrophic AMD with subfoveal involvement\|\|Geographic atrophy involving the center of the fovea\| And the Beckman Initiative for Macular Research, now the Stephen J. Ryan Initiative for Macular Research, has developed a new classification for age-related macular degeneration. Table 2. Beckman Initiative for Macular Research Classification for Age-Related Macular Degeneration \|Normal aging\|\|No or a few drupelets; drusen <63 µm\| \|Early AMD\|\|Drusen 63 µm–125 µm\| \|Intermediate AMD\|\|Drusen >125 µm\| \|Advanced AMD\|\|Geographic atrophy or neovascular AMD\| Multimodal geographic atrophy imaging technologies can help monitor progression of the disease, said Dr Dunbar. Spectral domain optical coherence tomography can define the boundaries of the geographic atrophy and reveal intraretinal changes, including the degradation of individual layers, the loss of retinal pigment epithelium, and the change in lesion size, he explained. And fundus autofluorescence offers better delineation of lesion boundaries than fundus photos. The enhanced signal at lesion boundaries might predict areas of lesion progression. "We'll have a better sense of what the incidence is and be able to follow these patients more closely," Dr Dunbar said. At the same time, researchers have begun to tease apart the complex of genetic and environmental factors involved in age-related macular degeneration, including 19 different genes and oxidative stress, that result in immune system dysregulation and attacks on the retina. Investigators have zeroed in on the alternative complement pathway of the immune system as a key link in the chain of events that leads to a damaged macula. "There are a number of treatments that might become available," Dr Dunbar reported. He listed two agents in phase 2 trials — GLG561 (Novartis) and APL-2 (Apellis Pharmaceuticals); one in phase 2/3 trials — avacincaptad pegol sodium (Zimura, Ophthatech); and one in phase 3 trials — lampalizumab (Genentech/Roche). These drugs inhibit various components of the alternative complement pathway. These findings herald a big change in the approach that optometrists will be taking to geographic atrophy, said Andrew Mick, an associate clinical professor of optometry at the UC Berkeley School of Optometry in California. "For an entire generation, we have essentially screened for this transformation from dry to wet," he told Medscape Medical News. Optometrists of the future will not only classify patients by the new ICD-10 codes, but will also, perhaps, identify those who can benefit from treatment, Dr Mick said. Dr Dunbar reports that he is on the advisory board of Genentech. Dr Mick has disclosed no relevant financial relationships. American Academy of Optometry (AAOpt) 2016: Abstract 165159. Presented November 10, 2016. Medscape Medical News © 2016 WebMD, LLC Send comments and news tips to [email protected]. Cite this: Changes Coming in the Management of Geographic Atrophy - Medscape - Nov 13, 2016.	3	8	0	0	2	0.827634	2	1,211
That little pain in the shoulder, wrist or hip, which has been there for more than a week, is quite annoying. It can be a tendonitis, an inflamed tendon. It is important that you treat tendonitis properly, as otherwise it can cause problems such as tendon rupture. Tendonitis is an inflammation in a tendon, a striated muscle that connects other muscles to the bones. They transfer muscle strength to the skeleton, allowing the body to move. The tendons are rigid but flexible structures, however they do not have much elasticity. This makes the damage common. Any of them can be affected, but the most common are those connected to the joints (knees, elbows, shoulders, hips, feet, ankles), as they move more often. The inflammatory process is a reaction of the body to infections or (as in most cases of tendonitis) injuries. It is the body’s method of bringing more nutrients and immune cells to the region, ensuring recovery. During inflammation, the area is hot and painful until everything is recovered. Tendonitis can have numerous causes, such as overexertion, infections and trauma. As a result, they bring pain, discomfort and movement difficulties. When ignored, they can cause serious problems such as rupture of the affected tendon. The difference between tendinitis and bursitis is the type of tissue affected. While tendonitis is an inflammation of the tendons, bursitis is the inflammation of the bursa , a small bag filled with synovial fluid that stays in the joints and reduces the friction of the bone with the tendons and muscles. Lubrication of synovial fluid is essential for joint movement to happen without pain, but when the bursa is inflamed, pain happens. However, bursitis should not be confused with tendonitis. These are two different conditions. Tendonitis can be divided into 4 types, which vary according to the region of the tendon that is affected. Are they: - Entesitis : affects the central structure of the tendon; - Tenosynovitis : the inflamed region is the tendon synovial sheath . This is a structure that is around the tendon, protecting it, like a sheath; - Peritendinitis : inflammation affects the region where the tendon connects to the muscle; - Ossifying tendonitis : deposits crystals that solidify in the tendon, causing inflammation. There are a number of different variations of tendonitis, since each region can be affected. We don’t list them all here, but some of the most common ones are: It is a type of tendonitis that affects the thumb tendon, often (as well as most tendonitis) caused by repetitive movements. It is a type of RSI. Carpal tunnel syndrome The carpal tunnel is an anatomical opening that is in the wrist, between the hand and the forearm, and is where nerves and tendons pass. This syndrome refers to the compression of one of the nerves, the median . The flexor tendons, responsible for the movement of the fingers, pass through the same tunnel and, therefore, they can be affected by the inflammation caused by the carpal tunnel syndrome, causing tendonitis in the region. Calcaneal or Achilles tendonitis This type of tendonitis affects the Achilles tendon , the one on the back of the heel, where supposedly the Spartan hero, whose only vulnerable point was the heel, was hit by a poisoned arrow that killed him. It is a place where tendonitis often affects and, like others, requires rest and medication for treatment. The ICD-10 code for this type of tendonitis is M76.6 . Patellar tendonitis (in the knee) Patellar tendonitis is one that affects the tendons of the knees, which help the muscles to extend the legs and that connect the tibia (the bone in the front of the leg) to the patella (the bone in the knee). It usually affects athletes, especially those whose sport involves jumping, such as volleyball or basketball. This type of tendonitis has the M76.5 code in the ICD-10 . Tendonitis in the shoulder The shoulders have three different tendons. The supraspinatus tendon , the subscapularis and the biceps tendon . These are the tendons responsible for the movement of the arms and shoulder at the three angles at which it is possible to move it (forwards and backwards, to one side and to the other, up and down). Hip tendonitis can affect runners and is often caused by repetitive strain. It affects the tendons that connect leg muscles to the hips and can cause stiffness that prevents people from running and sometimes even walking in a comfortable way. This type of tendonitis occurs due to deposits of calcium crystals in the tendon, often in the shoulders. The cause of this deposition is not known. It happens slowly and gradually, can cause discomfort and usually heals on its own, just like any other tendonitis. Calcium is partially or totally absorbed, but in some cases it can take time to happen, causing pain and discomfort. In ICD-10 , the code for this type of tendonitis is M75.3 when it affects the shoulder and M65.2 elsewhere. Tendonitis in the hand The hands house several tendons, responsible for each of the movements of the fingers. These movements can be repeated several times a day in an office environment, for example, or with games. Therefore, the hands are parts of the body that are greatly affected by tendonitis, which manifests with pain and discomfort. Tendonitis in the foot The feet, as well as the hands, have several tendons responsible for their movements. Although tendonitis in them is not as common as in the hands, it can also happen, causing the common problems of the disease. Tendonitis in the wrist Just as working with computers – often in offices – can cause tendonitis in the fingers and hands, the pulse can also be affected. The inflamed tendons cause the classic symptoms of the disease: pain, discomfort, heat, redness, and others. There are several other possible locations for tendonitis. Behind the knees, in the back, groin, wherever there is a tendon, inflammation is possible. The inflammations can be caused by several situations and vary from case to case. Therefore, it is important to take care of your body and go to the doctor if there is tendon pain, to avoid more severe damage caused by the condition. This condition is not exactly a type of tendonitis, as it does not only affect the tendons, but also muscles and nerves. But tendons are also affected, which puts tendonitis – when caused by repetitive strain – as a type of RSI. RSI, or Repetitive Strain Injury, is a common injury in the workplace. It is caused by repetitive movements and affects mainly (but not exclusively) the upper limbs. Shoulders, wrists and fingers are major victims of the inflammation caused by RSI. (Little curiosity: Did you know that your fingers have no muscles, only tendons?). Tendonitis can be caused by several situations such as overexertion, passing through inadequate posture and diseases that affect the tendons. Traumas and infections can also be responsible for the condition, in addition to several other causes capable of affecting these structures. Some of the causes of tendonitis are: Repetitive strain is one of the main causes of tendonitis. Forcing the tendons in the same way for months or sometimes even years can damage them, which in turn leads to inflammation. RSI is a condition often associated with office work, as the tendons of the fingers can be affected by typing and the use of the mouse and those of the wrists, by the position that the hands are when using the keyboard. Excessive effort can also cause damage that leads to inflammation in the tendons. Running, jumping, push-ups, lifting or holding weights in a way that forces the tendon fibers can cause the problem, especially when there is no rest or stretching. Poor posture can strain the tendons in your back, but there are several positions that can force others less related to the position we are in. For example, lying on your elbow while reading or moving on your cell phone can strain your shoulder. Any position that has positioned your body in an unnatural way can cause tendonitis. Certain autoimmune diseases can cause spontaneous inflammation in the tendons. This causes tendonitis as a consequence of the disease. Rheumatological diseases, such as arthritis, can cause tendon problems, creating pain and inflammation. In the same way that impacts can hurt muscles and bones, they can also cause damage to tendons, which, during recovery, can develop inflammation. Infections can cause intense inflammation. If someone has tendons affected by bacteria, the immune system will attack them to try to cure the infection. Depending on how resistant the bacteria are, the inflammation can be severe and cause serious problems. Most people, at some point in their lives, will experience tendon pain caused by inflammation. It is a common condition. However, some people may experience tendonitis more easily, frequently and with intensity. The main groups and risk factors for tendonitis are: The effort caused by constant training of athletes often leads to tendonitis, which varies from region to sport. Runners can have hip inflammation. Volleyball and basketball players, on their knees, while swimmers and throwers tend to feel their shoulders. Sports injuries can also lead to the condition. In football, a cart that hits the Achilles tendon, for example, can damage it and cause tendonitis. The stress increases the chances of you developing inflammation in the body as it increases the levels of epinephrine ( a hormone that increases the responses of the body to stress) in the blood. Normally, the body releases cortisol (a stress hormone with an anti-inflammatory effect) along with adrenaline, which prevents inflammation caused by the muscle tension that the substance causes. However, when the stress is constant, the opposite effect is not enough and inflammations can appear. Muscle tension can also cause the tendons to become more tensioned, an unnecessary effort and one that can cause damage. As a result, tendonitis can arise. Inflammation of the tendons can bring about some uncomfortable symptoms that may indicate the condition. Are they: The region of the affected tendon is painful, especially when movements are performed. This pain usually radiates to the affected limb. For example, if tendonitis is in the shoulder, the pain can spread to the arm. This pain is due to the use of an inflamed tendon. It becomes swollen and stiff, which makes the pain appear if moved. Mild redness is common in cases of tendonitis. The affected area may become hot and red, but it is important to be careful with this symptom. If the redness is very strong, it is possible that the damage is serious and the person should go to the hospital. The word “inflammation” comes from the Latin ” inflammatio “, that is, to ignite, to set fire. Inflammation is accompanied by heat in the affected tissue, which is an immune reaction that helps to eliminate possible bacteria that cannot survive at higher temperatures. Like redness, tendonitis can cause mild swelling. However, if it is large, there may be damage to the muscle structures in the region and the doctor should be consulted. One of the main symptoms of tendonitis is difficulty in movement . The tendon is one of the main structures related to movement and, when it is damaged and inflamed, it may have difficulty or even impossibility to fulfill its function. There may be difficulty in raising the leg or arm, accompanied by a feeling of weakness in the region in certain positions. The diagnosis of tendonitis can be made in some ways, but the physical examination is usually the main one, usually performed by the general practitioner , orthopedist or physiotherapist . Physical examination is the main test for diagnosing tendonitis. The doctor observes the way the part of the body affected by the symptoms moves, where and how it hurts, and through these observations, in addition to the touch, he can distinguish whether the affected region is the bone, muscle, nerve or tendon. When it is confirmed that it is the tendon, the diagnosis of tendonitis can be made. However, some additional tests may be ordered to identify possible causes or to assess the extent of inflammation or damage. Ultrasonography uses sound waves to build an image of the affected region. The images are not very detailed, but this exam is cheap and simple, in addition to having the ability to provide information that the physical exam alone cannot. Magnetic resonance imaging offers clearer and more detailed images of the affected region, but the use of radioactive material is necessary for the images to appear clearly, in addition to being an expensive exam. The information provided by an MRI is rarely necessary for the diagnosis and treatment of a simple tendonitis when there is no suspicion of any more dangerous condition. The X-ray is usually not used for the identification of tendinitis because the tendons do not appear in this exam. However, it can show when there is an accumulation of calcium in a tendon, showing a possible calcareous tendonitis. As long as the cause is curable, yes . In some cases, tendonitis is just a symptom of a more serious condition, such as an autoimmune disease, so all that is possible is to treat the inflammation, but in those cases it tends to reappear eventually. However, when the cause of tendonitis is just exaggerated effort or performed incorrectly, the cure is simple and prevention is simple. The main treatment for tendonitis is rest, but some medications can also help with inflammation, reducing the intensity of symptoms until the condition is gone. In some cases, other treatments may be necessary. Rest is the main method of treating tendonitis. Inflammation is nothing more than an effort by your immune system to repair what has been damaged or eliminate infections. Giving the time necessary for these repairs to be made resolves the situation. Avoiding the affected tendon as much as possible is the best solution. The recommended minimum is 3 days, but 5 days of rest may be required for a full recovery. Thereafter, prevention becomes key to preventing tendonitis from returning because of the same situation. Anti-inflammatory drugs are used to treat tendonitis to reduce inflammation and, consequently, symptoms. They are not always necessary, as the body is usually able to deal with inflammation easily, but in the most severe cases, medications help a lot. Cryotherapy is the application of ice. It increases vasoconstriction, which constricts blood vessels, reducing flow in the region. This reduces inflammation and is used for acute cases (which are not frequent) caused, for example, by trauma. The application of ice should be done for a maximum of 30 minutes to avoid damage from the cold, 4 to 6 times a day. Remember not to apply the ice directly to the skin. Use a cloth. When tendonitis is ignored and the effort continues to be applied to a specific tendon, it is possible that it will rupture . When the rupture is only partial, rest accompanied by immobilization may suffice, but if it is total (the tendon breaks completely), the treatment for this is surgery. Surgery for the ruptured tendon aims to reconnect the fibers, thus enabling recovery. The surgical method can also be used in cases of calcareous tendonitis, to remove the calcium deposit. It is usually not necessary, but it is an option. The operation should be done in cases where the resting treatment is not effective and in cases where there is total tendon rupture. Physiotherapy may be necessary if the tendon damage is severe. Physiotherapy treatment can help the patient to recover movements in cases of tendon rupture – partial or total – or when the muscles atrophy due to long periods without exercise. Muscle stretching and strengthening techniques are used, which helps to speed up the patient’s healing, in addition to preventing repetition of tendonitis or its causes. The practice of physical therapy is important. A frequent mistake is that patients use only anti-inflammatory drugs that are stopped after the symptoms end. This can resolve the acute case, but in these cases tendonitis usually returns after some time, sometimes stronger and more intense than before. Physical therapy can also prevent tendonitis from developing into chronic tendonitis or tendinosis, which often leads to tendon rupture. Medicines for tendonitis are anti-inflammatory drugs (such as corticosteroids), to reduce inflammation, and analgesics, which decrease pain. Often the same drug has both effects. The main ones used are: - Paracetamol (Tylenol); - Ibuprofeno (Advil); - Acetylsalicylic acid ( Aspirin ). - Prednisona ( Meticorten ). NEVER self-medicate or stop using a medication without first consulting a doctor. Only he will be able to tell which medication, dosage and duration of treatment is the most suitable for his specific case. The information contained in this website is only intended to inform, not in any way intended to replace the guidance of a specialist or serve as a recommendation for any type of treatment. Always follow the instructions on the package insert and, if symptoms persist, seek medical or pharmaceutical advice. You can perform some home treatments in conjunction with medical treatment to help resolve tendonitis. Certain foods have anti-inflammatory properties and can aid recovery. Ginger tea helps to reduce inflammation. To do this, just boil 500mL of water with a small piece of ginger dipped inside it. You can also use ginger as a spice for food. Knead rosemary leaves , mix them in a spoon of olive oil and then use a gauze pad to compress the tendinitis site to reduce inflammation. Leave it like this for a few minutes. Tendonitis, in milder cases, takes 1 to 3 weeks for full recovery. In cases where the tendon is severely damaged, it can take up to 10 weeks and when tendonitis becomes chronic, treatment can last from 3 to 9 months, depending on the progress of the disease and the quality of rest. The main exercise recommended for the prevention of tendonitis is stretching. It prepares the tendons for effort and prevents the condition. You must stretch your muscles before any physical exercise. It is important to remember that exercises for the treatment of tendonitis should only be recommended by physical therapists, since only the professional knows exactly how to exercise the tendon without causing further damage. The prognosis for tendonitis is usually positive. Rest is the main treatment and usually results in complete recovery of the tendon, which can be used again after a few days. Tendonitis can take 1 to 3 weeks to heal when it is caused by tendon overload. However, it can take longer, depending on several factors such as the quality of rest, the condition of the tendon and the progress of the disease, which can take up to months. There are not many complications for tendonitis, but it is important to remember that not treating the condition can have serious consequences. Tendonitis can become chronic when left untreated. Inflammation mechanisms can begin before recovery from a previous inflammatory process, which does not allow the tendon to improve. In such cases, treatment of the cause is necessary for the condition to be relieved. Tendinosis is an evolution of an untreated tendonitis. In this state, the tendon is degenerating and about to rupture because of inflammation and stress. It is essential that there is rest and physical therapy to avoid severe damage that may require surgery for recovery. Tendonitis, if ignored, can lead to tendon rupture. This happens mainly when athletes continue to struggle despite the pain, but it can happen even without sports. If you have tendon pain, rest is essential to prevent more serious damage. Tendon rupture may require surgery. Preventing tendonitis is the best way to avoid the problem. Some of the habits you can have to avoid the condition are: Especially before any physical exercise, stretching allows your body to prepare for efforts and protects your tendons from tendonitis, in addition, of course, from other damages that can affect the various structures of the body such as muscles and joints. Resting is what allows your limbs, muscles and tendons to recover from exercise. For each training session, it is important to get some rest so that everything will recover and you will not be damaged by tiredness . Even if you don’t exercise, rest is important as stress also increases your chances of developing inflammation. The practice of physical exercises leaves the body better conditioned for efforts that may be necessary. This strengthens all parts of your body, including the tendons, which, with training, become more resistant. Inadequate posture when sitting, lying down or driving are some of the main reasons why people develop tendonitis. Remember to keep your spine upright and your body in the correct position throughout the day. Tendonitis is an inflammation in any of the tendons in the body, which is full of them. It can cause pain and movement difficulties, and treatment usually involves resting to recover the affected tendon. Share it with your friends so they can learn a little about tendonitis!	2	9	0	0	6	0.421567	6	4,501
\|Subject: Eye Movement Analysis Using Non-spatial Calibration for the Diagnosis of Concussion\| \|Document #: MED.00137\|\|Publish Date: 06/28/2023\| \|Status: Reviewed\|\|Last Review Date: 05/11/2023\| Concussion, (also known as mild traumatic brain injury), occurs following direct or indirect external trauma to the head that causes a change in brain function. Because there is no single objective measure or combination of measures for diagnosis of concussion, physicians must rely on expert guidelines, available assessment tools and clinical judgment to make a diagnosis of concussion. Researchers are exploring eye movement analysis that uses temporal (rather than spatial) calibration to aid in the diagnosis of concussion. The EyeBOX® (Oculogica, Inc. [New York, NY]), is the first baseline-free, temporal calibration eye movement analysis device to assist physicians in objectively evaluating individuals with suspected concussion. Investigational and Not Medically Necessary: Eye movement analysis using non-spatial calibration is considered investigational and not medically necessary for the diagnosis of concussion. Diagnosis of Concussion Concussion occurs following direct or indirect external trauma to the head that causes a change in brain function. Concussion can affect a variety of clinical domains: physical, cognitive, and behavioral or emotional. The various neurological signs and symptoms of concussion may be nonspecific, subtle and transient, and may persist beyond the usual recovery timeframe. Alterations in balance, as well as cognitive or sensory disturbance, may pre-dispose the affected individual to further injury in the future (Stuart, 2020). Concussion diagnosis can be challenging because there is currently no generally accepted definition or diagnostic criteria for concussion and no single assessment has been accepted as being able to identify those with a concussion. Most individuals with a suspected head injury are examined using the 15-point Glasgow Coma Scale (GCS). However, the GCS is based on symptoms and is neither sufficiently sensitive to assess cognitive and neuropsychiatric deficits of concussion nor predictive of outcome. In addition to GCS evaluation, an individual suspected of having sustained a concussion will generally also undergo a CT scan of the head to detect brain tissue damage or intracranial lesions, however, a majority of individuals evaluated for concussion do not have detectable intracranial lesions after having a CT scan. Physicians must therefore rely on expert guidelines and available assessment tools and clinical judgment for concussion diagnosis. Availability of a non-invasive, radiation sparing test for concussion will help health care professionals determine the need for a CT scan in individuals suspected of having a concussion and help prevent unnecessary neuroimaging and associated radiation exposure. In recognition of the need for more concise and accurate assessment tools, researchers are exploring the use of eye tracking technology to aid in the diagnosis of concussion. Association of Oculomotor Dysfunction with Brain Injury Traumatic brain injury (TBI) can result in a variety of visual disturbances with many individuals exhibiting multiple visual defects in combination with a decline in overall health. Inasmuch as 6 of the 12 cranial nerves (CN) directly bear on the visual process, it is not surprising that numerous symptoms of oculomotor dysfunction might be reported in individuals who have sustained a TBI. Defects in primary vision such as visual acuity and visual fields, eye movement disorders including vergence, saccadic and smooth pursuit movements, and in more complex aspects of vision involving visual perception, motion vision, and visuo‐spatial function, have all been reported in TBI. Eye movement dysfunction may be an early sign of TBI (Armstrong, 2018). Cifu and colleagues (2015) conducted a study to determine whether computerized eye tracking could provide a more objective measure to diagnose and to monitor improvement of symptoms following a concussion. Eye-tracking data, collected via a head-mounted, video-based binocular eye tracker, was used to examine saccades, fixations, and smooth pursuit movement in a group of 60 military service members with postconcussive syndrome and a control group of 26 asymptomatic subjects, in order to determine if eye movement differences could be found and quantified. The diagnosis of concussion was confirmed by the study physiatrist’s history, a review of medical records, and physical examination. Different features of saccades, fixation, and smooth pursuit eye movements were analyzed. Participants with symptomatic concussion had statistically larger position errors, smaller saccadic amplitudes, smaller predicted peak velocities, smaller peak accelerations, and lengthier durations. Individuals with symptomatic concussion were also less likely to follow a target movement (less primary saccades). Overall, symptomatic concussion tracked the stepwise moving targets less accurately, revealing possible brain dysfunction. The authors concluded that this investigation represents an important initial step in the understanding of the role of both eye movement abnormalities and computerized eye tracking in the diagnosis and monitoring of symptomatic concussion, but additional studies investigating specific linkages between symptoms, eye-tracking abnormalities, and neuropathology are needed. In 2018 Howell and colleagues presented the results of a cross-sectional and multisite study to measure eye tracking performance of athletes who were diagnosed with a concussion and uninjured controls. Individuals who reported to two tertiary care sport concussion clinics within 10 days of concussion completed an objective eye tracking assessment. Only individuals who sustained a concussion during sports or by a mechanism involving forces similar to sports, such as being injured during recreational activities or falling from ground level, were included in the study. Subjects with more severe injury mechanisms, such as falling from a height or sustaining motor vehicle collisions, were excluded. Researchers identified and recruited healthy adolescent control participants between the ages of 11 and 18 years who were involved in a program at a sports injury prevention center or were children of hospital employees. No spatial calibration was used for tracking eye movement. A total of 79 participants completed the study, 44 with concussion (mean age = 14.1 ± 2.2 years, 39% female) and 35 controls (mean age = 14.3 ± 2.4 years, 57% female). Right eye skew along the bottom of the screen was significantly higher for the concussion cohort compared to controls (median = 0.022 [interquartile range = -0.263, 0.482] vs 0.377 [interquartile range = -0.574, -0.031]; p=0.002), but not the left eye. Among the variables explored, right eye skew was altered for adolescents with a concussion. The authors concluded that the use of objective eye-tracking technology that can quickly identify individuals with vision-specific disturbances after concussion may allow for earlier recognition of deficits soon after injury and allow for earlier specialist referral and intervention. Because participants in this study reported for care after a concussion to one of two specialized sport concussion clinics associated with a regional tertiary care hospital, findings from this cohort of individuals may not be generalizable to other populations of individuals with concussion. In a 2021 study, Oldham and colleagues reported the results of a study which examined the relationship between self-reported symptoms and concussion-related eye tracking impairments. The study design included three arms that compared gait performance between (a) adolescents with a concussion who have normal eye tracking, (b) adolescents with a concussion who have abnormal eye tracking, and (c) healthy controls. Eye tracking and gait assessments were completed on a total of 30 concussed participants (age: 14.4 ± 2.2 years, mean ± SD, 50% female) and 30 controls (age: 14.2 ± 2.2 years, 47% female). All eye tracking was binocular, and no spatial calibration was used to allow for the independent analysis of both pupils. The BOX score (a metric of pupillary disconjugacy) was used to quantify oculomotor dysfunction. Symptoms were gathered using the Post-Concussion Symptom Scale (PCSS), and gait speed was measured using triaxial inertial measurement units. The authors reported a significant association between total PCSS score and BOX score in the concussion group (β = 0.16, p=0.004, 95% confidence interval [CI]: 0.06-0.27), but this association was not seen in the control group (β = 0.21, p=0.08, 95%CI: -0.03 to 0.45). No significant associations between PCSS symptom profiles and BOX scores were observed in the concussion or control cohorts. Additionally, there were no significant differences in single-task or dual-task gait speed. The concussed cohort with impaired eye tracking reported higher total symptom severity, as well as worse symptom severity across the five PCSS symptom domain profiles. However, eye tracking deficits did not appear to be caused by any specific symptom domain. The diminished gait speeds in those with abnormal BOX scores were not statistically significant. The authors acknowledged that some of the limitations of the study included study participants being recruited from a regional tertiary care children’s hospital. Therefore, the results of the study cannot be generalized to other populations. Additionally, the sample size of individuals with an abnormal BOX score was limited and predominantly female. The authors suggested that future research efforts examine the role of gender differences in eye tracking with a larger abnormal group. Lastly, the researchers did not assess if participants required glasses or corrective devices. Temporal (Non-spatial) Tracking Device to Detect Concussion Bin Zahid and colleagues (2020) assessed an automated eye-tracking algorithm as a biomarker for concussion as defined by its symptoms and the clinical signs of convergence insufficiency and accommodation dysfunction. In this cross-sectional case-control study, a total of 56 concussed pediatric subjects and 83 uninjured pediatric controls underwent eye tracking prospectively. Participants were not spatially calibrated to the tracker to allow independent analysis of each pupil position over time. Researchers obtained metrics comparing velocity and conjugacy of eye movements over time and compared them with the correlation between Acute Concussion Evaluation (ACE) scores, accommodation, and convergence. The investigators found that the 12 eye-tracking metrics were significantly different between the concussed and non-concussed cohorts. They observed that a model to classify concussions as diagnosed by symptoms using the ACE had an area-under-the-curve (AUC) of 0.854. The researchers also indicated that an eye-tracking model built to identify near-point-of-convergence (NPC) disability achieved 95.8% specificity and 57.1% sensitivity for an AUC of 0.810. Eye tracking detected convergence and accommodative abnormalities as well as other types of oculomotor dysfunction associated with concussion. The authors noted that individuals without head injury but with body trauma or other orthopedic injuries were not studied; therefore, it is not known if the results of this study can be applied to individuals without a head injury. Also, the model-building data set consisted primarily of teens, whereas the control subjects in the cross-validation data set were generally older than 20 years of age. This could have led to a higher false-positive rate and a lower sensitivity in the cross-validation data set. Additional studies are needed to clarify whether patterns of eye-tracking abnormalities demonstrated after concussion are age dependent. The EyeBOX Device to Diagnose Concussion In 2018, the United States Food and Drug Administration (FDA) granted de novo approval to EyeBOX as the first non-invasive, baseline-free tool directed at diagnosing concussions. The FDA approval letter includes the following indications for use: During the examination, the EyeBOX displays a 220 second video for the individual to watch. As the individual watches the video, the EyeBOX measures and analyzes eye movements to provide objective data that is used to aid in the diagnosis of concussion. The test generates an aggregate score ranging from 0 to 20 which is referred to as the Box score. A Box score of less than 10 may correspond to eye movement that is consistent with a lack of concussion. A Box score of 10 or greater corresponds to eye movement that may be present in both individuals with or without concussion. Additionally, EyeBOX also generates a report which the physician would use to interpret the validity of the test results. The EyeBOX test takes approximately 4 minutes to complete and should be performed within 1 week of the head injury. The EyeBOX is not considered a standalone diagnostic test but should be used in conjunction with a neurological assessment and a comprehensive eye exam. EyeBOX differs from some other tests that utilize eye analysis technology to identify individuals that may have sustained a concussion. Other technologies require a baseline test, which is often completed at the beginning of a sport season, pre-injury, and is compared to subsequent test results at the time of a suspected concussion. However, when evaluating trauma subjects in the emergency room, a baseline concussion assessment is often not feasible. Because the EyeBOX does not require an initial or previous baseline examination results, it differs from the other technologies that utilize eye analysis data to rule out or confirm suspected concussion. Additionally, the EyeBOX technology utilizes temporal (not spatial) calibration, so instead of tracking what an individual is looking at, the EyeBOX tracks and measures how well the eyes move. In 2015, Samadani and colleagues discussed the challenges in making an accurate diagnosis of concussion or other forms of TBI and highlighted the differences between spatially and non-spatially calibrated eye tracking. Potential applications of the algorithm include improved diagnosis and detection of diseases ranging from internuclear ophthalmoplegia to strabismus, however its greatest initially recognized value is as a potential outcome measure or biomarker for brain injury and concussion. The author stated that the utility of non-spatially calibrated eye tracking will ultimately be determined by researchers and clinicians who will conduct additional clinical trials that demonstrate the value of non-spatially calibrated eye tracking. This article also includes an overview of two other published studies co-authored by this author which are discussed below (Samadani 2015[a]). Samadani and colleagues (2015c) conducted a study to identify disconjugacy gaze in individuals that had suffered a concussion, regardless of whether the trauma was apparent on brain imaging with CT scan. The researchers prospectively tracked the eye movement of 64 normal, healthy, non-injured control subjects and compared the findings to 75 trauma participants with either a positive head computed tomography (CT) scan (n=13), negative head CT (n=39), or nonhead injury (n=23) to determine whether eye tracking without spatial calibration would identify the disconjugate gaze associated with both structural brain injury and concussion. Tracking metrics were then correlated to a clinical concussion measurement tool (the Sport Concussion Assessment Tool 3 [SCAT3]) in trauma subjects. Five out of five measures of horizontal disconjugacy were increased in positive and negative head CT subjects relative to the noninjured control subjects. Only one of five vertical disconjugacy measures was significantly increased in brain-injured participants relative to controls. Balance testing (Balance Error Scoring System) did not reveal any significant differences in the two brain-injured groups relative to the nonhead-injury trauma group. Linear regression analysis of all 75 trauma subjects demonstrated that three metrics for horizontal disconjugacy negatively correlated with SCAT3 symptom severity score and positively correlated with total Standardized Assessment of Concussion score. Only 39 (11 of 23 nonhead-injured cohort, 22 of 39 negative head CT cohort, and 6 of 13 positive head CT cohort) of the 75 trauma participants returned at least once for follow-up evaluation. Though there were no differences in symptom severity among the participants who returned for follow-up versus those who did not in the CT- or CT+ groups, among the nonhead-injured controls, those with more symptoms on SAC assessment were more likely to complete follow-up (Mann-Whitney’s test, p=0.005). Abnormal eye-tracking metrics improved over time toward baseline in brain-injured subjects observed during follow-up. The authors concluded that the eye tracking device correlates with extent of symptoms assessed with SCAT3, and may quantitate physiological impact of brain injury regardless of whether it is evident on CT scan. While the authors concluded that eye tracking without spatial calibration may help quantify the severity of ocular motility disruption associated with concussion and structural brain injury, they also acknowledged some study limitations. For example, in the control cohort, the authors relied on self-report for ophthalmic and medical history. Many participants were hospital employees, research volunteers, colleagues, or friends of the investigative team and may not have been completely forthcoming about their past medical history, medications, and drugs used in the day preceding eye-tracking testing. The long-term impact of medications and other substances consumed more than 1 day prior to testing is unknown. Additionally, not all of the study participants in all comparison groups were on the same concomitantly administered medications. As an example, the medication Keppra occurred more commonly in one group than the others and may have contributed to abnormal eye movements in the positive head CT group. However, the negative head CT cohort had similar eye movement abnormalities as the positive head CT cohort and none of these participants had consumed Keppra. The authors also acknowledged that strabismus, some congenital conditions, and some conditions leading to acquired disconjugacy might yield a false positive with the algorithm. Lastly, the authors indicate that because neither formal optometric nor ophthalmic testing was performed in the trauma setting, it could be useful to conduct additional studies that compared eye movement assessments conducted by trained neurological or ophthalmic consultants to those conducted by the eye-tracking device. A review of the ClinicalTrials.gov database indicates that Dr. Uzma Samadani was the principal investigator of a clinical trial entitled “Use of Eye Movement Tracking to Detect Oculomotor Abnormality in Traumatic Brain Injury Patients” that was completed in June 2018 (ClinicalTrials.gov, 2018). However, at the time of this review, the results of this clinical trial have not been published. Although preliminary research exploring the use of eye movement analysis using non-spatial calibration to diagnose concussion appears promising, at this time there are very few published clinical studies, and the clinical utility of this technology is unproven. While there are some studies that suggest oculomotor dysfunction is present in some individuals with brain injury, there is a lack of peer-reviewed studies demonstrating that eye movement analysis using non-spatial calibration can be used to accurately and reliably diagnose concussion. Further well-designed studies on non-spatial eye movement analysis are needed to draw conclusions about the clinical utility of this technology. According to the Centers for Disease Control and Prevention (CDC): A TBI is caused by a bump, blow, or jolt to the head that disrupts the normal function of the brain. Not all blows or jolts to the head result in a TBI. The severity of a TBI may range from “mild” (i.e., a brief change in mental status or consciousness) to “severe” (i.e., an extended period of unconsciousness or memory loss after the injury). Most TBIs that occur each year are mild, commonly called concussions” (CDC, 2019). In 2020 there were more than 64,000 TBI-related brain injuries in the United States. The most common causes of TBI in the United States are fall, fire-arm related suicide, motor vehicle crashes and assaults (CDC, 2022). Concussion may affect multiple clinical domains: cognitive, physical, and emotional or behavioral. Whereas headache is the most commonly reported postconcussion symptom, dizziness, balance disturbances, and confusion or disorientation are also frequently reported. Although amnesia and loss of consciousness were once considered the hallmarks of concussion, neither is required for diagnosis (Scorza, 2019). Because there is no standard definition or single diagnostic test that can be used to diagnose concussion, healthcare practitioners must rely on clinical guidelines, imaging studies, assessment tools in conjunction with clinical judgment to make a diagnosis of concussion. The EyeBOX is being investigated as a tool that can assist in the diagnosis of concussion. Concussion: Injury to the brain resulting from a mild blow to the head, either with or without loss of consciousness. Also referred to as a mild traumatic brain injury (mTBI). Convergence: The ability to turn the two eyes inward toward each other in order to view a close object. Disconjugate eye movement (gaze). A failure of the eyes to simultaneously turn in the same direction. Glasgow Coma Scale (GCS): A scoring system to describe the level of consciousness in an individual following a traumatic brain injury. It is used to assist with measuring the severity of an acute brain injury. Vergence: The simultaneous movement of both eyes in opposite directions to obtain or maintain single binocular vision during focusing. The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. When services are Investigational and Not Medically Necessary: For the following procedure code, or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary. Eye-movement analysis without spatial calibration, with interpretation and report Peer Reviewed Publications: Government Agency, Medical Society, and Other Authoritative Publications: \|Websites for Additional Information\| Eye movement analysis Eye tracking analysis using temporal (non-spatial) calibration Mild traumatic brain injury (mTBI) The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. Medical Policy & Technology Assessment Committee (MPTAC) review. Updated review date, Background/Overview, References, and Websites for Additional Information sections. MPTAC review. Updated review date, References, and Websites for Additional Information. MPTAC review. Initial document development. Federal and State law, as well as contract language, including definitions and specific contract provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The member’s contract benefits in effect on the date that services are rendered must be used. Medical Policy, which addresses medical efficacy, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and we reserve the right to review and update Medical Policy periodically. No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, mechanical, photocopying, or otherwise, without permission from the health plan. © CPT Only - American Medical Association	2	26	1	0	0	0.643889	1	4,776
- The Arrhythmia Alliance and the International Cardiac Pacing and Electrophysiology Society have designated June 8-14, 2009 Arrhythmia Awareness Week and World Heart Rhythm Week. Like these organizations, the Society is committed to increasing awareness of cardiac arrhythmia disorders. — “Arrhythmia Awareness Week and World Heart Rhythm Week”, - WebMD explains what an abnormal heart rhythm or arrhythmia means for your heart. — “Arrhythmia (Irregular Heartbeats) Symptoms, Types, and Treatment”, - Find patient education information at the UCLA Cardiac Arrhythmia Center. — “Patient Education \| UCLA Cardiac Arrhythmia Center - Los”, arrhythmia.ucla.edu - Arrhythmia (irregular heartbeat or abnormal heart rhythm) symptoms include palpitations, dizziness, fainting, shortness of breath and chest discomfort. Learn how to recognize the warning signs and treatment of arrhythmia on . — “Heart Arrhythmia (Irregular Heartbeat) symptoms, warning”, - Cardiac dysrhythmia (also known as arrhythmia) is a term for any of a large and heterogeneous group of If an arrhythmia results in a heartbeat that is too fast, too slow or too weak to supply. — “Cardiac dysrhythmia - Wikipedia, the free encyclopedia”, - Cardiac arrhythmia is a term that denotes a disturbance of the heart rhythm. Cardiac arrhythmias can range in severity from entirely benign to immediately life-threatening. — “Cardiac Arrhythmia”, - Latest Arrhythmia/EP news by heartwire and editorial programs with renowned cardiologists. — “Arrhythmia/EP, Electrophysiology news, opinions and education”, - Founded nearly three decades ago, Arrhythmia Research Technology, Inc. (ART) has a broad portfolio of solutions and products that has been continually expanded over the years through the strategic acquisition and deployment of world class. — “Arrhythmia Research Technology Inc. (HRT) is "One to Watch”, - The SADS (Sudden Arrhythmia Death Syndromes) Foundation seeks to save the lives and support the families of children young adults who are genetically predisposed to sudden death due to heart rhythm abnormalities. — “Sudden Arrhythmia Death Syndromes (SADS) Foundation”, - List of 13 disease causes of Heart arrhythmia, patient stories, diagnostic guides, medical books excerpts online about Heart arrhythmia, 41 drug side effect causes, 26 drug interaction causes. Diagnostic checklist, medical tests, doctor questions. — “Heart arrhythmia - ”, - Arrhythmia and the heart - find out what arrhythmia is and how it effects the heart. — “Arrhythmia Patient Guide”, - Arrhythmia is any irregularity in your heart's natural rhythm. — “Arrhythmia - Texas Heart Institute Heart Information Center”, - Why Arrhythmia Matters. When arrhythmias are severe or long-lasting, If your arrhythmia needs treatment, learn about possible options and how to reach your. — “Arrhythmia”, - Arrhythmia: symptoms, cause, prevention, types, complications, treatment, long-term outlook, risks. — “Arrhythmia: symptoms, cause, prevention, types, complications”, - cardiac arrhythmia ( ¦kärdē′ak ā′ri th mēə ) ( medicine ) Any disturbance or irregularity of the If an arrhythmia results in a heartbeat that is too fast, too slow or too weak to supply. — “Cardiac dysrhythmia: Definition from ”, - Science and technology news stories tagged with keyword: arrhythmia. All science news about arrhythmia. — “ - arrhythmia”, - An arrhythmia is any disorder of your heart rate or rhythm. Your doctor can run tests to find out if you have an arrhythmia. Treatment to restore a normal heart rhythm may include medicines, an implantable cardioverter. — “Arrhythmia: MedlinePlus”, nlm.nih.gov - Any variation from the normal rhythm or rate of the heart beat Response to RSD1235 Compared to Placebo in Subjects With Atrial Arrhythmia After Heart Surgery. — “Arrhythmia - Arrythmia - information page with HONselect”, hon.ch - An arrhythmia is a problem with the rate or rhythm of the heartbeat. During an arrhythmia, the heart can beat too fast, too slow, or with an irregular rhythm. — “Cardiac heart arrhythmias”, nhlbi.nih.gov - Arrhythmia Facts plus the Latest News on Arrhythmia Treatments - HealthNewsflash. — “Arrhythmia - Causes, Symptoms & Treatment”, - A cardiac arrhythmia, also called heart or cardiac dysrhythmia, is a disturbance in the regular rhythm of the heartbeat. Heart arrhythmia simply means that the heart rhythm is irregular -- such as missing a heart beat or perhaps each beat does not follow the proper. — “Heart Arrhythmia prevention and treatment with natural”, related images for arrhythmia - Williams is breeding a * which her vet has stated has an arrhythmia Arrhythmia is an abnormal heart beat - Uncategorized Charnel House compilation released in the early 90s as the title suggests it features mostly rhythm centric artists or in a few cases rhythm centric tracks by artists usually better known - Slide1 jpg - Arrhythmia Review Course 2006 연세의료원 - jmrrtb jpg - Please click on images below to view photographs from the Conference - export government jpg monster tackle uk jpg arrhythmia squarespace jpg stevebernal jpg - Δείτε τα τεχνικά χαρακτηριστικά των καταγραφικών Cardioremote Braemar εδώ - daveanderson3 jpg - weka27c arrhythmia png - 경우엔 심장근들이 전기적 신호를 받지 못해 수축하지 못하기도 하고 또는 정상적인 박동의 형태를 갖추지 못하여 부정맥이 생길 수도 있다 - fine decorators jpg tourist page png arrhythmia first jpg 456 jpg - arrhythmia2big jpg - electbig jpg - Tear Sheet HIS SEC - weka27a2 arrhythmia png - stdavids arrhythmia jpg - arrhythmia ris 1 jpg - warpcd94 front jpg - Table 2 Study details and demographics Statins and Ventricular tachyarrhythmia Table 3 Study details and arrhythmia diagnosis Atrial Fibrillation AF Atrial Fibrillation CAD Coronary artery disease DCCV Direct Current Cardioversion - arrhythmia ris 2 jpg - arrhythmia 24 gif - the FirstHealth Specialty Centers Building located at 35 Memorial Drive in Pinehurst For more information call 910 715 1713 or toll free 800 213 3284 - for ablation Three months later he was asymptomatic except for rare skipping of the heartbeat His AF was cured and there was no need for further medications - Arrhythmia Review Course 2006 2 JPG - weka27b arrhythmia png - 3 Cathetersw20Pole jpg - HK IN PACE Arrhythmia Conference for Allied Health 2005 - Venue 176 James St Northbridge I walked past on my way to Gravity and heard music but didn t have time to stop anyone == == == Arrythmia Sat 19th September 98 == Front Room DJ Aphrodite UK Andrew Vranjes Echoic Shep Shuey plus a live set from Jase from Outta Space - Arrhythmia Holter png - arrhythmia3big jpg - warplp94p sidea jpg - and cutting edge electrophysiology care to Northern California This web site is maintained for the goal of patient and professional education - Instromedix Inc - taro1 jpg - Dr Wilsonwithmappingsoftware jpg - SinghNEW jpg - taro2 jpg - Sinus Arrhythmia Example 1 Sinus Arrhythmia Example 2 Premature Atrial Contractions PACs Example 1 related videos for arrhythmia - VIDEO: Cardiac Arrhythmia Irregular Heart Rhythm, Part 2 Free Heart Video Diary - Part 2: 's patient advocate Todd Hartley talks about his Supraventricular tachycardia (SVT) heart problem. What happens next? http is a women's online health community. - the valsalva maneuver and sinustachycardia / cardiac arrhythmia as per request, various attempts at the valsalva maneuver... and a couple of normal breathholds. :-) i was experiencing polytop premature ventricular contractions (extrasystoles) as well as supraventricular extrasystoles, and on top of that, sinustachycardia. hooray for my heart! FROM WIKIPEDIA: The Valsalva maneuver or Valsalva manoeuvre is performed by forcible exhalation against a closed airway. A modified version is done by expiring against a closed glottis. This will elicit the cardiovascular responses described below but will not force air into the Eustachian tubes. - Pediatric Cardiac Arrhythmia - Symptoms Andrew D. Blaufox, MD Pediatric Electrophysiology Schneider Children's Hospital . Associate Professor Clinical Pediatrics Albert Einstein College of Medicine. Medical School: Albert Einstein College of Medicine . Residency: Mount Sinai School of Medicine . Fellowship: Mount Sinai School of Medicine and Medical University of South Carolina - Arrhythmia (Best dance ever) Choreigraphed by: Richard Telan and Germund Sua Dancers: Max Morallo, Will Kim, Jay Santa Ana, Germund Sua, and Richard Telan - Irina - Et huomaa (Grimsoul's arrhythmia remix) Trance remix - arrhythmia myheartbeat arrhythmia before go to hospital-pvc-5-30-08 i was have a lots of pvcs and my heart was beating fast so i go to the er for it i was Admit in hospital that night and the nurse put me on monitor my heart beat i was have lots of pvcs and doctor put me on arrhythmia medicine i still have them and the medicine help a little and i'm feeling a little better :) - I Have a heart Problem called Arrhythmia Jacenta talking about her heart problem Arrhythmia. The operations done to my heart: 1. Electrophysiological Study 2. Catheter Ablation *What is Arrhythmia?? Arrhythmias are abnormal rhythms of the heart. Arrhythmias cause the heart to pump blood less effectively. Most cardiac arrhythmias are temporary and benign. Most temporary and benign arrhythmias are those where your heart skips a beat or has an extra beat. The occasional skip or extra beat is often caused by strong emotions or exercise. Nonetheless, some arrhythmias may be life-threatening and require treatment. - Nurse Navigators at the Texas Cardiac Arrhythmia Institute A call to the Center for Arrhythmias and Atrial Fibrillation connects you with a registered nurse specifically trained to assist patients who have a cardiac arrhythmia. The nurse will provide information regarding arrhythmias as well as guidance in setting up a consult with an electrophysiologist. All pre-consultation essentials will be clearly explained, including testing that may be required, the usual length of consultation, and what to expect when you visit with the electrophysiologist. If you live out of the Central Texas area, the nurse will even direct you to a list of Austin area accommodations. To learn more about Texas Cardiac Arrhythmia Institute please visit - arrhythmia how to dance arrhythmia, silent film, Herzrhythmusstörungen tanzen, stummfilm - Advancing Cardiac Arrhythmia Care with Implantable Devices and Laser Lead Extractions In this video from Brigham and Women's Hospital (BWH), Laurence Epstein performs a laser lead extraction and inserts an implantable cardioverter defibrillator (ICD) for a patient with ventricular tachycardia. Dr. Epstein uses minimal ventricular pacing, a technique developed by his colleague Michael O. Sweeney. - Kenny Gordon Experimental and Computational Arrhythmia Labor Kenny Gordon Experimental and Computational Arrhythmia Laboratory Dedication Ceremony - Pochakaite Malko - Arrhythmia Arrhythmia(Shigekazu Kuwahara/Kazuo Ogino) Pochakaite Malko: Shigekazu Kuwahara(b) Kazuo Ogino(key) Jyunzou Tateiwa(ds) Akihisa Tsuboy(vn) Live at Shinjyuku Marz (6th May, 2002) - arrhythmic ECG / EKG with auscultation heartbeat sound READ THIS FIRST! first of all, sorry about the bad video quality, but i had to record it with my (cheap) webcam in order to be able to sync in with the microphone recording. this is a video of my ECG with auscultation sound in real-time, where i do various things to trigger arrhythmia / alter the ECG reading. most of that is explained in the video itself. i labeled the arrhythmia when it first appeared: VES means ventricular extrasystole, which is equal to PVC (premature ventricular contraction). SES means superventricular extrasystole. LVOT means left ventricular outflow tract. APEX means tip of the heart. i am using a Hellige SMU intensive care monitor and a Logitech USB microphone. - VIDEO: Cardiac Arrhythmia Irregular Heart Beat, Todd Hartley Free Heart Video Diary - Part 1: 's patient advocate Todd Hartley talks about his Supraventricular tachycardia (SVT) heart problem. Find out as it happens. http is a women's online health community. - gas mask play and severe cardiac arrhythmia as i was playing around with my gas mask, doing breathholds, hyperventilating etc., i triggered quite interesting arrhythmia in my heart. in this video, you can see: - sinus / respiratory arrhythmia - sinustachycardia - polytop PVCs - ventricular bigeminus - ventricular trigeminus - polytop couplet - monotop couplet - cardiac arrhythmia EKG sinus tachycardia and lots of polytop extrasystoles. my heart is pretty electrically unstable. - Arrhythmia - Arriesgué En vivo - Arrhythmia Arrhythmia is an abnormal electrical activity in the heart, leading to problem with the rate or rhythm of the heartbeat. ECG used to detect this abnormal electrical activity as the heart beat may be showed too fast (tachycardia) or too slow (bradycardia) rate, and/or may also show regular or irregular rhythm, which all indicate different heart disease. - dead to me-arrhythmic palpitations Warm up Clash Club/Berlin - The Seven Fields Of Aphelion - saturation : arrhythmia 2010 Album "Periphery" - Pneumatic Detach - Grenadier (arrhythmia rmx) From the [re·vis·cer·a] album - The different types of arrhythmia Animation to show the different types of arrhythmia. Thecontent is intended for general information only and does not replace the need for personal advice from a qualified health professional. For more information visit our health information site - Holter Monitoring and Arrhythmia Review Site - reviews a new cardiac rhythm review & resource site - heart rhythms, telemetry, EKGs, holter monitoring, EP, and other cardiac resources. - What is Arrhythmia? What Is Arrhythmia? Dr. Himanshu H. Shukla, MD Explains. For more information: - Jan Allen: ARRHYTHMIA A look into the world of installation artist, Jan Allen, and the opening of Arrhythmia, an art exhibit that she put on to promote her theme of HeArt Art. - cardiac arrhythmia : CPVT in molecular detail The origin of cardiac arrhythmias: mutations in a calcium release channel. music by Filip Van Petegem ( This animation shows what's known about the structure of the Ryanodine Receptor, a large protein that allows calcium ions to move from the endoplasmic reticulum to... - Atrial Fibrillation: The Most Common Heart Arrhythmia Diseases of the heart and blood vessels are the leading causes of death and disability in men and women in the United States, but recent data demonstrates that you can have a positive impact on reducing your risk of cardiovascular disease through lifestyle changes. Join us for a comprehensive review of these complex, but now preventable and treatable, conditions. Series: UCSF Mini Medical School for the Public [8/2010] [Health and Medicine] [Show ID: 18544] - Leading Irregular Heartbeat (Arrhythmia) Treatments bit.ly Arrhythmias, commonly referred to as irregular heartbeats, skipped heartbeats, also include atrial fibrillation and a variety of other abnormal heart rhythm issues, including skipped, slow and fast heartbeats. Fortunately, new technology and techniques have produced many new cardiac arrhythmia treatment options, including minimally invasive arrhythmia surgical [correct?] treatments, for patients to consider. In this video about heart arrhythmias, one of the leading physicians in the field, Dr. Bing Liem, walks you through an overview problems generally in this area and reviews the latest in treatments. - Anti-arrhythmic Medications: Use and Side Effects View more videos at: HSC 407 - Did you know that there might be a cure for your racing heart, pounding chest and fainting spells? Recent clinical studies and advances in medical technology have led to new treatments that can control eliminate many abnormal heart rhythms. Irregular Heartbeats discusses how to recognize arrhythmia and what to do if you have it. - Sinus Arrhythmia ECG / EKG () ECG Simulator by Pace Symposia, Inc. showing Sinus Arrhythmia. Try our simulator free for 24-hours or purchase a license for as little as $9.99. . - Heart Arrhythmia Palpitations and the VALSALVA MANEUVER Heart Arrhythmias Palpitations Doing the Valsava Maneuver! Temp blood pressure for 5 seconds is over 150/120! - Treatment Options for Arrhythmia Arrhythmia's can cause your heart to beat to fast or too slow. Ohio State's Heart and Vascular Center offers a variety of treatment options for this condition. Watch to learn more about our treatment options from Dr. Charles Love and Dr. Emile Daoud and to hear from one of our patients, Dr. Michael Flamm. - What is cardiac arrhythmia? Dr. Jonathan Steinberg at St. Luke's Hospital in NYC. Jonathan S. Steinberg, MD, electrophysiologist and Director of the Al-Sabah Arrhythmia Service at St. Luke's and Roosevelt Hospitals in New York City, tells you what arrhythmia is, the symptoms of arrhythmia, and how it is treated. Visit our website at - Irregular Heart Beat, Arrhythmia, SVT..try not to worry Supraventricular tachycardia or random rapid heartbeat...very different from a heart attack. - What is Arrhythmia? How Do You Treat It? - The heart is the organ that we can feel, though we tend to take it for granted. Unless it starts to beat a little too fast for no reason. - .::arrhythmia::. Controlling an old IBM Selectric with 28 solenoids and my live heart beat. Machine poetry. - cardiac arrhythmias - Cardiac Arrhythmia Animated video about Cardiac Arrhythmia brought to you by MedFlux www.medflux.110 - echocardiography with sound and arrhythmia this is an echocardiography of my heart. i edited the single videos with fitting auscultation sounds from my own heart (recorded with a PC microphone; sorry for the poor quality) and added some descriptions. twitter about arrhythmia Blogs & Forum blogs and forums about arrhythmia “Live Music Band: Arrhythmia, Format: 4 piece, Genre: Grunge, Current Gigs: 0, Section: Blog” — Arrhythmia : Blog - Lemonrock live music gig guide, “The Stephen Cobb blog features posts by the best-selling author and award-winning film producer on topics ranging from technology to politics, society” — arrhythmia — The Stephen Cobb Blog, “Science and Technology go hand in hand and the two together help save lives. A new iphone app released by the charity "Arrhythmia Alliance" in the UK” — Heart Blog: Iphone App to Detect Heart Arrhythmia \| FHG Blog, “Home Forum Value Investing Arrhythmia Research Technology For starters, I would like to thank Jae and the group for the forum where we can all share ideas. I would also like to thank Jae” — Forum \| Old School Value, “An arrhythmia is a change in the rhythm of your heartbeat. When the heart beats too fast, An arrhythmia can also mean that your heart beats irregularly (skips a beat or has an” — Arrhythmia and Tachycardia, a heart issue :: , “When normal heart pulse is interrupted, the situation may lead to cardiac arrhythmia. Learn the natural cures to fight the syndrome” — Cardiac Arrhythmia - Heart Treatment - Heart Remedies \| Home, natural- “12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. arrhythmia's Home. Topic: 未分類 Monthly Archives. All Articles. Search This Blog. Title Contents. Recent Comments. Recent Trackbacks. Visitors Counter” — arrhythmia - Category: Uncategorized Articles, wretch.cc “Cardiac Arrhythmia Diagnosis. Cardiac Arrhythmia Treatment Options. Connect, Learn, and Classes. Dr. Natale's Blog. Videos. Photo Galleries. Facebook. Twitter” — Dr. Natale's Blog :: St. David's Texas Cardiac Arrhythmia, “Twilight Eclipse Cullen's Arrhythmia for EMS – MedicCast TV Episode Subscribe. MP3 Audio Podcast. iTunes \| Zune \| Podcast \| Blog. Twitter \| Facebook. Subscribe to the Podcast Studio” “Interested in cardiac arrhythmia? At http:/// you find posts and information relevant to cardiac arrhythmia” — Cardiac Arrhythmia - Zak Acupuncture Case Studies In London, related keywords for arrhythmia - arrhythmia definition - arrhythmia syncope center - arrhythmia symptoms - arrhythmia treatment - arrhythmia fact sheet - arrhythmia pictures - arrhythmia types - arrhythmia cardiac - arrhythmia icd 9 code - arrhythmia course - arrhythmia definition wikipedia - arrhythmia definition medical dictionary - arrhythmia definition treatment - arrhythmia definition surgery - arrhythmia definition webster - arrhythmia definition spanish - arrhythmia definition heart failure - arrhythmia definition causes - arrhythmia definition heart - supraventricular arrhythmia definition	2	23	1	0	0	0.888423	1	5,504
herpes zoster, also known as shingles, zoster, or zona, is a viral disease characterized by a painful skin rash with blisters involving a limited area. These “excludes” are used when two conditions cannot occur together, such as a congenital form versus an acquired form of the same condition. Viral conjunctivitis is often associated with an infection of the upper respiratory tract, a common cold, and/or a sore throat. Its symptoms include excessive watering and itching. the rash usually heals within two to four weeks; however, some people develop ongoing nerve pain which may last for months or years, a condition called postherpetic neuralgia. ICD-10 Research was designed and developed by Tim Dietrich, a custom software developer. Symptoms consist of redness (mainly due to vasodilation of the peripheral small blood vessels), swelling of the conjunctiva, itching, and increased lacrimation (production of tears). If this is combined with rhinitis, the condition is termed “allergic rhinoconjunctivitis”. The symptoms are due to release of histamine and other active substances by mast cells, which stimulate dilation of blood vessels, irritate nerve endings, and increase secretion of tears. Bacteria such as Chlamydia trachomatis or Moraxella can cause a non-exudative but persistent conjunctivitis without much redness. Bacterial conjunctivitis may cause the production of membranes or pseudomembranes that cover the conjunctiva. Pseudomembranes consist of a combination of inflammatory cells and exudates, and are loosely adherent to the conjunctiva, while true membranes are more tightly adherent and cannot be easily peeled away. Cases of bacterial conjunctivitis that involve the production of membranes or pseudomembranes are associated with Neisseria gonorrhoeae, β-hemolytic streptococci, and C. diphtheriae. Corynebacterium diphtheriae causes membrane formation in conjunctiva of non-immunized children. Irritant or toxic conjunctivitis show primarily marked redness. If due to splash injury, it is often present in only the lower conjunctival sac. With some chemicals, above all with caustic alkalis such as sodium hydroxide, there may be necrosis of the conjunctiva with a deceptively white eye due to vascular closure, followed by sloughing of the dead epithelium. This is likely to be associated with slit-lamp evidence of anterior uveitis. Conjunctivitis is identified by irritation and redness of the conjunctiva. Except in obvious pyogenic or toxic/chemical conjunctivitis, a slit lamp (biomicroscope) is needed to have any confidence in the diagnosis. Examination of the tarsal conjunctiva is usually more diagnostic than the bulbar conjunctiva. Conjunctivitis when caused by an infection is most commonly caused by a viral infection. Bacterial infections, allergies, other irritants and dryness are also common causes. Both bacterial and viral infections are contagious and passed from person to person, but can also spread through contaminated objects or water. The most common causes of acute bacterial conjunctivitis are Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae. Though very rare, hyperacute cases are usually caused by Neisseria gonorrhoeae or N. meningitidis. Chronic cases of bacterial conjunctivitis are those lasting longer than 3 weeks, and are typically caused by Staphylococcus aureus, Moraxella lacunata, or gram-negative enteric flora. Cultures are not often taken or needed as most cases resolve either with time or typical antibiotics. Swabs for bacterial culture are necessary if the history and signs suggest bacterial conjunctivitis but there is no response to topical antibiotics. Viral culture may be appropriate in epidemic case clusters. Conjunctival scrapes for cytology can be useful in detecting chlamydial and fungal infections, allergy, and dysplasia, but are rarely done because of the cost and the general lack of laboratory staff experienced in handling ocular specimens. Conjunctival incisional biopsy is occasionally done when granulomatous diseases (e.g., sarcoidosis) or dysplasia are suspected. There are more serious conditions that can present with a red eye such as infectious keratitis, angle closure glaucoma, or iritis. These conditions require the urgent attention of an ophthalmologist. Signs of such conditions include decreased vision, significantly increased sensitivity to light, inability to keep eye open, a pupil that does not respond to light, or a severe headache with nausea. Fluctuating blurring is common, due to tearing and mucoid discharge. Mild photophobia is common. However, if any of these symptoms are prominent, it is important to consider other diseases such as glaucoma, uveitis, keratitis and even meningitis or carotico-cavernous fistula. For the allergic type, cool water poured over the face with the head inclined downward constricts capillaries, and artificial tears sometimes relieve discomfort in mild cases. In more severe cases, nonsteroidal anti-inflammatory medications and antihistamines may be prescribed. Persistent allergic conjunctivitis may also require topical steroid drops. When appropriate, the choice of antibiotic varies, differing based on the cause (if known) or the likely cause of the conjunctivitis. Fluoroquinolones, sodium sulfacetamide, or trimethoprim/polymyxin may be used, typically for 7–10 days. Cases of meningococcal conjunctivitis can also be treated with systemic penicillin, as long as the strain is sensitive to penicillin. Conjunctivitis due to chemicals is treated via irrigation with Ringer’s lactate or saline solution. Chemical injuries (particularly alkali burns) are medical emergencies, as they can lead to severe scarring and intraocular damage. People with chemically induced conjunctivitis should not touch their eyes, regardless of whether or not their hands are clean, as they run the risk of spreading the condition to another eye. ^ Richards A, Guzman-Cottrill JA (May 2010). “Conjunctivitis”. Pediatr Rev 31 (5): 196–208. doi:10.1542/pir.31-5-196. PMID 20435711. ^ a b c d e f g h i “Facts About Pink Eye”. National Eye Institute. November 2015. Retrieved 8 March 2016. ^ a b c d e f g h i j Azari, AA; Barney, NP (23 October 2013). “Conjunctivitis: a systematic review of diagnosis and treatment.”. JAMA 310 (16): 1721–9. doi:10.1001/jama.2013.280318. PMID 24150468. ^ Forbes BA, Sahm DF, Weissfeld AS. Bailey & Scott’s Diagnostic Microbiology. 12th Edition. Mosby Elsevier, 2007. p. 834. ^ Bielory L, Friedlaender MH (February 2008). “Allergic conjunctivitis”. Immunol Allergy Clin North Am 28 (1): 43–58, vi. doi:10.1016/j.iac.2007.12.005. PMID 18282545. ^ “Pink Eye (Conjunctivitis)”. MedicineNet. ^ a b Zentani A, Burslem J (December 2009). “Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 4: use of litmus paper in chemical eye injury”. Emerg Med J 26 (12): 887. doi:10.1136/emj.2009.086124. PMID 19934140. ^ a b c d Hodge C, Lawless M (July 2008). “Ocular emergencies”. Aust Fam Physician 37 (7): 506–9. PMID 18592066. ^ a b Fisher, Bruce; Harvey, Richard P.; Champe, Pamela C. (2007). Lippincott’s Illustrated Reviews: Microbiology (Lippincott’s Illustrated Reviews Series). Hagerstown MD: Lippincott Williams & Wilkins. ISBN 0-7817-8215-5. ^ a b c d e f Azari, AA; Barney, NP (23 October 2013). “Conjunctivitis: a systematic review of diagnosis and treatment.”. JAMA: the Journal of the American Medical Association 310 (16): 1721–9. doi:10.1001/jama.2013.280318. PMID 24150468. ^ a b c Yanoff, Myron; Duker, Jay S. (2008). Ophthalmology (3rd ed.). Edinburgh: Mosby. pp. 227–236. ISBN 978-0-323-05751-6. ^ Lévêque N, Huguet P, Norder H, Chomel JJ (April 2010). “[Enteroviruses responsible for acute hemorrhagic conjunctivitis]”. Med Mal Infect (in French) 40 (4): 212–8. doi:10.1016/j.medmal.2009.09.006. PMID 19836177. ^ a b “Allergic Conjunctivitis”. familydoctor.org. Retrieved 2015-09-18. ^ a b Pamela Brooks – (2012-10-25). The Daily Telegraph: Complete Guide to Allergies. Retrieved 2014-04-15. ^ a b “What Is Allergic Conjunctivitis? What Causes Allergic Conjunctivitis?”. medicalnewstoday.com. Retrieved 2010-04-06. ^ Puéchal, X; Terrier, B; Mouthon, L; Costedoat-Chalumeau, N; Guillevin, L; Le Jeunne, C (March 2014). “Relapsing polychondritis.”. Joint, bone, spine : revue du rhumatisme 81 (2): 118–24. doi:10.1016/j.jbspin.2014.01.001. PMID 24556284. ^ Cantarini, Luca; Vitale, Antonio; Brizi, Maria Giuseppina; Caso, Francesco; Frediani, Bruno; Punzi, Leonardo; Galeazzi, Mauro; Rigante, Donato (2014). “Diagnosis and classification of relapsing polychondritis”. Journal of Autoimmunity. 48-49: 53–59. doi:10.1016/j.jaut.2014.01.026. ISSN 0896-8411. PMID 24461536. ^ a b Mark J. Mannis; Marian S. Macsai; Arthur C. Huntley (1996). Eye and skin disease. Lippincott-Raven. Retrieved 2014-04-23. ^ a b Longo, DL (2012). “Disorders of the Eye(Horton JC)”. Harrison’s Principles of Internal Medicine. McGra-Hill. ^ a b Isenberg, SJ (2003). “The ocular application of povidone-iodine.”. Community eye health / International Centre for Eye Health 16 (46): 30–1. PMID 17491857. ^ Rose P (August 2007). “Management strategies for acute infective conjunctivitis in primary care: a systematic review”. Expert Opin Pharmacother 8 (12): 1903–21. doi:10.1517/146565188.8.131.523. PMID 17696792. ^ Jimmy D. Bartlett; Siret D. Jaanus (2008). Clinical Ocular Pharmacology. Elsevier Health Sciences. pp. 454–. ISBN 0-7506-7576-4. ^ Visscher, KL; Hutnik, CM; Thomas, M (November 2009). “Evidence-based treatment of acute infective conjunctivitis: Breaking the cycle of antibiotic prescribing.”. Canadian Family Physician 55 (11): 1071–5. PMC 2776793. PMID 19910590. ^ Sheikh A, Hurwitz B (2006). Sheikh, Aziz, ed. “Antibiotics versus placebo for acute bacterial conjunctivitis”. Cochrane Database Syst Rev (2): CD001211. doi:10.1002/14651858.CD001211.pub2. PMID 16625540. ^ Sheikh, A; Hurwitz, B; van Schayck, CP; McLean, S; Nurmatov, U (12 September 2012). “Antibiotics versus placebo for acute bacterial conjunctivitis.”. Cochrane database of systematic reviews (Online) 9: CD001211. doi:10.1002/14651858.CD001211.pub3. PMID 22972049. ^ Isenberg, SJ; Apt, L; Valenton, M; Del Signore, M; Cubillan, L; Labrador, MA; Chan, P; Berman, NG (November 2002). “A controlled trial of povidone-iodine to treat infectious conjunctivitis in children”. American Journal of Ophthalmology 134 (5): 681–688. doi:10.1016/S0002-9394(02)01701-4. PMID 12429243. ^ Smeltzer, Suzanne C. (2010). Brunner & Suddarth’s textbook of medical-surgical nursing. (12th ed. ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 1787. ISBN 9780781785891. ^ “Chennai’s medical history unveiled”. The Times of India (Chennai). 23 August 2011. Retrieved 16 September 2012.	2	13	2	1	0	0.287535	3	3,055
Deep Vein Thrombosis: Everything You Should Know About Deep Vein Thrombosis and KOL #1 Dr. Harry Roger Büller DVT stands for DEEP VEIN THROMBOSIS. DVT is a partial or complete obstruction of the lumen of the venous vessel due to a fibrin thrombus. DVT causes a reduction in blood supply to surrounding tissues and a local inflammatory reaction with the capacity to embolize any blood vessel in the body. Deep vein thrombosis (DVT) is a disease with a high mortality rate. It is a reason for consultation in adults that happens relatively frequently. Deep vein thrombosis of the lower limbs is the most frequent and can be proximal (femoral, popliteal, and iliac veins) or distal (affecting the distal branches of the popliteal veins). These venous thrombi can become detached, migrate through the venous circulation to the right ventricle, and subsequently lodged in the pulmonary arteries, causing pulmonary embolism (PE). DVT: Key Researches Around the World The most prominent DVT researchers are: Paolo Prandoni (Arianna Anticoagulazione Foundation), Harry Roger Büller (Amsterdam University) and John Heit (Mayo Clinic). Before discussing a thrombotic event, it is necessary to mention Virchow's Triad: blood hypercoagulability, endothelial injury, and stasis. Hypercoagulability is the increased predisposition of an individual to excessive or inappropriate formation of blood clots; this condition can be hereditary or acquired. This condition causes alteration in the blood vessel, called tortuosity, and affects the vessel's endothelium, leading to adhesion and blood thrombi formation due to blood stasis (stagnation), resulting in slower blood flow. The approach to lower limb deep vein thrombosis includes the clinical history, focusing on risk factors for developing thrombotic events, a complete physical examination, and risk stratification. The symptoms are varied; the condition can be asymptomatic or symptomatic, manifested by a broad spectrum of signs and symptoms, so a timely diagnosis is essential. Patients with venous thrombosis in the lower limbs generally present the following features: - Localized pain - Swelling in one or both extremities - Bruising or discoloration of the area - Changes in pain perception - Other less specific findings, such as bruising In cases of pulmonary thromboembolism, a condition caused by the detachment of microthrombi into the pulmonary circulation, Symptoms may be absent, but it is important to note that it manifests with: - Dyspnea (sudden onset shortness of breath) - Chest pain - Hemoptysis (coughing up blood) After the physical examination findings mentioned above, the physician should include a predictive model (Wells test) and the D-dimer test to complement the clinical diagnosis. Its results will indicate whether or not there is a need to perform the pertinent complementary examinations that confirm the risk of pulmonary thromboembolism. On the other hand, laboratory tests can provide a differential diagnosis of other diseases, as well as the suspicious presence or complication of thromboembolism. Among them, the most requested are D-dimer and coagulation times, which allow the detection of hypercoagulable conditions. However, it is crucial to remember that other conditions or diseases can raise D-dimer, such as burns, pregnancy, cancer, and kidney failure. Another critical imaging study is the venous doppler ultrasound or echosonogram of the upper or lower limbs, being a simple, fast, safe, and non-invasive procedure. The doppler USG allows us to determine if there is occlusion of the lumen of a vessel and determines the diagnosis of venous thrombosis. What Is the ICD 10 Code for Deep Vein Thrombosis? The ICD / ICD 10 code for Deep Vein Thrombosis is "I82.40" (Acute embolism and thrombosis of unspecified deep veins of lower extremity). Deep Vein Thrombosis: Causes Multiple factors can contribute to the development of deep vein thrombosis. Among them are: - Age greater than 60 years - Smoking (including passive smokers) - Use of estrogen receptor modulators (tamoxifen, raloxifen) - Heart failure - Hypercoagulable diseases - Antiphospholipid antibody syndrome - Antithrombin deficiency - Factor V Leiden mutation (activated protein C resistance) - Thrombocytopenia induced by heparin - Hereditary fibrinolytic disorders - Increased Factor VIII - Increased factor XI - Paroxysmal nocturnal hemoglobinuria - Protein C deficiency - Protein S deficiency - Prothrombin gene mutation (GA variant) - Immobilization of patients in bed - Permeable venous catheters - Extremity injuries - Myeloproliferative neoplasm (hyperviscosity) - Nephrotic syndrome - Oral contraceptives or estrogen replacement therapy - Pregnancy and puerperium - History of venous thromboembolism - Sickle cell disease - Surgery within the previous three months - Traumatisms in general These risk factors predispose to different conditions leading to deep vein thrombosis in the upper and lower limbs. Deep vein thrombosis of the lower limb is most often due to: - Impaired venous return (e.g., in immobilized patients) - Endothelial injury or dysfunction (e.g., after leg fractures) Deep vein thrombosis of the upper limbs is most often due to: - Endothelial injury generated by central venous catheters, pacemakers, or intravenous drug addiction. - Tumor lesion compressing the superior vena cava (causing superior vena cava syndrome (symptoms such as facial swelling, dilated neck veins, and facial erythema). - Hypercoagulable states or subclavian vein compression in the thoracic outlet (exertional thrombosis or Paget-Schroetter syndrome). Thrombus formation leading to deep vein thrombosis usually begins at the cusps of the venous valves. Thrombi are composed of thrombin, fibrin, and erythrocytes with relatively few platelets (red thrombi); Without treatment, thrombi can spread proximally or into the lungs (pulmonary thromboembolism). Treatment of Deep Vein Thrombosis The treatment of deep vein thrombosis should focus on prevention, taking into account those people with risk factors such as obesity, smoking, hypertension, sedentary lifestyle, and limited mobility (postoperative or during convalescence from medical illnesses) should be paramount. If a patient has already presented deep vein thrombosis, the adequate treatment allows for avoiding or reducing complications in the short and long term. Pharmacological treatment with parenteral anticoagulants has allowed a decrease in morbidity and mortality. The main objective of anticoagulation is not only to eradicate the existing thrombus but to prevent the formation of new clots. Currently, the drugs used to treat deep vein thrombosis in the lower limbs are parenteral and oral anticoagulants, such as unfractionated heparin and low molecular weight heparin. Studies show that low molecular weight heparin is the drug of first choice in managing thrombotic events unless the patient has a contraindication that does not allow its use. Using these drugs two to four hours after initiation protects against future thrombotic events. Parenteral heparin should be co-administered with vitamin K antagonists such as warfarin for the first few days and with close control of clotting times and medical monitoring. Subsequently, warfarin will be the maintenance medication to prevent further thrombotic events. The maintenance phase must be maintained for weeks or months, depending on the patient, because the objective of anticoagulation is to avoid the recurrence of thrombotic events, and the decision to continue or suspend treatment must be personalized and taken based on the risk of bleeding. Another treatment option is the application of an inferior vena cava filter, which is a device inserted and moved through the venous system at the level of the femoral vein up to the inferior vena cava to locate and avoid the passage of emboli as well as their possible migration. The indications for using this device are: presenting recurrent episodes of venous thrombosis in patients who have already received anticoagulant treatment, acute pulmonary edema, proximal venous thrombosis, or absolute contraindication for anticoagulant therapy. Thrombolysis is a method that consists of administering a thrombotic drug into the venous system, aiming to eliminate the clot that obstructs a vessel's lumen. However, this method is uncommon due to the risk of bleeding, so a previous coagulation test is necessary to search for thrombophilias. Likewise, other complications that limit the use of this procedure are hemolysis, cardiac tamponade, perforation of the pulmonary arteries, and bradycardia. Contrast-enhanced venography confirms the diagnosis of DVT, but ultrasounds have replaced it due to being non-invasive, more readily performed, and nearly as accurate in detecting DVTs. Venography can indicate whether the ultrasound results are typical, but the pretest suspicion of deep vein thrombosis is high. The downside would be an allergy to contrast agents. Other tests include magnetic resonance, venography with intravenous contrast medium, and direct magnetic resonance imaging of thrombi, which is very useful in diagnosing pulmonary embolisms. Surgery to Treat Deep Vein Thrombosis Surgery is rarely necessary. However, in phlegmasia alba dolens or phlegmasia cerulea dolens, which do not respond to thrombolytics, it is essential to perform a thrombectomy, fasciotomy, or both to try to avoid gangrene that leads to limb loss. Prevention of Deep Vein Thrombosis: Deep vein thrombosis (DVT) is a disease with high morbidity and mortality, so it is necessary to prevent it. There are two primary objectives for applying prophylactic measures: the physical ones, aimed at combating venous stasis, and the more effective pharmacological ones, aimed at reducing hypercoagulability. This favors the prevention of thromboembolic complications, the reduction of related mortality, or the long-term sequelae of venous thromboembolism, such as post-thrombotic syndrome. For this, the prophylaxis of pulmonary thromboembolism consists of the application of physical and pharmacological measures, with a duration that depends on the evaluation of the thrombotic risk factors presented by each patient based on four main recommendations: - Keep hydrated - Avoid tobacco or smoking - Eat a healthy diet to avoid being overweight - Exercise regularly - Take rest measures on long trips, as well as do flexion and extension exercises (pumping) - Control of chronic diseases to avoid complications Includes active or passive mobilization and keeping the extremities elevated. Especially relevant after surgical interventions or limiting diseases that predispose to thromboembolic risks. Use of gradual compression elastic stockings or intermittent pneumatic compression boots. They consist of subcutaneous (SC), oral or intravenous administration of heparin, unfractionated heparin (UFH), low molecular weight (LMWH), or pentasaccharide. The most recommended drug is subcutaneous low molecular-weight heparin in a single daily dose without laboratory monitoring. Complications of Deep Vein Thrombosis Common complications of deep vein thrombosis include - Chronic venous insufficiency - Postphlebitic syndrome - Pulmonary embolism Chronic venous insufficiency is damage to the veins in the legs that prevents blood from flowing normally. Postphlebitic syndrome is a chronic venous insufficiency caused by a blood clot in the veins. Pulmonary embolism (PE) depends on the size and number of emboli: small emboli can obstruct a small-caliber pulmonary artery, causing the death of a piece of lung tissue (pulmonary infarction). In the case of a large pulmonary embolus, it can block the pulmonary artery, thus causing arterial hypotension, hypoxemia, and sudden death. Less commonly, deep vein thrombosis causes - Leuko phlegmasia dolens or phlegmasia cerulea are both responsible for the development of venous gangrene if they are not diagnosed and treated on time. - Infection in venous clots, in this phenomenon, is described as: - Suppurative thrombophlebitis of the jugular vein (Lemierre's syndrome). - Septic pelvic thrombophlebitis, in which postpartum pelvic thrombosis occurs, which then becomes infected and causes intermittent fever. - Suppurative (septic) thrombophlebitis, a bacterial infection of a superficial peripheral vein, includes infection and clot formation that often occurs due to the placement of a venous catheter. Venous Thromboembolism in Pregnancy It is a significant cause of morbidity and mortality in pregnancy; it can occur due to the following: - Capacitance and venous pressure in the legs increase, leading to stasis. - Pregnancy causes some degree of hypercoagulability. However, most thrombi and emboli develop postpartum and result from vascular trauma during delivery. The risk of developing deep vein thrombosis may increase for about six weeks after delivery. This risk is also higher with cesarean sections. Deep vein thrombosis is a pathological entity highly related to risk factors such as agents that cause hypercoagulability states and predisposing factors such as chronic diseases that affect circulation and favor venous stasis. Those associated with the use of drugs and devices such as venous catheters. Prevention and timely treatment decrease the risk of complications, and treatment with anticoagulant drugs is the choice for these patients. Dr. Harry Roger Büller: KOL #1 for Deep Vein Thrombosis According to KOL's technology, Dr. Harry Roger Büller is the top ranking Key Opinion Leader (worldwide) for Deep Vein Thrombosis. You can see Dr. Harry Roger Büller's KOL resume and other concepts for which they rank #1 worldwide. Harry Büller, MD, is professor of internal medicine, specializing in vascular medicine, at the Academic Medical Center in Amsterdam, The Netherlands. Professor Büller earned his MD and PhD from the University of Amsterdam. After graduating, he completed his research fellowship in hemostasis and thrombosis in the Departments of Medicine and Clinical Epidemiology and Biostatistics at McMaster University in Hamilton, Ontario, Canada. Professor Büller has authored and co-authored more than 650 scientific articles concerning topics in his field (H-index 95). He has been Co-Chairman of the Amsterdam Institute for Cardiovascular Research and is Chairman of the Vascular Medicine Working Group. He is a reviewer for The New England Journal of Medicine, The Lancet, Archives of Internal Medicine, and European Journal of Clinical Investigation, among others. Professor Büller was Chairman of the 2004 CHEST conference on antithrombotic therapy for venous thromboembolic disease: the Seventh American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy. He is the recipient of the Established Investigator Award presented by the Dutch Heart Foundation, and he received the Dutch Society for Vascular Medicine Award in 2005. Since 2008, he has served as Honorary Professor of the Royal Netherlands Academy of Arts and Sciences. Biography courtesy of: https://usern.tums.ac.ir/User/CV/HarryBuller Who are the top experts researching treatments for deep vein thrombosis? The top experts researching deep vein thrombosis are: Harry Roger Büller, Henri M Bounameaux and Jeffrey S Ginsberg. What are the top concepts researched in studies about deep vein thrombosis? The most researched concepts in studies of deep vein thrombosis are: deep vein thromboembolism, deep vein thrombophlebitis and deep vein thrombophlibitis. What are some of the top places that specialize in deep vein thrombosis? Recommended institutions that specialize in deep vein thrombosis: - California Institute For Deep Vein Thrombosis23823 Valencia Blvd #150, Valencia, CA 91355 Phone: +16617997444 - Premier Vein Clinic: David Naar, MD24700 Center Ridge Rd # 370, Westlake, OH 44145 Phone: +14406410433 - Dr. Khemendra Kumar Best Vascular Doctor \| Varicose Veins \| Deep Vein Thrombosis \| Varicocele \| DVT in NoidaChamber No. 3, opposite fire station, Mamura, Sector 66, Noida, Uttar Pradesh 201301, India Phone: +918095215100 - Mizonokuchikeiyu Clinic 溝の口慶友クリニックJapan, 〒213-0011 Kanagawa, Kawasaki, Takatsu Ward, Hisamoto, 3 Chome−1−31 ユーランド溝ノ口ビル 4F Phone: +81448508080 Recent articles about Deep Vein Thrombosis Exclusion Of Deep Vein Thrombosis Using The Wells Rule In Clinically Important... .. excluding deep vein thrombosis and whether this accuracy applies to different subgroups of patients. DESIGN: Meta-analysis of individual patient data. DATA SOURCES: Authors of 13 studies ... Known for Wells Rule \| Deep Vein Thrombosis \| Patients Cancer \| Individual Patient \| Data Meta Deep Vein Thrombosis During Pregnancy And The Puerperium .. of deep vein thrombosis during pregnancy and the puerperium using MEDLINE between 1966 and May 1998. Data were pooled using a random effects model. Fourteen studies included relevant ... Known for Deep Vein Thrombosis \| Pregnancy Puerperium \| Postpartum Period \| Objective Testing \| Risk Venous Deep Vein Thrombosis After Major Spinal Surgery .. of deep vein thrombosis after major spinal surgery in an east Asian population without antithrombotic prophylaxis. SUMMARY OF BACKGROUND DATA: Spinal surgery has been associated with few ... Known for Deep Vein Thrombosis \| Spinal Surgery \| Preschool Decompression \| Background Data \| Lower Extremities The Use Of D-Dimer Testing And Impedance Plethysmographic Examination In Patients... .. of deep vein thrombosis can be excluded in outpatients who present with clinical indications of deep vein thrombosis and whose results of D-dimer testing and impedance plethysmographic ... Known for Deep Vein Thrombosis \| Dimer Testing \| 3 Months \| Pretest Probability \| Predictive Tests Upper Extremity Deep Vein Thrombosis: A Community-Based Perspective .. extremity deep vein thrombosis diagnosed in 1999. METHODS: The medical records of all residents from Worcester, Massachusetts (2000 census=478,000) diagnosed with ICD-9 codes consistent ... Known for Deep Vein Thrombosis \| Upper Extremity \| Pulmonary Embolism \| Patients Lower \| Management Strategies Using An Age-Dependent D-Dimer Cut-Off Value Increases The Number Of Older... .. out deep vein thrombosis is less useful in older patients because of a lower specificity. An age-adjusted D-dimer cut-off value increased the proportion of older patients (>50 years) in ... Known for Deep Vein Thrombosis \| Dimer Cut \| Patients Age \| Fibrin Fibrinogen \| 50 Years Intermittent Pneumatic Compression Reduces The Risk Of Deep Vein Thrombosis... Deep vein thrombosis is a common complication of immobilising the lower limb after surgery. We hypothesised that intermittent pneumatic compression (IPC) therapy in outpatients who had ... Known for Deep Vein Thrombosis \| Achilles Tendon \| Lower Limb \| Intermittent Pneumatic \| Surgical Repair Deep Vein Thrombosis After Total Hip Arthroplasty In Korean Patients And D-Dimer... .. of deep vein thrombosis after total hip and surface replacement arthroplasty in Korean patients not receiving anticoagulation prophylaxis and to determine efficacy of plasma D-dimer levels ... Known for Deep Vein Thrombosis \| Hip Arthroplasty \| Ddimer Levels \| Postoperative Day \| Screening Test Superficial Thrombophlebitis And Deep Vein Thrombosis: A Controversial Association .. with deep vein thrombosis, a more severe condition that requires anticoagulant treatment, has been reported repeatedly with frequencies ranging from 12% to 44%.Methods: All consecutive ... Known for Superficial Thrombophlebitis \| Deep Vein Thrombosis \| 95 Confidence Interval \| 3month Followup Period \| Anticoagulant Treatment Comparison Of Four Strategies For Diagnosing Deep Vein Thrombosis: A... .. of deep vein thrombosis have been validated recently. The strategies use various combinations of assessment of a patient's clinical probability of having deep venous thrombosis, serial ... Known for Deep Vein Thrombosis \| Clinical Probability \| Diagnostic Strategies \| Ultrasound Patients \| Ultrasonography Venous	2	9	1	0	2	0.832002	3	4,830
Geriatric medicine involves health concerns of the elderly population, and these cover a number of syndromes and conditions. Dementia, urinary incontinence, osteoarthritis, diabetes, cardiovascular diseases, cerebrovascular diseases, hypertension, hearing concerns, and hyperthyroidism are some of the major conditions. Geriatricians carry out various examinations and offer counseling sessions for their patients. Practitioners in this field also screen patients for various psychosocial concerns. Dementia Codes - Medical and Psychiatric Codes Dementia is a condition that affects a number of old people and it is defined as the progressive and severe impairment of one's brain function that interferes with one's normal functioning. Dementia is usually irreversible. It may be mild, moderate, severe or profound. The new codes for dementia are provided in ICD-10 Chapter V: Mental and Behavioural Disorders. These codes signify various types of dementia and include medical codes and psychiatric codes. When billing for dementia, service providers should give the correct diagnostic codes for medical conditions causing irreversible dementia such as: • Alzheimer's disease • Frontotemporal dementia • Multi-infarct dementia • Parkinson's disease with dementia • Huntington's disease • Senile degeneration of the brain • Mild cognitive impairment • Dementia with Lewy bodies • Pick's disease • Binswanger's disease • Creutzfeldt-Jakob disease • Multiple sclerosis • Unspecified cerebral degeneration • Memory loss and late effects of CVD Psychiatric codes signify uncomplicated senile dementia, presenile dementia, senile dementia with delusional features, senile dementia with depressive features, senile dementia with delirium, arteriosclerotic dementia, dementia without behavioral disturbances, and dementia with behavioral disturbances. When coding, it is necessary to indicate whether the dementia occurred with or without behavioral disturbances such as violent behavior, aggressive behavior, wandering off and more. Reversible types of dementia are treatable and are most often caused by conditions such as brain tumors, chronic alcoholism, infections, certain deficiencies, heavy-metal poisoning, hyperthyroidism and so on. Providers can bill for pharmacologic, physical, occupational, speech-language and other therapies that are provided for their dementia patients. Payers require that providers clearly enter their primary diagnosis as well as the secondary diagnosis that support the medical necessity of the services provided. In case the patient suffers from an illness or injury not related to their dementia, the physician's primary diagnosis recorded in the claim should reflect clearly the need for the billed service. Factors that Have an Impact on Reimbursement • CMS does not regard certain diagnostic codes as regular medical codes. As a result, these are not reimbursed at the usual rate, sometimes these are not paid at all. The provider has to have in-depth knowledge regarding the assignment of the correct primary and secondary diagnostic codes to ensure full reimbursement. • Reporting all professional services in all settings such as inpatient, outpatient, home and nursing facilities, correctly using the appropriate CPT five digit codes • Appropriate use of evaluation and management (E/M) codes or the five digit codes used to report non-procedural professional services. These codes should clearly highlight the complexity of the service provided. Tests such as gait and balance assessment, mini mental status exam, history, physical and family interview do not have their own CPT codes. So these are included under E/M. A physician's interaction with the patient includes screening, procedure visit and visit for discussing results. For effective reimbursement, the correct diagnostic and procedural codes have to be assigned for each of these visits. During screening, the physician identifies the condition for which the appropriate diagnostic code has to be assigned. Any new problem that requires a differential diagnosis has to be documented during the procedure visit. The provider has to also ascertain whether requirements for a higher level code are met. Additional documentation includes valid diagnostic codes to justify a comprehensive exam, codes to report any co-existing conditions such as diabetes, weight loss, delirium and so on. This is important with regard to using higher levels of E/M coding. In the case of a patient with multiple problems, the doctor will have to spend more time to complete the assessment. It is the visit's complexity that would justify billing for the highest level E/M. • 99205 - Level 5 comprehensive exam for new patient • 99215 - Level 5 comprehensive exam for established patient • 96116 - neurobehavioral status examination Codes to Use for Care Management Provided • First hour - 99358 • Each additional 30 minutes - 99359 • Telephone services - 99371-3 Tips for Accurate Coding Review of systems (ROS), history of present illness (HPI), family, physical examination, social medical history, medical decision making, time spent for discussion of counseling, and organizing care, all these have to be taken into account when assigning E/M codes. When coding for dementia, under no circumstances should a lower level of service be reported using a higher level code. If you are to receive due reimbursement, medical necessity of a provided service is of course the primary consideration. Individual requirements of the CPT codes used are also a major criterion. The level of service reported should have sufficient supporting documentation. Geriatric Medical Coding - Outsource Strategies International (OSI), a leading medical billing and coding company in the US, provides a comprehensive suite of medical billing and coding outsourcing services.	4	7	1	0	0	0.943804	1	1,140
In 1988, doctors advising the American Centres for Disease Control (CDC) formulated a working case definition for a disorder they called chronic fatigue syndrome (CFS). It was thought to be a single illness, probably the result of infection, but not as 'neurological' as the established condition known as myalgic encephalomyelitis (ME). Unfortunately, the criteria for CFS actually selected a mixed population and now this term covers nearly everyone with profound, chronic, unexplained fatigue1. For instance, in articles published here and in the States, it has described cases of fatigue due to primary sleep disorders, simple nutritional deficiencies, stress and a number of psychiatric conditions. Another subgroup is ME. This can be summarised as a post-viral syndrome where the fatigue is closely linked to exertion, and where other symptoms suggest impaired circulation and central nervous system involvement. It's similar, though not identical, to some cases of fibromyalgia and Gulf War syndrome. Prevalence studies support this analysis. A study using the latest criteria estimated that about 2-3% of the general population may have CFS. Conversely, criteria used to identify ME-type syndromes select a much smaller population, about 0.1%2. Given the differences which have been found among the various fatigue syndromes, it's no longer valid to describe CFS as a single entity with a single cause3. Incidentally, CFS has remained a research diagnosis. There are no accepted criteria for use in clinical situations so GP's are still entitled to diagnose post-viral fatigue syndrome, listed as G93.3 under Diseases of the Nervous System in the International Classification of Diseases, volume 10 (ICD-10), or neurasthenia, category F48.0 found under psychiatric disorders4. Although the World Health Organisation no longer recommends the use of the term ME, the current reluctance to diagnose this condition probably has more to do with medical politics and current fashions rather than science or a desire for accuracy. In my view, the use of increasingly wider criteria and the obsession with fatigue has created much confusion and misunderstanding during the past decade. If one compares the descriptions of the symptoms of ME and CFS, the personalities of the patients and the prevalence rates, one can tentatively conclude that all patients with ME have CFS but that not everyone with CFS has ME. Almost every illness has a physical and psychological component so splitting disorders into the medical and psychiatric is simplistic to say the least. However, the fact is that many doctors still do not provide the same level of emotional and practical support to those with psychosomatic conditions. Moreover, only people with a physical disability qualify for the higher rate mobility component of DLA in the UK. As we have to deal with the real world and real prejudices, here is some of the evidence for ongoing 'physical' disease. In broadly-defined CFS, the research is equivocal and confusing. However, studies on more strictly defined groups have identified abnormalities within the brain5,6, muscles7, heart8, and immune system9. Some of these changes have been linked to the severity of the disease10. Less clear are the roles of stealth viruses11, metabolites like CFSUM1 (doubts have arisen since the early research has not been replicated, even by the same team12), mutant enteroviruses13 and the increased rates of cell death14. In short, there is some evidence for a persistent viral infection in a subgroup of patients, while in others, there are clear signs of immune system activation, muscle damage and other changes suggesting ongoing disease. Studies being completed at the moment are assessing whether low blood volume, the blood brain barrier and presence of certain pathogens (bacteria, parasites) in the gut play a significant role in CFS. The research suggests that among broadly-defined populations, there is a subgroup whose ongoing fatigue may be the direct result of excessive inactivity and maladaptive (irrational, unrealistic) beliefs15. This subgroup tends not to have the abnormalities discussed above. A small proportion of patients are thought to suffer from a somatisation disorder (i.e. hysteria) or depression which have been misdiagnosed. Please note that there is as yet no reasonable evidence that this explanation applies to the majority of people with CFS (see update elsewhere). Since this is such a mixed population, effective management depends on which subgroup one belongs to. For instance, some patients with signs of ongoing infection have responded to the appropriate anti-viral or immunity-boosting drugs8. Where there is a lack of certain vitamins (D, B12) or food sensitivities, supplementation and dietary modification have had impressive results16. Indeed, some American specialists now routinely check for and treat ongoing infections, nutritional deficiencies and low thyroxine levels17. In the UK, researchers have found that lifestyle advice e.g. about expenditure of energy, diet etc. plus stress management and counselling, can significantly reduce disability and distress18. As far as exercise is concerned, those who do not engage in 'excessive rest' or who tend to operate at their own activity ceilings should learn to pace themselves through the day18. However, for people whose fatigue appears to be maintained by unhelpful beliefs and behaviours, cognitive-behaviour therapy (CBT) plus graded activity is the treatment of choice19. In my opinion, the question to be answered is not so much whether patients should exercise but how much and when. NB. 'Graded' means that patients cannot reduce or stop activity when they feel ill, while gentle exercise and pacing are more flexible. Looking back over the literature on CFS, this decade was dominated by psychobabble and some very biased reporting in the UK medical press. However, science always rights itself and things are improving. What people need now, apart from more editorial balance in the medical journals, are two things. Firstly, we need better criteria to separate the different fatigue syndromes. Without them, researchers will continue to report inconsistent and confusing findings (see studies of cortisol levels, prevalence of depression, abnormalities of concentration and memory etc.). Secondly, doctors must begin to trust people with CFS. The message of the past ten years, seems to have been 'don't believe what your patients say.' In addition, the doctors and scientists who challenged this irrational attitude were isolated and insulted. It's a highly unscientific approach which not only caused a great deal of unnecessary hostility, but also wasted valuable time. Good science demands an open-mind, and that means listening to and respecting those with a different view20. Dr. Ellen Goudsmit. Chartered Health Psychologist. 1. Fukuda et al. Annals of Internal Medicine, 1994, 121, 953-959. (Current CDC criteria with references to older versions) For a definition of ME see Dowsett and Welsby, Postgraduate Medical Journal, 1990, 526-530. According to Dr. Melvin Ramsay, who wrote the most detailed descriptions of the illness, the typical symptoms of ME can be categorised in terms of three components: fatiguability, cerebral dysfunction and circulatory impairment. Muscle fatiguability is a dominant feature of the illness. It comes on after comparatively little physical effort and a period of 24 hours to five days may elapse before full muscle power is restored. Particularly affected are the weight bearing muscles in the leg, but Ramsay added that weaknesses could also occur elsewhere. Thus fatigue in the sphincter muscle might result in increased frequency of urination, and weakness of the masseter muscle could lead to dribbling of saliva from the mouth. Delayed recovery of muscle function has been documented (using objective tests) in people with a ME-like illness (Wood et al, in press) but not, to my knowledge, in studies on general CFS. The second component, cerebral dysfunction, is manifested by symptoms such as impaired memory and concentration, difficulties completing sentences and finding the right word, a reduced tolerance of loud noises, 'brain fatigue' and emotional lability. The third component could explain the facial pallor which is visible before a patient reports feeling ill, and having cold extremities, even when it's warm. Other typical symptoms include blurred vision, giddiness, general muscle pains and twitchings, abnormally low temperatures and 'feeling awful'. Ramsay also noted the recurrence of sore throats, feeling faint (cf. recent research on blood volume), and the increasing sensitivity to foods and drugs. Furthermore, he described the typical fluctuations in the severity of the symptoms, he advocated pacing and was open-minded about supplements (Pulse, 1983, Jan. 15th, 48). ME frequently follows infections, particularly during the months from May to November. The onset tends to be acute and sometimes biphasic, i.e. patients report an initial improvement, followed by a worsening. However, gradual onset cases are acknowledged. The 1994 CDC criteria for CFS require the presence of profound, unexplained fatigue lasting six months or more, plus four symptoms out of a list of eight. These include impaired concentration or memory, post-exertional malaise, new headaches, unrefreshing sleep, muscle and joint pain, sore throat and tender glands. In other words, the focus is on fatigue rather than fatiguability, and one can qualify for a diagnosis of CFS without evidence of cerebral dysfunction. As far as PVFS is concerned, some researchers believe it is identical to ME while others maintain that there are notable differences. In America, some patients prefer the term chronic fatigue and immune dysfunction syndrome (CFIDS). However, it's unclear how this differs from CFS and this name is rarely used in the medical press. Articles discussing the heterogeneity of CFS include Jason et al. American Psychologist, 1997, 52, 9, 973-983. Laymen can find more information on ME and CFS in Dr. Anne Macintyre's new book ME (Chronic Fatigue Syndrome - A Practical Guide) (Thorsons, 1998). 2. Ho-Yen and McNamara. British Journal of General Practice, 1991, 41, 324-326. See also Wessely et al. American Journal of Public Health, 1997, 87, 9, 1449-1455. Note the similar estimates using the Oxford and CDC 1994 criteria for CFS. 3. Even a straightforward separation of acute and gradual onset cases has proved illuminating. For instance, acute onset cases have slightly different immune system abnormalities than those with a gradual onset and they are less often associated with psychiatric disorders and stress. Mawle et al. Journal of Infectious Diseases, 1997, 175, 1, 136-141 and Reyes et al. Journal of Chronic Fatigue Syndrome, 1996, 2, 4, 17-33. See also DeLuca et al, Journal of Psychiatric Research, 1997, 31, 1, 83-90 or Christodoulou et.al. In Yehuda, S and Mostofsky, DI (eds.) Chronic Fatigue Syndrome. NY: Plenum Press. 1997. For a comparison of ME-like conditions and broadly-defined groups, compare Lerner et al with Surawy et al (details under notes 8 and 15). 4. ICD-10 is compiled by the World Health Organisation. It is acknowledged as the main classification system of disorders in the world. However, psychiatric illnesses tend to be diagnosed according to DSM-IV, a system compiled by the American Psychiatric Association but also used in the UK. 5. Costa et al. Quarterly Journal of Medicine, 1995, 88, 767-773, recently replicated using PET scans by Tirelli et al. American Journal of Medicine, 1998, 105, 3A 54s-58s. See also Costa and Richardson, Journal of Chronic Fatigue Syndrome, 1998, 4, 3, 23-38, and Schwartz et al. American Journal of Roentgenology, 1994, 162, 4, 943-951. 6. McGarry et al. Annals of Internal Medicine, 1994, 120, 11, 972-973. 7. Lane et al. Journal of Neurology, Neurosurgery and Psychiatry, 1998, 64, 362-267. See also Behan et al. Acta Neuropathologica, 1991, 83, 61-65 and Kuratsune et al. International Journal of Molecular Medicine, 1998, 2, 1, 51-56. 8. Lerner et al. Infectious Diseases in Clinical Practice, 1997, 6, 110-117. This study describes patients suffering from CMV who were helped by taking ganciclovir. 9. Hassan et al. Clinical Immunology and Immunopathology, 1998, 87, 60-67. See also Bennett et al, Journal of Clinical Immunology, 1997, 17, 3, 253-261 and Landay et al, Lancet, 1991, 338, 707-712. 10. See Landay et al and Hassan et al, above. 11. Martin and Anderson. Pathobiology, 1997, 65, 51-56 and Martin, ibid, 1997, 65, 57-60. 12. Conference report, Sydney 1998. 13. Bowles et al. Journal of Medicine, 1993, 24, 145-160. 14. Vojdani et al. Journal of Internal Medicine, 1997, 242, 6, 465-478. 15. Surawy et al. Behavior, Research and Therapy, 1995, 33, 535-544. See also Hickie et al. Psychological Medicine, 1995, 25, 925-935. Most of the research on broadly defined groups has failed to find the type of abnormalities reported in more strictly defined populations (e.g. the work by the Nijmegen team, the research by the CFS unit at King's etc.). 16. Hock. Journal of Chronic Fatigue Syndrome, 1997, 3, 3, 117-127 (re vitamin D). See also Borok, ibid., 1998, 4, 3, 39-57 (re food sensitivities) and Regland et al, Scandinavian Journal of Rheumatology, 1997, 26, 301-307 (B12). 17. Teitelbaum and Bird. Journal of Musculoskeletal Pain, 1995, 3, 4, 91-110. A drug of the future is Ampligen. However, it is probably not suitable for everyone with CFS. 18. Goudsmit. The Psychological Aspects and Management of CFS. PhD Thesis. 1996. Available from the British Thesis Service in various forms (phone 01937 546229). 19. Wessely et al. Chronic Fatigue and its Syndromes. Oxford University Press. 1998. This includes a detailed description of the personality, beliefs, and behaviour of patients who respond to CBT and graded exercise. However, it does not describe ME. See also Jason et al1 for critical comments, and note that graded exercise has not yet been tested in people with pure ME or PVFS. 20. See Wessely et al, note 19 and Surawy et al, note 15, for illustrations of this sceptical approach. Also recall that the Working Party who wrote the Royal Colleges Report did not include a single ME specialist or expert who disagreed with the CBT model. For years, I have advocated pacing as a strategy for coping with the illness. However, as a result of experience AND the latest research, I can now refine this advice. So in addition to pacing, Id like to introduce the concept of switching. Switching means changing activities to avoid tiring specific muscles. For instance, if youve been reading for a while, stop before your eye muscles get tired and do something which involves a different muscle group, e.g. walking, washing clothes, eating, talking. Do that for a while (stop before you reach your limit), then switch again (you can even go back to reading). The research behind pace and switch is the work by Paul et al (1999) - They found that our muscles lose strength in the same way as healthy people during exercise but that unlike everyone else, we continue to lose strength afterwards. A Consultant (who has been studying ME since 1955) wondered if stopping an activity before the tiredness set in might keep the additional loss of muscle strength to a minimum. He began switching, and it worked for him. I know that its not easy to stop activities which you havent finished but on the other hand, if you can extend your energy levels this way, why not give it a try? The same rule applies to mental exertion (i.e. switch before you start feeling tired). Also, remember to balance physical and mental activities with rest (and that doesnt mean watching TV). If youre in a relapse, you may have to be strict i.e. physical activity - rest - mental activity - rest etc. However, as you improve, you should be able to do more and rest less without paying for it. See what and how much you can manage in a day using this new method. It takes some self-discipline but what have you got to lose? Ellen Goudsmit (Dr.) Chartered Health Psychologist Copyright Dr. EM. Goudsmit September Chartered Health Psychologist/Archivist, London. All rights reserved. This article may not be reproduced without permission from the author. See the full copyright notice.	2	6	1	0	4	0.934827	5	3,632
Serving all people by providing personalized health and wellness through exemplary care, education and research. Explore health content from A to Z. I need information about... You have a condition called heart failure. It is also known as congestive heart failure (CHF). This condition causes symptoms such as getting tired very quickly and being short of breath. To help treat these symptoms, your healthcare provider is recommending a biventricular pacemaker and implantable cardioverter defibrillator (ICD). This is sometimes called a biventricular ICD. Or it is called cardiac resynchronization pacing with an ICD (CRT-D). A biventricular pacemaker and ICD is a small, lightweight device powered by batteries. This device helps keep your heart pumping normally. It also protects you from dangerous heart rhythms. Read on to learn more about this device and how it works. The heart is made up of 4 sections (chambers) that pump to move blood through the heart. The top 2 chambers are the left atrium and right atrium. These are filling chambers of the heart. The bottom chambers are the left ventricle and right ventricle. These are the pumping chambers of the heart. The heart has an electrical system. This system sends signals that make the atria and ventricles work together. This causes the heart to beat and move blood through the heart and lungs and out to the body. Heart failure weakens your heart muscle. As a result, the ventricles don’t pump as strongly as they should. The pathways that carry the heart's electrical signals are located in the heart muscle. They can also be damaged by CHF. This can cause a bundle branch block. A bundle branch block can throw off the timing of the heart's contraction. This can make the heart's squeezing contraction even weaker. A biventricular pacemaker and ICD help keep the heart pumping in a more normal way. The pacemaker device keeps the heart from beating too slowly. It tries to restore the normal squeezing pattern of the heart. This is called resynchronization pacing. This can lead to more efficient and stronger heart contraction. The ICD part of the device detects dangerously fast heart rhythms and stops them. If the device detects an abnormally fast heartbeat that can cause cardiac arrest, it will send a "shock" to the heart. The shock stops this dangerous heart rhythm and restores a normal heartbeat. Make sure to: Not eat or drink after midnight or 8 hours before your surgery Follow instructions from your doctor about bathing the night before and the morning of your procedure. You may need to use a special cleaning solution. Tell your doctor what medicines you take. This includes over-the-counter medicines such as ibuprofen. It also includes vitamins, herbs, and other supplements. You may need to stop taking some medicines before the procedure, such as blood thinners and aspirin. Tell your doctor if you are sensitive or allergic to anything. This includes medicines, latex, tape, and anesthetic medicines. Ask a family member or friend to take you home from the hospital Before your procedure you may need tests such as: Blood tests, to test your general health You will get medicine (anesthesia) so you won’t feel pain. Most likely, you will get medicine (sedation) that will make you drowsy or lightly asleep. The doctor will inject local pain medicine to numb the skin on your chest where the cut (incision) will be made. The doctor will make an incision where the device will be implanted. This is most often on the left side of the chest just below the collarbone (clavicle). The doctor makes a small “pocket” for the generator under the skin. The doctor will put a thin, flexible tube (catheter) into a vein leading to the right atrium. He or she will guide the device’s wires (leads) through the catheter to the heart. The doctor will use an X-ray monitor to move the leads into the right ventricle. He or she will usually also put a lead in the right atrium. The doctor will put the lead for the left ventricle into a vein that runs along the outside of this chamber. He or she will also use the X-ray monitor to put this lead in the correct spot. The device will stimulate the left ventricle from the outside. The other leads will stimulate the heart from inside the chambers. The doctor will attach the generator to the leads. He or she will send pulses through the leads to test the generator. This testing may cause your heart to race. The doctor will then put the generator into the pocket under your skin. The doctor will program the device based on the heart rate that’s best for you. He or she will check the device to see that it is working. The doctor will close the skin with stitches (sutures), surgical glue, or staples. Any stitches used will dissolve over time. If glue is used, it will seal the cut and prevent infection. A bandage will be put on the area. You will spend several hours in a recovery room. Once you are stable and awake, you will be put in a room that can monitor your heart rhythm. Your healthcare team will also watch your breathing and other vital signs. You’ll be given pain medicine if you need it. The team may place the arm on the side of the device in a sling. This is just for a short time, to keep the arm and shoulder still. You will have a chest X-ray to make sure the leads are where they should be. The doctor will also check that your lungs were not injured during the procedure. You can resume a normal diet as soon as you are able. You will be watched overnight. The team will check the device the next morning. You will likely go home the day after your procedure. You may need to take antibiotics for several days to prevent infection. Follow all the instructions your healthcare provider gives you for medicines, bathing, exercise, diet, and wound care. Ask your doctor when you can go back to work or start driving again. Don’t raise your arm above your shoulder on the side of your incision until your doctor says it’s OK to do so. This gives the leads a chance to secure themselves inside your heart. Make sure to keep all your follow-up appointments. This is so your doctor can download information from your device and check its settings. Be sure to tell your doctor how the device is working for you. Most devices can now be connected to a wireless home monitoring system via the internet. The monitor can download information from your device and send it to your doctor. This lets your doctor make sure the device is working as it should. Carry an ID card. When you first get your pacemaker, you’ll be given an ID card to carry. This card contains important information about the device. Show it to any doctor, dentist, or other provider you visit. Pacemakers may set off metal detectors. So you may need to show your card to security personnel. Be careful when using a cell phone. Hold it to the ear farthest from your pacemaker. Don’t carry the phone in your breast pocket, even when it’s turned off. Avoid very strong magnets. These include those used for an MRI or in hand-held security wands. Show your ID card when you go through security. Avoid strong electrical fields. These are made by radio transmitting towers and ham radios. They are also made by heavy-duty electrical equipment. A running engine makes an electrical field. Don't lean over the open hood of a running car. Most household and yard appliances will not cause any problems. If you use any large power tools, such as an industrial arc welder, talk to your doctor. Keep an eye on the battery. The battery inside the device is checked regularly. It will last 5 to 7 years, depending on how often it paces or has to stop dangerous heart rhythms. Once it starts to run down, you will need to have it changed. This is like the implantation surgery, but it takes less time. This is because the battery/generator is the only part that needs to be replaced. Be careful when driving. Your device has a defibrillator built in. You may not be allowed to drive for the first 6 months after you get the device. You may also not be allowed to drive for 6 months after the defibrillator delivers a shock. You will not be allowed to work as a commercial driver if you have an ICD. Call 911 if you have chest pain or trouble breathing. Call your healthcare provider if you have any of the following: Redness, severe swelling, severe pain, drainage, bleeding, or warmth at the incision site Incision site or opens up or does not heal well A fever of 100.4°F (38°C) or higher, or as directed by your healthcare provider Pain around the generator that gets worse Swelling in the arms or hands on the side of the incision Sudden weight gain Twitching chest or abdominal muscles Frequent or constant hiccups A shock from your device Very fast heartbeat that doesn’t stop Generator feels loose or like it is wiggling in the pocket under the skin Copyright © 2017 Baylor Scott & White Health. All Rights Reserved. \| 3500 Gaston Ave., Dallas, TX 75246-2017 \| 1.800.4BAYLOR	2	7	1	0	0	0.973033	1	2,004
For other uses of the word Mumps or MUMPS, see Mumps (disambiguation). Mumps Classification and external resources Child with mumps. ICD-10 B26 ICD-9 072 DiseasesDB 8449 MedlinePlus 001557 eMedicine emerg/324 emerg/391 ped/1503 MeSH D009107 Mumps (epidemic parotitis) is a viral disease of the human species, caused by the mumps virus. Before the development of vaccination and the introduction of a vaccine, it was a common childhood disease worldwide. It is still a significant threat to health in the third world, and outbreaks still occur sporadically in developed countries. Painful swelling of the salivary glands (classically the parotid gland) is the most typical presentation. Painful testicular swelling (orchitis) and rash may also occur. The symptoms are generally not severe in children. In teenage males and men, complications such as infertility or subfertility are more common, although still rare in absolute terms. The disease is generally self-limiting, running its course before receding, with no specific treatment apart from controlling the symptoms with pain medication. Signs and symptoms The more common symptoms of mumps are: - Parotid inflammation (or parotitis) in 60–70% of infections and 95% of patients with symptoms. Parotitis causes swelling and local pain, particularly when chewing. It can occur on one side (unilateral) but is more common on both sides (bilateral) in about 90% of cases. - Orchitis, referring to painful inflammation of the testicles. Males past puberty who develop mumps have a 30 percent risk of orchitis. Other symptoms of mumps can include dry mouth, sore face and/or ears and occasionally in more serious cases, loss of voice. In addition, up to 20% of persons infected with the mumps virus do not show symptoms, so it is possible to be infected and spread the virus without knowing it. Fever and headache are prodromal symptoms of mumps, together with malaise and anorexia. Mumps is a contagious disease that is spread from person to person through contact with respiratory secretions such as saliva from an infected person. When an infected person coughs or sneezes, the droplets aerosolize and can enter the eyes, nose, or mouth of another person. Mumps can also be spread by sharing food and drinks. The virus can also survive on surfaces and then be spread after contact in a similar manner. A person infected with mumps is contagious from approximately 6 days before the onset of symptoms until about 9 days after symptoms start. The incubation period (time until symptoms begin) can be from 14–25 days but is more typically 16–18 days. A physical examination confirms the presence of the swollen glands. Usually the disease is diagnosed on clinical grounds and no confirmatory laboratory testing is needed. If there is uncertainty about the diagnosis, a test of saliva, or blood may be carried out; a newer diagnostic confirmation, using real-time nested polymerase chain reaction (PCR) technology, has also been developed. An estimated 20%-30% of cases are asymptomatic. As with any inflammation of the salivary glands, serum amylase is often elevated. The most common preventative measure against mumps is a vaccination with a mumps vaccine, invented by Maurice Hilleman at Merck. The vaccine may be given separately or as part of the MMR immunization vaccine which also protects against measles and rubella. In the US, MMR is now being supplanted by MMRV, which adds protection against chickenpox. The WHO (World Health Organization) recommends the use of mumps vaccines in all countries with well-functioning childhood vaccination programmes. In the United Kingdom it is routinely given to children at age 15 months. The American Academy of Pediatrics recommends the routine administration of MMR vaccine at ages 12–15 months and at 4–6 years. In some locations, the vaccine is given again between 4 to 6 years of age, or between 11 and 12 years of age if not previously given. The efficacy of the vaccine depends on the strain of the vaccine, but is usually around 80%. The Jeryl Lynn strain is most commonly used in developed countries but has been shown to have reduced efficacy in epidemic situations. The Leningrad-Zagreb strain commonly used in developing countries appears to have superior efficacy in epidemic situations. Because of the outbreaks within college and university settings, many governments have established vaccination programs to prevent large-scale outbreaks. In Canada, provincial governments and the Public Health Agency of Canada have all participated in awareness campaigns to encourage students ranging from grade 1 to college and university to get vaccinated. Some anti-vaccine activists protest against the administration of a vaccine against mumps, claiming that the attenuated vaccine strain is harmful, and/or that the wild disease is beneficial. There is no evidence whatsoever to support the claim that the wild disease is beneficial, or that the MMR vaccine is harmful. Claims have been made that the MMR vaccine is linked to autism and inflammatory bowel disease, including one study by Andrew Wakefield (the paper was discredited and retracted in 2010 and Wakefield was later stripped of his license after his work was found to be an "elaborate fraud" ) that indicated a link between gastrointestinal disease, autism, and the MMR vaccine. However, all further studies since that time have indicated no link between vaccination with the MMR and autism. Since the dangers of the disease are well known, while the dangers of the vaccine are quite minimal, most doctors recommend vaccination. The WHO, the American Academy of Pediatrics, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention, the American Academy of Family Physicians, the British Medical Association and the Royal Pharmaceutical Society of Great Britain currently recommend routine vaccination of children against mumps. The British Medical Association and Royal Pharmaceutical Society of Great Britain had previously recommended against general mumps vaccination, changing that recommendation in 1987. In 1988 it became United Kingdom government policy to introduce mass child mumps vaccination programmes with the MMR vaccine, and MMR vaccine is now routinely administered in the UK. Before the introduction of the mumps vaccine, the mumps virus was the leading cause of viral meningoencephalitis in the United States. However, encephalitis occurs rarely (less than 2 per 100,000). In one of the largest studies in the literature, the most common symptoms of mumps meningoencephalitis were found to be fever (97%), vomiting (94%) and headache (88.8%). The mumps vaccine was introduced into the United States in December 1967: since its introduction there has been a steady decrease in the incidence of mumps and mumps virus infection. There were 151,209 cases of mumps reported in 1968. Since 2001, the case average was only 265 per year, excluding an outbreak of >6000 cases in 2006 attributed largely to university contagion in young adults. There is no specific treatment for mumps. Symptoms may be relieved by the application of intermittent ice or heat to the affected neck/testicular area and by acetaminophen/paracetamol (Tylenol) for pain relief. Aspirin is not used due to a hypothetical link with Reye's syndrome. Warm salt water gargles, soft foods, and extra fluids may also help relieve symptoms. According to the Department of Health of Minnesota there is no effective post-exposure recommendation to prevent secondary transmission, as well as the post-exposure use of vaccine or immunoglobulin is not effective. Patients are advised to avoid acidic foods and beverages, since these stimulate the salivary glands, which can be painful. Death is very unusual. The disease is self-limiting, and general outcome is good, even if other organs are involved. Known complications of mumps include: - Infection of other organ systems - Mumps viral infections in adolescent and adult males carry an up to 30% risk that the testes may become infected (orchitis or epididymitis), which can be quite painful; about half of these infections result in testicular atrophy, and in rare cases sterility can follow. - Spontaneous abortion in about 27% of cases during the first trimester of pregnancy. - Mild forms of meningitis in up to 10% of cases (40% of cases occur without parotid swelling) - Oophoritis (inflammation of ovaries) in about 5% of adolescent and adult females, but fertility is rarely affected. - Pancreatitis in about 4% of cases, manifesting as abdominal pain and vomiting - Encephalitis (very rare, and fatal in about 1% of the cases when it occurs) - Profound (91 dB or more) but rare sensorineural hearing loss, uni- or bilateral. Acute unilateral deafness occurs in about 0.005% of cases. After the illness, life-long immunity to mumps generally occurs; reinfection is possible but tends to be mild and atypical. EpidemiologyMain article: List of modern mumps outbreaks - ^ Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, Isselbacher KJ, Eds. (2004). Harrison's Principles of Internal Medicine (16th ed.). McGraw-Hill Professional. ISBN 0-07-140235-7. - ^ a b Hviid A, Rubin S, Mühlemann K (March 2008). "Mumps". The Lancet 371 (9616): 932–44. doi:10.1016/S0140-6736(08)60419-5. PMID 18342688. - ^ Preveden T, Jovanovic J, Ristic D (1996). "[Fertility in men after mumps infection without manifestations of orchitis]". Med Pregl 49 (3–4): 99–102. PMID 8692089. - ^ Shakhov EV, Krupin VN (1990). "[The clinico-statistical characteristics of the testicular generative function in male subfertility following mumps]". Urol Nefrol (Mosk) (2): 46–50. PMID 2368216. - ^ Tsvetkov D (1990). "[Spermatological disorders in patients with postmumps orchitis]". Akush Ginekol (Sofiia) 29 (6): 46–9. PMID 2100952. - ^ Bedford H (2005). "Mumps: current outbreaks and vaccination recommendations". Nurs Times 101 (39): 53–4, 56. PMID 16218124. - ^ Manson AL (1990). "Mumps orchitis". Urology 36 (4): 355–8. doi:10.1016/0090-4295(90)80248-L. PMID 2219620. - ^ [dead link] - ^ Mumps, FAQ For Young Adults, Ministry of Health and Long-Term Care, Ontario.ca - ^ Symptoms of mumps - ^ Letter:Compliance with Exclusion Requirements to Prevent Mumps Transmission, By Stephanie M. Borchardt, Preethi Rao, and Mark S. Dworkin, Volume 13, Number 10–October 2007 - ^ Conly J, Johnston B (January 2007). "Is mumps making a comeback?". Can J Infect Dis Med Microbiol 18 (1): 7–9. PMC 2542890. PMID 18923686. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2542890. - ^ Krause CH, Eastick K, Ogilvie MM (November 2006). "Real-time PCR for mumps diagnosis on clinical specimens--comparison with results of conventional methods of virus detection and nested PCR". J. Clin. Virol. 37 (3): 184–9. doi:10.1016/j.jcv.2006.07.009. PMID 16971175. - ^ Centers for Disease Control and Prevention (CDC) (April 2006). "Mumps epidemic--Iowa, 2006". MMWR Morb. Mortal. Wkly. Rep. (Centers for Disease Control and Prevention (CDC)) 55 (13): 366–8. PMID 16601665. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5513a3.htm. Retrieved 2009-11-13. - ^ Amylase: The Test, Lab Tests Online UK - ^ Skrha J, Stĕpán J, Sixtová E (October 1979). "Amylase isoenzymes in mumps". Eur. J. Pediatr. 132 (2): 99–105. doi:10.1007/BF00447376. PMID 499265. - ^ Offit PA (2007). Vaccinated: One Man's Quest to Defeat the World's Deadliest Diseases. Washington, DC: Smithsonian. ISBN 0-06-122796-X. - ^ PDF[dead link] - ^ Schlegel M, Osterwalder JJ, Galeazzi RL, Vernazza PL (1999). "Comparative efficacy of three mumps vaccines during disease outbreak in eastern Switzerland: cohort study". BMJ 319 (7206): 352. PMC 32261. PMID 10435956. http://bmj.com/cgi/pmidlookup?view=long&pmid=10435956. - ^ "Summary". WHO: Mumps vaccine. http://www.who.int/vaccines/en/mumps.shtml#summary. Retrieved 2006-04-18. - ^ Peltola H, Kulkarni PS, Kapre SV, Paunio M, Jadhav SS, Dhere RM (August 2007). "Mumps outbreaks in Canada and the United States: time for new thinking on mumps vaccines". Clin. Infect. Dis. 45 (4): 459–66. doi:10.1086/520028. PMID 17638194. - ^ Table 2: Provincial and Territorial recommendations for mumps-containing immunization, 2007, Information on Outbreaks of Mumps In Canada - Information for Health Professionals, Public Health Agency Canada - ^ "Critical flaws" in Andrew Wakefield's studies - ^ Andrew Wakefield's downfall - ^ "Retracted autism study an 'elaborate fraud,' British journal finds". CNN. 5 January 2011. http://www.cnn.com/2011/HEALTH/01/05/autism.vaccines/index.html. Retrieved 16 May 2011. - ^ Atkinson W, Humiston S, Wolfe C, Nelson R (Editors). (2006). Epidemiology and Prevention of Vaccine-Preventable Diseases (9th ed.). Centers for Disease Control and prevention. Fulltext. - ^ Kanra G, Isik P, Kara A, Cengiz AB, Secmeer G, Ceyhan M (2004). "Complementary findings in clinical and epidemiologic features of mumps and mumps meningoencephalitis in children without mumps vaccination". Pediatr Int 46 (6): 663–8. doi:10.1111/j.1442-200x.2004.01968.x. PMID 15660864. - ^ McNabb SJ, Jajosky RA, Hall-Baker PA, et al. (March 2008). "Summary of notifiable diseases--United States, 2006". MMWR Morb. Mortal. Wkly. Rep. 55 (53): 1–92. PMID 18354375. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5553a1.htm. Retrieved 2009-11-13. - ^ 2006 mumps outbreak occurred despite high vaccination rate - Los Angeles Times[dead link] - ^ "Mumps Clinical Information - Minnesota Dept. of Health". http://www.health.state.mn.us/divs/idepc/diseases/mumps/hcp/clinical.html. - ^ "Mumps". Complementary and Alternative Medicine Guide. University of Maryland Medical Center. http://www.umm.edu/altmed/articles/mumps-000112.htm. Retrieved 16 May 2011. - ^ a b c d e f g Senanayake SN (2008). "Mumps: a resurgent disease with protean manifestations". Med J Aust 189 (8): 456–9. PMID 18928441. http://www.mja.com.au/public/issues/189_08_201008/sen10220_fm.html. - Original version based on the National Library of Medicine's Medline Plus website. Update Date: 08/15/01. Update date included for cross-reference against newer versions. - NHS.uk – Encyclopedia – 'NHS Direct Online Health Encyclopaedia: Mumps', National Health Service (UK) - WHO.int – "Immunization, Vaccines and Biologicals: Mumps vaccine", World Health Organisation - MicrobiologyBytes: Paramyxoviruses" - nih.gov – "NIH database entry: complete genome of Miyahara strain of Mumps" - cdc.gov – Collection of information from the CDC concerning mumps - ontario.ca – Ontario Mumps Catch-Up Vaccination Campaign targeted at Students - TWU.ca, SFU.ca – Information from 2008 Mumps Outbreak in British Columbia - GNB.ca – New Brunswick Vaccination Campaign - gov.pe.ca – P.E.I. Vaccination Campaign - gov.yk.ca – Yukon Vaccination Campaign - Public Health Agency of Canada – Public Health Agency of Canada Vaccination Campaigns - Virus Pathogen Database and Analysis Resource (ViPR): Paramyxoviridae Oral pathology: Stomatognathic disease (K06, K11–K14, 523, 527–529) Vestibule of mouthCheilitis (Angular, Actinic) · Herpes labialis · Plasma cell cheilitis · Cheilitis granulomatosa · Chapped lipsCheilitis exfoliativa · Cheilitis glandularis · Allergic contact cheilitisDrug-induced ulcer of the lip · Epidermization of the lip Oral cavity properHard, soft, and periapical tissuesgingival disease: Gingivitis (Desquamative gingivitis), Pericoronitis, Necrotizing ulcerative gingivitis, Noma, Epulis · Acute necrotizing ulcerative gingivitis Salivary glandsSialadenitis (Parotitis) · Benign lymphoepithelial lesion · Necrotizing sialometaplasia · Ranula · Sialolithiasis · Mucocele of salivary gland TongueGlossitis (Geographic tongue) · Fissured tongue · Glossodynia · Black hairy tongue · Strawberry tongue · Caviar tongue · Median rhomboid glossitis · Osseous choristoma of the tongue · Smooth tongue GeneralStomatitis: Aphthous ulcer (Major aphthous ulcer) · Herpetic stomatitis To be grouped from dermAcquired dyskeratotic leukoplakia · Angina bullosa haemorrhagica · Behçet syndrome · Cutaneous sinus of dental origin · Cyclic neutropenia · Epulis fissuratum · Eruptive lingual papillitis · Melanocytic oral lesion · Melkersson–Rosenthal syndrome · Mucosal lichen planus · Oral Crohn's disease · Oral florid papillomatosis · Oral melanosis · Plasmoacanthoma · Proliferative verrucous leukoplakia · Pyogenic granuloma · Pyostomatitis vegetans · Recurrent intraoral herpes simplex infection · Stomatitis nicotina · Trumpeter's wart · Vestibular papillomatosisCategories: - Viral diseases - Oral pathology Wikimedia Foundation. 2010.	2	27	4	1	3	0.637711	8	4,319
ICD codes: C25 What is the ICD Code? The number of new cases of pancreatic cancer has been rising since the 1990s, particularly in women and men from older age groups. This article will give you more information about the risk factors, diagnosis and treatment options. At a glance - Doctors also refer to pancreatic cancer as pancreatic carcinoma. - Pancreatic carcinomas usually arise from the gland cells in the pancreatic ducts. - Pancreatic cancer rarely causes symptoms in its early stages. - This means that those affected only receive their diagnosis at an advanced stage. - The chances of recovery from pancreatic cancer are poor compared to other types of cancer. Note: The information in this article cannot and should not replace a medical consultation and must not be used for self-diagnosis or treatment. What is pancreatic cancer? Pancreatic cancer or pancreatic carcinoma are terms doctors usually use to refer to tumors that start in the gland cells in the ducts of the pancreas. These ducts pass digestive juices from the exocrine (pertaining to the secretion of a substance out through a duct) part of the pancreas to the intestines. Doctors refer to this as pancreatic (exocrine) ductal adenocarcinoma. Pancreatic cancer also develops from hormone-producing pancreatic cells, i.e. the endocrine tissue, but this is rarer. They are known as pancreatic neuroendocrine tumors (NETs). Pancreatic NETs will not be discussed in this article. What are the symptoms of pancreatic cancer? People who develop pancreatic cancer do not often get their diagnosis until a very late stage. This is because in the early stages of pancreatic cancer most patients do not develop any symptoms. If they do, they are usually not specific to pancreatic cancer. This means that these signs of illness can also indicate other diseases in the digestive tract. Symptoms of pancreatic cancer can include: - pain in the upper abdomen or back - weight loss - jaundice (especially in the case of tumors of the head of the pancreas) - fatty stools (as a result of a lack of digestive juices) - blood sugar dysregulation, potentially culminating in diabetes mellitus - loss of appetite - digestive problems such as nausea, vomiting or diarrhea It is strongly recommended that you consult your doctor if symptoms persist or if there is a new onset of symptoms of unknown cause. General Practitioners can already narrow down what is causing the symptoms and, if necessary, initiate further diagnostic steps with specialists. Pancreatic cancer: what are the causes and risk factors? It is still unknown precisely what causes pancreatic cancer, but it is believed there must be a combination of different factors. The risk of developing pancreatic cancer increases with age. As people get older, genetic changes (mutations) build up in the healthy cells of the pancreas. The more mutations there are, the higher the risk of cancer. There are a few factors that statistically increase the risk of pancreatic cancer. Some concern lifestyle, others are caused by pre-existing conditions: - tobacco consumption (active and passive smoking) - being very overweight (obesity) - certain pre-existing conditions such as diabetes (type 2 diabetes mellitus) or a chronic inflammation of the pancreas (pancreatitis) - high levels of alcohol consumption - family history: the first degree relatives of a patient with pancreatic cancer, i.e. parents, children or siblings have a greater risk of also developing it. The risk increases with the number of relatives affected. - genetic conditions: a small proportion of pancreatic carcinomas are attributed to inherited mutations. These mutations mainly occur in conjunction with genetic disorders (syndromes) such as Peutz-Jeghers syndrome or FAMMM syndrome, or inherited (hereditary) pancreatitis. Important: Even people who live healthy lifestyles and have no pre-existing health conditions can develop pancreatic cancer. But you can reduce your personal risk by avoiding preventable risk factors. How can pancreatic cancer be diagnosed? There are different and complementary diagnostic procedures available to doctors if they suspect pancreatic cancer. First, the doctor asks the patient if they have any pre-existing conditions and symptoms (medical history). This is then followed by a thorough physical examination. If doctors suspect pancreatic cancer they can further confirm the diagnosis with various imaging procedures. Possible investigations include: - an abdominal ultrasound through the abdominal wall, - an internal ultrasound (endoscopic ultrasound), - a CT scan and/or - various forms of magnetic resonance imaging (MRI). An examination of the stomach and duodenum combined with X-ray contrast images of the pancreatic duct and bile duct can verify the diagnosis. This investigation is called endoscopic retrograde cholangiopancreatography, in short: ERCP. This procedure involves taking tissue samples for microscopic examination. Further tests may be possible in addition to the imaging procedures mentioned: - determining if endogenous substances that point to cancer are present in the blood (tumor markers) - a chest X-ray (preferably as a CT scan) or a combination of positron emission tomography (PET) and CT to clarify how far the tumor has already spread A surgical procedure known as laparoscopy can also confirm the diagnosis of “pancreatic cancer”. This involves taking tissue samples for examining under the microscope. The laparoscopy can also establish whether the tumor has spread to the neighboring organs or the peritoneum. Detailed information about the processes and techniques used in imaging and surgical procedures in diagnosing cancer can be found on the German Cancer Research Center’s Cancer Information Service website (in German). How is pancreatic cancer treated? There are various ways of treating pancreatic cancer: surgical removal, radiation therapy or chemotherapy. Doctors usually try out new treatment approaches in clinical trials. The type of treatment suitable in each case depends above all on: - the stage of illness: is the tumor confined to the pancreas, advanced locally or are there already metastases? - the patient’s health: are there other conditions that should be considered when choosing treatment? How is cancer treated? The video below explains how cancer can be treated. This and other videos can also be found on YouTubeWatch now When is recovery possible? A cure is possible in the early stages of the disease if the surgeon is able to completely remove the tumor with enough of a safety margin. The operation should be carried out at centers with sufficient experience of pancreatic surgery (more than 20 such operations per year). Surgery may be contraindicated if - the tumor is too advanced locally (and, for example, has grown too close to vessels or has spread to the lymph nodes), - it has already spread to other organs - or the patient’s general condition is too poor. Depending on the method of surgery used, parts of the pancreas are preserved or else the surgeon removes the entire organ. It is usually also necessary to remove neighboring organs such as the gallbladder and bile duct, duodenum or spleen or parts of these organs. Experts also recommend removing at least 12 adjacent lymph nodes. The surgery is usually followed by 6 months of supportive (adjuvant) chemotherapy, if possible within 12 weeks of the start of treatment with the aim of improving the chances of recovery and avoiding a relapse. Follow-up (additive) chemotherapy can be helpful even if the tumor could not be removed completely. Is surgery still an option following therapy? Chemotherapy or chemoradiotherapy with subsequent surgery is an option for patients with a borderline operable tumor. The preceding (neoadjuvant) therapy is able to shrink the tumor to an extent that the surgeon can then completely surgically remove it. Surgery after initial chemotherapy can be considered even for locally advanced tumors. This should be decided by doctors from a center with the requisite experience. What treatment is there if there is no cure? A cure is usually no longer possible if the disease is already advanced. The focus is then on palliative treatments - that stop the disease from spreading further, - relieve pain and - alleviate tumor-related symptoms. Experts recommend starting with chemotherapy for locally advanced pancreatic cancer. Sometimes this is followed by a combined treatment of chemotherapy and radiotherapy (chemoradiotherapy). Within clinical trials, patients can also start treatment with radiotherapy or chemoradiotherapy. If the tumor has already formed metastases, the focus is on making sure the person affected has a good quality of life. Chemotherapy can delay tumor growth and relieve symptoms. Immunotherapy or targeted treatments are also an option for some patients. This depends on the specific characteristics of the tumor such as mutations (changes to the genetic material) or changes to the enzyme patterns in the cancer cells. However, these and other approaches are currently possible for research purposes only. Bile drainage is often required as a supportive treatment for pancreatic cancer. This involves, for example, a doctor inserting a tube (stent) into the bile ducts to prevent a backlog of bile or to relieve discomfort caused by biliary stasis. Diversion surgery may be required if the tumor hinders the passage of food. Do you want to find out more about each treatment method? What are the possible side effects and what can be done about them? You can find detailed information on the German Cancer Research Center’s Cancer Information Service website (in German). When does rehabilitation for pancreatic cancer make sense? Medical rehabilitation (rehab) should be offered to pancreatic cancer patients especially after treatment with the aim of cure. Possible rehabilitation measures are: - psychological care: psycho-oncological counseling services can help many patients to cope with their cancer disease. - nutrition advice: patients receive a personal diet plan and are told what happens when the pancreas doesn’t work properly. Some patients need medication that supports digestion. - diabetes mellitus: patients often have diabetes mellitus following pancreas surgery. The rehab involves training them in how to measure their blood sugar and perform insulin injections. - physiotherapy and sport: individually tailored sport and exercise therapy can improve muscle strength and cardiovascular performance. - return to everyday work: if those affected are of working age, a medical examiner clarifies whether the patient is able to work. What does pancreatic cancer aftercare look like? Was the aim of the treatment to effect a cure? Follow-up examinations then follow. There is no uniform aftercare regimen for pancreatic cancer patients: the doctors treating you usually determine the examinations on an individual basis. The aftercare aims to identify and treat the effects of the disease and treatment or a relapse in good time. The pancreatic cancer can’t be cured? Then regular examinations should monitor the course of the disease with the aim of maintaining the patient’s quality of life for as long as possible. What’s next? Living with pancreatic cancer There are various ways of supporting pancreatic cancer patients so that they can cope better with the disease and the effects of their treatment. What helps depends on the individual situation. - Exercise can help overcome tiredness and exhaustion. Specially trained therapists adapt it to individual performance. - People whose pancreas is removed in full or in part often suffer from digestive problems and develop diabetes mellitus, but appropriate medication can largely compensate for these problems. - Psycho-oncological counseling can help those affected when worries and fears become overwhelming. If the disease can no longer be cured and it advances, good medical and nursing care is very important. Many patients with pancreatic cancer suffer from severe emaciation (cachexia). It is very important for these patients’ quality of life to stabilize their weight with appropriate nutritional therapy. Distressing symptoms such as pain and nausea can be alleviated. And psychosocial support can help to maintain a good quality of life for as long as possible. Do you want to know how doctors can give you psychological support with advanced cancer? And how you can have a positive effect on your quality of life and how you can combat anxiety? You can find lots of information and reference points on aspects of disease management on the German Cancer Research Center’s Cancer Information Service website (in German). Contact for the treatment of pancreatic cancer Doctors of various specialties work closely together in the treatment of pancreatic cancer. Hospitals that are particularly experienced in the treatment of patients with pancreatic cancer can have this confirmed with certification. The German Cancer Society (DKG) regularly checks their compliance with certain professional requirements. You can find the addresses of the certified centers on the OncoMAP website. The German Society for General and Visceral Surgery (DGAV) also assesses the quality of surgical clinics and departments. The “Surgical working group for liver, gall bladder and pancreatic diseases” (Chirurgische Arbeitsgemeinschaft Leber-Galle-Pankreas) of the DGAV certifies centers that meet certain requirements. Link to the overview of the centers for surgical diseases of the pancreas Do you have further questions about dealing with the condition in everyday life and additional support options? You can find information about this on the website of the Cancer Information Service of the German Cancer Research Center (in German). If you have any questions about pancreatic cancer you can also make personal contact with the Cancer Information Service by dialing the freephone number 0800 - 420 30 40 or writing an email to [email protected] - Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V. (AWMF), Deutschen Krebsgesellschaft e.V. (DKG) und Deutschen Krebshilfe (DKH). S3-Leitlinie zum exokrinen Pankreaskarzinom. AWMF- Registernummer 032 – 010OL. 12.2021. Aufgerufen am 28.03.2022. - Deutsche Gesellschaft für Hämatologie und Onkologie (DGHO), Österreichische Gesellschaft für Hämatologie & Medizinische Onkologie (OeGHO), Schweizerische Gesellschaft für Hämatologie (SGH-SSH), Schweizerische Gesellschaft für Medizinische Onkologie (SGMO), Arbeitsgemeinschaft Internistische Onkologie (AIO). Pankreaskarzinom. ONKOPEDIA-Leitlinie. Aufgerufen am 20.05.2020. - Ducreux M, Cuhna AS, Caramella C, Hollebecque A, Burtin P, Goéré D, Seufferlein T, Haustermans K, Van Laethem JL, Conroy T, Arnold D; ESMO Guidelines Committee. Cancer of the Pancreas: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up. Ann Oncol 2015; 26 Suppl 5: v56-68.doi:10.1093/annonc/mdv295. Aufgerufen am 20.05.2020. - Heinemann V. Algorithmen zur Behandlung des Pankreaskarzinoms. Der Onkologe 2019. Ausgabe 8/2019. Aufgerufen am 20.05.2020. - Seufferlein T, Hammel P, Delpero JR, Macarulla T, Pfeiffer P, Prager GW, Reni M, Falconi M, Philip PA, Van Cutsem E. Optimizing the management of locally advanced pancreatic cancer with a focus on induction chemotherapy: Expert opinion based on a review of current evidence. Cancer Treat Rev. 2019; 77:1-10.doi:10.1016/j.ctrv.2019.05.007. Aufgerufen am 20.05.2020. - Zentrum für Krebsregisterdaten (ZfKD) des Robert Koch-Instituts (RKI). Bauchspeicheldrüsenkrebs (Pankreaskarzinom). Aufgerufen am 20.05.2020. In cooperation with the Cancer Information Service of the German Cancer Research Center (Krebsinformationsdienst des Deutschen Krebsforschungszentrums).As at:	2	10	0	0	2	0.507746	2	3,536
Arrhythmogenic right ventricular dysplasia \|This article needs additional citations for verification. (February 2009)\| \|Arrhythmogenic right ventricular dysplasia\| \|Classification and external resources\| Photomicrograph of an ARVC heart. Arrhythmogenic right ventricular dysplasia (ARVD), also called arrhythmogenic right ventricular cardiomyopathy (ARVC) or arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), is an inherited heart disease. ARVD is caused by genetic defects of the parts of heart muscle (also called myocardium or cardiac muscle) known as desmosomes, areas on the surface of heart muscle cells which link the cells together. The desmosomes are composed of several proteins, and many of those proteins can have harmful mutations. The disease is a type of nonischemic cardiomyopathy that involves primarily the right ventricle. It is characterized by hypokinetic areas involving the free wall of the right ventricle, with fibrofatty replacement of the right ventricular myocardium, with associated arrhythmias originating in the right ventricle. ARVC/D is an important cause of ventricular arrhythmias in children and young adults. It is seen predominantly in males, and 30-50% of cases have a familial distribution. - 1 Genetics - 2 Incidence - 3 Presentation - 4 Pathogenesis - 5 Ventricular arrhythmias - 6 Diagnosis - 7 Natural history - 8 Management - 9 Highly-publicised deaths from arrhythmogenic right ventricular dysplasia - 10 See also - 11 References - 12 External links It is usually inherited in an autosomal dominant pattern, with variable expression. Novel studies showed that mutations (point mutations) in genes encoding for desmosomal proteins (see intercalated disc) are the main causatives for the development of this disease. Recently it could be shown, that mutations in the DES gene could cause ARVC. Desmin is an intermediate filament protein, which is linked to the desmosomes. Different DES muations cause an abnormal aggregation of desmin and associated proteins. The penetrance is 20–35% in general, but significantly higher in Italy. Seven gene loci have been implicated in ARVD. However, about 50% of families that express ARVD that undergo genetic screening do not show linkage with any of the known chromosomal loci. It is unclear whether the pathogenesis varies with the different loci involved. Standard genetic screening test are currently tested and evaluated in different state of the art cardiovascular research centres and hospitals. Types include: The incidence of ARVD is about 1/10,000 in the general population in the United States, although some studies have suggested that it may be as common as 1/1,000. Recently, 1/200 were found to be carriers of mutations that predispose to ARVC It accounts for up to 17% of all sudden cardiac deaths in the young. In Italy, the incidence is 40/10,000, making it the most common cause of sudden cardiac death in the young population. Up to 80% of individuals with ARVD present with syncope or sudden cardiac death. The remainder frequently present with palpitations or other symptoms due to right ventricular outflow tract (RVOT) tachycardia (a type of monomorphic ventricular tachycardia). Symptoms are usually exercise-related. In populations where hypertrophic cardiomyopathy is screened out prior to involvement in competitive athletics, it is a common cause of sudden cardiac death. The first clinical signs of ARVD are usually during adolescence. However, signs of ARVD have been demonstrated in infants. The pathogenesis of ARVD is largely unknown. Apoptosis (programmed cell death) appears to play a large role. It is unclear why only the right ventricle is involved. The disease process starts in the subepicardial region and works its way towards the endocardial surface, leading to transmural involvement (possibly accounting for the aneurysmal dilatation of the RV). Residual myocardium is confined to the subendocardial region and the trabeculae of the RV. These trabeculae may become hypertrophied. Aneurysmal dilatation is seen in 50% of cases at autopsy. It usually occurs in the diaphragmatic, apical, and infundibular regions (known as the triangle of dysplasia). The left ventricle is involved in 50-67% of individuals. If the left ventricle is involved, it is usually late in the course of disease, and confers a poor prognosis. There are two pathological patterns seen in ARVD, Fatty infiltration and fibro-fatty infiltration. The first, fatty infiltration, is confined to the right ventricle. This involves a partial or near-complete substitution of myocardium with fatty tissue without wall thinning. It involves predominantly the apical and infundibular regions of the RV. The left ventricle and ventricular septum are usually spared. No inflammatory infiltrates are seen in fatty infiltration. There is evidence of myocyte (myocardial cell) degeneration and death seen in 50% of cases of fatty infiltration. The second, fibro-fatty infiltration, involves replacement of myocytes with fibrofatty tissue. A patchy myocarditis is involved in up to 2/3 of cases, with inflammatory infiltrates (mostly T cells) seen on microscopy. Myocardial atrophy is due to injury and apoptosis. This leads to thinning of the RV free wall (to < 3 mm thickness) Myocytes are replaced with fibrofatty tissue. The regions preferentially involved include the RV inflow tract, the RV outflow tract, and the RV apex. However, the LV free wall may be involved in some cases. Involvement of the ventricular septum is rare. The areas involved are prone to aneurysm formation. Right ventricular outflow tract tachycardia \|Monomorphic ventricular tachycardia originating from the right ventricular outflow tract.\| Ventricular arrhythmias due to ARVD typically arise from the diseased right ventricle. The type of arrhythmia ranges from frequent premature ventricular complexes (PVCs) to ventricular tachycardia (VT) to ventricular fibrillation (VF). While the initiating factor of the ventricular arrhythmias is unclear, it may be due to triggered activity or reentry. Ventricular arrhythmias are usually exercise-related, suggesting that they are sensitive to catecholamines. The ventricular beats typically have a right axis deviation. Multiple morphologies of ventricular tachycardia may be present in the same individual, suggesting multiple arrhythmogenic foci or pathways. Right ventricular outflow tract (RVOT) tachycardia is the most common VT seen in individuals with ARVD. In this case, the EKG shows a left bundle branch block (LBBB) morphology with an inferior axis. The differential diagnosis for the ventricular tachycardia due to ARVD include: - Congenital heart disease - Acquired heart disease - Tricuspid valve disease - Pulmonary hypertension - Right ventricular infarction - Bundle-branch re-entrant tachycardia - Pre-excited AV re-entry tachycardia - Idiopathic RVOT tachycardia In order to make the diagnosis of ARVD, a number of clinical tests are employed, including the electrocardiogram (EKG), echocardiography, right ventricular angiography, cardiac MRI, and genetic testing. 90% of individuals with ARVD have some EKG abnormality. The most common EKG abnormality seen in ARVD is T wave inversion in leads V1 to V3. However, this is a non-specific finding, and may be considered a normal variant in right bundle branch block (RBBB), women, and children under 12 years old. RBBB itself is seen frequently in individuals with ARVD. This may be due to delayed activation of the right ventricle, rather than any intrinsic abnormality in the right bundle branch. The epsilon wave \|The epsilon wave (marked by red triangle), seen in ARVD.\| The epsilon wave is found in about 50% of those with ARVD. This is described as a terminal notch in the QRS complex. It is due to slowed intraventricular conduction. The epsilon wave may be seen on a surface EKG; however, it is more commonly seen on signal averaged EKGs. Ventricular ectopy seen on a surface EKG in the setting of ARVD is typically of left bundle branch block (LBBB) morphology, with a QRS axis of -90 to +110 degrees. The origin of the ectopic beats is usually from one of the three regions of fatty degeneration (the "triangle of dysplasia"): the RV outflow tract, the RV inflow tract, and the RV apex. Signal averaged ECG Signal averaged ECG (SAECG) is used to detect late potentials and epsilon waves in individuals with ARVD. Echocardiography may reveal an enlarged, hypokinetic right ventricle with a paper-thin RV free wall. The dilatation of the RV will cause dilatation of the tricuspid valve annulus, with subsequent tricuspid regurgitation. Paradoxical septal motion may also be present. Fatty infiltration of the RV free wall can be visible on cardiac MRI. Fat has increased intensity in T1-weighted images. However, it may be difficult to differentiate intramyocardial fat and the epicardial fat that is commonly seen adjacent to the normal heart. Also, the sub-tricuspid region may be difficult to distinguish from the atrioventricular sulcus, which is rich in fat. Cardiac MRI can visualize the extreme thinning and akinesis of the RV free wall. However, the normal RV free wall may be about 3 mm thick, making the test less sensitive. Right ventricular angiography Right ventricular angiography is considered the gold standard for the diagnosis of ARVD. Findings consistent with ARVD are an akinetic or dyskinetic bulging localized to the infundibular, apical, and subtricuspid regions of the RV. The specificity is 90%; however, the test is observer dependent. Right ventricular biopsy Transvenous biopsy of the right ventricle can be highly specific for ARVD, but it has low sensitivity. False positives include other conditions with fatty infiltration of the ventricle, such as chronic alcohol abuse and Duchenne/Becker muscular dystrophy. False negatives are common, however, because the disease progresses typically from the epicardium to the endocardium (with the biopsy sample coming from the endocardium), and the segmental nature of the disease. Also, due to the paper-thin right ventricular free wall that is common in this disease process, most biopsy samples are taken from the ventricular septum, which is commonly not involved in the disease process. A biopsy sample that is consistent with ARVD would have > 3% fat, >40% fibrous tissue, and <45% myocytes. A post mortem histological demonstration of full thickness substitution of the RV myocardium by fatty or fibro-fatty tissue is consistent with ARVD. ARVD is an autosomal dominant trait with reduced penetrance. Approximately 40-50% of ARVD patients have a mutation identified in one of several genes encoding components of the desmosome, which can help confirm a diagnosis of ARVD. Since ARVD is an autosomal dominant trait, children of an ARVD patient have a 50% chance of inheriting the disease causing mutation. Whenever a mutation is identified by genetic testing, family-specific genetic testing can be used to differentiate between relatives who are at-risk for the disease and those who are not. ARVD genetic testing is clinically available. There is no pathognomonic feature of ARVD. The diagnosis of ARVD is based on a combination of major and minor criteria. To make a diagnosis of ARVD requires either 2 major criteria or 1 major and 2 minor criteria or 4 minor criteria. - Right ventricular dysfunction - Severe dilatation and reduction of RV ejection fraction with little or no LV impairment - Localized RV aneurysms - Severe segmental dilatation of the RV - Tissue characterization - Fibrofatty replacement of myocardium on endomyocardial biopsy - Conduction abnormalities - Epsilon waves in V1 - V3. - Localized prolongation (>110 ms) of QRS in V1 - V3 - Family history - Familial disease confirmed on autopsy or surgery - Right ventricular dysfunction - Mild global RV dilatation and/or reduced ejection fraction with normal LV. - Mild segmental dilatation of the RV - Regional RV hypokinesis - Tissue characterization - Conduction abnormalities - Family history - Family history of sudden cardiac death before age 35 - Family history of ARVD There is a long asymptomatic lead-time in individuals with ARVD. While this is a genetically transmitted disease, individuals in their teens may not have any characteristics of ARVD on screening tests. Many individuals have symptoms associated with ventricular tachycardia, such as palpitations, light-headedness, or syncope. Others may have symptoms and signs related to right ventricular failure, such as lower extremity edema, or liver congestion with elevated hepatic enzymes. Unfortunately, sudden death may be the first manifestation of disease. ARVD is a progressive disease. Over time, the right ventricle becomes more involved, leading to right ventricular failure. The right ventricle will fail before there is left ventricular dysfunction. However, by the time the individual has signs of overt right ventricular failure, there will be histological involvement of the left ventricle. Eventually, the left ventricle will also become involved, leading to bi-ventricular failure. Signs and symptoms of left ventricular failure may become evident, including congestive heart failure, atrial fibrillation, and an increased incidence of thromboembolic events. The goal of management of ARVD is to decrease the incidence of sudden cardiac death. This raises a clinical dilemma: How to prophylactically treat the asymptomatic patient who was diagnosed during family screening. A certain subgroup of individuals with ARVD are considered at high risk for sudden cardiac death. Characteristics associated with high risk of sudden cardiac death include: - Young age - Competitive sports activity - Malignant familial history - Extensive RV disease with decreased right ventricular ejection fraction. - Left ventricular involvement - Episode of ventricular arrhythmia Management options include pharmacological, surgical, catheter ablation, and placement of an implantable cardioverter-defibrillator. Prior to the decision of the treatment option, programmed electrical stimulation in the electrophysiology laboratory may be performed for additional prognostic information. Goals of programmed stimulation include: - Assessment of the disease's arrhythmogenic potential - Evaluate the hemodynamic consequences of sustained VT - Determine whether the VT can be interrupted via antitachycardia pacing. Regardless of the management option chosen, the individual is typically suggested to undergo lifestyle modification, including avoidance of strenuous exercise, cardiac stimulants (i.e.: caffeine, nicotine, pseudoephedrine) and alcohol. If the individual wishes to begin an exercise regimen, an exercise stress test may have added benefit. Pharmacologic management of ARVD involves arrhythmia suppression and prevention of thrombus formation. Sotalol, a beta blocker and a class III antiarrhythmic agent, is the most effective antiarrhythmic agent in ARVD. Other antiarrhythmic agents used include amiodarone and conventional beta blockers (i.e.: metoprolol). If antiarrhythmic agents are used, their efficacy should be guided by series ambulatory holter monitoring, to show a reduction in arrhythmic events. While angiotensin converting enzyme inhibitors (ACE Inhibitors) are well known for slowing progression in other cardiomyopathies, they have not been proven to be helpful in ARVD. Individuals with decreased RV ejection fraction with dyskinetic portions of the right ventricle may benefit from long term anticoagulation with warfarin to prevent thrombus formation and subsequent pulmonary embolism. Catheter ablation may be used to treat intractable ventricular tachycardia. It has a 60-90% success rate. Unfortunately, due to the progressive nature of the disease, recurrence is common (60% recurrence rate), with the creation of new arrhythmogenic foci. Indications for catheter ablation include drug-refractory VT and frequent recurrence of VT after ICD placement, causing frequent discharges of the ICD. An ICD is the most effective prevention against sudden cardiac death. Due to the prohibitive cost of ICDs, they are not routinely placed in all individuals with ARVD. Indications for ICD placement in the setting of ARVD include: - Cardiac arrest due to VT or VF - Symptomatic VT that is not inducible during programmed stimulation - Failed programmed stimulation-guided drug therapy - Severe RV involvement with poor tolerance of VT - Sudden death of immediate family member Since ICDs are typically placed via a transvenous approach into the right ventricle, there are complications associated with ICD placement and follow-up. Due to the extreme thinning of the RV free wall, it is possible to perforate the RV during implantation, potentially causing pericardial tamponade. Because of this, every attempt is made at placing the defibrillator lead on the ventricular septum. After a successful implantation, the progressive nature of the disease may lead to fibro-fatty replacement of the myocardium at the site of lead placement. This may lead to undersensing of the individual's electrical activity (potentially causing inability to sense VT or VF), and inability to pace the ventricle. Cardiac transplant surgery Cardiac transplant surgery may be performed in ARVD. It may be indicated if the arrhythmias associated with the disease are uncontrollable or if there is severe bi-ventricular heart failure that is not manageable with pharmacological therapy. All first degree family members of the affected individual should be screened for ARVD. This is used to establish the pattern of inheritance. Screening should begin during the teenage years unless otherwise indicated. Screening tests include: Highly-publicised deaths from arrhythmogenic right ventricular dysplasia - Columbus Crew midfielder Kirk Urso collapsed out with friends on August 5, 2012 and was pronounced dead an hour later. An autopsy later revealed the disease to be the likely culprit. - Sevilla FC and Spanish international left wing-back Antonio Puerta died from the condition, at the age of 22, on 28 August 2007, three days after suffering several cardiac arrests, while disputing a La Liga game against Getafe CF. - Englishman Matt Gadsby also died from the condition after collapsing on the pitch on 9 September 2006, while playing with his team Hinckley United in a Conference North game against Harrogate Town. - Model Krissy Taylor, sister of Niki Taylor, died from the disease at age 17 in 1995. - Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0. - James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. - ^ Klauke B, Kossmann S, Gaertner A, Brand K, Stork I, Brodehl A, Dieding M, Walhorn V, Anselmetti D, Gerdes D, Bohms B, Schulz U, Zu Knyphausen E, Vorgerd M, Gummert J, Milting H. De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy. Hum Mol Genet. 2010 Dec 1;19(23):4595-607. doi: 10.1093/hmg/ddq387. Epub 2010 Sep 9. - ^ Brodehl A, Hedde PN, Dieding M, Fatima A, Walhorn V, Gayda S, Šarić T, Klauke B, Gummert J, Anselmetti D, Heilemann M, Nienhaus GU, Milting H. Dual color photoactivation localization microscopy of cardiomyopathy-associated desmin mutants. J Biol Chem. 2012 May 4;287(19):16047-57. doi: 10.1074/jbc.M111.313841. Epub 2012 Mar 8. PMID: 22403400 - Lahtinen, AM; Lehtonen, E, Marjamaa, A, Kaartinen, M, Heliö, T, Porthan, K, Oikarinen, L, Toivonen, L, Swan, H, Jula, A, Peltonen, L, Palotie, A, Salomaa, V, Kontula, K (2011). "Population-prevalent desmosomal mutations predisposing to arrhythmogenic right ventricular cardiomyopathy". Heart rhythm : the official journal of the Heart Rhythm Society 8 (8): 1214–21. doi:10.1016/j.hrthm.2011.03.015. PMID 21397041. - Sen-Chowdhry S, Syrris P, McKenna WJ (November 2007). "Role of genetic analysis in the management of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy". J. Am. Coll. Cardiol. 50 (19): 1813–21. doi:10.1016/j.jacc.2007.08.008. PMID 17980246. - Overview of ARVD/C Genetic Testing - Fontaine G, Tonet J, Gallais Y, Lascault G, Hidden-Lucet F, Aouate P, Halimi F, Poulain F, Johnson N, Charfeddine H, Frank R. (2000). "Ventricular tachycardia catheter ablation in arrhythmogenic right ventricular dysplasia: a 16-year experience". Curr Cardiol Rep 2 (6): 498–506. doi:10.1007/s11886-000-0034-1. PMID 11203287. - Jardy, Adam. "Crew midfielder Kirk Urso, 22, dies after being rushed to hospital from bar". The Columbus Dispatch. The Dispatch Printing Company. Retrieved 21 September 2012. - Jardy, Adam. "Coroner: Crew's Urso died of a preexisting heart condition". The Columbus Dispatch. The Dispatch Printing Company. Retrieved 21 September 2012. - "Sevilla star suffers heart attack". BBC Sport. 2007-08-25. Retrieved 2007-08-25. - Sevilla star dies after collapse - "Cause of Death". Cardiac Inherited Disease Group. Archived from the original on 2007-09-30. Retrieved 2006-10-31. - "Shock at star player's death". icBirmingham.co.uk. 11 September 2006. Retrieved 2007-11-26. \|Wikimedia Commons has media related to Arrhythmogenic right ventricular dysplasia.\| - GeneReviews/NCBI/NIH/UW entry on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant - OMIM entries on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant	2	19	1	0	0	0.836355	1	5,241
Textbook of Psychiatry/Somatoform Disorders - 1 Introduction - 2 Terminology - 3 Phenomenology - 4 Pathogenesis - 5 Treatment - 6 Final Considerations - 7 References The somatoform disorders have in common the "repeated presentation of physical symptoms, together with persistent requests for medical investigations, in spite of repeated negative findings and reassurances by doctors that the symptoms have no physical basis" (World Health Organization, 1992). Psychiatrists worldwide use either the ICD-10 or DSM-IV systems of classification when diagnosing mental illness. For most conditions there is little difference between the two systems, but for the somatoform disorders the conditions included differ slightly – see Table 1 for details. Table 1: Comparison of Somatoform Disorders: ICD-10 vs. DSM-IV Somatoform Disorders (F45) Somatoform Disorders (300) \|Somatization disorder\|\|Somatization disorder\| \|Undifferentiated somatoform disorder\|\|Undifferentiated somatoform disorder\| \|Hypochondriacal disorders (includes Body dysmorphic disorder)\|\|Hypochondriasis\| \|Body dysmorphic disorder\| \|Somatoform autonomic dysfunction\| \|Persistent somatoform pain disorder\|\|Pain disorder\| \|Other somatoform disorders\| \|Somatoform disorder, unspecified\|\|Somatoform disorder, not otherwise specified\| For the purposes of this chapter we take an inclusive view of disorders loosely grouped under the somatoform label and cover the following conditions: • Somatization Disorder • Hypochondriacal Disorder • Somatoform Pain Disorder and Chronic Pain • Conversion (Dissociative Motor) Disorder • Body Dysmorphic Disorder • Functional Somatic Syndromes (e.g., chronic fatigue syndrome/myalgic encephalomyelitis, fibromyalgia, chronic pelvic pain, multiple chemical sensitivity). The Somatoform Disorders are important to recognise because they are relatively common, costly and almost invariably present to doctors other than psychiatrists. In addition, many doctors find patients with these disorders difficult to understand and treat. The feature that all of these illnesses have in common is the patient’s experience of medically unexplained symptoms, which refers to physical (or somatic) symptoms that are disproportionate to identifiable physical disease. The terminology is confusing in this area, as many terms are used interchangeably. For example, although we often use the term medically unexplained symptoms in this chapter you may also encounter terms such as "somatization," "functional symptoms" or "hysterical symptoms" seemingly referring to the same thing. It is possible for one patient to fulfil diagnostic criteria for several somatoform disorders at one time (e.g., somatoform pain disorder and dissociative disorder) which has led to criticism of current diagnostic systems, and it is likely that future versions of ICD/DSM will change how such disorders are defined (Kroenke, Sharpe et al. 2007). To make matters worse, psychiatrists often use different diagnostic terminology to that used by their medical colleagues; these differences can hamper doctors’ ability to come to a shared understanding of a patient’s problems. Take, for example, a woman who suffers from a wide number and range of symptoms for which no adequate pathological cause has been found. These symptoms have been present for many years, have resulted in marked disability and, despite a long history of consultations with many different doctors, there has been no improvement. The woman’s medically unexplained symptoms include fatigue, dizziness, headache, subjective limb weakness and painful joints. A psychiatrist makes a diagnosis of "somatization disorder," whilst a rheumatologist diagnoses "fibromyalgia" and a neurologist "chronic fatigue syndrome/myalgic encephalomyelitis." The patient herself rejects all of these diagnoses and prefers to think of herself as having "multiple chemical sensitivity." In the field of the somatoform disorders, the labels often say more about the specialty of the person applying them than any underlying pathology. The lesson to learn here is that these diagnostic labels are descriptive, often overlapping and seldom uncontentious. Clinical Symptoms and Classification All somatoform disorders are highly co-morbid (i.e., co-exist) with each other and with anxiety and depression. Therefore screening for anxiety and depression, which are treatable, should be undertaken in any patient presenting with a medically unexplained syndrome. In the following section we go through the somatoform disorders in turn and highlight their diagnostic features. The diagnostic descriptions are based on ICD-10 criteria where possible. We emphasise from the outset that the classification of the so called somatoform disorders is a mess, which we hope (perhaps optimistically) will be improved in the current revisions of both ICD and DSM: i) Somatization Disorder The patient has a history of multiple and recurrent medically unexplained symptoms (>6 symptoms) starting in early adult life and lasting for at least 2 years. The symptoms cause distress and impairment and lead to repetitive consultations with medical personnel that are typically unhelpful. There is usually a history of unnecessary or unhelpful investigations or procedures and the patient may have a high level of disability. These patients commonly present to many different specialists and are high users of health care resources. ii) Hypochondriacal Disorder The patient is persistently preoccupied (for > 6 months) and distressed with the possibility of having one or more serious illnesses. This health anxiety persists despite repeated medical reassurance that they do not suffer from the feared illness(es). There is overlap with obsessive-compulsive disorder. iii) Somatoform Pain Disorder and Chronic Pain The patient has persistent (> 6 months), severe and distressing pain that is not fully explained by a physical disorder and they are pre-occupied by their pain symptoms. Chronic pain is also a common symptom in somatization disorder. iv) Conversion (or Dissociative Motor) Disorder The patient has motor or sensory symptoms (e.g., seizures, paralysis, loss of speech, blindness) for which there is inadequate physical explanation. There is usually considerable disability associated with the symptoms. The patient should not be intentionally feigning the symptoms. This disorder was of great interest to early neurologists and psychiatrists including Charcot, Janet and Freud, when it was known as hysteria. The term conversion disorder originally implied that psychological symptoms (or conflicts) were converted to motor symptoms, although this rather simplistic view is now outdated (Halligan, Bass et al. 2000). Nevertheless, in practice clinicians treating these patients expect to be able to determine psychological or emotional factors that are contributing to the patient’s presentation. v) Body Dysmorphic Disorder The patient has a persistent preoccupation that a part of the body is diseased or deformed, when to an objective observer it is not. The patient will often pursue surgical or other cosmetic treatments in order to correct the perceived deformity and therefore commonly present to dermatologists or cosmetic surgeons. In ICD-10 this disorder is classified within hypochondriacal disorder, but DSM-IV prefers to keep it as a distinct disorder. Many psychiatric researchers believe that body dysmorphic disorder would actually be better classified as an anxiety disorder because there is often considerable overlap with obsessive compulsive disorder. iv) Functional Somatic Syndromes The functional somatic syndromes refer to a number of related syndromes that have been characterised by the reporting of somatic symptoms and resultant disability rather than on the evidence of underlying conventional disease processes. Many such syndromes have been described. Some of these - such as irritable bowel syndrome - are well recognised within mainstream medicine but others - such as sick building syndrome - are not. All however share the feature of a disconnection between subjective symptomatology and objective biomedical pathology. Most medical specialities have at least one functional somatic syndrome – see Table 2 for examples. Table 2: Functional somatic syndromes by medical speciality \|Medical Specialty\|\|Functional Somatic Syndrome\| \|Gastroenterology\|\|Irritable bowel syndrome\| Repetitive strain injury \|Cardiology\|\|Non cardiac chest pain\| \|Infectious Disease\|\|Chronic fatigue syndrome/myalgic encephalomyelitis (sero-negative) Lyme Disease \|Respiratory Medicine\|\|Hyperventilation syndrome\| \|Dentistry\|\|Atypical facial pain Temporomandibular joint dysfunction \|Ear Nose & Throat\|\|Globus syndrome\| \|Non allied syndromes\|\|Gulf War syndrome Sick building syndrome Multiple chemical hypersensitivity Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), irritable bowel syndrome and fibromyalgia, have been more extensively researched than most other functional somatic syndromes, which has led to specific pathophysiological mechanisms being advanced for each and the development of widely accepted diagnostic criteria. Nevertheless, as yet no specific explanation is compelling and it remains the case that the similarities between the different syndromes are sufficiently striking for there to be a compelling case for considering them together (Barsky and Borus 1999; Wessely, Nimnuan et al. 1999). Commonly used diagnostic criteria for the three most well known functional somatic syndromes are outlined below: Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) (Fukuda, Straus et al. 1994) - 6 months disabling fatigue - Substantially reduced activity - At least 4 of these symptoms: - Impaired memory or concentration - Sore throat - Tender glands - Aching/stiff muscles - Multiple joint pains - New Headaches - Unrefreshing sleep - Post-exertional fatigue Irritable bowel syndrome (Rome Foundation, 2006) - Recurrent abdominal pain or discomfort at least 3 days per month in the last 3 months associated with ≥2 of the following: - Improvement with defecation - Onset associated with a change in frequency of stool - Onset associated with a change in the form (appearance) or the stool Fibromyalgia (Wolfe, Smythe et al. 1990) - Widespread pain in combination with… - Tenderness at ≥11 of 18 specific tender point sites Somatic symptoms are common and are the main reason why people seek medical care. Around a third of somatic symptoms that are seen in primary care can be classified as medically unexplained (Kroenke, 2003), whilst the proportion is at least as high in secondary care clinics (Nimnuan, Hotopf et al. 2001; Reid, Wessely et al. 2001; Carson, Best et al. 2003). The prevalence (frequency) of the specific somatoform disorders varies depending on the setting and the diagnostic criteria used. For example the population prevalence of strictly defined somatisation disorder is around 0.5%, but rises to as much as 16.6% when abridged criteria are used (Creed and Barsky, 2004). Likewise the population prevalence of hypochondriacal disorder has been estimated at between 0.02% and 7.7%, with abridged criteria suggesting a prevalence as high as 10.7% (Creed and Barsky, 2004). Body dysmorphic disorder is believed to be present in approximately 1-2% of the general population (Mackley, 2005). Fewer studies have looked at the epidemiology of somatoform pain or conversion disorders, and once again differing diagnostic criteria and populations lead to difficulties in interpretation. Prevalence estimates for the commonest functional somatic syndromes are shown in Table 3. Most epidemiological research in the functional somatic syndromes has focussed on the prevalence of CFS/ME, fibromyalgia and irritable bowel syndrome - probably because operational criteria exist for these disorders. Table 3: Prevalence figures for a sample of functional somatic syndromes \|Functional Somatic Syndrome\|\|Estimated population prevalence\| \|Chronic fatigue syndrome\|\|0.007 – 0.56% (Ranjith, 2005)\| \|Irritable bowel syndrome\|\|3 – 20% (Brandt, Bjorkman et al. 2002)\| \|Fibromyalgia\|\|0.5 – 5% (Neumann and Buskila, 2003)\| \|Non cardiac chest pain\|\|25% (Fass and Dickman, 2006)\| \|Chronic pelvic pain\|\|15% women (Zondervan and Barlow, 2000)\| \|Tension-type headache\|\|38% (Jensen and Stovner, 2008)\| Most research shows that women suffer from somatoform disorders more frequently than men, with the probable exceptions of hypochondriacal disorder and body dysmorphic disorder. A low level of education is also a risk factor. Other aetiological factors are reviewed below under "Assessment." Allow adequate time Adequate time should be allowed for assessment of patients with medically unexplained symptoms. Although this can be difficult in the setting of a busy primary care clinic or medical outpatients, time spent engaging the patient and gaining a full history will pay dividends later. Patients with severe and enduring medically unexplained symptoms will often have had negative experiences of medical care in the past (Reid, Ewan et al. 1991) (Deale and Wessely, 2001) and it is important that the patient feels believed whenever they are seen by a new health care professional. Therefore good communication skills are important. Start with the symptoms A good place to start is by taking an exhaustive and full history of all current symptoms. This is not solely for (or even for the purposes of) making a diagnosis, but to demonstrate to the patient that they are being taken seriously and it gives an indication of the way that the patient relates to their symptoms. Duration, severity, exacerbating and relieving factors should be explored for the main symptoms. One of the most neglected questions is to ask the patient what their concerns are about their symptoms (e.g., are they worried that they have cancer?). As a general rule, the more symptoms someone has, the more likely they are to be medically unexplained. It is useful to understand how impaired someone is by their symptoms on a day to day basis and how their illness impacts on their life. When the opportunity arises, psychosocial difficulties should be explored; the easiest way to do this is to use the patient’s own terminology to ask about an area more fully (e.g., if a patient mentions they are "stressed," you can use this word to ask them what is difficult for them in their life). This can help you understand the patient’s illness behaviour better i.e., how does the patient behave when they are symptomatic? Do their symptoms enable them to avoid situations that are stressful? Understanding what the patient attributes their symptoms to can help you explain how unhelpful patterns may have emerged (e.g., a person with CFS/ME who believes their symptoms are due to work stress will behave and manage their symptoms very differently from someone who attributes identical symptoms to a persistent viral infection. Review previous notes It is preferable to have read previous notes and investigations before meeting the patient, although this is not always possible. It is essential to review old notes before ordering more investigations, as repeating old investigations for previously investigated symptoms can lead to iatrogenic harm (Page and Wessely, 2003). A notes review can add valuable information on previous symptoms or past diagnoses (including somatoform disorders). It also offers an important insight into how the patient interacts with doctors and other doctors’ opinions of the patients’ problems. Rule out anxiety and depression Patients with anxiety or depression commonly present with physical rather than emotional symptoms. Both anxiety and depression are often experienced physically (e.g., anxiety can present with difficulty swallowing, stomach unease, sweaty palms; depression can present with weight loss, poor appetite, low energy). However, most patients will talk about the emotional symptoms of anxiety and depression if the topic is approached sensitively. Because the terms "anxiety" and "depression" are not universally understood, it is useful to have some probing questions you can use that are suitable for the culture in which you are working. Some examples of questions that are suitable for use in the Western setting are shown in Table 4. Table 4: Example probe questions when screening for anxiety or depression \|Do you often feel tense? Do you find yourself worrying a lot? Do you ever feel panicky? Is it difficult for you to relax? Do you feel keyed-up most of the time? \|Do you feel low or down very much? Do you still enjoy things as much as you used to? Do you feel slowed down? Are you often aware of feeling sad or miserable? Do you feel hopeful about the future? Communication For patients with medically unexplained symptoms the first consultation with a new doctor is important. As mentioned above, these patients have often had negative experiences of medical consultations in the past, so an empathic manner and sensitively taken history can be therapeutic in itself. It is never a good idea to imply that you don’t find a patient’s symptoms credible or that there is "nothing wrong" because investigations have been negative. The patient’s symptoms are real and often uncomfortable, even if their patho-physiology is unclear. Many doctors dislike it if a patient expresses negative sentiments about their colleagues or other services. For the most part it is not necessary to enter into an argument with the patient about the rights and wrongs of their previous medical encounters, instead respond to the emotional content of what the patient is saying rather than the specifics (e.g., "that must have made you feel very angry"). One issue around all medically unexplained syndromes is when do they become medically explained? Everyone remembers genuine breakthroughs in our understanding of health and disease; one such example being the discovery that General Paresis of the Insane (GPI) (sufferers of which could be found in all the asylums of Europe at the end of the 19th century) was a manifestation of neurosyphilis. When, a generation later, penicillin was found to kill the causative agent, GPI largely disappeared. In our own time, generations of doctors had been taught that peptic ulcer was due to excessive acid secretion, itself the result of stress: that is until Helicobacter Pylori was identified. But we should also pause for thought. First, the traffic is not all one way. For every previously viewed unexplained or psychiatric illness whose "medical" cause is identified, there is an equal and opposite traffic, as previously viewed medical entities such as visceral proptosis, autointoxication, floating kidneys, chronic appendicitis and so on and so on make the opposite journey. Second, many of the mechanisms that we highlight in this contribution do not cease to be relevant once a causative organism or factor is identified – far from it. The same issues remain relevant, for example psychosocially informed treatments (e.g., Cognitive Behavioural Therapy) do not lose their effectiveness, which is not surprising given that they are of proven efficacy in improving outcome in conditions as diverse as cancer, rheumatoid arthritis, multiple sclerosis, HIV related illness and so on. Somatoform disorders are best thought of as multi-factorial in origin. It is rare than one mechanism (be it emotional or physical) is responsible for a patient’s symptoms. When thinking about why a patient is suffering from medically unexplained symptoms, the traditional psychiatric formulation is helpful i.e., what are the predisposing, precipitating and maintaining factors in this person’s symptoms? It can also be useful to think about how someone’s symptoms may have a physiological (as opposed to patho-physiological) explanation. Genetics There is evidence that the general tendency to experience symptoms has a partly heritable basis (Gillespie, Zhu et al. 2000). Furthermore the evidence for the role of genetics in specific somatoform disorders has also increased in recent years. For example twin studies have shown that CFS/ME is substantially heritable (Buchwald, Herrell et al. 2001) and there is also evidence that chronic pain states, including fibromyalgia, might have a genetic component (Buskila, 2007), as might irritable bowel syndrome (Talley, 2006). There may be some genetic liability for hypochondriacal disorder and somatisation disorder, but this has been less investigated (Kendler, Walters et al. 1995; Noyes, Holt et al. 1997). Neuroendocrine changes Changes within the neuroendocrine system offer an interesting explanation for some of the biological changes seen in the somatoform disorders, although the story is not totally coherent. Most intensive research in this field has been done in CFS/ME and fibromyalgia. There is some evidence of low circulating cortisol in CFS/ME, which is in contrast to the pattern seen in major depression (Parker, Wessely et al. 2001; Cleare 2003). In addition the serotonergic system may be overactive in CFS/ME (Parker, Wessely et al. 2001). A reduction in the responsivity of the hypothalamic-pituitary-adrenal (HPA) axis has also been shown in fibromyalgia (Parker, Wessely et al. 2001). Neuroendocrine changes in irritable bowel syndrome have been less examined, although there is some evidence of abnormal activity of the HPA axis and also that the gut may be over activated by corticotrophin releasing hormone in those with the condition (Fukudo, Nomura et al. 1998). It is likely that at least some of the neuroendocrine abnormalities that have been observed are secondary and these abnormalities are probably best viewed as maintaining factors. Infection or injury Injury and infection may play a precipitating role in some somatoform disorders and this idea has been most explored for conditions such as CFS/ME and fibromyalgia. In clinical practice patients often cite an injury as the precipitant to chronic pain conditions such as fibromyalgia and this has some limited support in the literature (Al-Allaf, Dunbar et al. 2002). It is generally accepted that there is no single infective agent involved in the pathogenesis of CFS/ME (Afari and Buchwald 2003) or irritable bowel syndrome (Talley and Spiller 2002). Prospective cohort studies - the only way to determine causality - have confirmed that exposure to Epstein-Barr virus (EBV) increases he risk of CFS/ME (White, Thomas et al. 1998), as have Q fever, Lyme Disease (Prins, van der Meer et al. 2006) and viral illnesses requiring hospitalisation (Hotopf, Noah et al. 1996). However, psychiatric morbidity, female gender and prolonged convalescence are still the most important predictors of developing CFS/ME following infection (Hotopf, Noah et al. 1996; Candy, Chalder et al. 2003). As we write the world’s media are reporting a great breakthrough in the struggle to identify the cause of CFS/ME; a new retrovirus (XMRV) has been identified in 67% of a large series of CFS/ME patients in the USA but only 3% of controls (Lombardi, Ruscetti et al. 2009) - an association that is stronger than that between smoking and lung cancer. The finding is contained in the journal Science, a peer reviewed journal of outstanding reputation. It is indeed genuinely exciting and if true will indeed represent perhaps the single most important change in our understanding of the illness so far. Clinical practice will indeed change, and in the not too distant future, new and novel treatments should emerge. Of course the findings may not stand up to scrutiny, and there have been other equally dramatic claims made in this field before, which have not stood the test of time and replication. But, assuming that this new breakthrough is indeed just that, does that mean that all previous knowledge about CFS is rendered obsolete? Not at all. Perhaps a new drug will abolish CFS, but that seems unlikely. There will remain a major role for the kind of understanding and interventions that are the focus of this chapter, just as they remain important in so many other illnesses and diseases. Deconditioning Physical deconditioning offers an appealing mechanism for the maintenance of symptoms in the somatoform disorders. There is some evidence for reduced physical fitness in fibromyalgia (Valim, Oliveira et al. 2002) and reduced exercise capacity in CFS/ME when compared to sedentary controls (Fulcher and White, 2000). For patients with chronic and severe somatoform disorders (such as somatisation disorder) the physical effects of years of reduced activity or the use of aids such as wheelchairs can be profound. Such patients present an enormous rehabilitation challenge. Central dysfunction Some preliminary neuroimaging studies have been conducted in conversion disorder, CFS/ME, irritable bowel syndrome and pain syndromes that suggest that central mechanisms may play a role in these disorders. For example several functional neuroimaging studies have suggested that inhibitory networks are abnormally activated in conversion disorder (Aybek, Kanaan et al. 2008). At present, the usefulness of neuroimaging research in somatoform disorders is limited, but taken as a whole probably does support the idea of aberrant patterns of brain activation in these conditions (particularly in response to relevant probes such as experimentally induced pain). It is not known whether these changes pre-exist the illness or have developed secondarily. Childhood experiences Experience in childhood appears to be relevant to the development of somatoform disorders later in life. Longitudinal studies show that children who experience parental ill health in childhood are more likely to develop medically unexplained symptoms as adults (Hotopf, Mayou et al. 1999). Whether childhood illness increases the likelihood of adult somatoform disorders is less clear – certainly childhood medically unexplained illness appears to do so (Hotopf, Wilson-Jones et al. 2000). Childhood sexual abuse increases the risks of adult somatoform disorders (Paras, Hassan Murad et al. 2009). Stressful events Stressful events can precipitate the onset of a somatoform disorder and are known to occur more frequently in the period leading up to the onset of medically unexplained symptoms (Craig, Drake et al. 1994). A similar picture has been shown for CFS/ME, with patients experiencing "dilemmas" in the months preceding onset (Hatcher and House, 2003). Chronic stress (or life events) has also been shown to be important in the onset and maintenance of symptoms in irritable bowel syndrome (Creed, Craig et al. 1988; Bennett, Tennant et al. 1998) and fibromyalgia (Anderberg, Marteinsdottir et al. 2000). Trauma such as sexual abuse (Paras, Hassan Murad et al. 2009) or involvement in a disaster (van den Bergh, Grievink et al. 2005) also appears to be a risk factor for the development of a range of somatoform disorders Personality It is often presumed that personality factors are an important predisposing and maintaining factor in somatoform disorders, although there is little supporting evidence. Emotional instability (or neuroticism) may prolong the course of hypochondriacal disorder (olde Hartman, Borghuis et al. 2009) and, along with introversion, has been found to be a risk factor for the development of CFS/ME (Kato, Sulllivan et al. 2006; Prins, van der Meer et al. 2006). Patients with non-epileptic seizures (a type of conversion disorder) have been found to have high rates of personality disorder (Bowman and Markand, 1996). Clinically, patients with co-morbid personality disorder can be very challenging to manage. Illness beliefs Illness beliefs are enormously important in the maintenance (and possibly precipitation) of somatoform disorders. Beliefs link bi-directly to both behaviours and emotions, which means that by altering one of these domains the other two are likely to be affected – see the diagram below. Patients with CFS/ME are more likely to make physical illness attributions for a selection of common symptoms compared to controls (Butler, Chalder et al. 2001); perhaps in consequence and are more likely to believe their illness will be chronic and have serious consequences when compared to patients with chronic medical conditions (Weinman, Petrie et al. 1996). Illness worry is related to disability in fibromyalgia, but not in rheumatoid arthritis (Robbins and Kirmayer, 1990). Likewise, those with irritable bowel syndrome score more highly on hypochondriacal and bodily preoccupation scales than control groups (Gomborone, Dewsnap et al. 1995). Making physical attributions for unexplained symptoms is natural – the problem is what these may imply for the person’s concepts of self efficacy, acceptable treatment and likely prognosis. Deale et al showed that for patients with CFS to recover, it was not necessary that their illness attributions changed (e.g., "the illness is physical and caused by a virus"), but instead improvement was linked to change in beliefs such as "doing too much makes me worse," "I need to rest to get better" and so on (Deale, Chalder et al. 1998). In other words, physical illness attributions can act as a confounder or marker for more unhelpful beliefs that are associated with maladapative coping responses. The term "symptom amplification" is used to describe the manner in which innocuous symptoms become incorrectly attributed and then incorporated into a patient’s understanding of their illness, which leads to further incorrect attribution of other symptoms as they arise (Barsky and Borus, 1999). These beliefs and attitudes about symptoms may act as a mechanism that then guides the patient to adopt avoidant behaviours, leading to limitation of activity, which in turn leads to the secondary deconditioning and neuroendocrine effects outlined above. Avoidance behaviours are invariably based on the patient’s understanding of their illness (e.g., "when I feel fatigued, I cause myself further harm if I exercise") and are often possible to work with during treatment (Deale, Chalder et al. 1998). Living Environment We have discussed above the possible importance of the early family environment in predisposing someone to suffer from medically unexplained symptoms (e.g., by experiencing the illness of a parent in early life), however the behaviour and attitude of close family and friends can also play a role in the maintenance of medically unexplained symptoms. For example partners of patients with CFS/ME are more likely to make physical attributions about their partner’s symptoms than the partners of fracture clinic patients (Butler, Chalder et al. 2001). Clinically it is often as relevant to understand the illness beliefs of close family as it is the patient’s – particularly when the family are providing high levels of care and support. Financial Reward The financial "reward" to be gained from disability payments or litigation has been argued to play a role in the maintenance of ill-health in those suffering from somatoform disorders (Malleson, 2002). For example, being in receipt of sickness benefit or certification has been shown to be a poor prognostic sign in CFS/ME (Cope, David et al. 1994; Bentall, Powell et al. 2002) and fibromyalgia (Wigers, 1996), whilst the whiplash syndrome does not appear to exist in countries without an insurance/compensation culture (Schrader, Obelieniene et al. 1996). Media Several functional somatic syndromes including CFS/ME, Gulf War syndrome and repetitive strain injury, have gained public credibility in spite of widespread medical scepticism as to their very existence. The role of the media in this process has often been highlighted (Shorter, 1995; Barsky and Borus, 1999; Hazemeijer and Rasker, 2003). The availability and explosion in internet sites has also meant that patients may inadvertently be exposed to information that is inaccurate or even harmful (Armstrong, 2000; Kisely, 2002). The assessment itself can be therapeutic, particularly if time is taken to provide a clear explanation for symptoms, which is not perceived by the patient to blame them. The doctor may need to avoid colluding with the patient, but also avoid denying the reality of the symptoms. Research has shown that "empowering" explanations are the most beneficial for patients with medically unexplained symptoms (i.e., explanations that provide a tangible mechanism, de-emphasise blame and provide the opportunity for self-management) (Salmon, Peters et al. 1999). The provision of clear information in different forms (i.e., verbal and written) is necessary. Patients with medically unexplained symptoms often appear to be seeking reassurance, but this can be difficult to deliver effectively. It is counter-productive to tell a patient that "there is nothing wrong," when their symptoms are proof that there is. On the other hand it is important to counter specific illness fears that the patient may hold (e.g., "My symptoms mean I’ve got cancer," "This rash shows that I have HIV," "If I do too much I will permanently damage my spine") if that is not the case. This is why it is important to have asked the patient what they believe is wrong. Patients with hypochondriacal disorder will often attempt to elicit repeated reassurance, which fails to provide reassure for any length of time (Deale, 2007). If there is evidence of anxiety or depression at first assessment, then this should be treated in the usual way. Doing so will often, although not always, lead to a significant improvement in the patient’s somatic symptoms. A doctor that sees a patient with medically unexplained symptoms for follow-up has an important role to play in managing that patient’s interaction with medical services. Even if the doctor does not perceive themselves to be providing active therapy, they can be aware of potentially iatrogenic interventions (i.e., harm caused by doctors) (Page and Wessely, 2003). They can also provide regular follow-up that is not contingent on the patient being symptomatic, thereby discouraging the need for the patient to complain of symptoms in order to elicit care. It is sometimes possible to agree beforehand that only a certain proportion of the session will be devoted to discussing symptoms, and leave it to the patient to decide the content of the second half of the interview. Overall cognitive behavioural therapy (CBT) is known to be an efficacious treatment for the range of the conditions loosely grouped under the somatoform disorders (Sumathipala, 2007). CBT and similar therapies have shown specific usefulness in the treatment of hypochondriacal disorder (Thomson and Page, 2007), CFS/ME (Chambers, Bagnall et al. 2006), irritable bowel syndrome (Brandt, Bjorkman et al. 2002), fibromyalgia (Rossy, Buckelew et al. 1999) and burning mouth syndrome (Zakrzewska, Glenny et al.). CBT can be adapted for use in any of these disorders, but like most medical treatments relies on the patient being sufficiently motivated to participate. One of the first goals in CBT is for the therapist and patient to come to a shared understanding of the patient’s problems using a CBT framework – the therapist often uses diagrams like the one on page 18 to illustrate this. Evidence is lacking for useful psychotherapeutic treatments for conversion disorder (Martlew, Baker et al. 2007), although preliminary studies have shown that, once again, CBT may be useful (Goldstein, Deale et al. 2004). Overall there is evidence that antidepressant medication is useful in the treatment of somatoform disorders (O'Malley, Jackson et al. 1999; Sumathipala, 2007), although it is not possible to generally recommend the use of one type of antidepressant over another. For the functional somatic syndromes there are some specific recommendations, for example tricyclic antidepressants are effective in treating fibromyalgia (Arnold, Keck et al. 2000), abdominal pain in irritable bowel syndrome (Brandt, Bjorkman et al. 2002) and premenstrual tension (Steiner, Steinberg et al. 1996). On the other hand antidepressants have not been found to be useful in CFS/ME without co-morbid depression (Whiting, Bagnall et al. 2001). In general the effectiveness of antidepressants in these disorders increases if the patient has evidence of co-morbid depression or anxiety, however medication is probably less effective than psychological approaches. It can be necessary to rationalise inappropriate medication, as some patients with somatoform disorders are prescribed medication that is unnecessary or even harmful. This needs to be done by (or in conjunction with) primary care and the rationale discussed with the patient in advance. In clinical practice it is common to combine a psychotherapeutic and pharmacological approach to management. The patient may have strong feelings about treatment and these should be taken into consideration. In developed countries treatment for somatoform disorders can sometimes be provided by specialists (e.g., consultation-liaison psychiatrists) attached to general hospitals, although provision is often patchy and as in developing countries much of the burden falls to primary care. Factitious disorder or Munchausen’s syndrome is listed separately (adjacent to the somatoform disorders) in DSM-IV classification, whilst ICD-10 classes it amongst the personality disorders. Malingering is not considered to be a psychiatric disorder by either system. However the distinction of factitious disorder or malingering from the somatoform disorders can be unclear, so for the sake of completeness we mention them here. Diagnostic features are outlined below. Factitious disorder is probably a rare condition about which little is known, although persons suffering from this disorder are likely to have significant personality disturbance and a background of neglect or abuse. Malingering is more common, although quite how common is unknown due to the nature of the behaviour. • Persistent faking of symptoms or self-infliction of wounds to produce symptoms • Persistent visits to hospital in order to gain care for these symptoms (may move from hospital to hospital to avoid detection) • No external gain (e.g., financial) is apparent, so the gain is viewed as being psychological • Deliberate falsification of a medical condition • The falsification (or exaggeration) is for financial or other obvious material gain Afari, N. and D. Buchwald (2003). "Chronic fatigue syndrome: a review." American Journal of Psychiatry 160: 221-236. Al-Allaf, A. W., K. L. Dunbar, et al. (2002). "A case-control study examining the role of physical trauma in the onset of fibromyalgia syndrome." Rheumatology 41(4): 450-3. Anderberg, U., I. Marteinsdottir, et al. (2000). "The impact of life events in female patients with fibromyalgia and in female healthy controls." European Psychiatry 15: 295-301. Armstrong, R. (2000). "Fibromylagia: is recovery impeded by the internet?" Archives Internal Medicine 160: 1039. Arnold, L. M., P. E. Keck, et al. (2000). "Antidepressant treatment of fibromyalgia. A meta-analysis and review." Psychosomatics 41: 104-113. Aybek, S., R. Kanaan, et al. (2008). "The neuropsychiatry of conversion disorder." Current Opinion Psychiatry 21: 275-280. Barsky, A. and J. Borus (1999). "Functional somatic syndromes." Annals of Internal Medicine 130: 910-921. Bennett, E., C. Tennant, et al. (1998). "Level of chronic life stress predicts clinical outcome in irritable bowel syndrome." Gut 43: 256-261. Bentall, R., P. Powell, et al. (2002). "Predictors of response to treatment for chronic fatigue syndrome." British Journal of Psychiatry 181: 248-252. Bowman, E. and O. Markand (1996). "Psychodynamics and psychiatric diagnoses of pseudoseizure subjects." American Journal of Psychiatry 153(1): 57-63. Brandt, L., D. Bjorkman, et al. (2002). "Systematic review on the management of irritable bowel syndrome in North America." American Journal of Gastroenterology 97(11): S7-S26. Buchwald, D., R. Herrell, et al. (2001). "A Twin study of chronic fatigue." Psychosomatic Medicine 63: 936-943. Buskila, D. (2007). "Genetics of chronic pain states." Best Practice & Research in Clinical Rheumatology 21(3): 535-547. Butler, J., T. Chalder, et al. (2001). "Causal attributions for somatic sensations in paitents with chronic fatigue syndrome and their partners." Psychological Medicine 31: 97-105. Butler, J., T. Chalder, et al. (2001). "Causal attributions for somatic sensations in patients with chronic fatigue syndrome and their partners." Psychological Medicine 31: 97-105. Candy, B., T. Chalder, et al. (2003). "Predictors of fatigue following the onset of infectious mononucleosis." Psychological Medicine 33: 847-855. Carson, A., S. Best, et al. (2003). "The outcome of neurology outpatients with medically unexplained symptoms: a prospective cohort study." Journal of Neurology Neurosurgery and Psychiatry 74: 897-900. Chambers, D., A.-M. Bagnall, et al. (2006). "Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome / myalgic encephalomyelitis: an updated systematic review." Journal of the Royal Society of Medicine 99: 506-520. Cleare, A. (2003). "The neuroendocrinology of chronic fatigue syndrome." Endocrine Reviews 24(2): 236-252. Cope, H., A. David, et al. (1994). "Predictors of chronic "postviral" fatigue." Lancet 344: 864-868. Craig, T., H. Drake, et al. (1994). "The South London somatisation study II: influence of stressful life events and secondary gain." British Journal of Psychiatry 165: 248-258. Creed, F. and A. Barsky (2004). "A systematic review of the epidemiology of somatisation disorder and hypochondriasis." Journal of Psychosomatic Research 56: 391-408. Creed, F., T. Craig, et al. (1988). "Functional abdominal pain, psychiatric illness and life events." Gut 29: 235-242. Deale, A. (2007). "Psychopathology and treatment of severe health anxiety." Psychiatry 6(6): 240-246. Deale, A., T. Chalder, et al. (1998). "Illness beliefs and treatment outcome in chronic fatigue syndrome." Journal of Psychosomatic Research 45: 77-83. Deale, A., T. Chalder, et al. (1998). "Illness beliefs and treatment outcome in chronic fatigue syndrome." Journal of Psychosomatic Research 45(1): 77-83. Deale, A. and S. Wessely (2001). "Patients' perceptions of medical care in chronic fatigue syndrome." Social Science & Medicine 52: 1859-1864. Fass, R. and R. Dickman (2006). "Non-cardiac chest pain: an update." Neurogastroenterology Motility 18: 408-417. Fukuda, K., S. Straus, et al. (1994). "The chronic fatigue syndrome: a comprehensive approach to its definition and study." Annals of Internal Medicine 121: 953-959. Fukudo, S., T. Nomura, et al. (1998). "Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome." Gut 42(6): 845-849. Fulcher, K. Y. and P. D. White (2000). "Strength and physiological response to exercise in patients with chronic fatigue syndrome." Journal of Neurology Neurosurgery and Psychiatry 69: 302-307. Gillespie, N., G. Zhu, et al. (2000). "The genetic aetiology of somatic distress." Psychological Medicine 30: 1051-1061. Goldstein, L., A. Deale, et al. (2004). "An evaluation of cognitive behavioral therapy as a treatment for dissociative seizures." Cognitive and Behavioral Neurology 17: 41-49. Gomborone, J., P. Dewsnap, et al. (1995). "Abnromal illness attitudes in patients with irritable bowel syndrome." Journal of Psychosomatic Research 39(2): 227-230. Halligan, P., C. Bass, et al. (2000). "New approaches to conversion hysteria." BMJ 320: 1488-1489. Harrison, S. (2002). Temporomandibular joint pain. Assessment and Management of Orofacial Pain. J. Zakrzewska and S. Harrison. Amsterdam, Elsevier Science BV: 191-208. Hatcher, S. and A. House (2003). "Life events, difficulties and dilemmas in the onset of chronic fatigue syndrome: a case-control study." Psychological Medicine 33: 1185-1192. Hazemeijer, I. and J. Rasker (2003). "Fibromyalgia and the therapeutic domain. A philosophical study on the origins of fibromyalgia in a specific social setting." Rheumatology 42: 507-515. Hotopf, M., R. Mayou, et al. (1999). "Childhood risk factors for adults with medically unexplained symptoms: results from a national birth cohort study." American Journal of Psychiatry 156(11): 1796-800. Hotopf, M., N. Noah, et al. (1996). "Chronic fatigue and minor psychiatric morbidity after viral meningitis: a controlled study." Journal of Neurology, Neurosurgery and Psychiatry 60(5): 504-509. Hotopf, M., C. Wilson-Jones, et al. (2000). "Childhood predictors of adult medically unexplained syndromes." British Journal of Psychiatry 176(3): 273-280. Jensen, R. and L. Stovner (2008). "Epidemiology and comorbidity of headache." Lancet Neurology 7: 354-361. Kato, K., P. Sulllivan, et al. (2006). "Premorbid predictors of chronic fatigue." Archives General Psychiatry 63: 1267-1272. Kendler, K., E. Walters, et al. (1995). "A twin-family study of self-report symptoms of panic-phobia and somatization." Behavior Genetics 25(6): 499-515. Kisely, S. R. (2002). "Treatments for chronic fatigue syndrome and the internet: a systematic survey of what your patients are reading." Australian and New Zealand Journal of Psychiatry 36: 240-245. Kroenke, K. (2003). "Patients presenting with somatic complaints: epidemiology, psychiatric co-morbidity and management." International Journal of Methods in Psychiatric Research 12(1): 34-43. Kroenke, K., M. Sharpe, et al. (2007). "Revising the classification of somatoform disorders: key questions and preliminary recommendations." Psychosomatics 48: 277-285. Lombardi, V., F. Ruscetti, et al. (2009). "Detection of an infectious retrovirus, XMRV, in blood cells of patients with Chronic Fatigue Syndrome." Science DOI 10.1126/science.1179052. Mackley, C. (2005). "Body dysmorphic disorder." Dermatologic Surgery 31: 553-558. Martlew, J., G. Baker, et al. (2007) "Behavioural treatments for non-epileptic attack disorder." Cochrane Database of Systematic Reviews DOI: 10.1002/14651858. Neumann, L. and D. Buskila (2003). "Epidemiology of fibromyalgia." Current Pain & Headache Reports 7: 362-368. Nimnuan, C., M. Hotopf, et al. (2001). "Medically unexplained symptoms: an epidemiological study in seven specialities." Journal of Psychosomatic Research 51: 361-367. Noyes, R., C. Holt, et al. (1997). "A family study of hypochondriasis." The Journal of Nervous and Mental Disease 185: 223-232. O'Malley, P., J. Jackson, et al. (1999). "Antidepressant therapy for unexplained symptoms and symptom syndromes." The Journal of Family Practice 48(12): 980-990. olde Hartman, T. C., M. S. Borghuis, et al. (2009). "Medically unexplained symptoms, somatisation disorder and hypochondriasis: Course and prognosis. A systematic review." Journal of Psychosomatic Research 66(5): 363-377. Page, L. and S. Wessely (2003). "Medically unexplained symptoms: exacerbating factors in the doctor-patient encounter." Journal of the Royal Society of Medicine 96: 223-227. Paras, M., M. Hassan Murad, et al. (2009). "Sexual abuse and lifetime diagnosis of somatic disorders." JAMA 302(5): 550-561. Parker, A., S. Wessely, et al. (2001). "The neuroendocrinology of chronic fatigue syndrome and fibromyalgia." Psychological M edicine 31: 1331-1345. Prins, J., J. van der Meer, et al. (2006). "Chronic fatigue syndrome." Lancet 367: 346-355. Ranjith, G. (2005). "Epidemiology of chronic fatigue syndrome." Occupational medicine 55: 13-19. Reid, J., C. Ewan, et al. (1991). "Pilgrimage of pain: the illness experiences of women with repetition strain injury and the search for credibility." Social Science and Medicine 32: 601-612. Reid, S., S. Wessely, et al. (2001). "Medically unexplained symptoms in frequent attenders of secondary health care: retrospective cohort study." BMJ 322: 767-769. Robbins, J. and L. Kirmayer (1990). "Illness worry and disability in fibromyalgia syndrome." International Journal of Psychiatry in Medicine 20: 49-63. Rome Foundation (2006) "Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders." http://www.romecriteria.org/assets/pdf/19_RomeIII_apA_885-898.pdf. Rossy, L., S. Buckelew, et al. (1999). "A meta-analysis of fibromyalgia treatment interventions." Annals of Behavioral Medicine 21(2): 180-191. Salmon, P., S. Peters, et al. (1999). "Patients' perceptions of medical explanations for somatisation disorders: Qualitative analysis." BMJ 318(7180): 372-376. Schrader, H., D. Obelieniene, et al. (1996). "Natural evolution of late whiplash syndrome outside the medicolegal context." Lancet 347: 1207-11. Shorter, E. (1995). "Sucker-punched again! Physicians meet the disease-of-the-month syndrome." Journal of Psychosomatic Research 39(2): 115-118. Steiner, M., S. Steinberg, et al. (1996). "Fluoxetine in the treatment of premenstrual dysphoria." New England Journal of Medicine 332: 1529-1534. Sumathipala, A. (2007). "What is the evidence for the efficacy of treatments for somatoform disorders? A critical review of previous intervention studies." Psychosomatic Medicine 69: 889-900. Talley, N. (2006). "Genes and environment in irritable bowel syndrome: one step forward." Gut 55: 1694-1696. Talley, N. and R. Spiller (2002). "Irritable bowel syndrome: a little understood organic bowel disease?" Lancet 360: 555-564. Thomson, A. and L. Page (2007) "Psychotherapies for hypochondriasis." Cochrane Database of Systematic Reviews DOI: 10.1002/14651858. Valim, V., L. Oliveira, et al. (2002). "Peak oxygen uptake and ventilatory anaerobic threshold in fibromyalgia." Journal of Rheumatology 29: 353-357. van den Bergh, B., L. Grievink, et al. (2005). "Medically unexplained physical symptoms in the aftermath of disasters." Epidemiologic Reviews 27(1): 92-106. Weinman, J., K. Petrie, et al. (1996). "The illness perception questionnaire: a new method for assessing the cognitive representation of illness." Psychology and Health 11: 431-445. Wessely, S., C. Nimnuan, et al. (1999). "Functional somatic syndromes: one or many?" Lancet 354: 936-939. White, P., J. Thomas, et al. (1998). "Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever." British Journal of Psychiatry 173: 475-481. Whiting, P., A. Bagnall, et al. (2001). "Interventions for the treatment and management of chronic fatigue syndrome: a systematic review." Journal of the American Medical Association 286: 1360-1368. Wigers, S. (1996). "Fibromyalgia outcome: the predictive values of symptom duration, physical activity, disability pension and critical life events - a 4.5 year prospective study." Journal of Psychosomatic Research 41(3): 235-243. Wolfe, F., H. Smythe, et al. (1990). "The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: report of the multicenter criteria committee." Arthritis and Rheumatism 33: 160-173. World Health Organization (1992). The ICD-10 Classification of Mental and Behavioural Disorders. Geneva. Zakrzewska, J., A. Glenny, et al. "Interventions for the treatment of burning mouth syndrome (Cochrane Review)." Cochrane Library 2. 2004. Zondervan, K. and D. Barlow (2000). "Epidemiology of chronic pelvic pain." Best Practice & Research in Clinical Obstetrics & Gynaecology 14(3): 403-414.	2	8	0	0	3	0.926717	3	11,768
From Wikipedia, the free encyclopedia - View original article \|Classification and external resources\| Acute angle closure glaucoma of the right eye. Note the mid sized pupil, which was nonreactive to light, and injection (nonuniform redness) of the conjunctiva. \|This article uses bare URLs for citations, which may be threatened by link rot. (January 2014)\| \|Classification and external resources\| Acute angle closure glaucoma of the right eye. Note the mid sized pupil, which was nonreactive to light, and injection (nonuniform redness) of the conjunctiva. Glaucoma is a term describing a group of ocular disorders with multi-factorial etiology united by a clinically characteristic intraocular pressure-associated optic neuropathy. This can permanently damage vision in the affected eye(s) and lead to blindness if left untreated. It is normally associated with increased fluid pressure in the eye (aqueous humour). The term "ocular hypertension" is used for people with consistently raised intraocular pressure (IOP) without any associated optic nerve damage. Conversely, the term 'normal tension' or 'low tension' glaucoma is used for those with optic nerve damage and associated visual field loss, but normal or low IOP. The nerve damage involves loss of retinal ganglion cells in a characteristic pattern. The many different subtypes of glaucoma can all be considered to be a type of optic neuropathy. Raised intraocular pressure (above 21 mmHg or 2.8 kPa) is the most important and only modifiable risk factor for glaucoma. However, some may have high eye pressure for years and never develop damage, while others can develop nerve damage at a relatively low pressure. Untreated glaucoma can lead to permanent damage of the optic nerve and resultant visual field loss, which over time can progress to blindness. Glaucoma can be roughly divided into two main categories, "open-angle" and "closed-angle" (or "angle closure") glaucoma. The angle refers to the area between the iris and cornea, through which fluid must flow to escape via the trabecular meshwork. Closed-angle glaucoma can appear suddenly and is often painful; visual loss can progress quickly, but the discomfort often leads patients to seek medical attention before permanent damage occurs. Open-angle, chronic glaucoma tends to progress at a slower rate and patients may not notice they have lost vision until the disease has progressed significantly. When the scleral venous sinus is blocked to where aqueous humor is not reabsorbed at a faster rate than it is being secreted, elevated pressure within the eye occurs. Pressure in the anterior and posterior chambers pushes the lens back and puts pressure on the vitreous body. The vitreous body presses the retina against the choroid and compresses the blood vessels that feed the retina. Without a sufficient blood supply, retinal cells will die and the optic nerve may atrophy, causing blindness. Typically, the nerves furthest from the focal point fail first because of their distance from the central blood supply to the eye; thus, vision loss due to glaucoma tends to start at the edges with the peripheral visual field, leading to progressively worse tunnel vision. Glaucoma has been called the "silent thief of sight" because the loss of vision often occurs gradually over a long period of time, and symptoms only occur when the disease is quite advanced. Once lost, vision cannot normally be recovered, so treatment is aimed at preventing further loss. Worldwide, glaucoma is the second-leading cause of blindness after cataracts. It is also the leading cause of blindness among African Americans. Glaucoma affects one in 200 people aged 50 and younger, and one in 10 over the age of eighty. If the condition is detected early enough, it is possible to arrest the development or slow the progression with medical and surgical means. The two main types of glaucoma are open-angle glaucoma and closed-angle glaucoma (also called angle closure glaucoma). Open-angle glaucoma accounts for 90% of glaucoma cases in the United States. It is painless and does not have acute attacks. The only signs are gradually progressive visual field loss, and optic nerve changes (increased cup-to-disc ratio on fundoscopic examination). Closed-angle glaucoma accounts for less than 10% of glaucoma cases in the United States, but as many as half of glaucoma cases in other nations (particularly Asian countries). About 10% of patients with closed angles present with acute angle closure crises characterized by sudden ocular pain, seeing halos around lights, red eye, very high intraocular pressure (>30 mmHg), nausea and vomiting, suddenly decreased vision, and a fixed, mid-dilated pupil. It is also associated with an oval pupil in some cases. Acute angle closure is an emergency. Of the several causes for glaucoma, ocular hypertension (increased pressure within the eye) is the most important risk factor in most glaucomas, but in some populations, only 50% of people with primary open-angle glaucoma actually have elevated ocular pressure. No clear evidence indicates vitamin deficiencies cause glaucoma in humans. It follows, then, that oral vitamin supplementation is not a recommended treatment for glaucoma. Caffeine increases intraocular pressure in those with glaucoma, but does not appear to affect normal individuals. Many people of East Asian descent are prone to developing angle closure glaucoma due to shallower anterior chamber depths, with the majority of cases of glaucoma in this population consisting of some form of angle closure. Inuit also have a 20 to 40 times higher risk of developing primary angle closure glaucoma. Women are three times more likely than men to develop acute angle closure glaucoma due to their shallower anterior chambers. People of African descent are three times more likely to develop primary open angle glaucoma. Positive family history is a risk factor for glaucoma. The relative risk of having primary open angle glaucoma (POAG) is increased approximately 2–4 fold for individuals who have a sibling with glaucoma. Glaucoma, particularly primary open angle glaucoma, is associated with mutations in several different genes (including MYOC, ASB10, WDR36, NTF4, TBK1 genes), although most cases of glaucoma do not involve these genetic mutations. Normal tension glaucoma, which comprises one-third of POAG, is also associated with genetic mutations (including OPA1 and OPTN genes). Various rare congenital/genetic eye malformations are associated with glaucoma. Occasionally, failure of the normal third trimester gestational atrophy of the hyaloid canal and the tunica vasculosa lentis is associated with other anomalies. Angle closure-induced ocular hypertension and glaucomatous optic neuropathy may also occur with these anomalies, and modelled in mice. Other factors can cause glaucoma, known as "secondary glaucomas", including prolonged use of steroids (steroid-induced glaucoma); conditions that severely restrict blood flow to the eye, such as severe diabetic retinopathy and central retinal vein occlusion (neovascular glaucoma); ocular trauma (angle recession glaucoma); and uveitis (uveitic glaucoma). In a large study in the UK, glaucoma patients had a 29% increased incidence of systemic hypertension compared to age- and sex-matched controls. \|This section includes a list of references, but its sources remain unclear because it has insufficient inline citations. (June 2012)\| The underlying cause of open-angle glaucoma remains unclear. Several theories exist on its exact etiology. However, the major risk factor for most glaucomas, and the focus of treatment, is increased intraocular pressure, i.e. ocular hypertension. Intraocular pressure is a function of production of liquid aqueous humor by the ciliary processes of the eye, and its drainage through the trabecular meshwork. Aqueous humor flows from the ciliary processes into the posterior chamber, bounded posteriorly by the lens and the zonules of Zinn, and anteriorly by the iris. It then flows through the pupil of the iris into the anterior chamber, bounded posteriorly by the iris and anteriorly by the cornea. From here, the trabecular meshwork drains aqueous humor via Schlemm's canal into scleral plexuses and general blood circulation. In open/wide-angle glaucoma, flow is reduced through the trabecular meshwork, due to the degeneration and obstruction of the trabecular meshwork, whose original function is to absorb the aqueous humor. Loss of aqueous humor absorption leads to increased resistance and thus a chronic, painless buildup of pressure in the eye. In close/narrow-angle, the iridocorneal angle is completely closed because of forward displacement of the final roll and root of the iris against the cornea, resulting in the inability of the aqueous fluid to flow from the posterior to the anterior chamber and then out of the trabecular network. This accumulation of aqueous humor causes an acute increase of pressure and pain. The inconsistent relationship of glaucomatous optic neuropathy with ocular hypertension has provoked hypotheses and studies on anatomic structure, eye development, nerve compression trauma, optic nerve blood flow, excitatory neurotransmitter, trophic factor, retinal ganglion cell/axon degeneration, glial support cell, immune system, aging mechanisms of neuron loss, and severing of the nerve fibers at the scleral edge. Screening for glaucoma is usually performed as part of a standard eye examination performed by optometrists, orthoptists and ophthalmologists. Testing for glaucoma should include measurements of the intraocular pressure via tonometry, changes in size or shape of the eye, anterior chamber angle examination or gonioscopy, and examination of the optic nerve to look for any visible damage to it, or change in the cup-to-disc ratio and also rim appearance and vascular change. A formal visual field test should be performed. The retinal nerve fiber layer can be assessed with imaging techniques such as optical coherence tomography, scanning laser polarimetry, and/or scanning laser ophthalmoscopy. Owing to the sensitivity of all methods of tonometry to corneal thickness, methods such as Goldmann tonometry should be augmented with pachymetry to measure central corneal thickness (CCT). A thicker-than-average cornea can result in a pressure reading higher than the 'true' pressure, whereas a thinner-than-average cornea can produce a pressure reading lower than the 'true' pressure. Because pressure measurement error can be caused by more than just CCT (i.e., corneal hydration, elastic properties, etc.), it is impossible to 'adjust' pressure measurements based only on CCT measurements. The frequency doubling illusion can also be used to detect glaucoma with the use of a frequency doubling technology perimeter. Examination for glaucoma also could be assessed with more attention given to sex, race, history of drug use, refraction, inheritance and family history. \|What Test Examines\|\|How Examination is Accomplished\| \|Tonometry\|\|Inner eye pressure\|\|The eye is numbed via eye drops. The examiner then uses a tonometer to measure the inner pressure of the eye through pressure applied by a puff of warm air or a tiny tool.\| \|Ophthalmoscopy (dilated eye exam)\|\|Shape and color of the optic nerve\|\|The pupil is dilated via the application of eye drops. Using a small magnification device with a light on the end, the examiner can examine the magnified optic nerve.\| \|Perimetry (visual field test)\|\|Complete field of vision\|\|The patient looks straight ahead and is asked to indicate when light passes the patient's peripheral field of vision. This allows the examiner to map the patient’s field of vision.\| \|Gonioscopy\|\|Angle in the eye where the iris meets the cornea\|\|Eye drops are used to numb the eye. A hand-held contact lens with a mirror is placed gently on the eye to allow the examiner to see the angle between the cornea and the iris.\| \|Pachymetry\|\|Thickness of the cornea\|\|The examiner places a pachymeter gently on the front of the eye to measure its thickness.\| \|Nerve fiber analysis\|\|Thickness of the nerve fiber layer\|\|Using one of several techniques, the nerve fibers are examined.\| The United States Preventive Services Task Force as of 2013 states there is insufficient evidence to recommend for or against screening for glaucoma. There is thus no national screening programs in the US. There is in the UK. Those at risk are advised to have a dilated eye examination at least once a year. The modern goals of glaucoma management are to avoid glaucomatous damage and nerve damage, and preserve visual field and total quality of life for patients, with minimal side effects. This requires appropriate diagnostic techniques and follow-up examinations, and judicious selection of treatments for the individual patient. Although intraocular pressure is only one of the major risk factors for glaucoma, lowering it via various pharmaceuticals and/or surgical techniques is currently the mainstay of glaucoma treatment. Vascular flow and neurodegenerative theories of glaucomatous optic neuropathy have prompted studies on various neuroprotective therapeutic strategies, including nutritional compounds, some of which may be regarded by clinicians as safe for use now, while others are on trial. Because of the important role of the visual system in balance and maintaining posture in human beings, glaucoma patients should consider themselves at greater risk of falls, and would be advised to take the necessary precautions to help prevent any accidents. In addition, since the peripheral visual system has such a high contribution to this intrinsic balancing mechanism, the severity of glaucoma and degree of visual field obstruction should also be considered. Because of the relationship of glaucoma with age, other associated factors affecting balance (i.e. impaired proprioception) may also be present, further increasing the risk of falls. Of interesting note, one cohort of open-angle glaucoma patients had their ability to maintain posture measured (via measurements of sway) in binocular (two-eyed) and monocular (one-eyed, using both affected and unaffected eyes) conditions, as well as with their eyes closed. These patients had increased sway (worse balance) in their one-eyed conditions compared to the two-eyed conditions, and reduced sway (better balance) when using one eye than when their eyes were closed, but there were no significant differences between the two monocular conditions, with the unaffected eye having only slightly (but not significantly) reduced sway than when using their affected eyes. All patients in each condition displayed increased sway compared to their age-matched controls. Intraocular pressure can be lowered with medication, usually eye drops. Several different classes of medications are used to treat glaucoma, with several different medications in each class. Each of these medicines may have local and systemic side effects. Adherence to medication protocol can be confusing and expensive; if side effects occur, the patient must be willing either to tolerate them, or to communicate with the treating physician to improve the drug regimen. Initially, glaucoma drops may reasonably be started in either one or in both eyes. Poor compliance with medications and follow-up visits is a major reason for vision loss in glaucoma patients. A 2003 study of patients in an HMO found half failed to fill their prescriptions the first time, and one-fourth failed to refill their prescriptions a second time. Patient education and communication must be ongoing to sustain successful treatment plans for this lifelong disease with no early symptoms. Both laser and conventional surgeries are performed to treat glaucoma. Surgery is the primary therapy for those with congenital glaucoma. Generally, these operations are a temporary solution, as there is not yet a cure for glaucoma. Canaloplasty is a nonpenetrating procedure using microcatheter technology. To perform a canaloplasty, an incision is made into the eye to gain access to the Schlemm's canal in a similar fashion to a viscocanalostomy. A microcatheter will circumnavigate the canal around the iris, enlarging the main drainage channel and its smaller collector channels through the injection of a sterile, gel-like material called viscoelastic. The catheter is then removed and a suture is placed within the canal and tightened. By opening the canal, the pressure inside the eye may be relieved, although the reason is unclear, since the canal (of Schlemm) does not have any significant fluid resistance in glaucoma or healthy eyes. Long-term results are not available. Argon laser trabeculoplasty (ALT) may be used to treat open-angle glaucoma. It is a temporary solution, not a cure. A 50-μm argon laser spot is aimed at the trabecular meshwork to stimulate opening of the mesh to allow more outflow of aqueous fluid. Usually, half of the angle is treated at a time. Traditional laser trabeculoplasty uses a thermal argon laser in an argon laser trabeculoplasty procedure. A newer type of laser trabeculoplasty uses a "cold" (nonthermal) laser to stimulate drainage in the trabecular meshwork. This newer procedure, selective laser trabeculoplasty (SLT), uses a 532-nm, frequency-doubled, Q-switched Nd:YAG laser, which selectively targets melanin pigment in the trabecular meshwork cells. Studies show SLT is as effective as ALT at lowering eye pressure. In addition, SLT may be repeated three to four times, whereas ALT can usually be repeated only once. Nd:YAG laser peripheral iridotomy (LPI) may be used in patients susceptible to or affected by angle closure glaucoma or pigment dispersion syndrome. During laser iridotomy, laser energy is used to make a small, full-thickness opening in the iris to equalize the pressure between the front and back of the iris, thus correcting any abnormal bulging of the iris. In people with narrow angles, this can uncover the trabecular meshwork. In some cases of intermittent or short-term angle closure, this may lower the eye pressure. Laser iridotomy reduces the risk of developing an attack of acute angle closure. In most cases, it also reduces the risk of developing chronic angle closure or of adhesions of the iris to the trabecular meshwork. Diode laser cycloablation lowers IOP by reducing aqueous secretion by destroying secretory ciliary epithelium. The most common conventional surgery performed for glaucoma is the trabeculectomy. Here, a partial thickness flap is made in the scleral wall of the eye, and a window opening is made under the flap to remove a portion of the trabecular meshwork. The scleral flap is then sutured loosely back in place to allow fluid to flow out of the eye through this opening, resulting in lowered intraocular pressure and the formation of a bleb or fluid bubble on the surface of the eye. Scarring can occur around or over the flap opening, causing it to become less effective or lose effectiveness altogether. Traditionally, chemotherapeutic adjuvants, such as mitomycin C (MMC, 0.5–0.2 mg/ml) or 5-fluorouracil (5-FU, 50 mg/ml), are applied with soaked sponges on the wound bed to prevent filtering blebs from scarring by inhibiting fibroblast proliferation. Contemporary alternatives include the sole or combinative implementation of nonchemotherapeutic adjuvants, such as collagen matrix implant or other biodegradable spacers, to prevent super scarring by randomization and modulation of fibroblast proliferation in addition to the mechanical prevention of wound contraction and adhesion. Professor Anthony Molteno developed the first glaucoma drainage implant, in Cape Town in 1966. Since then, several different types of implants have followed on from the original, the Baerveldt tube shunt, or the valved implants, such as the Ahmed glaucoma valve implant or the ExPress Mini Shunt and the later generation pressure ridge Molteno implants. These are indicated for glaucoma patients not responding to maximal medical therapy, with previous failed guarded filtering surgery (trabeculectomy). The flow tube is inserted into the anterior chamber of the eye, and the plate is implanted underneath the conjunctiva to allow flow of aqueous fluid out of the eye into a chamber called a bleb. The ongoing scarring over the conjunctival dissipation segment of the shunt may become too thick for the aqueous humor to filter through. This may require preventive measures using antifibrotic medications, such as 5-fluorouracil or mitomycin-C (during the procedure), or other nonantifibrotic medication methods, such as collagen matrix implant, or biodegradable spacer, or later on create a necessity for revision surgery with the sole or combinative use of donor patch grafts or collagen matrix implant. And for glaucomatous painful blind eye and some cases of glaucoma, cyclocryotherapy for ciliary body ablation could be considered to be performed. TR BioSurgical has commercialized a new implant specifically for veterinary medicine, called TR-ClarifEYE. The implant consists of a new biomaterial, the STAR BioMaterial, which consists of silicone with a very precise homogenous pore size, a property which reduces fibrosis and improves tissue integration. The implant contains no valves and is placed completely within the eye without sutures. To date, it has demonstrated long-term success (longer than a year) in a pilot study in medically refractory dogs with advanced glaucoma. The most common surgical approach currently used for the treatment of glaucoma is trabeculectomy, in which the sclera is punctured to alleviate intraocular pressure. Nonpenetrating deep sclerectomy (NPDS) surgery is a similar, but modified, procedure, in which instead of puncturing the scleral bed and trabecular meshwork under a scleral flap, a second deep scleral flap is created, excised, with further procedures of deroofing the Schlemm's canal, upon which, percolation of liquid from the inner eye is achieved and thus alleviating intraocular pressure, without penetrating the eye. NPDS is demonstrated to cause significantly fewer side effects than trabeculectomy. However, NPDS is performed manually and requires higher level of skills that may be assisted with instruments. In order to prevent wound adhesion after deep scleral excision and to maintain good filtering results, NPDS as with other non-penetrating procedures is sometimes performed with a variety of biocompatible spacer or devices, such as the Aquaflow collagen wick, ologen Collagen Matrix, or Xenoplast glaucoma implant. Laser-assisted NPDS is performed with the use of a CO2 laser system. The laser-based system is self-terminating once the required scleral thickness and adequate drainage of the intraocular fluid have been achieved. This self-regulation effect is achieved as the CO2 laser essentially stops ablating as soon as it comes in contact with the intraocular percolated liquid, which occurs as soon as the laser reaches the optimal residual intact layer thickness. As of 2010, there were 44.7 million people in the world with open angle glaucoma. The same year, there were 2.8 million people in the United States with open angle glaucoma. By 2020, the prevalence is projected to increase to 58.6 million worldwide and 3.4 million the United States. Internationally, glaucoma is the second-leading cause of blindness, after cataracts. Glaucoma is also the leading cause of blindness in African Americans, who have higher rates of primary open angle glaucoma. Bilateral vision loss can negatively affect mobility and interfere with driving. Natural compounds of research interest in glaucoma prevention or treatment include: fish oil and omega-3 fatty acids, alpha lipoic acid, bilberries, vitamin E, cannabinoids, carnitine, coenzyme Q10, curcurmin, Salvia miltiorrhiza, dark chocolate, erythropoietin, folic acid, Ginkgo biloba, ginseng, L-glutathione, grape seed extract, green tea, magnesium, melatonin, methylcobalamin, N-acetyl-L cysteine, pycnogenols, resveratrol, quercetin and salt. However, most of these compounds have not demonstrated effectiveness in clinical trials. Magnesium, ginkgo, salt and fludrocortisone, are already used by some physicians. (Note: fludrocortisone is not a natural compound, but a steroid.) Studies in the 1970s showed marijuana, when smoked or eaten, effectively lowers intraocular pressure by about 25%, as much as standard medications. In an effort to determine whether marijuana, or drugs derived from it, might be effective as a glaucoma treatment, the US National Eye Institute supported research studies from 1978 to 1984. These studies demonstrated some derivatives of marijuana lowered intraocular pressure when administered orally, intravenously, or by smoking, but not when topically applied to the eye. In 2003, the American Academy of Ophthalmology released a position statement which said, "studies demonstrated that some derivatives of marijuana did result in lowering of IOP when administered orally, intravenously, or by smoking, but not when topically applied to the eye. The duration of the pressure-lowering effect is reported to be in the range of 3 to 4 hours". However, the position paper qualified that statement by stating marijuana was not more effective than prescription medications, and "no scientific evidence has been found that demonstrates increased benefits and/or diminished risks of marijuana use to treat glaucoma compared with the wide variety of pharmaceutical agents now available." The first patient in the United States federal government's Compassionate Investigational New Drug program, Robert Randall, was afflicted with glaucoma and had successfully fought charges of marijuana cultivation because it was deemed a medical necessity (U.S. v. Randall) in 1976. The world's smallest computer system, one millimeter square in size, has been developed by researchers at the University of Michigan, and is designed to be implanted in a person's eye as a pressure monitor to continuously track the progress of glaucoma. The processor consists of an ultra-low-power microprocessor, a pressure sensor, memory, a thin-film battery, a solar cell, and a wireless radio with an antenna that can transmit data to an external reader device. The survey team of Dr.Yoshiki Sasai, working at the RIKEN of Center for Developmental Biology (CDB) in Japan, succeeded in making a retina cell in three dimensions from embryonic stem cells, as was reported in Nature (7 April 2011). It was the first such success in the world, and Dr. Sasai said the goal for putting it to practical use in the retinas of human for clinical applications was within two years. Glaucoma has been classified into specific types: Variants of primary glaucoma Primary angle closure glaucoma is caused by contact between the iris and trabecular meshwork, which in turn obstructs outflow of the aqueous humor from the eye. This contact between iris and trabecular meshwork (TM) may gradually damage the function of the meshwork until it fails to keep pace with aqueous production, and the pressure rises. In over half of all cases, prolonged contact between iris and TM causes the formation of synechiae (effectively "scars"). These cause permanent obstruction of aqueous outflow. In some cases, pressure may rapidly build up in the eye, causing pain and redness (symptomatic, or so called "acute" angle closure). In this situation, the vision may become blurred, and halos may be seen around bright lights. Accompanying symptoms may include headache and vomiting. Diagnosis is made from physical signs and symptoms: pupils mid-dilated and unresponsive to light, cornea edematous (cloudy), reduced vision, redness, and pain. However, the majority of cases are asymptomatic. Prior to very severe loss of vision, these cases can only be identified by examination, generally by an eye care professional. Once any symptoms have been controlled, the first line (and often definitive) treatment is laser iridotomy. This may be performed using either Nd:YAG or argon lasers, or in some cases by conventional incisional surgery. The goal of treatment is to reverse, and prevent, contact between iris and trabecular meshwork. In early to moderately advanced cases, iridotomy is successful in opening the angle in around 75% of cases. In the other 25%, laser iridoplasty, medication (pilocarpine) or incisional surgery may be required. Primary open-angle glaucoma is when optic nerve damage results in a progressive loss of the visual field. This is associated with increased pressure in the eye. Not all people with primary open-angle glaucoma have eye pressure that is elevated beyond normal, but decreasing the eye pressure further has been shown to stop progression even in these cases. The increased pressure is caused by trabecular blockage. Because the microscopic passageways are blocked, the pressure builds up in the eye and causes imperceptible very gradual vision loss. Peripheral vision is affected first, but eventually the entire vision will be lost if not treated. Diagnosis is made by looking for cupping of the optic nerve. Prostaglandin agonists work by opening uveoscleral passageways. Beta blockers, such as timolol, work by decreasing aqueous formation. Carbonic anhydrase inhibitors decrease bicarbonate formation from ciliary processes in the eye, thus decreasing formation of Aqueous humor. Parasympathetic analogs are drugs that work on the trabecular outflow by opening up the passageway and constricting the pupil. Alpha 2 agonists (brimonidine, apraclonidine) both decrease fluid production (via. inhibition of AC) and increase drainage. Neovascular glaucoma, an uncommon type of glaucoma, is difficult or nearly impossible to treat, and is often caused by proliferative diabetic retinopathy (PDR) or central retinal vein occlusion (CRVO). It may also be triggered by other conditions that result in ischemia of the retina or ciliary body. Individuals with poor blood flow to the eye are highly at risk for this condition. Neovascular glaucoma results when new, abnormal vessels begin developing in the angle of the eye that begin blocking the drainage. Patients with such condition begin to rapidly lose their eyesight. Sometimes, the disease appears very rapidly, especially after cataract surgery procedures. A new treatment for this disease, as first reported by Kahook and colleagues, involves use of a novel group of medications known as anti-VEGF agents. These injectable medications can lead to a dramatic decrease in new vessel formation and, if injected early enough in the disease process, may lead to normalization of intraocular pressure. Toxic glaucoma is open angle glaucoma with an unexplained significant rise of intraocular pressure following unknown pathogenesis. Intraocular pressure can sometimes reach 80 mmHg (11 kPa). It characteristically manifests as ciliary body inflammation and massive trabecular oedema that sometimes extends to Schlemm's canal. This condition is differentiated from malignant glaucoma by the presence of a deep and clear anterior chamber and a lack of aqueous misdirection. Also, the corneal appearance is not as hazy. A reduction in visual acuity can occur followed neuroretinal breakdown. Associated factors include inflammation, drugs, trauma and intraocular surgery, including cataract surgery and vitrectomy procedures. Gede Pardianto (2005) reported on four patients who had toxic glaucoma. One of them underwent phaecoemulsification with small particle nucleus drops. Some cases can be resolved with some medication, vitrectomy procedures or trabeculectomy. Valving procedures can give some relief, but further research is required. Absolute glaucoma is the end stage of all types of glaucoma. The eye has no vision, absence of pupillary light reflex and pupillary response, and has a stony appearance. Severe pain is present in the eye. The treatment of absolute glaucoma is a destructive procedure like cyclocryoapplication, cyclophotocoagulation, or injection of 99% alcohol. In open-angle glaucoma, the typical progression from normal vision to complete blindness takes about 25 years to 70 years without treatment, depending on the method of estimation used. The intraocular pressure can also have an effect, with higher pressures reducing the time until blindness.	2	14	0	0	1	0.417697	1	7,204
April 14, 2020 - by Parul Saini, Webmedy team HIPAA is for Health Insurance Portability and Accountability Act. Declared in 1996 HIPAA is a federal rule that establishes a national standard to preserve medical records and other personal health data. The HIPAA laws apply to: Business associates of a protected entity are not openly controlled by the laws, but necessary contracts require them to protect the privacy of personally identifiable information. It is an act that gives security requirements and data privacy, to put patients' medical data safe. The Privacy Rule needs medical providers to give people access to their PHI. After an individual demands data in writing (typically utilizing the provider's form for this purpose), a provider has up to 30 days to give a copy of the data to the person. A person may demand the information in an electric form or hard-copy, and the provider is committed to trying to agree to the demanded format. For providers employing an electronic health record (EHR) system that is verified using CEHRT (Certified Electronic Health Record Technology) standards, people must be enabled to get the PHI in electronic form. These laws are known as the Transaction Code Set Standards. The ultimate rules for EDI and Code sets were executed on October 16, 2003. Many of the transaction management standards are yet under analysis and have not been declared. The goal of these regulations is to regulate the electronic interchange of information (transactions) among trading partners. These activities are mandated to be in the ANSI ASC X12 variant 4010 formats. The HIPAA Code Set Regulations set a uniform standard of data components applied to document reasons why patients are examined and the methods performed during health care appointments. Analyses - ICD 9/10; Procedures - CPT 4, CDT; Supplies/Devices - HCPCS; Additional Clinical Data - Health Level Seven (HL7). HIPAA detailed administrative codes established for use in connection with certain transactions and HIPAA ejected state-specific local codes. These laws set rules for preserving individually identifiable health information and for ensuring the rights of individuals to have more authority over such information. Privacy rules represent the rights of individuals and safety rules describe the method and technology needed to assure privacy. These laws set standards for the security of electronically guarded health information (PHI). It sets out three types of security safeguards needed for compliance: administrative, physical, and technical. The following are the standards and specifications: This includes policies and procedures intended to simply show how the entity will comply with the act of: These laws set the standard individual health identifier for health care providers to clarify administrative processes, such as referrals and billing, to advance the efficiency of data, and decrease costs. The NPI replaces all other identifiers used by health plans, Medicare, Medicaid, and other government programs. But, the NPI does not substitute a provider's DEA number, state license number, or tax identification number. The NPI is 10 digits (may be alphanumeric), with the last digit holding a checksum. The NPI cannot include any enclosed intellect; in other words, the NPI is just a number that does not itself have any further meaning. The law brings heavy civil and criminal fines for negligence to comply. US DHHS Office for Civil Rights will impose civil fines that may involve fines from $100 per breach to $25,000 per calendar year. US Department of Justice will impose criminal penalties which may add up to 10 years of confinement and a $250,000 penalty.	3	5	0	0	1	0.375787	1	718
Non-Random Selection of Cancer-Causing Mutations in Tissue-Specific Stem Cells Cause Cancer - 1. Institute for Advanced Study, Simons Center for Systems Biology, Princeton, USA Tissue-specific stem cells are the target for selected mutations in oncogenes or tumor suppressor genes that enhance the fitness of these cells, resulting in a self-limited clonal expansion and eventual cancer development. The initial or truncal mutations in the stem cell select for subsequent mutations that enhance their fitness, producing a reproducible order of mutations, selected for in each tissue type, during cancer development. Mutations in stem cells occur randomly, but the selection for increased fitness, occurs non-randomly, conferring a functional order on the selection of mutations. Tissue-specific stem cells are “units of natural selection” for somatic stem cells throughout life. This is why inherited cancer-causing mutations, which, by definition, are initial or truncal mutations, are observed to cause cancers with limited tissue specificities, even though the mutations are present in stem cells for all tissue types. n future studies, we need to understand why the same signal transduction pathways function differently in different tissue-specific stem cells. We also need to understand the truncal mutations for each cancer type, so as to eradicate the stem cell clones for that cancer before they produce a malignant tumor. To accomplish these objectives, we need to carry out new kinds of clinical trials with drugs that target mutations in tissue-specific stem cells. Levine AJ (2020) Non-Random Selection of Cancer-Causing Mutations in Tissue-Specific Stem Cells Cause Cancer. JSM Clin Oncol Res 8(1): 1063. - Tissue specific stem cells - selection of mutational order - inherited predispositions - units of natural selection CpG cytosine-3’5’: guanosine monophosphate; LGR5: leucine-rich repeat containing G-coupled receptor-5; WNT: wingless; LPR 6: low density lipoproteion receptor-6; Fzd5: frizzled receptor d5; APC: adenomatous polyposis coli; SMAD: transcription factor for the TGF-beta pathway; TGF-beta transforming groth factor beta; Ras: rat sarcoma; BRCA 1/2: breast cancer gene; PTEN: phosphatase and tensin homolog; TSC1/2: tuberous sclerosis proteins 1,2; WT 1: Wilms tumor; ATM: ataxia telangiectasia mutant. A Stem Cell Classification Throughout any complex organism’s development, including sexual maturity, adult life, and aging, there are many different stem cell types that arise and populate the organism. The fertilized egg is the totipotent stem cell that is the forerunner of all cell types. In many multicellular animals, it produces a spherical blastocyst, where a subset of stem cells (inner cell mass cells in mammals) produce the organism and the outer trophoblast cells produce the membranes of the fetus. The symmetry and topology of the blastocyst is broken by gastrulation, forming anterior-posterior poles, dorsal-ventral sides and a sphere-totorus transition. Three sets of stem cells, endoderm, mesoderm and ectodermal produce a subset of tissue-types in the body of the organism. As these tissues form, tissue-specific stem cells become responsible for producing the many different tissues of the organism and the many different cell types that populate a tissue. Tissue-specific stem cells function in the fetus to produce the organs. In mammals, they function throughout life to replace normal and damaged or aging tissues. In humans, tissue-specific stem cells in the crypt, reproduce a new endodermal lining every four days . In skin, tissue-specific stem cells located in the hair follicle, produce new skin clones every 28 days . In the hematopoietic system, tissue-specific stem cells located in the bone marrow, replicate to create a variety of progenitor cells that produce mesenchymal derivatives, which populate both the blood and tissues in a variety of organs . In humans and mice, these tissue specific stem cells are the target cells for mutations that lead to tissue-specific cancers . Changes, Tissue Regeneration and Tissue Replacement In many invertebrates, such as the planarian flat worms, cutting the worm in half causes the frontend to regenerate a backend, and the backend to regenerate a frontend. This is accomplished by a differentiated cell in the area of the cut, that is reprogrammed epigenetically to dedifferentiate, losing epigenetic marks, and forming what is termed a blastema . The blastema then regenerates a head or tail, depending upon its location in the worm. Similarly, vertebrates such as fish, amphibians and even some reptiles, can regenerate a tail or appendage as an adult using these same dedifferentiating strategies. In experiments carried out by Yamanaka and Takahashi, using mouse or human fibroblasts in cell culture, which were epigenetically reprogrammed with four transcription factors, produced inner cell mass-like stem cells that could differentiate into many or all mouse tissues in vivo or diverse cell types in vitro . It is curious that this is the case with mammalian fibroblasts, even though these animals are not capable of regenerating limbs, and utilize tissue-specific stem cells to regenerate selected tissues. However, the efficiency with which the Yamanaka factors reprogram differentiated mammalian cells is poor (0.1-1%) and the time it takes to accomplish this is long (weeks to months) in culture. This makes a good deal of sense because epigenetic marks, and cell and tissue types, must be stable and resistant to change. The mechanisms that form the basis for this stability have been explored by Jaenisch and his colleagues . They made a conditional mutation in the DNA methyl-transferase-1 gene of mice. This is the copy DNA methyl-transferase gene, whose protein will identify a methylated CpG dinucleotide on a DNA template strand and methylate a cytosine on the newly synthesized DNA strand so that the DNA epigenetic marks are inherited in a tissue-specific fashion. In this experiment, the DNA methyl-transferase-1 activity is destroyed by the Cre-Lox mediated mutation placed in this gene (similar to the cancer causing mutation in that gene). The resultant cells divide twice and then undergo apoptosis . A few cells can escape the apoptosis and go on to be transformed and cause a cancer . When the p53 gene is also deleted, along with the DNA-methyl-transferase-1 gene, apoptosis fails to occur, and the cell produces a cancer. Most interestingly, when the Yamanaka factors reprogram a differentiated cell carrying a temperature sensitive p53 mutation at the restrictive temperature (non-functional p53), they very efficiently produce stem cells (up to 80% efficiency) in a short period of time, while at the non-restrictive temperature (p53 is active), the efficiency is low and the time to reset the epigenetic program is long . Thus, it appears that a p53-regulated activity is important for epigenetic stability . This is just one of the reasons why the p53 gene is the most commonly mutated gene in human cancers , and why there is epigenetic instability and epithelial to mesenchymal transitions, in cancerous tissues. Tissue-Specific Stem Cells Tissue-specific stem cells are the targets of mutations that produce tissue- and cell- type-specific cancers. This was demonstrated by the isolation of tissue-specific stem cells from normal tissues, which are cloned and produce organoids in cell culture, and are shown to produce many or all of the cell types in normal tissues . When these stem cells are cloned from cancerous tissues, they harbor the mutations that cause these cancers . These stem cells from many diverse tissues have in common that they all express Lgr5 G-protein coupled receptors on their cell surface. This receptor is coupled to the Wnt ligand receptors LRP-6 and Fzd5, and when internalized into the cell together, potentiate the Wnt pathway, increasing its downstream transcription and replicating the stem cells that then differentiate into the many different cell types of that tissue . Over a life-time, these tissue-specific stem cells replicate and accumulate about 40 mutations per year (both cancer-causing and non-cancer-causing mutations) . This was demonstrated by obtaining stem cells from organoids (small intestine, colon and liver), derived from individuals 3 to 87 years-old, and sequencing whole genome DNA from the stem cells. These tissue-specific stem cells reproduce themselves in a specific location in a tissue, producing a pool of stem cells, some of which become committed to differentiate into tissue components. These stem cells thus become Darwinian units of selection for reproductive fitness . When mutations occur in pathways that have an impact upon cell division, cell death, or DNA repair processes (the loss of which increases the mutation rate), these mutations affect the fitness of the stem cell, in some cases increasing the concentration of stem cells carrying the mutation, producing a self-limited benign tumor . Such initial or truncal mutations in a tissue-specific stem cell produce a small clone of cells in the tissue, as has been observed with notch mutations in skin and esophagus [16, 17] and leukemias [18-23] harboring DNA methyltransferase 3 beta (epigenetic) and p53 (DNA damage response) mutations. In cells shed in uterine fluid from women who develop ovarian cancer, ultra-deep sequencing has enabled the detection of p53 mutations. Ultra-deep sequencing has also enabled detection of age-related p53 mutations in normal healthy women . Not every oncogene product or tumor suppressor gene mutation is functional in a tissue-specific stem cell [24, 25]. Different tissue-specific stem cells have different mutations in tumor suppressor genes or oncogenes that result in observed phenotypes, such as increased fitness or self-limited clonal cell growth. This could be due to a lack of transcription of the causal gene in a tissue-specific stem cell or to a lack of activity of the gene product . In fact, this is why inherited tumor suppressor gene mutations or inherited defective DNA repair gene mutations, which are by definition initial or truncal mutations, demonstrate a distinct tissue- or cell-type phenotype [24,26]. Table 1 lists a number of inherited mutations of tumor suppressor or DNA repair genes that demonstrate an early age of onset of a tissue-specific cancer, even though many of these genes are expressed in a wide variety of tissue types. The Order of Mutations Producing a Tumor Matters Vogelstein and his colleagues [27,28] were the first to suggest that in colon cancers, mutations occur or are selected for in a specific order, with APC mutations occurring first, producing a small benign tumor, activating RAS mutations occurring next, producing a larger benign tumor, inactivating SMAD4 mutations occurring third, producing a large benign tumor, and inactivating p53 mutations occurring last, producing a malignant tumor. They did this by collecting colonoscopy samples from many different individuals and reconstructing the events by the size and state of the tumor. This idea was confirmed by obtaining normal colon organoids and introducing the mutations for APC, RAS, SMAD4 and p53, using a CRISPR/Cas9 mutational mechanism, to introduce mutations into the tissue-specific stem cells in different orders of addition. The most efficient order to produce an organoid that was tumorigenic in nude mice was APC, followed by RAS, followed by SMAD4, and then by p53. P53 mutations introduced first, or before the other oncogenes, had no impact alone . The concept that the order of mutations mattered was proven experimentally by introducing a transposon into a mouse genome that moved around the genome causing insertion mutations and abnormal gene expression. The transposon was expressed in the cells of the intestine, inserting randomly throughout the genome. Under these conditions, 50% of the mice developed an intestinal tumor and survived for 85 days. When homozygous inherited p53 mutations were present in the germ line of these mice, half the mice survived for 65 days. When SMAD4 mutations were present in the germ line of these mice, half the mice died in 55 days. When a conditional Kras mutation was activated just after birth in the intestine, half the mice lived for 40 days, and when a homozygous inherited APC mutation was present in the germ line, half the mice died with intestinal tumors in 20 days . The APC gene was therefore the most efficient initial or truncal mutation in producing an intestinal tumor most rapidly. The order of mutations is random, but the selection for these mutations is non-random in each particular tissue-specific stem cell (Table 1). In slim stem cells in the colon, APC mutations enhance the fitness of the cell, producing a clonal expansion of stem cells, whereas Kras, SMAD4, and p53, which are required after APC for a malignant tumor to arise, do not increase the fitness of the stem cell unless APC is present. That the initial truncal mutation can affect the order of the genes contributing to a tumor received further support when the inherited initial truncal mutation was Smad4. In this case, two thirds of the intestinal tumors had activating mutations in R-spondin-1 (Rspo-1) and Rspo-2, which enhance the WNT pathway by targeting a different gene than APC . Thus, having an initial truncal mutation in the TGF-beta pathway in a slim stem cell seems to have changed the gene that preferentially is selected for mutation in the order of selection for fitness of a tumor . This is observed in about 10% of human colon cancers. Although this is the best studied example of the observation that the order of mutational selection is important for the optimal selection of a tumor, there are a large number of other examples where mutational order matters [24, 26]. Inherited p53 mutations, Li-Fraumeni Syndrome The simplest way to determine which tumor suppressor genes or DNA repair gene defects are functional in tissue-specific stem cells is to examine the phenotypes of inherited mutations that act as initial truncal mutations in humans. By determining the tissue types and frequencies of different tumors, the age interval in which tumors arise and the excess risk of developing a tissue-specific tumor compared to the general population, one can begin to classify the oncogenes and tumor suppressor genes that initiate cancers in humans [26, 31]. For example, some individuals who inherit a cancer-causing p53 mutation may develop an adrenal cortical carcinoma at 6 months to 4 years of age, a choroidplexis papilloma/carcinoma at 6 months to 3 years of age, a medullary blastoma at 2-9 years of age, and a rhabdomyosarcoma at 1-4 years of age, and these tumors have an excess risk of 100-200 times the population not carrying an inherited p53 mutation. Liposarcomas are observed from 1-50 years of age and leiomyosarcomas at 20-60 years of age, whereas breast cancers (ER+/PR+) are commonly observed at 18-45 years of age in 50-70% of the women with inherited p53 mutations [26, 31]. These tumors appear at 50-100-fold excess risk. Colon tumors, lung cancers, pancreatic tumors and ovarian tumors all occur very late in life, 50-70 years of age, at an excess risk of 2-4- fold, from that observed in the general population (Table 2). It is of some interest that ectoderm and mesoderm derived stem cells produce tissue-specific stem cells with inherited p53 mutations that lead to tumors much earlier in life and at much higher excess risk, than endoderm-derived tissue-specific stem cells with p53 mutations. This is not occurring because endodermal tissue-specific stem cells do not require p53 mutations to form a tumor (table 2). Spontaneous p53 mutations occur at very high frequencies in ovarian, colon, stomach, pancreatic and lung cancers, but in those cancers, a p53 mutation is selected for as one of the last mutations in a series leading to the transition from benign to malignant tumors. In those tissues, p53 mutations have no impact upon tissue-specific stem cells as initial truncal mutations, as seen in the low excess risk of these tumors in inherited patients, and the very late time of development of these cancers in inherited forms of mice and humans [30-31]. Table 1: Examples of Mutations that Cause Inherited Tissue Specific Cancers at Early Ages. \|Mutated Gene\|\|Tissue Specific Cancers\| \|Retinoblastoma\|\|Retinoblasts, followed by Osteogenic sarcomas\| \|P53\|\|Medulary blastoma, Adrenal corticocarcinoma, Rhabdomyosarcoma, Sarcomas\| \|BRCA-1/2\|\|Ovarian cancers, Breast cancers\| \|PTEN\|\|Cowden Disease, Hamartomas, Breast cancers\| \|Lynch Syndrome -Mismatch repair \|Polyps of the colon\| DISCUSSION AND CONCLUSIONS The target cells for spontaneous mutations that lead to cancer development are tissue-specific stem cells . Because of exposure to mutagens and the replication of these stem cells over time, they accumulate about forty spontaneous mutations per year of life . There are hundreds of oncogenes and tumor suppressor genes, and it takes mutations in only about 2-5 of these genes to initiate a malignant cancer. There are also hundreds of genes that encode different DNA repair functions. Inherited or spontaneous mutations in these DNA repair genes contribute to an enhanced mutation rate and an earlier onset of cancer. These are the reasons why the age of a person is such an important variable for cancer development. Cancer rates rise logarithmically with age , although in cases where an inherited mutation contributes to cancer, the incidence commonly occurs at a younger age. Each tissue-specific stem cell type that contributes to the repair and renewal of each tissue of the body, responds to a random mutation in only a small subset of tumor suppressor genes or oncogenes, by increasing its fitness or clonal replication, producing a self-limiting benign clonal expansion [24-26]. Although mutations are random in their occurrence, selection of a mutation for an increased fitness is not random among the oncogenes and tumor suppressor genes. Functional mutations are specific to tissue stem cell types. This means that there are a limited number of mutations that can act as an initial or truncal mutation for a specific tissue type [24,26]. Inherited mutations function, by definition, as initial or truncal mutations in a subset of tissue-specific stem cells, and, as such, inform us as to what gene mutations are functional for increased fitness in the human body. This explains why inherited tumor suppressor genes demonstrate a clear tissue tumor specificity in causing cancers, but the same gene mutations are found at very high frequencies in different tissues when they occur as spontaneous mutations. Tables 1 and 2 demonstrate the tissues that develop tumors at a high excess risk with inherited p53 mutations (and other tumor suppressor genes) because they function as initial or truncal mutations in that tissue-specific stem cell, whereas the very same mutations function, in a series of mutations, as late onset spontaneous mutations in other tissues with a very low excess risk as inherited tumors. They only function later in life after other mutations have accumulated in the tissue-specific stem cell. This is not to say that these mutations occur in a specific order, they do not, mutations occur randomly. It is functional selection for increased fitness that occurs in a specific order, ultimately producing a malignant cancer. Both the type of tissue-specific stem cell and the order of functional mutations, modulate the development of a cancer [24-26]. An increasing number of examples of these ideas are being documented in the literature [24-26]. These observations help to explain why drug development for cancers was, from the beginning, limited by tissue specificity and why drug approvals came with an associated tissue type. More interesting have been the drugs that target a specific gene or even a specific mutation in a gene (BRAF, RAS, ABL, etc.). They are functioning differently in different tissue types of cancers even with the exact same mutation. They are, of course, functioning in different tissue-specific stem cells. The signal transduction pathways we draw in thousands of publications need to be understood as approximations, which can function differently in their circuitry or feed-back or feed-forward mechanisms, in different stem or progenitor cell populations. Drugs focused upon targeted gene mutations or even allele-specific mutations, have a good deal to teach us as they are explored in different human cancers with the same mutation in a different tissue type. This interpretation of what is happening in a cancer stem cell may call for a new kind of drug and a new kind of clinical trial, carried out to understand more about cancer development rather than to get to registration first. The comparison of the same mutant allele in inherited mutations versus spontaneous mutations (in the same or different tissues) is not something that drug companies would normally pursue. Perhaps, there is a role for the NCI or private foundations to explore this by setting up small clinical trials at cancer centers that do not necessarily develop drugs, but use them to understand the basis of cancer development, and, in the end, learn how to cure cancers before they ever arise as malignant or metastatic tumors. Table 2: Selected Examples of Somatic p53 Mutations that occur at high frequencies and Function as Late mutations in the order of Cancer Development. \|Non Small Cell Lung Adenocarcinoma\|\|70%\| The author would like to thank Suzanne Christen for help with the manuscript and Neal Copeland and Nancy Jenkins for a critical reading of the manuscript. This work was supported by a grant from the NCI, POI-CA087497-18. CONFLICTS OF INTEREST The author is the founder of a Biotech company that is attempting to synthesize small molecule reactivators of p53 mutations. He is also the chair of the Janssen Scientific Advisory Board. 4. Sato T, Stange DE, Ferrante M, Vries RGJ, Van Es JH, Van den Brink S, et al. Long- term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology. 2011; 141: 1762-1772. 7. Jackson-Grusby L, Beard C, Possemato R, Tudor M, Fambrough D, Csankovszki G, et al. Loss of genomic methylation causes p53- dependent apoptosis and epigenetic deregulation. Nat Genet. 2001; 27: 31-39. 14. Salk JJ, Loubet-Senear K, Maritschnegg E, Valentine CC, Williams LN, Higgins JE, et al. Ultra- sensitive TP53 sequencing for cancer detection reveals progressive clonal selection in normal tissue over a century of human lifespan. Cell Rep. 2019; 28: 132-144. 15. Martincorena I, Roshan A, Gerstung M, Ellis P, Van Loo P, McLaren S, et al. Tumor evolution high burden and pervasive positive selection of somatic mutations in normal human skin. Science. 2015; 348: 880- 886. 19. Busque L, Patel JP, Figueroa ME, Vasanthakumar A, Provost S, Hamilou Z, et al. Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. Nat Genet. 2012; 44: 1179- 1181. 21. Acuna-Hidalgo R, Sengal H, Steehouwer M, van der Vorst M, Vermeulen SH, Kiemeney LALM, et al. Ultra- sensitive sequencing identifies high prevalence of clonal hematopoiesis associated mutations throughout adult life. Am J Hum Genet. 2017; 101: 50-64. 28. Baker SJ, Preisinger AC, Jessup JM, Paraskeva C, Markowitz S, Willson JKV, et al. p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Res. 1990; 50: 7717-7722. 30. Takeda H, Wei Z, Koso H, Rust AG, Yew CCK, Mann MB, et al. Transposon mutagenesis identifies genes and evolutionary forces driving gastrointestinal tract tumor progression. Nat Genet. 2015; 47: 142-150.	2	13	0	0	3	0.459258	3	5,294
2 Objectives Discuss different types of mitochondrial disease Recognize common featuresReview options for treatment if they existFocus on RITE diseases/topicsRITE type questions 3 Mitochondrial Diseases SummaryEncephalopathyMyopathyNeuropathyCardiomyopathyRetinopathyExercise intoleranceShort statureHearing lossElevated lactateRagged red fibersInheritanceMaternal, recessive, orsporadicTreatment:Creatine, Co-Q10, ketogenic diet (other than beta oxidation defects with high carb diet), carnitine, avoidance of fasting, supportive 4 Mitochondrial Disorders or “Cytopathies” Result from mutations in mitochondrial or nuclear genes resulting in failures of oxidative phosphorylation characterized by:Genetic and clinical heterogeneityPainful ACRONYMS and Eponyms (or both!)Lactic acidosisSome treatments exist, but no curesCould try creatine or CoQ10 5 Types of diseaseAlpers DiseaseBarth syndromeBeta-oxidation DefectsCarnitine-Acyl-Carnitine DeficiencyCarnitine DeficiencyCreatine Deficiency SyndromesCo-Enzyme Q10 DeficiencyComplex I DeficiencyComplex II DeficiencyComplex III DeficiencyComplex IV DeficiencyComplex V DeficiencyCOX DeficiencyCPEOCPT I DeficiencyCPT II DeficiencyGlutaric Aciduria Type IIKSSLactic AcidosisLCADLCHADLeigh Disease or SyndromeLHONLIC (Lethal Infantile Cardiomyopathy)Luft DiseaseMADMCADMELASMERRFMIRASMitochondrial CytopathyMitochondrial DNA DepletionMitochondrial EncephalopathyMitochondrial MyopathyMNGIENARPPearson SyndromePyruvate Carboxylase DeficiencyPyruvate Dehydrogenase DeficiencyPOLG MutationsRespiratory ChainSCADSCHADVLCAD– The United Mitochondrial Disease Foundation 6 Types of disease found in RITE database Beta-oxidation DefectsCreatine Deficiency SyndromesCo-Enzyme Q10 DeficiencyCPEOGlutaric Aciduria Type IIKSSLactic AcidosisLeigh Disease or SyndromeLHONMADMELASMERRFMitochondrial DNA DepletionMitochondrial EncephalopathyMitochondrial MyopathyNARPPyruvate Dehydrogenase DeficiencyRespiratory Chain– The United Mitochondrial Disease Foundation 8 Mitochondrial Disorders: Inheritance About ½ of mitochondrial diseases are inherited from mitochondrial DNA in a maternal fashionThe other ½ are due to nuclear mutations that affect mitochondrial functionMany are sporadic mutations 11 Mitochondrial Myopathy - Pathology Normal SDHSuccinyl Dehydrogenase)SDH +Ragged Red FibersCOX –Cytochrome oxidaseParacrystalline inclusions (MELAS) 12 AnswerThis substance is found in high concentrations in serum and CSF of patients with mitochondrial cytopathies. 13 Question What is lactic acid? Lactate and glucose levels in various disease:Mitochondrial cytopathy – low glucose, high lactate14 questions in 14 years 14 AnswerThis anesthetic infusion used for sedation inhibits mitochondrial fatty acid oxidation, oxidative phosphorylation, carnitine palmitoyl transferase, and secondarily inhibits Complex II. 15 Question What is propofol? Propofol infusion syndrome More common in children than adultsmetabolic acidosis, heart failure, renal failure, hyperkalemia and rhabdoPrevent by giving carbohydrate load/infusion (children have limited carbohydrate reserves)Treat by hemofiltration3 times in 14 years 16 Case 1 16 year-old boy CC: Ataxia and droopy eyelids. HPI: PMH: Exam: His ptosis started at age 5 and his parents note that he turns his head more then usual when trying to look around. He also has noted that his balance is off and he occasionally drops objects.PMH:short staturediabetescomplete heart blockExam:Bilateral ptosis and restricted bilateral horizontal eye movements. His fundoscopic exam reveals pigmentary retinopathy. His has 4/5 strength in his proximal arms and legs and is unable to tandem walk.Workup:Serum lactate is slightly elevated. CSF shows elevated protein and lactate. Muscle biopsy shows ragged red fibers.Diagnosis? 17 Case 1 – Kearns-Sayre Syndrome 16 year-old boyCC: Ataxia and droopy eyelids.HPI:His ptosis started at age 5 and his parents note that he turns his head more then usual when trying to look around. He also has noted that his balance is off and he occasionally drops objects.PMH:short staturediabetescomplete heart blockExam:Bilateral ptosis and restricted bilateral horizontal eye movements. His fundoscopic exam reveals pigmentary retinopathy. His has 4/5 strength in his proximal arms and legs and is unable to tandem walk.Workup:Serum lactate is slightly elevated. CSF shows elevated protein and lactate. Muscle biopsy shows ragged red fibers.Genetics: mtDNA deletions, usually sporadic5 question in 14 years 18 Kearns-Sayre Syndrome Insidiously progressive disease with CPEO before the age of 20.Symptoms/Clinical Features:Mitochondrial Myopathy (proximalweaknessCPEOretinal degeneration (pigmentary retinopathy)cardiac conduction defects (heart block)Ataxia/cerebellar syndromeOther symptoms include small stature, deafness, dementia, delayed puberty, and endocrine dysfunctionLaboratory: Increased CSF protein and lactateMRI- bilateral subcortical white matter T2 hyperintensitiesinvolving basal ganglia, thalamus, and brainstemPathology: ragged red fibersNote: Pearson’s syndrome- sideroblastic anemia,pancreatic insufficiency, and low birth weight precede KSS symptoms. 19 Chronic Progressive External Ophthalmoplegia PtosisSymmetric ophthalmoplegia with relative sparing of downgazeFacial weakness, frontalisDysarthriaSparing of ciliary and iris musclesCommon presentation of any mitochondrial myopathyLid surgery is usually not performed due to risk for exposure keratopathyCan be isolated or part of KSS 20 Case 2 14 year old girl CC: New onset seizures HPI: Normal up until 2 months prior to presentation when she started having falls. She then had several seizures, when her parents brought her to the hospital. She became comatose and was intubated. After extubation and waking, she had difficulty using the right side of her bodyPMH:Normal childhood and development, previously healthyExam:Cogwheel rigidity in the right arm and wrist, cervical dystonia, bradykinesia and apraxia on the right. Diffuse hyperreflexia, worse right than left, and right Babinksi sign.Workup:MRI shows changes in the basal ganglia, thalamusSpectroscopy shows increased lactate peakDiagnosis? 21 Case 2 – Leigh’s Disease 14 year old girl CC: New onset seizures HPI: Normal up until 2 months prior to presentation when she started having falls. She then had several seizures, when her parents brought her to the hospital. She became comatose and was intubated. After extubation and waking, she had difficulty using the right side of her bodyPMH:Normal childhood and development, previously healthyExam:Cogwheel rigidity in the right arm and wrist, cervical dystonia, bradykinesia and apraxia on the right. Diffuse hyperreflexia, worse right than left, and right Babinksi sign.Workup:MRI shows changes in the basal ganglia, thalamusSpectroscopy shows increased lactate peakDiagnosis? 22 Case 2 – Leigh’s DiseaseSubacute Necrotizing Encephalomyelopathy (SNEM)Clinical FeaturesDevelopmental delay or psychomotor regressionBrainstem dysfunctionRespiratory disorders (episodic hyperventilation)OphthalmoplegiaAtaxiaDystoniaSeizures, lactic acidosis, vomiting, weaknessPeripheral neuropathy, reduced nerve conduction velocity, demyelinationGeneticsMutations in either mtDNA or nuclear DNAPyruvate dehydrogenase (PDHC) most commonImaging/PathologyBilateral, symmetric necrotizing lesions with spongy changes, microcysts in the basal ganglia, thalamus, brainstem, and spinal cordPrognosisPoor, survival of months from disease onset5 questions in 14 years 25 Case 3 20 year old woman CC: Right-sided weakness HPI: New symptom of right-sided face, arm, and leg weakness, started yesterday along with a headacheNausea, vomitingRoommate noticed she was sleepy today and not her normal selfPMH:HeadachesSensorineural hearing lossDiabetesExam:Short statureRight homonymous hemianopsia, right hemiparesis, language problemsWorkup:Serum lactic acidosisMRI 27 Mitochondrial Encephalopathy Lactic Acidosis and Stroke-Like Episodes (MELAS) Clinical features-MyopathyEncephalopathy with headaches and vomitingStroke like symptoms: hemiparesis, hemianopsia most commonShort stature, hearing loss, lactic acidosis and diabetesMutation- mtDNA point mutationsLaboratory: Lactic acidosis with exerciseMRI: T1-weighted hyperintense cortical signal that are compatible with cortical laminar necrosis & cytotoxic edema. Lesions do not conform to single vascular territories. Also see bilateral basal ganglia calcifications, cerebellar and cerebral atrophy.Pathology: ragged red fibersTreatment: Carnitine, Co-Enzyme Q10, Vitamin K, Vitamin C, L-Arginine8 questions in 14 years 28 Case 4 22 year old man CC: Vision loss HPI: Blind spot in central visual field in right eye, onset over 5-6 days, painlessDiagnosed originally with optic neuritisPresents for second time 2 months later with similar subacute vision painless central vision loss in left eyePMH:None – healthy otherwiseExam:Central visual field loss bilaterally, color desaturation, relatively preserved peripheral visionWorkup:MRI brain - normalVisual field testingLP – negative for OCB, IgG index normal 31 Case 4 – Leber’s Hereditary Optic Neuropathy Bilateral subacute optic neuropathy caused by mtDNA mutations.Clinical Features:Painless, severe and permanent subacute central visual loss.Can be initially unilateral- with second eye often affected in following 1-2 months.Usually starts in Late teens/early adulthood.Can occasionally be associated with MS like symptoms/lesionsFundoscopic exam: Telangiectatic microangiopathy, disc pseudoedema, microangiopathy, or vascular tortuosity.Pathology:mtDNA point mutationsNo ragged red fibers seen on pathology- only mitochondrial disease with this.2 questions in 14 years 32 Case 5 17 year old girl CC: Numbness and clumsiness HPI: Has always been clumsy, but recently she started falling and tripping over objectsShe says that she has a hard time feeling the ground, trips easily over cracks in the sidewalk or on carpetFeels a little weak in the legs, has some difficulty standing from a low-seated chairPMH:Poor vision, has glassesLearning disorder, has an IEPExam:MS WNL. CNs show decreased visual acuity, ptosis, fundus exam shows…Proximal LE weakness and decreased sensation distally in lower extremities.Brisk patellar reflexesFNF and HKS shows significant dysmetria.Gait ataxiaWorkup:MRI brain - normalEMG shows peripheral sensory polyneuropathy, worse LE than UE 33 Case 5 - Neuropathy, Ataxia, Retinitis Pigmentosa (NARP) Clinical featuresSensory neuropathyCerebellar ataxiaRetinitis pigmentosaProximal weakness myopathyPtosisMutationmtDNA point mutation that is the same as seen in KSS and Leigh’sEMGSensorimotor polyneuropathy, myopathic features on needle examPathologyRagged red fibersTreatment?Gene therapy and skin-derived pluripotent stem cell grafts are being studiedFor retinitis pigmentosaVitamin A, lutein, docosahexaenoic acid, acetazolamide, calcium channel blockers, and valproic acid1 question in 14 years – does not have opsoclonus 34 Case 622 year old manCC: Seizures and limb jerking, also has weakness and clumsinessHPI:In the last year, has developed seizures of staring, followed by rhythmic jerking of the upper extremities. Occasionally, he has jerking muscle twitches in his arms without loss of consciousnessHas fallen twice in the last 6 months at home walking down the stairs and feels a little unsteady while walking, feeling both weak in his legs and having difficulty feeling the ground with his feetNoted some problems with coursework, now getting failing grades in college – he previously graduated high school without difficultyPMH:Hearing lossShort statureIdiopathic cardiomyopathy diagnosed on echo, ordered for mild murmur on examExam:MS, CNs, reflexes are normalProximal LE weakness and decreased sensation distally in lower extremities.FNF and HKS shows mild dysmetria.Gait ataxia 35 Case 6Workup:Biopsy:EMG: Small amplitude, short duration motor unit action potentialsLP: Elevated lactate and pyruvateDiagnosis ? 36 Case 6 - Myoclonic Epilepsy with Ragged Red Fibers (MERRF) Clinical Features:Starts in 20’s to 30’sProximal muscle weaknessEpilepsy with MyoclonusDementiaAtaxiaCardiomyopathyAlso get pyramidal tract signs, neuropathy, optic nerve atrophy, and neurosensory hearing loss.Mutation: mtDNA point mutations or deletions or POLG-1 mutationLaboratory: Increased CSF lactate and pyruvate.EMG: Myopathic featuresPathology: Neuronal loss in dentate, inferior olive, substantia nigra, gliosis in the cerebellar cortex, and degeneration of the posterior column.Treatment: Treat Seizures with Keppra rather than VPA, as VPA can cause hepatic failure in these pts with increased frequency.3 question in 14 years 37 Cases 7, 8, and 9 3 month old girl Recurrent episodes of hypoglycemia, hypotonia, and profound acidosis35 year old manElevated CK and recurrent rhabdomyolysis after vigorous exercise60 year old womanAsymptomaticWhat type of mitochondrial disease could they all have? 38 Beta Oxidation Defects Autosomal recessiveVery Long-Chain Acyl-CoA Dehydrongenase DeficiencyLong-Chain Acyl-CoA Dehydrongenase DeficiencyLong-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencyMultiple Acyl-CoA Dehydrogenase Deficiency/Glutaritic Aciduria Type IIMedium-Chain Acyl-CoA Dehydrongenase DeficiencyShort-Chain Acyl-CoA Dehydrogenase Deficiency.Short-chain-3-hydroxyacyl-CoA dehydrogenase (SCHAD) deficiencyCommon features include liver disease, heart disease, encephalopathyMay include pigmentary retinopathy, neuropathy, myoglobinuriaTreatment: High carbohydrate, low fat diet, administration of medium-chain triglyceride oil, and diet supplementation with carnitine and/or riboflavin. Avoidance of fasting.5 questions in 14 years 39 Cases 7, 8, and 9 3 month old girl Recurrent episodes of hypoglycemia, hypotonia, and profound acidosisMore likely shorter chain defect35 year old manElevated CK and recurrent rhabdomyolysis after vigorous exerciseMore likely longer chain defect60 year old womanAsymptomaticAny beta oxidation defect 40 Case 10 14 year old girl CC: Dystonia and cognitive regression HPI: Met normal milestones until about 18 months and began toe walkingInitially spoke in sentences, but regressed to single words onlySignificant cognitive impairment, but able to physically keep up with peers until last year when she began to have dystonic posturing of extremitiesNow is having agitation, outbursts, crying and screaming episodesDystonia also now involves face, jaw, neck, trunk, and tonguePMH:Cognitive impairmentEpilepsyExam:MS – impaired language, follows only simple 1-word commandsCNs – abnormal dystonic posturing of head with neck rotationStrength full but tone increased, reflexes brisk but equal, no obvious sensory changes, cannot do complicated coordination test, gait is stiff-appearing 41 Case 10 Workup: MRI – no significant abnormalities Muscle biopsy – no ragged red fibersCK – not elevated, if anything ~ lowNerve conduction/EMG – no neuropathic or myopathic changesSkin biopsy - normalCopper level, ceruloplasmin – normal rangeUrine organic acids, plasma amino acids normalVLCFA (Beta oxidation diseases) normalNiemann-Pick A and B, Fragile X, Rett – negativeDiagnosis? 42 Creatine Deficiency Syndromes Autosomal recessiveGuanidinoaceteate Methyltransferase Deficiency (GAMT Deficiency)L-Arginine:Glycine Amidinotransferase Deficiency (AGAT Deficiency)X-linkedSLC6A8-Related Creatine Transporter Deficiency (SLC6A8 Deficiency)All have mental retardation, seizures, speech delay.GAMT - behavioral disorder - including autistic behaviors; movement disordersSLC6A8Growth retardationMales: mild to severe mental retardationFemales: learning and behavior problemsIn a review of 27 patients with GAMT deficiency, oral creatine supplementation improved behavior abnormalities in all patients, epilepsy in most patients and movement disorder in half of patients. Intellectual ability and speech did not respond. Treatment response appeared more favorable in younger patients.1 question in 14 years* Mercimek-Mahmutoglu S, Stoeckler-Ipsiroglu S, Adami A, et al. GAMT deficiency: features, treatment, and outcome in an inborn error of creatine synthesis. Neurology Aug 8;67(3):480-4. 43 AnswerMitochondrial depletion, caused by this drug, can result in myalgias, weakness, and elevated CK in patients with HIV 44 QuestionWhat is AZT?AZT – a thymidine analog that inhibits reverse transcriptase and mtDNA polymerase (POLG) causing mitochondrial depletion, weakness, myalgias, elevated CK, ragged red fibers\4 questions in 14 years 45 AnswerThis anti-epileptic should not be used in patients with mitochondrial depletion syndromes because of the risk of hepatotoxicity 46 Question What is valproic acid? Because of the risk of liver damage, valproic acid is contraindicated in patients with mitochondrial disease, as they are particularly susceptible 48 CPT DeficiencyTransport of LCFA from cytosol into the mitochondrial matrix via β-oxidation Autosomal recessiveCPT IHepatomegaly, mostly occurring in infantsReye’s syndrome “attacks” with fasting or illnessTreatment can include maintaining high glucose intake and medium-chain triglyceride supplementationCPT II“Benign” adult form (more than 200 families reported) is characterized by episodes of rhabdomyolysis triggered by prolonged exercise.Infantile-type CPT2 presents as severe attacks of hypoketotic hypoglycemia, occasionally associated with cardiac damage commonly responsible for sudden death before 1 year of age. In addition to these symptoms, features of brain and kidney dysorganogenesis are frequently seen in the neonatal-onset CPT2 deficiency, almost always lethal during the first month of life. Treatment involves avoidance of fasting and/or exercise, a low fat diet enriched with medium chain triglycerides and carnitine.3 questions in 14 years contained carnitine deficiency, but none were the correct answer 49 Carnitine/Acylcarnitine Translocase Deficiency Deficiency of this transport protein results in impaired long-chain fatty acid oxidation and causes the accumulation of long-chain acylcarnitines outside the mitochondria and in plasma.Begins soon after birthSeizuresArrhythmiasHypoketotic hypoglycemiaHyperammoniemiaHepatomegalyCardiomyopathyMany infants with CACT deficiency do not survive the newborn period. Some affected individuals have a less severe form of the condition and do not develop signs and symptoms until early childhood. These individuals are at risk for liver failure, nervous system damage, coma, and sudden death. 50 Co-Enzyme Q10 Deficiency Just like all other mitochondrial diseaseAtaxiaEncephalopathyMyopathyEndocrine abnormalitiesCauses in myopathy in patients started on a statin.3 question in 14 years 51 Mitochondrial Diseases SummaryEncephalopathyMyopathyNeuropathyCardiomyopathyRetinopathyExercise intoleranceShort statureHearing lossElevated lactateRagged red fibersInheritanceMaternal, recessive, orsporadicTreatment:Creatine, Co-Q10, ketogenic diet (other than beta oxidation defects with high carb diet), carnitine, avoidance of fasting, supportive	2	43	0	0	4	0.750926	4	4,660
International Classification of Diseases Revision Steering Group Topic Advisory Group World Health Assembly World Health Organization Anaphylaxis as a rare disease: definitions, epidemiology and unmet needs Since the term “anaphylaxis” was first coined by Charles Richet and Paul Portier [ 1], it has rapidly spread all over the world and its clinical importance as an emergency condition is now well accepted. Anaphylaxis is nowadays recognized as a severe, life-threatening systemic hypersensitivity reaction characterized by rapid onset and the potential to endanger life through airway, breathing, or circulatory problems. It is usually, although not always, associated with skin and mucosal changes [ 2– 4]. This multi-faceted condition can manifest at any age and any health professional may be faced by it. In recent years there has been an increasing number of publications aimed at heightening awareness of this issue (Fig. 1). Regional epidemiological data cite anaphylaxis incidence rates ranging from 1.5 to 7.9 per 100 000 person-years in European countries [ 4] and estimated in at 5.1% (95% CI, 3.4 to 6.8%) in the United States [ 5]. Based on these statistics, anaphylaxis would fit well the definition of a rare disease, although it is not currently listed in rare diseases registries [ 6]. The epidemiological criteria for designating a condition a “rare disease” vary depending on the reference in consideration but, conceptually, rare diseases can be defined as life-threatening or chronic debilitating disorders which are of low prevalence and typically require combined efforts to address them. The global epidemiological morbidity [ 7] and mortality [ 8] data for anaphylaxis remain unclear due to the lack of standardized tools for capturing harmonized and accurate data, particularly in the International Classification of Diseases, Injuries and Cause of Death (ICD). This fact has a direct impact on the awareness it receives for healthcare planning and resource allocation, quality patient management and public health policy. Anaphylaxis in the International Classification of Diseases The ICD is a global standard diagnostic classification for mortality and morbidity statistics maintained by the World Health organization (WHO). Currently the majority of countries use the tenth revision of ICD (ICD-10) or adaptations thereof [ 9]. ICD-10 has inherited a structure from previous versions of ICD in which topographic distribution frequently takes precedence over underlying mechanisms, triggers or any of the concepts currently used for allergic and hypersensitivity conditions. As a result, only two terms in ICD-10 for anaphylaxis are hidden within section T78 of Other and unspecified effects of external causes under the unsatisfactory title Adverse effects, not elsewhere classified [ 10]. The inadequacy of this classification is a major reason for the under-notification of anaphylaxis in vital statistics [ 8]. In development since 2007, ICD-11 is intended not only to rectify deficiencies in ICD-10 and to incorporate changes demanded by scientific advances, but also to take advantage of the revolution in electronic data handling since the publication of ICD-10 a quarter of a century ago. ICD-11 may be regarded as a suite of classifications which is based on a detailed and comprehensive polyhierarchical web-like Foundation (Fig. 2) in which any single disease entity may be represented in more than one location. From this Foundation may be extracted any number of traditional tabular lists, which differ from the Foundation in that a single entity may appear in only one location (as in ICD-10 and, as in the latter’s proposed replacement, the ICD-11 for Mortality and Morbidity Statistics (ICD-11 MMS)). This will also permit the construction of a range of specialist classifications in which the detail contained in the Foundation is retained but which can link to ICD-11 MMS. In order to create a more appropriate classification for allergic and hypersensitivity conditions in ICD-11, a detailed action plan was coordinated in 2012 based on scientific evidence for the necessity of change; each step has been documented by peer-reviewed publications [ 7, 8, 11– 19]. The continuing close collaboration between our group and WHO has the backing of the Joint Allergy Academies, composed by representatives of American Academy of Allergy Asthma and Immunology (AAAAI), European Academy of Allergy and Clinical Immunology (EAACI), World Allergy Organization (WAO), American College of Allergy Asthma and Immunology (ACAAI), Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI), Latin American Society of Allergy, Asthma and Immunology (SLAAI). The main outcome of this process has been the construction of the Allergic and hypersensitivity conditions section within the new chapter, Disorders the Immune System, which has been incorporated into ICD-11 [ 16, 20] (Fig. 3). The “Anaphylaxis” sub-section is one of 8 main headings in this new section. To further inform the allergy community and to ensure that the revision process is transparent as advised in the ICD-11 revision agenda, we report the building process we used for the pioneering “Anaphylaxis” subsection of ICD-11. Building the “Anaphylaxis” subsection of ICD-11 The design of the anaphylaxis subsection was based on the Allergic and hypersensitivity diseases proposal, which had been validated by crowd-sourcing and simplified according to ICD Revision Steering Group (RSG) guidance. The construction of the new Allergic and hypersensitivity conditions section of the ICD-11 resulted by intensive scientific, academic and technical discussions to ensure comparability and consistency. The development of the “Anaphylaxis” sub-section involved strong academic input and extensive consultation and agreement from the relevant Topic Advisory Groups (TAGs) and Expert Working Groups (EWGs) (Fig. 4). The intensive exchange of e-mails and teleconference/videoconferences started in February 2014 and was the basis for the submission of proposals into the online ICD-11 beta draft platform. All the actions of the Allergy Working Group have so far been undertaken with RSG guidance. The innovatory electronic authoring and browsing platforms developed for the ICD Revision Project enabled ICD-11 to be assembled and refined in a sophisticated manner including metadata such as definitions, synonyms and causal mechanisms for each concept and support for a complex polyhierarchical structure. One of the most relevant innovations enables proposals for additions or changes to be made online [ 20]. The system allows for 4 types of proposal: enhancement of content attached to entity (adding or revising metadata), addition of new entity as child of existing entity, deletion of entity and, for more radical proposals, complex hierarchical changes (Fig. 5). Each submitted proposal has to be supported with a rationale and peer-reviewed references, and requires addition of metadata to a standardized template, the “content model”, which includes: title, definition, synonyms, narrower term, exclusions, body system, body site, signs and symptoms, causal agents and causal mechanisms [ 20]. The ICD-11 beta draft platform [ 20] can be considered a WHO web-observatory in which the representatives of RSG and TAGs can monitor the proposal submissions and comments. Based on these, the RSG members can approve, partially approve or reject a proposal. Each proposal is then scrutinized by WHO and, if accepted, can then be implemented and incorporated into the current version of ICD-11, following which the change will be visible in the Browser. A proposal may be rejected in part or in full with the reasons for the decision provided by commentaries to the proposal. Alternatively further clarification may be sought from the proposer. In order to document the construction process fully, we analyzed all of the above actions in order to describe the historic and current status of the Anaphylaxis sub-section and analyze the reasons for the principal changes. For this evaluation we considered actions related exclusively to this sub-section and proposals related to the patient’s background (e.g. personal history of anaphylaxis). Some proposals related to the topic were submitted during the revision process in order to adjust the higher ICD-11 hierarchy in general (e.g. removal of all anaphylaxis and allergic or hypersensitivity conditions from the parent Adverse effects, not elsewhere classified after the construction of the new section). We did not include proposals not directly related to the patient, such as Family history of anaphylaxis. The “Anaphylaxis” sub-section of ICD-11 Most of the proposals for the construction of the Anaphylaxis sub-section were submitted to the online ICD-11 Beta draft platform in the period from February to March 2015, but the hierarchical structure was adjusted later following additional comments and proposals. During this process, we submitted a total of 35 proposals, of which 25 (71.5%) were content enhancement proposals or complex hierarchical changes. Of the 35 proposals, 27 (77%) were implemented, 7 (20%) remain to be implemented (Fig. 6). The only rejected one was related to the proposal of adding a new entity ( Anaphylaxis classified by clinical severity). Justifications were provided. As a result of all the previous actions, the new “Anaphylaxis” sub-section was constructed, with 11 entities classified under 7 main headings: Anaphylaxis due to allergic reaction to food, Drug-induced anaphylaxis, Anaphylaxis due to insect venom, Anaphylaxis provoked by physical factors, Anaphylaxis due to inhaled allergens, Anaphylaxis due to contact with allergens and Anaphylaxis secondary to mast cell disorders. Allergic and hypersensitivity disorders are managed not only by allergists but also by specialists from a range of different disciplines. As a consequence, intensive scientific and technical discussions with TAGs and EWGs were essential for achieving consensus for the new classification, which will for the first time enable anaphylaxis to be properly represented within ICD. Since anaphylaxis has never been addressed by a single section in the ICD, it was to be expected that most of the proposals were for content enhancement and complex hierarchical change. These kinds of proposals, in general, support the building processes of new structures. The only partially implemented proposal appeared as such because the incorrect proposal type (deletion of entity) was inadvertently selected for removal of the link to a second parent, which is a hierarchical change. As explained above, the polyhierarchical structure of the ICD-11 Foundation enables any given entity to be linked to more than one parent (Fig. 2). The only rejected proposal concerned the addition of “Anaphylaxis classified by clinical severity” as a new entity. The reason for the rejection was that ICD-11 enables diagnoses to be linked to a range of parameters by the addition of one or more “extensions” in a process termed post-coordination. WHO has been promoting this classification strategy in which a stem entity (e.g. Anaphylaxis) can be more fully defined by linking it to a range of different value sets including severity, anatomical location and causal agent [ 20]. All the proposals that have yet to be implemented are related to “personal history of” or to instances where the use of post-coordination would enable the intended meaning to be captured, such as severity grade or allergens and triggers. Some limitations of the current study may have to be considered. Since the online ICD-11 beta draft is not final and is updated regularly, the current results may not be reproduced if reanalyzed in the future with the same methodology. Although this manuscript presents some technical aspects of classification and new ICD-11 concepts, its aim is also to serve as an introduction to ICD-11 for ICD end-users in the allergy community using anaphylaxis as an example. The construction of the new section dealing with anaphylaxis means that the latter will now be recognized as a clinical condition requiring specific documentation and management. By allowing all the relevant diagnostic terms for anaphylaxis to be included in the ICD-11 MMS, WHO has recognized their importance not only to clinicians but also to epidemiologists, statisticians, health care planners and other stakeholders. Importantly the new classification will enable the collection of more accurate epidemiological data to support quality management of patients with allergies, better health care planning and decision-making and public health measures to reduce the morbidity and mortality attributable to allergy. Examples are the availability of adrenaline auto-injectors in all countries for patients at risk, the provision of resuscitation kits in public places and the implementation of prevention campaigns in surgical and radiology departments. The Orphanet, lead by the French National Institution of Health and Medical Research (INSERM) and the French Ministry of Health, is responsible for developing an inventory of rare diseases and a classification system which could serve as a template to update International terminologies. When the WHO launched the revision process of the ICD, a rare diseases TAG was established. So far 5,400 rare diseases listed in the Orphanet database have an endorsed representation in the foundation layer of ICD-11 [ 21], but anaphylaxis is not yet into the list. For the first time, anaphylaxis is now properly classified and has attained greater visibility within ICD. Additionally to all the benefits expected by the actions to update terminology, definitions and classification of allergic and hypersensitivity conditions through the ICD-11 revision, we strongly believe that anaphylaxis is a public health priority and that in order to support awareness and quality clinical management of patients it should therefore be formally added to the list of rare diseases. We are extremely grateful to all the representatives of the ICD-11 Revision Project with whom we have been carrying on fruitful discussions, helping us to refine the classification presented here: Robert Jakob, Linda Best, Nenad Kostanjsek, Robert J G Chalmers, Jeffrey Linzer, Linda Edwards, Ségolène Ayme, Bertrand Bellet, Rodney Franklin, Matthew Helbert, August Colenbrander, Satoshi Kashii, Paulo E. C. Dantas, Christine Graham, Ashley Behrens, Julie Rust, Megan Cumerlato, Tsutomu Suzuki, Mitsuko Kondo, Hajime Takizawa, Nobuoki Kohno, Soichiro Miura, Nan Tajima and Toshio Ogawa. Joint Allergy Academies: American Academy of Allergy Asthma and Immunology (AAAAI), European Academy of Allergy and Clinical Immunology (EAACI), World Allergy Organization (WAO), American College of Allergy Asthma and Immunology (ACAAI), Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI), Latin American Society of Allergy, Asthma and Immunology (SLAAI). Availability of data and materials Data sharing not applicable to this article as no datasets were generated or analyzed during the current study. The ICD-11 beta draft platform is open to the public. LKT and PD contributed to the construction of the document (designed the study, analyzed and interpreted the data, and wrote the manuscript). RJGC, SA and MAC contributed to tuning the document and revision of the manuscript. All authors read and approved the final manuscript. The authors declare that they do not have any conflict of interests related to the contents of this article. Consent for publication Pascal Demoly and Luciana Kase Tanno received an unrestricted AstraZeneca ERS-16-11927 grant through CHRUM administration. Ethics approval and consent to participate Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.	2	10	1	0	2	0.644845	3	3,460
Cracking the ICD-10 Codebook for Audiologists Tamala S. Bradham The International Classification of Diseases (ICD) is the standard diagnostic tool used for clinical purposes, epidemiological research, and global health management (World Health Organization [WHO], 2014a). ICD allows administrators, researchers, and health care professionals to monitor and track mortality and morbidity, incidence and prevalence of diseases, and other health data, as well as reimbursement for services rendered. Since 1979, the United States has been using the ninth version (ICD-9-CM [Clinical Modification]), although there have been multiple attempts to implement ICD-10-CM in the United States. The current ICD-10 compliance deadline is October 1, 2015. The new ICD-10 will include the ICD-10-CM and ICD-10-PCS (procedure coding system). The ICD-10 is owned by WHO. The clinical modification was developed by the Centers for Disease Control and Prevention (CDC) for use in the U.S. health care industry. The procedure coding system (i.e., ICD-9-PCS and ICD-10-PCS) was developed by the Centers for Medicare & Medicaid Services (CMS) for use in the United States for inpatient hospital settings only. Also of importance, in May 1990, ICD-10 codes were endorsed by the Forty-third World Health Assembly and have been adopted by most developed countries. The 11th version, ICD-11, is now being prepared and will be finalized in 2017. ICD-10 offers the U.S. health care system several benefits. In ICD-9, there is a lack of clinical accuracy, a limited number of available codes, and a restrictive coding structure (CMS, 2014). Furthermore, the United States is not able to compare mortality and morbidity data globally, as most developed countries already employ ICD-10 (American Academy of Professional Coders [AAPC], 2014a; Bowman, 2014). Transitioning will result in moving from 14,025 to 69,823 diagnosis codes and from 3,824 to 71,924 procedure codes (CDC, ASHA has developed a number of resources to help audiologists transition to ICD-10, including an ICD-9 to ICD-10 online mapping tool that allows one to enter an ICD-9 code, which is then mapped to the appropriate ICD-10 code(s). ASHA also has mapping spreadsheets for audiology codes and a list of ICD-10 audiology codes. To more about ICD-10 for audiology, please visit ASHA's website. ICD-10 and Documentation In surveys of health care leaders on major IT challenges in health care organizations over the next 3 years, ICD-10 implementation is listed as the number one concern and documentation is listed second (Letourneau, 2013). Nachimson Advisors (2011) estimated increased documentation costs associated with an ICD‐10 implementation ranging "from $44,000 for a small practice to $1.76 million for a large practice" (p. 5). For ICD-10 coding, thorough, timely, and succinct documentation of a patient's visit will be necessary to minimize claim denials (Carr, 2013; Hertz, 2013; Husty & Newell, 2013; Leenheer, 2012; Levy, 2013). It will be essential for audiologists to document using very specific diagnostic and treatment terminology. Some states or payers may require greater specificity, laterality, stages of healing, cause and location of the injury, treatments tried, and acute or chronic disease state, to name a few examples in clinical documentation (AAPC, 2014b; see Appendix A for an example). reported that health care providers are not currently documenting information that will be necessary for appropriate ICD-10 coding, which will ultimately affect reimbursement under the new codes. With the current ICD-9 system, the most common reasons for improper payments during a recovery audit (by recovery audit contractors [RAC]) were (1) services did not meet medical necessity criteria, (2) services were incorrectly coded, and (3) supporting documentation that was submitted did not support the ordered service (CMS, 2012). It is plausible that, with ICD-10 coding, RAC may see a rise in incorrect coding and insufficient documentation. A field study by the American Health Information Management Association (AHIMA; 2003) found that, although ICD-10-CM codes could be applied to medical records without any changes to documentation practices, coding specificity would be improved if documentation was better. Does This Mean for Audiology Practices? To help audiologists be successful with the transition from ICD-9 to ICD-10, ASHA (2014a) developed an ICD-10-CM Preparation Checklist. Checklist items include (1) training, (2) better documentation, and (3) monitoring and communicating. Clinical and administrative staff will require significant time learning new codes and work flows. The learning curve is expected to be steep for both clinicians and administrative staff (AAPC, 2014b). AAPC reported that inadequate training could result in "reduced productivity levels for as long as 6 months due to increased re-work for denied claims, adjustments, and pended claims, and coders directing an increasing amount of queries to physicians when documentation is not adequate to support the higher level of specificity required with ICD-10" (AAPC, 2014b, p. 9). Having a thorough understanding of the ICD-10 codes will be essential, especially because many practices do not have coders to determine which codes would maximize reimbursement and meet compliance standards. It is also important to know that ICD-10 codes for hearing loss are very different than ICD-9 hearing loss codes. For example, for a sensory hearing loss, ICD-9 codes used would have been 389.11 for bilateral sensory hearing loss or 389.17 for unilateral sensory hearing loss. For ICD-10, the clinician will use H90.3 Sensorineural hearing loss, bilateral or H90.41 Sensorineural hearing loss, unilateral, right ear, with unrestricted hearing on the contralateral side if the patient has hearing loss in the right ear and normal hearing in the left ear or H90.42 Sensorineural hearing loss, unilateral, left ear, with unrestricted hearing on the contralateral side if the hearing loss is in the left ear and there is normal hearing in the right ear. If the patient has a different type of hearing loss in each ear, then the clinician will use H90.5 Unspecified sensorineural hearing loss and H90.8 Mixed conductive and sensorineural hearing loss, unspecified if the patient has a sensorineural hearing loss in the right ear and a mixed hearing loss in the left ear. There is a proposal before the National Center for Health Statistics to add new codes for when an audiologist uses "restricted hearing on the contralateral side"; however, there will be no revisions until 2016 at the earliest. Based on case history and presenting complaints, audiologists need to determine what test(s) will address the reason(s) for the patient's visit or what activities will address the treatment goals/plan. The procedures or interventions performed and billed should be based on the patient's presenting complaints and should be medically necessary. The diagnosis should support the patient's complaint(s) and the procedure(s) performed. In the event the test results are normal, the diagnosis code should report the signs and symptoms of the patient's Documentation should include the following components: - date and time of when the evaluation and treatment were - history/background and presenting complaints, - procedures and activities to be performed to address the - assessment/interpretation of the evaluation and - recommendations/plan of care to address the findings, - signature of the provider. When coding for diagnosis, audiologists should use as many ICD-10 codes as necessary to substantiate medical necessity for the visit. If the payer requires Z codes, here are some case examples for how these can be used when test results are normal: Example 1: Child comes in for a hearing test prior to a speech-language evaluation. The parent does not have any concerns about hearing but does not know why the child is not talking. The audiology test results are normal. Use F80.1 Expressive language disorder. Example 2: Toddler passed newborn hearing screening but has a risk factor. Toddler comes in at 12 months for audiology follow-up Scenario 1. Test results are normal. History reveals a family history of congenital hearing loss. Use Z01.10 Encounter for examination of ears and hearing without abnormal findings AND Z82.2 Family history of deafness and hearing loss. Scenario 2. Test results are inconclusive. History reveals that the toddler underwent ECMO. (OAEs and tympanograms are normal; sound field at 2,000 Hz is at 20 dB HL.) Use Z01.10 Encounter for examination of ears and hearing without abnormal findings AND Z92.81 Personal history of extracorporeal membrane Scenario 3. Test results are inconclusive. History reveals prematurity and low birth weight. (Note: Documentation would need to specify weight and gestational age. OAEs are normal; tympanograms are flat; sound field at 2000 Hz is at 30 dB HL.) Use Z01.110 Encounter for hearing examination following failed hearing screening OR Z01.118 Encounter for examination of ears and hearing with other abnormal findings AND P07.36 Preterm newborn, gestational age 33 completed weeks AND P07.17 Other low birth weight newborn, 1750-1999 For assistance with mapping ICD-9 codes to ICD-10 codes or vice versa, please refer to ASHA's Mapping Tools (2014b) as well as ICD-10-CM Diagnosis Codes Related to Hearing and Vestibular Disorders for assistance with learning the code (2014c). With extensive training and thorough documentation, audiologists should be well-positioned to remain viable during the transition from ICD-9 to ICD-10. To date, there have been no studies that have specifically evaluated the denial rates and timeliness of reimbursement for services in audiology practices with ICD-10 implementation. Audiology practices will more than likely experience an increase in denial rates and prolonged duration before receiving reimbursement as the health care industry works through the transition. Thus, to manage ICD-10 implementation and cash flow, it will be necessary to have oversight of the denials using a monthly scorecard system that tracks completed tasks associated with ICD-10 and number of denials (HFMA, 2013). Health care systems also will need to develop a process for managing errors and resolving vendor issues (CMS, 2014). With ICD-10 implementation, sharing success stories, highlighting people who have been "champions" in the process, and being transparent with staff and patients on how the health care system is handling ICD-10 will be pivotal to engaging people in the process and minimizing financial impacts to the system. Audiologists cannot overcommunicate about this system change. At some point, the United States will transition to a new ICD system. It is essential for audiologists to learn as much as they can about ICD-10 codes, review their current documentation systems and determine how to prepare for potential changes, and have a dashboard/monitoring system to keep track of the claims and denials for proactively managing this transition. ASHA offers, in addition to previously mentioned resources, a checklist to determine ICD-10 readiness. To minimize delayed payments and to maximize reimbursement with ICD-10, Leenheer (2012) recommended that clinicians (1) complete an assessment of existing documentation and develop an action plan from the findings, (2) implement an easy-to-use electronic documentation system, and (3) obtain education and ongoing trainings. Documentation of the patient's visit is "key to a successful transition to ICD-10" (Leenheer, 2012, p. 112). There are several tools and training materials available to help with this transition (ASHA, 2014a, b, c). The benefits of ICD-10 include (1) improved quality of care; (2) potential cost savings from increased accuracy of payments and reduction of unpaid claims (i.e., fewer rejected claims); (3) improved tracking of public health data; and (4) upgrades to improve IT data integrity, fraud detection, and cost analysis capabilities. While this change to ICD-10 does come at a price, many of the projected financial challenges can be mitigated with proper planning, training, and IT management. The potential benefits over the long term cannot be overlooked. Much appreciation is extended to the following people who have taught me a great deal about ICD-10 codes: Mary Sue Fino-Szumski, Ronald Kintz, Cathy Lackey, Tammy Reno, Shawn Scarbrough, and Lori Sells. Tamala S. Bradham, PhD, CCC-A, is a quality consultant in the Center for Quality, Safety, and Risk Prevention at Vanderbilt University Medical Center, where she is at the forefront of health care reform, evidence-based practices, and population health and practice management. Her research interests include auditory, speech, and language outcomes in children with hearing loss; cochlear implants; discharge practices; and family-centered practices in health care. Formerly, she was on the faculty at the Vanderbilt Bill Wilkerson Center, where she was the associate director of services at the National Center for Childhood Deafness and Family Communication. In this role, she developed and managed services for children with hearing loss, which included serving on the pediatric cochlear implant team, providing audiologic (re)habilitation and speech-language services, and teaching at the Mama Lere Hearing School. She is the former coordinator for ASHA Special Interest Group 9, Hearing and Hearing Disorders in Childhood. Contact her at [email protected]. American Academy of Professional Coders. (2014a). ICD-10 FAQ . Retrieved from www.aapc.com/icd-10/faq.aspx American Academy of Professional Coders. (2104b). ICD-10: The history, the impact, and the keys to success . Retrieved from www.aapc.com/icd-10/icd-10-white-paper.aspx American Health Information Management Association. (2003). ICD-10-CM field testing project report on findings . Retrieved from www.ahima.org/~/media/AHIMA/Files/HIM-Trends/FinalStudy_000.ashx American Speech-Language-Hearing Association. (2014a). ICD-10-CM preparation checklist . Retrieved from www.asha.org/Practice/reimbursement/coding/ICD10-Checklist/ American Speech-Language-Hearing Association. (2014b). ICD-9 to ICD-10 mapping tool . Retrieved from www.asha.org/icdmapping.aspx American Speech-Language-Hearing Association. (2014c). 2014 ICD-10-CM diagnosis codes related to hearing and vestibular disorders . Retrieved from www.asha.org/uploadedFiles/ICD-10-Codes-Audiology.pdf Bowman, S. (2014). Why ICD-10 is worth the trouble. Journal of AHIMA, 79 (3), 24–29. Carr, K. J. (June 2013). Closing the ICD-10 revenue gap. Healthcare Financial Management, 67 (6), Centers for Medicare & Medicaid Services. (2012). Recovery auditing in Medicare and Medicaid for fiscal year 2012 . Retrieved from www.cms.gov/Research-Statistics-Data-and-Systems/Monitoring-Programs/Medicare-FFS-Compliance-Programs/Recovery-Audit-Program/Downloads/Report-To-Congress-Recovery-Auditing-in-Medicare-and-Medicaid-for-Fiscal-Year-2012_013114.pdf Centers for Disease Control and Prevention ICD-10 Transition Workgroup. (2013). The ICD-10 transition and public health surveillance—What you need to know . Retrieved from www.cdc.gov/nchs/icd/data/CDC_ICD-10_Transition_FactSheet_12_2013.pdf Centers for Medicare & Medicaid Services. (2014). Introduction to ICD-10: A guide for provider's services . Retrieved Healthcare Financial Management Association. (2013). Readying your denials management strategy for ICD-10. Healthcare Financial Management, 67 (2), 2–8. Hertz, B. T. (2013). Countdown to ICD-10: Why lack of preparation could ultimately jeopardize your practice's income. Medical Economics, 90 (21), 18–28. Husty, T. M., & Newell, L. M. (2013). ICD-10: Cracking the code. Healthcare Financial Management, 67 (7), 32–35. Leenheer, C. (2012, September). The clinical documentation advantage protecting the revenue cycle under ICD-10. Healthcare Financial Management, 66 (9), 104–112. R. (2013). ICD-10: Minimizing the financial hit. HealthLeaders, 16 Levy, B. (2013, March). ICD-10: 5 steps to a comprehensive financial impact analysis. Healthcare Financial Management, 67 (3), Nachimson Advisors, LLC. (2008, October). The impact of implementing ICD‐10 on physician practices and clinical laboratories: A report to the ICD-10 coalition . Retrieved from www.nachimsonadvisors.com/Documents/ICD-10%20Impacts%20on%20Providers.pdf Sanders, T. B., Bowens, F. M., Pierce, W., Stasher-Booker, B., Thompson, E. Q., & Jones, W. A. (2012). The road to ICD-10-CM/PCS implementation: Forecasting the transition for providers, payers, and other healthcare organizations. Perspectives in Health Information World Health Organization. (2014a). International classification of diseases (ICD). Retrieved from www.who.int/classifications/icd/en/ World Health Organization. (2014b). Classifications: International Classification of Diseases (ICD) information sheet . Retrieved from www.who.int/classifications/icd/factsheet/en/ World Health Organization. (n.d.). History of the development of the ICD . Retrieved from http://www.who.int/classifications/icd/en/HistoryOfICD.pdf	4	16	0	0	9	0.406927	9	4,257
Diagnostic criteria for infective endocarditis. Modified from Durak et al., 1994. Since the initial use of prosthetic heart valves, the use of cardiac prosthesis and implantable devices has revolutionized the therapeutic options available to patients (de Oliveira et al.,2009). Cardiac Permanent PaceMakers (PPMs) have been implanted since the early 1960s. Over the past 50 years there have been tremendous advances in both the design of the device and the software employed. In the mid 1960s, transvenous leads were developed that could be inserted through a vein and thence into the heart, thus preventing the need for a thoracotomy. The development of ‘active fixation’ leads ensured a better contact with the endocardium and the presence of a steroid eluting tip helped to reduce any inflammation that might result. The introduction of the lithium iodine battery has dramatically increased the battery life to well over ten years. Radiofrequency programming became available in the 1970s, allowing simple adjustments to be made to pacemaker’s settings without the need for surgery. Today, permanent pacemakers and ICD (Implantable Cardiac Defibrillator), together with any adjustments, can be completed within minutes using a portable computer. Information regarding events such as periods of bradycardia, tachycardia or ventricular fibrillation can be stored within the memory of the device and accessed by the specialist during the routine checkup. To maintain atrio-ventricular synchrony, dual chamber pacing was then introduced. Moreover, in the late 1990s, pacemaker technology had improved to the extent that it became possible to increase the pacing rate to match the patient’s activity level (Allen et al., 2006). A wide range of cardiac implantable electronic devices (CIEDs) are now available, including ICDs and cardiac resynchronization systems. PPMs are commonly used in patients with atrioventricular conduction block, sick sinus syndrome, and symptomatic sinus bradycardia, whereas ICDs target primarily patients at risk for life-threatening ventricular arrhythmias. Since clinical trials have consistently demonstrated the ability of the ICD to reduce mortality in selected patients with moderate-to-severe left ventricular systolic dysfunction, the indications for CIEDs have expanded dramatically and the rate of implantation has greatly rosen. A recent analysis showed that rate of implantation in US between 1997 and 2004 rose by 19% and 60% for PPMs and ICDs, respectively. Approximately 70% of device recipients were 65 years of age or older, and more than 75% of them had one or more coexisting illnesses. The rate of ICD implantation has increased in the elderly (70 to 79 years of age) and very elderly (80 years of age or older). The 2001 World Survey found that in developed countries, between 20% and 35% of CIED recipients were more than 80 years old. The National Hospital Discharge Survey found a 49% increase in the number of new CIED implantations, including both PPMs and ICDs. In 2003, although the absolute number of PPMs implantations was higher than that of ICDs (180284 versus 57436 implanted devices) most of the increase in CIED device implantation was due to ICD implantations (160% and 31% increases in ICD and PPM implantations, respectively) (Baddour et al., 2010). Despite their unquestioned clinical importance and diffusion, CIEDs may be linked to several complications, including infections, and the consequences of them may be catastrophic. Therefore, development of strategies for the prevention of device associated infections is crucial (Borer et al., 2004). The reported rate of infection after implantation of permanent endocardial devices ranges between 0.13% and 12.6%, depending on definition. The wide use of CIEDs and increasing age of patients set the stage for higher role of associated infections and related hospitalizations increased of about 3-fold (Baddour et al., 2010). Moreover, the cost of treating device-associated infections may be enormous, thus leading to increased healthcare expenses (Borer et al., 2004). Precise data regarding the actual healthcare burden of CIED infections are not available. The financial impact is due to multiple factors, including the costs of device removal, cost of new device (which would be required in the majority of patients) and costs related to cardiac and other medical evaluations, diagnostic procedures, surgical interventions for infected device removal, medical therapy, and increased length of stay in intensive care unit (Baddour et al., 2010). 2. Epidemiology of CIED associated infections CIED infections have been recognized as a source of major comorbidity since the early 1970s. In earlier years, the rates of PPM infection ranged widely between 0.13% and 19.9%. Although most infections have been limited to the pocket, frank PPM endocarditis accounted for approximately 10% of PPM infections. The decreased size of ICDs allowed implantation without thoracotomy. Initially, abdominal implantation with tunneling was required. Subsequently, the entire device could be implanted prepectorally; with these less extensive operations the infection rate lowered to less than 7%. In a study on all ICD primary implantations, replacements, and revisions at a single center, there were 21 ICD-related infections (1.2%) among 1700 procedures. Among 959 patients with long-term follow-up, the infection rate was 3.2% with abdominal and 0.5% with pectoral systems respectively (Mela et al., 2001). However, globally, the rate of CIED infection has been increasing. Cabell et al. reported that the rate of cardiac device infections (PPMs, ICDs, valves, and ventricular assist devices) increased from 0.94 to 2.11 per 1000 patients between 1990 and 1999, a 124% increase during the study period. The rate of frank endocarditis was relatively unchanged (0.26 and 0.39 cases/1000 patients, respectively) (Cabell et al., 2004). These findings were similar to that analyzed in Olmsted County, Minnesota, from 1975 to 2004. A total of 1524 patients were included with a total person-time follow-up of 7578 years. The incidence of CIED infection was 1.9/1000 device years (95% confidence interval [CI] 1.1 to 3.1), with an incidence of pocket infection alone of 1.37/1000 device-years (95% CI 0.62 to 0.75) and an incidence of pocket infection with bloodstream infection or device-related endocarditis of 1.14/1000 device-years (95% CI 0.47 to 2.74) (Uslan et al., 2007). Notably, the cumulative probability of CIED infection was higher among patients with ICDs than among those with PPMs. The National Hospital Discharge Survey similarly showed that between 1996 and 2003, the number of hospitalizations for CIED infections increased 3.1-fold (2.8-fold for PPMs and 6.0-fold for ICDs). The numbers of CIED infection–related hospitalizations increased out of proportion to rates of new device implantation. Moreover, CIED infection increased the risk of in-hospital death by more than 2-fold (Voigt et al., 2010). 3. Definition and clinical presentation CIED pocket infection is defined on the ground of signs and symptoms of local infection associated with microbiological confirmation based on results of cultures of intraoperatively collected fluid samples, explanted CIED, or purulent discharge from the pocket site. CIED infection can present as acute or chronic syndromes that can be both early or tardive. In the early, acute form, the short time elapsed between device implantation and occurrence of infection may prompt the diagnosis. In chronic and tardive infections there is often a delay between the onset of symptoms and the diagnosis. This may be due to the fact that CIED-related infections are not routinely considered in the differential diagnosis. In other cases, possible clues to the diagnosis are ignored. Clinical manifestations of pacemaker infection are linked to the portion of the device involved. Moreover, signs and symptoms may be limited to the insertion pocket or be systemic or absent altogether (Cacoub et al,. 1998). A CIED-related infection is considered nosocomial when occurs 48 hours after admission and is not incubating at the time of admission. Infection of CIED is regarded as health care associated if patient received intravenous therapy at home, attended an outpatient hemodialysis center in the previous 30 days, was hospitalized in an acute care hospital for 2 days in the 90 days before admission, or resided in a nursing home or long-term care facility. In contrast, CIED-related infection is recognized as community acquired if it does not fit the above definitions (Tablan et al., 2003). 3.1. Clinical presentation In the vast majority of cases, local inflammation of the generator-pocket site is present, including erythema (34%), pain (32%), swelling (21%), warmth (11.5%), and drainage through a fistulous or poorly healed incision (25%). In most severe cases cutaneous erosion (23%) with percutaneous exposure of the generator and/or leads may be seen. All these signs can be associated or not with bacteremia (Cacoub et al,. 1998). These local changes usually prompt medical attention. Some patients present with systemic symptoms that include malaise, fatigue, anorexia, or decreased functional capacity. Sometimes isolated local symptoms occurr without fever. Chua et al. reported the presence of localized signs without systemic involvement in 69% (88 of 123) of patients, a combination of local and systemic signs and symptoms in 20% (25 of 123), and systemic signs and symptoms alone in 11% (13 of 123) of patients (Chua et al., 2000). In implanted patients with unexplained fever CIED associated endocarditis should be ruled out. In CIED recipient isolated bacteremia pro,t medical investigation to rolu out endocarditis. Pacemaker endocarditis should be considered in all patients with cardiac pacemakers and chronic fever, recurrent bronchitis, pulmonary infection, and recurrent or persistent pocket infection (Cacoub et al., 1998; Klug et al., 1997). In some patients, involvement of lungs may be evident, including pleural effusions, pneumonia, pulmonary abscess, recurrent pulmonary embolism. Recurrent bronchitis is evident in 32% to 43% of patients with pacemaker endocarditis. A serious complication of pacemaker infection is generator or lead erosion through the skin. This can be the consequence of primary infection or can be the result of pressure on the overlying tissue, resulting in erosion and subsequent contamination. Erosion has been noted to be more common after elective pacemaker replacement than initial implantation (Harcombe et al., 1998). Other rare conditions associated to CIED infections are thrombosis of a vein where leads were in place (subclavian vein or superior vena cava), symptomatic pulmonary embolism, septic arthritis, vertebral, sternal or femoral osteomyelitis, splenic, brain, liver and perinephric abscess (Sohail et al., 2007a). In patients with pacemaker infection bacterial pathogens can be found in blood or pacemaker pockets. Pacemaker’s hardware can be colonized as well. The most common pathogens in pocket infections are skin flora, and, specifically, Staphylococcus aureus and coagulase-negative staphylococci, including Staphylococcus epidermidis. Rarely, enteric Gram-negative bacilli can be found. Repeated cultures and percutaneous aspirates should help make the distinction between normal skin flora and pathogenic culture isolates (Gandelman at al., 2007). Staphylococcal species cause most of CIED infections and account for 60%-80% of cases in most reported series (Fig.1). A variety of coagulase-negative Staphylococcus (CoNS) species have been described a causative agents of CIED infections. CoNS are a common cause of microbiological specimen contamination, and thus, repeated isolation of the same species of CoNS with an identical antibiotic susceptibility pattern is advisable to be diagnostic. Polymicrobial infection sometimes involves more than one species of CoNS. The prevalence of oxacillin resistance among staphylococcal strains has varied among studies ranging from 4 to 22% (Sohail et al., 2007a; Viola et al., 2010). Several factors are responsible for the higher propensity of Staphylococci to cause CIED infections. Staphylococci are frequent colonizer of human skin and contamination of CIED generator, electrode leads or pocket tissue at the time of implantation is the predominant mechanism for the majority of the pocket infections. Staphylococci express on their membranes several adherence factors that enable them to bind the foreign materials and establish chronic infection. In addition, these organisms are capable of producing biofilm on the device surface which helps them to evade host defences and limit antimicrobial penetration. Finally, Staphylococci are the predominant pathogens responsible for secondary catheter-related bloodstream infections as they can seed the intravenous leads during an episode of bacteremia. Corynebacterium species, Propionibacterium acnes, Gram-negative bacilli, including Pseudomonas aeruginosa, and Candida species account for a minority of CIED infections. Fungi other than Candida and nontuberculosis mycobacteria are rarely responsible for CIED infection (Sohail et al., 2010). The microorganisms that cause CIED infections may be acquired either endogenously from the skin of patients or exogenously from the hospital environment. An association has been found between the presence of preaxillary skin flora and the pathogens isolated from pacemaker infection. Although low concentrations of methicillin-resistant CoNS have been detected in patients with no previous healthcare contact and no recent antibiotic exposure, a CIED infection due to multidrug-resistant staphylococci suggests that a healthcare environment is the site where infection was acquired (Da Costa et al., 1998a). Pacemaker endocarditis usually presents with bacterial growth in both blood and hardware cultures. Although there is no uniform agreement regarding the rate of positive blood cultures in pacemaker endocarditis, S. epidermidis and S. aureus occur most frequently. Other pathogens include Corynebacterium sp., Pseudomonas aeruginosa, and Aspergillus niger. In one study, polymicrobial infections were found in 18.1% (Cacoub et al., 1998). The generator is placed within a surgically created space known as pocket. Electrode leads are attached to the generator and travel within the venous system to the right heart. Pacemaker infection can be limited to the superficial portion of the pocket and leads or involve deeper intravascular and intracardiac components. The latter is known as pacemaker endocarditis. Among patients with pacemaker endocarditis, vegetations can occur on the tricuspid valve, the electrodes, and the right atrial or ventricular endocardium. The pocket may become infected at the time of implantation, during subsequent surgical manipulation, or if the generator or subcutaneous electrodes erode the overlying skin. In this latter case, erosion can also occur as a secondary event due to underlying infection. Pacemaker endocarditis can be linked to several factors, including pacemaker lead contamination during placement, spread of the organisms along the wires from the superficial component, or hematogenous seeding of the intravascular electrodes and wires during a bacteriemic episode. While Gram-posivie bacteriamias can cause CIED infections, hematogenous seeding of a CIED is unlikely to occur in cases of Gram-negative bacteremia. The disruption of the physiologic blood flow through the tricuspid valve often caused by a pacing lead passing through the valve and associated regurgitation may contribute to pacemaker infection. Microbial adherence to endothelium has been shown to increase in areas of high shear turbulence (Baddour et al., 2010). CIED infection is the result of the interaction between the device, the microbe, and the host. 4.2.1. Devices factors Initial adhesion of bacteria to the device is mediated by physico-chemical properties of the plastic surface, such as hydrophobicity, surface tension, and electrostatic charge. Factors like the nature of plastic polymer, irregularity of its surface, and its shape, can all affect bacterial adherence to the device. Plastic polymers that encase medical devices, as well as the pathogens that adhere to them, are hydrophobic. An irregularly surfaced device favours microbial adherence more than a smoothed surfaced one. When this physiochemical interaction exists, the risk of CEID infection is related to subsequent invasive manipulation of the device and may be linked to a limited experience of the physician performing the procedure (Darouiche, 2001). 4.2.2. Microbial factors Bacteria, particularly Gram-positive cocci, can adhere to and be engulfed by endothelial cells that lie on endothelialized lead after a certain period of time. This is thought to be an important mechanism of device infection by the hematogenous route. Microbial adherence may be linked also to interactions of bacterial surface with proteins on device’s surface. CoNS may adhere directly to plastic polymers of the surface of the device via fimbria-like surface protein structures or via a capsular polysaccharide (Veenstra et al., 1996). Bacteria may also adhere to host matrix proteins that coat the surface of an implanted device. Host extracellular matrix proteins include fibrinogen, fibronectin, and collagen that are layered on implanted biomaterials. None of the major virulence factors or toxins of S Aureus have been found in CoNS, and it seems clear that the development and persistence of CoNS infections, which are so often associated with foreign materials, are due to different mechanisms, such as microbiological adherence. On the contrary, Staphylococci have a variety of surface adhesins that allow the pathogen to establish a focus of infection. Subsequent accumulation of bacteria on the device’s surface requires the production of polysaccharide intercellular adhesin, which is strongly linked to with the staphylococcal cell surface and mediates cell-to-cell adhesion. The layers of bacteria on the surface of an implanted device are encased in this extracellular slime and constitute a biofilm. Biofilm is defined as a surface-associated community of one or more microbial species that are firmly attached to each other and the solid surface and are encased in an extracellular polymeric matrix that holds the biofilm together. Bacteria in a biofilm are more resistant to antibiotics and host defences, perhaps as a result of the dense extracellular matrix that protects the microbes included in the interior of the community (Lazăr & Chifiriuc, 2010). When a free-floating bacterial cell enters the biofilm, it undergoes a phenotypic shift, in which expression of large groups of genes is up-regulated. Phenotypic variation is thought to support the persistence of infection due to staphylococci in a biofilm that coats the surface of a CIED. Small colony variants are phenotypes that have caused CIED infections and harbor several characteristics that are thought to enhance the survival of staphylococci either in a biofilm or in endothelial cells covering the device, including resistance to certain antibiotics (Baddour et al., 1990; Boelens et al., 2000). 4.3. Risk factors Several studies have identified host or procedural factors that may be associated with CIED infections. Among the host factors, the strongest association is between renal failure and risk of CIED infection. Risk of device infection appears to be particularly high in patient with end-stage renal failure who are undergoing chronic hemodialysis via an implanted central catheter. These patients are at risk of recurrent bacteremia from their dialysis catheter and subsequent secondary seeding of the tranvenous device leads or pulse generator. Renal failure is also associated with immune dysfunction that further increases the odd of CIED infections in these patients (Bloom et al.,2006). Anticoagulant therapy with warfarin has also been linked to a higher risk of CIED infection. Precise reasons for this association are unclear but are likely related to the increased risk of pocket hematoma, which may lead to delayed wound healing or need for surgical drainage in some cases. Reopening the pocket to drain a large hematoma increases the risk of pocket contamination with skin flora and subsequent CIED infection (Lekkerkerker et al., 2009). Use of immunosuppressive medications, especially long term corticosteroids therapy, has also been identified as a risk factor for CIED infections (Sohail et al., 2007b). Procedure-related factors may also play an important role in the development of CIED infections. In a prospective cohort of 6319 patients receiving CIED implantation in 44 medical centers, Klug et al. identified 42 patients who developed CIED infection during 1 year of follow-up. Factors associated with an increased risk of infection included fever within 24 hours before implantation, use of preprocedural temporary pacing, and early reintervention. Implantation of a new system compared with partial or complete system replacement and use of periprocedural antimicrobial prophylaxis were both associated with a lower risk of infection (Klug et al., 2007). There is evidence that perioperative antimicrobial prophylaxis is associated with a reduction in CIED infections (Bertaglia et al., 2006; Da Costa et al., 1998b; de Oliveira et al., 2009). Other small studies suggest that pectoral transvenous device placement is associated with significantly lower rates of CIED infection than those implanted abdominally or by thoracotomy. Thus, the use of a pectoral approach is not only less invasive but also appears to confer an ancillary benefit of lower infection risk (Mela et al., 2001). Physician experience in CIED implantation may also play a role in the rate of subsequent CIED infection. In a study of Medicare administrative data, Al-Khatib et al. found a significantly higher risk of ICD infection within 90 days of device implantation in patients whose device was placed by physicians in the lowest quartile of implantation volume. Rates of mechanical complications at 90 days were also higher for lower-volume physicians (Al-Khatib et al., 2005). 5.1. Clinical and microbiological diagnosis In all patients with suspected CIED infection diagnosis is linked to both local and systemic signs of inflammation associated to positive microbiological culture of the skin pocket or other materials. Signs and symptoms of systemic inflammation include malaise, fever with or without chill, leucocytosis and, in most severe cases, hypotension. A new onset valvular murmur suggests CIED endocarditis. Local signs of infection include redness and oedema and pain of the skin pocket. Definitive diagnosis of CIED infection is linked to microbiological cultures. Usually, samples are taken from the generator pocket. Alternatively, once the device has been removed, samples from lead tips may be cultured to identify the causative organism and support a diagnosis of CIED infection. Gram staining, anaerobic and aerobic bacterial cultures, should all be performed. If the initial Gram stain is negative, both tissue and the lead tip should be cultured for fungi and mycobacteria. Percutaneous aspiration of the device pocket is not recommended because of its low diagnostic accuracy and the theoretical risk of introducing microorganisms into the pocket site or spreading germ into the blood stream. Contamination of leads may also occur at the time of their extraction throught a contamined skin pocket; this may explain some of the positive lead-tip cultures found in patients without systemic manifestation and with negative blood cultures. If a CIED-related endocarditis is suspected, at least two sets of blood cultures should be obtained before starting any antimicrobial therapy. Positive blood cultures, particularly due to staphylococcal species, provide a strong clue that the clinical syndrome is due to CIED infection (Baddour et al., 2010). 5.2. Instrumental diagnosis 5.2.1. Transthoracic and transesophageal echocardiography Endocarditis is clinically confirmed when valvular or lead neostructures consistent with vegetations are detected on echocardiography, or if the Duke criteria for infective endocarditis are met (Table 1)(Klug et al., 1997, Durak et al. 1994). Vegetation is defined as an oscillating intracardiac mass which can be seen on the electrodes, the leads or the cardiac valve leaflets. To be diagnostic, vegetation should be noted in more than one echocardiographic plane (Klug et al., 1997; Sanfilippo et al., 1991; Victor et al., 1999). Both transtoracic echocardiography (TTE) and transesophageal echocardiography (TEE) may be employed, even though TEE is more accurate and is the actual gold standard. \|Definite infective endocarditis\| \|Microorganisms: demonstrated by culture or histology in vegetation, in a vegetation that has embolized, or in intracardiac abscess, or demonstrated by culture of the lead\| \|Two major criteria, or one major and three minor criteria, or five minor criteria\| \|Positive blood culture for infective endocarditis\| \|Typical microorganisms for infective endocarditis from two separate blood cultures\| \|Streptococcus viridans, Streptococcus bovis, HACEK group, or\| \|Community-acquired Staphylococcus aureus or enterococci, in the absence of a primary focus, or\| \|Persistently positive blood culture, defined as microorganism consistent with infective endocarditis from\| \|Blood cultures drawn "/12 hours apart, or\| \|All of three or a majority of four or more separate blood cultures, with first and last drawn at least 1 hour apart\| \|Evidence of endocardial involvement:\| \|Positive echocardiogram for infective endocarditis:\| \|Oscillating intracardiac mass on PM leads or on the endocardial structure in contact with PM leads\| \|Abscess in contact with PM leads\| \|Vascular phenomena: arterial embolism, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, Janeway lesions\| \|Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots\| \|Echocardiogram: consistent with infective endocarditis but not meeting major criterion as noted previously (sleevelike appearance)\| \|Microbiological evidence: positive blood culture but not meeting major criterion as noted previously\| TTE is not helpful in ruling out a diagnosis of lead-related endocarditis, particularly in adults, due to its poor sensitivity. Moreover, patients can develop both right-sided (lead-related) and left-sided endocarditis. Actually, sensitivity of TTE for left-sided and for perivalvular extension of infection is lower than TEE. On the contrary several indirect echocardiographic features of endocarditis may be better seen with TEE. They include pericardial effusion, ventricular dysfunction or dyssynchrony, and pulmonary vascular pressure estimations. TEE may be not always available and can be discomfortable for the patients. For these reasons, even if TEE rapresents the gold standard for the diagnosis of CIED infections, and is recommended for the initial diagnosis, TTE can be used during the course of patient’s illness for additional studies or follow-up. It is important to underlyine that an echocardiographyc image of a mass adherent to the lead may be a sterile thrombus or infected vegetation and it is impossible to distinguish between the two with echocardiography. Masses that are detected in patients without positive blood cultures or other signs of infection are likely to sterile vegetation (thrombus). In addition, the failure to visualize a mass adherent to a lead with TEE does not exclude lead infection. Thus, even when vegetation is demonstrated, differential diagnosis may be difficult if microbiological culture are not positive. Clear guidelines for CIED infection diagnosis are lacking. Based on clinical practice and expert opinion, a summary of recommendations for diagnosis of CIED infections is provided in Table 2. \|1. All patients should have at least 2 sets of blood cultures drawn at the initial evaluation before initiation of antimicrobial therapy. (Level of Evidence: C)\| \|2. Generator-pocket tissue Gram’s stain and culture and lead-tip culture should be obtained when the CIED is explanted. (Level of Evidence: C)\| \|3. Patients with suspected CIED infection who either have positive blood cultures or who have negative blood cultures but have had recent antimicrobial therapy before blood cultures were obtained should undergo TEE for CIED infection or valvular endocarditis. (Level of Evidence: C)\| \|4. All adults suspected of having CIED-related endocarditis should undergo TEE to evaluate the left-sided heart valves, even if transthoracic views have demonstrated lead-adherent masses. In pediatric patients with good views, transthoracic echocardiography may be sufficient. (Level of Evidence: B)\| \|Patients should seek evaluation for CIED infection by cardiologists or infectious disease specialists if they develop fever or bloodstream infection for which there is no initial explanation. (Level of Evidence: C)\| \|Percutaneous aspiration of the generator pocket should not be performed as part of the diagnostic evaluation of CIED infection. (Level of Evidence: C)\| 5.2.2. Positive Emission Tomography (PET) Infection staging and identification of other septic locations may be very important in order to monitor treatment efficacy before any re-implantation. It might be useful to assess the extension of infectious disease (staging) in these patients by non-invasive whole-body imaging, and Fluoro-18 desoxyglucose (18F-FDG) PET is a potential candidate for this purpose. The use of 18F-FDG PET imaging in inflammatory processes is related to the high affinity of inflammatory cells such as neutrophils, lymphocytes and macrophage for 18F-FDG. 18F-FDG PET shows high diagnostic accuracy when infection affects the box of generator but is slightly less reliable when the leads are involved. Globally, sensitivity and specificity are optimal for box infection even if mild physiological uptake may be seen in normal cases. Physiologically, a slight 18F-FDG uptake may be observed around the box even in not infected patients, particularly in the area of the muscle interface. However, uptake around the box is much higher in case of infection. Leads infection represents a different challenge. The size of the leads and the size of the vegetation are both very small and may easily be below the theoretical resolution of the PET system. For leads, sensitivity and specificity are lower, and diagnosis is based upon visualization of mild focal uptake along the leads. Interpretation of negative cases should be cautious, particularly if patients have received prolonged antibiotherapy (Bensimhon et al., 2010). The significant morbidity and mortality associated with device infections and the need for device removal make prevention of infections extremely important. Prevention of CIED infection can be addressed before, during, and after device implantation. Before implanting intravascular devices, it is important to ensure that patients do not have clinical signs of infection. In this case definitive implantation should be posponed after the resolution of infection. Once CIEDs are implanted, both pharmacological and non pharmacological strategies can be adopted in order to reduce risk of infection. 6.1. Pharmacological strategies A meta-analysis of 7 randomized studies on 2023 patients examining the impact of systemic antibiotics on the risk of pacemaker-related infections suggested that systemic antibiotic prophylaxis significantly reduces the incidence of serious infective complications after pacemaker implantation (Da Costa et al., 1998b). A following observational study was performed to assess the safety and long-term efficacy of a simple scheme of antibiotic prophylaxis, and to identify the predictors of long-term infective complications in patients undergoing pacemaker implantation or replacement. This study showed the efficacy of a single dose of cefazolin in preventing infective complications (Bertaglia et al., 2006). Finally a prospective, randomized, double-blinded, placebo-controlled trial was developed to determine whether prophylactic antibiotic administration reduces the incidence of infection related to device implantation was. This double blinded study included 1000 consecutive patients who presented for primary device implantation or generator replacement randomized in a 1:1 fashion to prophylactic antibiotics or placebo. Intravenous administration of 1 g of cefazolin or placebo was done immediately before the procedure. Follow-up was performed at 10 days and 1, 3, and 6 months after discharge. The primary end point was any evidence of infection at the surgical incision (pulse generator pocket), or systemic infection related to the procedure. The safety committee interrupted the trial after 649 patients were enrolled because of a significant difference in favor of the antibiotic arm and concluded that antibiotic prophylaxis significantly reduces infectious complications in patients undergoing implantation of pacemakers or cardioverter-defibrillators (de Oliveira et al., 2009). Most experts continue to advocate a first-generation cephalosporin, such as cefazolin, as prophylaxis agent. Although not generally recommended, some authors advocate the use of vancomycin, particularly in centers where oxacillin resistance among staphylococci is high. If vancomycin is used, then it should be administered 90 to 120 minutes before the procedure. Vancomycin also represents an alternative to a first-generation cephalosporin in patients who are allergic to cephalosporins (Sohail et al., 2007b). In patients who are allergic to both cephalosporins and vancomycin, daptomycin and linezolid are alternative agents for prophylaxis. Antibiotic prophylaxis is also recommended if subsequent invasive manipulation of the CIED is required. Currently, there are no data to support the administration of postoperative antibiotic therapy, and this is not recommended because of the risk of drug adverse events, selection of drug-resistant organisms, and costs (Baddour et al., 2010). 6.2. Non pharmacological strategies Several preventive measures are recommended in combination with prophylactic antibiotics. Using a strictly aseptic technique during implantation is of paramount importance, including surgical scrubbing, use of standard operating room, facemasks, caps, and sterile gowns and gloves, and the use of sterile, dry gauze pads to cover surgical incisions (Voet et al., 1999). Other preventive strategies include to limit the duration of temporary pacing to the shortest time and to limit the number of people in the room during the procedure to those absolutely necessary. Prevention of hematoma during the procedure is important, and several interventions have been used, although there are no data to support their use (Lekkerkerker et al., 2009). This can be achieved by meticulous cauterization of bleeding sites and packing the pocket with antibiotic-soaked sponges to provide tamponade while leads are being placed. The application of topical thrombin may be helpful, particularly in anticoagulated patients. Irrigation of the pocket is useful to remove debris and may reveal persistent bleeding that could lead to a pocket hematoma. In addition, irrigation with an antimicrobial-containing solution for pocket cleansing has been used. Use of monofilament suture for closure of the subcuticular layer may avoid superficial postoperative cellulitis. A compressive dressing applied 12-24 hours after skin closure may further decrease the risk of hematoma formation. In the immediate postoperative period, recent data indicate that low-molecular-weight heparin predisposes to hematoma formation and should be avoided (Robinson et al., 2009). A hematoma should be evacuated only when there is increased tension on the skin. Needle aspiration should otherwise be avoided because of the risk of introducing skin flora into the pocket and subsequent development of infection. Finally, routine ambulatory care follow-up after CIED placement to detect early infectious complications has been performed in many centers and this is actively recommended (Deuling et al., 2009). 7.1. Conservative treatment Optimal management of CIED infection depends on the clinical presentation and causative pathogen. Conservative treatment with antibiotics alone without removal of the device may be sufficient in patients with local signs without sepsis, endocarditis or skin erosion. Seven to ten days of antibiotic therapy with an oral agent with activity against staphylococci is reasonable (Gandelman et al., 2007). 7.2. Device removal Complete removal of all hardware is the recommended treatment for patients with established CIED infection or sepsis (Chua et al., 2000; Sohail et al., 2007a). This includes cases in which a localized pocket infection occurs in the absence of signs of systemic infection. Complete removal of hardware is needed because infection relapse rates due to retained hardware are high (Field et al., 2007). Erosion of any part of the CIED should imply contamination of the entire system, including the intravascular portion of leads, and complete device removal should be performed. Complete CIED removal should be performed when patients undergo valve replacement or repair for infective endocarditis, because the CIED could serve as a nidus for relapsing infection and subsequent seeding of the surgically treated heart valve. An epicardial system should be considered if a new CIED is required after valve surgery with initial CIED removal. Device removal is also recommended in those patients with S. aureus bacteremia with clinical or echocardiographic evidence of CEID infection, un-explained bacteremia, or relapsing bacteremia after antibiotic treatment (Chamis et al., 2001). 7.2.1. Approach to hardware removal Two techniques for removing pacemaker systems are currently available: invasive thoracotomy and percutaneous extraction. The choice of the less invasive percutaneous technique is usually based on time elapsed from implantation, vegetation size, absence of vegetation on the tricuspid valve, and the general conditions of the patient. Percutaneous lead extraction has become the preferred method for removal of CIED hardware. However, these procedures involve significant risks, including cardiac tamponade, hemothorax, pulmonary embolism, lead migration, and death, even in experienced hands. Thus, the performance of these procedures should be limited to centers with the appropriate facilities and training, including the presence of immediate availability of cardiothoracic surgery to provide backup in the event of complications. In high-volume centers, percutaneous lead removal can be accomplished relatively safely with a high rate of success (Jones et al., 2008). A primary surgical approach to lead removal in patients with CIED infection should be limited to patients who have significant retained hardware after one attempt at percutaneous removal. Another scenario in which a preference for surgical lead removal has been advocated is in patients with lead vegetations >2 cm in diameter, because of concerns about the risk of pulmonary embolism with percutaneous lead extraction. Experience suggests, however, that percutaneous removal in patients with large vegetations can be done without precipitating a clinically apparent pulmonary embolism. Until additional data are available, decisions regarding percutaneous versus surgical removal of leads with vegetations larger than 2 cm in diameter should be individualized and based on a patient’s clinical parameters and the extractor’s evaluation (Field et al., 2007; Gandelman et al., 2007; Sohail et al., 2007a). Antimicrobial therapy is adjunctive in patients with CIED infection, and complete device removal should not be delayed, regardless of timing of initiation of antimicrobial therapy. Selection of the appropriate antimicrobial agent should be based on identification and in vitro susceptibility testing results. Because most infections are due to staphylococcal species, treatment agent should be effective against those germs. In case of oxacillin resistant infections is suspected, vancomycin should be administered initially as empirical antibiotic coverage until microbiological results are known. Patients with infections due to oxacillin-susceptible staphylococcal strains can be given cefazolin or nafcillin alone with discontinuation of vancomycin. Vancomycin should be continued in patients who are not candidates for betalactam antibiotic therapy and those with infections due to oxacillin-resistant staphylococci. Compared with Gram-positive infections, Gram-negative and fungi are less frequently isolated and empiric coverage against those microorganisms is not routinely indicated; it should be started after microbiological identification has been performed. Pathogen identification and in vitro susceptibility testing can be used to guide treatment in patients with nonstaphylococcal CIED infections. When microbiological culture are available, a de-escalation approach should be considered in order to minimize the development of antimicrobial resistances (De Gaudio et al., 2010). There are no clinical trial data to define the optimal duration of antimicrobial therapy for CIED infections, regardless of the extent of infection, or to determine when conversion to an oral agent is appropriate once complete device removal has been achieved. Factors that influence duration of therapy include the extent of device infection, the causative organism, the persistence of positive blood cultures, and associated complications such as valvular involvement, septic thrombophlebitis, or osteomyelitis. Blood cultures should be obtained from all patients after device removal. Therapy can be switched to an oral regimen once susceptibility results are known if there is an oral agent available that is active against the pathogen and the infected CIED has been removed. At least two weeks of parenteral therapy are recommended after removal of an infected device and for patients with bloodstream infection. Patients with sustained (>24 hours) positive blood cultures despite CIED removal and appropriate antimicrobial therapy should receive parenteral therapy for at least 4 weeks, even if TEE is negative for valvular vegetations. 7.2.2. Hardware reimplantation It is important to assess the need for new device placement in any patient with an infected CIED. Based of available data, one third to one half of patients will not require new CIED placement. There are several factors, including reversal of the pathological processes that precipitated the need for CIED implantation and lack of appropriate clinical indications, that may obviate the need for new CIED placement (Sohail et al., 2007b). Adequate debridement and control of infection at all sites, both at the generator site and metastatic, if present, must be achieved before new device placement (Baddour et al., 2010). Removal of infected hardware should not be attempted until a careful assessment of a new implantation strategy has been performed, particularly in patients with pacemakers for complete heart block and resynchronization therapy devices. When implantation of a new device is necessary, it should be performed on the counterlateral side if possible to avoid relapsing device infection. If this is not possible, a transvenous lead can be tunneled to a device placed subcutaneously in the abdomen. Implantation is usually postponed to allow for resolution of infection, but patients who are CIED dependent represent a challenge, because they cannot be discharged with a temporary pacemaker. Active-fixation leads attached to pacing generators or defibrillators are now being used as a bridge until PPM implantation is deemed appropriate. Use of active-fixation leads connected to external devices permits earlier mobilization of patients dependant on cardiac stimulators and has been associated with a reduced risk of pacing-related adverse events, including lead dislocation, and local infection (Braun et al., 2006). Optimal timing of device replacement is unknown. There have been no prospective trials that examined timing of new device replacement and risk of relapsing infection; however, several investigators recommend waiting for blood cultures to be negative before a new device is placed (Gandelman et al., 2007; Sohail et al., 2007a) Currently, 3 million implanted cardiac pacing systems and 180000 implantable cardioverter-defibrillators exist worldwide. The rate of device implantations is increasing due to the aging of the general population and the development of new indications. Although conferring obvious benefits, the use of these implantable devices is associated with some complications. Infections must be considered as a serious and potentially fatal complication. The clinical presentation of device infection ranges from superficial wound infection to frank device-related endocarditis. The incidence of infection related to pacemakers varies from 0.13% to 19.9% in prospective and retrospective studies. Serious complications, such as endocarditis and sepsis, may occur in 0.5% of patients. In addition, infectious complications have a significant economic impact to health care systems due to the high cost of treatment. Data to guide treatment of patients with this condition are limited. However, the consensus from the published literature recommends prompt and complete device removal, combined with antimicrobial therapy of appropriate duration. Conservative treatment without explantation of all hardware is frequently unsuccessful. Given the progressive rise in antimicrobial-resistant bacteria in general, and gram-positive pathogens in particular, treatment of cardiovascular infections is likely to become more difficult in the future. Finally, because a substantial number of patients may no longer require such devices, reimplantation should be done only after the continued need for such therapy has been reassessed.	2	26	2	0	0	0.502873	2	9,757
ICD codes: C61 What is the ICD Code? Around 60,000 men get prostate cancer every year in Germany. This makes it the most common type of cancer in men. This article provides an overview of screening, diagnostic and therapy options for prostate cancer. At a glance - Prostate cancer is also known as prostate carcinoma. - The main risk factors for prostate cancer include age and family predisposition. - Men can have their prostate examined by a doctor under the national cancer screening program. The national screening program does not include measuring the prostate-specific antigen (PSA) level in the blood. - In its early stages, prostate cancer is only rarely accompanied by symptoms. - Most men with prostate cancer can be cured. Even if the cancer cannot be cured, it often progresses slowly. Rapid progression is rarer. - Possible side effects of treatment include involuntary loss of urine (urinary incontinence), erectile problems and bowel problems, such as bleeding and pain. Note: The information in this article cannot and should not replace a medical consultation and must not be used for self-diagnosis or treatment. What is prostate cancer? Medical practitioners refer to malignant tumors that occur in a man’s prostatic gland (prostate) as prostate cancer or prostate carcinoma. The prostate is one of the internal sex organs in a man. Doctors differentiate between three tumor stages: - Localized: the cancer is only growing in the prostate. - Locally advanced: the cancer cells are growing beyond the prostate, for example, into the seminal vesicles. - Advanced or metastatic: the cancer cells are spreading to the lymph nodes, bones or other organs. What are the symptoms of prostate cancer? Around 60,000 men get prostate cancer every year in Germany. In most cases, the disease is detected at an early stage, when patients do not normally have any symptoms. Even if the condition is more advanced, patients frequently do not have typical symptoms. This means that the symptoms they have could also be caused by other illnesses. The symptoms of prostate carcinoma may include: - difficulty urinating – the bladder cannot be spontaneously emptied - discomfort when urinating - aching bones - blood in the urine or seminal fluid - difficulties during sex Difficulty urinating often occurs as men get older. This is because the prostate gets bigger with age and presses on the urethra. This benign (harmless) enlargement of the prostate is known by medical practitioners as benign prostatic hyperplasia (BPH). If the symptoms persist over several weeks, a visit to the doctor is recommended. The doctor can start narrowing down what is causing the symptoms and, if necessary, initiate further diagnostic steps by specialists. Prostate cancer: what are the causes and risk factors? The risk of developing prostate cancer increases with age. As men age, genetic changes (mutations) increase in the cells of the prostate gland. The more mutations there are, the greater the risk of prostate cancer. Most men are between 70 and 80 years old when diagnosed. Prostate cancer occurs relatively rarely before the age of 50. Another major risk factor for prostate cancer is family history. If a close relative, such as a father or brother, has prostate cancer, the risk of cancer increases relative to the general male population. In this case, it may be useful to find out about prostate screening at a younger age than 45. You can find out about which options are available in the section of this article dealing with screening. What prostate cancer screening options are available? In Germany, national screening program for cancers of the sex organs starts at age 45. Men are entitled to an annual screening, in which their doctor asks about symptoms and examines their external sex organs. The doctor will also carry out a digital rectal exam (DRE), feeling the prostate with a finger. The national screening program does not include measuring the prostate-specific antigen (PSA) level in the blood. The statutory health insurance funds do not usually pay for PSA screening. Men can have this screening done as an individual health service (IGeL) and cover the cost themselves. The reason for this is that, to date, studies have not clearly demonstrated that nationwide PSA screening does more good than harm. Men who are thinking of having their PSA tested should find out about the benefits and drawbacks for themselves. Urologists and General Practitioners can provide detailed information about this. Someone who understands the benefits and potential risks that apply in their individual situation is better able to decide for or against having the test done. Would you like to know more about prostate cancer screening or PSA testing? And find out about the benefits and drawbacks of PSA screening? More information is available on the website of the German Cancer Research Center’s Cancer Information Service (in German). What is the outlook for prostate cancer? Prostate cancer progresses very differently in different men. In most men, prostate cancer grows quite slowly compared with many other cancers. Less aggressive prostate carcinomas often remain undetected throughout a man’s life if he has no symptoms. This means that many patients have a normal life expectancy even after receiving a diagnosis of prostate cancer. In other men, prostate cancer can advance quite quickly and secondary tumors are also identified at the time of diagnosis. This type of metastatic prostate cancer is usually incurable. Prostate cancer can also recur after therapy (relapse). In some cases, curative treatment can be administered again in the event of a relapse. What tests are involved in diagnosing prostate cancer? If prostate carcinoma is suspected, doctors can use a range of complementary diagnostic methods. Initially, a basic diagnosis comprises the following steps: - taking the patient’s case history, asking about pre-existing conditions, symptoms and family history - performing a physical examination and feeling the prostate by means of a digital rectal exam (DRE) - measuring the prostate-specific antigen (PSA) level - scanning the prostate using multi-parametric magnetic resonance imaging (mp‑MRI) - if necessary, using additional imaging techniques, such as transrectal ultrasound (TRUS) - taking a tissue sample (biopsy) for histological examination General Practitioners can take the first steps of a basic diagnosis themselves. Specialists such as urologists and radiologists are responsible for subsequent testing. Specialist outpatient clinics also have trained staff and the equipment required. Prostate tissue samples are required to verify the diagnosis. In most cases, urologists take 10 to 12 biopsies in accordance with a fixed (systematic) plan. These biopsies are subjected to a histological examination (i.e. examination on a cellular level) in a lab. In addition, specific samples can be taken from areas identified using imaging techniques. These findings, together with the PSA level, indicate how likely it is that the tumor has spread beyond the prostate. If the risk is elevated, the following imaging methods can also be used: - computed tomography (CT) - magnetic resonance imaging (MRI) - bone or skeletal scintigraphy - positron emission tomography (PET), in particular using a specific radioactive substance as a marker (i.e. PSMA-PET) – usually in combination with a CT scan (PSMA-PET/CT) Would you like to know how doctors test for prostate cancer? And when further tests are used to determine how far the cancer has spread? You can find out more about diagnostic procedures on the website of the Cancer Information Service of the German Cancer Research Center (in German). How is prostate cancer treated? Prostate cancer can be treated in a number of ways. The treatment can act against the tumor in the prostate area or throughout the body. The following five factors determine which treatment is best in each individual case: - the stage of the disease - the prostate-specific antigen (PSA) level in the blood - how aggressive the tumor is - the patient’s general state of health - the patient’s own goals and values Localized prostate cancer If tumor growth is limited to the prostate, a long-term cure is often possible. Patients can choose from a range of standard treatments. Based on what is currently known, these offer similar chances of recovery. However, they differ in terms of their side effects and long-term effects: - complete surgical removal (radical prostatectomy): there are two types of surgical procedure – one with a robot and one without. Both cure prostate cancer equally well. - external irradiation through the skin (percutaneous radiotherapy) - internal irradiation (brachytherapy with radioactive sources in the prostate) Active surveillance may be equally beneficial. This method is considered if the prostate cancer is less aggressive. It means that no treatment is administered initially. Instead, regular check-ups are required. If the prostate cancer becomes more aggressive, doctors then begin curative treatment. Minimally invasive focal (localized) therapies may also be considered under certain circumstances. However, it is not yet clear whether these are as effective as standard treatments. In individual cases, doctors may also combine different types of therapy. For example, an operation may be followed by radiotherapy. Alternatively, urologists may administer radiotherapy in parallel with hormone withdrawal. For more detailed information about treatment of localized prostate cancer and about supports for sound decision-making, see the patient guide published by the Cancer Information Service. There are various techniques for surgical removal of the prostate (prostatectomy), i.e., open surgery, laparoscopic surgery or robot-assisted surgery. The following videos explain what is involved in each of these types of surgery. What is an open prostatectomy? What is a laparoscopic prostatectomy? What is a robotic prostatectomy? Advanced or metastatic prostate cancer When the disease has reached this stage, it is usually incurable. In this situation, hormone withdrawal therapy is a key part of treatment. It removes the testosterone (male sex hormone) that the prostate cancer cells need to grow. In this way, doctors can suppress the prostate cancer and keep it in check for a certain time. Treatment for patients with advanced and metastatic prostate cancer can be very complex. Doctors and urologists therefore have a range of other systemic treatment options, some of which can be combined: - Chemotherapy: doctors administer drugs (cytostatics) that slow down cell growth or prevent cell division. - Targeted treatment: doctors administer drugs known as PARP inhibitors, which inhibit the repair of damaged genetic material in the cancer cells. - Radionuclide therapy: doctors administer drugs (radiopharmaceuticals) that accumulate in the prostate cancer cells themselves and destroy them through nuclear radiation. - Supportive treatment methods: these include drugs that act on the bones and external radiotherapy. In the case of bone metastases, they can help to alleviate aching, prevent broken bones, and generally improve the man’s quality of life. In some cases, it may make sense to not treat patients who are symptom-free. Doctors recommend this “watchful waiting” approach if the patient is of advanced age, for example, or if other health issues take precedence. Do you want to learn more about the various treatment options for prostate cancer and their possible side effects? Which options are relevant to you and what is meant by medical terms such as “castration-resistant” or “oligometastatic”? You can find detailed descriptions of the treatments used on the German Cancer Research Center’s Cancer Information Service website (in German). How is cancer treated? The video below explains how cancer can be treated. This and other videos can also be found on YouTubeWatch now What rehabilitation and aftercare options are available for prostate cancer? Cancer treatment can be both mentally and physically exhausting. Medical rehabilitation (rehab) following cancer treatment can help patients regain their strength. It also aims to help them deal with the consequences of the disease and treatment in the best possible way. Rehab for prostate cancer patients is specialized, i.e., the program includes specialized urological care. In general, urological rehab is based around the person’s medical history, the specific therapy and the limitations that exist. Urological rehab may include: - pelvic floor exercise to help regain control of urination - explaining possible treatments for weak erections - exercise therapy to prevent complications from hormone withdrawal, such as metabolic disorders and osteoporosis - psychological support - nutritional advice What happens after treatment? Prostate cancer aftercare is intended to detect any recurrence (relapse) at an early stage, as well as any long-term effects of treatment. Once treatment has been completed, patients are examined regularly, initially at short intervals, then at longer ones. Doctors ask about symptoms, carry out physical examinations, and measure the prostate-specific antigen (PSA) level in the blood. Want to know more about prostate cancer rehabilitation and aftercare? How PSA levels fall at different rates after an operation and after radiotherapy? And how progression is monitored if the disease is at an advanced stage? You can find more information on the website of the German Cancer Research Center’s Cancer Information Service. How to enjoy a good quality of life with prostate cancer Many prostate cancer patients want to be active in order to help themselves recover. There are a number of ways they can do this. What can help them to cope better with the disease and the consequences of treatment depends on the individual situation: - Over time, rehab and physiotherapy can help improve or even eliminate incontinence. - Patients find out how to deal with impotence and sexuality through rehab or by talking to doctors. - Exercise can help overcome tiredness and exhaustion. This should be adapted to the patient’s physical ability. - A balanced, healthy diet or even nutritional therapy can promote well-being and prevent poor nutrition. - Psycho-oncological counseling can help if worry and anxiety dominate patients’ lives. If it is no longer possible to cure the cancer and it is becoming more advanced, good medical and nursing care are very important. Adverse symptoms such as pain and breathlessness can be alleviated. Psychosocial support can also help patients maintain a good quality of life for as long as possible. What points of contact are there for prostate cancer? When treating prostate cancer, doctors from different fields work together closely. Hospitals that are particularly experienced in treating patients with prostate cancer can get certification to prove this. The German Cancer Society (DKG) regularly checks their compliance with certain professional requirements. You can find the addresses of the certified centers on the OncoMAP website. Urological university hospitals in Germany are listed on the urology portal (Urologenportal) website run jointly by the German Society of Urology (Deutsche Gesellschaft für Urologie) and the Association of German Urologists (Berufsverband der Deutschen Urologen). Do you have further questions about dealing with the condition in everyday life and additional support options? You can find information about this on the website of the Cancer Information Service of the German Cancer Research Center (in German). If you have any questions about prostate cancer, you can also contact the Cancer Information Service directly on freephone 0800 420 30 40 or by e-mail at [email protected]. - Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V. (AWMF), Deutsche Krebsgesellschaft e.V. (DGK), Deutsche Krebshilfe (DKH). Prostatakarzinom. S3-Leitlinie. Version 6.0. Leitlinienprogramm Onkologie. AWMF-Registernummer 043/022OL. Aufgerufen am: 18.06.2021. - European Association of Urology (EAU). Prostate cancer. EAU Guidelines. Edn. presented at the EAU Annual Congress Milan 2021. ISBN 978-94-92671-13-4. Aufgerufen am 18.06.2021. - Zentrum für Krebsregisterdaten (ZfKD) des Robert Koch-Instituts (RKI). Prostatakrebs (Prostatakarzinom). Aufgerufen am 18.06.2021. In cooperation with the Cancer Information Service of the German Cancer Research Center (Krebsinformationsdienst des Deutschen Krebsforschungszentrums).As at:	2	8	1	0	2	0.69889	3	3,521
As orthopaedic surgeons and their practice teams ready themselves for the implementation of ICD-10, a team-based transition action plan is essential. One step in making the transition is known as “mapping.” Mapping describes the process of comparing the codes currently used in ICD-9 to those that will be used in ICD-10 for the same condition or injury. Mapping helps to illustrate the differences in documentation requirements between ICD-10 and ICD-9. It enables physicians to identify whether they are meeting the increased documentation elements required to report ICD-10 codes at the highest levels of specificity. If they aren’t, there is time to identify and correct deficiencies, to begin using the more granular diagnosis code descriptions, and to receive feedback and make improvements. Because ICD-10 uses a completely new structure (3 to 7 characters) and varied character patterns, orthopaedic groups will initially use code mapping as a transition tool to learn the new system. Eventually, however, as they become more comfortable coding in ICD-10, they can stop using the ICD-9 code set as a reference point. To begin your mapping activities, identify the practice’s top 25 or 30 ICD-9 codes using the billing system. Then identify the ICD-10 equivalents. Because ICD-10 has many more codes than ICD-9, a one-to-one mapping is not always possible. For example, ICD-9 has about 17 codes for a femur fracture while ICD-10 has more than 2,600 codes for a femur fracture. Practices need to fully implement the documentation requirements (code descriptions) defined by ICD-10 before Oct. 1, 2015. The most basic form of mapping was developed by the Centers for Medicare & Medicaid Services (CMS) and is called GEMs, or General Equivalency Mappings. Using them, practices can identify the ICD-10 code that resembles the same condition or injury in ICD-9. Although the GEMs offered by CMS are free, they may not provide the best mapping. For example, Table 1 shows some mapping examples drawn from a “real-life” frequency report, representing the levels of specificity that many groups use. Close review of these examples shows that the GEMs ICD-10 alternative for each ICD-9 code is an unspecified code option for the condition or injury. However, this may be a clue that ICD-10 has multiple options for that code, especially if the word “unspecified” appears before the anatomic site. The ICD-9 code for rotator cuff (726.10) has several options for multiple forms of tear in ICD-10. The same is true with respect to fracture type (ICD-9 code 813.42). Laterality options are not displayed in any of these GEMs mapping results, but the need for designating laterality is indicated by the use of “unspecified” before the anatomic site. Furthermore, GEMs mapping provides the code that would apply for an initial encounter (see Table 1, ICD-9 codes 813.42 and 836.0), designated by the 7th character “A.” However, other 7th character options could apply. (See “When 7 Is Not a Lucky Number,” AAOS Now, November 2014.) These examples show that GEMs provides a starting place, but its mapping results are not fully specific. Using codes resulting from a GEMs mapping for claim submission would not be appropriate when more specific codes could be reported. Although using GEMs is good as a learning tool, it is not useful as a long-term solution in practice. This is a critical point for practices to consider when electronic health records and practice management software vendors offer to provide cross-walk tools. Vendors who say that their mapping is based on GEMs should be asked how the system will help the practice assign the most detailed level of specificity because GEMs won’t be enough. Other mapping options Once a practice has identified the GEMs crosswalk codes, it can take two approaches. Option 1 is to invest in a more detailed mapping tool or software program. The American Medical Association publication ICD-10-CM Mappings is one option. The 2015 release of the AAOS Orthopaedic Code-X program also will have more detailed mappings and cross references to CPT. This will greatly improve the speed and efficiency of searching for ICD-10 codes. Option 2 is for the practice to develop its own mapping table using the ICD-10 book. Key steps include the following: - Generate a CPT frequency list for each provider, and identify their top 15 to 25 ICD-9 codes. - Use the CMS GEMs file to identify the ICD-10 GEMs crosswalk code(s) for each ICD-9 code on the list. The GEMs data is stored in an ASCII file that can be imported into any spreadsheet program, but the codes do not include the decimal point found in the ICD-9 and ICD-10 books. For example, ICD-9 code 719.56 will appear as the number 71956, and ICD-10 code M25.669 will appear as M25669. In addition, there are no GEMs crosswalk options for ICD-9 codes that are designated as needing to be coded to a higher level (often designated with a red plus sign). If the frequency report includes these types of unspecified codes, claims denials are probable. - Locate the GEMs ICD-10 crosswalk code(s) in the tabular section of the ICD-10 book, or look them up in the AAOS Code-X. When using Code-X, go to the “ICD-10 Search By Keyword” screen, and enter the base characters (eg, M25.66, M66.2, M75.10) in the Code field. The system will produce a list of both the unlisted and more specific codes that apply. - Study the details of the code’s category and create a list of the description parameters that apply. For this stage, it’s not necessary to write down every ICD-10 code in detail; the focus should be on the descriptor elements that lead to greater code specificity. The point is to generate a template that will prompt the physician to document each element necessary to lead to the correct code. Table 2 displays more detailed options that could apply to the four ICD-9 code examples from Table 1. For ICD-9 code 719.56, laterality is the only element of detail that adds new code options: M25.661 Stiffness of right knee, NEC, and M25.662, Stiffness of left knee, NEC. For ICD-9 code 726.10, in addition to laterality, the ICD-10 code is selected based on the type of rotator cuff rupture or tendon type. For ICD-9 code 813.42, selection options include laterality, fracture site, alignment, Salter Harris classification, and the encounter stage. Options for ICD-9 code 836.0 are laterality, tear type, and encounter stage. The ICD-10 examples that include the hyphen character indicate that additional alpha or numeric characters are required to correlate with the specific details described (laterality, site, alignment, encounter). When performing this type of mapping analysis, groups may find that they’ve been using unspecified ICD-9 codes when more specific codes exist. Learning the details of ICD-10 will help to prevent groups from carrying this coding bad habit with them during the implementation transition. It is important for each member of the practice who uses diagnosis codes to actually look at ICD-10 to get a feel of what the code descriptors look like and the associated documentation requirements. When to start The time to start mapping is now. Completing this exercise will help physicians and staff to understand how documentation details become essential to code specificity in ICD-10. For more information, attend one of the AAOS ICD-10 education workshops, kicking off in Dallas in January 2015. Sarah Wiskerchen, MBA, CPC, is a senior consultant with KarenZupko & Associates, Inc. She is an instructor for the 2015 AAOS CPT and ICD-10 coding workshops. New ICD-10 Education Program Coming “ICD-10 by the Numbers” is a 10-program series cosponsored by the AAOS and KarenZupko & Associates. The AAOS Practice Management and Coding, Coverage, and Reimbursement Committees are overseeing the program. The first program in the series—“Introduction: ICD-10-CM Architecture & Structure, Osteoarthritis, Joint Pain”—walks the learner through the basics of the ICD-10 code structure and demonstrates how to correctly apply ICD-10 codes to clinical cases. It also introduces a set of specific orthopaedic diagnosis groups—osteoarthritis and joint pain—to demonstrate how to apply the new coding concepts. The 10 modules can serve as a training program to educate those responsible for diagnostic coding on how to correctly apply ICD-10 coding principles. They also demonstrate the importance of anatomic specificity in patient documentation for accurate coding of the most common orthopaedic diagnoses in each orthopaedic specialty area. Look for details on this new educational program in January.	4	8	2	0	6	0.354438	8	2,026
Diagnostic and Statistical Manual of Mental Disorders The Diagnostic and Statistical Manual of Mental Disorders (DSM), published by the American Psychiatric Association, offers a common language and standard criteria for the classification of mental disorders. It is used, or relied upon, by clinicians, researchers, psychiatric drug regulation agencies, health insurance companies, pharmaceutical companies, the legal system, and policy makers together with alternatives such as the International Statistical Classification of Diseases and Related Health Problems (ICD), produced by the World Health Organization (WHO). The DSM is now in its fifth edition, DSM-5, published on May 18, 2013. The DSM evolved from systems for collecting census and psychiatric hospital statistics, and from a United States Army manual. Revisions since its first publication in 1952 have incrementally added to the total number of mental disorders, although also removing those no longer considered to be mental disorders. The International Statistical Classification of Diseases and Related Health Problems (ICD), produced by the World Health Organization (WHO), is the other commonly used manual for mental disorders. It is distinguished from the DSM in that it covers health as a whole. It is in fact the official diagnostic system for mental disorders in the US, but is used more widely in Europe and other parts of the world. The coding system used in the DSM is designed to correspond with the codes used in the ICD, although not all codes may match at all times because the two publications are not revised synchronously. While the DSM has been praised for standardizing psychiatric diagnostic categories and criteria, it has also generated controversy and criticism. Critics, including the National Institute of Mental Health, argue that the DSM represents an unscientific and subjective system. There are ongoing issues concerning the validity and reliability of the diagnostic categories; the reliance on superficial symptoms; the use of artificial dividing lines between categories and from ‘normality’; possible cultural bias; medicalization of human distress. The publication of the DSM, with tightly guarded copyrights, now makes APA over $5 million a year, historically totaling over $100 million. - 1 Uses and definition - 2 History - 3 DSM-IV-TR - 4 Criticism - 5 See also - 6 References - 7 External links Uses and definition Many mental health professionals use the manual to determine and help communicate a patient’s diagnosis after an evaluation; hospitals, clinics, and insurance companies in the US also generally require a DSM diagnosis for all patients treated. The DSM can be used clinically in this way, and also to categorize patients using diagnostic criteria for research purposes. Studies done on specific disorders often recruit patients whose symptoms match the criteria listed in the DSM for that disorder. An international survey of psychiatrists in 66 countries comparing use of the ICD-10 and DSM-IV found the former was more often used for clinical diagnosis while the latter was more valued for research. The current version of the DSM characterizes a mental disorder as “a clinically significant behavioral or psychological syndrome or pattern that occurs in an individual [which] is associated with present distress...or disability...or with a significant increased risk of suffering.” It also notes that “...no definition adequately specifies precise boundaries for the concept of ‘mental disorder’...different situations call for different definitions”. It states that “there is no assumption that each category of mental disorder is a completely discrete entity with absolute boundaries dividing it from other mental disorders or from no mental disorder” (APA, 1994 and 2000). There are attempts to adjust the wording for the upcoming DSM-V.[dated info] The initial impetus for developing a classification of mental disorders in the United States was the need to collect statistical information. The first official attempt was the 1840 census, which used a single category, “idiocy/insanity”. Three years later, the American Statistical Association made an official protest to the U.S. House of Representatives stating that “the most glaring and remarkable errors are found in the statements respecting nosology, prevalence of insanity, blindness, deafness, and dumbness, among the people of this nation” and pointing out that in many towns African-Americans were all marked as insane, and the statistics were essentially useless. The Association of Medical Superintendents of American Institutions for the Insane was formed in 1844, changing its name in 1892 to the American Medico-Psychological Association, and in 1921 to the present American Psychiatric Association (APA). Edward Jarvis and later Francis Amasa Walker helped expand the census, from 2 volumes in 1870 to 25 volumes in 1880. Frederick H. Wines was appointed to write a 582-page volume called “Report on the Defective, Dependent, and Delinquent Classes of the Population of the United States, As Returned at the Tenth Census (June 1, 1880)” (published 1888). Wines used seven categories of mental illness: dementia, dipsomania (uncontrollable craving for alcohol), epilepsy, mania, melancholia, monomania and paresis. These categories were also adopted by the Association. In 1917, together with the National Commission on Mental Hygiene (now Mental Health America), the APA developed a new guide for mental hospitals called the “Statistical Manual for the Use of Institutions for the Insane”. This included 22 diagnoses and would be revised several times by the APA over the years. Along with the New York Academy of Medicine, the APA also provided the psychiatric nomenclature subsection of the US general medical guide, the Standard Classified Nomenclature of Disease, referred to as the “Standard”. World War II saw the large-scale involvement of US psychiatrists in the selection, processing, assessment, and treatment of soldiers. This moved the focus away from mental institutions and traditional clinical perspectives. A committee headed by psychiatrist Brigadier General William C. Menninger developed a new classification scheme called Medical 203, that was issued in 1943 as a War Department Technical Bulletin under the auspices of the Office of the Surgeon General. The foreword to the DSM-I states the US Navy had itself made some minor revisions but “the Army established a much more sweeping revision, abandoning the basic outline of the Standard and attempting to express present day concepts of mental disturbance. This nomenclature eventually was adopted by all Armed Forces”, and “assorted modifications of the Armed Forces nomenclature [were] introduced into many clinics and hospitals by psychiatrists returning from military duty.” The Veterans Administration also adopted a slightly modified version of Medical 203. In 1949, the World Health Organization published the sixth revision of the International Statistical Classification of Diseases (ICD), which included a section on mental disorders for the first time. The foreword to DSM-1 states this “categorized mental disorders in rubrics similar to those of the Armed Forces nomenclature.” An APA Committee on Nomenclature and Statistics was empowered to develop a version specifically for use in the United States, to standardize the diverse and confused usage of different documents. In 1950, the APA committee undertook a review and consultation. It circulated an adaptation of Medical 203, the VA system, and the Standard’s Nomenclature to approximately 10% of APA members. 46% replied, of which 93% approved, and after some further revisions (resulting in its being called DSM-I), the Diagnostic and Statistical Manual of Mental Disorders was approved in 1951 and published in 1952. The structure and conceptual framework were the same as in Medical 203, and many passages of text were identical. The manual was 130 pages long and listed 106 mental disorders. These included several categories of “personality disturbance”, generally distinguished from “neurosis” (nervousness, egodystonic). In 1952, the APA listed homosexuality in the DSM as a sociopathic personality disturbance. Homosexuality: A Psychoanalytic Study of Male Homosexuals, a large-scale 1962 study of homosexuality, was used to justify inclusion of the disorder as a supposed pathological hidden fear of the opposite sex caused by traumatic parent–child relationships. This view was widely influential in the medical profession. In 1956, however, the psychologist Evelyn Hooker performed a study that compared the happiness and well-adjusted nature of self-identified homosexual men with heterosexual men and found no difference. Her study stunned the medical community and made her a hero to many gay men and lesbians, but homosexuality remained in the DSM until May 1974. In the 1960s, there were many challenges to the concept of mental illness itself. These challenges came from psychiatrists like Thomas Szasz, who argued that mental illness was a myth used to disguise moral conflicts; from sociologists such as Erving Goffman, who said mental illness was merely another example of how society labels and controls non-conformists; from behavioural psychologists who challenged psychiatry’s fundamental reliance on unobservable phenomena; and from gay rights activists who criticised the APA’s listing of homosexuality as a mental disorder. A study published in Science by Rosenhan received much publicity and was viewed as an attack on the efficacy of psychiatric diagnosis. Although the APA was closely involved in the next significant revision of the mental disorder section of the ICD (version 8 in 1968), it decided to go ahead with a revision of the DSM. It was published in 1968, listed 182 disorders, and was 134 pages long. It was quite similar to the DSM-I. The term “reaction” was dropped, but the term “neurosis” was retained. Both the DSM-I and the DSM-II reflected the predominant psychodynamic psychiatry, although they also included biological perspectives and concepts from Kraepelin’s system of classification. Symptoms were not specified in detail for specific disorders. Many were seen as reflections of broad underlying conflicts or maladaptive reactions to life problems, rooted in a distinction between neurosis and psychosis (roughly, anxiety/depression broadly in touch with reality, or hallucinations/delusions appearing disconnected from reality). Sociological and biological knowledge was incorporated, in a model that did not emphasize a clear boundary between normality and abnormality. The idea that personality disorders did not involve emotional distress was discarded. An influential 1974 paper by Robert Spitzer and Joseph L. Fleiss demonstrated that the second edition of the DSM (DSM-II) was an unreliable diagnostic tool. They found that different practitioners using the DSM-II were rarely in agreement when diagnosing patients with similar problems. In reviewing previous studies of 18 major diagnostic categories, Fleiss and Spitzer concluded that “there are no diagnostic categories for which reliability is uniformly high. Reliability appears to be only satisfactory for three categories: mental deficiency, organic brain syndrome (but not its subtypes), and alcoholism. The level of reliability is no better than fair for psychosis and schizophrenia and is poor for the remaining categories”. Seventh printing of the DSM-II, 1974 As described by Ronald Bayer, a psychiatrist and gay rights activist, specific protests by gay rights activists against the APA began in 1970, when the organization held its convention in San Francisco. The activists disrupted the conference by interrupting speakers and shouting down and ridiculing psychiatrists who viewed homosexuality as a mental disorder. In 1971, gay rights activist Frank Kameny worked with the Gay Liberation Front collective to demonstrate against the APA’s convention. At the 1971 conference, Kameny grabbed the microphone and yelled, “Psychiatry is the enemy incarnate. Psychiatry has waged a relentless war of extermination against us. You may take this as a declaration of war against you.” This activism occurred in the context of a broader anti-psychiatry movement that had come to the fore in the 1960s and was challenging the legitimacy of psychiatric diagnosis. Anti-psychiatry activists protested at the same APA conventions, with some shared slogans and intellectual foundations. Presented with data from researchers such as Alfred Kinsey and Evelyn Hooker, the seventh printing of the DSM-II, in 1974, no longer listed homosexuality as a category of disorder. After a vote by the APA trustees in 1973, and confirmed by the wider APA membership in 1974, the diagnosis was replaced with the category of “sexual orientation disturbance”. In 1974, the decision to create a new revision of the DSM was made, and Robert Spitzer was selected as chairman of the task force. The initial impetus was to make the DSM nomenclature consistent with the International Statistical Classification of Diseases and Related Health Problems (ICD), published by the World Health Organization. The revision took on a far wider mandate under the influence and control of Spitzer and his chosen committee members. One goal was to improve the uniformity and validity of psychiatric diagnosis in the wake of a number of critiques, including the famous Rosenhan experiment. There was also a need to standardize diagnostic practices within the US and with other countries after research showed that psychiatric diagnoses differed markedly between Europe and the USA. The establishment of these criteria was an attempt to facilitate the pharmaceutical regulatory process. The criteria adopted for many of the mental disorders were taken from the Research Diagnostic Criteria (RDC) and Feighner Criteria, which had just been developed by a group of research-orientated psychiatrists based primarily at Washington University in St. Louis and the New York State Psychiatric Institute. Other criteria, and potential new categories of disorder, were established by consensus during meetings of the committee, as chaired by Spitzer. A key aim was to base categorization on colloquial English descriptive language (which would be easier to use by federal administrative offices), rather than assumptions of etiology, although its categorical approach assumed each particular pattern of symptoms in a category reflected a particular underlying pathology (an approach described as “neo-Kraepelinian”). The psychodynamic or physiologic view was abandoned, in favor of a regulatory or legislative model. A new “multiaxial” system attempted to yield a picture more amenable to a statistical population census, rather than just a simple diagnosis. Spitzer argued that “mental disorders are a subset of medical disorders” but the task force decided on the DSM statement: “Each of the mental disorders is conceptualized as a clinically significant behavioral or psychological syndrome.” The personality disorders were placed on axis II along with mental retardation. The first draft of the DSM-III was prepared within a year. Many new categories of disorder were introduced, while some were deleted or changed. A number of the unpublished documents discussing and justifying the changes have recently come to light. Field trials sponsored by the U.S. National Institute of Mental Health (NIMH) were conducted between 1977 and 1979 to test the reliability of the new diagnoses. A controversy emerged regarding deletion of the concept of neurosis, a mainstream of psychoanalytic theory and therapy but seen as vague and unscientific by the DSM task force. Faced with enormous political opposition, the DSM-III was in serious danger of not being approved by the APA Board of Trustees unless “neurosis” was included in some capacity; a political compromise reinserted the term in parentheses after the word “disorder” in some cases. Additionally, the diagnosis of ego-dystonic homosexuality replaced the DSM-II category of “sexual orientation disturbance”. Finally published in 1980, the DSM-III was 494 pages and listed 265 diagnostic categories. It rapidly came into widespread international use and has been termed a revolution or transformation in psychiatry. However, Robert Spitzer later criticized his own work on it in an interview with Adam Curtis, saying it led to the medicalization of 20-30 percent of the population who may not have had any serious mental problems. When DSM-III was published, the developers made extensive claims about the reliability of the radically new diagnostic system they had devised, which relied on data from special field trials. However, according to a 1994 article by Stuart A. Kirk: Twenty years after the reliability problem became the central focus of DSM-III, there is still not a single multi-site study showing that DSM (any version) is routinely used with high reliably by regular mental health clinicians. Nor is there any credible evidence that any version of the manual has greatly increased its reliability beyond the previous version. There are important methodological problems that limit the generalisability of most reliability studies. Each reliability study is constrained by the training and supervision of the interviewers, their motivation and commitment to diagnostic accuracy, their prior skill, the homogeneity of the clinical setting in regard to patient mix and base rates, and the methodological rigor achieved by the investigator... In 1987, the DSM-III-R was published as a revision of the DSM-III, under the direction of Spitzer. Categories were renamed and reorganized, and significant changes in criteria were made. Six categories were deleted while others were added. Controversial diagnoses, such as pre-menstrual dysphoric disorder and masochistic personality disorder, were considered and discarded. “Sexual orientation disturbance” was also removed and was largely subsumed under “sexual disorder not otherwise specified”, which can include “persistent and marked distress about one’s sexual orientation.” Altogether, the DSM-III-R contained 292 diagnoses and was 567 pages long. Further efforts were made for the diagnoses to be purely descriptive, although the introductory text stated that for at least some disorders, “particularly the Personality Disorders, the criteria require much more inference on the part of the observer” (p. xxiii). In 1994, DSM-IV was published, listing 297 disorders in 886 pages. The task force was chaired by Allen Frances. A steering committee of 27 people was introduced, including four psychologists. The steering committee created 13 work groups of 5–16 members. Each work group had approximately 20 advisers.[clarification needed] The work groups conducted a three-step process: first, each group conducted an extensive literature review of their diagnoses; then, they requested data from researchers, conducting analyses to determine which criteria required change, with instructions to be conservative; finally, they conducted multicenter field trials relating diagnoses to clinical practice. A major change from previous versions was the inclusion of a clinical significance criterion to almost half of all the categories, which required that symptoms cause “clinically significant distress or impairment in social, occupational, or other important areas of functioning”. Some personality disorder diagnoses were deleted or moved to the appendix. A “text revision” of the DSM-IV, known as the DSM-IV-TR, was published in 2000. The diagnostic categories and the vast majority of the specific criteria for diagnosis were unchanged. The text sections giving extra information on each diagnosis were updated, as were some of the diagnostic codes to maintain consistency with the ICD. The DSM-IV-TR was organized into a five-part axial system. The first axis incorporated clinical disorders. The second axis covered personality disorders and intellectual disabilities. The remaining axes covered medical, psychosocial, environmental, and childhood factors functionally necessary to provide diagnostic criteria for health care assessments. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM), the DSM-V, was approved by the Board of Trustees of the American Psychiatric Association (APA) on December 1, 2012. Published on May 18, 2013, the DSM-5 contains extensively revised diagnoses and, in some cases, broadens diagnostic definitions while narrowing definitions in other cases. The DSM-5 is the first major edition of the manual in twenty years, and the Roman numerals numbering system has been discontinued to allow for greater clarity in regard to revision numbers. A significant change in the fifth edition is the proposed deletion of the subtypes of schizophrenia. During the revision process, the APA website periodically listed several sections of the DSM-5 for review and discussion. The DSM-IV is a categorical classification system. The categories are prototypes, and a patient with a close approximation to the prototype is said to have that disorder. DSM-IV states, “there is no assumption each category of mental disorder is a completely discrete entity with absolute boundaries” but isolated, low-grade and noncriterion (unlisted for a given disorder) symptoms are not given importance. Qualifiers are sometimes used, for example mild, moderate or severe forms of a disorder. For nearly half the disorders, symptoms must be sufficient to cause “clinically significant distress or impairment in social, occupational, or other important areas of functioning,” although DSM-IV-TR removed the distress criterion from tic disorders and several of the paraphilias due to their egosyntonic nature. Each category of disorder has a numeric code taken from the ICD coding system, used for health service (including insurance) administrative purposes. The DSM-IV organizes each psychiatric diagnosis into five dimensions (axes) relating to different aspects of disorder or disability: - Axis I: All psychological diagnostic categories except mental retardation and personality disorder - Axis II: Personality disorders and mental retardation - Axis III: General medical condition; acute medical conditions and physical disorders - Axis IV: Psychosocial and environmental factors contributing to the disorder - Axis V: Global Assessment of Functioning or Children’s Global Assessment Scale for children and teens under the age of 18 Common Axis II disorders include personality disorders: paranoid personality disorder, schizoid personality disorder, schizotypal personality disorder, borderline personality disorder, antisocial personality disorder, narcissistic personality disorder, histrionic personality disorder, avoidant personality disorder, dependent personality disorder, obsessive-compulsive personality disorder; and intellectual disabilities. Common Axis III disorders include brain injuries and other medical/physical disorders which may aggravate existing diseases or present symptoms similar to other disorders. The DSM-IV-TR states, because it is produced for the completion of federal legislative mandates, its use by people without clinical training can lead to inappropriate application of its contents. Appropriate use of the diagnostic criteria is said to require extensive clinical training, and its contents “cannot simply be applied in a cookbook fashion”. The APA notes diagnostic labels are primarily for use as a “convenient shorthand” among professionals. The DSM advises laypersons should consult the DSM only to obtain information, not to make diagnoses, and people who may have a mental disorder should be referred to psychological counseling or treatment. Further, a shared diagnosis or label may have different causes or require different treatments; for this reason the DSM contains no information regarding treatment or cause. The range of the DSM represents an extensive scope of psychiatric and psychological issues or conditions, and it is not exclusive to what may be considered “illnesses”. The DSM-IV does not specifically cite its sources, but there are four volumes of “sourcebooks” intended to be APA’s documentation of the guideline development process and supporting evidence, including literature reviews, data analyses and field trials. The Sourcebooks have been said to provide important insights into the character and quality of the decisions that led to the production of DSM-IV, and hence the scientific credibility of contemporary psychiatric classification. Reliability and validity concerns The revisions of the DSM from the 3rd Edition forward have been mainly concerned with diagnostic reliability—the degree to which different diagnosticians agree on a diagnosis. It was argued that a science of psychiatry can only advance if diagnosis is reliable. If clinicians and researchers frequently disagree about a diagnosis with a patient, then research into the causes and effective treatments of those disorders cannot advance. Hence, diagnostic reliability was a major concern of DSM-III. When the diagnostic reliability problem was thought to be solved, subsequent editions of the DSM were concerned mainly with “tweaking” the diagnostic criteria. Unfortunately, neither the issue of reliability (accurate measurement) or validity (do these disorders really exist) was settled. However, most psychiatric education post DSM-III focused on issues of treatment—especially drug treatment—and less on diagnostic concerns. In fact, Thomas R. Insel, M.D., Director of the NIMH, has recently stated the agency would no longer fund research projects that rely exclusively on DSM criteria due to its lack of validity. Field trials of DSM-5 brought the debate of reliability back into the limelight as some disorders showed poor reliability. For example Major Depressive Disorder a common mental illness had a poor reliability Kappa statistic of 0.28 indicating that clinicians frequently disagreed on this diagnosis in the same patients. The most reliable diagnosis was Major Neurocognitive Disorder with a Kappa of 0.78 By design, the DSM is primarily concerned with the signs and symptoms of mental disorders, rather than the underlying causes. It claims to collect them together based on statistical or clinical patterns. As such, it has been compared to a naturalist’s field guide to birds, with similar advantages and disadvantages. The lack of a causative or explanatory basis, however, is not specific to the DSM, but rather reflects a general lack of pathophysiological understanding of psychiatric disorders. As DSM-III chief architect Robert Spitzer and DSM-IV editor Michael First outlined in 2005, “little progress has been made toward understanding the pathophysiological processes and etiology of mental disorders. If anything, the research has shown the situation is even more complex than initially imagined, and we believe not enough is known to structure the classification of psychiatric disorders according to etiology.” The DSM’s focus on superficial symptoms is claimed to be largely a result of necessity (assuming such a manual is nevertheless produced), since there is no agreement on a more explanatory classification system. Reviewers note, however, that this approach is undermining research, including in genetics, because it results in the grouping of individuals who have very little in common except superficial criteria as per DSM or ICD diagnosis. Despite the lack of consensus on underlying causation, advocates for specific psychopathological paradigms have nonetheless faulted the current diagnostic scheme for not incorporating evidence-based models or findings from other areas of science. A recent example is evolutionary psychologists’ criticism that the DSM does not differentiate between genuine cognitive malfunctions and those induced by psychological adaptations, a key distinction within evolutionary psychology, but one widely challenged within general psychology. Another example is a strong operationalist viewpoint, which contends that reliance on operational definitions, as purported by the DSM, necessitates that intuitive concepts such as depression be replaced by specific measurable concepts before they are scientifically meaningful. One critic states of psychologists that “Instead of replacing ‘metaphysical’ terms such as ‘desire’ and ‘purpose’, they used it to legitimize them by giving them operational definitions...the initial, quite radical operationalist ideas eventually came to serve as little more than a ‘reassurance fetish’ (Koch 1992) for mainstream methodological practice.” A 2013 review published in the European archives of psychiatry and clinical neuroscience states “that psychiatry targets the phenomena of consciousness, which, unlike somatic symptoms and signs, cannot be grasped on the analogy with material thing-like objects.” As an example of the problem of the superficial characterization of psychiatric signs and symptoms, the authors gave the example of a patient saying they “feel depressed, sad, or down,” showing that such a statement could indicate various underlying experiences: “not only depressed mood but also, for instance, irritation, anger, loss of meaning, varieties of fatigue, ambivalence, ruminations of different kinds, hyper-reflectivity, thought pressure, psychic anxiety, varieties of depersonalization, and even voices with negative content, and so forth.” The structured interview comes with “danger of over confidence in the face value of the answers, as if a simple ‘yes’ or ‘no’ truly confirmed or denied the diagnostic criterion at issue.” The authors gave an example: A patient who was being administered the Structured Clinical Interview for the DSM-IV Axis I Disorders denied thought insertion, but during a “conversational, phenomenological interview,” a semi-structured interview tailored to the patient, the same patient admitted to experiencing thought insertion, along with a delusional elaboration. The authors suggested 2 reasons for this discrepancy: That the patient didn’t “recognize his own experience in the rather blunt, implicitly either/or formulation of the structured-interview question,” or the experience didn’t “fully articulate itself” until the patient started talking about his experiences. Despite caveats in the introduction to the DSM, it has long been argued that its system of classification makes unjustified categorical distinctions between disorders, and uses arbitrary cut-offs between normal and abnormal. A 2009 psychiatric review noted that attempts to demonstrate natural boundaries between related DSM syndromes, or between a common DSM syndrome and normality, have failed. Some argue that rather than a categorical approach, a fully dimensional, spectrum or complaint-oriented approach would better reflect the evidence. In addition, it is argued that the current approach based on exceeding a threshold of symptoms does not adequately take into account the context in which a person is living, and to what extent there is internal disorder of an individual versus a psychological response to adverse situations. The DSM does include a step (“Axis IV”) for outlining “Psychosocial and environmental factors contributing to the disorder” once someone is diagnosed with that particular disorder. Because an individual’s degree of impairment is often not correlated with symptom counts, and can stem from various individual and social factors, the DSM’s standard of distress or disability can often produce false positives. On the other hand, individuals who do not meet symptom counts may nevertheless experience comparable distress or disability in their life. Some psychiatrists also argue that current diagnostic standards rely on an exaggerated interpretation of neurophysiological findings and so understate the scientific importance of social-psychological variables. Advocating a more culturally sensitive approach to psychology, critics such as Carl Bell and Marcello Maviglia contend that the cultural and ethnic diversity of individuals is often discounted by researchers and service providers. In addition, current diagnostic guidelines have been criticized as having a fundamentally Euro-American outlook. Although these guidelines have been widely implemented, opponents argue that even when a diagnostic criteria set is accepted across different cultures, it does not necessarily indicate that the underlying constructs have any validity within those cultures; even reliable application can only demonstrate consistency, not legitimacy. Cross-cultural psychiatrist Arthur Kleinman contends that the Western bias is ironically illustrated in the introduction of cultural factors to the DSM-IV: the fact that disorders or concepts from non-Western or non-mainstream cultures are described as “culture-bound”, whereas standard psychiatric diagnoses are given no cultural qualification whatsoever, is to Kleinman revelatory of an underlying assumption that Western cultural phenomena are universal. Kleinman’s negative view toward the culture-bound syndrome is largely shared by other cross-cultural critics, common responses included both disappointment over the large number of documented non-Western mental disorders still left out, and frustration that even those included were often misinterpreted or misrepresented. Many mainstream psychiatrists have also been dissatisfied with these new culture-bound diagnoses, although not for the same reasons. Robert Spitzer, a lead architect of the DSM-III, has held the opinion that the addition of cultural formulations was an attempt to placate cultural critics, and that they lack any scientific motivation or support. Spitzer also posits that the new culture-bound diagnoses are rarely used in practice, maintaining that the standard diagnoses apply regardless of the culture involved. In general, the mainstream psychiatric opinion remains that if a diagnostic category is valid, cross-cultural factors are either irrelevant or are only significant to specific symptom presentations. One of the results was the development of the Azibo Nosology by Daudi Ajani Ya Azibo as an alternative to the DSM to treat African and African American patients. Medicalization and financial conflicts of interest It has also been alleged that the way the categories of the DSM are structured, as well as the substantial expansion of the number of categories, are representative of an increasing medicalization of human nature, which may be attributed to disease mongering by psychiatrists and pharmaceutical companies, the power and influence of the latter having grown dramatically in recent decades. Of the authors who selected and defined the DSM-IV psychiatric disorders, roughly half have had financial relationships with the pharmaceutical industry at one time, raising the prospect of a direct conflict of interest. The same article concludes that the connections between panel members and the drug companies were particularly strong in those diagnoses where drugs are the first line of treatment, such as schizophrenia and mood disorders, where 100% of the panel members had financial ties with the pharmaceutical industry. In 2005, then American Psychiatric Association President Steven Sharfstein released a statement in which he conceded that psychiatrists had “allowed the biopsychosocial model to become the bio-bio-bio model”. However, although the number of identified diagnoses has increased by more than 200% (from 106 in DSM-I to 365 in DSM-IV-TR), psychiatrists such as Zimmerman and Spitzer argue it almost entirely represents greater specification of the forms of pathology, thereby allowing better grouping of more similar patients. William Glasser, however, refers to the DSM as “phony diagnostic categories”, arguing that “it was developed to help psychiatrists – to help them make money”. In addition, the publishing of the DSM, with tightly guarded copyrights, has in itself earned over $100 million for the American Psychiatric Association. Clients and survivors \|This section needs additional citations for verification. (February 2014)\| A client is a person who accesses psychiatric services and may have been given a diagnosis from the DSM, while a survivor self-identifies as a person who has endured a psychiatric intervention and the mental health system (which may have involved involuntary commitment and involuntary treatment). Some individuals are relieved to find that they have a recognized condition that they can apply a name to and this has led to many people self-diagnosing. Others, however, question the accuracy of the diagnosis, or feel they have been given a “label” that invites social stigma and discrimination (the terms “mentalism” and “sanism” have been used to describe such discriminatory treatment). Diagnoses can become internalized and affect an individual’s self-identity, and some psychotherapists have found that the healing process can be inhibited and symptoms can worsen as a result. Some members of the psychiatric survivors movement (more broadly the consumer/survivor/ex-patient movement) actively campaign against their diagnoses, or the assumed implications, and/or against the DSM system in general. The Mad Pride movement has been particularly vocal in its criticism of the DSM. Additionally, it has been noted that the DSM often uses definitions and terminology that are inconsistent with a recovery model, and such content can erroneously imply excess psychopathology (e.g. multiple “comorbid” diagnoses) or chronicity. Psychiatrist Allen Frances has been critical of proposed revisions to the DSM-5. In a 2012 New York Times editorial, Frances warned that if this DSM version is issued unamended by the APA, it will “medicalize normality and result in a glut of unnecessary and harmful drug prescription.” In a December 2, 2012 blog post in Psychology Today, Frances lists the ten “most potentially harmful changes” to DSM-5: - Disruptive Mood Dysregulation Disorder, for temper tantrums - Major Depressive Disorder, includes normal grief - Minor Neurocognitive Disorder, for normal forgetting in old age - Adult Attention Deficit Disorder, encouraging psychiatric prescriptions of stimulants - Binge Eating Disorder, for excessive eating - Autism, defining the disorder more specifically, possibly leading to decreased rates of diagnosis and the disruption of school services - First time drug users will be lumped in with addicts - Behavioral Addictions, making a “mental disorder of everything we like to do a lot.” - Generalized Anxiety Disorder, includes everyday worries - Post-traumatic stress disorder, changes opening “the gate even further to the already existing problem of misdiagnosis of PTSD in forensic settings.” Frances and others have published debates on what they see as the six most essential questions in psychiatric diagnosis: - are they more like theoretical constructs or more like diseases - how to reach an agreed definition - whether the DSM-5 should take a cautious or conservative approach - the role of practical rather than scientific considerations - the issue of use by clinicians or researchers - whether an entirely different diagnostic system is required. In 2011,a psychologist Brent Robbins co-authored a national letter for the Society for Humanistic Psychology that has brought thousands into the public debate about the DSM. Approximately 14,000 individuals and mental health professionals have signed a petition in support of the letter. Thirteen other American Psychological Association divisions have endorsed the petition. Robbins has noted that under the new guidelines, certain responses to grief could be labeled as pathological disorders, instead of being recognized as being normal human experiences. - Relational disorder (proposed DSM-5 new diagnosis) - Classification of mental disorders - Chinese Classification and Diagnostic Criteria of Mental Disorders - DSM-IV Codes - Global Assessment of Functioning (GAF) Scale - International Statistical Classification of Diseases and Related Health Problems (ICD) - Psychodynamic Diagnostic Manual - Structured Clinical Interview for DSM-IV (SCID) - Diagnostic classification and rating scales used in psychiatry - Research Domain Criteria (RDoC), a framework being developed by the National Institute of Mental Health - Rosenhan experiment - Lane, Christopher. "The NIMH Withdraws Support for DSM-5". Psychology Today. - Allen Frances (17 May 2013). "The New Crisis in Confidence in Psychiatric Diagnosis". Annals of Internal Medicine. - Dalal PK, Sivakumar T. (2009) Moving towards ICD-11 and DSM-5: Concept and evolution of psychiatric classification. Indian Journal of Psychiatry, Volume 51, Issue 4, Page 310-319. - Kendell, R., Jablensky, A (January 2003). "Distinguishing Between the Validity and Utility of Psychiatric Diagnoses". American Journal of Psychiatry 160 (1): 4–12. doi:10.1176/appi.ajp.160.1.4. PMID 12505793. - Baca-Garcia, E., Perez-Rodriguez, M. M., Basurte-Villamor, I., Del Moral, A. L. F., Jimenez-Arriero, M. A., De Rivera, J. L. G., Saiz-Ruiz, J., Oquendo, M. A. (March 2007). "Diagnostic stability of psychiatric disorders in clinical practice". The British Journal of Psychiatry 190 (3): 210–6. doi:10.1192/bjp.bp.106.024026. PMID 17329740. - Pincus, H. A., Zarin, DA, First, M (1998). "Clinical Significance" and DSM-IV". Arch Gen Psychiatry 55 (12): 1145; author reply 1147–8. doi:10.1001/archpsyc.55.12.1145. PMID 9862559. - Greenberg, Gary (January 29, 2012). "The D.S.M.’s Troubled Revision". The New York Times. - Mezzich, Juan E. (2002). "International Surveys on the Use of ICD-10 and Related Diagnostic Systems" (guest editorial, abstract). Psychopathology 35 (2–3): 72–75. doi:10.1159/000065122. PMID 12145487. Retrieved 2008-09-02. - "Trademark Electronic Search System (TESS)". Retrieved 2010-02-03. - Dan J. Stein, Katharine A. Phillips, Derek Bolton, K.W.M Fulford, John Z. Sadler, and Kenneth S. Kendler What is a Mental/Psychiatric Disorder? From DSM-IV to DSM-V Psychol Med. 2010 November; 40(11): 1759–1765. - "Proposed Revision: Definition of a Mental Disorder". American Psychiatric Association. Archived from the original on January 8, 2013. Retrieved December 20, 2011. - History of the DSM Nathaniel Deyoung, Purdue University. Retrieved 9th Sept 2013 - Statistical manual for the use of institutions for the insane (1918) University of Michigan via Internet Archive - Greenberg, S; Shuman, DW; Meyer, RG (2004). "Unmasking forensic diagnosis". International Journal of Law and Psychiatry 27 (1): 1–15. doi:10.1016/j.ijlp.2004.01.001. PMID 15019764. - Houts A.C. (2000). "Fifty years of psychiatric nomenclature: Reflections on the 1943 War Department Technical Bulletin, Medical 203". Journal of Clinical Psychology 56 (7): 935–967. doi:10.1002/1097-4679(200007)56:7<935::AID-JCLP11>3.0.CO;2-8. PMID 10902952. - Grob, GN. (1991) Origins of DSM-I: a study in appearance and reality Am J Psychiatry. April;148(4):421–31. - John M. Oldham (2005). "Personality Disorders". FOCUS 3: 372–382. - Edsall, p. 247. - Edsall, p. 310. - Marcus, p. 58–59. - Medicating Children: ADHD and Pediatric Mental Health - Rick Mayes, Catherine Bagwell, Jennifer L. Erkulwater - Google Books. Books.google.com. 2009-01-01. ISBN 9780674031630. Retrieved 2013-12-03. - Stuart A, Kirk & Herb Kutchins (1994). "The Myth of the Reliability of DSM". Journal of Mind and Behavior, 15(1&2). - Mayes, R. & Horwitz, AV. (2005). "DSM-III and the revolution in the classification of mental illness". J Hist Behav Sci 41 (3): 249–67. doi:10.1002/jhbs.20103. PMID 15981242. - Wilson, M. (1993 March;). "DSM-III and the transformation of American psychiatry: a history". Am J Psychiatry 150 (3): 399–410. PMID 8434655. - Spitzer, Robert L.; Fleiss, Joseph L. (1974). "A re-analysis of the reliability of psychiatric diagnosis". British Journal of Psychiatry 125: 341–347. doi:10.1192/bjp.125.4.341. PMID 4425771. - Kirk, Stuart A.; Kutchins, Herb (1994). "The Myth of the Reliability of DSM". Journal of Mind and Behavior 15 (1&2): 71–86. Retrieved 2008-03-04. - Ronald Bayer Homosexuality and American Psychiatry: The Politics of Diagnosis (1981). - McCommon, B. (2006) Antipsychiatry and the Gay Rights Movement Psychiatr Serv 57:1809, December doi 10.1176/appi.ps.57.12.1809 - Rissmiller, DJ, D.O., Rissmiller, J. (2006) Letter in reply Psychiatr Serv 57:1809-a-1810, December 2006 doi 10.1176/appi.ps.57.12.1809-a - Spitzer, R.L. (1981). "The diagnostic status of homosexuality in DSM-III: a reformulation of the issues". Am J Psychiatry 138 (2): 210–215. PMID 7457641. - Speigel, A. (2005) The Dictionary of Disorder: How one man revolutionized of 2005-01-03. - Cooper, JE, Kendell, RE, Gurland, BJ, Sartorius, N, Farkas, T (April 1969). "Cross-national study of diagnosis of the mental disorders: some results from the first comparative investigation". The American Journal of Psychiatry. 10 Suppl: 21–9. PMID 5774702. - Lane, Christopher (2007). Shyness: How Normal Behavior Became a Sickness. Yale University Press. p. 263. ISBN 0-300-12446-5. - Spiegel, Alix. (18 January 2002.) “81 Words”. In Ira Glass (producer), This American Life. Chicago: Chicago Public Radio. - Allen Frances, Avram H. Mack, Ruth Ross, and Michael B. First (2000) The DSM-IV Classification and Psychopharmacology. - Schaffer, David (1996) A Participant’s Observations: Preparing DSM-IV Can J Psychiatry 1996;41:325–329. - APA Summary of Practice-Relevant Changes to the DSM-IV-TR. - "DSM-5 Gets APA’s Official Stamp of Approval". Medscape.com. Retrieved 2012-12-05. - Peter Kinderman (20 May 2013). "Explainer: what is the DSM?". The Conversation Australia. The Conversation Media Group. Retrieved 21 May 2013. - Sharon Jayson (12 May 2013). "Books blast new version of psychiatry’s bible, the DSM". USA Today. Retrieved 21 May 2013. - Catherine Pearson (20 May 2013). "DSM-5 Changes: What Parents Need To Know About The First Major Revision In Nearly 20 Years". The Huffington Post. Retrieved 21 May 2013. - "Schizophrenia and Other Psychotic Disorders". American Psychiatric Association. Retrieved May 6, 2010. - Lena H. Sun (17 May 2013). "Psychiatry’s revamped DSM guidebook fuels debate". The Washington Post. Retrieved 21 May 2013. - "Home". DSM-5 Development. American Psychiatric Association. 2012. Retrieved 21 May 2013. - Maser, JD. & Patterson, T. (2002) Spectrum and nosology: implications for DSM-5 Psychiatric Clinics of North America, December, 25(4)p855-885 - "DSM: Frequently Asked Questions \| psychiatry.org". Psych.org. Retrieved 2012-11-25. - "DSM-IV Sourcebook Volume 1". Appi.org. Retrieved 2013-12-03. - "DSM-IV Sourcebook Volume 2". Appi.org. Retrieved 2013-12-03. - "DSM-IV Sourcebook Volume 3". Appi.org. Retrieved 2013-12-03. - "DSM-IV Sourcebook Volume 4". Ajp.psychiatryonline.org. Retrieved 2013-12-03. - Poland, JS. (2001) Review of Volume 1 of DSM-IV sourcebook - Poland, JS. (2001) Review of vol 2 of DSM-IV sourcebook - Insel, Tom. "NIMH Director". Director’s Blog. NIMH Website. Retrieved 2 September 2013. - Freedman, Robert. "The Initial Field Trials of DSM-5: New Blooms and Old Thorns". - Paul R. McHugh (2005) Striving for Coherence: Psychiatry’s Efforts Over Classification JAMA. 2005;293(no.20)2526-2528. - Spitzer and First (2005) Classification of Psychiatric Disorders. JAMA.2005; 294: 1898-1899. - "Dominic Murphy, PhD; Steven Stich, PhD (1998) Darwin in the Madhouse". Ruccs.rutgers.edu. Retrieved 2013-12-03. - Leda Cosmides, PhD; John Tooby, PhD (1999) Toward an Evolutionary Taxonomy of Treatable Conditions “J of Abnormal Psychology.” 1999;108(3):453-464. - McNally, RJ (March 2001). "On Wakefield’s harmful dysfunction analysis of mental disorder". Behaviour research and therapy 39 (3): 309–14. doi:10.1016/S0005-7967(00)00068-1. PMID 11227812. - DW Hands (2004) On Operationalisms and Economics Journal of Economic Issues - Julie Nordgaard, Louis A. Sass (June 2013). "The psychiatric interview: validity, structure, and subjectivity". European archives of psychiatry and clinical neuroscience 263 (4): 353–364. doi:10.1007/s00406-012-0366-z. PMID 23001456. - Spitzer, Robert L, M.D., Williams, Janet B.W, D.S.W., First, Michael B, M.D., Gibbon, Miriam, M.S.W., Biometric Research - Maser, JD & Akiskal, HS. et al. (2002) Spectrum concepts in major mental disorders Psychiatric Clinics of North America, Vol. 25, Special issue 4 - Krueger, RF.; Watson, D.; Barlow, DH. et al. (2005). "Introduction to the Special Section: Toward a Dimensionally Based Taxonomy of Psychopathology". Journal of Abnormal Psychology 114 (4): 491–493. doi:10.1037/0021-843X.114.4.491. PMC 2242426. PMID 16351372. - Bentall, R. (2006). "Madness explained : Why we must reject the Kraepelinian paradigm and replace it with a ‘complaint-orientated’ approach to understanding mental illness". Medical hypotheses 66 (2): 220–233. doi:10.1016/j.mehy.2005.09.026. PMID 16300903. - Chodoff, P. (2005) Psychiatric Diagnosis: A 60-Year Perspective Psychiatric News June 3, 2005 Volume 40 Number 11, p17 - Wakefield, Jerome C.; PhD, MF; PhD, MB; PhD, DSW; Schmitz, Mark F.; First, Michael B.; MD; Horwitz, Allan V. (2007). "Extending the Bereavement Exclusion for Major Depression to Other Losses: Evidence From the National Comorbidity Survey". Arch Gen Psychiatry 64 (4): 433–440. doi:10.1001/archpsyc.64.4.433. PMID 17404120. - Spitzer, RL, Wakefield, JC. (1999 December;). "DSM-IV diagnostic criterion for clinical significance: does it help solve the false positives problem?". Am J Psychiatry 156 (12): 1856–64. PMID 10588397. - Widiger TA, Sankis LM (2000). "Adult psychopathology: issues and controversies". Annu Rev Psychol 51: 377–404. doi:10.1146/annurev.psych.51.1.377. PMID 10751976. - Shankar Vedantam, Psychiatry’s Missing Diagnosis: Patients’ Diversity Is Often Discounted Washington Post: Mind and Culture, June 26 - Kleinman A (1997). "Triumph or pyrrhic victory? The inclusion of culture in DSM-IV". Harv Rev Psychiatry 4 (6): 343–4. doi:10.3109/10673229709030563. PMID 9385013. - Bhugra, D. & Munro, A. (1997) Troublesome Disguises: Underdiagnosed Psychiatric Syndromes Blackwell Science Ltd - Atwell, Irene; Azibo, Daudi A. (1991). “Diagnosing personality disorder in Africans (Blacks) using the Azibo nosology: Two case studies.” Journal of Black Psychology, Vol 17(2), pp. 1–22. Abstract retrieved from APA PsychNet on December 27, 2013. - Healy D (2006) The Latest Mania: Selling Bipolar Disorder PLoS Med 3(4): e185. - Cosgrove, Lisa, Krimsky, Sheldon,Vijayaraghavan, Manisha, Schneider, Lisa, Financial Ties between DSM-IV Panel Members and the Pharmaceutical Industry - Sharfstein, SS. (2005) Big Pharma and American Psychiatry: The Good, the Bad, and the Ugly Psychiatric News August 19, 2005 Volume 40 Number 16 - "(Susan Bowman, 2006)". The National Psychologist. 2006-11-01. Retrieved 2013-12-03. - Sanism in Theory and Practice May 9/10, 2011. Richard Ingram, Centre for the Study of Gender, Social Inequities and Mental Health. Simon Fraser University, Canada - How Using the Dsm Causes Damage: A Client’s Report Journal of Humanistic Psychology, Vol. 41, No. 4, 36-56 (2001) - Michael T. Compton (2007) Recovery: Patients, Families, Communities Conference Report, Medscape Psychiatry & Mental Health, October 11–14, 2007 - Frances, A (May 11, 2012). Diagnosing the D.S.M.New York Times (opinion) - Frances, Allen J. (December 2, 2012). "DSM 5 Is Guide Not Bible—Ignore Its Ten Worst Changes APA approval of DSM-5 is a sad day for psychiatry". Psychology Today. Retrieved 9 March 2013. - Phillips, James et al.; Frances, Allen; Cerullo, Michael A; Chardavoyne, John; Decker, Hannah S; First, Michael B; Ghaemi, Nassir; Greenberg, Gary et al. (January 13, 2012). "The Six Most Essential Questions in Psychiatric Diagnosis: A Pluralogue. Part 1: Conceptual and Definitional Issues in Psychiatric Diagnosis". Philosophy, Ethics, and Humanities in Medicine (BioMed Central) 7 (3): 1–51. doi:10.1186/1747-5341-7-3. ISSN 1747-5341. PMC 3305603. PMID 22243994. Retrieved 24 January 2012. - "Professor co-authors letter about America’s mental health manual". Point Park University. December 12, 2011. - Erin Allday (November 26, 2011). "Revision of psychiatric manual under fire". San Francisco Chronicle. - Official DSM-5 development website - Topic Center from the Psychiatric Times: DSM-5 - DSM-IV-TR Official Site[dead link] - American Psychiatric Association - Diagnostic Criteria from DSM-IV-TR - The Multiaxial System of Diagnosis in DSM-IV Criteria - American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition: DSM-IV-TR®. American Psychiatric Pub. ISBN 978-0-89042-025-6. - Robert L. Spitzer (2002). Dsm-Iv-Tr Casebook: A Learning Companion to the Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Pub. ISBN 978-1-58562-059-3. - DSM-IV-TR In Action Powerpoint slide handouts by G. Scott Sparrow	2	56	5	1	0	0.742362	6	11,626
Von Hippel-Lindau syndrome is an inherited disorder characterized by the formation of tumors and cysts in many different parts of the body. Tumors called hemangioblastomas are characteristic of von Hippel-Lindau syndrome. These growths are made of newly formed blood vessels. Although they are typically noncancerous, they can cause serious or life-threatening complications. Hemangioblastomas that develop in the brain and spinal cord can cause headaches, vomiting, weakness, and a loss of muscle coordination . Hemangioblastomas can also occur in the retina which may cause vision loss. People with von Hippel-Lindau syndrome commonly develop cysts in the kidneys, pancreas, and genital tract. They are also at an increased risk of developing a type of kidney cancer called clear cell renal cell carcinoma and a type of pancreatic cancer called a pancreatic neuroendocrine tumor. Von Hippel-Lindau syndrome is also associated with a type of tumor called a pheochromocytoma, which most commonly occurs in the adrenal glands. Pheochromocytomas are usually noncancerous. They may cause no symptoms, but in some cases they are associated with headaches, panic attacks, excess sweating, or dangerously high blood pressure that may not respond to medication. Pheochromo-cytomas are particularly dangerous if they develop during pregnancy. About 10 percent of people with von Hippel-Lindau syndrome develop endolymphatic sac tumors, which are noncancerous tumors in the inner ear. These growths can cause hearing loss in one or both ears, as well as ringing in the ears and problems with balance. Without treatment, these tumors can cause sudden profound deafness. Mutations in the VHL gene cause von Hippel-Lindau syndrome. The VHL gene is a tumor suppressor gene, which means it keeps cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in this gene prevent production of the VHL protein or lead to the production of an abnormal version of the protein. An altered or missing VHL protein cannot effectively regulate cell survival and division. As a result, cells grow and divide uncontrollably to form the tumors and cysts that are characteristic of von Hippel-Lindau syndrome. We provide sequencing analysis for the VHL gene which is the only known gene to be associated with the forms of von Hippel-Lindau syndrome listed below. \|\|patients without pheochromocytoma; mutations grossly alter or lead to the absence of the proteins produced by the VHL gene. \|\|patients with pheochromocytoma and low risk of renal cell carcinoma; subtle or missense mutations of the VHL gene observed. \|\|patients with pheochromocytoma and high risk of renal cell carcinoma \|\|patients with familial pheochromocytoma without hemangioblastoma or renal cell carcinoma. Methodology: Sequencing of entire coding region Purpose: Confirmation of Clinical Diagnosis ICD-10 code Q85.8 Test Requisition: Sequencing Requisition CPT Codes: 81404 Cost: $396.00 Turn-around-time: 3-4 weeks 1. Lonser RR, Glenn GM, Walther M, Chew EY, Libutti SK, Linehan WM, Oldfield EH (2003). “von Hippel-Lindau disease”. Lancet. 361(9374):2059-67. Review. 2. Maher ER, Neumann HP, Richard S (2011). “von Hippel-Lindau disease: a clinical and scientific review”. Eur J Hum Genet.19(6):617-23. 3. Richard S, Graff J, Lindau J, Resche F (2004).”Von Hippel-Lindau disease”. Lancet. 363(9416):1231-4. 4. Sano T, Horiguchi H (2003). “Von Hippel-Lindau disease”. Microsc Res Tech. 60(2):159-64. Review. 5. Shehata BM, Stockwell CA, Castellano-Sanchez AA, Setzer S, Schmotzer CL, Robinson H (2008). “Von Hippel-Lindau (VHL) disease: an update on the clinico-pathologic and genetic aspects”. Adv Anat Pathol. 15(3):165-71. 6. Shuin T, Yamasaki I, Tamura K, Okuda H, Furihata M, Ashida S (2006). “Von Hippel-Lindau disease: molecular pathological basis, clinical criteria, genetic testing, clinical features of tumors and treatment”. Jpn J Clin Oncol. 36(6):337-43. Review.	2	3	2	0	2	0.783267	4	1,030
\|This article needs additional citations for verification. (January 2010) (Learn how and when to remove this template message)\| Types of classification Alternatively, diseases may be classified according to the organ system involved, though this is often complicated since many diseases affect more than one organ. A chief difficulty in nosology is that diseases often cannot be defined and classified clearly, especially when cause or pathogenesis are unknown. Thus diagnostic terms often only reflect a symptom or set of symptoms (syndrome). Traditionally diseases were defined as syndromes by their symptoms. When more information is available, they are also defined by the damage they produce. When cause is known, they are better defined by their cause, though still important are their characteristics. Probably the last described kind of diseases are molecular diseases, defined by their molecular characteristics. This was introduced in November 1949, with the seminal paper, "Sickle Cell Anemia, a Molecular Disease", in Science magazine, Linus Pauling, Harvey Itano and their collaborators laid the groundwork for establishing the field of molecular medicine. Several classifications of diseases have been historically proposed, and normally all of them assign a code to every supported disease. Some of them codify diseases following the path of the classification tree, and others like SNOMED use a multifactor classification system. The most known coding system is the World Health Organization ICD-Series, but there are other accepted classifications like DOCLE, NANDA or SNOMED Historically there were others like Berkson Coding System that are not maintained anymore. There are also coding systems for symptoms presents in the diseases and biological findings. They are normally included in medical dictionaries, also with a codification system. Some of them are MeSH (Medical Subject Headings), COSTART (Coding Symbols for Thesaurus of Adverse Reaction Terms) or MedDRA (Medical Dictionary for Regulatory Activities) Other systems like Current Procedural Terminology do not deal directly with diseases but with the related procedures. Extended nosology and general medical conditions Medical conditions, like diseases, can be defined by cause, pathogenesis (mechanism by which the disease is caused), or by a collection of symptoms, medical signs and biomarkers, particularly when the other two definitions are not available (idiopathic diseases). From a nosological point of view, medical conditions could be divided in disorders, diseases, syndromes, lesions and injuries, each one with some specific meaning: - In medicine, a disorder is a functional abnormality or disturbance. Medical disorders can be categorized into mental disorders, physical disorders, genetic disorders, emotional and behavioral disorders, and functional disorders. The term disorder is often considered more value-neutral and less stigmatizing than the terms disease or illness, and therefore is a preferred terminology in some circumstances. In mental health, the term mental disorder is used as a way of acknowledging the complex interaction of biological, social, and psychological factors in psychiatric conditions. However, the term disorder is also used in many other areas of medicine, primarily to identify physical disorders that are not caused by infectious organisms, such as metabolic disorders. - The term disease broadly refers to any condition that impairs the normal functioning of the body. For this reason, diseases are associated with dysfunctioning of the body's normal homeostatic process. Commonly, the term disease is used to refer specifically to infectious diseases, which are clinically evident diseases that result from the presence of pathogenic microbial agents, including viruses, bacteria, fungi, protozoa, multicellular organisms, and aberrant proteins known as prions. An infection that does not and will not produce clinically evident impairment of normal functioning, such as the presence of the normal bacteria and yeasts in the gut, or of a passenger virus, is not considered a disease. By contrast, an infection that is asymptomatic during its incubation period, but expected to produce symptoms later, is usually considered a disease. Non-infectious diseases are all other diseases, including most forms of cancer, heart disease, and genetic disease. - Illness and sickness are generally used as synonyms for disease. However, these terms are occasionally used to refer specifically to the patient's personal experience of his or her disease. In this model, it is possible for a person to have a disease without being ill (to have an objectively definable, but asymptomatic, medical condition), and to be ill without being diseased (such as when a person perceives a normal experience as a medical condition, or medicalizes a non-disease situation in his or her life). - Normally four main types of diseases are considered: pathogenic diseases, deficiency diseases, hereditary diseases, and physiological diseases. - A syndrome is the association of several medical signs, symptoms, and or other characteristics that often occur together. Some syndromes, such as Down syndrome, have only one cause; others, such as Parkinsonian syndrome, have multiple possible causes. In other cases, the cause of the syndrome is unknown. A familiar syndrome name often remains in use even after an underlying cause has been found, or when there are a number of different possible primary causes. - In cases of viral infections, like HIV, it is important to make a difference between the infection (considered as a disease, even while it is silent) and the associated symptoms (a syndrome). In the case of HIV the syndrome is named AIDS - Injury and lesions - Injury is damage to the body. This may be caused by accidents, falls, hits, weapons, and other causes. Major trauma is injury that has the potential to cause prolonged disability or death. Lesion is any abnormality in the tissue of an organism (in layman's terms, "damage"), usually caused by disease or trauma. Lesion is derived from the Latin word laesio meaning injury. Similar to the ICD-10 the World Health Organization produces the International Classification of External Causes of Injury (ICECI). Sequelae of resolved diseases sometimes are considered inside lesions and other times inside diseases. Some medical conditions cannot be classified in any of these groups, but they can still be important enough to be considered as medical conditions. For example, to be a carrier of a genetical disease, or a viral infection unable to progress to disease, normally is not considered inside any of the previous groups. Cases of infections able to progress, but with low possibilities, like latent tuberculosis, are also considered outside the category of diseases. The term "medical condition" can also be applied to physiological states outside the context of disease, as for example when referring to "symptoms of pregnancy". It can also refer to the normal residual scars of a disease after it has resolved, for example lungs fibrosis after a tuberculosis. Ayurveda is an elaborate system of medicine developed in India. In China the Huangdi Neijing is another ancient text. In the West, Hippocrates was one of the earliest writers on the subject of disease. The Metzora (parsha) also includes an early discussion of the treatment of skin diseases. In the 10th century the Arabian psychologist Najab ud-din Unhammad classified a nosology of nine major categories of mental disorders, which included 30 different mental illnesses in total. Some of the categories he described included obsessive-compulsive disorders, delusional disorders, degenerative diseases, involutional melancholia, and states of abnormal excitement.[verification needed] In the 18th century, the taxonomist Carl Linnaeus, Francois Boissier de Sauvages, and psychiatrist Philippe Pinel developed an early classification of physical illnesses. Thomas Sydenham's work in the late 17th century might also be considered a nosology. In the 19th century, Emil Kraepelin and then Jacques Bertillon developed their own nosologies. Bertillon's work, classifying causes of death, was a precursor of the modern code system, the International Classification of Diseases. - Nosology is used extensively in public health, to allow epidemiological studies of public health issues. Analysis of death certificates requires nosological coding of causes of death. - Nosological classifications are used in medical administration, such as filing of health insurance claims, and patient records, among others - Clinical coder - Diagnosis code - Differential diagnosis - International Statistical Classification of Diseases and Related Health Problems (ICD) - ICD-10 (ICD 10th Revision) - Medical classification - Pathology (study of disease) - Category:Diseases and disorders (Wikipedia's categorization of diseases) - L Pauling, H Itano, SJ Singer, I Wells. "Sickle Cell Anemia, a Molecular Disease". Science, 25 November 1949, vol. 110, no. 2865, pp. 543-548. - Babre, Deven (1 January 2010). "Medical Coding in Clinical Trials". Perspect Clin Res. 1 (1): 29–32. PMC . PMID 21829779 – via PubMed Central. - Starkstein S E, Leentjens A F G (2008). "The nosological position of apathy in clinical practice". J Neurol Neurosurg Psychiatry. 79: 1088–1092. doi:10.1136/jnnp.2007.136895. - Abenhaim, Lucien et al. The Prognostic Consequences in the Making of the Initial Medical Diagnosis of Work-Related Back Injuries. Spine Journal, 1995 - "Regents Prep: Living Environment: Homeostasis". Oswego City School District Regents Exam Prep Center. Retrieved 2012-11-12. - Millon, Theodore (2004), Masters of the Mind: Exploring the Story of Mental Illness from Ancient Times to the New Millennium, John Wiley & Sons, p. 38, ISBN 978-0-471-46985-8 - Smith R. In search of "non-disease." BMJ : British Medical Journal. 2002;324(7342):883-885. - Snider, G. L. (2003). "Nosology for Our Day". American Journal of Respiratory and Critical Care Medicine. 167 (5): 678–683. doi:10.1164/rccm.200203-204PP. - C. S. Herrman, The Bipolar Spectrum, SSRN (Social Science Research Network, 5 August 2010) - International Classification of Diseases by the World Health Organization.	2	7	1	0	0	0.703379	1	2,179
Make Cleft Lip and Palate Repair a Priority in July You’ll need a strong background in anatomy and medical terminology to code it right. July is National Cleft and Craniofacial Awareness and Prevention Month, making this a great time to learn more about these types of birth defects and how to code the surgical procedures surgeons perform to repair them. Know the Facts About Craniofacial Defects Orofacial clefts (clefts of the lip and palate) are the second-most common birth defects in the United States (Down syndrome is the first). A study published by the Centers for Disease Control and Prevention (CDC) and the National Birth Defects Prevention Network concluded that, between 2004-2006, one in 1,574 babies was born with a cleft palate and one in 940 babies was born with a cleft lip. A “cleft” is a gap between the baby’s upper lip and/or palate where cells and tissues didn’t join properly during the embryonic period. A baby’s facial features are formed by the end of the first trimester, making a cleft easy to detect in an anatomy screening ultrasound, generally between 18 and 26 weeks gestation. A cleft lip, as shown in Figure A (on page 22), can be a small slit (incomplete) or a large opening that goes through the lip into the nose (complete). And it can be on one side (unilateral) or both sides (bilateral) of the lip or, rarely, in the middle of the lip. A cleft palate, as shown in Figure B (on page 22), may involve both the front (hard) and back (soft) parts of the palate, or just one part. Left-sided clefts are more common than right-sided clefts. Approximately one-third of clefts involve the lip and alveolar ridge. Two-thirds extend through the entire palate. Some clefts may involve the lip and hard palate, but not the soft palate. Less common craniofacial defects are craniosynostosis (the baby’s skull fuses too early); microtia (the external portion of the ear does not form properly); and anotia (the external portion of the ear is missing). Complications Associated with Orofacial Defects After a diagnosis of a cleft lip and/or palate is made, there is nothing to do but wait. After the baby is born, surgery to repair the orofacial defect is necessary to allow for normal functions of the mouth — to eat and speak, for example. Other complications associated with clefts include ear infections, hearing loss, and misplaced teeth. Surgeons generally work with a care team to address these issues in a coordinated way. A care team may include: a surgeon, a speech-language pathologist, a pediatric dentist, an orthodontist, a geneticist, a nurse, a psychologist, an audiologist, a pediatrician, and other specialists. Clinton Morrison, MD, team leader at the Cleft and Craniofacial Center, University of Rochester Medicine’s Golisano Children’s Hospital, in Rochester, N.Y., says it’s important for coders to understand that surgery is medically necessary and not just cosmetic. “I think there is a common misconception that the issues surrounding cleft lip and palate are handled entirely at the initial operations, and that secondary issues are largely cosmetic,” Morrison said. “Really, many of the secondary surgeries are staged at specific intervals revolving around growth and development and intentionally not handled at the primary operations such as the nasal deformity, bony reconstruction of the gum line, and orthognathic jaw surgery. These secondary surgeries are medically necessary and related to the underlying congenital deformity.” Confirm Proper Procedure Coding Surgery to repair a cleft lip usually occurs in the first three to four months of life and is recommended within the first 12 months of life. Surgery to repair a cleft palate is recommended within the first 18 months of life, or earlier if possible. Medical codes for cleft lip and palate repairs are found under the Digestive System in the Surgery section of the CPT® codebook. Coding from the Operative Report Following is an operative report for surgery to repair a left, complete cleft lip and palate. The highlighted text provides the necessary information to properly code the procedure. Date of Surgery: * Surgeon: , MD Assistants: , MD Pre-operative Diagnosis: Left complete cleft lip and palate Post-operative Diagnosis: Same Operative Procedure: Left primary cleft lip repair with tip rhinoplasty and septal repositioning Indication for Procedure: * is an 18 wk.o. male who has been diagnosed with left complete cleft lip and palate. * is being taken to the operating room today for elective lip repair. Risks and benefits of the procedure were discussed. All questions were addressed. The family was eager to proceed. Findings: Left complete cleft lip and palate with associated cleft nasal deformity Immediate Postop Condition: Stable to PACU Disposition: PACU, admit Estimated Blood Loss: 5 cc IV Fluids Given: 50 cc Urine Output: Not recorded DVT Prophylaxis: Not indicated for age Description of Procedure: The patient was taken to the operating room and placed supine on the operating table. After the smooth and routine induction of general anesthesia, the patient was prepped and draped in the usual sterile fashion. A formal time-out was performed in the room and all were in agreement. I began by marking out a Fisher anatomical subunit cleft lip repair. This included a 3 mm substitution triangle above the white roll, as well as a Nordhoff type dry vermillion substitution triangle. Once I was happy with my markings, I tattooed the key points with ink and injected Marcaine with epinephrine for hemostasis. I inserted a throat pack. After waiting appropriately for hemostasis, I began with the medial lip incisions, including the back cut above the white roll. I then continued incision intraorally mucosally to the cleft margin. I then trimmed the marginal tissues. I then performed a limited muscle dissection medially taking care not to disrupt the marginal component of the orbicularis. I also freed the abnormal medial muscle attachments to the anterior nasal spine. Subsequently, I performed my cutaneous lateral lip incisions, heading to the cleft margin intraorally, and then extending along the alveolus laterally to allow the mucosa to advance. I elevated the abnormal muscle attachments to the maxilla in a supraperiosteal place, taking care to preserve the infraorbital nerves. I also released the muscle from the lateral ala. I then performed muscle dissection on the cutaneous and mucosal segments to free this up for approximation. Next, I dissected the anterior nasal spine to find the nasal septum, and performed a limited anterior septoplasty. I freed the septum from its abnormal attachments pulling it to the non-cleft side, and brought it to midline. I held this in its new location with a 4.0 PDS suture anchored to periosteum. I continued dissection into the nose elevating nasal mucosal flaps for nasal lining closure. I performed a limited tip rhinoplasty freeing the lower lateral cartilages from the skin envelope on the cleft side and performed interdomal sutures with 4.0 PDS to elevate the cleft alar cartilage and improve nasal projection. I then set about closing the cleft lip proper. I closed the oral mucosa with 5.0 interrupted chromic sutures. I also inset the Nordhoff flap with 5.0 chromic. I closed the nasal floor with 5.0 Monocryl interrupted sutures, and performed muscle closure with 4.0 Monocryl interrupted sutures. I then inset the cutaneous lip with 5.0 Monocryl. 8-0 Vicryl was used for cutaneous closure of the Fisher triangle and white roll. Dermabond was used for the vertical limb of closure. Using 5-0 PDS, I performed lower lateral redraping sutures in buried fashion. The wound was cleaned, the throat pack was removed, and he was transferred back to anesthesia for extubation. * tolerated the procedure well and was transferred to the recovery room awake and in good condition. I was present and scrubbed throughout the entire operation. Based on this documentation, coding is: 40700, 30460 Lip Repair (Cheiloplasty) CPT® code 40700 Plastic repair of cleft lip/nasal deformity; primary, partial or complete, unilateral describes a partial or complete repair of a cleft lip on one side. If the cleft lip affects both sides and is repaired in a single surgery, report 40701 Plastic repair of cleft lip/nasal deformity; primary bilateral 1-stage procedure. If the repair will require a second surgery, report 40702 Plastic repair of cleft lip/nasal deformity; primary bilateral, 1 of 2 stages for the first surgery and 40720 Plastic repair of cleft lip/nasal deformity; secondary, by recreation of defect and reclosure for the second surgery. If the secondary procedure is performed on both sides of the face, append modifier 50 Bilateral procedure to 40720. A parenthetical note instructs, “To report rhinoplasty only for nasal deformity secondary to congenital cleft lip, see 30460 [Rhinoplasty for nasal deformity secondary to congenital cleft lip and/or palate, including columellar lengthening; tip only], 30462 [Rhinoplasty for nasal deformity secondary to congenital cleft lip and/or palate, including columellar lengthening; tip, septum, osteotomies].” CPT® Assistant (December 2014, Vol. 24, Issue 12) elaborates on when it’s appropriate to use these codes: Question: A physician performs a primary lip and nose repair on an infant for cleft lip and palate deformity. Does the assignment of code 40700 … include the lip repair as well as repair and reshaping of the nose (rhinoplasty)? Answer: No. Code 40700 does not include cleft lip rhinoplasty, which may be reported separately with codes 30460 or 30462. In a cleft lip repair, because the defect is closed, the nostril sill [… ] is re-established and the nostril is narrowed. This procedure is referred to as the cleft lip/nasal deformity (ie, the soft tissue of the nose that may be corrected with the cleft lip repair) and it is included in code 40700. Codes 30460 … and 30462 … are used to report cleft lip rhinoplasty procedures involving cartilaginous work and columellar lengthening. These procedures are not considered an inclusive component of the plastic repair of cleft lip codes (40700-40720), and can be reported separately with codes 30460 and 30462, when performed. Palate and Uvula Repair Coding cleft palate repairs is more complicated because the structure is more complicated. The codes are: 42200 Palatoplasty for cleft palate, soft and/or hard palate only 42205 Palatoplasty for cleft palate, with closure of alveolar ridge; soft tissue only 42210 with bone graft to alveolar ridge (includes obtaining graft) 42215 Palatoplasty for cleft palate; major revision 42220 secondary lengthening procedure 42225 attachment pharyngeal flap 42235 Repair of anterior palate, including vomer flap CPT® Assistant (July 2014, Vol. 24, Issue 7) clarifies use of some of these codes in a Q&A. Question: Our surgeon performed 2-flap palatoplasty to repair a bilateral cleft palate. The surgeon repaired the hard palate using vomer flaps and during the same session performed an intravelar veloplasty to repair the soft palate. Alloderm was placed over the nasal lining around the junction of the soft and hard palate. Should we report both 42200 and 42235, or should we report 42200 alone (along with the unlisted code for the Alloderm placement)? Answer: If both the hard and soft palates (secondary palate) are repaired concomitantly, report code 42200 … because this includes the maneuvers necessary to effect closure of the hard and soft palates posterior to the incisive foramen. Code 42235 … is reported for the primary palate (anterior to the incisive foramen) and would not be appropriate to report in this case. The Alloderm placement is reported with code 42299, Unlisted procedure, palate, uvula. When reporting an unlisted code to describe a procedure or service, it is necessary to submit supporting documentation (eg, procedure report) along with the claim to provide an adequate description of the nature, extent, and the need for the procedure, as well as the time, effort, and equipment necessary to provide the service. Verify Diagnosis Codes Diagnosis codes for cleft lip and cleft palate are in the Q35-Q37 range in chapter 17 of the ICD-10-CM codebook. Selection is based on the location and extent of the defect. For example, coding for the adjacent operative note is Q36.9 Cleft lip, unilateral and Q30.2 Fissured, notched and cleft nose. Be Aware of Your Environment Craniofacial birth defects can be genetic or environmental. A 2014 surgeon general’s report confirmed that maternal smoking during early pregnancy can cause orofacial clefts in babies. According to the CDC, approximately 6 percent of orofacial clefts in the United Sates are caused by smoking during early pregnancy (i.e., first five weeks). “This means that over 400 babies could be born without orofacial clefts each year in the United States if women did not smoke early in pregnancy,” the CDC said. Parker S.E., Mai C.T., Canfield M.A., Rickard R., Wang Y., Meyer R.E., for the National Birth Defects Prevention Network. Updated national birth prevalence estimates for selected birth defects in the United States, 2004-2006. Birth Defects Research Part A: Clinical and Molecular Teratology. 2010; 88:1008–16 CDC Features, Life Stages & Population: www.cdc.gov/features/cleft-lip-prevention Latest posts by Renee Dustman (see all) - Flu Vaccine Coding and Billing Update - September 15, 2017 - With Days Remaining, New MIPS Resources - September 15, 2017 - 2018 QPP Proposed Rule Excludes More Clinicians from MIPS - September 7, 2017	4	26	19	0	3	0.522736	22	3,194
Read your latest personalised notifications No account yet? Start here Don't miss out Ok, got it Table of contents 3. Pathophysiology - Mechanism of Disease in Relation with the Cardiovascular System 4. Strategies for Diagnosing SARS-CoV-2 5. Protective Measures for Health Care Personnel and Patients in Cardiology 6. Triage Systems (Reorganization and Redistribution) 7. Diagnosis of Cardiovascular Conditions in COVID-19 Patients 8. Categorization of Emergency/Urgency of Invasive Procedures 9. Management/Treatment Pathways 10. Treatment of SARS-CoV-2 infection 11. Patient Information 13. List of Figures 14. List of Tables 15. List of References Last updated on 28 May 2020 Download document as PDF Submit your comments Download change history log The SARS-CoV‑2 causing COVID-19 has reached pandemic levels since March 2020. In the absence of vaccines or curative medical treatment, COVID-19 exerts an unprecedented global impact on public health and health care delivery. Owing to the unexpected need for large capacities of intensive care unit (ICU) beds with the ability to provide respiratory support and mechanical ventilation, temporary redistribution and reorganization of resources within hospitals have become necessary with relevant consequences for all medical specialties. In addition, protective measures against SARS-CoV‑2 gain particular significance for health care personnel (HCP) in direct contact with patients suffering from COVID-19 as well as for ambulatory and hospitalized patients without infection. In view of finite health care resources, health care providers are confronted with ethical considerations on how to prioritize access to care for individual patients as well as providing care for COVID-19 while not neglecting other life-threatening emergencies. Of note, assays to detect the virus in asymptomatic and symptomatic patients have important limitations in terms of sensitivity and specificity and will be complemented by tests for antibodies to identify those that already have been infected previously. SARS-CoV‑2 not only causes viral pneumonia but has major implications for the CV system. Patients with CV risk factors including male sex, advanced age, diabetes, hypertension and obesity as well as patients with established CV and cerebrovascular disease have been identified as particularly vulnerable populations with increased morbidity and mortality when suffering from COVID-19. Moreover, a considerable proportion of patients may develop cardiac injury in the context of COVID-19 which portends an increased risk of in-hospital mortality. Aside from arterial and venous thrombotic complications presenting as acute coronary syndromes (ACS) and venous thromboembolism (VTE), myocarditis plays an important role in patients with acute heart failure (HF). Moreover, a wide range of arrhythmias has been reported to complicate the course of COVID-19 including potential pro-arrhythmic effects of medical treatment targeted at COVID-19 and associated diseases. Owing to redistribution of health care resources, access to emergency treatment including reperfusion therapy may be affected depending on the severity of the epidemic at a local level. This is further aggravated by increasing concerns of delayed presentation of CV emergencies as patients are afraid to seek medical attention during the pandemic. For all these reasons, the European Society of Cardiology (ESC) has assembled a group of experts and practitioners with experience in the care of COVID-19 patients to provide a guidance document relevant for all aspects of CV care during the COVID-19 pandemic. While the document is comprehensive, it is important to point the reader to what the document is unable to do and what the limitations are: By 10 March 2020, 4296 persons world-wide had died from COVID-19 infection. By 7 May, 3.67 million had tested positive and more than 250 000 had died.1 The overall case-fatality rate is very country-specific for COVID-19 infection and depending on the phase of the epidemic, testing, registration, demography, healthcare capacity and governmental decisions.2 For most countries, it is uncertain how the registration is organized which makes the comparison of case-fatality rates between countries difficult. The excess death rate is a more reliable approach to compare the impact of the COVID-19 pandemic in different countries. An article in the New York Times demonstrated that there are large differences in the excess date rates. Germany has only an excess death rate of 4% which is surprisingly low in comparison with other countries or cities such as Italy (49%), the United Kingdom (65%) (UK), Spain (67%) or New York City (297%).3 Furthermore, COVID-19 infection has similar infection rates in both sexes; however, mortality rates are higher in men.4 Daily situation reports of the COVID-19 pandemic are disseminated by the WHO on their website. After the start of the COVID-19 pandemic in Wuhan, China, the epicenter of the epidemic is now in Europe. Figure 1 gives an overview of the evolution of laboratory-confirmed cases of COVID-19 in Europe. A large Chinese study analyzed 72 314 patient records which consisted of 44 672 (61.8%) confirmed cases, 16 186 (22.4%) suspected cases, and 889 (1.2%) asymptomatic cases.4 Among confirmed cases in this study, 12.8% had hypertension, 5.3% diabetes and 4.2% CVD.4 Strikingly, these numbers are lower than the prevalence of CVD risk factor in a typical Chinese population, but it is important to mention that these are not age-adjusted and 53% of cases had missing data on comorbidities.5 A study including 5700 patients from New York City, Long Island, and Westchester County (United States of America (USA)) reported a similar message that hypertension (56.6%), obesity (41.7%), diabetes (33.8%), coronary artery disease (11.1%) and congestive heart failure (6.9%) were the most common comorbidities.6 In comparison, the prevalence of hypertension, obesity and diabetes in the general population in the USA is respectively 45%, 42.4% and 10.5%.7-9 In early retrospective analysis based on data from 138 patients in Wuhan, China, approximately 50% of patients with COVID-19 infection had one or more comorbidities.10 Moreover, in patients admitted with a severe COVID-19 infection this proportion was as high as 72%.10 It remains vague whether diabetes, hypertension and CVD are causally linked or associated due to age.6 However, an important message is the fact that patients who develop severe disease are more likely to be vulnerable because of comorbid disease, including CVD. Ethnicity seems to be linked to susceptibility and outcomes of a COVID-19 infection.11, 12 Data from the United Kingdom show that one third of patients admitted to an intensive care unit due to COVID-19 infection were from an ethnic minority background.11, 13 Reports from the USA reveal the same message that ethnic minority groups have also been disproportionately affected by COVID-19 infections.12 There are multiple potential mechanisms such socioeconomic, cultural, or lifestyle factors and genetic predisposition. Also, pathophysiological differences in susceptibility or response to infection such as increased risk of admission for acute respiratory tract,14 an increased prevalence of vitamin D deficiency,15 increased inflammatory burden, and higher prevalence of cardiovascular risk factors such as insulin resistance and obesity than in white populations.11, 16 Verity et al.17 estimated that the case fatality ratio in China (adjusted for demography) was 1.38% but estimated case-fatality depends very much on the testing strategy of non-severe cases as many cases remain unverified. Case-fatality is highest in older age groups: The case fatality ratio was 0.32 in patients aged < 60 years of age in comparison with 6.4% in patients aged > 60 years.17 In Italy case fatality ranged from 0% below age 30 years to 3.5% for age 60–69 years and 20% above age 80 years.18 Higher mortality of a COVID-19 infection in older age groups was also revealed in an American dataset.6 This underlines the fact that increasing age is an important risk factor for severe course of COVID-19 infections. Underlying CVD is also associated with higher risk for a severe COVID-19 infection. In a retrospective cohort study of 72 314 cases in China19 patients with CV comorbidities had fivefold higher mortality risk (10.5%), however, without age adjustment. Multinational cohort analyses will give more insights in the prevalence and risk of CV comorbidities in COVID-19 infection. There are several potential mechanisms explaining why the course of the disease is more severe in patients with underlying CV risk factors and CVD.20 These are described in sections 3 and 9. Preceding coronaviruses outbreaks such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) were associated with a significant burden of CV comorbidities and complications.20,21 Common cardiac complications in SARS were hypotension, myocarditis, arrhythmias, and sudden cardiac death (SCD).22,23 Diagnostic workup during SARS infection revealed electrocardiographic changes, sub-clinical left ventricular (LV) diastolic impairment and troponin elevation. MERS was associated with myocarditis and HF.22 COVID-19 infection seems to have comparable cardiac manifestations. Autopsies of patients with COVID-19 infection revealed infiltration of the myocardium by interstitial mononuclear inflammatory cells.24 COVID-19 infections are associated with increased cardiac biomarkers levels due to myocardial injury.24-26 The myocardial injury and the increased levels of biomarkers are likely associated with infection-induced myocarditis and ischaemia.27 In a study by Shi et al.26 in 416 patients of whom 57 died, cardiac injury was a common finding (19.7%). In the patients who died, 10.6% had coronary artery disease (CAD), 4.1% had HF, and 5.3% had cerebrovascular disease.26 Moreover, in multivariable adjusted models, cardiac injury was significantly and independently associated with mortality (hazard ratio [HR]: 4.26).26 Similarly, in a study by Guo et al.25, elevated troponin T levels due to cardiac injury was associated with significantly higher mortality. These patients were more likely to be men, to be older and to have more comorbidities such as hypertension, coronary heart disease.25 Severe COVID-19 infections are also potentially associated with cardiac arrhythmias at least in part due to infection-related myocarditis.10 Next to acute complications, COVID-19 infection may also be linked with an elevated long-term CV risk. It is well established that in patients with pneumonia, hypercoagulability and systemic inflammatory activity can persist for a long period.2,20 Moreover, follow-up studies of the SARS epidemic demonstrated that patients with a history of SARS-coronavirus infection often had hyperlipidaemia, CV system abnormalities or glucose metabolism disorders.20-22 However, SARS was treated with pulses of methylprednisolone which could be the explanation for the long-term perturbation of lipid metabolism rather than a consequence of the infection itself.24 Naturally, no long term effects of a COVID-19 infection are known yet but these effects of a SARS-coronavirus infection justify surveillance of recovered COVID-19 infection patients. COVID-19 is caused by a novel betacoronavirus officially named by the WHO as SARS-CoV‑2. Coronaviruses are enveloped, single-stranded ribonucleic acid (RNA) viruses with surface projections that correspond to surface spike proteins.28 The natural reservoir of SARS-CoV‑2 seems to be the chrysanthemum bat,29 but the intermediate host remains unclear. SARS-CoV‑2 is highly virulent and the transmission capacity is greater than the previous SARS virus (outbreak in 2003), with high abundance in infected people (up to a billion RNA copies/mL of sputum) and long-term stability on contaminated surfaces.30 SARS-CoV‑2 is more stable on plastic and stainless steel than on copper and cardboard, and viable virus has been detected for up to 72 hours after application to these surfaces.30 While the infectivity of SARS-CoV‑2 is greater than that of influenza or SARS-coronavirus, more data are needed for accurate assessment.31 Transmission occurs primarily by a combination of spread by droplet, and direct and indirect contact, and may possibly be airborne as well. The viral incubation period is 2–14 days, (mostly 3–7 days).32 It is contagious during the latency period. SARS-CoV‑2 can initially be detected 1–2 days prior to onset of upper respiratory tract symptoms. Mild cases were found to have an early viral clearance, with 90% of these patients repeatedly testing negative on reverse transcriptase polymerase chain reaction (RT-PCR) by day 10 post-onset. By contrast, all severe cases still tested positive at or beyond day 10 post-onset.33 Median duration of viral shedding was 20 days (interquartile range: 17–24) in survivors.34 The longest observed duration of viral shedding in survivors was 37 days.34 The host receptor through which SARS-CoV‑2 enters cells to trigger infection is ACE2 (Figure 2).35,36 ACE2 is a multifunctional protein. Its primary physiological role is the enzymatic conversion of angiotensin (Ang) II to Ang-(1–7), and Ang I to Ang-(1–9), which are CV protective peptides.37 In the context of COVID-19, however, ACE2 is also involved in SARS through its function as the coronavirus receptor.38 Binding of the SARS-CoV‑2 spike protein to ACE2 facilitates virus entry into lung alveolar epithelial cells, where it is highly expressed, through processes involving cell surface associated transmembrane protein serine 2 (TMPRSS2)39 (Figure 2). Within the host cell cytoplasm, the viral genome RNA is released and replicates leading to newly formed genomic RNA, which is processed into virion-containing vesicles that fuse with the cell membrane to release the virus. SARS-CoV‑2 is spread mainly through the respiratory tract by droplets, respiratory secretions and direct contact. The RAS/ACE2 seems to be disrupted by SARS-CoV‑2 infection, which likely plays a pathogenic role in severe lung injury and respiratory failure in COVID-19.40 In addition to the lungs, ACE2 is highly expressed in human heart, vessels and gastrointestinal tract.41,42 COVID-19 is primarily a respiratory disease, but many patients also have CVD, including hypertension, acute cardiac injury and myocarditis (Figure 3 from Guzik et al.43).21,44 This may be secondary to the lung disease, since acute lung injury itself leads to increased cardiac workload and can be problematic especially in patients with pre-existing HF. CVD may also be a primary phenomenon considering the important (patho)physiological role of the RAS/ACE2 in the CV system and the fact that ACE2 is expressed in human heart, vascular cells and pericytes.45 The prevalence of pre-existing hypertension seems to be higher in COVID-19 patients who develop severe disease versus those who do not.34,46 This seems to also be true for acute respiratory distress syndrome (ARDS) or death. These earlier studies were not age-adjusted and the impact of age still needs to be addressed. The mechanisms underlying potential relationships between hypertension and COVID-19 are thought most likely to relate confounding due to age and associated comorbidities.47 Previous speculation proposed that treatment of hypertension with RAS inhibitors may influence SARS-CoV‑2 binding to ACE2, promoting disease.48 This is based on some experimental findings that RAS inhibitors cause a compensatory increase in tissue levels of ACE2,49 and that ACE-inhibitors or ARBs may be detrimental in patients exposed to SARS-CoV-2.50 It is however important to emphasize that there is no clear evidence that using angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) lead to up-regulation of ACE2 in human tissues. The available data from blood samples suggest that there is no association between circulating levels of ACE2 and use of RAAS antagonists.51 It also appears that in experimental models ARBs may have a potentially protective influence.52,53 A recent observational study of over 8910 patients from 169 hospitals in Asia, Europe, and North America, did not show a harmful association of ACEIs or ARBs with in-hospital mortality,54 while a Wuhan study demonstrated that in 1128 hospitalized patients use of ACEI/ARB was associated with lower risk of COVID-19 infection or serious complication or deaths from COVID-19 infection.47, 54-60 The recent data are all-cause mortality compared with ACEI/ARB non-users.60 This is in line with prior guidance from major CV Societies, that stated that patients on ACEIs or ARBs should not stop their treatment.51,61 Myocarditis appears in COVID-19 patients several days after initiation of fever. This indicates myocardial damage caused by viral infection. Mechanisms of SARS-CoV-2-induced myocardial injury may be related to upregulation of ACE2 in the heart and coronary vessels.44,61 Respiratory failure and hypoxia in COVID-19 may also cause damage to the myocardium and immune mechanisms of myocardial inflammation may be especially important.27,44,61 For example, cardiac injury leads to activation of the innate immune response with release of proinflammatory cytokines, as well as to the activation of adaptive auto-immune type mechanisms through molecular mimicry. Inflammatory mechanisms and activation of immune responses underlie a large range of CVDs including atherosclerosis, HF and hypertension.62,63 This dysregulation may have different degrees in COVID-19. Firstly another receptor through which SARS-CoV‑2 may enter cells is cluster of differentiation 209 (CD209).64 CD209 is expressed in macrophages promoting virus invasion into immune cells in cardiac and vascular tissues. More importantly, in severe cases of COVID-19, systemic increases of numerous cytokines including IL-6 IL-2, IL-7, granulocyte colony-stimulating factor, C-X-C motif chemokine 10 (CXCL10), chemokine (C-C motif) ligand 2, and tumour necrosis factor-α have all been observed in subjects with COVID-19,65 which corresponds to the characteristics of a cytokine release syndrome (CRS). Altered vascular permeability can result in non-cardiogenic pulmonary oedema and promotes ARDS as well as multi-organ dysfunction. High serum IL-6 levels are a common feature in CRS. IL-6 is a clinical predictor of mortality in COVID-19.66 Thus IL-6 targeting may be permissive for use in COVID-19 to tackle the CRS. Finally, it has been shown that hypertension is associated with circulating lymphocytes in patients67 and CD8 T cell dysfunction with development of CVD.68 CD8 T cells are a pillar of antiviral immunity, thus their dysfunction can make the organism inefficiently target virally infected cells. As evidenced by previous epidemics, including SARS and MERS, highly sensitive and specific laboratory diagnostics are essential for case identification, contact tracing, animal source finding, and efficient and rational containment measures.69 Precise case identification is essential in order to isolate vulnerable individuals. Based on current epidemiological analysis, CVD conveys risk of a more severe outcome of COVID-19;21,44 therefore, testing should be particularly widely considered in CVD patients. Moreover, in similarity to influenza, efficient testing of carers and people in contact with high risk patients may allow protection of subjects with multiple comorbidities. The decision to test should be based on clinical and epidemiological factors and linked to an assessment of the likelihood of infection, in particular when availability of tests is limited. Available testing strategies are outlined below (Table 1). While isolation of the virus itself using electron microscopy would be the most specific diagnostics, it requires biosafety level-3 facilities which are not available in most healthcare institutions. Serum antibody and antigen detection tests would be the easiest and fastest, but have not yet been validated, and there may be cross-reactivity with other coronaviruses, especially SARS-coronavirus. Furthermore, antibodies are not measurable in the initial phase of the infection. Therefore, real-time PCR remains the most useful laboratory diagnostic test for COVID-19 worldwide. Comparative specificity and sensitivity of these tests needs to be carefully assessed, when more data is available. It is important to note that negative results of molecular testing (RT-PCR) do not preclude SARS-CoV‑2 infection and should not be used as the sole basis for patient management decisions but must be combined with clinical observations, patient history, and epidemiological information. There are a number of factors that may lead to a negative result in an infected individual. These include poor quality of the specimen (small material), collection late or very early in the infection, poor handling/shipping as well as technical reasons inherent in the test such as virus mutation or PCR inhibition. Therefore, retesting is recommended after 48 hours in clinically suspected cases that test negative. It is essential that adequate standard operating procedures are in use and that staff are trained for appropriate specimen collection, storage, packaging, and transport. This must be observed in order for testing to be reliable and safe for staff and patients. The optimal testing material includes nasal swab rather than pharyngeal. In order to obtain a sufficiently deep swab, the sample must be obtained by experienced and trained staff. According to a comparative study using lung CT as comparator, the sensitivity of nasopharyngeal swab may be limited to 60–70%.72 It has also been concluded that the test does not seem to change clinical decisions and diagnostic considerations in subjects with pretest probability exceeding 60–70% (e.g. subjects with positive epidemiological and clinical criteria fulfilled). This however does not indicate that such tests should not be performed to confirm infection, but it is important that the test is repeated if there is clinical suspicion of COVID-19 infection. Lung CT has a high sensitivity for diagnosis of COVID-19 in hospitalized patients who are RT-PCR positive. In a study undertaken between 06 January and 06 February 2020 in Tongji Hospital, Wuhan, China, in a population of 1014 patients – when using RT-PCR as a reference, the sensitivity of lung CT imaging for COVID-19 was 97%.72 Importantly, 60–93% of patients had initial positive lung CT consistent with COVID-19 before the initial positive RT-PCR results. Nucleic acid shedding is also an important tool to verify patient improvement, although 42% of patients showed improvement of follow-up lung CT scans before the RT-PCR results turning negative.72 It is important, however, that nucleic acid shedding does not always indicate presence of live virus. Widespread testing strategies included drive-through testing in South Korea. However, testing capacity may be insufficient. Thus testing priorities have been suggested by individual health systems such as one proposed by Centers for Disease Control for the United States (US) (Table 2). Sample pooling strategy has been proposed in relation to sample collection as the most cost-efficient tool for population-wide screening, for example at airports. Taking into account that there are only a few documents regarding type and level of protection of HCP, the ESC Guidance Document considered the WHO document,73 the American Center for Disease Control and Prevention guidelines on COVID-19,74 the European Centre for Disease Control guidelines on COVID-19;75 but also Chinese data76,77 and experiences from European countries with the largest outbreaks of COVID-19. Importantly, the ESC Guidance document aims to suggest a high level of protection for HCP in the worst transmission scenario of SARS-CoV‑2 infection. Different settings, such as countries with no cases, countries with sporadic cases, countries experiencing case clusters in time, geographic location and/or common exposure should prepare to respond to different public health scenarios, recognizing that there is no one size fits all approach to managing cases and outbreaks of COVID-19. Each country should dynamically assess its risk and rapidly change the definitions according to their local situation, depending on the phase of the epidemic, demography, healthcare capacity, and governmental/local health authorities’ decisions. In a recent report related to 138 confirmed COVID-19 cases, 41.3% were considered acquired infection from the hospital, and more than 70% of these patients were HCP.78 Health care workers are in fact at increased risk for contracting the virus, as demonstrated by Wu and colleagues, who reported that in China 1716 of the 44 672 (3.8%) infected individuals were professionals (see later).19 Generally, protection against COVID-19 needs to be differentiated according to the level of risk based on patient presentation, type of procedures and interaction and HCP risk status. Table 3 provides general recommendations. The precautions taken depend on COVID-19 case definition as defined in Table 4. The level of protection of HCP depends on patient risk status, setting and procedure performed (Table 5). In addition to personal protective equipment (PPE) for HCP, all suspected/probable or confirmed SARS-CoV‑2 patients should wear a disposable surgical mask when in room with HCP or other persons. FFP3, FFP2 and N95 are designed to achieve a very close facial fit and very efficient filtration of airborne particles. Powered air-purifying respirator (PAPR) is a type of PPE consisting of a respirator in the form of a hood, which takes ambient air contaminated with pathogens, actively filters these hazards, and delivers the clean air to the user's face and mouth (Figure 4). All HCP should be well-versed in proper techniques for donning and removing PPE including eye protection (Figure 5 and Figure 6).77 Because there is no time to wait for nasopharyngeal swab result, the procedure should be performed in a dedicated COVID-19 catheterization laboratory if available and patients should be triaged according to Table 4. In regions with high rates of community transmission, it is reasonable to regard all patients as possible SARS-CoV‑2 positive and HCP protected accordingly (Table 5) Most of the electrophysiology (EP) activity is being markedly reduced or suspended in areas that have been severely affected by COVID-19 outbreak. Residual EP activity should be maintained for selected categories of patients (Table 7 and Table 13). Protection of the HCP:83 The major issue is that the viral load in the airway is probably very high and very contagious.84 This poses significant risks for HCP performing non-invasive ventilation by CPAP or invasive ventilation with orotracheal intubation. Accordingly, a high level of vigilance is necessary to prevent contracting the infection when managing patients using CPAP, when intubation is performed or the transesophageal echocardiogram (TEE) probe is inserted. It is now well known that CV patients who develop a COVID-19 infection have a higher risk of poor in-hospital outcome.20 This is why it is mandatory to effectively protect them from being in contact with infected subjects whose COVID-19-related symptoms are still not evident or not specific. Wang et al reported a significant percentage of hospital-associated transmission of the virus (12.3% of all patients) in a cohort of hospitalized patients with novel coronavirus-infected pneumonia in Wuhan, China at the start of the pandemic.10 Based on this data, patients accessing the hospital for an acute cardiac disease with no signs or symptoms of viral infection should complete their diagnostic workflow in a clean area and finally access a COVID-19-free ward. All the measures to keep chronic cardiac outpatients at home as much as possible as well as to limit in-hospital stay of cardiac patients to the shortest acceptable time should be implemented. The adoption of a restrictive visitor policy is also strongly recommended.85 Elective procedures should be avoided during the current COVID-19 pandemic so as not to overload the health system or increase the risk of disease propagation. In this context, in order to minimize risk for COVID-19 transmission, the use of telemedicine is highly desirable especially for vulnerable groups, such as older patients. Additionally, telemedicine provides an opportunity for tele-consultations with different specialists and professionals, thus allowing patients to receive a comprehensive therapeutic approach without moving from home to the outpatient clinic or to the hospital. Also telerehabilitation (or home based rehabilitation with telephone contact with the rehab team) is an option for patients discharged from the hospital after an acute event. Finally telemedical follow up of HF and device patients is becoming more and more standard and may be considered. Telemedicine has been considered relevant in contributing to viral outbreak containment while preventing patient health from deteriorating because of misdiagnosed or mistreated CVDs.86 Beyond telemedicine ‘home care’ and ‘mobile clinics’ are currently proposed as a way to prevent unnecessary movement of patients towards hospitals, provided that nurses and physicians wear the appropriate PPE. This solution could prevent clinical instability of many cardiac diseases (i.e. chronic HF), assure patient adherence to long-term treatment and contribute to a ‘community-centred’ form of care that might be more advantageous than a purely ‘patient-centred’ care model, where only infected, hospitalized patients consume most of the available resources of the healthcare system.87 When CV patients temporarily access the hospital facilities for diagnostic or therapeutic reasons they should always protect themselves by systematically wearing surgical masks, practicing social distancing and appropriate washing/cleaning their hands with alcoholic solutions, which should be provided by the hospital staff.88 Patients should also be protected by HCP donning surgical masks, depending on the local community prevalence of COVID-19. Patient triage is of paramount importance when medical services are overwhelmed by a pandemic and healthcare resources are limited. This is particularly true for the COVID-19 epidemic, whose outbreak is currently seriously challenging the healthcare systems across the world. Some peculiar aspects of this pandemic, potentially affecting triage of cardiac patients, should be outlined: Hub centres are committed to provide acute reperfusion to all patients requiring an urgent PCI. Patients with STEMI or high-risk NSTEMI should be triaged by the emergency medical services team and timely transported to hub centres, if feasible. As a general rule we recommend that the number of catheterization laboratories available for primary PCI should not be reduced during the pandemic, to avoid an increase in door-to-balloon time, to diminish the risk of infection during transfer for both professionals and/or patients, and to unload the health care system. Regional STEMI networks should adapt to dynamic changes of the pandemic in every region according to local medical and logistic resources. As an example, in Lombardy, Italy, a system of specialized COVID-19 referral hospitals has been defined at the start of the virus epidemic, reducing by more than 60% the number of previous referral centres with 24 hour/7 day capacity to perform a primary PCI.91 Active shifts have been also assigned to interventional cardiologists, in order to satisfy the foreseen increased number of STEMI or NSTEMI patients arriving at the hospital.92 The ambulance networks also need to be reorganized in order to bring the patients straight to the COVID-19 referral hospital, skipping the spoke centres from where a secondary transportation could be difficult to arrange and time-consuming. The major objective of this rearrangement is primarily to allow for a timely treatment of the acute CVD, despite the unavoidable epidemic-related delays. It is also functional to secure patients to COVID-19-dedicated hospitals or to hospitals with isolated COVID-19 dedicated facilities when patients with acute CVDs are highly suspect for COVID-19 infection. China has been the first country to receive specific recommendations for a transport work programme directly by the country Health Authorities.93 In countries highly affected by the COVID-19 pandemic EDs have been re-organized to provide possible COVID-19 patients with dedicated access areas and isolated facilities from their first arrival to the hospital. Local protocols for rapidly triaging patients with respiratory symptoms should be issued with the aim of differentiating patients with CVDs from COVID-19 patients. In China for example patients with no geographical or family history of virus infection, fever, respiratory symptoms, fatigue or diarrhoea were considered ‘COVID-19 unlikely’ and their CVD was usually treated with standard protocols.94 A check-list should be adopted to quickly differentiate patients with possible or probable COVID-19 infection from non-infected patients (Table 3 and Table 4). Patients with mild, stable diseases should be discharged from the ED as soon as possible (Figure 8), with the suggestion to stay at home in quarantine if a COVID-19 infection is suspected or confirmed. Conversely, patients in need of hospital admission for acute CVD with concomitant possible/probable SARS-CoV‑2 infection (Table 4) should rapidly undergo testing and be managed as SARS-CoV-2 infected until they have two negative tests within 48 hours. Patients in need of hospital admission not suspected of SARS-CoV‑2 infection can be managed according to standard of care. ICU beds are mainly devoted to complicated COVID-19 patients in need of intensive care, who frequently present with underlying CVD and poor prognosis.19,95 Provided that in a pandemic situation the ethical value of maximizing benefits is recognized as the most relevant to drive resource allocation,96 this might invariably disadvantage patients with advanced age and more severe CVD who will not be prioritized for advanced care provision. Acute CV patients who tested negative (and without clinical suspicion for) COVID-19 infection, should be accurately identified and admitted, if feasible, to dedicated areas ICUs or ICCUs free from COVID-19 patients (‘clean’ ICUs or ICCUs), particularly in COVID-19 referral hospitals. If a fully ‘clean’ facility is not available, because of overwhelming numbers of COVID-19 patients, it should be guaranteed that airborne isolation rooms are set up in the facility, effectively separating patients with COVID-19 infection from all the others to minimize their infective risk. Such organization should also allow for adequate protection of HCP and well-defined pathways to and from the isolated rooms, in order to contain the spread of infection.97 Intermediate care units (also identifiable as ICCUs level II or I according to the Association for Acute Cardiovascular Care position paper98) share the same problems of ICUs, being usually equipped with CPAP machines for non-invasive ventilation. The same solutions already discussed for ICUs are therefore also applicable to intermediate care units. Triaging CV patients in need of CPAP from COVID-19 patients with pneumonia is mandatory, but still isolated rooms for COVID-19 positive CV patients (with acute HF for example) different from rooms for COVID-19 negative CV patients are very much needed. The symptom of chest pain or tightness is common in patients with active COVID-19 infection. It is usually poorly localized and may be associated with breathlessness due to the underlying pneumonia. Associated profound hypoxaemia together with tachycardia may result in chest pain and electrocardiographic changes suggestive of myocardial ischaemia. Where biomarkers are altered, Type 2 myocardial infarction (MI) may be suggested. Patients with ACS do, however, experience the more typical symptoms related to ischaemia. The presence of a COVID-19 infection can make the differential diagnosis more difficult, as shortness of breath and respiratory symptoms may be present and may precede or precipitate cardiac signs and symptoms. Dyspnoea (shortness of breath) is one of the typical symptoms in COVID-19. Of 1099 adult inpatients and outpatients in China, 18.7% presented with dyspnoea.80 With increasing disease severity, the proportion of dyspnoea significantly increases (31–55% in hospitalized patients and up to 92% of patients admitted to ICUs).10,65 Cough is present in 59.4–81.1% of patients with COVID-19, irrespective of disease severity.34,99 Unproductive (dry) cough is more frequent, whereas sputum production is present in 23.0–33.7%.10,34,65,80 ARDS is characterized by bilateral opacifications on chest imaging (e.g. bilateral ground glass opacifications on CT) and hypoxaemia that cannot be explained by other causes.100 Among 1099 adult inpatients and outpatients in China, ARDS occurred in 3.4%,80 but in hospitalized patients, the rates are significantly higher (19.6–41.8%).10,34,99 The median time from disease onset to ARDS is 8–12.5 days.65 The risk of ARDS increases with older age (≥ 65 years old), presence of comorbidities (hypertension, diabetes), neutrophilia, lymphocytopenia, elevated laboratory markers of organ dysfunction (e.g. lactate dehydrogenase [LDH]), inflammation (C reactive protein) and D-dimer.99 Mortality of patients treated for ARDS in COVID-19 is high (e.g. 52–53%).10,34,65,66,80,99,100 An early, accurate, and rapid diagnosis of CS in patients with confirmed or suspected COVID-19 is essential.101 The exact incidence of CS in these patients is unknown. However, the median duration between onset of symptoms and admission to ICU in critically ill COVID-19 patients has been 9–10 days, suggesting a gradual respiratory deterioration in most patients.102 A simple, actionable classification scheme for CS diagnosis has recently been proposed.103 In critically ill COVID-19 patients at risk for CS (such as those with large AMI, acute decompensated HF; Society for Cardiovascular Angiography and Interventions stage A)103 and sepsis, a mixed aetiology of CS and septic shock should be considered in addition to the sole cardiogenic component. Parameters allowing for a differential diagnosis between CS and septic shock, such as the presence of vasodilatation and central venous oxygen saturation values may be assessed. In selected cases, such as in patients with unclear reasons for haemodynamic deterioration, invasive haemodynamic monitoring via a pulmonary artery catheter may provide useful information. The diagnostic work-up of critically ill patients with confirmed or suspected COVID-19 infection requires specific considerations: There is very limited literature available on the occurrence of arrhythmia in the context of an infection by the SARS-CoV‑2 virus. In a study of 138 hospitalized patients with COVID-19 in Wuhan, arrhythmia was reported in 16.7% of total patients and in 16 of 36 patients admitted to the ICU (44%), although the authors did not further specify its type.10 In a subsequent publication from the same institution, ventricular tachycardia (VT)/ventricular fibrillation (VF) was reported as a complication of the COVID-19 disease in 11 of 187 patients (5.9%), with a significantly higher incidence in patients with elevated troponin T.25 However, the largest observational study from China, with 1099 patients from 552 hospitals, did not report any arrhythmia.80 Hypoxaemia and a systemic hyperinflammation status may lead to new-onset atrial fibrillation (AF), although there are no published data so far. However, important consideration should be given to rhythm management (drug interactions with COVID-19 treatment) and anticoagulation. The clinical presentation of brady- or tachyarrhythmias in the context of COVID-19 does not differ from those previously described (i.e. palpitations, dyspnoea, dizziness, chest pain, syncope, etc.). However, there are concerns that in areas where the epidemic is extended, hospitals have experienced a significant decrease in emergency consultations for cardiac. Whether the underlying reason is concern for in-hospital contagion, a result of self-isolation measures or a saturation of the EDs and ambulances needs to be explored. Pneumonia and severe influenza infections have been associated with a markedly increased short term risk of MI and subsequent mortality, that is more common among patients at older age, nursing home resident, and patients with history of HF, coronary disease or hypertension.105-108 Moreover, for influenza epidemics it has been demonstrated that there is a consistent rise in autopsy-confirmed coronary deaths.109 Fatal AMIs have also been observed in the short term after coronavirus associated SARS.110 Notably, recent data from China suggest that myocardial injury during COVID-19 infection – as indicated by elevated troponin levels – represent one predictor of a higher risk of CV complications and an adverse clinical outcome.25,26 Moreover, an increased rate of thromboembolic events has been observed in the context of COVID-19 infection. So far no specific ECG changes have been described in patients with SARS-CoV‑2 infection. Therefore, we have to assume that the overall minimal level of myocardial injury associated with the infection (see the following section on biomarkers) does not translate into characteristic ECG manifestations in the majority of patients, although ST-segment elevation in the setting of myocarditis have been described.61 As a consequence, the same ECG diagnostic criteria for cardiac conditions apply in patients affected by SARS-CoV‑2 infection and in the general population. Little is known about COVID-19 infection and arrhythmias. One report on 138 patients described an arrhythmia (not further specified) in 16.7% and the prevalence increased to 44.4% in the 16 patients who were admitted to the ICU.10 For considerations of arrhythmia and corrected QT interval (QTc) prolongation of COVID-19 therapies see section 10.1. COVID-19 is a viral pneumonia that may result in severe systemic inflammation and ARDS, and both conditions have profound effects on the heart.26,34,111 As a quantitative marker of cardiomyocyte injury, the concentrations of cardiac troponin I/T in a patient with COVID-19 should be seen as the combination of the presence/extent of pre-existing cardiac disease AND the acute injury related to COVID-19.34,66,89,111-113 Cohort studies from patients hospitalized with COVID-19 in China showed that 5–25% of patients had elevations in cardiac troponin T/I, and this finding was more common in patients admitted to the ICU and among those who died.24-26,66,111 Concentrations remained in the normal range in the majority of survivors. In non-survivors, troponin levels progressively increased in parallel with the severity of COVID-19 and the development of ARDS (Figure 10). 24,26,34,66,111 Mild elevations in cardiac troponin T/I concentrations (e.g. < 2–3 times the ULN), particularly in an older patient with pre-existing cardiac disease, do NOT require work-up or treatment for T1MI, unless strongly suggested by angina chest pain and/or ECG changes (Figure 11). Such mild elevations are in general well explained by the combination of possible pre-existing cardiac disease AND/OR the acute injury related to COVID-19. Marked elevations in cardiac troponin T/I concentrations (e.g. > 5 times the ULN) may indicate the presence of shock as part of COVID-19, severe respiratory failure, tachycardia, systemic hypoxaemia, myocarditis, Takotsubo syndrome or T1MI triggered by COVID-19.26,34,89,111 In the absence of symptoms or ECG changes suggestive of T1MI, echocardiography should be considered in order to diagnose the underlying cause. Patients with symptoms and ECG changes suggestive of T1MI should be treated according to ESC-guidelines irrespective of COVID-19 status.24,66,113,114 BNP/NT-proBNP as quantitative biomarkers of haemodynamic myocardial stress and HF are frequently elevated among patients with severe inflammatory and/or respiratory illnesses.26,115-117 While experience in patients with COVID-19 is limited, very likely the experience from other pneumonias can be extrapolated to COVID-19.26,115-117 As quantitative markers of haemodynamic stress and HF, the concentrations of BNP/NT-proBNP in a patient with COVID-19 should be seen as the combination of the presence/extent of pre-existing cardiac disease AND/OR the acute haemodynamic stress related to COVID-19.26,115-117 At least to some extent, the release of BNP/NT-proBNP seems to be associated with the extent of right ventricular haemodynamic stress. D-dimers are generated by cleavage of fibrin monomers by prothrombin and indicate the presence of thrombin formation or reflect an unspecific acute phase response from infection or inflammation. D Dimers also may indicate the presence of disseminated intravascular coagulation associated with shock.118 It is tempting to speculate that markers of activated coagulation or impaired fibrinolysis might contribute to acute myocardial injury, eventually also affecting coronary capillaries. Therefore, markers of haemostasis including activated partial thromboplastin time, prothrombin time, fibrin degradation products and D-Dimers should be monitored routinely. In particular, elevations of D-Dimers have been associated with poor outcome.84 Although the D-dimers have a lower specificity for the diagnosis of acute PE, 32–53% of patients still have a normal D-dimer and the vast majority has D dimers below 1000 ng/ml.10,34,80 Therefore, recommended diagnostic algorithms combing pre-test probability assessment and D dimer tests can be used in case of suspected acute PE.119 In particular, algorithms applying a pre-test probability dependent D-dimer threshold may yield a decent specificity.120-122 The potential mechanisms underlying myocardial injury in those with COVID-19 infection are not fully understood. However, in keeping with other severe inflammatory and/or respiratory illnesses, direct (‘non-coronary’) myocardial injury is most likely the cause. Myocarditis, septic shock, tachycardia, severe respiratory failure, systemic hypoxaemia, Takotsubo syndrome or T1MI triggered by COVID-19, are alternative causes. Direct myocardial involvement mediated via ACE2, cytokine storm, or hypoxia induced excessive intracellular calcium leading to cardiac myocyte apoptosis have been suggested as alternative mechanisms.2,48,123 As quantitative biomarkers of haemodynamic myocardial stress and HF, intracardiac filling pressures and end-diastolic wall stress seem to be the predominant triggers of the release of BNP/NT-proBNP.115-117 As in patients without COVID-19, cardiac troponin T/I concentrations should be measured whenever on clinical grounds T1MI is suspected.113 In patients with COVID-19, diagnostic algorithms for rapid rule out and/or rule-in of MI in patients with acute chest discomfort such as the ESC high-sensitivity cardiac troponin (hs-cTn) T/I 0/1-h algorithm can be expected to provide comparable performance characteristics as in other challenging subgroups with higher baseline concentrations such as the elderly and patients with renal dysfunction: very high safety for rule-out and high accuracy for rule-in, but reduced efficacy with a higher percentage of patients remaining in the observe zone.113,124-126 Detailed clinical assessment including chest pain characteristics, assessment of COVID-19 severity, hs-cTn T/I measurement at 3 hours, and cardiac imaging including echocardiography are the key elements for the identification of MI in this heterogeneous subgroup.113,124-126 Similarly, BNP/NT-proBNP should be measured whenever on clinical grounds HF is suspected.26,115-117 In patients who are not critically ill, rule-in cut-offs for HF maintain high positive predictive value even in patients with pneumonia.26,115-117 In contrast, currently recommended cut-offs should not be applied in critically-ill patients, as most critically-ill patients have substantial elevations in BNP/NT-proBNP, most likely due to the near-universal presence of haemodynamic stress and HF in these patients.26,115-117 It is a matter of ongoing debate whether cardiac troponin T/I should be measured as a prognostic marker in patients with COVID-19. The strong and consistent association with mortality observed in the currently available reports of patients hospitalized with COVID-19, with some evidence suggesting cardiac troponin T/I even as an independent predictor of mortality, should be seen in favour of this approach.25,26,34,111 On the other hand, at this point in time, based on three arguments we consider a more conservative approach even more appropriate.26,34,66,89,111-113 First, beyond cardiac troponin T/I other routinely available clinical and laboratory variables have also emerged as strong predictors of death in COVID-19 including older age, higher Sequential Organ Failure Assessment (SOFA) score, D dimers, IL-6 and lymphocyte count. It is unlikely that cardiac troponin T/I provides incremental value to a full model. Second, there is a recent risk of inappropriate diagnostic and therapeutic interventions triggered based in cardiac troponin T/I concentrations measured for prognostic purposes. Third, in patients with COVID-19 as well as with other pneumonias or patients with ARDS, at this point in time, no specific therapeutic intervention can be justified based on the use of cardiac troponin T/I as a prognostic marker.26,34,66,89,111-113 Therefore, routine measurements of cardiac troponin T/I and/or BNP/NT-proBNP in patients with COVID-19 given the current very limited evidence for incremental value for clinical decision-making is discouraged. Non-urgent or elective cardiac imaging should not be performed routinely in patients with suspected or confirmed COVID-19 infection. Accordingly, non-urgent or elective exams should be postponed until the COVID-19 infection has ceased (Table 6).127,128 Echocardiography can be performed bedside to screen for CV complications and guide treatment. POCUS, FoCUS and critical care echocardiography are probably the preferred modalities to image patients with COVID-19. Limited evidence exists for the use of lung ultrasound to differentiate ARDS (single and/or confluent vertical artefacts, small white lung regions) from HF.129 The presence of dilated right ventricle and pulmonary hypertension may indicate contrast CT to rule out PE. In COVID-19 infected patients, echocardiography should focus solely on the acquisition of images needed to answer the clinical question in order to reduce patient contact with the machine and HCP. It should not be forgotten that the risk of infection remains in the reading rooms and therefore the material used should be also frequently sanitized. Cardiac CT should be performed when there is a potential impact on clinical management, including evaluation of symptomatic suspected CAD, acute symptomatic heart valve dysfunction, left ventricular assist device (LVAD) dysfunction, PE, urgent structural intervention.130 Cardiac CT is preferred to TEE to rule out the presence of intracardiac thrombus. In patients with acute chest pain and suspected obstructive CAD, CCTA is the preferred non-invasive imaging modality since it is accurate, fast and minimizes the exposure of patients. In patients with respiratory distress, lung CT is recommended to evaluate imaging features typical of COVID-19 and differentiate from other causes (HF, PE).94 However, it should not be used to screen for or as a first-line test to diagnose COVID-19 and should be reserved for hospitalized patients.131 A dedicated CT scanner for patients with suspected or confirmed COVID-19 is preferred. As in other imaging modalities, local standards for prevention of virus spread and protection of personnel should be followed. Many of the diagnoses can be evaluated with other imaging modalities that limit the risk of virus spread. Nuclear cardiology tests require long acquisition times and exposure of patients and personnel.132 The use of PET-CT can be limited to patients with suspected endocarditis of prosthetic valves or intracardiac devices when other imaging modalities are inconclusive or to avoid the performance of a TEE which is associated with larger risk of spreading. Single photon emission computed tomography (SPECT) or PET may also be used for diagnosing ischaemia in patients with suspected obstructive CAD when CCTA is not appropriate or available. The risks of contamination during a CMR scan is probably similar to a CT scan, but lower than during an echocardiographic study. Only clinically urgent CMR scans should be accepted.133 Longer time exposure in the scanner will probably increase the chances of contamination of equipment and staff. In order to minimize the examination time, shortened CMR protocols focused to address the clinical problem should be used.133 A dedicated MR scanner for patients with suspected or confirmed COVID-19 is a clear advantage. Allow time for a deep cleaning after each patient with suspected or confirmed COVID-19 infection. The role of CMR in COVID-19 patients is currently not clear. Accepted diagnostic indications for CMR should be considered as appropriate in these patients, but should not be performed unless clinically necessary and after a reconsideration of best suited imaging technique.128 Another important attention is the use of CMR contrast in patients with COVID-19. Renal function might be decreased in patients with COVID-19 and might contradict a clinically urgent CMR scan. One indication for an acute CMR might be suspicion of acute myocarditis, which has been reported in patients with COVID-19.134 Typical symptoms might be elevated troponins, ventricular dysfunction and/or severe arrhythmias that cannot be explained by other diagnostics and imaging methods.20 Performance of exercise testing (either conventional, Echo or nuclear) has major limitations in the COVID-19 era. During exercise the patient increases breath rate and the amount of aerosol or droplets production, even if wearing a surgical mask (that could strongly affect his/her exercise capacity). This problem is further increased since rooms of outpatient clinics are rarely large and well aerated. Performance of exercise testing is discouraged in COVID-19 suspect or positive patients and, in general, in every patient in COVID-19 epidemic or potentially epidemic areas. Alterative diagnostic methods for CAD not requiring exercise should be used as an alternative to exercise testing whenever possible. There remain conditions where exercise testing is necessary. These mainly concern patients with heart failure. Cardiopulmonary exercise testing remains the method of choice for the assessment of exercise capacity, a well-known prognostic index, and for the indication to heart transplantation in patients with heart failure. In addition, exercise testing is proposed as the method of choice for the diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with breathlessness and intermediate scores for HFpEF diagnosis. A low-level exercise may be, however, sufficient in these cases.135 In COVID-19-infected patients with clinical presentation compatible with CVD, three main entities should be considered: The rearrangement of the healthcare service required to face the COVID-19 pandemic has posed a series of relevant issues on prioritization of cardiac invasive procedures.136 Different regions in Europe and worldwide differ substantially in terms of local healthcare resources, epidemic density of the COVID-19 outbreak, changes of the epidemic over time and therefore access to healthcare services other than COVID-19 care. These differences have a wide range of implications for national/regional healthcare services, national health care authorities and in-hospital redistribution of resources. Regions (also within the same country) may be categorized into three groups according to the degree of involvement in the epidemic, with subsequent different implications for the healthcare system as summarized in Table 7. The indications provided in this document refer mainly to the scenario of heavy involvement and, in part, to the scenario of moderate involvement. Importantly, healthcare services should continue to be provided according to standard-of-care as described by current clinical practice guidelines, as long as the degree of regional involvement in the epidemic allows it. The rationale to importantly reduce the number of elective hospitalizations is three-fold: This strategy comes at the expense of time-to-treatment delays for urgent CV interventions and extension of waiting times for patients in need of elective coronary, heart valve or other CV interventions. In this context, a strategy is needed to identify patients who are in a condition allowing to postpone procedures and those who are not. An obvious concern is to maintain the standard-of-care and timely access of patients with ACS including AMI to reperfusion therapy. In patients with chronic coronary syndromes (CCS), principles of prioritization can be based on risk stratification, taking into account prognostic implications of symptoms and the presence of known critical disease of the left main stem or of the proximal left anterior descending (LAD) coronary artery at prior coronary angiogram or at CCTA.137 Similarly, patients with decompensated, symptomatic, severe aortic stenosis (AS) scheduled for transcatheter aortic valve replacement should be prioritized.138 Table 8 summarizes a categorization of invasive cardiac procedures according to urgency that may be implemented at areas affected by the COVID-19 outbreak. The management of patients with NSTE-ACS should be guided by risk stratification.113 Testing for SARS-CoV‑2 should be performed as soon as possible following first medical contact, irrespective of treatment strategy, in order to allow HCP to implement adequate protective measures and management pathways (section 5). Patients should be categorized into 4 risk groups (i.e. very high risk, high risk, intermediate risk, and low risk) and managed accordingly (Figure 12). Patients with Troponin rise and no acute clinical signs of instability (ECG changes, recurrence of pain) might be managed with a primarily conservative approach. Non-invasive imaging using CCTA may speed-up risk stratification, avoid an invasive approach139 allowing early discharge. For patients at high risk, medical strategy aims at stabilization whilst planning an early (< 24 hours) invasive strategy. The time of the invasive strategy may however be longer than 24 hours according to the timing of testing results. If feasible, a dedicated area to manage these patients while waiting for the test result should be arranged in the emergency department. In the case of positive SARS-CoV‑2 test, patients should be transferred for invasive management to a COVID-19 hospital equipped to manage COVID-19-positive patients. Patients at intermediate risk should be carefully evaluated taking into consideration alternative diagnoses to T1MI, such as Type II MI, myocarditis, or myocardial injury due to respiratory distress or multiorgan failure or Takotsubo. In the event any of the differential diagnoses seem plausible, a non invasive strategy should be considered and CCTA should be favored, if equipment and expertise are available. When there is a positive SARS-CoV‑2 test, patients should be transferred for invasive management to a COVID-19 hospital equipped to manage COVID-19-positive patients. At times of high demand on the infrastructure and reduced availability of catheterization laboratories or operators, non-invasive conservative management might be considered with early discharge from the hospital and planned clinical follow-up. The COVID-19 pandemic should not compromise timely reperfusion of STEMI patients. In line with current guidelines, reperfusion therapy remains indicated in patients with symptoms of ischaemia of < 12 hours duration and persistent ST-segment elevation in at least two contiguous ECG leads.114 Concurrently, the safety of HCP should be ensured.136 To that purpose, and in the absence of previous SARS-Co-V2 testing, all STEMI patients should be managed as if they are COVID-19 positive. We provide general guidance to address the healthcare system organization and delineate possible pathways for specific STEMI settings. The proposed actions are not evidence-based, may need to be adapted to meet local hospital and health authority regulations and may be subject to change in view of the evolving COVID-19 pandemic. While general measures for healthcare systems on redistribution of hub and spoke hospital networks for CV emergency and reorganization of ED and hospital paths are described in sections 7 and 8, respectively, the main principles of STEMI management in the COVID-19 pandemic are the following: Specific pathways for management of STEMI patients are illustrated in Figure 13. It is suggested to perform left ventriculography during catheterization of any ACS patients to reduce the need for echocardiography and shorten hospital stay. The treatment of the non-culprit lesions should be managed according to patients’ clinical stability as well as angiographic features of those lesions. In the presence of persistent symptomatic evidence of ischaemia, subocclusive stenoses, and/or angiographically unstable non-culprit lesions, PCI during the same hospitalization should be considered. Treatment of other lesions should be delayed, planning a new hospitalization after the peak of the outbreak. CS and OHCA are time-dependent diseases needing relevant resources and optimal trained systems and dedicated networks for optimal outcome. In general, treatment of CS and OHCA should follow current guidelines and current evidence.101,114,137,140,141 However, considering that in an overwhelmed critical care system stressed by the pandemic COVID-19 infection it will not be possible for all the patients to receive ICU treatment due to limited resources. This leads to difficult situations based also on the four widely recognized principles of medical ethics (beneficence, non-maleficence, respect for autonomy and equity) which are also crucial under conditions of resource scarcity. If resources available are insufficient to enable all patients to receive the ideally required treatment, then multiple groups have considered and recommend fundamental principles to be applied in accordance with the following rules of precedence: Triage strategies, based on current evidence and a previously established critical care triage protocol developed by working groups for use during a worldwide influenza pandemic,142 are summarised in Table 11 and Table 12. Specific recommendations are provided for patients with and without concomitant infection in Figure 14. Two scenarios will be considered: The infection should be suspected according to recently defined epidemiological and clinical criteria.143 HCP managing patients with CCS in geographical areas heavily affected by the COVID-19 pandemic should consider the following main points: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been identified as a potential risk factor for serious clinical presentation of SARS-CoV‑2 infection.144 Potential impact of chronic aspirin therapy has been questioned. However, at the low dose administered in CCS, aspirin has very limited anti inflammatory effect. Therefore, CCS patients should not withdraw aspirin for secondary prevention. Statin therapy has been variably associated with favourable outcomes in patients admitted with influenza or pneumonia.145,146 On the other side, patients with COVID-19 have been sometimes reported to develop severe rhabdomyolysis or increased liver enzymes.147 In these latter cases, it may be prudent to temporarily withhold statin therapy. For CCS patients treated with antihypertensive drugs please refer to section 9.7. Non-invasive testing in patients with CCS is tailored upon different clinical presentations.148 In regions with high rate of SARS-CoV‑2 infection, evaluation of asymptomatic CCS patients with non invasive testing should be postponed in order not to expose these patients to an unnecessary risk of infection or overload the health care systems. For symptomatic patients with suspected CAD and a pre-test probability of 5–15%, functional imaging for detection of myocardial ischaemia or CCTA are normally recommended as initial tests to diagnose CAD. In regions with critical situation and medical system overloaded by the COVID-19 pandemic, CAD screening even in symptomatic patients should probably be postponed in the majority of patients. Yet, if necessary, depending upon local availability and expertise, CTA should be preferred (section 7.4). However, the increased workload of CT departments should be acknowledged; they have been heavily disrupted by the high request of pulmonary CT for patients with COVID-19. In addition, feasibility/accuracy of CCTA might be hampered in patients with COVID-19 for the common occurrence of tachycardia and at times severe renal dysfunction. In case CCTA is not suitable (e.g. inability of heart rate control, etc.) or available, non-invasive testing should be postponed. Alternative imaging modalities should be discouraged during the acute pandemic phase unless severe ischaemia is suspected, to minimize the access of the patients to healthcare system (SPECT/PET) or to prevent a close contact between patients and personnel (stress echocardiography). For known CCS patients, clinical follow-up should be done mostly via tele-health (a dedicated telephone line should be made available to patients). Physicians could therefore address most of the patients’ concerns related to continuation or changes in medical therapy. Possible onset/recurrence of unstable symptoms should be estimated within the clinical history of the patient in order to weigh the need for hospitalization and diagnostic testing. Symptomatic patients with very high clinical likelihood of obstructive CAD are generally referred to ICA without prior non-invasive diagnostic testing.148 However, even in these patients, medical treatment should be attempted first in order to reserve ICA with possible ad-hoc revascularization only in case of clinical instability, especially in regions were healthcare systems are heavily overloaded by patients with COVID-19.149 Revascularization (either by PCI or coronary artery bypass graft [CABG]), can be postponed in most CCS patients. However, in hospitals whose ICUs are dedicated to or overloaded with high numbers of patients with COVID-19, the impact on CABG deferral might be even more pronounced. Priority is given to keep ICU beds available for COVID-19 patients requiring critical care. Therefore, healthcare systems might identify COVID-19-free hospitals serving as hubs for selected CCS patients in whom invasive and surgical procedures cannot be postponed. In these latter patients, SARS-CoV‑2 infection should be ruled out by nasopharyngeal swab/tracheobronchial aspiration and/or CT scan before hospital admission. Alternatively, in selected patients, hybrid revascularization CABG/PCI or even full-PCI can be considered by the heart team based on patient’s clinical conditions and local situation (see Table 13). Patients with CV comorbidities are at increased risk of the more severe presentation and complications of COVID-19. In a meta-analysis of 6 studies (n = 1527), hypertension and cardio/cerebrovascular diseases were present in 17.1%, and 16.4%, of hospitalized COVID-19 patients, respectively, and conferred ~2-fold and ~3-fold higher risk, respectively, for the more severe COVID-19.150 In 21 patients admitted to an ICU for severe COVID-19, 7 (33.3%) patients developed dilated cardiomyopathy, characterized by globally decreased LV systolic function, clinical signs of CS, elevated creatine kinase (CK), or troponin I levels, or hypoxaemia, without a past history of systolic dysfunction.89 An analysis of mortality causes in COVID-19 patients (150 hospitalized/68 dead) revealed that myocardial damage/HF and combined respiratory failure/myocardial damage/HF were responsible for 7% and 33% of fatal cases, respectively.66 There are several, not mutually exclusive, mechanisms of acute HF in COVID-19 such as: Incidence, underlying mechanisms and risk factors of SARS-CoV‑2-associated myocarditis are currently unclear. Recently, a high viral load has been reported in 4 patients who subsequently developed fulminant myocarditis.33 One published case involved a 38-year-old male presenting with chest pain, hypotension, bilateral pneumonia with pleural effusions and ST segment elevation, but with normal CT coronary angiogram.104 Echocardiography demonstrated dilatation and a marked decrease in LV ejection fraction (LVEF), and a 2 mm thick pericardial effusion. Troponin I and BNP levels were notably high. The patient successfully recovered after receiving high-dose parenteral glucocorticoid anti inflammatory therapy and immunoglobulin, along with other therapeutic measures. During the COVID-19 outbreak, patients with chronic HF should be advised to closely follow protective measures aimed at preventing disease transmission (e.g. self-isolation, social distancing, frequent hand washing, use of hand sanitizers and wearing a face mask in public spaces). Ambulatory stable HF patients (with no cardiac emergencies) should refrain from hospital visits. Routine clinical methods, ECG (arrhythmias, myocardial ischaemia, myocarditis) and chest X-ray (cardiomegaly, COVID-19 pneumonia) can provide a diagnostic clue. Due to the relatively low sensitivity of chest X-ray to detect COVID-19 pneumonia, patients with a high degree of clinical suspicion (tachypnoea, hypoxaemia), but with ambiguous chest X-ray findings, should be referred to chest CT.152 Laboratory findings, such as increased erythrocyte sedimentation rate, fibrinogen and C-reactive protein, and lymphocytopenia, may suggest COVID-19 pneumonia. TTE is very important, not only to evaluate pre-existing LV dysfunction in HF, but also to assess patients suspected of having SARS CoV 2-associated myocarditis.153 During all medical procedures, an attention should be given to prevent viral transmission to HCP. SARS-CoV‑2 utilizes the ACE2 receptors for cell entry and some data indicate that ACEIs and ARBs may upregulate ACE2,154 thus hypothetically increasing the susceptibility to the infection. Recently, a case series of 12 patients with COVID-19-associated ARDS, demonstrated that plasma Ang II levels were markedly elevated and linearly associated with viral load and lung injury.33 This has led to a suggestion that ARB treatment could have a beneficial effect in curbing the Ang II-mediated lung injury. Clearly, further research in required to resolve the controversies regarding the role of ACEI/ARB in COVID-19. There is currently no clinical evidence of an association between ACEI/ARB treatment and the susceptibility to infection, or the clinical course. Withdrawal of medical treatment in HF patients may increase the risk of worsening HF.155 Available data do not support discontinuation of ACEI/ARB and it could be recommended that HF patients continue guideline-directed medical therapy, including beta blockers, ACEI, ARB, or sacubitril/valsartan, and mineralocorticoid receptor antagonists, irrespective of COVID-19.156 COVID-19 patients may become hypotensive due to dehydration and haemodynamic deterioration, hence adjustment of medication doses should be considered. The more widespread use of telemedicine should be encouraged to minimize the risk of SARS-CoV‑2 transmission, in both HF patients, and HCP. Whenever possible, this technology should be utilized to provide medical advice and follow-up of stable HF patients, and to reserve direct patient provider contact for the emergency situations. It is advisable that HCP make a telephone contact with the ambulatory chronic HF patient to verify the need for the hospital visit, but also to provide psychological support. If feasible (and necessary), home delivery and mailing of standard HF drugs to the patients is a viable option. Due to the nature of the device, LVAD patients have an increase susceptibility to the infection, and every measure should be used to prevent viral transmission. Cautious monitoring and management of anticoagulation therapy is advised, because both COVID-19 and antiviral medications can affect anticoagulant dosing. If technically feasible, assessment of LVAD function by telemonitoring is preferable. General recommendations for all LVAD patients should be also applied, regardless of COVID-19. The susceptibility to the infection and the clinical course of COVID-19 in heart transplant recipients is not known. Recently, two cases (one mild, another more severe) of COVID-19 have been described in heart transplant recipients in China.159 Importantly, the presenting symptoms were similar to those of immunocompetent individuals, including fever, elevated inflammatory markers (e.g. C-reactive protein), lymphocytopenia and chest CT demonstrating bilateral ground-glass opacities. The treatment of the patient with more severe infection included temporary discontinuation of baseline immunosuppressant medications and institution of high-dose glucocorticoids, immunoglobulins and fluroquinolone antibiotics, along with other treatment measures. Of note, both patients recovered and remained rejection-free. Yet another report of 87 heart transplant recipients from China, indicated that high-degree adherence to preventive measures (see above), resulted in a low rate of possible infection and transition to manifest illness (e.g. 4 patients were reported to have airway tract infection and 3 of them had a negative SARS-CoV‑2 test result, whilst 1 patient was not tested).160 Importantly, all patients fully recovered after treatment. Although VHD has not been explicitly linked to increased morbidity and mortality in early COVID-19 case series, up to 40% of the patients admitted to the ICU had pre-existing congestive HF.89 VHD mainly affects the elderly and the symptoms of disease progression (mainly dyspnoea) may mimic those of lung infection or infiltration. In addition, VHD may aggravate the course of COVID-19 infection and complicate haemodynamic management of the systemic inflammatory response (cytokine storm),161 ARDS, and any superimposed bacterial septicaemia (observed in up to one third of ICU patients).65 Elective surgical and transcatheter interventions for VHD consume significant health care resources and many (or all, according to circumstances) may be inappropriate during the pandemic given the immense pressure on acute and intensive care facilities. However, patients with severe VHD must remain under close telephone surveillance and be encouraged to report progressive symptoms. Concentration of resources on the treatment of pandemic victims guides decisions with the overall aim of avoiding shortage of ICU beds and ventilators. Prioritization of valve interventions should therefore balance the immediate and short-term prognosis of individual patients against available resources and the risk to patients and HCP of acquiring in-hospital infection. In this respect, use of less invasive procedures (particularly transcatheter aortic valve implantation [TAVI] via transfemoral approach performed under conscious sedation and/or local anaesthesia), may present an opportunity to minimize ICU and hospital stay. The need for clinical decision making by Heart Teams remains of paramount importance and use of telemedicine (or other means of virtual communication) is essential if face-to-face meetings are difficult (or impossible) during the acute phase of the pandemic. The prognosis of patients with severe aortic stenosis (AS) depends on several factors, including age, symptomatic status, peak aortic jet velocity/mean transvalvular gradient,162,163 LVEF, pulmonary hypertension,164 and elevated biomarkers (natriuretic peptides or troponin).165-167 Mortality of patients with severe symptomatic AS who are treated conservatively is high, reaching 50% at 1 year and 70–80% at 2 years.168 Deferring surgical aortic valve replacement (SAVR) or TAVI by several months may therefore affect prognosis. In the context of the COVID-19 pandemic, the Heart Team should undertake systematic individual risk assessment based on objective criteria that determine disease progression. Priority should be given to patients with syncope or HF (New York Heart Association [NYHA] Class III/IV), high or very high transvalvular gradients and those with reduced LV function Table 8, whereas a watchful waiting strategy is more appropriate in those with minimal or no symptoms. TAVI (or balloon aortic valvuloplasty) may be considered in haemodynamically unstable patients (COVID-19 positive/negative). However, the potential benefits of valve intervention in a critically ill COVID-19 positive patient (no cases reported to date) should be carefully weighed against the likelihood of futility given the > 60% mortality of COVID-19 positive patients admitted to ICU.169 All cases should be discussed by the Heart Team and indications for TAVI extended to intermediate170,171 and selected low-risk patients.172,173 Increased use of transfemoral TAVI (when feasible) may allow optimal utilization of resources by avoiding general anaesthesia and intubation, shortening (or preventing) ICU stay and accelerating hospital discharge and recovery.174 The management of MR differs according to its aetiology and presentation. Chronic primary MR (flail leaflet and Barlow disease) is usually stable and well tolerated. In contrast, SMR is a more variable entity and whilst many patients remain stable under guideline directed medical and device treatment (including sacubitril/valsartan and cardiac resynchronization therapy when indicated),175 others may develop unstable HF syndromes that are refractory to medical treatment, particularly in the context of acute infection.176 In the context of the COVID-19 pandemic, priority should be given to the treatment of patients with acute primary MR complicating AMI or IE, and those with severe primary or SMR who remain symptomatic despite guideline-directed medical and device treatment and seem likely to require hospital admission. All other patients should be managed conservatively.175-178 Transcatheter mitral edge-to-edge repair may be considered in anatomically suitable high-risk or inoperable patients with acute MR (excluding those with IE) or highly selected patients with decompensated primary MR or SMR refractory to guideline-directed medical and device treatment. Despite a low risk of complications requiring ICU admission,179 the procedure requires general anaesthesia (in distinction to transfemoral TAVI) and prolonged echocardiographic guidance, thereby exposing interventionists and anaesthetists to the risk of COVID-19 transmission. Use of temporary circulatory support (intra-aortic balloon pump or Impella) should be restricted to patients with a good prospect for recovery in the context of available ICU resources. Initial reports from China noted that hypertension was one of the most common co-morbidities (20–30% of cases) associated with the need for ventilatory support due to severe respiratory complications of COVID-19 infection.10,65,80,99,180 These analyses did not adjust for age, which is important because hypertension is very common in older people (~50% in people aged over 60 years are hypertensive) and hypertension prevalence increases sharply in the very old. Older age is also the most important risk factor for severe complications and death due to COVID-19, thus, a high frequency of hypertension would be expected in older patients with severe infection because of their older age. Indeed, a higher frequency of hypertension would be expected in older COVID-19-infected patients, than has been reported. It now seems likely that the reported association between hypertension and risk of severe complications or death from COVID-19 infection is confounded by the lack of adjustment for age and other unmeasured confounders.47 There is currently no evidence to suggest that hypertension per se is an independent risk factor for severe complications or death from COVID-19 infection. RAS blockade with ACEIs or ARBs are the foundation of antihypertensive therapy in the current ESC-ESH Guidelines for the management of arterial hypertension (2018).181 The recommended treatment of hypertension for most patients is combinations of an ACEI or ARB with a calcium channel blocker (CCB) or thiazide/thiazide like diuretic.181 Concern has been expressed that treatment with ACEIs or ARBs might increase the risk of infection, or developing the severe consequences of infection with COVID-19.21,46,182 This concern originates from a hypothesis that links the observations that COVID-19 invades cells by binding to the enzyme ACE2 which is ubiquitous and expressed on the surface of alveolar cells in the lung.39,41,183 In some animal studies, but not all, ACEIs or ARBs have been shown to increase ACE2 levels mainly in cardiac tissue.49,184,185 Importantly, there have been no studies showing that RAS-blocking drugs increase ACE2 levels in human tissues and no studies in animals or humans showing that RAS-blocking drugs increase ACE2 levels in the lung, or that the level of ACE2 expression in the lung is rate limiting for COVID-19 infection. Moreover, there have been no studies in humans demonstrating an independent link between RAS blocker use and the development of severe complications of COVID-19 infection, after adjustment for age and other comorbidities. Recently a series of observational cohort studies have been published which consistently show that treatment with RAS blockers does not increase the risk of COVID-19 infection, or increase the risk of severe complications or death from COVID-19 infection.54-60 In one study, there was even a substantial reduction in risk of severe complications or death from COVID-19 infection in patients with diabetes mellitus.56 These recent findings are very important and provide reassurance to patients and their doctors that prior speculation about the safety of RAS blockers in the context of COVID-19 infection has not been proven. Indeed, studies in animal models of infection with influenza or coronaviruses have suggested that ACE2 is important in protecting the lung against severe injury and that RAS-blocking drugs are also protective against severe lung injury due to these viruses.186-188 Human studies of RAS-blockade or recombinant ACE2 to prevent respiratory decompensation in COVID-19 infected patients have been suggested, planned or are ongoing.189,190 In summary, there is currently no evidence to suggest that ACEIs or ARBs increase the risk associated with COVID-19 infection and there is no reason why these drugs should be discontinued due to concern about COVID-19 infection. Treatment of hypertension when indicated, should continue to follow the existing ESC-ESH guideline recommendations.191 Most patients with hypertension require only infrequent visits to the clinic to manage their hypertension. Many patients with treated hypertension will be in self isolation to reduce the risk of COVID-19 infection and unable to attend for their usual routine clinical review. When possible, patients should monitor their own BP as frequently as they usually would, using a validated home BP monitor.181 Videoconference or telephone consultation with patients when required may facilitate urgent physician follow up until normal clinic attendance resumes. Most patients who are hospitalized, will have more severe infection and be hospitalized for respiratory support. They are likely to be older with comorbidities such as hypertension, diabetes and chronic kidney disease. Patients with severe disease may also develop multi-organ complications in severe disease. Hypertensive patients may also have LV hypertrophy or heart disease and be at increased risk of developing arrhythmias, particularly when hypoxic.192 Plasma potassium levels should be monitored because arrhythmias may be exacerbated by the frequent occurrence of low plasma potassium levels or hypokalaemia that was first noted in SARS coronavirus infection193 and early reports suggests is also prominent in hospitalized COVID-19-infected patients.194 This is thought to be due to increased urinary loss of potassium, which may be exacerbated by diuretic therapy. If patients are acutely unwell and become hypotensive or develop acute kidney injury due to their severe disease, antihypertensive therapy may need to be withdrawn. Conversely, parenteral antihypertensive drugs are rarely but sometimes needed for hypertensive patients who are ventilated and have sustained and significant increases in BP after withdrawal of their usual treatment (i.e. grade 2 hypertension, BP > 160/100 mmHg) but the objective in these acute situations is to maintain BP below these levels and not aim for optimal BP control. Although solid evidence is unavailable to date, a number of case reports suggest that the incidence of PE in patients with COVID-19 infection may be high.195-197 Taking this into account, together with COVID-19-associated systemic inflammation, coagulation activation, hypoxaemia and immobilization, anticoagulation at standard prophylactic doses should be considered for all patients admitted to the hospital with COVID-19 infection. Patients with COVID-19 infection often present with respiratory symptoms and may also report chest pain and haemoptysis.80 These symptoms largely overlap with the presentation of acute PE which may cause underdiagnosis of this relevant complication.198 Unexpected respiratory worsening, new/unexplained tachycardia, a fall in BP not attributable to tachyarrhythmia, hypovolaemia or sepsis, (new-onset) ECG changes suggestive of PE, and signs of deep vein thrombosis of the extremities should trigger a suspicion of PE. It is recommended to only order diagnostic tests for PE when it is clinically suspected, although it is recommended to keep a low threshold of suspicion. The specificity of D-dimer tests may be lower in patients with COVID-19 compared to other clinical settings. Even so, it is still advised to follow diagnostic algorithms starting with pre-test probability and D-dimer testing, especially when pre-test probability dependent D-dimer thresholds are being used.120-122 This may help to rationalize the deployment of resources and personnel for transporting a patient to the radiology department with all the associated isolation precautions. In the clinical scenario of a patient with COVID-19, who has just undergone CT of the lungs but the findings cannot explain the severity of respiratory failure, CT pulmonary angiography may [or should] be considered before leaving the radiology department. When acute PE is confirmed, treatment should be guided by risk stratification in accordance with the current ESC guidelines.119 Patients in shock should receive immediate reperfusion therapy. Haemodynamically stable patients may be treated with either unfractionated heparin (UFH), low molecular weight heparin (LMWH) or a NOAC, depending on the possibility of oral treatment, renal function and other circumstances. When choosing the appropriate drug and regimen (parenteral versus oral) for initial, in-hospital anticoagulation, the possibility of rapid cardiorespiratory deterioration due to COVID-19 should be taken into account. Of note, some of the investigational drugs for COVID-19 may have relevant interactions with NOACs. In particular, this may be the case for lopinavir/ritonavir via Cytochrome P450 3A4 (CYP3A4) and/or P-glycoprotein (P-gp) inhibition. In such cases, the bleeding risk may be elevated and NOACs should be avoided. Because close monitoring is necessary which may contribute to spreading of the infection, vitamin K antagonists (VKAs) should only be considered in special circumstances such as the presence of mechanical prosthetic valves or the antiphospholipid syndrome.119 Very few data are available on antiarrhythmic management specifically in COVID-19 patients. Therefore, this text reflects a consensus based on limited evidence. This text will be updated if more information becomes available. The general principles of management of patients with cardiac arrhythmias and cardiac implantable devices during the COVID-19 pandemic are based on: Several national societies and health services including the Heart Rhythm Society, National Health Service (UK) and the Cardiac Society of Australia and New Zealand have issued similar local recommendations to achieve these goals and guide the management of patients with cardiac arrhythmias and cardiac implantable devices during the COVID-19 pandemic.199-201 Below, we review considerations for implantable cardiac device monitoring and follow-up, elective and urgent EP procedures and treatment options of cardiac arrhythmias during the COVID-19 pandemic. The categorization of EP procedures in the context of COVID-19 is depicted in Table 14. In summary, all elective ablation and cardiac device implantation procedures should be postponed, and antiarrhythmic medications should be reviewed and intensified if necessary, to allow control of symptomatic arrhythmia recurrences during the COVID-19 pandemic period. Urgent EP procedures in patients without suspected or confirmed COVID-19 infection should be performed in a designated non-infected catheterization laboratory area, while limiting direct contact with personnel, and with the appropriate use of PPE (Section 5) during the procedure. In patients with suspected or confirmed COVID-19 infection, the procedure should be performed in a designated catheterization laboratory area, while limiting direct contact with personnel, and with the appropriate use of PPE (Section 5) during the procedure. If intubation is required, this should be performed outside the EP laboratory to avoid contamination. The hospital stay and all ancillary procedures (ECG, echocardiography) should be reduced to minimum and be performed after clinical reassessment of their necessity. The incidence and type of cardiac arrhythmias as a direct consequence of COVID-19 infection is currently unknown. In a single centre retrospective study including 138 patients hospitalized with COVID-19 pulmonary infection in Wuhan, China, cardiac arrhythmias occurred in 23 patients (16.7%) and acute cardiac injury in 10 (7.2%) patients (defined as troponin rise, or new ECG and echocardiographic abnormalities). Cardiac arrhythmias were considered a major complication and occurred more frequently in patients who were transferred to the ICU as opposed to the patients treated on the general ward (16 [44%] of 36 patients vs. 7 [6.9%] of 102 patients, p < 0.001, respectively).10 However, the type and duration of arrhythmias was not specified in this report. In general, the acute treatment of arrhythmias should not be significantly different from their management in non-COVID-19 patients and should be in line with the current ESC, European Heart Rhythm Association and related guidelines.202-208 22.214.171.124.1. Supraventricular Tachycardia There are no specific reports on the incidence of non-AF/atrial flutter type of paroxysmal supraventricular tachycardia (PSVT) during COVID-19 infection. In theory, exacerbation of known PSVT or new-onset PSVT may occur in patients with COVID-19 infection. Special considerations during the COVID-19 pandemic are the transient unavailability of catheter ablation procedures for definitive treatment, the risk of nosocomial infection during repeated ED visits, and the possibility of therapy interactions with AADs (see Section 10). 126.96.36.199.2. Atrial Fibrillation and Flutter There are no specific reports on the occurrence of AF during COVID-19 infection. It is likely that AF may be triggered by COVID-19 infection (fever, hypoxia, adrenergic tone), either new onset or recurrent. In patients with severe pneumonia, ARDS and sepsis, the incidence of AF during hospitalization is known to be high. Reportedly 23–33% of critically ill patients with sepsis or ARDS had AF recurrence and 10% developed new-onset AF.202,209-211 New-onset AF in sepsis and ARDS has been associated with higher short- and long-term mortality, very high long-term recurrence rate and increased risk of HF and stroke.202,209-211 In a recent report from Italy, among 355 COVID-19 patients who died (mean age 79.5 years, 30% women), retrospective chart review identified a history of AF in 24.5%.18 This finding supports the estimates that especially older patients admitted to the hospital (and ICU) with COVID-19 associated pneumonia, ARDS and sepsis frequently develop new-onset or recurrent AF, which may further complicate management. Specific precipitating factors in this setting are hypokalaemia and hypomagnesaemia (induced by nausea, anorexia, diarrhoea and medications), metabolic acidosis, the use of inotropic agents (especially dobutamine and dopamine), ventilator dyssynchrony, volume overload, increased sympathetic tone, inflammation, hypoxia, ischaemia, bacterial superinfection and myocardial injury.202 As in all patients with AF, treatment goals have to consider ventricular rate control, rhythm control and thromboembolic prophylaxis. Specifically in the context of COVID-19 infection, the following considerations should be made (Figure 16): 188.8.131.52.3. Ventricular Arrhythmias Although there are no reports on the incidence of ventricular arrhythmias in the general population of patients with COVID-19 infection, a recent single centre retrospective study from Wuhan analyzed the occurrence and significance of malignant ventricular arrythmias in 187 hospitalized patients with confirmed COVID-19 infection. Among the 187 patients (mean age 58 ±14.7 years, 49% male), 43 (23%) patients died during hospitalization. Overall, 66 (35.3%) patients had underlying CVD including hypertension (32.6%), coronary heart disease (11.2%), and cardiomyopathy (4.3%), and 52 (27.8%) patients exhibited myocardial injury as indicated by elevated Troponin T levels. During hospitalization, malignant ventricular arrhythmias (defined as sustained VT or VF) occurred in 11 (5.9%) patients. VT/VF occurred more frequently in patients with elevated troponin levels (17.3% vs. 1.5%, p < 0.001).25 These findings suggest that new-onset malignant ventricular arrhythmia is a marker of acute myocardial injury and may warrant more aggressive immunosuppressive and antiviral treatment. In patients with a history of CVD and ventricular arrhythmias, exacerbation of the known VT/VF may occur due to COVID-19 infection as trigger. Although reports are not available for COVID-19, a correlation between increased appropriate ICD therapies and influenza epidemic has been shown.212 Special considerations during the COVID-19 pandemic are depicted in Figure 17 and summarized below: There are no specific reports on the occurrence of COVID-19 infection in patients with channelopathies. However, COVID-19 infection may occur in patients with known congenital LQTS, Brugada syndrome (BS), catecholaminergic polymorphic ventricular tachycardia (CPVT) and short QT syndrome, with a risk of pro-arrhythmia. The specific interactions of these channelopathies and COVID-19 has been reviewed in a recent review.213 In theory, exacerbation of known conduction system or sinus node disease or new-onset high degree AV block or sinus node dysfunction may occur in patients with COVID-19 infection, especially in case of myocardial involvement. Other mechanisms of AV block in COVID-19 are vagally mediated due to neuroinvasion, or hypoxia. A case of transient AV block in a critical COVID patient was recently published.215 One experimental study from 1999 has shown that coronavirus-infected rabbits have ECG abnormalities including 2nd degree AV block secondary to myocarditis and HF.212 In critically ill patients in the ICU, transient bradycardia and asystole may occur due to patient turning for prone respiration, intubation, or trachea suction and is probably due to transient increased vagal tone.202 Hypoxaemia should be ruled out. A heart rate/temperature discordance was observed in patients with COVID-19:10,102 The heart rate at admission was about 80 beats per minute (bpm), slower than expected in these patients with fever. This has also been observed in other infectious disease such as typhoid fever. Special considerations for permanent PM implantation in patients with COVID-19 are the poor prognosis of patients requiring mechanical ventilation, increased risk of bacterial superinfection and device infection in the critically ill patients, risk of nosocomial infection during device implantation in COVID-19 negative patients (see above) and transient bradyarrhythmic side effects of antiviral therapy. Treatment strategies against SARS-CoV‑2 potentially use a combination of several drugs exerting synergistic effects. Despite the lack of definitive evidence on their efficacy, drugs with suspected viricide effect that are being used ‘off-label’ include chloroquine/hydroxychloroquine, protease inhibitors (like lopinavir-ritonavir or, in a minority of cases, darunavir-cobicistat), remdesivir and azithromycin.217-220 In specific cases, interferon and, for the ARDS glucocorticoids and/or tocilizumab, may also be administered.221 Chloroquine has been widely used as an antimalarial drug and in the treatment of rheumatological diseases like systemic lupus erythematosus and rheumatoid arthritis, and has been found to inhibit SARS-CoV‑2 growth in vitro.218-220 Hydroxychloroquine is an analogue of chloroquine with less gastric intolerance and less concerns for drug interactions. In vitro, hydroxychloroquine was found to be more potent than chloroquine in inhibiting SARS-CoV‑2.220 A recent small clinical study reported that SARS-CoV‑2 positivity in nasopharyngeal secretions is significantly decreased at day 6 after inclusion (i.e. day 10 after symptom onset) in hydroxychloroquine-treated COVID-19 patients (n = 26) versus patients who received supportive care only (n = 16). However, several major limitations (small sample size; non-homogeneous groups with differences in viral loads, number of days since onset of symptoms and quality of follow-up; and rather late administration of the drug, close to the expected time of viral clearance), raise doubts about the significance of the findings.218 The current evidence therefore does not imply yet a translation of (hydroxy)chloroquine in vitro activity to clinically relevant outcomes. Results of ongoing clinical trials of chloroquine/hydroxychloroquine efficacy in the treatment of SARS-CoV‑2 should be awaited before definite recommendations are provided for or against the use of these drugs. One major concern with these drugs is the very rare risk of QTc prolongation and TdP/sudden death. A recent metanalysis on arrhythmogenic cardiotoxicity of the quinolines and structurally related antimalarial drugs suggested that this risk is minimal (no events of SCD or documented VF of TdP in 35 448 individuals, 1207 of whom were taking chloroquine).222 However, during COVID-19 infection, the QT-related risk may be amplified by concomitant use of other QTc-prolonging drugs and/or electrolyte imbalances (hypokalaemia, hypomagnesaemia and/or hypocalcaemia). A second concern with chloroquine/hydroxychloroquine is the potential occurrence of conduction disturbances, although these are rare and appear to be linked mostly to long-term treatment (Table 15). The protease inhibitor lopinavir-ritonavir has shown to be effective against SARS-coronavirus and MERS-coronavirus in vitro and in animal models.223-226 A recent randomized controlled open-label trial suggested that in hospitalized patients with severe COVID-19, lopinavir-ritonavir combined therapy does not provide additional benefit to standard of care.227 The main criticism of this study is the delayed time from illness onset to treatment assignment (median 13 days). Importantly, no pro-arrhythmic major adverse events were described in either arm and there was only one QTc prolongation in the lopinavir ritonavir arm (no details on the degree or the existence of other concomitant QTc prolonging factors).227 However, important drug-drug interactions have been described (mainly because these potent CYP3A4 inhibitors interfere with (hydroxy)chloroquine metabolism) that should be taken into consideration. In some combinations, dose adjustments or changes may be needed (Table 15). When lopinavir-ritonavir is not available and/or the patient is intolerant, darunavir-cobicistat is used as an alternative. In vitro and animal studies suggest that remdesivir (GS-5734) is effective against zoonotic and epidemic SARS-coronavirus and MERS-coronavirus.228-230 Several randomized controlled studies are underway in the current SARS-CoV‑2 epidemic. In vitro studies suggest a better efficacy of remdesivir compared to lopinavir-ritonavir.230 An advantage of remdesivir is that no significant drug interactions have been described. However, there are no reports on its effect on QTc duration. Unfortunately, currently it is not widely available worldwide (only in clinical trials or for compassionate use from Gilead Sciences, Inc.). The anecdotal evidence supporting the use of azithromycin (being a weak CYP3A4 inhibitor) comes from the above-mentioned open-label small non-randomized study of hydroxychloroquine treated COVID-19 patients (n = 26) versus patients who received supportive care only (n = 16). In 6 patients, the addition of azithromycin to hydroxychloroquine showed significant SARS-CoV‑2 positivity reduction in nasopharyngeal secretions compared to hydroxychloroquine alone.218 Azithromycin has in isolated cases been associated with QTc prolongation and TdP mainly in individuals with additional risk factors.231,232 Two studies have evaluated the association of chloroquine and azithromycin for the prevention and treatment for malaria in Africa with 114 and 1445 individuals, respectively in the arm treated with the combination.233,234 The association of chloroquine and azithromycin showed an acceptable safety profile. For a detailed overview of all known direct or indirect (through drug-drug interactions) arrhythmological effects of experimental pharmacological therapies in COVID-19 patients, see Table 15. QTc prolongation by some drugs can theoretically lead to polymorphic VT (TdP). This is however a very rare complication, and the consideration has to be balanced versus the anticipated benefit of therapy for the COVID-19 patient. Figure 19 provides a practical flow chart for the management of patients to prevent TdP, for guidance on the timing and repetition of ECG recording, and on QTc measurements that would alter therapy. Other guidance flowcharts have been published.213, 262 Briefly, the following steps are required to reduce the risk of drug induced TdP: Bradycardia prolongs QT and facilitates TdP. While some COVID-19 drugs have a weak bradycardic effect, the concomitant use of beta-blockers, CCBs, ivabradine and digoxin should also be evaluated. If digoxin is considered mandatory for the patient, plasma level monitoring should be considered (with ensuing dose reduction if needed). For patients with wide QRS complex (≥ 120 ms) due to bundle branch block or ventricular pacing, QTc adjustment is needed. Formulae are available, but a simpler approach may be to use a QTc cut off of 550 ms instead of 500 ms. Others propose a rule of thumb to calculate QT minus (QRS width 100 ms). A standard 12-lead ECG may not always be easy to obtain, given the enormous burden of increasing numbers of COVID-19 patients on healthcare providers. Enhanced use of modern handheld ECG devices should be considered in order to reduce traditional ECG recording as much as possible to preserve resources and limit virus spread. In a recent study, the QTc in lead‐I and lead‐II derived from a standard 12-lead ECG was compared with a rhythm strip from a handheld ECG device in 99 healthy volunteers and 20 hospitalized patients in sinus rhythm treated with dofetilide or sotalol.264 QT on the handheld device had an excellent agreement with standard 12‐lead ECG both in the normal range and in patients with QT prolongation.264 This handheld ECG device (KardiaMobile 6L Alivecor) had a high specificity for detecting a QTc > 450 ms and should thus be considered as an effective outpatient tool for monitoring patients with prolonged QTc. Recently, KardiaMobile6L received expedited approval from the FDA for QT monitoring and can thus be used in COVID-19 patients treated with QT prolonging drugs such as chloroquine or hydroxychloroquine. Many cardiac patients or patients with other CV history will have an indication for anticoagulation. Table 16 lists the possible interactions of COVID-19 therapies with VKAs, NOACs, LMWHs and UFH. The table includes information that was derived from several drug interaction sites, which have been referenced. Drug SmPCs often do not contain information for older drugs and/or drugs with a narrow spectrum of indications (like chloroquine). Antimalarial drugs have a P-glycoprotein inhibiting effect, which may affect NOAC plasma levels. COVID-19 patients on oral anticoagulation may be switched over to parenteral anticoagulation with LMWH and UFH when admitted to an ICU with a severe clinical presentation. We would like to rephrase here also the conventional dose reduction criteria for NOACs, for those patients in whom oral treatment for stroke prevention in AF patients, can be continued. For more details, including the assessment of renal (and liver) function and other considerations in patients taking a NOAC, please see the 2018 EHRA Practical Guide on the use of NOACs in patients with AF.265 Of note, none of the NOACs is recommended in patients with a creatinine clearance (CrCl) <15 ml/min according to the EU label. For patients with impaired swallowing, NOACs can be administered in the following ways: There are many pending questions about the COVID-19 pandemic.274 What is the full spectrum of disease severity? How is the transmissibility? What is the role of asymptomatic/pre-symptomatic infected persons? How long is the virus present? What are the risk factors for severe illness? Knowledge is being accumulated very fast and our task is to deliver key information for patients with CVD. There are several clinical features associated worse short-term outcome of SARS-CoV‑2 manifestations.54 These include asthma, age > 65-year-old, COPD, chronic HF, cardiac arrythmias, coronary artery disease. Female sex, statin therapy or ACE inhibitors appear to be independent protective factors. The effect of social background and ethnicity on survival needs some clarification. A cause-and-effect relationship between drug therapy and survival should not be inferred given the lack of ongoing randomized trials. Patients should be informed and take appropriate precautions with emphasis on measures for social distancing when the potential risk is high and medical resources are scarce. The following information is important for individuals with CVD: Additionally, individuals should be encouraged to follow the instruction of the Department of Health and local authorities in the resident countries as these may differ. Maintain a healthy lifestyle (e.g. eat healthy, quit smoking, restrict alcohol intake, get adequate sleep and keep physically active).276 Isolation and physical restrictions may lead to inactivity and increased risk of VTE, in combination with co-morbidities. Physical activity should be strongly encouraged either in a home setting or outdoor areas with social space and will also improve well-being. Maintaining social network should be encouraged remotely. Figure 1 Cumulative laboratory-confirmed cases of COVID-19 in Europe (World Health Organization) Figure 2 Critical role of ACE2 in the regulation of viral invasion in ACE2 expressing cells (Created using BioRender Academic). Figure 3 Cardiovascular involvement in COVID-19 – key manifestations and hypothetical mechanisms. Figure 4 Different types of masks to be used according to type of procedures and levels of risk. Figure 5 Guidance on donning personal protective equipment (PPE) to manage COVID-19 patients (modified from the "Handbook of COVID-19 Prevention and Treatment").77 Figure 6 Guidance on removing personal protective equipment (PPE) to manage COVID-19 patients (modified from the "Handbook of COVID-19 Prevention and Treatment").77 Figure 7 How do I protect myself? Figure 8 Algorithm for triaging patients admitted to the ER for a suspected acute CV disease Figure 9 Considerations in patients with suspected (or at risk for) cardiogenic shock and possible COVID-19 infection Figure 10 Temporal changes in high-sensitivity cardiac troponin I concentrations from illness onset in patients hospitalized with COVID-19. Differences between survivors and non-survivors were significant for all time points shown. ULN denotes upper limit of normal (adapted from Zhou et al.34) Figure 11 High-sensitivity cardiac troponin (hs-cTn) T/I concentrations should be interpreted as quantitative variables. Figure 12 Recommendations for management of patients with NSTE-ACS in the context of COVID-19 outbreak Figure 13 Management of patients with STEMI during COVID-19 pandemic Figure 14 Management of patients with cardiogenic shock (CS)/out-of-hospital cardiac arrest (OHCA) during COVID-19 pandemic Figure 15 Hypertension management in the COVID-19 context Figure 16 Atrial tachyarrhythmias Figure 17 Ventricular tachyarrhythmias Figure 18 Channelopathies Figure 19 QTc management Figure 20 Patient information during the COVID-19 pandemic Part 1 Figure 21 Patient information during the COVID-19 pandemic Part 2 Table 1 Types of diagnostic approaches in COVID-1954, 65; *-still in experimental phase, now available for research; POC – point of care Table 2 Testing priorities for COVID-19 pandemic according to Center for Disease Control, US Table 3 General recommendations for Health Care Personnel, with adaption differentiated according to local community level of risk and containment strategies Table 4 Patient risk status73 Table 5 SARS-CoV‑2 related personal protection management73, 81 Table 6 Non-invasive cardiovascular stress testing and imaging tests with the potential for deferral in the light of the COVID pandemic (Reproduced from Gluckman127) Table 7 Impact on the healthcare system and regional involvement in the epidemic Table 8 Strategical categorization of invasive cardiac procedures during the COVID-19 outbreak Table 9 Recommendations for fibrinolytic therapy (Extracted from 114) Table 10 Doses of fibrinolytic agents and antithrombotic co-therapies (Extracted from 114) Table 11 Detailed inclusion and exclusion criteria for triage in intensive care unit upon admission (modified from Christian et al)142 Table 12 Criteria for little or no likelihood of benefit with ICU treatment (occurrence of at least 1 criterion) Table 13 Management of chronic coronary syndromes during COVID-19 pandemic Table 14 Categorization of electrophysiological procedures in the context of COVID-19 Table 15 Arrhythmological considerations of novel experimental pharmacological therapies in COVID-19 infection Table 16 Interactions of anticoagulant drugs with COVID-19 therapies Table 17 Concomitant conditions that may be associated with more severe course of SARS-CoV‑2 infection. Many of these features are confounded by age Table 18 Potential interactions of drugs used to cure COVID-19 The European Society for Cardiology. ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic. https://www.escardio.org/Education/COVID-19-and-Cardiology/ESC-COVID-19-Guidance. (Last update: 28 May 2020). The document is not a guideline. The recommendations are the result of observations and personal experience from health care providers at the forefront of the COVID-19 pandemic. © The European Society of Cardiology 2020. All rights reserved. Our mission: To reduce the burden of cardiovascular disease. © 2020 European Society of Cardiology. All rights reserved.	2	65	0	0	1	0.527298	1	24,202
General description of procedure, equipment, technique Ventricular assist devices (VAD) can be used to support the left ventricle (LVAD), right ventricle (RVAD), or both ventricles (BiVAD). VAD were developed to support patients with circulatory failure with failing organ systems and/ or near death to sustain life until cardiac transplantation became feasible. The refinement of the devices and the improvements in outcomes has led to the widespread use of LVAD to support patients with advanced heart failure indefinitely. A durable VAD is implanted by a cardiac surgeon via a sternotomy and has a percutaneous driveline or connection to provide power and control of the device. Current devices weigh 1 lb or less and can deliver up to 10 L of flow per minute. The HeartMate II (Thoratec Corp) is FDA approved for bridge to transplant and destination therapy. It is implanted by a sternotomy and is a continuous flow LVAD (Figure 1, Figure 2). VADs do not have sealed batteries contained internally, hence the need for the driveline to provide electrical power; the potential for infection remains a limitation of VAD. All VADs require anticoagulation and antiplatelet therapy; bleeding and stroke are complications. Indications and patient selection Left ventricular assist devices (LVAD) are approved for two indications: bridge to transplant (BTT) and destination therapy (DT). The Food and Drug Administration (FDA) approves devices based upon these two indications. Although not designated by Centers for Medicare and Medicaid Services (CMS), many patients fall into an undifferentiated category or “bridge to decision.” Essentially, a bridge to decision patient is quite ill with comorbidities that might preclude an immediate decision regarding transplant candidacy. With successful LVAD support, many patients improve and become eligible for cardiac transplantation consideration. VAD BTT are considered for patients listed for cardiac transplantation that require hemodynamic support. Generally patients considered for VAD BTT are inotrope dependent and/or have cardiorenal limitations (hypotension and renal insufficiency), negating the use of neurohormonal antagonists. Patients intolerant of ACE inhibitors and beta blockers are generally quite ill and referred for LVAD consideration. Patients with pulmonary hypertension may also be considered for an LVAD, which can fully unload the left ventricle and reduce the pulmonary artery pressure. Patients with advanced heart failure considered for LVAD as DT are generally ineligible for cardiac transplantation due to age and or comorbidities. LVAD is a potentially life-sustaining therapy that will enhance the quality of life in patients otherwise unlikely to survive more than 6 to 12 months. In clinical trials, about 75% of patients were inotrope dependent. In properly selected patients, LVAD will prolong life and improve quality of life dramatically compared to medical therapy. Patient selection is based upon standard criteria established by CMS and published guidelines. (http://www.ishlt.org/ContentDocuments/JHLT_Feb13_MCS_Guidelines.pdf) Approved for heart transplant by a local selection committee and active or planned UNOS (United Network of Organ Sharing) listing of patient. Suitability for cardiac transplantation is based upon functional limitation and is generally evaluated with a metabolic stress test and other variables to estimate risk. Brain natriuretic peptide level, frequent hospitalizations for heart failure, and Seattle Heart Failure Model score are commonly used to predict mortality and to guide suitability for listing for transplantation. Stable outpatients are infrequently advised to consider LVAD BTT. An LVAD is often needed to sustain the patient’s life and end organ function until a heart donor is available. Examples include: Failing end organs with renal and hepatic dysfunction Inability to tolerate BB or ACE Often inotropic dependent Poor functional capacity and quality of life Frequent hospitalization for heart failure Various risk scores have been developed to estimate the mortality rate before hospital discharge after LVAD implant. The HeartMate II risk score multivariate predictors of 90-day mortality include age, albumin, creatinine, international normalized ration (INR), and implanting center volume. Per CMS definitions, the patient should be ineligible for heart transplant: often due to chronologic age and comorbid conditions. Typically, approximately 75% of patients are on continuous inotropes. NYHA class IV on maximal medical therapy for >60 to 90 days. Ejection fraction <25% Most with peak oxygen consumption <12 ml/kg/min. The patient has the appropriate body size (≥1.5 m2) to support the LVAD implantation. Use of INTERMACS levels guides patient selection http://www.uab.edu/intermacs/ Patients are assigned an INTERMACS level, 1-7, with a modifier for uncontrolled ventricular arrhythmias. INTERMACS level 1 patients, which are the sickest (“crash and burn”), also have the highest 30-day mortality after LVAD. Most patients undergoing LVAD today are INTERMACS level 2 and 3, which indicates chronic inotropic support. Risk scores have been developed to examine, low/medium/high risk patients using common clinical variables that predict mortality in hospitals postoperation until discharge. In general avoid critically ill patients with frank or impending renal, hepatic, or pulmonary failure due to elevated mortality rates. Patients with multiorgan failure are very high risk. Patients with severe heart failure, on a ventilator, with impending renal failure with elevated MELD scores and right heart failure are complex to care for and have increased mortality. For patients in shock and or multiorgan failure, ECMO or a percutaneous VAD such as Tandem Heart or Impella may be used. A heart failure specialist will help determine whether the patient should go to the OR for heart transplant, versus LVAD, versus no surgical therapy due to risk. Contraindications to LVAD therapy are complex and require consultation with a heart failure cardiologist and an experienced LVAD surgeon. Inability to provide informed consent Inability to receive prolonged anticoagulation and antiplatelet therapy ESRD requiring renal replacement therapy Other irreversible life-limiting disease (e.g., malignancy, advanced emphysema, cirrhosis with elevated MELD score) Cerebrovascular disease and increased risk of stroke based upon neurologic consultation Inability or refusal to receive blood products Inability to be educated regarding VAD operation and or be compliant with a complex medical regimen Prohibitive and irreversible right heart failure Prohibitive and irreversible pulmonary hypertension and elevated pulmonary vascular resistance Inability to be placed on cardiopulmonary bypass due to aortic calcification and or additional anatomic limitations Lack of support from family and others to comply with a complex treatment regimen Lack of resources (e.g., insurance) to provide for ongoing medical care including dressing changes and follow-up care after VAD implant Details of how the procedure is performed VAD implantation is performed by a cardiac surgeon using standardized surgical techniques. Most often a full incision median sternotomy is required. The patient is placed on cardiopulmonary bypass and typically cannulated after the chest is opened. An apical core is removed from the left ventricle (LV) and the inflow cannula is inserted in the LV and sutured in place. The outflow graft is an end to side anastomosis to the descending aorta. The VAD is placed in the chest or in the abdominal cavity, depending on the size of the VAD used. A driveline is tunneled and exits via the skin in the right or left lower quadrant. The batteries and controller are external to the body. Interpretation of results Recent published clinical trials and postmarket approval studies have clearly demonstrated the outcomes in patients implanted with VAD. Additionally, the INTERMACS registry contains outcomes from over 145 participating sites and over 9,200 subjects enrolled. INTERMACS is a prospective registry that collects clinical data including follow-up early postoperation and every 6 months. Major outcomes, including death, explant, rehospitalization, and adverse events, are publicly reported at the website. Quality of life and level of function is also collected and reported. BTT clinical trials typically require 6 months of follow-up and assess mortality, survival to transplant, explant, device failure, and major adverse events, including stroke, device failure, infection, and bleeding. DT clinical trials typically require 24 months of follow-up and they assess mortality, explant, device failure, and major adverse events. A smaller percentage of patients in DT clinical trials receive a transplant, as inclusion criteria specifies that those enrolled are not eligible for heart transplantation. The FDA requires postmarket approval studies such that a cohort of patients implanted after approval are followed and outcomes are compared to a reference group of patients implanted with a previously approved VAD. Typically the “control” group is obtained from the INTERMACS registry and postapproval trials are nonrandomized. These postapproval trials ensure that outcomes are equal or exceed the outcomes observed when the VAD was initially implanted in the context of a clinical trial. Outcomes (applies only to therapeutic procedures) Survival with VAD will be reviewed for BTT, DT clinical trials, and the INTERMAC registry. Expected survival rate for patients with LVAD BTT at 6 months is approximately 90% and the 30-day survival rate is approximately 95%. Competing outcomes for patients implanted with the HeartMate II LVAD BTT in a postmarket approval study at 6 months were: 90% transplanted, recovery, or ongoing support Expected survival with HeartMate II continuous flow LVAD DT at 12 months and 24 months are 68% and 58%, respectively. Major adverse events include disabling stroke, and reoperation to repair or replace VAD. In the HeartMate II DT trial, the following adverse events were observed with the continuous flow LVAD: Pump replacement 9%; 0.06 events/patient-year Ischemic and hemorrhagic stroke 18%; 0.13 events/patient-year LVAD thrombosis 4%; 0.02 events/patient-year Current INTERMACS registry data for VAD continuous flow survival in a cohort of 5,436 patients: 80%: 12 months survival 70%: 24 months survival 59%: 36 months survival 47%: 48 months survival The INTERMACS registry demonstrates that the majority of LVAD recipients have improved ability to perform usual activities of daily living as shown in the Figure 4. The HeartMate II experience has shown an increase in the 6-minute walk test of +156 meters, which is remarkable. Patient self-reported measures including the Minnesota Living with Heart Failure and the Kansas City Cardiomyopathy Scores both favorably improved. Although survival, functional capacity, and quality of life improve challenges remain as many patients are readmitted to the hospital and suffer complications, including GI bleeding, infections, and heart failure (Figure 3, Figure 4). Alternative and/or additional procedures to consider No alternatives to VAD therapy except cardiac transplantation or palliative care. Patients considered for VAD in general have very poor quality of life and expected mortality in excess of 30% at 12 months or higher. The ACC/AHA heart failure guidelines suggest for stage D heart failure: cardiac transplantation, LVAD as BTT or DT, palliative inotropes, or hospice/palliative care. The projected mortality for heart failure patients on chronic inotropic therapy is approximately 50% at 6 months and over 90% at 1 year. In addition, only cardiac transplantation and VAD therapy can provide a remarkable improvement in functional capacity (improved 6-minute walk) and quality of life. Complications and their management Complications after VAD remain challenging. All patients require anticoagulation and antiplatelet agents. All devices have a percutaneous drive line to link the implanted pump with the power supply and the controller. Major complications include: Ischemic and hemorrhagic stroke Right heart failure The INTERMACS registry indicates the only 30% of patients are free of infection, bleeding, stroke, device malfunction, and death 12 months after device implant (Figure 5). Infection: driveline infection is well controlled with mobilization of the drive line at the time of implant, patient education regarding dressing changes, and being careful to maintain the integrity of the driveline interface with the skin by immobilizing the driveline. Experienced centers report driveline infection rates of less than 5% to 10%. A serious driveline infection can spread and involve the pump pocket, often leading to bacteremia and the need for chronic antibiotic suppression. Rarely a device change or urgent transplant is required for uncontrolled pump pocket infection and bacteremia. Incision and drainage is uncommon but can be effective for recurrent infections. GI Bleeding: 20% of continuous flow VAD patients experience bleeding that can be epistaxis, and upper or lower GI bleeding. There is a propensity for bleeding from AV malformations. This may be related to a relative lack of pulsatile flow. When transfusions are required, both aspirin and warfarin are stopped and an upper and lower endoscopy is performed for GI bleeding. A negative capsule endoscopy is sometimes required. Occasionally angiography and interventional radiology may be consulted to control bleeding. Patients with continuous flow LVAD may develop acquired reduction in Von Willebrand multimers and hence be at risk for bleeding. Right heart failure: It is important to carefully select patients for LVAD expected to have improvement in right ventricular function. If a patient requires inotropic therapy to support RV function >14 days after LVAD implant, increased mortality is expected. A variety of risk scores to predict RV failure after LVAD have been developed. In general a patient with severe RV dysfunction assessed by echo, CVP >20 cm H20, and severe tricuspid regurgitation is of concern for RV failure. Alternatives are to consider BIVAD support or a total artificial heart. Patients that go back to the operating room for an RVAD have increased mortality. A small percentage of patients that have done well for many months will return with volume overload and poor RV function. An echo and right heart catheter should be performed to assess the severity of the hemodynamic abnormality and to determine if the RV failure can be ameliorated by additional unloading of the left ventricle. In general, most patients respond to intravenous diuretics. A small percentage may require chronic inotropic therapy in addition to the LVAD. Device malfunction is rare. If alarms sound immediate, interrogation by a VAD coordinator is required. Very rarely a patient will require urgent surgery for pump replacement for a catastrophic device malfunction. Device thrombosis: This is a spectrum usually characterized by hemolysis, abnormal pump function, inadequate unloading of the left ventricle, and clinical heart failure. The published clinical trials indicate this occurs in <5% to 10% of cases treated with adequate anticoagulation. If a patient presents with heart failure, check for hemolysis and request a VAD interrogation by the VAD coordinator. If hemolysis and anemia are present, the VAD should be checked for alarms and the patient should be very carefully assessed for evidence of heart failure/inadequate unloading of the LV. Rarely device thrombosis will require urgent VAD replacement. Most cases are treated with heparin and intensified anticoagulation and improve. Stroke is a devastating complication and can be ischemic or hemorrhagic. In general adequate anticoagulation is mandated to reduce the risk of VAD thrombosis and stroke. Hemorrhagic stroke is often fatal. Any change in neurologic function is a medical emergency and requires immediate imaging of the brain and consultation with the stroke service. Anticoagulation is generally held until brain imaging is completed and evaluated. No specific VAD parameters need to be changed when stroke occurs. Patients with known extensive cerebrovascular disease and or prior SAH may be at increased risk and should be carefully assessed by a neurologist before considering VAD therapy. Emerging data suggests that meticulous blood pressure control is also important to reduce the risk of stroke and that the mean arterial pressure (MAP) should be <85 mm Hg. After prolonged VAD support (>18 months), the leaflets of the aortic valve may become fused and lead to the development of aortic insufficiency. Any VAD patient that has a change in their condition from a cardiac perspective should undergo a careful echo assessment. What’s the evidence? Miller, LW. “Use of a continuous-flow device in patients awaiting heart transplantation”. N Engl J Med,. vol. 357. 2007. pp. 885-96. (This report describes the pivotal clinical trial providing evidence for the U.S. FDA approval of the continuous flow LVAD as a bridge to transplant and demonstrates the advances compared to the pulsatile LVAD.) Slaughter, MS, Rogers, JG, Milano, CA. “HeartMate II Investigators. Advanced heart failure treated with continuous-flow left ventricular assist device”. N Engl J Med. vol. 361. 2009. pp. 2241-51. (This report describes the pivotal clinical trial providing evidence for the U.S. FDA approval of the continuous flow LVAD as chronic destination therapy and demonstrates the advances compared to the pulsatile LVAD.) Rogers, JG. “Continuous flow left ventricular assist device improves functional capacity and quality of life of advanced heart failure patients”. J Am Coll Cardiol. vol. 55. 2010. pp. 1826-34. (This review describes the impressive improvements in NYHA class, quality of life, and 6-minute walk distance with the use of a continuous flow LVAD.) Starling, RC. “Results of the post-U.S. Food and Drug Administration-approval study with a continuous flow left ventricular assist device as a bridge to heart transplantation: a prospective study using the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support)”. J Am Coll Cardiol. vol. 57. 2011. pp. 1890-8. (This report demonstrates that results with the continuous flow LVAD post-BTT approval after wide use are comparable or superior to outcomes in the pivotal clinical trial.) Aaronson, KD. “Use of an intrapericardial, continuous-flow, centrifugal pump in patients awaiting heart transplantation”. Circulation,. vol. 125. 2012. pp. 3191-200. (This report reviews the pivotal clinical trial comparing the HVAD (centrifugal pump) with the axial flow LVAD in a bridge to transplant clinical trial.) Matthews, JC. “The right ventricular failure risk score a pre-operative tool for assessing the risk of right ventricular failure in left ventricular assist device candidates”. J Am Coll Cardiol. vol. 51. 2008. pp. 2163-72. (Predicting adequate RV function post-LVAD is challenging; this study provides a risk assessment tool to assess the severity of RV function and outcomes post-LVAD.) Kirklin, JK, Naftel, DC, Kormos, RL. “Fifth INTERMACS annual report: risk factor analysis from more than 6,000 mechanical circulatory support patients”. J Heart Lung Transplant. vol. 32. 2013. pp. 141-56. (A wealth of LVAD information is contained in this INTERMACS report of the U.S. registry with over 6,000 implants.) Cowger, J, Sundareswaran, K, Rogers, JG. “Predicting survival in patients receiving continuous flow left ventricular assist devices: the HeartMate II risk score”. J Am Coll Cardiol. vol. 61. 2013. pp. 313-21. (The derivation and validation of the HeartMate II Risk score is a valuable article to review to help in selection of patients for LVAD.) Park, SJ, Milano, CA, Tatooles, AJ. “Outcomes in advanced heart failure patients with left ventricular assist devices for destination therapy”. Circ Heart Fail. vol. 5. 2012. pp. 241-8. (This report demonstrates that results with the continuous flow LVAD post-DT approval after wide use are comparable or superior to outcomes in the pivotal clinical trial in destination therapy patients.) Russell, SD, Rogers, JG, Milano, CA. “Renal and hepatic function improve in advanced heart failure patients during continuous-flow support with the HeartMate II left ventricular assist device”. Circulation. vol. 120. 2009. pp. 2352-7. (This impressive article chronicle that end organ function will improve in critically ill patients successfully treated with continuous flow LVAD therapy.) Copyright © 2017, 2013 Decision Support in Medicine, LLC. All rights reserved. No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC. The Licensed Content is the property of and copyrighted by DSM. - General description of procedure, equipment, technique - Indications and patient selection - Details of how the procedure is performed - Interpretation of results - Outcomes (applies only to therapeutic procedures) - Alternative and/or additional procedures to consider - Complications and their management - What’s the evidence?	2	10	0	0	1	0.740556	1	4,586
Origin: When was the model first used? What kind of payment system is used, such as prospective, retrospective, or concurrent? Who pays for care? What is the access structure, such as gatekeeper, open-access, and so forth? How does the model affect patients? Include pros and cons. How does the model affect providers? Include pros and cons. In 1932 the American Medical Association (AMA) adopted a strong position against prepaid group practices, favoring instead indemnity-type insurance that protects the policyholder from expenses by reimbursement (Jones & Bartlett, 2007). As one of the first health policies in the U.S., indemnity plans are considered traditional health plans. Indemnity insurance plans have three options. Two of them are reimbursement plans (Howell, R., 2014). One typically covers 80 percent while the patient covers 20. The other option covers 100 percent. The third option pays the insured a certain amount each day for a maximum number of days. Indemnity plans are fee-for-service plans (retrospective). With an indemnity plan the patient pays for care. Afterwards the patient must submit a claim in order to be reimbursed. Indemnity plans are non-network based plans with open-access. This gives insured individuals flexibility when choosing doctors, hospitals, and health care facilities. No primary care physician (PCP) is necessary. No referrals are needed. Indemnity plans provide patients with flexibility and control over their medical care. No PCP must be selected. No referrals are needed to obtain services. The drawback however, is that patients must submit claims in order to receive reimbursement for services. This can take time. Indemnity plans only reimburse services covered by the insurer. Services not covered will require full payment from the patient. Providers can require the costs for services up front to guarantee they are getting what they charge. Providers are not required to help patients with the necessary paperwork needed for reimbursement. This potentially saves providers time and resources if they decide to ask for funds in full before service. The drawback to indemnity plans is that patients may not have all the funds required to front the bill. Expensive services can detour patients from seeking care. Consumer-directed health plan Consumer-directed health plans (CDHP) were the result of public backlash against managed care and the rise in health care expenditures (Bundorf,K. M., 2012). CDHP’s were first introduced in the late 1990s. CDHP’s aim to control costs by putting responsibility for health care decisions into the hands of patients. Patients with a CDHP are required to pay for medical services in a fee-for-service type payment plan (retrospective). Patients pay for costs out of pocket until a maximum out-of-pocket limit is met. The insurance company covers additional costs after the maximum limit is reached. The insurer fully reimburses the medical provider. Unless a claim is submitted (AET), in which case only a portion is reimbursed. With a CDHP the patient is required to pay 100 percent of the pharmaceutical and medical expenses. Once the yearly deductible is met, the patient will is only required to cover a certain percentage of costs. The percentage varies depending on the provider. Of course, there are plans that cover 100 percent of their in-network costs. Patients with a CDHP gain access to a network of providers that their insurance company contracts with. The patient is not required to choose a primary care physician, and is not required to obtain a referral to see a specialist for medical care (Aetna, 2012). CDHP’s offer increased consumer control over health care dollars (Furlow, E., n.d.). Patients have better support tools (online, phone). They also have more power to make decisions. Alternatively, increased decision making ability allows patients to forgo care. This can delay diagnosis and treatment. Ultimately, reducing the effectiveness of the plan altogether. Potential for higher payment amounts at time of service. Alternatively, there is a potential for greater debt amounts. Larger debts will make it necessary for health care providers to be more aggressive for collections. Providers will also encounter increased staff costs in order to follow-up with patients in advance of treatment, as well as in subsequent collection efforts (Fifth Third Bank, 2008). HealthPartners of Minneapolis pioneered point-of-service (POS) plans in 1961, but the concept took 25 years to get off the starting blocks (Dimmit, B., 1996). In 1986 CIGNA Healthcare launched Flexcare, the first POS plan. By 1995 forty percent of employers with at least 200 employees offered POS plans. Providers within a point-of-service network are usually paid a capitated fee. The fee is fixed and does not alter regardless of services rendered. POS plans operate using a prospective payment system. Insurance companies reimburse providers an agreed amount that is decided before a patient receives services. Patients are responsible for paying a co-payment when visiting a doctor. After the patient is seen, the provider submits claim forms to the insurer for the services rendered. Once the claims are processed the insurer will reimburse the provider (Austin & Wetle, 2012). If a patient goes out-of-network, they are required to pay the provider in full. Afterwards the patient can submit a claim for reimbursement. Point-of-service insurance plans utilize gatekeepers. This is the primary care physician for the insured individual. Patients are not required to obtain referrals from their primary care physician to seek medical care services from an out-of-network provider. Although it is recommended. If a patient goes out-of-network they’ll typically have to pay the majority of costs. Unless the primary care provider makes a referral to an out-of-network provider, in which case, the medical plan will pick up the tab (Small Business Majority, n.d.). Patients can easily go out of network. They have geographic flexibility that allows them to access doctors virtually anywhere. Compared to an HMO, patients have more choices. On the other hand, deductibles can be costly (Gustke, C., 2013). Provider’s in-network require a small copay. Out-of-network providers require patients to appease a high deductible. POS’s might not be worth it if you never use out-of-network providers. Out-of-network care requires patients to submit their own claims. Reimbursement can takes months to recover. POS’s are very similar to HMO’s and PPO’s. POS plans may have restrictive guidelines for health care providers. Some POS plans require the use of a primary care physician (PCP). PCP’s are responsible for routine care, all referrals, obtaining precertification for in-network services, and filling out paperwork for in-network care. Preferred provider organizations Preferred provider organizations (PPO) originated in the 1970’s. PPO’s were created from the rules of fee-for-service care. PPO’s steer employees to cooperating doctors and hospitals that have agreed to a predetermined plan for keeping costs down (Kiplinger, 2014). PPO’s negotiate a contract with providers, specialists, hospitals, and pharmacies to create a unified network. The providers within the network agree on a set rate to provide health care services at a lower rate than they normally charge for services (Kiplinger, 2014). PPO’s use a prospective and retrospective system. This is to ensure that the provider is only doing medically necessary tests and treatments for the injury being claimed, rather than trying to gain a larger reimbursement. With a PPO the insured pay a deductible to the insurer. After the deductible is paid, the insurer then covers any additional medical expenses incurred. Preventative care services are not subject to the deductible (Kiplinger, 2014). Some patients are required to make co-payments for certain services, or are required to cover a percentage of the total cost for medical services rendered. PPOs are open-access plans. PPOs allow patients to seek medical care with any provider, whether in-network or out-of-network. Patients are not required to obtain a referral, they are also not required to select a primary care physician. Patients with a PPO plan have the freedom to choose almost any medical provider or facility they want for their medical services. If a patient seeks medical care within their network, their costs will be relatively low. Patients are not required to choose a primary care physician. They are also not required to go through their primary care physician to see a specialist if said specialist is in the PPO network. On the other hand, when a patient receives care from a provider outside of their PPO network, costs can be higher and sometimes not covered at all. For in-network providers, PPO’s guarantee a large amount of patients. Most patients would rather receive care in-network opposed to paying more for out-of-network. The prospect of a larger amount of patients enrolled in the PPO can generate more income for the provider. On the other hand a provider can lose money if they are not fully reimbursed for medical services rendered, because they are not paid a capitated fee. Health savings account Health savings accounts (HSA) were signed into law in December 2003. HSA’s were created by a provision of the Medicare Prescription Drug Improvement and Modernization Act (Stevens, S., 2005). HSA’s are used in conjunction with high-deductible insurance plans to help offset the costs of medical expenses. Health savings accounts use a fee-for-service type payment plan (retrospective). When a patient receives medical care they are responsible for paying for the medical services. Once their high deductible insurance maximum is met, the insurance company will then cover any additional medical expenses. With a HSA the patient is responsible for medical expenses. Since the patient is required to have a high-deductible insurance plan in order to qualify for a health savings account, their own personal money is used to pay for the coverage. On average a high deductible begins around $1,100 for individuals and $2,200 for family plans. Money inside of an HSA is used to pay for expenses. This money is tax free and can be used to cover many other additional qualified medical services. Health savings account plans are open-access. The patient has the freedom to choose their medical provider and facilities are their own discretion. Referrals are not required and there are no networks from which a patient must choose from. Patients with a HSA have the freedom to manage their accounts and finances themselves. Patients control how money is spent, and have the freedom to choose their place of care. Any money deposited into a HSA is theirs, even if an employer contributes to it. The patient is not required to pay taxes on any money that is in their HSA, or any money used on qualified medical expenses. Potential disadvantages for patients include unpredictability of illness and budget. If money withdrawn from the HSA is used for nonmedical expenses it will be taxed. Fines can also occur. A high deductible can be difficult for some to afford. Providers benefit from direct payments received from patients. Eliminating the middle man saves time and resources. On the other hand, this makes patients more consciousness about the services they use. Some patients may opt out of treatment to avoid expense. Austin, A. & Wetle. V. (2012) The United States Health Care System, Combining Business, Health, and Delivery. (2nd ed.) Upper Saddle River, NJ: Pearson Education Barsukiewicz, C.K., Raffel, M.W., & Raffel, N. K. (2010) The U.S. Health System: Origins and Functions. (6th ed.) Mason, OH: Cengage Learning Bundorf, K. M. (2012) Consumer-Directed Health Plans: Do They Deliver? Retrieved from http://www.rwjf.org/content/dam/farm/reports/reports/2012/rwjf402405 Aetna. (2012). Summary of Benefits and Coverage. Retrieved from Furlow, E. (n.d.) Exploring Consumer-Directed Health Care. Retrieved from https://www.ciab.com/WorkArea/DownloadAsset.aspx?id=318 Fifth Third Bank. (2008). The Impact of Consumer-Directed Health Care on Providers. Retrieved from https://www.53.com/doc/cm/rc-cdh-provider-impact-10012008.pdf Stevens, S. (2005). Pros and Cons of Health Savings Accounts. Retrieved from http://www.forbes.com/feeds/mstar/2004/04/08/mstar1_11_14978_132.html Kiplinger. (2014) What to Know About Preferred-Provider Organizations. Retrieved from http://www.kiplinger.com/article/insurance/T027-C000-S001-preferred-provider-organizations.html Dimmitt, B. (1996). Can Point-of-Service Go The Distance? Retrieved from http://av4kc7fg4g.search.serialssolutions.com.ezproxy.apollolibrary.com/?ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info:sid/summon.serialssolutions.com&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Can+point-of-service+go+the+distance%3F&rft.jtitle=Business+and+Health&rft.au=Dimmitt%2C+Barbara&rft.date=1996-08-01&rft.pub=Medical+Economics+Inc&rft.issn=0739-9413&rft.volume=14&rft.issue=8&rft.spage=42&rft.externalDocID=10005483¶mdict=en-US Small Business Majority. (n.d.) Group Coverage Options. Retrieved from http://healthcoverageguide.org/part-one/group-coverage-options/#Point-of-Service+Plans+%28POS%29 Gutske, C. (2013) Pros and Cons of Health Insurance POS Plans. Retrieved from http://www.bankrate.com/finance/insurance/pros-cons-health-insurance-pos-plans.aspx Cite this page Health Insurance Matrix. (2016, Apr 15). Retrieved from https://studymoose.com/health-insurance-matrix-essay	2	6	0	0	1	0.624976	1	3,136
Peripheral Arterial Occlusive Disease. Peripheral arterial occlusive disease is four times more prevalent in diabetics than in non-diabetics.11 The. The researchers concluded that peripheral neuropathy and nerve dysfunction could already be present without a diagnosis of diabetes. Medical professionals. Do You Have Numbness, Tingling, or Burning Pain in Your Feet? Numbness, tingling or burning in your feet is most often caused by peripheral neuropathy. Athena Diagnostics' CMT Initial Genetic Assessment can test for these four genes first at a. A definitive molecular diagnosis or peripheral neuropathy can:. Jul 1, 2015. Physicians are faced with 3 distinct challenges in caring for patients with peripheral neuropathy: (1) how to efficiently and effectively screen (in. It can be hard to diagnose peripheral neuropathy, because symptoms can vary. People who have diabetes need to get a complete foot examination every year. Peripheral neuropathy can be difficult to diagnose. In almost 50 percent of neuropathy cases, a cause cannot be found. This can be reduced to about one- third at. ★ Diabetic Peripheral Neuropathy Symptoms ★ :: Diabetes Blood Sugar Levels Chart – The 3 Step Trick that Reverses Diabetes Permanently in As Little as. Peripheral neuropathy is characterized by numbness, tingling, and/or pain, typically in the hands and feet, although these symptoms can occur in other areas of Apr 6, 2017. The main symptoms of peripheral neuropathy can include: numbness. complications. Read more about diagnosing peripheral neuropathy. May 30, 2016. Peripheral neuropathy means these nerves don't work properly. Peripheral. Blood tests may be done to look for causes of nerve damage. ★ What Is Diabetic Peripheral Neuropathy ★ :: Alternative Medicine For Diabetic Nerve Pain – The 3 Step Trick that Reverses Diabetes Permanently in As. Oct 31, 2013. But neuropathy can result from other causes as well. Diagnosing peripheral neuropathy is best done by electromyography (EMG) and nerve. Foods For Diabetics List Icd 9 Code For Diabetes With Peripheral Neuropathy Read More; Diabetes Cure Shake Diabetes Cure Shake Read More; Risk Factors For. 20 million people in the United States suffer from some sort of neuropathy, and chronic pain is lonely, isolating, and so hard for others to understand how. Information about types of neuropathy like diabetic, peripheral, optic, cranial, alcoholic, etc. Symptoms like loss of sensation in the affected areas, and. Peripheral neuropathy can affect your day-to-day life in a variety of ways. It's important to. Many health conditions can cause peripheral neuropathy. The damage. Blood tests, such as glucose, vitamin B12 level, and thyroid function tests; Serum/urine. Peripheral neuropathy is a problem that affects the peripheral nerves. It can be hard to diagnose peripheral neuropathy, because symptoms can vary. People. Side Effects of Levaquin may cause peripheral neuropathy, aortic aneurysm or aortic dissection. Levaquin lawsuits are being reviewed nationwide. ★★ Icd 9 Code Diabetic Peripheral Neuropathy ★★ ::The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days.[ ICD 9 CODE DIABETIC. PERIPHERAL NEUROPATHY THERAPY TREATMENT. These symptoms can occur independently or all together. The most important part of effectively treating neuropathy is diagnosing the the underlying cause and specific nerve or. Some of the most common causes of peripheral neuropathy are preventable or treatable to some. ★★ Peripheral Neuropathy Diabetes ★★ ::The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days.[ PERIPHERAL NEUROPATHY DIABETES. Apr 4, 2017. If your healthcare provider suspects nerve damage, he or she will take an extensive medical history and do a number of neurological tests to. How to Treat Neuropathy in Feet. Neuropathy is a disease affecting the peripheral nervous system (PNS). Your PNS controls body movements, sensations, and. Peripheral neuropathy can also be caused by medications and chemicals. It can interfere with the senses, with movement, or with the function of internal organs. Taxol Peripheral Neuropathy Treatment Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent, of taxol- induced hyperalgesia and can be prevented by treatment with minocycline. and Vitamin B6. What Is Peripheral Neuropathy? Peripheral neuropathy (PN) is numbness or. Celiac disease, or gluten sensitivity, is an autoimmune inflammatory disease that damages the villi – the small, finger-like projections that line the. Peripheral Neuropathy. When peripheral nerves that carry information to and from the brain don't work properly, there can be damage to a single nerve or a. Chronic Immune Demyelinating Polyneuropathy (CIDP). Site presented by Bill Tillier. This information is taken directly from a pamphlet produced by a. Neuropathy is a disease in which the peripheral nerves of the body are injured. There are multiple diseases that could cause nerve injury and neuropathy. Diabetic proximal neuropathy, or amyotrophy, is the muscle weakness and wasting caused by years of high blood sugar. You can prevent and reverse it. Here. Neuropathy is the medical term for nerve damage. Neuropathy is a common complication of type 1 and type 2 diabetes; up to 26 percent of people with type 2. Diabetic Neuropathy natural treatment using vitamins supplements herbs, alternative therapy and remedy and the role of diet and food June 15 2017 by Ray. The symptoms of peripheral neuropathy can vary greatly depending on what. of neurological tests to determine the location and extent of your nerve damage. Brachial plexus neuropathy (BPN) can cause severe pain in your shoulder area. Read about additional symptoms and treatment options. The Rebuilder is 94% effective as a neuropathy treatment. Immediate relief. FDA registered. See how the Rebuilder can help peripheral neuropathy. More Neuropathy Articles ... - What Does Diabetic Neuropathy Pain Feel Like: @ Treatment Diabetic Peripheral Neuropathy ★★ Best Grains For Diabetics The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days. Symptoms of Diabetic Peripheral Neuropathy. sharp pains that feel like an electrical current. This ar... - Diabetic Peripheral Neuropathy Wikipedia: ★ Reversing Diabetic Peripheral Neuropathy ★ :: Diabetic Feet Problems - The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days. ★★ Treatment Diabetic Neuropathy Wikipedia ★★ ::The 3 Step Trick that Reverses Diabetes Permanently ... - High Power Laser Therapy Peripheral Neuropathy: Sep 4, 2015. High power laser therapy is revolutionizing the non-surgical treatment of. Nerve compression or damage to peripheral nerves, dorsal roots or the. Some of these conditions include: neuropathy with any part of the upper or. High Power Lase... - Pathophysiology Of Neuropathy In Diabetes Mellitus: Diabetes mellitus is a common metabolic disease worldwide affecting approx. of the vasa nervorum is important in the pathogenesis of neuropathy. ★ Pathophysiology Of Diabetes Mellitus Type 2 ★ :: What Are Diabetic Foot Pain Symptoms - The 3 Step Tric... - Can Extreme Stress Cause Peripheral Neuropathy: Aug 18, 2017. These nerves can be affected by various causes such as diabetes, viruses, metabolic problems, autoimmune diseases, etc. Whatever the cause of peripheral neuropathy on any patient, stress has a clear negative effect on the same. When we ... - Ascending Peripheral Sensory Neuropathy: Define ascending neuropathy. ascending. especially of the peripheral nervous system. hereditary motor and sensory neuropathy - a form of neuropathy that. Evaluation of Peripheral Neuropathy. Evaluation of Peripheral Neuropathy •Sensory exam: pin pric...	2	8	0	0	1	0.829764	1	1,749
Interstitial cystitis affects mostly women, but did you know it can also affect men? It’s true. Here, we explore the diagnosis and treatment of this condition, along with coding for interstitial cystitis in ICD-10-CM, CPT, and HCPCS. What Is Interstitial Cystitis? Interstitial cystitis (IC), otherwise known as painful bladder syndrome (PBS), bladder pain syndrome (BPS) or chronic pelvic pain, is chronic inflammation of the bladder wall. Most IC patients experience pelvic pain that comes and goes, pressure or discomfort in the bladder and pelvic area, and the need to urinate often and urgently. Unfortunately, there is no cure for IC, but treatments can improve the symptoms. According to the Interstitial Cystitis Association: - 3 to 8 million women in the U.S. may have IC, making that about 3 to 6 percent of all women in the U.S. - 1 to 4 million men in the U.S. have IC, but the number could be higher due to a mistaken diagnosis, such as chronic prostatitis/chronic pain syndrome. - Many adults begin their IC symptoms in childhood. Causes of Interstitial Cystitis The cause of interstitial cystitis is unknown, but researchers believe one or more events may lead to the condition. In fact, many researchers believe a trigger may damage the bladder or bladder lining initially and eventually cause IC to develop. Some of these triggers are: - Bladder trauma (such as from pelvic surgery) - Bladder overdistention (possibly due to long periods without being able to access a toilet) - Pelvic floor muscle dysfunction - Autoimmune disorder - Bacterial infection (cystitis) - Primary neurogenic inflammation (hypersensitivity or inflammation of pelvic nerves) - Spinal cord trauma Once damage occurs to the bladder wall, potassium or other particles are then allowed to leak into the bladder lining. This may further damage the bladder and cause chronic nerve pain. Interstitial cystitis symptoms can be different from one individual to the next and can also change in the same individual over time. Some IC cases are milder than others, with some of the milder cases causing no disruption to their lives. Conversely, some of the more severe cases may have symptoms that come and go and result in significant disruption. Symptoms may include some or all of these: - Pain or discomfort. This may get worse as the bladder fills up. In women, the pain or discomfort occurs in the bladder, lower back, lower abdominal, urethral, vaginal, or rectal areas. Also, IC is often associated with the menstrual period and sexual intercourse. In men with IC, pain may be felt in the testicular, scrotal, and/or perineal area and with ejaculation. - Urinary frequency. Patients may experience frequency during the day or night or both, and in severe cases, up to 40 times a day, according to the Office on Women’s Health. In early or mild cases of IC, frequency may be the only symptom. - Urinary urgency. Patients may feel the need to urinate immediately. Pain, pressure, or spasms may also be experienced with urgency. - Hunner’s ulcers and/or bleeding in the bladder. Hunner’s ulcers are red patches or lesions that can lead to stiffened tissue and reduced bladder capacity. Bleeding in the bladder lining (glomerulations) is common. The symptoms of a urinary tract infection (UTI) are similar to or the same as those found in IC. There is a difference, however. Lisa Hawes, M.D., female urology specialist at Chesapeake Urology, explains the difference in this way: “In women who have interstitial cystitis, urine culture results will be negative, meaning that no bacteria are found in the urine as with a urinary tract infection.” Also, with interstitial cystitis, women may experience pain during sexual intercourse, another symptom not commonly associated with a UTI. There is no one test to diagnose interstitial cystitis since the symptoms of IC are similar to those of other bladder disorders. However, there are tests that physicians, usually a urologist or gynecologist, can perform to rule out other possible diagnoses. These exclusions include such conditions as urinary tract cancer and bladder cancer in both men and women, and chronic prostatitis or chronic pelvic pain syndrome in men. The diagnosis of IC is made based on: - the presence of bladder-related pain, often in combination with frequency and urgency - the absence of other conditions that could lead to the patient’s symptoms According to the Urology Care Foundation, a physician may diagnose IC by doing the following: - Medical history. The physician will take a thorough history and inquire about the patient’s symptoms. - Physical and neurological exam. The physician will examine the abdomen, pelvis, and rectum in women. In men, the abdomen, prostate, and rectum will be examined. Since mental health and/or anxiety problems can affect IC, a neurological exam will be done in all patients. - Baseline voiding and pain tests. This information can help to find out what affects the pain level and how often the patient urinates, which may suggest a different diagnosis. - Urine test. The physician will get a urine sample and look at it under a microscope or send it to a lab to determine if organisms, germs, pus, or white blood cells are present. If so, there could be an infection and antibiotics are needed. If, however, the symptoms continue for weeks or months and there is no sign of infection, IC should be suspected. - Urodynamic tests. Two small catheters are inserted into the bladder, and then the body is filled with water and then drained. This is done to determine how the lower urinary tract is functioning. Urodynamics can be quite painful for IC patients. - Cystoscopy. A cystoscope, a thin tube with an eyepiece on the end, may be used to see inside the bladder. It is placed in the bladder through the urethra. The procedure can rule out other problems such as bladder cancer and, if ulcers and IC symptoms are present, IC is a pretty definite diagnosis. If a cystoscopy is done in an operating room, any bladder tumors, stones, bleeding, or ulcers that are seen can be taken care of immediately. This involves the physician taking a tissue sample, called a biopsy, to help in the diagnosis. Currently, there is no cure for IC, but there are treatments that can improve the patient’s symptoms, according to the American Urological Association’s Treatment Guidelines. The more conservative therapies should be started first before proceeding to the less conservative therapies as needed. Most patients require a combination of treatments in order to control their symptoms. Treatment therapies include: First line of treatment - IC education, diet modification, bladder retraining, stress management, and healthy sleep habits. Second line of treatment - Physical therapy to help with pelvic floor, lower abdomen, and back muscles - Pain medicines to include: - Over-the-counter medicines: such as aspirin, NSAIDs, ibuprofen, and Naproxen sodium - Non-narcotic pain medicines: such as Phenazopyridine Plus, Pyridium, and Uribel - Topical medicines: such as lidocaine patch or vaginal and rectal diazepam - Narcotic pain medicines: such as hydrocodone, oxycodone, and methadone - Antidepressants such as Elavil, Prozac, Cymbalta and Wellbutrin - Antihistamines such as Hydroxyzine, Claritin, Benadryl, and Singulair - Pentosan Polysulfate Sodium such as Elmiron - Bladder instillations such as DMSO (dimethyl sulfoxide), Sodium Hyaluronate, Heparin, and bladder cocktails Third line of treatment - Surgical Procedures such as fulguration with laser or electrocautery for Hunner’s ulcers - Cystoscopy under anesthesia with short-duration, low-pressure hydrodistention if the first and second line of treatments haven’t provided enough symptom control Fourth Line of Treatment - Intra-bladder Botox (BTX-A) if the patient is comfortable with self-catheterization - Neuromodulation (also known as electrical nerve stimulation), such as UrgentPC, InterStim, Eon Mino, and IF3WAVE; if successful, a neuorstim device implant or consistent neurostim treatments Fifth Line of Treatment - Immunosuppressants, such as Cyclosporine A, CellCept, and Mycophenolate mofetil, to be taken orally Sixth Line of Treatment - Major surgery such as substitution cystoplasty, urinary diversion with or without cystectomy Treatments That Should NOT be performed, according to the American Urological Association (AUA) and reported by the Interstitial Cystitis Association, include: - Long-term antibiotics when there is no proven infection - Bacillus Calmette-Guerin (BCG) instillations - Resiniferatoxin instillations - High pressure, long-duration hydrodistension - Long-term oral steroids Although not part of the above list, the Interstitial Cystitis Association points out that the potassium sensitivity test is not useful. In addition, the American Urological Association states it unnecessarily painful to patients and is not used as often as it once was. ICD-10-CM codes for interstitial cystitis can be found in the coding manual in Chapter 14. Diseases of the genitourinary system (N00-N99), and specifically under N30-N39 Other diseases of the urinary system (N30-N39) and N30 Cystitis. Interstitial cystitis (chronic) is further broken down into two codes for without and with hematuria since blood in the urine (hematuria) is often the first sign of IC. These codes are: N30.10 – Interstitial cystitis (chronic) without hematuria; and N30.11 – Interstitial cystitis (chronic) with hematuria Two common treatments for IC include a cystoscopy with hydrodistention and a bladder instillation. Cystoscopy with hydrodistention (hydrodilation) is often done on an outpatient basis under general or local anesthesia. A physician inserts fluid into the bladder to stretch it and uses a cystoscope to look inside. This allows the physician to see any changes associated with IC, such as glomerulations or petechial hemorrhages (tiny red marks on the bladder wall). Hunner’s ulcers may also be seen in a small number of IC cases. Depending on the anesthesia documented, one of these two codes may be reported: 52260 – Cystourethroscopy, with dilation of bladder for interstitial cystitis; general or conduction (spinal) anesthesia 52265 – Cystourethroscopy, with dilation of bladder for interstitial cystitis; local anesthesia These codes may only be used when the procedure is performed on IC patients. In a bladder instillation, the physician fills the bladder with a therapeutic solution, or bladder cocktail, through a catheter. There may be several different drugs in the cocktail. When reporting for a bladder instillation, the following CPT code should be assigned: 51700 – Bladder irrigation, simple, lavage and/or instillation Per AMA Guidelines, “Codes 51701-51702 are reported only when performed independently. Do not report 51701-51702 when catheter insertion is an inclusive component of another procedure.” As a rule, local anesthesia, if used, is not billed separately, as it is considered part of the initial procedure. The use of lidocaine or other local analgesic is also not usually reported separately. Besides CPT code 51700 for the bladder instillation, you will also need to report the code for the drug instilled. For example, if the documentation indicates that 50 ml of dimethyl sulfoxide (DMSO) 50% aqueous irrigation solution was instilled into the bladder, the appropriate HCPCS code would be: J1212 – Injection, DMSO, dimethyl sulfoxide, 50%, 50 ml According to United Healthcare’s Policy Guideline, coverage of DMSO will depend on the individual insurance plan and what is reasonable and necessary. DMSO may not be considered reasonable and necessary for treatment of another condition other than interstitial cystitis. Hopefully, you now have a better understanding of interstitial cystitis and how it is diagnosed and treated. In addition, you can hopefully assign the appropriate ICD-10-CM code for IC with and without hematuria and the CPT and HCPCS codes for two common treatments of IC (cystoscopy with hydrodistention and bladder instillation/DMSO). The following video also explains interstitial cystitis and its treatments. The ICD-10-CM and CPT/HCPCS codes provided here remain current and accurate based on the 2020 coding changes. If you found this article helpful, be sure to check out: - Sacral Neuromodulation / Stimulation Procedure Coding - Difference Between Parkinsonism and Parkinson’s Disease (with ICD-10 Coding) - Parkinson’s and Deep Brain Neurostimulator Coding in CPT - Identify Hypothermia and Correctly Report Diagnoses in ICD-10-CM - What You Should Know About PAM and Why PAM is Not Your Friend	4	12	7	2	3	0.969485	12	2,968
Long QT syndrome \|Long QT syndrome\| \|Classification and external resources\| Schematic representation of normal ECG trace (sinus rhythm) with waves, segments, and intervals labeled. The QT interval is marked by blue stripe at bottom. Long QT syndrome (LQTS) is a rare inherited heart condition in which delayed repolarization of the heart following a heartbeat increases the risk of episodes of torsades de pointes (TDP, a form of irregular heartbeat that originates from the ventricles). These episodes may lead to palpitations, fainting, and sudden death due to ventricular fibrillation. Episodes may be provoked by various stimuli, depending on the subtype of the condition. The condition is so named because of the appearances of the electrocardiogram (ECG/EKG), on which there is prolongation of the QT interval. In some individuals the QT prolongation occurs only after the administration of certain medications. - 1 Genetics - 2 Pathophysiology - 3 Diagnosis - 4 Treatment options - 5 Prognosis - 6 Epidemiology - 7 History - 8 See also - 9 References - 10 External links Genes and mutations LQTS can arise from mutation of one of several genes. These mutations tend to prolong the duration of the ventricular action potential (APD), thus lengthening the QT interval. LQTS can be inherited in an autosomal dominant or a much less common autosomal recessive fashion. The autosomal recessive forms of LQTS tend to have a more severe phenotype, with some variants having associated syndactyly (LQT8) or congenital neural deafness (LQT1). A number of specific gene loci have been identified that are associated with LQTS. Genetic testing for LQTS is clinically available and may help to direct appropriate therapies . The most common causes of LQTS are mutations in the genes KCNQ1 (LQT1), KCNH2 (LQT2), and SCN5A (LQT3); the following is a list of all known genes associated with LQTS: \|LQT1\|\|192500\|\|alpha subunit of the slow delayed rectifier potassium channel (KvLQT1 or KCNQ1)\|\|The current through the heteromeric channel (KvLQT1 + minK) is known as IKs. These mutations often cause LQT by reducing the amount of repolarizing current. This repolarizing current is required to terminate the action potential, leading to an increase in the action potential duration (APD). These mutations tend to be the most common yet least severe.\| \|LQT2\|\|152427\|\|alpha subunit of the rapid delayed rectifier potassium channel (hERG + MiRP1)\|\|Current through this channel is known as IKr. This phenotype is also probably caused by a reduction in repolarizing current.\| \|LQT3\|\|603830\|\|alpha subunit of the sodium channel (SCN5A)\|\|Current through this channel is commonly referred to as INa. Depolarizing current through the channel late in the action potential is thought to prolong APD. The late current is due to the failure of the channel to remain inactivated. As a consequence, it can enter a bursting mode, during which significant current enters abruptly when it should not. These mutations are more lethal but less common.\| \|LQT4\|\|600919\|\|anchor protein Ankyrin B\|\|LQT4 is very rare. Ankyrin B anchors the ion channels in the cell.\| \|LQT5\|\|176261\|\|beta subunit MinK (or KCNE1), which coassembles with KvLQT1\|\|-\| \|LQT6\|\|603796\|\|beta subunit MiRP1 (or KCNE2), which coassembles with hERG\|\|-\| \|LQT7\|\|170390\|\|potassium channel KCNJ2 (or Kir2.1)\|\|The current through this channel and KCNJ12 (Kir2.2) is called IK1. LQT7 leads to Andersen-Tawil syndrome.\| \|LQT8\|\|601005\|\|alpha subunit of the calcium channel Cav1.2 encoded by the gene CACNA1c.\|\|Leads to Timothy's syndrome.\| Drug induced QT prolongation is usually a result of treatment by anti-arrhythmic drugs such as amiodarone and sotalol or a number of other drugs that have been reported to cause this problem (e.g., cisapride). Some anti-psychotic drugs, such as haloperidol and ziprasidone, have a prolonged QT interval as a rare side-effect. Genetic mutations may make one more susceptible to drug-induced LQT. LQT1 is the most common type of long QT syndrome, making up about 30 to 35 percent of all cases. The LQT1 gene is KCNQ1, which has been isolated to chromosome 11p15.5. KCNQ1 codes for the voltage-gated potassium channel KvLQT1 that is highly expressed in the heart. It is believed that the product of the KCNQ1 gene produces an alpha subunit that interacts with other proteins (in particular, the minK beta subunit) to create the IKs ion channel, which is responsible for the delayed potassium rectifier current of the cardiac action potential. Mutations to the KCNQ1 gene can be inherited in an autosomal dominant or an autosomal recessive pattern in the same family. In the autosomal recessive mutation of this gene, homozygous mutations in KVLQT1 leads to severe prolongation of the QT interval (due to near-complete loss of the IKs ion channel), and is associated with increased risk of ventricular arrhythmias and congenital deafness. This variant of LQT1 is known as the Jervell and Lange-Nielsen syndrome. Furthermore it has recently been shown that LQT1 patients also have an endocrine phenotype. During a glucose load, LQT1 patients respond with an exaggerated insulin secretion followed by a temporary insulin resistance. When the resistance diminish, LQT1 patients are at risk for hypoglycaemia. Most individuals with LQT1 show paradoxical prolongation of the QT interval with infusion of epinephrine. This can also unmark latent carriers of the LQT1 gene. The LQT2 type is the second most common gene location that is affected in long QT syndrome, making up about 25 to 30 percent of all cases. This form of long QT syndrome most likely involves mutations of the human ether-a-go-go related gene (hERG) on chromosome 7. The hERG gene (also known as KCNH2) is part of the rapid component of the potassium rectifying current (IKr). (The IKr current is mainly responsible for the termination of the cardiac action potential, and therefore the length of the QT interval.) The normally functioning hERG gene allows protection against early after depolarizations (EADs). Most drugs that cause long QT syndrome do so by blocking the IKr current via the hERG gene. These include erythromycin, terfenadine, and ketoconazole. The hERG channel is very sensitive to unintended drug binding due to two aromatic amino acids, the tyrosine at position 652 and the phenylalanine at position 656. These amino acid residues are poised so that a drug binding to them will block the channel from conducting current. Other potassium channels do not have these residues in these positions and are, therefore, not as prone to blockage. The LQT3 type of long QT syndrome involves mutation of the gene that encodes the alpha subunit of the Na+ ion channel. This gene is located on chromosome 3p21-24, and is known as SCN5A (also hH1 and NaV1.5). The mutations involved in LQT3 slow the inactivation of the Na+ channel, resulting in prolongation of the Na+ influx during depolarization. However, the mutant sodium channels inactivate more quickly, and may open repetitively during the action potential. A large number of mutations have been characterized as leading to or predisposing to LQT3. Calcium has been suggested as a regulator of SCN5A, and the effects of calcium on SCN5A may begin to explain the mechanism by which some these mutations cause LQT3. Furthermore, mutations in SCN5A can cause Brugada syndrome, cardiac conduction disease and dilated cardiomyopathy. In rare situations, some affected individuals can have combinations of these diseases. is an autosomal dominant relatively uncommon form of LQTS. It involves mutations in the gene KCNE1, which encodes for the potassium channel beta subunit MinK. In its rare homozygous forms, it can lead to Jervell and Lange-Nielsen syndrome is an autosomal dominant relatively uncommon form of LQTS. It involves mutations in the gene KCNE2, which encodes for the potassium channel beta subunit MiRP1, constituting part of the IKr repolarizing K+ current. Andersen-Tawil syndrome is an autosomal dominant form of LQTS associated with skeletal deformities. It involves mutation in the gene KCNJ2, which encodes for the potassium channel protein Kir 2.1. The syndrome is characterized by Long QT syndrome with ventricular arrhythmias, periodic paralysis, and skeletal developmental abnormalities as clinodactyly, low-set ears and micrognathia. The manifestations are highly variable. Timothy's syndrome is due to mutations in the calcium channel Cav1.2 encoded by the gene CACNA1c. Since the Calcium channel Cav1.2 is abundant in many tissues, patients with Timothy's syndrome have many clinical manifestations including congenital heart disease, autism, syndactyly, and immune deficiency. This newly discovered variant is caused by mutations in the membrane structural protein, caveolin-3. Caveolins form specific membrane domains called caveolae in which among others the NaV1.5 voltage-gated sodium channel sits. Similar to LQT3, these particular mutations increase so-called 'late' sodium current, which impairs cellular repolarization. This novel susceptibility gene for LQT is SCN4B encoding the protein NaVβ4, an auxiliary subunit to the pore-forming NaV1.5 (gene: SCN5A) subunit of the voltage-gated sodium channel of the heart. The mutation leads to a positive shift in inactivation of the sodium current, thus increasing sodium current. Only one mutation in one patient has so far been found. GIRK4 is involved in the parasympathetic modulation of the heart. Clinically the patients are characterized by only modest QT prolongation but an increased prospency for atrial arrhythmias . Jervell and Lange-Nielsen syndrome In untreated individuals with JLNS, about 50 percent die by the age of 15 years due to ventricular arrhythmias. Romano-Ward syndrome is an autosomal dominant form of LQTS that is not associated with deafness. The diagnosis is clinical and is now less commonly used in centres where genetic testing is available, in favour of the LQT1 to 10 scheme given above. All forms of the long QT syndrome involve an abnormal repolarization of the heart. The abnormal repolarization causes differences in the refractory period of the heart muscle cells (myocytes). After-depolarizations (which occur more commonly in LQTS) can be propagated to neighboring cells due to the differences in the refractory periods, leading to re-entrant ventricular arrhythmias. It is believed that the so-called early after-depolarizations (EADs) that are seen in LQTS are due to re-opening of L-type calcium channels during the plateau phase of the cardiac action potential. Since adrenergic stimulation can increase the activity of these channels, this is an explanation for why the risk of sudden death in individuals with LQTS is increased during increased adrenergic states (i.e., exercise, excitement) -- especially since repolarization is impaired. Normally during adrenergic states, repolarizing currents will also be enhanced to shorten the action potential. In the absence of this shortening and the presence of increased L-type calcium current, EADs may arise. The so-called delayed after-depolarizations (DADs) are thought to be due to an increased Ca2+ filling of the sarcoplasmic reticulum. This overload may cause spontaneous Ca2+ release during repolarization, causing the released Ca2+ to exit the cell through the 3Na+/Ca2+-exchanger, which results in a net depolarizing current. The diagnosis of LQTS is not easy since 2.5% of the healthy population have prolonged QT interval, and 10–15% of LQTS patients have a normal QT interval. A commonly used criterion to diagnose LQTS is the LQTS "diagnostic score". The score is calculated by assigning different points to various criteria (listed below). With four or more points, the probability is high for LQTS; with one point or less, the probability is low. A score of two or three points indicates intermediate probability. - QTc (Defined as QT interval / square root of RR interval) - ≥ 480 ms - 3 points - 460-470 ms - 2 points - 450 ms and male gender - 1 point - Torsades de pointes ventricular tachycardia - 2 points - T wave alternans - 1 point - Notched T wave in at least 3 leads - 1 point - Low heart rate for age (children) - 0.5 points - Syncope (one cannot receive points both for syncope and torsades de pointes) - With stress - 2 points - Without stress - 1 point - Congenital deafness - 0.5 points - Family history (the same family member cannot be counted for LQTS and sudden death) - Other family members with definite LQTS - 1 point - Sudden death in immediate family members (before age 30) - 0.5 points Those diagnosed with long QT syndrome are usually advised to avoid drugs that would prolong the QT interval further or lower the threshold for TDP. In addition to this, there are two intervention options for individuals with LQTS: arrhythmia prevention and arrhythmia termination. Arrhythmia suppression involves the use of medications or surgical procedures that attack the underlying cause of the arrhythmias associated with LQTS. Since the cause of arrhythmias in LQTS is after depolarizations, and these after depolarizations are increased in states of adrenergic stimulation, steps can be taken to blunt adrenergic stimulation in these individuals. These include: - Administration of beta receptor blocking agents, which decreases the risk of stress-induced arrhythmias. Beta blockers are the first choice in treating Long QT syndrome. In 2004, it was shown that genotype and QT interval duration are independent predictors of recurrence of life-threatening events during beta-blockers therapy. To be specific, the presence of QTc >500ms and LQT2 and LQT3 genotype are associated with the highest incidence of recurrence. In these patients, primary prevention with ICD (Implantable cardioverter-defibrillator) implantation can be considered. - Potassium supplementation: If the potassium content in the blood rises, the action potential shortens, and due to this reason it is believed that increasing potassium concentration could minimize the occurrence of arrhythmias. It should work best in LQT2, since the HERG channel is especially sensitive to potassium concentration, but the use is experimental and not evidence-based. - Mexiletine, a sodium channel blocker: In LQT3, the problem is that the sodium channel does not close properly. Mexiletine closes these channels and is believed to be usable when other therapies fail. It should be especially effective in LQT3, but there is no evidence based documentation. - Amputation of the cervical sympathetic chain (left stellectomy). This may be used as an add-on therapy to beta blockers, but modern therapy favors mostly ICD implantation if beta blocker therapy fails. Arrhythmia termination involves stopping a life-threatening arrhythmia once it has already occurred. One effective form of arrhythmia termination in individuals with LQTS is placement of an implantable cardioverter-defibrillator (ICD). Also, external defibrillation can be used to restore sinus rhythm. ICDs are commonly used in patients with syncopes despite beta blocker therapy, and in patients having experienced a cardiac arrest. It is hoped that, with better knowledge of the genetics underlying the long QT syndrome, more precise treatments will become available. The risk for untreated LQTS patients having events (syncopes or cardiac arrest) can be predicted from their genotype (LQT1-8), gender, and corrected QT interval. - High risk (> 50%) QTc > 500 ms LQT1 & LQT2 & LQT3 (males) - Intermediate risk (30-50%) QTc > 500 ms LQT3 (females) QTc < 500 ms LQT2 (females) & LQT3 - Low risk (< 30%) QTc < 500 ms LQT1 & LQT2 (males) Inherited long QT interval syndrome affects about 1 in 7,000 people. The first documented case of Long QT syndrome was described in Leipzig by Meissner in 1856, where a deaf girl died after her teacher yelled at her. When the parents were told about her death, they told that her older brother who also was deaf died after a terrible fright. This was several decades before the ECG was invented, but is likely the first described case of Jervell and Lange-Nielsen syndrome. In 1957, the first case documented by ECG was described by Anton Jervell and Fred Lange-Nielsen, working in Tønsberg, Norway. Italian pediatrician Cesarino Romano, in 1963, and Irish pediatrician Owen Conor Ward, in 1964, separately described the more common variant of Long QT syndrome with normal hearing, later called Romano-Ward syndrome. The establishment of the International Long-QT Syndrome Registry in 1979 allowed numerous pedigrees to be evaluated in a comprehensive manner. This helped in detecting many of the numerous genes involved. - Cardiac action potential - Short QT syndrome - Steve Konowalchuk, a former hockey player who retired after being diagnosed with Long QT syndrome - Morita H, Wu J, Zipes DP (August 2008). "The QT syndromes: long and short". Lancet 372 (9640): 750–63. doi:10.1016/S0140-6736(08)61307-0. PMID 18761222. - Hedley PL; Jorgensen P; Schlamowitz S; Wangari, Romilda et al. (2009). "The genetic basis of long QT and short QT syndromes: a mutation update". Human Mutation 30 (11): 1486–511. doi:10.1002/humu.21106. PMID 19862833. - Goldman 2011, pp. 185 - Arrhythmia/Electrophysiology The Jervell and Lange-Nielsen Syndrome Natural History, Molecular Basis, and Clinical Outcome Peter J. Schwartz, MD; Carla Spazzolini, DVM; Lia Crotti, MD; Jørn Bathen, MD; Jan P. Amlie, MD; Katherine Timothy, RN; Maria Shkolnikova, MD; Charles I. Berul, MD; Maria Bitner-Glindzicz, MD; Lauri Toivonen, MD; Minoru Horie, MD; Eric Schulze-Bahr, MD; Isabelle Denjoy, MD; https://circ.ahajournals.org/content/113/6/783.abstract. Circulation. 2006; 113: 783-790 doi: 10.1161/CIRCULATIONAHA.105.592899 - Torekov SS, Iepsen E, Christiansen M et al. (2014). "KCNQ1 Long QT syndrome patients have hyperinsulinemia and symptomatic hypoglycemia.)". Diabetes. PMID 24357532. - Tristani-Firouzi M, Jensen JL, Donaldson MR et al. (2002). "Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome)". J. Clin. Invest. 110 (3): 381–8. doi:10.1172/JCI15183. PMC 151085. PMID 12163457. - Wang F, Liu J, Hong L et al. (2013). "The phenotype characteristics of type 13 long QT syndrome with mutation in KCNJ5 (Kir3.4-G387R).)". Heart Rhythm 10 (10): 1500. PMID 23872692. - Moric-Janiszewska E, Markiewicz-Łoskot G, Loskot M, Weglarz L, Hollek A, Szydlowski L (2007). "Challenges of diagnosis of long-QT syndrome in children". Pacing Clin Electrophysiol 30 (9): 1168–1170. doi:10.1111/j.1540-8159.2007.00832.x. PMID 17725765. - Schwartz PJ, Moss AJ, Vincent GM, Crampton RS (1993). "Diagnostic criteria for the long QT syndrome. An update". Circulation 88 (2): 782–4. doi:10.1161/01.CIR.88.2.782. PMID 8339437. - "QT Drug List by Risk Groups". Arizona Center for Education and Research on Therapeutics. Retrieved 2010-07-04. - Priori SG, Napolitano C, Schwartz PJ et al. (2004). "Association of long QT syndrome loci and cardiac events among patients treated with beta-blockers". JAMA 292 (11): 1341–4. doi:10.1001/jama.292.11.1341. PMID 15367556. - Compton SJ, Lux RL, Ramsey MR et al. (1996). "Genetically defined therapy of inherited long-QT syndrome. Correction of abnormal repolarization by potassium". Circulation 94 (5): 1018–22. doi:10.1161/01.CIR.94.5.1018. PMID 8790040. - Ellinor PT, Milan DJ, MacRae CA (2003). "Risk stratification in the long-QT syndrome". N. Engl. J. Med. 349 (9): 908–9. doi:10.1056/NEJM200308283490916. PMID 12944579. - Goldman 2011, pp. 366 - Tranebjaerg L, Bathen J, Tyson J et al. (1999). "Jervell and Lange-Nielsen syndrome: a Norwegian perspective". American Journal of Medical Genetics 89 (3): 137–46. doi:10.1002/(SICI)1096-8628(19990924)89:3<137::AID-AJMG4>3.0.CO;2-C. PMID 10704188. - Jervell A, Lange-Nielsen F (July 1957). "Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval and sudden death". Am. Heart J. 54 (1): 59–68. doi:10.1016/0002-8703(57)90079-0. PMID 13435203. - Romano C, Gemme G, Pongiglione R (September 1963). "Rare cardiac arrythmias of the pediatric age. II. Syncopal attacks due to paroxysmal ventricular fibrillation". Clin Pediatr (Bologna) (in Italian) 45: 656–83. PMID 14158288. - Ward OC (April 1964). "A new familial cardiac syndrome in children". J Ir Med Assoc 54: 103–6. PMID 14136838. - Moss AJ; Schwartz PJ (2005). "25th Anniversary of the International Long-QT Syndrome Registry". Circulation 111 (9): 1199–1201. doi:10.1161/01.CIR.0000157069.91834.DA. PMID 15753228. - Goldman, Lee (2011). Goldman's Cecil Medicine (24th ed.). Philadelphia: Elsevier Saunders. p. 1196. ISBN 1437727883.	2	31	5	1	0	0.921875	6	5,434
Ghost Cell Glaucoma Ghost cell glaucoma is a secondary open-angle glaucoma caused by degenerated red blood cells (ghost cells) blocking the trabecular meshwork. Ghost cell glaucoma ICD 365.63 Following a vitreous hemorrhage episode, blood breakdown products may accumulate in the trabecular meshwork. Hemolyzed erythrocytes may obstruct aqeous outflow and lead to a secondary open-angle glaucoma known as ghost cell glaucoma. Ghost cell glaucoma may occur after vitreous hemorrhage. Causes of ghost cell glaucoma include ocular trauma, systemic diseases such as diabetes or sickle cell disease/trait, iritis (Fuchs heterochromic iridocyclitis, herpes simplex, herpes zoster, etc.), intraocular tumors (retinoblastoma, malignant melanoma, etc.), uveitis glaucoma hyphema syndrome, rubeosis iridis, iris varices, papillary microhemangiomas, and ocular surgery including but not limited to cataract extraction, laser trabeculoplasty and iridotomy. One case report of ghost cell glaucoma after a snake bite has been reported. Ghost cell glaucoma has also been reported to occur spontaneously. Risk factors for posttraumatic glaucoma include advancing age, visual acuity on presentation worse than 20/200, iris injury, lens injury, hyphema, and angle recession. Risk factors for ghost cell glaucoma include vitreous hemorrhage. Angle recession is not seen in ghost cell glaucoma. A constellation of histopathologic findings may develop in the vitreous following vitreous hemorrhage. After 3-10 days, red blood cell (RBC) clots undergo fibrinolysis and red blood cells may diffuse throughout the vitreous cavity. At this time, breakdown of red blood cells also occurs. The hemoglobin that remains within the cell denatures and forms clumps called Heinz bodies, which adhere to the inner surface of the plasma membrane. The extracellular hemoglobin also becomes denatured and clumped, often forming small to large accumulations that tend to adhere to vitreous strands. The adherence to and the entrapment within vitreous strands prevents these extracellular clumps of hemoglobin from moving freely and from passing into the anterior chamber. Loss of hemoglobin from the red blood cells produces ghost cells and hemoglobin spherules. During the conversion to the ghost cell form, intracellular hemoglobin is lost, presumably through leaky membranes, into the extracellular vitreous spaces. Ghost cells appear as small, spherical, khaki-colored cells and do not adhere to each other or to the vitreous strands and are free to move anteriorly. They gain access to the anterior chamber through a disrupted anterior hyaloid face, which can occur from previous surgery (pars plana vitrectomy, cataract extraction, or capsulotomy), trauma or spontaneous disruption. Ghost cells are generally 4 to 7 micrometers in size and less pliable than normal RBCs. As a result of their loss of pliability, ghost cells remain longer in the anterior chamber because their rigidity makes it difficult for them to escape through the trabecular meshwork. This causes obstruction of the trabecular meshwork and secondary glaucoma. The cells develop within 1-3 months of a vitreous hemorrhage. It is important to note that the presence of ghost cells does not necessarily lead to development of ghost cell glaucoma. Ghost cell glaucoma is a clinical diagnosis. Diagnostic findings include presence of heme in the vitreous, ghost cells in the anterior chamber, delayed onset of increased intraocular pressure, an open angle on gonioscopy with possible presence of ghost cells layering over the trabecular meshwork inferiorly due to gravity , and often a disrupted anterior hyaloid face. Historically, the diagnosis of ghost cell glaucoma was made by phase-contrast microscopy* of anterior chamber (AC) aspirate, paraffin embedding after centrifugation of AC aspirate, or staining of the sample with 1 % methyl violet. Heinz bodies, spherical erythrocytes with denaturized hemoglobin granules bound to the internal surface of the cell membrane, are observed with H&E staining. Ghost cell glaucoma was originally described by Campbell et al in 1976. Once it was also termed “hemophthalmitis” which was a misnomer as usually there is no evidence of active inflammation and this term has been since abandoned. Clinically, patients present with intraocular pressure (IOP) spikes (as high as 60 to 70 mmHg) and a history of vitreous hemorrhage resulting from trauma, surgery, or preexisting retinal disease 1-3 months prior to presentation. The IOP may be markedly elevated, causing corneal edema. The anterior chamber is filled with small, circulating, tan colored cells. If fresh red blood cells exist, two or more different layers of cells are seen, with the lighter khaki-colored layer of ghost cells appearing on top of a heavier, red blood cell layer, imparting a candy-striped appearance. The cellular reaction appears out of proportion to the aqeous flare. The conjunctiva tends not be inflamed unless the IOP is markedly elevated or there is a history of previous surgery. Gonioscopy reveals either a normal appearing open angle; an open angle covered by a fine layer of khaki-colored cells, which have slightly to moderately discolored the trabecular meshwork; or a heavy layer filling the angle, generally inferiorly, with cells composing an early pseudohypopyon. The vitreous has the appearance of an old hemorrhage, with characteristic khaki coloration of RBCs and clumps of extracellular pigmentation from degenerated hemoglobin. The symptoms relate to the etiology. Pain secondary to trauma or surgery may be experienced by the patient. However, less pain is reported than expected from a severely elevated IOP. Patients with high IOP may also present with blurry vision, headache, brow ache, nausea and/or vomiting. The diagnosis of ghost cell glaucoma is usually clinical. The history and paracentesis with phase-contrast microscopy of the aspirate would confirm this diagnosis. For spontaneous hemorrhages, complete blood count with coagulation profile and sickle cell prep in African American patients are warranted. Differential Diagnosis of Ghost cell glaucoma includes Angle Recession glaucoma, Hemolytic glaucoma, Hemosiderotic glaucoma, Uveitic glaucoma, Neovascular glaucoma and Acute angle closure (Mechanical secondary to trauma). Hemosiderotic Glaucoma is a late onset glaucoma following intraocular hemorrhage with iron deposition in and damage to the trabecular meshwork. This extremely rare glaucoma is more chronic, does not have ghost cells in the anterior chamber, and is characteristically associated with a slight discoloration of the meshwork. It occurs many years after the original injury, in contrast to the ghost cell glaucoma, which occurs within weeks to months after the original injury. Hemolytic Glaucoma is a type of secondary glaucoma where red blood cell debris and macrophages block the trabecular meshwork after a vitreous hemorrhage. In ghost cell glaucoma, little to no red blood cell debris and few to no macrophages are found in the trabecular meshwork. Neovascular glaucoma is differentiated from ghost cell glaucoma by the absence of ghost cells within the anterior chamber and the presence of neovascularization at the papillary margin and in the angle. The history of vitreous hemorrhage, disruption of the hyaloid face, a multitude of tiny khaki-colored cells, a relatively non inflamed conjunctiva, and an absence of keratic precipitates differentiates ghost cell glaucoma from uveitis and endophthalmitis. Ghost cell glaucoma usually resolves once the vitreous hemorrhage has cleared. Medical therapy with aqeous suppressants is the preferred initial approach. Surgical intervention is often necessary because of a persistently elevated intraocular pressure despite maximum medical therapy. Aqeous suppressants are the first line approach. Monotherapy or a combination of topical alpha adrenergic agonists, beta adrenergic blockers, parasympathomimmetics, prostaglandin analogues, and carbonic anhydrase inhibitors may be used. An oral carbonic anyhdrase inhibitor may be added. Intravenous Mannitol or Diamox may be used for extremely high IOPs in acute settings. This may occur once cells reaccumulate in the trabecular meshwork after initial clearing. Surgery might be required to clear the cell load from the trabecular meshwork. This can be accomplished by AC paracentesis and irrigation, pars plana vitrectomy (PPV), and/or a trabeculectomy. If AC washout lowers the intraocular pressure successfully but the pressure rises again because of the further entrance of ghost cells from the vitreous, a washout of the AC can be repeated. If this relatively simple and safe procedure is unsuccessful, vitrectomy to remove the contents of the vitreous cavity may be required. For refractory glaucoma caused by chronic obstruction of trabecular meshwork by ghost cells, trabeculectomy or usage of glaucoma drainage device is warranted. If the IOP is uncontrolled, this may lead to optic nerve damage, however given the number of treatment options that are available, this is rare. Also, ghost cell glaucoma usually resolves once the hemorrhage clears. Prognosis of ghost cell glaucoma is usually excellent as the condition is typically transient, although it may last many months. Eventually, the supply of erythrocyte ghosts in the vitreous cavity become exhausted and cells stop passing forward into the anterior chamber. If ghost cells linger, surgical treatment options are available as discussed above. Albert DM & Miller JW. Principles and Practice of Opthalmology. Third Edition. Philadelphia, PA. W.B Saunders Company © 2000 and Elsevier, Inc © 20008. Campbell DG, Simmons RJ, & Grant WM. Ghost cells as a cause of glaucoma. Am J Ophthalmol. 1976; 81:441-440. Cioffi GA, Durcan FJ, Girkin CA, Gross RL, Netland PA, Samples JR, Samuelson TW, O’Connell SS & Barton K. Glaucoma. Last major revision 2008-2009. San Francisco, CA. American Academy of Ophthalmology. Copyright 2010. Girkin CA, McGwin G, Cherie L, Robert M & Ferenc K. Glaucoma after ocular contusion: A cohort study of the United States eye injury registry. Journal of Glaucoma. 2005; 14(6): 470-473. Ritch R, Shields MB & Krupin T. The Glaucomas. Volume 2. St. Louis, MI. C.V. Mosby Company. © 1989. Rojas L, Ortiz G, Gutierrez M & Corredor, S. Ghost Cell Glaucoma Related to Snake Poisoning. Arch Ophthalmol. 2001; 119 (8): 1212-1213. Shetlar DJ, Chevez-Barrios P, Dubovy S, Rosa RH, Syed N, Wilson MW, Pelton RW & Pe’er J. Ophthalmic Pathology and Intraocular Tumors. Last major revision 2007-2008. San Francisco, CA. American Academy of Ophthalmology. Copyright 2010. Spraul CW & Grossniklaus HE. Vitreous Hemorrhage. Surv Ophthalmol. 1997; 42(1): 3-39. Mansour AM, Chess J, Starita R. Nontraumatic ghost cell glaucoma- a case report. Ophthalmic Surg. 1986;17:34-36. - Phase contrast microscopy imparts contrast to unstained biological material by transforming phase differences of light caused by differences in refractive index between cellular components into differences in amplitude of light, i.e., light and dark areas, which can be observed.	2	6	1	0	0	0.548611	1	2,692
To begin with, it is necessary to accentuate the difference between the terms ‘telehealth’ and ‘telemedicine’. The Health Resources Services Administration defines telehealth as the use of electronic information and telecommunication technologies to support long distance clinical healthcare, patient and professional healthcare provider related education, public health, and health administration. Telehealth includes remote nonclinical and clinical services. Telemedicine includes remote clinical services and interactive health communications between clinicians. Simply put, all telemedicine is telehealth, but not likewise. Telehealth physical therapy can be delivered through such approaches as video conferencing, remote patient monitoring (RPM), store and forward, and mobile health (mHealth). Using store and forward in telehealth physical therapy assumes taking a picture of the healthcare issue and sending it to a healthcare provider to receive evidence-based consulting . This kind of telemedicine in physical therapy is not synchronized, or not immediately viewed in real time. In contrast, RPM can be either synchronized (real-time monitoring) or unsynchronized (data is sent per doctor’s request. MHealth is an approach to make digital manipulations with health data (store, resend, process, etc.) using digital devices (smartphones, tablets, laptops). As it is seen from the description of each approach, in many cases, effective delivery of telehealth physical therapy requires combining several methods. Telemedicine in physical therapy includes delivering hybrid (in-person and remotely) healthcare services. Examples of telemedicine services are RPM during a follow-up period after a patient is discharged from the hospital, collecting vital signs remotely, consulting regarding post-op and/or chronic disease treatment via video conference, and so on . Telehealth physical therapy has become more affordable for a greater amount of people. This relates to the fact that telehealth physical therapy CPT codes were recently reviewed to expand the list of covered telemedicine services. Specifically, the Centers for Medicare and Medicaid Services (CMS) for the US federal healthcare delivery programs has revised (added new services to the list) the codes 99091, 99453, 99454, 99457, and 99458. These telehealth physical therapy CPT codes ensure reimbursement to healthcare providers for “reviewing remotely collected RPM data and consulting patients regarding their RPM data”. Today, healthcare providers can receive reimbursement for educating, training, and consulting patients how to do telehealth physical therapy using available means of remote medical assistance to the fullest. Monitoring patient treatment adherence (exercising, walking regimes, etc.) by means of: Creating and leading educational discussion groups for orthopedic patients and their loved ones about diagnoses and rehabilitation plans Referring patients to other healthcare providers Creating pre-recorded educational videos in accordance with Home Exercise Plan (HEP). Nowadays, telehealth physical therapy gains momentum. This tendency is predefined by numerous advantages associated with receiving telehealth physical therapy.[3, 1] Telehealth physical therapy is a complementary (and in a growing number of cases, alternative) means of receiving professional medical assistance. Using telemedicine in physical therapy is an advantageous alternative for in-person visits for those patients who live far from the clinic.[3, 1] Telehealth physical therapy saves drive time and waiting time in the clinic, as well as reduces financial expenditure (sick day leave, transportation costs, etc.). If you have concerns regarding home safety, telehealth physical therapy is a nice opportunity to receive evidence-based consulting on how to increase your home safety Telehealth physical therapy services eliminate the risks of getting infected with contagious diseases including COVID-19 when coming to healthcare facilities.[3, 1] Telemedicine physical therapy increases patient treatment adherence to rehab programs.[3, 1] Patients tend to follow home exercise programs developed by physicians/physical therapists more often if their treatment progression is monitored at home. Telehealth physical therapy software presumes using the same digital devices as you use for daily communication and information retrieving (smartphones, tablets, laptops, computers). Telemedicine physical therapy is often delivered using Zoom, Skype, and FaceTime. Thus, to receive remote healthcare, you will need to ask your physician exactly which software you should install to be compatible with the clinic. Some examples of telemedicine physical therapy platforms that one may come across are InSync and Vsee.[2, 6] For example, Vsee provides a possibility for the patient to manage their healthcare digital data using Cloud Clinic storage. This approach is convenient because patients can refer to their healthcare data anytime and anywhere, no longer needing to find hard copies of their medical records. Vsee telemedicine physical platform provides solutions for NASA, Walmart Clinics, Trinity Hospitals, and other giants. To find a telehealth physical therapy provider, you need to contact your health insurance company. Then, call the proposed clinics to verify whether they deliver telehealth physical therapy services. If they do, talk to the telehealth physical therapy provider to learn more about the terms, procedures, solutions, and software required for receive remote care. ComeBack Mobility telehealth PT solution is a real-time remote patient monitoring based on using a portable device (smart crutch tips) along with smartphone software (mobile app). This means of telemedicine physical therapy is elaborated for orthopedic patients recovering after an injury/surgery deploying a staged weight-bearing rehab program. To learn in detail about the telehealth physical therapy services provided, read more about ComeBack Mobility Smart Crutch Tips. Weight-bearing tracking service to control the load on the injured leg during rehabilitation For Healthcare Provider For Procurement Department Office: 500 7th Ave, 8 floor, office 115, New York, NY 10018, USA Warehouse: 301 E 103rd St, New York, NY 10029, USA Contact us: [email protected] 279 5172 9 am - 6 pm EST	3	8	3	0	0	0.228741	3	1,233
Most ICD-9 codes are three digits to the left of a decimal point and one or two digits to the right of one. For example: 250.0 is diabetes with no complications. 530.81 is gastroesophageal reflux disease (GERD). Follow this link for full answer Nevertheless, what is meant by ICD codes? ICD stands for the International Classification of Disease. The ICD provides a method of classifying diseases, injuries, and causes of death. Still further, what is the difference between ICD-10 and ICD-9 codes? A: The major differences between the two coding systems include the number of characters involved. ICD-9 has up to five characters while ICD-10 has up to seven. ICD-10 adds laterality to the coding system, which ICD-9 lacks. ICD-10 offers much more specificity, including episode of care, body area, etc. Furthermore there, what are ICD-9 and 10 codes used for? An ICD-9-CM code (which will become an ICD-10-CM code this year on October 1) is used to describe a symptom, condition, or disease that is being treated, also known as the diagnosis code. How do I find my diagnosis code? A Five-Step ProcessStep 1: Search the Alphabetical Index for a diagnostic term. ... Step 2: Check the Tabular List. ... Step 3: Read the code's instructions. ... Step 4: If it is an injury or trauma, add a seventh character. ... Step 5: If glaucoma, you may need to add a seventh character. 25 Related Questions Answered ICD-10-CM is a seven-character, alphanumeric code. Each code begins with a letter, and that letter is followed by two numbers. The first three characters of ICD-10-CM are the “category.” The category describes the general type of the injury or disease. The category is followed by a decimal point and the subcategory. The ICD-10-CM (International Classification of Diseases, Tenth Revision, Clinical Modification) is a system used by physicians and other healthcare providers to classify and code all diagnoses, symptoms and procedures recorded in conjunction with hospital care in the United States. There are over 70,000 ICD-10-PCS procedure codes and over 69,000 ICD-10-CM diagnosis codes, compared to about 3,800 procedure codes and roughly 14,000 diagnosis codes found in the previous ICD-9-CM. ICD-10 codes begin with a letter, while the first digit of an ICD-9 code can be either alpha or numeric. Currently, the U.S. is the only industrialized nation still utilizing ICD-9-CM codes for morbidity data, though we have already transitioned to ICD-10 for mortality. For services provided after September 30th, Medicare will no longer accept ICD-9-CM codes. The ICD is important because it provides a common language for reporting and monitoring diseases. This allows the world to compare and share data in a consistent and standard way – between hospitals, regions and countries and over periods of time. Table 5ICD-9-CM diagnosis codes defining diabetes \|Diabetes mellitus without mention of complications\|\|250.0x\| \|Diabetes with ketoacidosis\|\|250.1x\| \|Diabetes with hyperosmolarity\|\|250.2x\| \|Diabetes with other coma\|\|250.3x\| ICD-10-CM diagnosis codes will tell the story of each patient encounter, describe etiologies of the disease process, explain the complications of care, provide a basis for medical necessity, support coverage for payment purposes, identify incidence of disease, and support statistical tracking for healthcare practices, ... The correct procedure for assigning accurate diagnosis codes has six steps: (1) Review complete medical documentation; (2) abstract the medical conditions from the visit documentation; (3) identify the main term for each condition; (4) locate the main term in the Alphabetic Index; (5) verify the code in the Tabular ... F41. 9 is a billable/specific ICD-10-CM code that can be used to indicate a diagnosis for reimbursement purposes. What are the 5 main steps for diagnostic coding? - Step 1: Search the Alphabetical Index for a diagnostic term. - Step 2: Check the Tabular List. - Step 3: Read the code's instructions. - Step 4: If it is an injury or trauma, add a seventh character. - Step 5: If glaucoma, you may need to add a seventh character. ICD-10 codes were developed by the World Health Organization (WHO) . ICD-10-CM codes were developed and are maintained by CDC's National Center for Health Statistics under authorization by the WHO. ICD-10 codes identify medical diagnoses and help insurance companies understand why the care you were provided was necessary. They work in tandem with CPT Codes and are required on every claim submission. At Better, we validate the accuracy of the ICD-10 codes on every claim we file. Diagnosis codes are always required on prescriptions for Medicare Part B claims. In addition some Prior Authorizations will require the submission of a diagnosis code. Even though it is not a covered HIPAA transaction, a Workers Compensation claim might also require a diagnosis code based on the injury of the patient. PRIMARY DIAGNOSIS (ICD) is the International Classification of Diseases (ICD) code used to identify the PRIMARY DIAGNOSIS. PRIMARY DIAGNOSIS (ICD) is used by the Secondary Uses Service to derive the Healthcare Resource Group 4 . The Czech Republic, Denmark, Romania, Slovakia, and Thailand implemented ICD-10 for mortality coding in 1994, and since that time 33 additional countries have joined them. The United States began using ICD-10 to code and classify mortality data from death certificates in January 1999. Inpatient acute care providers report ICD-10-CM diagnosis and ICD-10-PCS procedure codes on claims to assign the appropriate Medicare Severity-Diagnosis Related Group (MS-DRG) codes used to calculate payment. Providers use code set to report procedures performed only in U.S. inpatient hospital health care settings. The ICD-10 is the new, mandatory standard for reporting diagnosis codes and procedure codes on all health care claims – including those submitted to Medicare. ... ICD-10 must be used for all health care services. The CPT code describes what was done to the patient during the consultation, including diagnostic, laboratory, radiology, and surgical procedures while the ICD code identifies a diagnosis and describes a disease or medical condition. ... CPT codes are more complex than ICD codes. The ICD-9-CM consists of: a tabular list containing a numerical list of the disease code numbers in tabular form; an alphabetical index to the disease entries; and. a classification system for surgical, diagnostic, and therapeutic procedures (alphabetic index and tabular list). Codes are used today to: - Facilitate payment of health services. - Evaluate patients' use of health care facilities (utilization patterns) - study health care costs. - Research the quality of health care. - Predict health care trends. - Plan for future health care needs. On January 16, 2009, the U.S. Department of Health and Human Services (HHS) released the final rule mandating that everyone covered by the Health Insurance Portability and Accountability Act (HIPAA) implement ICD-10 for medical coding. Current Procedural Terminology (CPT) is a medical code set that is used to report medical, surgical, and diagnostic procedures and services to entities such as physicians, health insurance companies and accreditation organizations. ... CPT is a registered trademark of the American Medical Association. The most widely used classifications of disease are (1) topographic, by bodily region or system, (2) anatomic, by organ or tissue, (3) physiological, by function or effect, (4) pathological, by the nature of the disease process, (5) etiologic (causal), (6) juristic, by speed of advent of death, (7) epidemiological, and ...	4	7	0	0	2	0.561031	2	1,771
Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin coloration (cyanosis). For those who survive, a decreased quality of life is common. \|Acute respiratory distress syndrome\| \|Other names\|\|Respiratory distress syndrome (RDS), adult respiratory distress syndrome, shock lung, wet lung\| \|Specialty\|\|Critical care medicine\| \|Symptoms\|\|Shortness of breath, rapid breathing, bluish skin coloration, chest pain, loss of speech\| \|Complications\|\|Blood clots, Collapsed lung (pneumothorax), Infections, Scarring (pulmonary fibrosis)\| \|Usual onset\|\|Within a week\| \|Diagnostic method\|\|Adults: PaO2/FiO2 ratio of less than 300 mm Hg\| Children: oxygenation index > 4 \|Differential diagnosis\|\|Heart failure\| \|Treatment\|\|Mechanical ventilation, ECMO\| \|Prognosis\|\|35 to 90 % risk of death\| \|Frequency\|\|3 million per year\| Causes may include sepsis, pancreatitis, trauma, pneumonia, and aspiration. The underlying mechanism involves diffuse injury to cells which form the barrier of the microscopic air sacs of the lungs, surfactant dysfunction, activation of the immune system, and dysfunction of the body's regulation of blood clotting. In effect, ARDS impairs the lungs' ability to exchange oxygen and carbon dioxide. Adult diagnosis is based on a PaO2/FiO2 ratio (ratio of partial pressure arterial oxygen and fraction of inspired oxygen) of less than 300 mm Hg despite a positive end-expiratory pressure (PEEP) of more than 5 cm H2O. Cardiogenic pulmonary edema, as the cause, must be excluded. The primary treatment involves mechanical ventilation together with treatments directed at the underlying cause. Ventilation strategies include using low volumes and low pressures. If oxygenation remains insufficient, lung recruitment maneuvers and neuromuscular blockers may be used. If these are insufficient, extracorporeal membrane oxygenation (ECMO) may be an option. The syndrome is associated with a death rate between 35 and 50%. Globally, ARDS affects more than 3 million people a year. The condition was first described in 1967. Although the terminology of "adult respiratory distress syndrome" has at times been used to differentiate ARDS from "infant respiratory distress syndrome" in newborns, the international consensus is that "acute respiratory distress syndrome" is the best term because ARDS can affect people of all ages. There are separate diagnostic criteria for children and those in areas of the world with fewer resources. Signs and symptomsEdit The signs and symptoms of ARDS often begin within two hours of an inciting event, but have been known to take as long as 1–3 days; diagnostic criteria require a known insult to have happened within 7 days of the syndrome. Signs and symptoms may include shortness of breath, fast breathing, and a low oxygen level in the blood due to abnormal ventilation. Other common symptoms include muscle fatigue and general weakness, low blood pressure, a dry, hacking cough, and fever. Complications may include the following: - Lungs: barotrauma (volutrauma), pulmonary embolism (PE), pulmonary fibrosis, ventilator-associated pneumonia (VAP) - Gastrointestinal: bleeding (ulcer), dysmotility, pneumoperitoneum, bacterial translocation - Neurological: hypoxic brain damage - Cardiac: abnormal heart rhythms, myocardial dysfunction - Kidney: acute kidney failure, positive fluid balance - Mechanical: vascular injury, pneumothorax (by placing pulmonary artery catheter), tracheal injury/stenosis (result of intubation and/or irritation by endotracheal tube) - Nutritional: malnutrition (catabolic state), electrolyte abnormalities Other complications that are typically associated with ARDS include: - Atelectasis: small air pockets within the lung collapse - Complications that arise from treatment in a hospital: blood clots formed by lying down for long periods of time, weakness in muscles that are used for breathing, stress ulcers, and issues with mental health and depression. - Failure of multiple organs - Pulmonary hypertension or increase in blood pressure in the main artery from the heart to the lungs. This complication typically occurs due to the restriction of the blood vessel due to inflammation of the mechanical ventilation There are direct and indirect causes of ARDS depending whether the lungs are initially affected. Direct causes include pneumonia (including bacterial and viral), aspiration, inhalational lung injury, lung contusion, chest trauma, and near-drowning. Indirect causes include sepsis, shock, pancreatitis, trauma (e.g. fat embolism), cardiopulmonary bypass, TRALI, burns, increased intracranial pressure. Fewer cases of ARDS are linked to large volumes of fluid used during post-trauma resuscitation. ARDS is a form of fluid accumulation in the lungs not explained by heart failure (noncardiogenic pulmonary edema). It is typically provoked by an acute injury to the lungs that results in flooding of the lungs' microscopic air sacs responsible for the exchange of gases such as oxygen and carbon dioxide with capillaries in the lungs. Additional common findings in ARDS include partial collapse of the lungs (atelectasis) and low levels of oxygen in the blood (hypoxemia). The clinical syndrome is associated with pathological findings including pneumonia, eosinophilic pneumonia, cryptogenic organizing pneumonia, acute fibrinous organizing pneumonia, and diffuse alveolar damage (DAD). Of these, the pathology most commonly associated with ARDS is DAD, which is characterized by a diffuse inflammation of lung tissue. The triggering insult to the tissue usually results in an initial release of chemical signals and other inflammatory mediators secreted by local epithelial and endothelial cells. Neutrophils and some T-lymphocytes quickly migrate into the inflamed lung tissue and contribute in the amplification of the phenomenon. The typical histological presentation involves diffuse alveolar damage and hyaline membrane formation in alveolar walls. Although the triggering mechanisms are not completely understood, recent research has examined the role of inflammation and mechanical stress. One research group has reported that broncho-alveolar lavage fluid in later-stage ARDS often contains trichomonads, in an amoeboid form (i.e. lacking their characteristic flagellum) which makes them difficult to identify under the microscope. Diagnostic criteria for ARDS have changed over time as understanding of the pathophysiology has evolved. The international consensus criteria for ARDS were most recently updated in 2012 and are known as the "Berlin definition". In addition to generally broadening the diagnostic thresholds, other notable changes from the prior 1994 consensus criteria include discouraging the term "acute lung injury," and defining grades of ARDS severity according to degree of decrease in the oxygen content of the blood. According to the 2012 Berlin definition, adult ARDS is characterized by the following: - lung injury of acute onset, within 1 week of an apparent clinical insult and with the progression of respiratory symptoms - bilateral opacities on chest imaging (chest radiograph or CT) not explained by other lung pathology (e.g. effusion, lobar/lung collapse, or nodules) - respiratory failure not explained by heart failure or volume overload - decreased PaO 2 ratio (a decreased PaO 2 ratio indicates reduced arterial oxygenation from the available inhaled gas): - mild ARDS: 201 – 300 mmHg (≤ 39.9 kPa) - moderate ARDS: 101 – 200 mmHg (≤ 26.6 kPa) - severe ARDS: ≤ 100 mmHg (≤ 13.3 kPa) - The Berlin definition requires a minimum positive end expiratory pressure (PEEP) of 5 cmH 2O for consideration of the PaO 2 ratio. This degree of PEEP may be delivered noninvasively with CPAP to diagnose mild ARDS. The 2012 "Berlin criteria" are a modification of the prior 1994 consensus conference definitions (see history). Radiologic imaging has long been a criterion for diagnosis of ARDS. Original definitions of ARDS specified that correlative chest X-ray findings were required for diagnosis, the diagnostic criteria have been expanded over time to accept CT and ultrasound findings as equally contributory. Generally, radiographic findings of fluid accumulation (pulmonary edema) affecting both lungs and unrelated to increased cardiopulmonary vascular pressure (such as in heart failure) may be suggestive of ARDS. Ultrasound findings suggestive of ARDS include the following: - Anterior subpleural consolidations - Absence or reduction of lung sliding - "Spared areas" of normal parenchyma - Pleural line abnormalities (irregular thickened fragmented pleural line) - Nonhomogeneous distribution of B-lines (a characteristic ultrasound finding suggestive of fluid accumulation in the lungs) Acute respiratory distress syndrome is usually treated with mechanical ventilation in the intensive care unit (ICU). Mechanical ventilation is usually delivered through a rigid tube which enters the oral cavity and is secured in the airway (endotracheal intubation), or by tracheostomy when prolonged ventilation (≥2 weeks) is necessary. The role of non-invasive ventilation is limited to the very early period of the disease or to prevent worsening respiratory distress in individuals with atypical pneumonias, lung bruising, or major surgery patients, who are at risk of developing ARDS. Treatment of the underlying cause is crucial. Appropriate antibiotic therapy is started as soon as culture results are available, or if infection is suspected (whichever is earlier). Empirical therapy may be appropriate if local microbiological surveillance is efficient. Where possible the origin of the infection is removed. When sepsis is diagnosed, appropriate local protocols are followed. The overall goal of mechanical ventilation is to maintain acceptable gas exchange to meet the body's metabolic demands and to minimize adverse effects in its application. The parameters PEEP (positive end-expiratory pressure, to keep alveoli open), mean airway pressure (to promote recruitment (opening) of easily collapsible alveoli and predictor of hemodynamic effects), and plateau pressure (best predictor of alveolar overdistention) are used. Previously, mechanical ventilation aimed to achieve tidal volumes (Vt) of 12–15 ml/kg (where the weight is ideal body weight rather than actual weight). Recent studies have shown that high tidal volumes can overstretch alveoli resulting in volutrauma (secondary lung injury). The ARDS Clinical Network, or ARDSNet, completed a clinical trial that showed improved mortality when people with ARDS were ventilated with a tidal volume of 6 ml/kg compared to the traditional 12 ml/kg. Low tidal volumes (Vt) may cause a permitted rise in blood carbon dioxide levels and collapse of alveoli because of their inherent tendency to increase shunting within the lung. Physiologic dead space cannot change as it is ventilation without perfusion. A shunt is a perfusion without ventilation within a lung region. Low tidal volume ventilation was the primary independent variable associated with reduced mortality in the NIH-sponsored ARDSNet trial of tidal volume in ARDS. Plateau pressure less than 30 cm H 2O was a secondary goal, and subsequent analyses of the data from the ARDSNet trial and other experimental data demonstrate that there appears to be no safe upper limit to plateau pressure; regardless of plateau pressure, individuals with ARDS fare better with low tidal volumes. Airway pressure release ventilationEdit No particular ventilator mode is known to improve mortality in acute respiratory distress syndrome (ARDS). Some practitioners favor airway pressure release ventilation when treating ARDS. Well documented advantages to APRV ventilation include decreased airway pressures, decreased minute ventilation, decreased dead-space ventilation, promotion of spontaneous breathing, almost 24-hour-a-day alveolar recruitment, decreased use of sedation, near elimination of neuromuscular blockade, optimized arterial blood gas results, mechanical restoration of FRC (functional residual capacity), a positive effect on cardiac output (due to the negative inflection from the elevated baseline with each spontaneous breath), increased organ and tissue perfusion and potential for increased urine output secondary to increased kidney perfusion. A patient with ARDS, on average, spends between 8 and 11 days on a mechanical ventilator; APRV may reduce this time significantly and thus may conserve valuable resources. Positive end-expiratory pressureEdit Positive end-expiratory pressure (PEEP) is used in mechanically ventilated people with ARDS to improve oxygenation. In ARDS, three populations of alveoli can be distinguished. There are normal alveoli that are always inflated and engaging in gas exchange, flooded alveoli which can never, under any ventilatory regime, be used for gas exchange, and atelectatic or partially flooded alveoli that can be "recruited" to participate in gas exchange under certain ventilatory regimens. The recruitable alveoli represent a continuous population, some of which can be recruited with minimal PEEP, and others can only be recruited with high levels of PEEP. An additional complication is that some alveoli can only be opened with higher airway pressures than are needed to keep them open, hence the justification for maneuvers where PEEP is increased to very high levels for seconds to minutes before dropping the PEEP to a lower level. PEEP can be harmful; high PEEP necessarily increases mean airway pressure and alveolar pressure, which can damage normal alveoli by overdistension resulting in DAD. A compromise between the beneficial and adverse effects of PEEP is inevitable. The 'best PEEP' used to be defined as 'some' cmH 2O above the lower inflection point (LIP) in the sigmoidal pressure-volume relationship curve of the lung. Recent research has shown that the LIP-point pressure is no better than any pressure above it, as recruitment of collapsed alveoli—and, more importantly, the overdistension of aerated units—occur throughout the whole inflation. Despite the awkwardness of most procedures used to trace the pressure-volume curve, it is still used by some[who?] to define the minimum PEEP to be applied to their patients. Some new ventilators can automatically plot a pressure-volume curve. PEEP may also be set empirically. Some authors[who?] suggest performing a 'recruiting maneuver'—a short time at a very high continuous positive airway pressure, such as 50 cmH 2O (4.9 kPa)—to recruit or open collapsed units with a high distending pressure before restoring previous ventilation. The final PEEP level should be the one just before the drop in PaO 2 or peripheral blood oxygen saturation during a step-down trial. A large randomized controlled trial of patients with ARDS found that lung recruitment maneuvers and PEEP titration was associated with high rates of barotrauma and pneumothorax and increased mortality. Intrinsic PEEP (iPEEP) or auto-PEEP—first described by John Marini of St. Paul Regions Hospital—is a potentially unrecognized contributor to PEEP in intubated individuals. When ventilating at high frequencies, its contribution can be substantial, particularly in people with obstructive lung disease such as asthma or chronic obstructive pulmonary disease (COPD). iPEEP has been measured in very few formal studies on ventilation in ARDS, and its contribution is largely unknown. Its measurement is recommended in the treatment of people who have ARDS, especially when using high-frequency (oscillatory/jet) ventilation. The position of lung infiltrates in acute respiratory distress syndrome is non-uniform. Repositioning into the prone position (face down) might improve oxygenation by relieving atelectasis and improving perfusion. If this is done early in the treatment of severe ARDS, it confers a mortality benefit of 26% compared to supine ventilation. However, attention should be paid to avoid the SIDS in the management of the respiratory distressed infants by continuous careful monitoring of their cardiovascular system. Several studies have shown that pulmonary function and outcome are better in people with ARDS who lost weight or whose pulmonary wedge pressure was lowered by diuresis or fluid restriction. As of 2019, it is uncertain whether or not treatment with corticosteroids improves overall survival. Corticosteroids may increase the number of ventilator-free days during the first 28 days of hospitalization. One study found that dexamethasone may help. The combination of hydrocortisone, ascorbic acid, and thiamine also requires further study as of 2018. Inhaled nitric oxide (NO) selectively widens the lung's arteries which allows for more blood flow to open alveoli for gas exchange. Despite evidence of increased oxygenation status, there is no evidence that inhaled nitric oxide decreases morbidity and mortality in people with ARDS. Furthermore, nitric oxide may cause kidney damage and is not recommended as therapy for ARDS regardless of severity. Alvelestat (AZD 9668) had been quoted according to one review article. Extracorporeal membrane oxygenationEdit Extracorporeal membrane oxygenation (ECMO) is mechanically applied prolonged cardiopulmonary support. There are two types of ECMO: Venovenous which provides respiratory support and venoarterial which provides respiratory and hemodynamic support. People with ARDS who do not require cardiac support typically undergo venovenous ECMO. Multiple studies have shown the effectiveness of ECMO in acute respiratory failure. Specifically, the CESAR (Conventional ventilatory support versus Extracorporeal membrane oxygenation for Severe Acute Respiratory failure) trial demonstrated that a group referred to an ECMO center demonstrated significantly increased survival compared to conventional management (63% to 47%). As of 2019, there is no evidence showing that treatments with exogenous surfactants, statins, beta-blockers or n-acetylcysteine decreases early mortality, late all-cause mortality, duration of mechanical ventilation, or number of ventilator-free days. The overall prognosis of ARDS is poor, with mortality rates of approximately 40%. Exercise limitation, physical and psychological sequelae, decreased physical quality of life, and increased costs and use of health care services are important sequelae of ARDS. The annual rate of ARDS is generally 13–23 people per 100,000 in the general population. It is more common in people who are mechanically ventilated with acute lung injury (ALI) occurring in 16% of ventilated people. Rates increased in 2020 due to COVID-19, with some cases also appearing similar to HAPE. Worldwide, severe sepsis is the most common trigger causing ARDS. Other triggers include mechanical ventilation, sepsis, pneumonia, Gilchrist's disease, drowning, circulatory shock, aspiration, trauma—especially pulmonary contusion—major surgery, massive blood transfusions, smoke inhalation, drug reaction or overdose, fat emboli and reperfusion pulmonary edema after lung transplantation or pulmonary embolectomy. However, the majority of patients with all these conditions mentioned do not develop ARDS. It is unclear why some people with the mentioned factors above do not develop ARDS and others do. Pneumonia and sepsis are the most common triggers, and pneumonia is present in up to 60% of patients and may be either causes or complications of ARDS. Alcohol excess appears to increase the risk of ARDS. Diabetes was originally thought to decrease the risk of ARDS, but this has shown to be due to an increase in the risk of pulmonary edema. Elevated abdominal pressure of any cause is also probably a risk factor for the development of ARDS, particularly during mechanical ventilation. Acute respiratory distress syndrome was first described in 1967 by Ashbaugh et al. Initially there was no clearly established definition, which resulted in controversy regarding the incidence and death of ARDS. In 1988, an expanded definition was proposed, which quantified physiologic respiratory impairment. 1994 American-European Consensus ConferenceEdit In 1994, a new definition was recommended by the American-European Consensus Conference Committee which recognized the variability in severity of pulmonary injury. The definition required the following criteria to be met: - acute onset, persistent dyspnea - bilateral infiltrates on chest radiograph consistent with pulmonary edema - hypoxemia, defined as PaO 2 < 200 mmHg (26.7 kPa) - absence of left atrial (LA) hypertension - pulmonary artery wedge pressure < 18 mmHg (obtained by pulmonary artery catheterization) - if no measured LA pressure available, there must be no other clinical evidence to suggest elevated left heart pressure. 2 < 300 mmHg (40 kPa), then the definitions recommended a classification as "acute lung injury" (ALI). Note that according to these criteria, arterial blood gas analysis and chest X-ray were required for formal diagnosis. Limitations of these definitions include lack of precise definition of acuity, nonspecific imaging criteria, lack of precise definition of hypoxemia with regards to PEEP (affects arterial oxygen partial pressure), arbitrary PaO 2 thresholds without systematic data. 2012 Berlin definitionEdit In 2012, the Berlin Definition of ARDS was devised by the European Society of Intensive Care Medicine, and was endorsed by the American Thoracic Society and the Society of Critical Care Medicine. These recommendations were an effort to both update classification criteria in order to improve clinical usefulness and to clarify terminology. Notably, the Berlin guidelines discourage the use of the term "acute lung injury" or ALI, as the term was commonly being misused to characterize a less severe degree of lung injury. Instead, the committee proposes a classification of ARDS severity as mild, moderate, or severe according to arterial oxygen saturation. The Berlin definitions represent the current international consensus guidelines for both clinical and research classification of ARDS. ARDS is the severe form of acute lung injury (ALI), and of transfusion-related acute lung injury (TRALI), though there are other causes. The Berlin definition included ALI as a mild form of ARDS. However, the criteria for the diagnosis of ARDS in the Berlin definition excludes many children, and a new definition for children was termed pediatric acute respiratory distress syndrome (PARDS); this is known as the PALICC definition (2015). There is ongoing research on the treatment of ARDS by interferon (IFN) beta-1a to aid in preventing leakage of vascular beds. Traumakine (FP-1201-lyo) is a recombinant human IFN beta-1a drug, developed by the Finnish company Faron Pharmaceuticals, which is undergoing international phase-III clinical trials after an open-label, early-phase trial showed an 81% reduction-in-odds of 28-day mortality in ICU patients with ARDS. The drug is known to function by enhancing lung CD73 expression and increasing production of anti-inflammatory adenosine, such that vascular leaking and escalation of inflammation are reduced. Aspirin has been studied in those who are at high risk and was not found to be useful. An intravenous ascorbic acid treatment was tested in the 2019 RCT, in people with ARDS due to sepsis and there was no change in primary endpoints. - ^ a b c d e f g h i j k l m n o p q r s t Fan, E; Brodie, D; Slutsky, AS (20 February 2018). "Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment". JAMA. 319 (7): 698–710. doi:10.1001/jama.2017.21907. PMID 29466596. S2CID 3451752. - ^ "ARDS". mayoclinic.org. Mayo Clinic. Retrieved June 4, 2022. - ^ Cheifetz, Ira M (25 May 2017). "Pediatric ARDS". Respiratory Care. 62 (6): 718–731. doi:10.4187/respcare.05591. PMID 28546374. - ^ a b c Matthay, MA; Zemans, RL; Zimmerman, GA; Arabi, YM; Beitler, JR; Mercat, A; Herridge, M; Randolph, AG; Calfee, CS (14 March 2019). "Acute respiratory distress syndrome". Nature Reviews. Disease Primers. 5 (1): 18. doi:10.1038/s41572-019-0069-0. PMC 6709677. PMID 30872586. - ^ Fanelli, Vito; Ranieri, V. Marco (2015-03-01). "Mechanisms and clinical consequences of acute lung injury". Annals of the American Thoracic Society. 12 Suppl 1: S3–8. doi:10.1513/AnnalsATS.201407-340MG. ISSN 2325-6621. PMID 25830831. - ^ a b c Bernard G, Artigas A, Brigham K, Carlet J, Falke K, Hudson L, Lamy M, Legall J, Morris A, Spragg R (1994). "The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination". Am J Respir Crit Care Med. 149 (3 Pt 1): 818–24. doi:10.1164/ajrccm.149.3.7509706. PMID 7509706. - ^ Bakowitz, Magdalena (August 2012). "Acute lung injury and the acute respiratory distress syndrome in the injured patient". Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 20: 54. doi:10.1186/1757-7241-20-54. PMC 3518173. PMID 22883052. - ^ Marino (2006), pp 435 - ^ a b Bakowitz, Magdalena; Bruns, Brandon; McCunn, Maureen (2012-08-10). "Acute lung injury and the acute respiratory distress syndrome in the injured patient". Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 20: 54. doi:10.1186/1757-7241-20-54. ISSN 1757-7241. PMC 3518173. PMID 22883052. - ^ a b c d e f Irwin RS, Rippe JM (2003). Irwin and Rippe's Intensive Care Medicine (5th ed.). Lippincott Williams & Wilkins. ISBN 978-0-7817-3548-3. - ^ Cherkas, David (Nov 2011). "Traumatic Hemorrhagic Shock: Advances In Fluid Management". Emergency Medicine Practice. 13 (11): 1–19, quiz 19–20. PMID 22164397. - ^ Boyle, AJ; Mac Sweeney, R; McAuley, DF (August 2013). "Pharmacological treatments in ARDS; a state-of-the-art update". BMC Med. 11: 166. doi:10.1186/1741-7015-11-166. PMC 3765621. PMID 23957905. - ^ Duboucher C, Barbier C, Beltramini A, Rona M, Ricome JL, Morel G, Capron M, Pierce RJ, Dei-Cas E, Viscogliosi E (September 2007). "Pulmonary Superinfection by Trichomonads in the Course of Acute Respiratory Distress Syndrome". Lung. 185 (5): 295–301. doi:10.1007/s00408-007-9022-1. ISSN 0341-2040. PMID 17701244. S2CID 12175132. - ^ Duboucher C (March 2021). "SARS-CoV-2 and superimposed infection by trichomonads". Journal of Infection. 82 (3): e22–e23. doi:10.1016/j.jinf.2020.11.038. PMC 7834870. PMID 33271170. - ^ a b Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS (Jun 2012). "Acute respiratory distress syndrome: the Berlin Definition. ARDS Definition Task Force". JAMA. 307 (23): 2526–33. doi:10.1001/jama.2012.5669. PMID 22797452. S2CID 36276275. - ^ Ferguson ND, Fan E, Camporota L, Antonelli M, Anzueto A, Beale R, Brochard L, Brower R, Esteban A, et al. (Oct 2012). "The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material". Intensive Care Med. 38 (10): 1573–82. doi:10.1007/s00134-012-2682-1. PMID 22926653. S2CID 13556499. Erratum in: Intensive Care Med. 2012 Oct;38(10):1731-2. PMID 22926653 - ^ "Acute Respiratory Distress Syndrome". The Lecturio Medical Concept Library. Retrieved 27 June 2021. - ^ Volpicelli, Giovanni; Elbarbary, Mahmoud; Blaivas, Michael; Lichtenstein, Daniel A.; Mathis, Gebhard; Kirkpatrick, Andrew W.; Melniker, Lawrence; Gargani, Luna; Noble, Vicki E. (2012-04-01). "International evidence-based recommendations for point-of-care lung ultrasound". Intensive Care Medicine. 38 (4): 577–591. doi:10.1007/s00134-012-2513-4. ISSN 1432-1238. PMID 22392031. - ^ Malhotra A (2007). "Low-tidal-volume ventilation in the acute respiratory distress syndrome". N Engl J Med. 357 (11): 1113–20. doi:10.1056/NEJMct074213. PMC 2287190. PMID 17855672. - ^ Hager, DN; Krishnan, JA; Hayden, DL; Brower, RG; ARDS Clinical Trials Network (November 2005). "Tidal volume reduction in patients with acute lung injury when plateau pressures are not high". American Journal of Respiratory and Critical Care Medicine. 172 (10): 1241–5. doi:10.1164/rccm.200501-048cp. PMC 2718413. PMID 16081547. - ^ Bein, T; Grasso, S; Moerer, O; Quintel, M; Guerin, C; Deja, M; Brondani, A; Mehta, S (2016). "The standard of care of patients with ARDS: ventilatory settings and rescue therapies for refractory hypoxemia". Intensive Care Medicine. 42 (5): 699–711. doi:10.1007/s00134-016-4325-4. PMC 4828494. PMID 27040102. - ^ Frawley, P. Milo; Habashi, Nader M. (May 2001). "Airway Pressure Release Ventilation: Theory and Practice". AACN Clinical Issues. 12 (2): 234–246. doi:10.1097/00044067-200105000-00007. PMID 11759551. - ^ Kaplan, Lewis J.; Bailey, Heatherlee; Formosa, Vincent (2 July 2001). "Airway pressure release ventilation increases cardiac performance in patients with acute lung injury/adult respiratory distress syndrome". Critical Care. 5 (4): 221–6. doi:10.1186/cc1027. PMC 37408. PMID 11511336. - ^ Carsetti, Andrea; Damiani, Elisa; Domizi, Roberta; Scorcella, Claudia; Pantanetti, Simona; Falcetta, Stefano; Donati, Abele; Adrario, Erica (2019-04-04). "Airway pressure release ventilation during acute hypoxemic respiratory failure: a systematic review and meta-analysis of randomized controlled trials". Annals of Intensive Care. 9 (1): 44. doi:10.1186/s13613-019-0518-7. ISSN 2110-5820. PMC 6449410. PMID 30949778. - ^ Cavalcanti, Alexandre Biasi; Suzumura, Érica Aranha; Laranjeira, Ligia Nasi; Paisani, Denise de Moraes; Damiani, Lucas Petri; Guimarães, Helio Penna; Romano, Edson Renato; Regenga, Marisa de Moraes; Taniguchi, Luzia Noriko Takahashi; Teixeira, Cassiano; Oliveira, Roselaine Pinheiro de (2017-10-10). "Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial". JAMA. 318 (14): 1335–1345. doi:10.1001/jama.2017.14171. ISSN 0098-7484. PMC 5710484. PMID 28973363. - ^ Sud S, Friedrich JO, Adhikari NK, et al. (8 Jul 2014). "Effect of prone positioning during mechanical ventilation on mortality among patients with acute respiratory distress syndrome: a systematic review and meta-analysis". CMAJ. 186 (10): E381–90. doi:10.1503/cmaj.140081. PMC 4081236. PMID 24863923. - ^ a b Bhandari, Abhishta P.; Nnate, Daniel A.; Vasanthan, Lenny; Konstantinidis, Menelaos; Thompson, Jacqueline (2022-06-06). "Positioning for acute respiratory distress in hospitalised infants and children". The Cochrane Database of Systematic Reviews. 2022 (6): CD003645. doi:10.1002/14651858.CD003645.pub4. ISSN 1469-493X. PMC 9169533. PMID 35661343. - ^ a b c Lewis, Sharon R.; Pritchard, Michael W.; Thomas, Carmel M.; Smith, Andrew F. (July 23, 2019). "Pharmacological agents for adults with acute respiratory distress syndrome". The Cochrane Database of Systematic Reviews. 7 (7): CD004477. doi:10.1002/14651858.CD004477.pub3. ISSN 1469-493X. PMC 6646953. PMID 31334568. - ^ Villar, J.; Ferrando, C.; Martínez, D.; Ambrós, A.; Muñoz, T.; Soler, J. A.; Aguilar, G.; Alba, F.; González-Higueras, E.; Conesa, L. A.; Martín-Rodríguez, C.; Díaz-Domínguez, F. J.; Serna-Grande, P.; Rivas, R.; Ferreres, J.; Belda, J.; Capilla, L.; Tallet, A.; Añón, J. M.; Fernández, R. L.; González-Martín, J. M.; dexamethasone in ARDS network (2020). "Dexamethasone treatment for the acute respiratory distress syndrome: A multicentre, randomised controlled trial". The Lancet. Respiratory Medicine. 8 (3): 267–276. doi:10.1016/S2213-2600(19)30417-5. PMID 32043986. S2CID 211077493. - ^ Moskowitz, A; Andersen, LW; Huang, DT; Berg, KM; Grossestreuer, AV; Marik, PE; Sherwin, RL; Hou, PC; Becker, LB; Cocchi, MN; Doshi, P; Gong, J; Sen, A; Donnino, MW (29 October 2018). "Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation". Critical Care. 22 (1): 283. doi:10.1186/s13054-018-2217-4. PMC 6206928. PMID 30373647. - ^ Adhikari, NK; Burns, KE; Friedrich, JO; Granton, JT; Cook, DJ; Meade, MO (14 April 2007). "Effect of nitric oxide on oxygenation and mortality in acute lung injury: systematic review and meta-analysis". BMJ (Clinical research ed.). 334 (7597): 779. doi:10.1136/bmj.39139.716794.55. PMC 1852043. PMID 17383982. - ^ Adhikari, NK; Dellinger, RP; Lundin, S; Payen, D; Vallet, B; Gerlach, H; Park, KJ; Mehta, S; Slutsky, AS; Friedrich, JO (February 2014). "Inhaled nitric oxide does not reduce mortality in patients with acute respiratory distress syndrome regardless of severity: systematic review and meta-analysis". Critical Care Medicine (Systematic Review & Meta-Analysis). 42 (2): 404–12. doi:10.1097/CCM.0b013e3182a27909. PMID 24132038. S2CID 12204105. - ^ Herrero R., Rojas Y., Esteban A. (2014) Novel Pharmacologic Approaches for the Treatment of ARDS. In: Vincent JL. (eds) Annual Update in Intensive Care and Emergency Medicine 2014. Annual Update in Intensive Care and Emergency Medicine, vol 2014. Springer, Cham. https://doi.org/10.1007/978-3-319-03746-2_18 - ^ Makdisi, G; Wang, IW (July 2015). "Extra Corporeal Membrane Oxygenation (ECMO) review of a lifesaving technology". Journal of Thoracic Disease. 7 (7): E166–76. doi:10.3978/j.issn.2072-1439.2015.07.17. PMC 4522501. PMID 26380745. - ^ Hemmila, MR; Rowe, SA; Boules, TN; Miskulin, J; McGillicuddy, JW; Schuerer, DJ; Haft, JW; Swaniker, F; Arbabi, S; Hirschl, RB; Bartlett, RH (October 2004). "Extracorporeal life support for severe acute respiratory distress syndrome in adults". Annals of Surgery. 240 (4): 595–605, discussion 605–7. doi:10.1097/01.sla.0000141159.90676.2d. PMC 1356461. PMID 15383787. - ^ Brogan, TV; Thiagarajan, RR; Rycus, PT; Bartlett, RH; Bratton, SL (December 2009). "Extracorporeal membrane oxygenation in adults with severe respiratory failure: a multi-center database". Intensive Care Medicine. 35 (12): 2105–14. doi:10.1007/s00134-009-1661-7. PMID 19768656. S2CID 526020. - ^ Peek, GJ; Mugford, M; Tiruvoipati, R; Wilson, A; Allen, E; Thalanany, MM; Hibbert, CL; Truesdale, A; Clemens, F; Cooper, N; Firmin, RK; Elbourne, D; CESAR trial, collaboration (17 October 2009). "Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial". Lancet. 374 (9698): 1351–63. doi:10.1016/S0140-6736(09)61069-2. PMID 19762075. S2CID 15191122. - ^ Sangalli, Fabio; Patroniti, Nicolò; Pesenti, Antonio, eds. (2014). ECMO-Extracorporeal Life Support in Adults. ISBN 978-88-470-5427-1. - ^ Lewandowski K, Lewandowski M (2006). "Epidemiology of ARDS". Minerva Anestesiol. 72 (6): 473–7. PMID 16682918. - ^ Guo, YR; Cao, QD; Hong, ZS; Tan, YY; Chen, SD; Jin, HJ; Tan, KS; Wang, DY; Yan, Y (13 March 2020). "The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status". Military Medical Research. 7 (1): 11. doi:10.1186/s40779-020-00240-0. PMC 7068984. PMID 32169119. - ^ Solaimanzadeh, I (20 March 2020). "Acetazolamide, Nifedipine and Phosphodiesterase Inhibitors: Rationale for Their Utilization as Adjunctive Countermeasures in the Treatment of Coronavirus Disease 2019 (COVID-19)". Cureus. 12 (3): e7343. doi:10.7759/cureus.7343. PMC 7096066. PMID 32226695. - ^ Goldman, Lee (2011). Goldman's Cecil Medicine (24th ed.). Philadelphia: Elsevier Saunders. p. 635. ISBN 978-1437727883. - ^ Vlaar, Alexander P. J.; Binnekade, Jan M.; Prins, David; van Stein, Danielle; Hofstra, Jorrit J.; Schultz, Marcus J.; Juffermans, Nicole P. (March 2010). "Risk factors and outcome of transfusion-related acute lung injury in the critically ill: A nested case–control study*". Critical Care Medicine. 38 (3): 771–778. doi:10.1097/CCM.0b013e3181cc4d4b. PMID 20035217. S2CID 12118692. - ^ Moss M, Bucher B, Moore FA, Moore EE, Parsons PE (1996). "The role of chronic alcohol abuse in the development of acute respiratory distress syndrome in adults". JAMA. 275 (1): 50–4. doi:10.1001/jama.1996.03530250054027. PMID 8531287. - ^ Moss M, Guidot DM, Steinberg KP, et al. (2000). "Diabetic patients have a decreased incidence of acute respiratory distress syndrome". Crit Care Med. 28 (7): 2187–92. doi:10.1097/00003246-200007000-00001. PMID 10921539. S2CID 29504738. - ^ Koh GC, Vlaar AP, Hofstra JJ, et al. (2012). "In the critically ill patient, diabetes predicts mortality independent of statin therapy but is not associated with acute lung injury: A cohort study". Crit Care Med. 40 (6): 1835–1843. doi:10.1097/CCM.0b013e31824e1696. PMC 3379571. PMID 22488007. - ^ Ashbaugh D, Bigelow D, Petty T, Levine B (1967). "Acute respiratory distress in adults". Lancet. 2 (7511): 319–23. doi:10.1016/S0140-6736(67)90168-7. PMC 1923469. PMID 4143721. - ^ Ware L, Matthay M (2000). "The acute respiratory distress syndrome". N Engl J Med. 342 (18): 1334–49. doi:10.1056/NEJM200005043421806. PMID 10793167. - ^ Abraham, Edward; Matthay, Michael A.; Dinarello, Charles A.; Vincent, Jean-Louis; Cohen, Jonathan; Opal, Steven M.; Glauser, Michel; Parsons, Polly; Fisher, Charles J.; Repine, John E. (January 2000). "Consensus conference definitions for sepsis, septic shock, acute lung injury, and acute respiratory distress syndrome: Time for a reevaluation". Critical Care Medicine. 28 (1): 232–235. doi:10.1097/00003246-200001000-00039. PMID 10667529. S2CID 19636525. - ^ "Meet the New ARDS: Expert panel announces new definition, severity classes". PulmCCM. 30 December 2012. - ^ Khemani, RG; et al. (2019). "Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational study". The Lancet. Respiratory Medicine. 7 (2): 115–128. doi:10.1016/S2213-2600(18)30344-8. PMC 7045907. PMID 30361119. - ^ Pediatric Acute Lung Injury Consensus Conference, Group. (June 2015). "Pediatric acute respiratory distress syndrome: consensus recommendations from the Pediatric Acute Lung Injury Consensus Conference". Pediatric Critical Care Medicine. 16 (5): 428–39. doi:10.1097/PCC.0000000000000350. PMC 5253180. PMID 25647235. - ^ Bellingan, Geoff; Maksimow, Mikael; Howell, David C.; Stotz, Martin; Beale, Richard; Beatty, Monika; Walsh, Timothy; Binning, Alexander; Davidson, Alan (February 2014). "The effect of intravenous interferon-beta-1a (FP-1201) on lung CD73 expression and on acute respiratory distress syndrome mortality: an open-label study". The Lancet. Respiratory Medicine. 2 (2): 98–107. doi:10.1016/S2213-2600(13)70259-5. ISSN 2213-2600. PMID 24503265. - ^ Kiss, Jan; Yegutkin, Gennady G.; Koskinen, Kaisa; Savunen, Timo; Jalkanen, Sirpa; Salmi, Marko (November 2007). "IFN-β protects from vascular leakage via up-regulation of CD73". European Journal of Immunology. 37 (12): 3334–3338. doi:10.1002/eji.200737793. ISSN 1521-4141. PMID 18034430. S2CID 8089872. - ^ "PulmCrit- CITRIS-ALI: Can a secondary endpoint stage a coup d'état?". PulmCrit. 1 October 2019. - Marino, Paul (2006). The ICU Book. Baltimore: Williams & Wilkins. ISBN 978-0781748025. - Martin GS, Moss M, Wheeler AP, Mealer M, Morris JA, Bernard GR (1 August 2005). "A randomized, controlled trial of furosemide with or without albumin in hypoproteinemic patients with acute lung injury". Crit. Care Med. 33 (8): 1681–7. doi:10.1097/01.CCM.0000171539.47006.02. PMID 16096441. S2CID 38941988. - Jackson WL, Shorr AF (1 June 2005). "Blood transfusion and the development of acute respiratory distress syndrome: more evidence that blood transfusion in the intensive care unit may not be benign". Crit. Care Med. 33 (6): 1420–1. doi:10.1097/01.CCM.0000167073.99222.50. PMID 15942365. - Mortelliti MP, Manning HL (May 2002). "Acute respiratory distress syndrome". Am Fam Physician. 65 (9): 1823–30. PMID 12018805. Archived from the original on 2008-09-06. Retrieved 2005-08-28. - Metnitz, P. G. H.; Bartens, C.; Fischer, M.; Fridrich, P.; Steltzer, H.; Druml, W. (17 February 1999). "Antioxidant status in patients with acute respiratory distress syndrome". Intensive Care Medicine. 25 (2): 180–185. doi:10.1007/s001340050813. PMID 10193545. S2CID 11377820. - ARDSNet—the NIH / NHLBI ARDS Network - ARDS Support Center—information for patients with ARDS	2	53	18	5	0	0.920816	23	10,656
\|Integrative Therapy Quick Links:\| - Amyloidosis, arrhythmia, arrhythmogenic right ventricular cardiomyopathy, arrhythmogenic right ventricular dysplasia, ARVC, ARVD, broken heart syndrome, CAD, cardiac resynchronization therapy, congestive heart failure, coronary artery disease, CRT, dilated cardiomyopathy, diuresis, endomyocardial fibrosis, familial hypertrophic cardiomyopathy, HCM, heart disease, heart failure, hypertrophic cardiomyopathy, ICD, implantable cardioverter-defibrillator, ischemic cardiomyopathy, myocardium, peripartum cardiomyopathy, postnatal cardiomyopathy, pregnancy-induced hypertension (preeclampsia), primary cardiomyopathy, restrictive cardiomyopathy, sarcoidosis, secondary cardiomyopathy, stress cardiomyopathy. - Cardiomyopathy refers to several diseases that affect the myocardium (heart muscle) and are associated with mechanical and/or electrical dysfunction. In cardiomyopathy, abnormal heart function results from weakness or structural changes in the myocardium. - There are four main types of cardiomyopathy as defined by the American Heart Association (AHA): arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, hypertrophic cardiomyopathy, and restrictive cardiomyopathy. They are then categorized into two groups: primary or secondary. Primary cardiomyopathies may be genetic (inherited) or acquired (develop the condition). Secondary cardiomyopathies result from an underlying condition such as diabetes, thyroid disorders, chronic alcohol consumption, infection, or drugs/toxins (e.g., heavy metals, anthracyclines, cocaine). Clinical presentation varies from asymptomatic (without symptoms) to sudden cardiac death. - Therapies for cardiomyopathy aim to reduce the symptoms of heart failure and the risk of complications such as arrhythmia (irregular heartbeat or abnormal heart rhythm). Treatments may involve drugs, implantable cardioverter-defibrillators (ICDs), or cardiac resynchronization therapy (CRT) to regulate the heartbeat and reduce the risk of fatal arrhythmias. In some cases, heart transplant may be necessary. General measures that may reduce mortality and prevent future occurrences of heart failure include controlling blood pressure and weight (through diet and exercise), reducing alcohol and sodium consumption, and quitting smoking. Signs and symptoms - General: The symptoms of cardiomyopathy are similar to the symptoms commonly seen in heart failure, particularly congestion (backed up blood) caused by abnormal heart function. The symptoms of congestion include shortness of breath, fatigue, and swelling, particularly in the legs and feet. Other symptoms such as dizziness, lightheadedness, and fainting develop as the body tries to compensate for the heart's reduced pumping ability. As the heart beats faster, its muscle thickens, and the ventricles (pumping chamber) may stretch to accommodate more blood. Damage to the ventricles may cause them to pump irregularly, further reducing the efficient delivery of blood to the body. - Symptoms of congestive heart failure (CHF, a condition in which the heart cannot pump enough blood to meet the body's needs) include: a dry, hacking cough, especially when lying down; confusion, sleepiness, and disorientation may occur in older individuals; dizziness, fainting, fatigue, or weakness; fluid buildup (edema), especially in the legs, ankles, and feet; increased urination at night; nausea; abdominal swelling, tenderness, or pain; weight gain due to fluid buildup; weight loss as nausea causes a loss of appetite and as the body fails to absorb food well; rapid breathing, bluish skin, and feelings of restlessness, anxiety, and suffocation; shortness of breath and lung congestion as the blood backs up in the lungs; and wheezing and spasms of the airways similar to asthma. - In arrhythmogenic right ventricular cardiomyopathy (ARVC), symptoms of heart failure are less common than other forms of cardiomyopathy. Instead, tachycardia (fast heartbeat) and angina (chest pain) are typical symptoms. - Many cardiomyopathies present no obvious symptoms in early stages. Sometimes, sudden heart failure and/or death are the first symptoms of cardiomyopathy. - General: Because the most common symptom of cardiomyopathy is heart failure, diagnosis of cardiomyopathy follows similar guidelines for evaluating heart failure. Physical examination, blood tests, electrocardiogram (ECG or EKG), echocardiogram, chest X-ray, magnetic resonance imaging (MRI), cardiac catheterization, stress test, and nuclear stress test are used to diagnose cardiomyopathy. These tests may also reveal structural defects in the heart muscle (myocardium) that are characteristic of cardiomyopathy. - Physical examination and medical history: During a physical examination, a doctor will look for underlying causes of the problem and assess heart function. A stethoscope is used to detect murmurs (abnormal heart sounds) that may indicate a leaky or narrowed valve and to detect fluid accumulation in the lungs. The doctor also looks for enlarged veins in the neck and for edema (swelling) in the legs, particularly the ankles, feet, and/or the abdomen. - A patient history may include information about risk factors, such as family medical history, past surgeries and medications, history of chest pain, high blood pressure (including treatments), heart attack, recent viral illness, or recent pregnancy. - Blood tests: Blood tests may include: blood cell counts to test for conditions such as anemia (low red blood cells); electrolyte levels, including sodium, potassium, and calcium; nutrient levels, such as vitamins and trace minerals; tests for kidney function, including blood urea nitrogen (BUN) and creatinine levels; and testing for homocysteine and/or C-reactive protein (CRP), both markers of inflammation and heart disease. Brain natriuretic peptide (BNP) is a test used to measure the amount of BNP hormone in the blood and also used to diagnose heart failure. Brain natriuretic peptide (BNP) is a hormone produced at higher levels by the failing heart muscle. - Electrocardiogram (ECG or EKG): An electrocardiogram (ECG or EKG) is a noninvasive test used to measure electrical activity in the heart. Electrical sensors called leads are attached to predetermined positions on the arms, legs, and chest to record electrical activity and help assess heart function. The heart's rhythm of contraction is controlled by the sinoatrial node (SA node), often called the pacemaker. Electrical impulses generated from the SA node spread through the heart via a nodal tissue pathway that coordinates the events leading to heart beat. This conduction system initiates and coordinates the muscular activity of the heart. - Echocardiogram: An echocardiogram, or echo, is an ultrasound examination of the heart that produces detailed images of the organ. It may be used to detect abnormalities in the structure of the heart and to measure the amount of blood ejected from the heart. During an echocardiogram, a microphone-like device (transducer) is used to transmit and receive ultrasonic waves that travel through the chest wall to the heart and are reflected back to the transducer. The reflected sound waves are translated into images of the heart, including the valves, chambers, and walls. - Echocardiogram also is used to measure the pressure change (gradient) between the left ventricle and the aorta (largest artery of the body), to assess thickening of the walls of the heart, to evaluate pumping function, and to measure the amount of dilation (increased diameter) of the left ventricle. - Chest X-ray, magnetic resonance imaging (MRI), or computerized tomography (CT) scan: X-rays, MRIs, and CT scans are useful in visualizing structural defects in the heart that cause cardiomyopathy. These defects include enlargement of the heart or thickening of the myocardium. - Cardiac catheterization: Cardiac catheterization may be performed in individuals with angina and in those with a history of heart attack to determine if coronary heart disease (CHD) is causing heart failure. Cardiac catheterization with angiograms (x-ray images of blood vessels) of the coronary arteries and the left ventricle can be used to monitor heart function. - Cardiac catheterization involves injecting a small amount of radioactive dye, called a contrast agent, into the left ventricle through a catheter (a thin flexible tube). A special camera is then used to determine how much of the dye is ejected from the heart with each beat. The infusion of dye typically produces a characteristic "hot flash" sensation throughout the body that lasts 10-15 seconds. - Stress test: In some individuals, a less invasive procedure called a stress test is used to assess the possibility of coronary heart disease (CAD). If the results of this procedure suggest the presence of CAD, a subsequent referral for cardiac catheterization is likely. - Several types of stress tests may be used by doctors to access heart function. In some cases, the individual simply walks on a treadmill while connected to an ECG. Another type uses intravenous (IV, or in the veins) medication, usually a platelet inhibitor like dipyridamole (Persantine®), which reproduces the stress of exercise on the heart. - Nuclear stress test: Nuclear stress tests involve injecting a radioactive substance, most commonly technetium or Tc-99m sestamibi (Cardiolite®), into a vein. A special camera (gamma camera) is then used to obtain images of the heart during rest and immediately following exercise on a treadmill as the radioactivity flows through the heart. The radioactivity levels used are not harmful. - A nuclear test called a radionuclide ventriculography or multiple gated acquisition (MUGA) scanning allows doctors to see how much blood the heart pumps with each beat, also known as the ejection fraction. The MUGA scan gives an accurate and reproducible means of measuring and monitoring the actual amount of blood ejected from the heart. The tests use a small amount of radioactive material injected into the veins. A special camera detects the radioactive material as it flows through the heart. - Individuals with an allergy to iodine or shellfish have special considerations and may not be able to have this test because the dye contains iodine. The use of medications, including the antihistamine diphenhydramine (Benadryl®) and/or prednisone (Deltasone®), prior to the administration of the dyes (contrast media), may help to prevent or decrease the chance of an allergic reaction. - Classifying heart failure: Results of these tests help doctors determine the cause of CHF and develop a program to treat the heart. To determine the best course of treatment, doctors may classify heart failure using one of two scales. The New York Heart Association scale classifies heart failure in categories from one to four. In class I heart failure, the mildest form, individuals can perform everyday activities and not feel winded or fatigued. Individuals with class II have slight limitation of physical activity and ordinary physical activity may result in fatigue, palpitation (pounding or racing), shortness of breath, or chest pain. Those with class III have marked limitation of physical activity and less than ordinary activity causes fatigue, palpitation, shortness of breath, or chest pain. Class IV is the most severe, and individuals have shortness of breath even at rest. - The American College of Cardiology scale uses letters A-D. The system includes a category for individuals who are at risk of developing heart failure. Early stage heart failure includes stage A (individuals are at risk for developing heart failure without evidence of heart dysfunction) and stage B (there is evidence of heart dysfunction without symptoms). Advanced stage heart failure includes stage C (there is evidence of heart dysfunction with symptoms) and stage D (there are symptoms of heart failure despite maximal therapy). Doctors can use these classifications to identify the risk factors and begin early, more aggressive treatment to help prevent or delay heart failure. - The most common complication of most types of cardiomyopathy (dilated, hypertrophic, and restrictive) is heart failure, which may be fatal. Arrhythmias (abnormal heartbeats) and angina (chest pain) may also occur, especially in arrhythmogenic right ventricular cardiomyopathy (ARVC) in which heart failure is less common. - Treatment for cardiomyopathy aims at treating heart failure. This involves reducing symptoms, treating the underlying cause of the condition when possible, and using medications to prevent further deterioration of heart function. For arrhythmogenic right ventricular cardiomyopathy (ARVC), in which heart failure is less common, treatment is directed at preventing arrhythmia (irregular heartbeat). - Lifestyle changes: - Lifestyle changes may help reduce symptoms such as fatigue, shortness of breath, and edema (swelling). These modifications may include dietary changes (such as a restricted salt intake of less than 2,000 milligrams daily), abstaining from alcohol, smoking cessation, and exercising regularly (under the supervision of a doctor). - A combination of medications is used to treat congestive heart failure (CHF). Depending on the symptoms, individuals with CHF may take one, two, or more of these drugs. Several types of medications have proved useful in the treatment of heart failure including: angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, digoxin, diuretics, and aldosterone antagonists. - Angiotensin-converting enzyme (ACE) inhibitors: Angiotensin-converting enzyme (ACE) inhibitors are medications that dilate or widen blood vessels to lower blood pressure, improve blood flow, and decrease the workload on the heart. Some examples of ACE inhibitors include enalapril (Vasotec®), lisinopril (Prinivil®, Zestril®), and captopril (Capoten®). - Side effects of ACE inhibitors include chronic, nonproductive cough (occurs in about 10% of patients), dizziness or weakness (caused by low blood pressure), increased potassium levels, skin rashes, and angioedema (sudden swelling of the lips, face, and cheeks; if this occurs, the patient must seek medical attention immediately). - Angiotensin II (A-II) receptor blockers (ARBs): Angiotensin receptor blockers, or ARBs, have many of the beneficial effects of ACE inhibitors, but they do not cause a persistent cough. They may be an alternative for individuals who cannot tolerate ACE inhibitors. Some examples of ARBs include losartan (Cozaar®) and valsartan (Diovan®). - Digoxin (Lanoxin®): Digoxin (Lanoxin®) increases the strength of the heart muscle contractions. Digoxin also tends to slow the heartbeat. Digoxin reduces heart failure symptoms and improves the individual's ability to live with CHF. Side effects may include blurred vision, cardiac problems (such as irregular heartbeat or heart block), diarrhea, headaches, loss of appetite, hypotension (low blood pressure), and nausea and vomiting. Rarely, digoxin may cause a disturbance of color (typically yellow and green) and halos around light. Most side effects are dose-dependent and occur when blood levels of the drug are more than the therapeutic range. - Beta-blockers: Beta-blockers are a class of drugs that slows the heart rate and reduces blood pressure. Some examples include carvedilol (Coreg®), metoprolol (Lopressor®), and propranolol (Inderal®). These medicines also reduce the risk of some abnormal heart rhythms. Beta-blockers may reduce signs and symptoms of heart failure and improve heart function. Beta-blockers are started at low doses that are gradually increased over a period of several months. During the first several weeks of treatment, some patients experience worsening symptoms, due to a decrease in oxygen circulation in the body. Other side effects include low blood pressure, difficulty breathing, sexual dysfunction, nausea, and weakness with exertion. - Diuretics: Diuretics or water pills decrease the amount of fluid in the body typically by increasing the rate of urination. Commonly prescribed diuretics for heart failure include hydrochlorothiazide (Diuril®) and furosemide (Lasix®). Diuretics also decrease fluid in the lungs, helping individuals breathe more easily. Common side effects include frequent urination and low potassium blood levels (hypokalemia) or high potassium levels (hyperkalemia), depending on the diuretic. Because of this, blood tests are performed periodically and a potassium supplement is prescribed if blood levels are low. Individuals may be asked to eat more fruits high in potassium, such as bananas and oranges, while on diuretic therapy. Other side effects include low sodium levels (hyponatremia), increased blood sugar (hyperglycemia), increased cholesterol (hyperlipidemia), rash, joint disorders (e.g., gout), impotence (men), menstrual irregularities (women), and breast enlargement in men. - Aldosterone antagonists: Aldosterone antagonists are primarily potassium-sparing diuretics, but they have additional properties that help the heart work better, may reverse scarring of the heart, and may help individuals with severe heart failure live longer. Aldosterone antagonists include spironolactone (Aldactone®) and eplerenone (Inspra®). Unlike other diuretics, spironolactone can raise the level of potassium in the blood to dangerous levels. Healthcare professionals recommend eliminating high-potassium foods, such as bananas, lentils, nuts, peaches, potatoes, salmon, tomatoes, and watermelon while taking aldosterone antagonists. - Others: A medication called BiDil® is a single pill that combines hydralazine and isosorbide dinitrate, both of which dilate and relax the blood vessels. BiDil® increases survival when added to standard therapy in African American individuals with advanced heart failure. This is the first drug studied and approved for a specific racial group following the results of a human trial that found the medication reduced death, hospitalizations, and symptoms of heart failure among black patients who tried other agents. Further studies will be necessary to determine if this combination medicine will be helpful for others with heart failure. Side effects may include blurred vision, dry mouth, irregular heartbeat, blood in the urine or stools, numbness or tingling in the arms or legs, and fainting. - Doctors often prescribe other medications such as HMG-CoA reductase inhibitors (statin) drugs for cholesterol reduction. Some examples are atorvastatin (Lipitor®) and lovastatin (Mevacor®). They may cause liver problems or muscle pain. Anti-arrhythmic drugs may also be prescribed to control irregular heartbeats, including diltiazem (Cardizem®, Cardizem CR®) and verapamil (Calan®, Calan SR®). - Individuals may be hospitalized for a few days if complications arise as a result of CHF symptoms. While in the hospital, individuals may receive additional medications such as intravenous (IV, or into the veins) dobutamine (Dobutrex®), milrinone, (Primacor®), and nitroglycerin. These drugs work quickly to help the heart pump better and relieve symptoms. Individuals may also receive supplemental oxygen through a mask or small tubes placed in the nose. If severe heart failure is present, the individual may need to use supplemental oxygen long term. - Individuals hospitalized with severe CHF may be given an intravenous drug called nesiritide (Natrecor®). Nesiritide is a synthetic version of a naturally occurring hormone in the body called brain natriuretic peptide (BNP). BNP is secreted in high levels by the heart in response to a failing heart. However, it is not clear if nesiritide is better than other intravenous medications for severe heart failure. Studies are ongoing to evaluate the safety and effectiveness of nesiritide in heart failure. - Other treatments: - Aquapheresis: In some cases, heart failure persists or worsens in spite of treatment. An ultrafiltration process called aquapheresis, which uses a mechanical system called the Aquadex FlexFlowT, may be used to remove excess fluids and salt in CHF individuals who do not respond to lifestyle modifications and medication. In this treatment, blood is withdrawn using catheters (small tubes) inserted into veins in the arm, leg, or neck. The blood is then passed through a filter that removes excess fluid and is returned to the body. Studies have reported that ultrafiltration can remove more fluid at a faster rate than medication. The length of each treatment depends on the rate at which fluid can be removed from the body and the amount that must be removed. Low blood pressure (hypotension) may occur. - Angioplasty: CHF caused by reduced blood flow in the heart as a result of blockages (plaques) in one or more coronary arteries may be treated using coronary angioplasty. In this procedure, a hollow tube (catheter) is inserted through an artery (usually the femoral artery in the groin), into the coronary artery, and to the blockage. A small balloon is then inserted through the catheter and is inflated to open the blocked artery. There is a slight risk for damage to the artery during angioplasty, but heart failure symptoms usually improve following the procedure. Stenting is used along with balloon angioplasty. Stenting involves placing a mesh-like metal device into an artery at a site narrowed by plaque. The stent is mounted on a balloon-tipped catheter, threaded through an artery, and positioned at the blockage. The balloon is then inflated, opening the stent. Then the catheter and deflated balloon are removed, leaving the stent in place. The opened stent keeps the vessel open and stops the artery from collapsing. Re-closure may occur with both balloon angioplasty and stenting. Doctors may prescribe blood thinning medications to help keep the arteries open, including aspirin, warfarin (Coumadin®), and clopidogrel (Plavix®). - Coronary artery bypass graft surgery (CABG): A coronary artery bypass surgery (CABG) may be recommended if the individual has severe coronary artery disease (CAD) in addition to CHF. This may improve the blood supply to the heart. CABG surgery uses blood vessel grafts, which usually come from the patient's own arteries and veins located in the chest, leg, or arm. The graft goes around the clogged artery to create new pathways for oxygen-rich blood to flow to the heart. Some problems associated with CABG include a heart attack (occurs in five percent of patients), stroke (occurs in five percent, with the risk greatest in those more than 70 years old), blood clots, death (occurs in 1-2% of individuals), and wound infection (occurs in 1-4%). Infection is most often associated with obesity, diabetes, or having had a previous CABG. In about 30% of patients, post-pericardiotomy syndrome may occur anywhere from a few days to six months after surgery. The symptoms of this syndrome are fever and chest pain. Symptoms may be treated with medications, including antibiotics (for infection), nitroglycerin, and anti-inflammatory drugs. The incision in the chest or the graft site (if the graft was from the leg or arm) may be itchy, sore, numb, or bruised. Some individuals report memory loss, loss of mental clarity, or "fuzzy thinking" following a CABG. - Implantable cardiac defibrillator (ICD): An implantable cardiac defibrillator (ICD) may be used to treat severe heart failure. An ICD is a small electronic device that is surgically implanted under the skin in the chest to monitor heart rhythm. When an abnormal rhythm is detected, the defibrillator delivers an electrical shock to the heart to restore normal heart rhythm. - Intra-aortic balloon pump (IABP): An intra-aortic balloon pump (IABP) is a device that is inserted through an artery in the groin (femoral artery) and then placed within the main artery (aorta). An IABP is an inflatable balloon that expands and deflates in coordination with each heartbeat. It can be left in place for days to weeks, and decreases the strain on the heart and increases blood flow throughout the body. - Valve replacement surgery: Individuals with heart failure caused by an abnormal heart valve may require valve repair or valve replacement surgery. These are open-heart procedures in which an abnormal valve is repaired or replaced with a porcine valve (from pig tissue), a mechanical valve (made of synthetic material), or a homograft valve (from a human donor). Complications include bleeding, blood clots, infection, kidney failure, stroke, heart attack, valve rejection, and death. A homograft valve is preferred, as these valves are not associated with a significant risk for blood clot formation and, thus, do not require blood thinner therapy. Most individuals remain in the hospital for a week after surgery, and recovery takes approximately 3-4 weeks, after which most patients may resume leisure activities and many return to work. Approximately 60% of individuals who have valve replacement have a 10-year post-surgery survival rate. - Left ventricular assist device: A left ventricular assist device (LVAD) is a mechanical pump that is surgically implanted in the upper abdomen to bypass the left ventricle and pump blood throughout the body. This device may be used in patients with end-stage heart failure who are awaiting heart transplantation. Long-term use of the device in patients with severe heart failure is being explored and has not yet been defined. - Pacemaker: If individuals with CHF experience abnormal heart rhythms that will not respond to medication therapy, the irregular heart rhythms may be corrected with a pacemaker. A pacemaker is a small, battery-powered device that is usually implanted near the collarbone. Pacemakers can be surgically placed into the chest (a permanent pacemaker) through a small incision, or they can be worn outside the body (a temporary pacemaker) and attached to the heart through a wire that is threaded through a neck vein. Temporary pacemakers are used only while an individual is in the hospital. - The surgery needed to implant a permanent pacemaker is considered a minor surgical procedure. The procedure may take 1-2 hours to complete. The area where the pacemaker will be inserted will be numbed with an injection of an anesthetic such as lidocaine (Xylocaine®). The individual should not feel any pain during the procedure, and should inform the doctor or staff if he or she is having pain so that more anesthetic medication may be given. One or more electrode-tipped wires run from the pacemaker through the blood vessels to the inner heart. If the heart rate is too slow or if it stops, the pacemaker sends out electrical impulses that stimulate the heart to beat at a steady, proper rate. The more advanced pacemakers can monitor and pace either the atria or ventricles (or both) in proper sequence to maximize the amount of blood being pumped from the heart. The pacemaker's batteries may need to be changed every 5-10 years. It is recommended by the American Heart Association (AHA) to limit exposure to devices that may interfere with pulse generators such as cellular phones, CB radios, electric blankets, and microwaves. - It is normal for the surgical wound to be somewhat painful and swollen for a few days after the procedure. This can usually be controlled with medications, such as tramadol (Ultram®) or ibuprofen (Motrin®). The wound may also appear mildly red for a few days; however, if the area of redness enlarges, a doctor should be notified due to the potential for a serious infection. If there are no other problems, most individuals who have a permanent pacemaker surgically implanted can go home the next day. They may usually return to normal activities within six weeks. For several weeks after having a pacemaker implanted, the individual may be asked not to lift more than five pounds or raise the affected arm over their shoulder. - Heart transplant: In some cases, despite the use of optimal therapies, the individual's condition continues to deteriorate, due to progressive CHF. In selected individuals, heart transplantation is a viable treatment option. Candidates for a heart transplant are generally younger than age 70, do not smoke, and do not have severe or irreversible diseases affecting the other organs. Additionally, a transplant is done only when it is clear that the individual's prognosis (expected outcome) on the continued medical treatment is poor. Transplant patients require close medical follow-up while taking needed drugs that suppress the immune system because of the risk of rejection of the transplanted heart. They are even monitored for possible development of CAD in the transplanted heart. - Although there are thousands of patients on waiting lists for a heart transplant at any given time, the number of operations performed each year is limited by the number of available donor organs. For these reasons, heart transplantation is a realistic option in only a small subset of the large numbers of patients with CHF. - Strong scientific evidence: - Hawthorn: Hawthorn (Crataegus spp.), a flowering shrub of the rose family has an extensive history of use in cardiovascular disease dating back to the 1st Century. Increased blood flow to the heart and heart performance has been observed in animals when given hawthorn supplements. Extracts of the leaves and flowers of hawthorn have been reported as effective in the treatment of mild-to-moderate congestive heart failure (CHF), improving exercise capacity and reducing symptoms of cardiac insufficiency. However, whether hawthorn is as effective as drugs considered standard-of-care for heart failure (such as angiotensin converting enzyme (ACE) inhibitors, diuretics, or beta-adrenergic receptor blockers) is unclear, as is the effect of the combined use of hawthorn with these drugs. Nonetheless, hawthorn is a potentially beneficial treatment for patients who cannot or will not take prescription drugs and may offer additive benefits to established therapies. Further study is warranted. - Avoid if allergic to hawthorn or to members of the Crataegus species. Avoid with a history of low blood pressure, irregular heartbeat, asthma, low blood pressure when standing, or insomnia. Use cautiously in elderly patients. Avoid if pregnant or breastfeeding. - Good scientific evidence: - Arginine: Studies of arginine in patients with chronic heart failure (CHF) have shown mixed results. Some studies report improved exercise tolerance. Additional studies are needed to confirm these findings. - Avoid if allergic to arginine, or with a history of stroke, or liver or kidney disease. Avoid if pregnant or breastfeeding. Use caution if taking blood-thinning drugs (like warfarin or Coumadin®) and blood pressure drugs or herbs or supplements with similar effects. Blood potassium levels should be monitored as arginine may increase potassium levels. L-arginine may worsen symptoms of sickle cell disease. Caution is advised in patients taking prescription drugs to control blood sugar levels. - Berberine: Berberine is a bitter-tasting, yellow, plant alkaloid with a long history of medicinal use in Chinese and Ayurvedic medicine. Berberine is present in the roots, rhizomes, and stem bark of various plants including Hydrastis canadensis (goldenseal), Coptis chinensis (coptis or goldenthread), Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree turmeric). Preliminary clinical research suggests that berberine, in addition to a standard prescription drug regimen for chronic CHF, may improve quality of life, heart function, and risk of mortality. Further research is necessary. - Berberine has been reported to cause nausea, vomiting, hypertension (high blood pressure), respiratory failure, and paresthesias (abnormal sensations such as numbness or tingling). Use cautiously in patients with diabetes. Avoid if allergic or hypersensitive to berberine, to plants that contain berberine [Hydrastis canadensis (goldenseal), Coptis chinensis (coptis or goldenthread), Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree turmeric)], or to members of the Berberidaceae family. Avoid in newborns due to potential for increase in free bilirubin, jaundice, and development of kernicterus (a type of brain damage). Use cautiously with cardiovascular disease, gastrointestinal disorders, hematologic disorders, leucopenia, kidney disease, liver disease, respiratory disorders, cancer, hypertyraminemia, diabetes, or hypotension (low blood pressure). Use cautiously in children, due to lack of safety information. Use cautiously in individuals with high exposure to sunlight or artificial light. Use cautiously for longer than eight weeks, due to theoretical changes in bacterial gut flora. Use cautiously if taking anticoagulants, antihypertensives, sedatives, anti-inflammatories, medications metabolized by CYP P450 3A4 including cyclosporin, or any prescription medications. Avoid if pregnant or breastfeeding. - Coleus: Coleus species have been used in Asian traditional medicine for several indications. Since the 1970s, research was predominantly concentrated on forskolin, a root extract of Coleus forskohlii. A small number of studies suggest that forskolin may improve cardiovascular function in patients with cardiomyopathy. However, these trials are small and of poor quality. Larger studies are needed. - Coleus is generally regarded as safe, although long-term safety data are lacking. Avoid with a known allergy or hypersensitivity to Coleus forskohlii and related species. Rash may occur in sensitive individuals. Inhalation of forskolin may cause sore throat, upper respiratory tract irritation, mild-to-moderate cough, tremor, or restlessness. Coleus eye drops may produce a milky covering over the eyes. Use cautiously in patients with heart disease, asthma, thyroid disorders, diabetes, a history of bleeding, hemostatic disorders or drug-related hemostatic problems, low blood pressure, or in patients at risk for low blood pressure. Discontinue use in patients at least two weeks prior to surgical or dental procedures, due to risk of bleeding. Avoid in patients with active bleeding. Avoid during pregnancy. - Creatine: Creatine is naturally synthesized in the human body from amino acids primarily in the kidney and liver, and transported in the blood for use by muscles. Cardiac creatine levels have been reported as depressed in patients with chronic CHF. Several studies report that creatine supplementation is associated with improved heart muscle strength, body weight, and endurance in patients with heart failure. However, it is not clear what dose may be safe or effective. Supplementation is also reported to increase creatine in the skeletal muscle in these patients, helping to increase strength and endurance. Well-designed studies comparing creatine with drugs used to treat heart failure are needed. - Avoid if allergic to creatine or with diuretics (such as hydrochlorothiazide, furosemide (Lasix®)). Use caution in asthma, diabetes, gout, kidney, liver, or muscle problems, stroke or a history of these conditions. Avoid dehydration. Avoid if pregnant or breastfeeding. - Selenium: Keshan disease is a cardiomyopathy (heart disease) restricted to areas of China in people having an extremely low selenium status. Prophylactic administration of sodium selenite has been shown to significantly decrease the incidence of this disorder. Organic forms of selenium (such as selenized yeast or Se-yeast) may have better bioavailability than selenite and thus may be better preventative treatments for Keshan disease. Selenium is used to treat and prevent selenium deficiency (for example in those with HIV or receiving enteral feedings). - Selenium is a trace element and hypersensitivity is unlikely. Avoid individuals with a known allergy/hypersensitivity to products containing selenium. - The level of selenium exposure that will cause chronic toxicity is not known. Selenium toxicity may cause gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea, garlic-like breath odor, and metallic taste), neuromuscular-psychiatric disturbances (weakness/fatigue, lightheadedness, irritability, hyperreflexia, muscle tenderness, tremor, and peripheral neuropathy), dermatologic changes (skin rash/dermatitis/flushing, fingernail loss/thickening/blotching/streaking/paronychia, and hair changes/loss), liver dysfunction, kidney dysfunction, thrombocytopenia (low blood platelets), immune alterations (natural killer cell impairment), thyroid dysfunction (decreased T3), reduced sperm motility, or growth retardation. - Unclear or conflicting scientific evidence: - Aconite: The toxic effects associated with aconite limit its ability to be used to treat heart failure, including reno-cardiovascular disease and left ventricular function. Further study is needed. - Aconite is highly toxic and is not safe for human consumption. Avoid with heart disease, heart dysfunction, irregular heartbeat, hemodynamic instability (abnormal blood flow), gastrointestinal disorders, ulcers, reflux esophagitis, ulcerative colitis, spastic colitis, and diverticulosis. Use caution with diabetes and suicidal tendencies. Avoid if younger than 18 years. Avoid if pregnant or breastfeeding. - Astragalus: Astragalus (Astragalus membranaceus) is used in combination with other herbs in Chinese medicine to treat various heart diseases. There is some evidence that astragalus may offer symptomatic improvement for chronic heart failure. Recommendations cannot be made until well-designed clinical trials have been conducted. - Avoid if allergic to astragalus, peas, or any related plants or with a history of Quillaja bark-induced asthma. Avoid with aspirin or aspirin products or herbs or supplements with similar effects. Avoid with inflammation (swelling) or fever, stroke, transplant or autoimmune diseases (such as HIV/AIDS or human immunodeficiency virus/acquired immunodeficiency syndrome). Stop use two weeks before surgery/dental/diagnostic procedures with a risk of bleeding and avoid use immediately after these procedures. Use cautiously with bleeding disorders, diabetes, high blood pressure, lipid disorders, or kidney disorders. Use cautiously with blood-thinners, blood sugar drugs, or diuretics, or herbs and supplements with similar effects. Avoid if pregnant or breastfeeding. - Ayurveda: Ayurveda, which originated in ancient India more than 5,000 years ago, is probably the world's oldest system of natural medicine. Preliminary evidence suggests that sodium nimbidinate, made from the traditional Ayurvedic herb Nimba/Neem/Arishta (Azadirachta indica), may be an effective diuretic in patients with congestive heart failure (CHF). More studies are needed to confirm this effect. - Ayurvedic herbs should be used cautiously because they are potent and some constituents may be potentially toxic if taken in large amounts or for a long time. Some herbs imported from India have been reported to contain high levels of toxic metals. Ayurvedic herbs may interact with other herbs, foods, and drugs. A qualified healthcare professional should be consulted before taking. - Camphor: Preliminary evidence indicates that a German combination product of camphor and extract of hawthorn berries (Korodin® Herz-Kreislauf-Tropfen) may reduce overall symptoms in patients with functional cardiovascular disease. While these early findings are promising, further research is required before any recommendation can be made. - Camphor and camphor-containing products are generally applied as topical formulations. Ingestion of such preparations is not recommended, as they are potentially poisonous and may induce a number of adverse and potentially fatal side effects. Caution is advised for use of any internal preparations of camphor due to their potential toxicity. - Coenzyme Q10 (CoQ10): CoQ10 is produced by the human body and is necessary for the basic functioning of cells. The evidence for CoQ10 in the treatment of heart failure is controversial and remains unclear. Different levels of disease severity have been studied (New York Heart Association classes I through IV). Better research is needed in this area, studying effects on quality of life, hospitalization, and death rates. There is also conflicting evidence from research on the use of CoQ10 in patients with dilated or hypertrophic cardiomyopathy. - CoQ10 is generally safe in recommended dosages, but further studies are needed. - Allergy associated with CoQ10 supplements has not been reported, although rash and itching have been reported rarely. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk and do not use immediately after these procedures. Use caution with a history of blood clots, diabetes, high blood pressure, heart attack, or stroke, or with anticoagulants (blood thinners), antiplatelet drugs (such as aspirin, warfarin, clopidogrel (e.g., Plavix®), or blood pressure, blood sugar, cholesterol or thyroid drugs. Avoid if pregnant or breastfeeding. - Ginseng: A clinical study on the effect of Panax ginseng on CHF did not show a clear benefit of combining digoxin with ginseng. The relatively small study size and the use of a drug instead of a standardized extract limit the value of the evidence. Additional research is needed. - Ginseng may also lower blood pressure. Caution is used when taking ginseng supplements, as adverse effects and drug interactions are possible. Ginseng supplements should not be used if pregnant or breastfeeding unless otherwise directed by a doctor. - Goldenseal: Limited available study suggests that berberine (the active compound of goldenseal) in addition to a standard prescription drug regimen for CHF may improve quality of life and decrease ventricular premature complexes (VPCs) and mortality. Further research is needed to confirm these results. - Use cautiously in patients with gastrointestinal disorders, cardiovascular disease, bleeding disorders or in those taking anticoagulants, diabetes or in those taking antidiabetic agents. Use cautiously in infants with increased bilirubin levels or individuals with glucose-6-phosphate deficiency. Use cautiously in pregnancy. - Hawthorn: Herbal combinations containing hawthorn have been found effective in the treatment of functional cardiovascular disorders. However, due to a lack of information on the use of hawthorn alone, there is not enough evidence to recommend for or against this use of hawthorn. - Avoid if allergic to hawthorn or to members of the Crataegus species. Avoid with a history of low blood pressure, irregular heartbeat, asthma, low blood pressure when standing, or insomnia. Use cautiously in elderly patients. Avoid if pregnant or breastfeeding. - L-carnitine: L-carnitine, carnitine, or acetyl-L-carnitine, is an amino acid found in the body. Although preliminary results are promising, there is insufficient available clinical evidence for the use of L-carnitine in CHF. - Avoid with a known allergy or hypersensitivity to carnitine. Use cautiously with peripheral vascular disease, hypertension (high blood pressure), alcohol-induced liver cirrhosis, and diabetes. Use cautiously in low birthweight infants and individuals on hemodialysis. Use cautiously if taking anticoagulants (blood thinners), beta-blockers, or calcium channel blockers. Avoid if pregnant or breastfeeding. - Meditation: Meditation may improve quality of life in elderly patients, and may potentially reduce the risk for CHF. However, there is not enough evidence to make a conclusion. - Use cautiously with underlying mental illnesses. People with psychiatric disorders should consult with their primary mental healthcare professional(s) before starting a program of meditation, and should explore how meditation may or may not fit in with their current treatment plan. Avoid with risk of seizures. The practice of meditation should not delay the time to diagnosis or treatment with more proven techniques or therapies, and should not be used as the sole approach to illnesses. - Oleander: The term oleander refers to two plants: Nerium oleander (common oleander) and Thevetia peruviana (yellow oleander). Both plants contain heart-active cardiac glycoside chemicals (similar to the prescription drug digoxin) and have been associated with serious side effects in humans, including death. The plants have been used to treat CHF in China and Russia for decades, but scientific evidence supporting this use is limited to small, poorly designed studies. Human research began in the 1930s, but was largely abandoned due to serious gastrointestinal and heart toxicity. - All parts of the oleander plant, including flowers, leaves, and nectar are considered toxic and may cause death. Avoid if allergic to oleander or other cardiac glycosides such as digoxin. Avoid with a history of irregular heartbeat (arrhythmia), seizures, liver or kidney disease, depression, or asthma. Avoid if pregnant or breastfeeding. - Passion flower: An extract containing passionflower and hawthorn has been studied for potential enhancement of exercise capacity in CHF patients. Individuals using this combination of herbs have experienced improvements in symptoms; however, any positive effects may have resulted from hawthorn, which is more commonly used for congestive heart failure. High quality human research of passion flower alone and compared to prescription drugs used for this condition is needed. - Avoid if allergic to passionflower or any of its constituents. Avoid consuming raw Passiflora fruit (Passiflora adenopoda), due to possible cyanide constituents. Passionflower extracts may cause drowsiness in sensitive individuals. Avoid driving or operating heavy machinery while taking passionflower. Use cautiously with low blood pressure. Avoid if pregnant or breastfeeding. - Physical therapy: Both supervised and home-based exercise training may enhance exercise capacity in patients with CHF. However, consensus has not been obtained regarding a standard rehabilitation program for these patients, and the literature often suggests individually-tailored programs. Due to the lack of standardization, duration of treatment, and various outcomes' measures, more study is needed before a conclusion can be made. - Not all physical therapy programs are suited for everyone, and patients should discuss their medical history with a qualified healthcare professional before beginning any treatments. Physical therapy may aggravate pre-existing conditions. Persistent pain and fractures of unknown origin have been reported. Physical therapy may increase the duration of pain or cause limitation of motion. Pain and anxiety may occur during the rehabilitation of patients with burns. Both morning stiffness and bone erosion have been reported in the literature although causality is unclear. Erectile dysfunction has also been reported. Physical therapy has been used in pregnancy and although reports of major adverse effects are lacking in the available literature, caution is advised nonetheless. All therapies during pregnancy and breastfeeding should be discussed with a licensed obstetrician/gynecologist before initiation. - Relaxation therapy: Early studies suggest that progressive muscle relaxation training may benefit patients with heart failure when used in combination with standard care. - Avoid with psychiatric disorders such as schizophrenia/psychosis. Jacobson relaxation (flexing specific muscles, holding that position, and then relaxing the muscles) should be used cautiously with illnesses such as heart disease, high blood pressure, or musculoskeletal injury. Relaxation therapy is not recommended as the sole treatment approach for potentially serious medical conditions, and should not delay the time to diagnosis or treatment with more proven techniques. - Selenium: Low selenium levels have been associated with the development of cardiomyopathy, and selenium supplementation is likely of benefit in such cases (for example in Keshan disease and Chagas' disease). However, most cases of cardiomyopathy are not due to low selenium levels and therefore selenium may not be helpful. It has been suggested that low selenium levels may be a risk factor for coronary heart disease, although this remains unclear. - Avoid if allergic or sensitive to products containing selenium. Avoid with a history of nonmelanoma skin cancer. Selenium is generally regarded as safe for pregnant or breastfeeding women. However, animal research reports that large doses of selenium may lead to birth defects. - Taurine: Taurine is a nonessential amino acid-like compound, found in high abundance in the tissues of many animals, especially sea animals, and in much lower concentrations in plants, fungi, and some bacteria. Preliminary study suggests that taurine may be beneficial as an adjunct to traditional medications for symptoms of CHF. Further study is warranted to confirm these findings. - Taurine appears to be safe in recommended dosages. As an amino acid, it is unlikely that there are allergies related to this constituent. However, allergies may occur from multi-ingredient products that contain taurine. Use cautiously in patients with high cholesterol, low blood pressure, coagulation disorders, potential for mania, or epilepsy. Avoid alcohol or exercise after consumption of energy drinks containing taurine, caffeine, glucuronolactone, B vitamins, and other ingredients. Use cautiously if pregnant or breastfeeding; taurine is a natural component of breast milk - Thiamin: Thiamin (also spelled "thiamine") is a water-soluble B-complex vitamin, previously known as vitamin B1 or aneurine. Thiamin was isolated and characterized in the 1920s, and thus was one of the first organic compounds to be recognized as a vitamin. Chronic severe thiamin deficiency may cause heart failure (wet beriberi), a condition that merits thiamin supplementation. Currently, it is not clear if thiamin supplementation is beneficial in patients with heart failure due to other causes. However, it is reasonable for patients with heart failure to take a daily multivitamin including thiamin, because some of these individuals may be thiamin deficient. Diuretics may lower thiamin levels. Since diuretics are commonly administered to patients with heart failure, patients taking diuretics are at an increased risk of thiamin deficiency. This area remains controversial, and further evidence is necessary before a conclusion can be reached. Excessive alcohol consumption may cause thiamin deficiency. - Avoid if allergic or hypersensitive to thiamin. Rare hypersensitivity/allergic reactions have occurred with thiamin supplementation. Skin irritation, burning, or itching may rarely occur at injection sites. Large doses may cause drowsiness or muscle relaxation. Use cautiously if pregnant or breastfeeding with doses higher than the U.S. Recommended Daily Allowance (RDA). - Thymus extract: The thymus is a lobular gland located under the breastbone near the thyroid gland. It reaches its maximum size during early childhood and plays a large role in immune function. Preliminary evidence suggests that thymus extract may increase left ventricular function, exercise tolerance, and survival in patients with cardiomyopathy. Additional research is needed to confirm these results. - It is important to use high quality thymus gland supplements due to contamination concerns. Avoid if allergic or hypersensitive to thymus extracts. Use bovine thymus extract supplements cautiously due to potential for exposure to the virus that causes mad cow disease. Avoid use with an organ transplant or other forms of allografts or xenografts. Avoid if receiving immunosuppressive therapy, with thymic tumors, myasthenia gravis (neuromuscular disorder), untreated hypothyroidism, or if taking hormonal therapy. Avoid if pregnant or breastfeeding; thymic extract increases human sperm motility and progression. - Traditional Chinese medicine (TCM): Many studies of traditional Chinese medicine (TCM) herbs have focused on treatment of CHF. Further research of better design is needed before recommendations can be made. - Chinese herbs can be potent and may interact with other herbs, foods or drugs. Consult a qualified healthcare professional before taking. There have been reports of manufactured or processed Chinese herbal products being tainted with toxins or heavy metals or not containing the listed ingredients. Herbal products should be purchased from reliable sources. Avoid ma huang, which is the active ingredient in ephedra. Avoid ginseng if pregnant or breastfeeding. - Fair negative scientific evidence: - Guided imagery: Therapeutic guided imagery may be used to help individuals relax and focus on images associated with personal issues they are confronting. Preliminary human research does not report benefits of guided imagery in congestive heart failure (CHF). - Guided imagery is usually intended to supplement medical care, not to replace it, and guided imagery should not be relied on as the sole therapy for a medical problem. Contact a qualified healthcare provider if mental or physical health is unstable or fragile. Never use guided imagery techniques while driving or doing any other activity that requires strict attention. Use cautiously with physical symptoms that may be brought about by stress, anxiety, or emotional upset because imagery may trigger these symptoms. If feeling unusually anxious while practicing guided imagery, or with a history of trauma or abuse, speak with a qualified healthcare provider before practicing guided imagery. - General: Coronary artery disease (CAD) and hypertension (high blood tension) may cause or worsen existing cardiomyopathy. Therefore, preventative measures for cardiomyopathy aim at reducing the risk of CAD. - Smoking cessation: Smoking damages blood vessels, reduces the amount of oxygen in the blood, and makes the heart beat faster. If an individual smokes, a doctor may help recommend a program or treatment option to help them quit. Individuals are not considered for a heart transplant if smoking is continued. - Weight control: It is recommended that individuals weigh themselves each morning after urination, but before breakfast. Notify a doctor if there is a weight gain of three or more pounds in a day. Weight gain may indicate fluid build-up. - Being overweight contributes to other risk factors for stroke, such as high blood pressure, cardiovascular disease, and diabetes. Weight loss of as little as ten pounds may lower blood pressure and improve cholesterol levels. - Exercise may lower blood pressure, increase the level of high density lipoprotein (HDL cholesterol or good cholesterol), and improve the overall health of blood vessels and heart. It also helps control weight, control diabetes, and reduce stress. Cardiac rehabilitation programs exist for individuals recovering from heart surgery. Cardiac rehabilitation is a medically supervised program to help heart patients recover quickly and improve their overall physical, mental, and social functioning. The goal is to stabilize, slow, or even reverse the progression of cardiovascular disease, thereby reducing the risk of heart disease, another cardiac event, or death. Cardiac rehabilitation programs include: counseling so the individual can understand and manage the disease process; an exercise program; counseling on nutrition; helping the patient modify risk factors such as high blood pressure, smoking, high blood cholesterol, physical inactivity, obesity, and diabetes; providing vocational guidance to enable the patient to return to work; information on physical limitations; lending emotional support; and counseling on appropriate use of prescribed medications. A doctor may help initiate an exercise program and cardiac rehabilitation tailored to the individual with congestive heart failure (CHF). - Salt restriction: Too much sodium (from salt) contributes to water retention, which makes the heart work harder. Excess sodium may causes shortness of breath and swollen legs, ankles, and feet. For individuals with heart failure the recommended sodium intake is no more than 2,000 milligrams daily. Some substitutes or "lite" salts contain a mixture of salt and other compounds. To get that familiar salty taste, individuals may use too much of the substitute and actually not reduce sodium intake. In addition, many salt substitutes contain potassium chloride. Too much potassium may be harmful. A dietitian may help outline a healthy, low-salt diet. - Stress management: Stress may cause an increase in blood pressure along with increasing the blood's tendency to clot. Managing stress may be vital to keeping a heart healthy. - Diet modification: Eating healthy foods is important. A heart-healthy diet includes five or more daily servings of fruits and vegetables, foods rich in soluble fiber (such as oatmeal and beans), foods rich in calcium (dairy products, spinach), soy products (such as tempeh, miso, tofu, and soy milk), and foods rich in omega-3 fatty acids, including cold-water fish, such as salmon, mackerel, and tuna. Pregnant women and women who plan to become pregnant in the next several years should limit their weekly intake of cold-water fish because of the potential for mercury contamination. Limiting red meats and high fat foods (such as doughnuts, cookies, and chips) is recommended by healthcare professionals. - Alcohol: Excessive use of alcohol may weaken the heart muscle or increase the risk of abnormal heart rhythms, increasing the risk of cardiomyopathy and resultant heart failure. Alcohol may also interact with some medications used to treat heart conditions. However, moderate alcohol consumption (such as one glass of red wine daily) may be beneficial for heart health. - Swelling: Leg, ankle, and foot edema can be improved by elevating the legs above heart level for 30 minutes 3-4 times daily. Leg elevation alone may be sufficient therapy for patients with mild venous insufficiency, but is usually not adequate for more severe cases. In addition, it may not be practical for those who work to elevate their legs several times daily. - Leg edema (swelling) can also be prevented and treated with the use of compression stockings. Many types are available, including knee-high, thigh-high, and pantyhose. Knee-high stockings are sufficient for most individuals; thigh-high stockings are less desirable because they tend to provide too much pressure behind the knees, reducing blood flow in the veins, and causing discomfort. The stockings should be put on as early as possible in the morning when edema is minimal. Healthcare professionals can help with choosing the right compression stocking for each individual. - Contraception: Because women who have previously had peripartum cardiomyopathy are at increased risk of developing cardiomyopathy with future pregnancies, they may consider contraception to prevent future pregnancies. - This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com). - Allard ML, Jeejeebhoy KN, Sole MJ. The management of conditioned nutritional requirements in heart failure. Heart Fail Rev. 2006 Mar;11(1):75-82. - American Heart Association (AHA). . - Centers for Disease Control and Prevention (CDC). . - Dauchet L, Amouyel P, Hercberg S, et al. Fruit and vegetable consumption and risk of coronary heart disease: a meta-analysis of cohort studies. J Nutr. 2006 Oct;136(10):2588-93. - Hunt SA; American College of Cardiology; American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol. 2005 Sep 20;46(6):e1-82. - Hypertrophic Cardiomyopathy Association. . - Kaski JP, Elliott P; ESC Working Group. The classification concept of the ESC Working Group on myocardial and pericardial diseases for dilated cardiomyopathy. Herz. 2007 Sep;32(6):446-51. - Maron BJ, Thompson PD, Ackerman MJ, et al. Recommendations and considerations related to preparticipation screening for cardiovascular abnormalities in competitive athletes: 2007 update: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation. 2007 Mar 27;115(12):1643-455. - Maron BJ, Towbin JA, Thiene G, et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation. 2006 Apr 11;113(14):1807-16. - National Heart, Lung, and Blood Institute (NHLBI). . - National Institutes of Health (NIH). . - Natural Standard: The Authority on Integrative Medicine. . - Riegel B, Moser DK, Powell M, et al. Nonpharmacologic care by heart failure experts. J Card Fail. 2006 Mar;12(2):149-153. - Sen-Chowdhry S, Morgan RD, Chambers JC, et al. Arrhythmogenic cardiomyopathy: etiology, diagnosis, and treatment. Annu Rev Med. 2010;61:233-53. - Wexler RK, Elton T, Pleister A, et al. Cardiomyopathy: an overview. Am Fam Physician. 2009 May 1;79(9):778-84. - General: Cardiomyopathy refers to several diverse diseases that affect the myocardium (heart muscle). Different forms of cardiomyopathy have distinct causes. Primary cardiomyopathies may be inherited, acquired, or both. Secondary cardiomyopathies are caused by other conditions, including diabetes, thyroid disorders, chronic alcohol consumption, infection, or drugs/toxins (e.g., heavy metals, anthracyclines, cocaine). - Arrhythmogenic right ventricular cardiomyopathy (ARVC): Arrhythmogenic right ventricular cardiomyopathy (ARVC, formerly known as arrhythmogenic right ventricular dysplasia or ARVD) is a genetic disease caused by mutations in genes that affect heart muscle cells. The most common genetic causes of ARVC are mutations in the plakophilin 2 (PKP2) gene, which produces a protein that helps myocardial cells attach to each other. Mutations in PKP2 that cause ARVD result in defective forms of the plakophilin 2 protein. Although mutations in PKP2that cause ARVC are usually autosomal dominant, which means that they would affect both sexes equally, ARVC occurs in men three times more often than in women. It is unclear why more men are affected; however, it appears that physical activity may increase the risk of arrhythmia (abnormal heart beat) in ARVD. - Dilated cardiomyopathy: There are multiple factors (primary or secondary) that may cause different forms of dilated cardiomyopathy. The most common form, ischemic cardiomyopathy, is most often caused by coronary artery disease (CAD) and/or high blood pressure; however, viral infections, other heart diseases, or genetics may also lead to ischemic cardiomyopathy. Peripartum cardiomyopathy is diagnosed in pre- or postnatal mothers when other known causes of dilated cardiomyopathy have been excluded. It is unclear what exactly causes peripartum cardiomyopathy; however, risk factors include obesity, pregnancy-induced hypertension (preeclampsia), multiple pregnancy (such as twins or triplets), or being more than 30 years of age. Stress (physical or emotional) or excessive alcohol consumption may also cause dilated cardiomyopathy - Hypertrophic cardiomyopathy (HCM): Hypertrophic cardiomyopathy (HCM) is a genetic disease caused by mutations in genes that produce sarcomere proteins. Sarcomeres are units of myofibrils, which are threadlike strands that make up the muscle that contracts the heart. Because HCM is usually inherited, having a parent with the condition increases the risk of inheriting the gene that causes HCM. While HCM is often asymptomatic, physical activity greatly increases the risk of complications and sudden death, due to HCM. - Restrictive cardiomyopathy: Restrictive cardiomyopathy is usually secondary to another acquired or inherited heart disease (such as amyloidosis, endomyocardial fibrosis, or sarcoidosis). It may also occur after a heart transplant, and having any disease or injury that affects the heart muscle may increase the risk of restrictive cardiomyopathy. Heritable forms of restrictive cardiomyopathy are most often caused by mutations in genes that produce troponin, a muscle protein that aids in muscle contraction. - Arrhythmogenic right ventricular cardiomyopathy (ARVC): Arrhythmogenic right ventricular cardiomyopathy (ARVC, formerly known as arrhythmogenic right ventricular dysplasia or ARVD) is a genetic disease that can be passed through families. Having a parent with ARVC increases the risk of developing the condition. ARVC occurs in men three times more often than in women; however, it is unclear why more men are affected. Physical activity may increase the risk of arrhythmia (abnormal heart beat) in ARVD. - Dilated cardiomyopathy: Because there are multiple factors (primary or secondary) that can cause the different forms of dilated cardiomyopathy, there are also many different risk factors. For the most common form of dilated cardiomyopathy, ischemic cardiomyopathy, major risk factors are coronary artery disease (CAD) and high blood pressure. However, viral infections, other heart diseases, or genetics may also increase the risk of ischemic cardiomyopathy. For peripartum cardiomyopathy that occurs in women during the last month of pregnancy or first five months following birth, risk factors include obesity, pregnancy-induced hypertension (preeclampsia), multiple pregnancy (such as twins or triplets), or being more than 30 years of age. Women who have previously had peripartum cardiomyopathy are also at increased risk of developing cardiomyopathy with future pregnancies. Physical or emotional stress may worsen (or even cause) cardiomyopathy. Excessive alcohol consumption may also increase the risk of dilated cardiomyopathy. - Hypertrophic cardiomyopathy (HCM): Like ARVC, hypertrophic cardiomyopathy (HCM) is also a genetic disease that is inherited. Having a parent with the condition increases the risk of developing HCM. While HCM is often asymptomatic (without symptoms), physical activity greatly increases the risk of complications (e.g., atrial fibrillation) and death, due to HCM. - Restrictive cardiomyopathy: Restrictive cardiomyopathy is usually secondary to another acquired or inherited heart disease (such as amyloidosis, endomyocardial fibrosis, or sarcoidosis). It may also occur after a heart transplant. Having any disease or injury that affects the heart muscle may increase the risk of restrictive cardiomyopathy. Having a parent with the condition increases the risk of heritable forms of restrictive cardiomyopathy. Types of the disease - There are four main types of cardiomyopathy as defined by the American Heart Association (AHA): arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy, hypertrophic cardiomyopathy (HCM), and restrictive cardiomyopathy. Dilated cardiomyopathy may result from multiple causes and is the most common form of cardiomyopathy that affects the overall population of North America. HCM is genetic in origin, and is the most common cause of sudden death in athletes. Restrictive cardiomyopathy and ARVC are considered to be rarer forms of the disease. - The different types of cardiomyopathy are further classified by the AHA as primary or secondary. Primary cardiomyopathies cannot be attributed to other conditions (such as heart disease). Instead, they may be caused by genetic (inherited) factors, acquired factors, or a combination of genetic and acquired traits. Acquired causes of cardiomyopathy include inflammatory cardiomyopathy (myocarditis), post- or peripartum cardiomyopathy, and stress cardiomyopathy (broken heart syndrome). Secondary cardiomyopathy occurs as a result of another condition, such as an infection or a metabolic disease (e.g., diabetes or coronary heart disease). - Arrhythmogenic right ventricular cardiomyopathy (ARVC): Arrhythmogenic right ventricular cardiomyopathy (ARVC, formerly known as arrhythmogenic right ventricular dysplasia or ARVD) is a genetic disease that causes the myocardium to become fatty and fibrous. Though it mainly affects the right ventricle of the heart, it may also affect the left ventricle. In contrast to other forms of cardiomyopathy, ARVC seldom results in heart failure. However, it does cause abnormal heart function such as arrhythmia (abnormal heartbeat), which may be fatal. - Dilated cardiomyopathy: In dilated cardiomyopathy, the myocardium becomes weak, enlarged, and unable to pump blood efficiently. The prevalence of dilated cardiomyopathy in the United States is 36 per 100,000. It is considered the most common form of cardiomyopathy. After coronary artery disease (CAD) and hypertension (high blood pressure), dilated cardiomyopathy is the third most common cause of heart failure in the United States. - There are several types of dilated cardiomyopathy, which are caused by multiple factors (primary or secondary). The three types of dilated cardiomyopathy include ischemic cardiomyopathy, peripartum cardiomyopathy, and stress cardiomyopathy. - Ischemic cardiomyopathy is the most common form of dilated cardiomyopathy. It is most often caused by CAD or high blood pressure; however, viral infections, other heart diseases, or genetics may also contribute to ischemic cardiomyopathy. - Peripartum cardiomyopathy is usually diagnosed in women in their last month of pregnancy, or in the first five months following birth (also called postpartum cardiomyopathy). Although it is rare (affecting one in 1,000-4,000 live births), peripartum cardiomyopathy is more prevalent in women who are over age 30, obese, have pregnancy-induced hypertension (preeclampsia), or multiple births. - Excessive alcohol use may also cause dilated cardiomyopathy. - Hypertrophic cardiomyopathy (HCM): In hypertrophic cardiomyopathy (HCM), the myocardium is thickened. As a result, it becomes difficult for the heart to pump blood. Nearly one-half of deaths due to HCM occur during or after physical activity. Sudden death occurs due to lethal heart rhythm disturbances (ventricular fibrillation and ventricular tachycardia). It is the most common cause of sudden cardiac death in athletes as a result of structural heart changes in response to intense training. Because HCM is typically an inherited disorder, it is also called familial HCM. It is estimated that one of 500 people has the gene for HCM. However, it may also be acquired resulting from high blood pressure or aortic stenosis (narrowing or obstruction of the aortic valve causing restricted blood flow). Symptoms of HCM include chest pain, shortness of breath, dizziness, palpitations, and fatigue. - Restrictive cardiomyopathy: In restrictive cardiomyopathy, the heart is unable to function properly, due to stiffness of the myocardium. The heart is usually normal size (or slightly larger), but the myocardium of one or both ventricles (cavities or chambers) cannot relax after each heartbeat because of stiffness in the heart. Instead, the ventricles are restricted and do not fill with enough blood. Restrictive cardiomyopathy may have a genetic cause, or it may result from another myocardial disease. - Other: Stress cardiomyopathy (also known as broken heart syndrome or Takotsubo cardiomyopathy) is triggered by sudden intense physical or emotional stress (e.g., death of a loved one, fear, extreme anger). The clinical presentation is similar to that of a heart attack. The most common symptoms are chest pain, shortness of breath, and low blood pressure. Copyright © 2011 Natural Standard (www.naturalstandard.com) The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.	2	10	0	0	1	0.957885	1	15,632
\|Classification and external resources\| (A) Normal electrocardiogram pattern in the precordial leads V1-3, (B) changes in Brugada syndrome (type B) The Brugada syndrome is a genetic disease that is characterised by abnormal electrocardiogram (ECG) findings and an increased risk of sudden cardiac death. It is named by the Spanish/Belgian cardiologists Pedro Brugada and Josep Brugada. It is the major cause of sudden unexplained death syndrome (SUDS), also known as sudden adult death syndrome (SADS), and is the most common cause of sudden death in young men without known underlying cardiac disease in Thailand and Laos. Although the ECG findings of Brugada syndrome were first reported among survivors of cardiac arrest in 1989, it was only in 1992 that the Brugada brothers recognized it as a distinct clinical entity, causing sudden death by causing ventricular fibrillation (a lethal arrhythmia) in the heart. Genetics and pathophysiology \|B1\|\|601144\|\|SCN5A\|\|alpha subunit of the sodium channel. Current through this channel is commonly referred to as INa. Loss of function in this channel leads to an unopposed Ito current (KCND2)\| \|B2\|\|611778\|\|GPD1L\|\|Glycerol-3-phosphate dehydrogenase like peptide\| \|B3\|\|114205\|\|CACNA1C\|\|Alpha subunit of cardiac L-type calcium channel.\| \|B4\|\|600003\|\|CACNB2\|\|Beta-2 subunit of the voltage dependent L-type calcium channel.\| \|B5\|\|604433\|\|KCNE3 which coassembles with KCND3\|\|Beta subunit to KCND3. Modulates the Ito potassium outward current\| \|B6\|\|600235\|\|SCN1B\|\|Beta-1 subunit of the sodium channel SCN5A\| Approximately 20% of the cases of Brugada syndrome have been shown to be associated with mutations in the gene that encodes for the sodium ion channel in the cell membranes of the muscle cells of the heart (the myocytes). The gene, named SCN5A, is located on the short arm of the third chromosome (3p21). Loss-of-function mutations in this gene lead to a loss of the action potential dome of some epicardial areas of the right ventricle. This results in transmural and epicardial dispersion of repolarization. The transmural dispersion underlies ST-segment elevation and the development of a vulnerable window across the ventricular wall, whereas the epicardial dispersion of repolarization facilitates the development of phase 2 reentry, which generates a phase 2 reentrant extrasystole that captures the vulnerable window to precipitate ventricular tachycardia and/or fibrillation that often results in sudden cardiac death. At present time however, all the reported patients who died because of the disease and were submitted to detailed autopsy study have shown a structural right ventricular pathology underlying the syndrome. Over 160 mutations in the SCN5A gene have been discovered to date, each having varying mechanisms and effects on function, thereby explaining the varying degrees of penetration and expression of this disorder. An example of one of the mechanisms in which a loss of function of the sodium channel occurs is a mutation in the gene that disrupts the sodium channel's ability to bind properly to ankyrin-G, an important protein mediating interaction between ion channels and cytoskeletal elements. Very recently a mutation in a second gene, Glycerol-3-phosphate dehydrogenase 1-like gene (GPD1L) has been shown to result in Brugada syndrome in a large multigenerational family (London, 2006). This gene acts as an ion channel modulator in the heart, although the exact mechanism is not yet understood. Recently Antzelevitch has identified mutations in the L-type calcium channel subunits (CACNA1C (A39V and G490R) and CACNB2 (S481L)) leading to ST elevation and a relatively short QT interval (below 360 ms). For a comprehensive list of all mutations see In 2013, Bezzina et al showed that common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome. This condition is inherited in an autosomal dominant pattern and is more common in males. In addition it has a higher prevalence in most Asian populations. In some cases, the disease can be detected by observing characteristic patterns on an electrocardiogram, which may be present all the time or might be elicited by the administration of particular drugs (e.g., Class IA (ajmaline) or class 1C (flecainide) antiarrhythmic drugs that block sodium channels and cause appearance of ECG abnormalities) or resurface spontaneously due to as yet unclarified triggers. Brugada syndrome has three different ECG patterns. - Type 1 has a coved type ST elevation with at least 2 mm (0.2 mV) J-point elevation a gradually descending ST segment followed by a negative T-wave. - Type 2 has a saddle back pattern with a least 2 mm J-point elevation and at least 1 mm ST elevation with a positive or biphasic T-wave. Type 2 pattern can occasionally be seen in healthy subjects. - Type 3 has either a coved (type 1 like) or a saddle back (type 2 like) pattern with less than 2 mm J-point elevation and less than 1 mm ST elevation. Type 3 pattern is not uncommon in healthy subjects. The pattern seen on the ECG is persistent ST elevations in the electrocardiographic leadsV1-V3 with a right bundle branch block (RBBB) appearance with or without the terminal S waves in the lateral leads that are associated with a typical RBBB. A prolongation of the PR interval (a conduction disturbance in the heart) is also frequently seen. The ECG can fluctuate over time, depending on the autonomic balance and the administration of antiarrhythmic drugs. Adrenergic stimulation decreases the ST segment elevation, while vagal stimulation worsens it. (There is a case report of a patient who died while shaving, presumed due to the vagal stimulation of the carotid sinus massage.) The administration of class Ia, Ic and III drugs increases the ST segment elevation, as does fever. Exercise decreases ST segment elevation in some patients but increases it in others (after exercise when the body temperature has risen). The changes in heart rate induced by atrial pacing are accompanied by changes in the degree of ST segment elevation. When the heart rate decreases, the ST segment elevation increases and when the heart rate increases the ST segment elevation decreases. However, the contrary can also be observed. The cause of death in Brugada syndrome is ventricular fibrillation. The episodes of syncope (fainting) and sudden death (aborted or not) are caused by fast polymorphic ventricular tachycardias or ventricular fibrillation. These arrhythmias appear with no warning. While there is no exact treatment modality that reliably and totally prevents ventricular fibrillation from occurring in this syndrome, treatment lies in termination of this lethal arrhythmia before it causes death. This is done via implantation of an implantable cardioverter-defibrillator (ICD), which continuously monitors the heart rhythm and will defibrillate an individual if ventricular fibrillation is noted. Recent studies have evaluated the role of quinidine, a Class Ia antiarrhythmic drug, for decreasing VF episodes occurring in this syndrome. Quinidine has been found to both decrease the number of VF episodes and correct spontaneous ECG changes, possibly via inhibiting Ito channels. Some drugs have been reported to induce the type-1 ECG and/or (fatal) arrhythmias in Brugada syndrome patients. Patients with Brugada syndrome can prevent arrhythmias by avoiding these drugs or using them only in controlled conditions. Those with risk factors for coronary artery disease may require an angiogram before ICD implantation. - Nademanee K, Veerakul G, Nimmannit S et al. (1997). "Arrhythmogenic marker for the sudden unexplained death syndrome in Thai men". Circulation 96 (8): 2595–2600. PMID 9355899. - Vatta M, Dumaine R, Varghese G et al. (February 2002). "Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome". Hum. Mol. Genet. 11 (3): 337–45. doi:10.1093/hmg/11.3.337. PMID 11823453. - Brugada J, Brugada P, Brugada R (July 1999). "The syndrome of right bundle branch block ST segment elevation in V1 to V3 and sudden death--the Brugada syndrome". Europace 1 (3): 156–66. doi:10.1053/eupc.1999.0033. PMID 11225790. - Martini B, Nava A, Thiene G et al. (December 1989). "Ventricular fibrillation without apparent heart disease: description of six cases". Am. Heart J. 118 (6): 1203–9. doi:10.1016/0002-8703(89)90011-2. PMID 2589161. - Brugada P, Brugada J (November 1992). "Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report". J. Am. Coll. Cardiol. 20 (6): 1391–6. doi:10.1016/0735-1097(92)90253-J. PMID 1309182. - Antzelevitch C, Pollevick GD, Cordeiro JM et al. (2007). "Loss-of-Function Mutations in the Cardiac Calcium Channel Underlie a New Clinical Entity Characterized by ST-Segment Elevation, Short QT Intervals, and Sudden Cardiac Death". Circulation 115 (4): 442–229. doi:10.1161/CIRCULATIONAHA.106.668392. PMC 1952683. PMID 17224476. - Delpon E, Cordeiro JM, Núñez L et al. (2008). "Functional Effects of KCNE3 Mutation and its Role in the Development of Brugada Syndrome". Circulation Arrhythmia and Electrophysiology 1 (3): 209–18. doi:10.1161/CIRCEP.107.748103. PMC 2585750. PMID 19122847. - Watanabe H, Koopmann TT, Le Scouarnec S et al. (June 2008). "Sodium channel β1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans". J. Clin. Invest. 118 (6): 2260–8. doi:10.1172/JCI33891. PMC 2373423. PMID 18464934. - Bezzina, Connie R; Barc, Julien; Mizusawa, Yuka; Remme, Carol Ann; Gourraud, Jean-Baptiste; Simonet, Floriane; Verkerk, Arie O; Schwartz, Peter J; Crotti, Lia; Dagradi, Federica; Guicheney, Pascale; Fressart, Véronique; Leenhardt, Antoine; Antzelevitch, Charles; Bartkowiak, Susan; Schulze-Bahr, Eric; Zumhagen, Sven; Behr, Elijah R; Bastiaenen, Rachel; Tfelt-Hansen, Jacob; Olesen, Morten Salling; Kääb, Stefan; Beckmann, Britt M; Weeke, Peter; Watanabe, Hiroshi; Endo, Naoto; Minamino, Tohru; Horie, Minoru; Ohno, Seiko; Hasegawa, Kanae; Makita, Naomasa; Nogami, Akihiko; Shimizu, Wataru; Aiba, Takeshi; Froguel, Philippe; Balkau, Beverley; Lantieri, Olivier; Torchio, Margherita; Wiese, Cornelia; Weber, David; Wolswinkel, Rianne; Coronel, Ruben; Boukens, Bas J; Bézieau, Stéphane; Charpentier, Eric; Chatel, Stéphanie; Despres, Aurore; Gros, Françoise; Kyndt, Florence; Lecointe, Simon; Lindenbaum, Pierre; Portero, Vincent; Violleau, Jade; Gessler, Manfred; Tan, Hanno L; Roden, Dan M; Christoffels, Vincent M; Marec, Hervé Le; Wilde, Arthur A; Probst, Vincent; Schott, Jean-Jacques; Dina, Christian; Redon, Richard (2013). "Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death". Nature Genetics. doi:10.1038/ng.2712. ISSN 1061-4036. - Hedley PL; Jørgensen P; Schlamowitz S; Moolman-Smook, Johanna et al. (2009). "Brugada syndrome". Human Mutation 30 (9): 1256–66. doi:10.1002/humu.21066. PMID 19606473. - Antzelevitch C (2007). "Genetic basis of Brugada syndrome". Heart rhythm : the official journal of the Heart Rhythm Society 4 (6): 756–7. doi:10.1016/j.hrthm.2007.03.015. PMC 1989771. PMID 17556198. - http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=brugada Overview of Brugada Syndrome Genetic Testing - Antzelevitch C, Brugada P, Borggrefe M et al. (2005). "Brugada Syndrome. Report of the second consensus conference". Heart Rhythm 2 (4): 429–440. doi:10.1016/j.hrthm.2005.01.005. PMID 15898165. - Belhassen B, Glick A, Viskin S (2004). "Efficacy of quinidine in high-risk patients with Brugada syndrome". Circulation 110 (13): 1731–7. doi:10.1161/01.CIR.0000143159.30585.90. PMID 15381640. - Postema, PG; Wolpert, C, Amin, AS, Probst, V, Borggrefe, M, Roden, DM, Priori, SG, Tan, HL, Hiraoka, M, Brugada, J, Wilde, AA (September 2009). "Drugs and Brugada syndrome patients: review of the literature, recommendations and an up-to-date website (www.brugadadrugs.org)". Heart rhythm : the official journal of the Heart Rhythm Society 6 (9): 1335–41. doi:10.1016/j.hrthm.2009.07.002. PMC 2779019. PMID 19716089. - BrugadaDrugs.org, maintained by Brugada specialists, contains a list of drugs to avoid in patients with the Brugada syndrome - GeneReviews: Brugada syndrome - Behr: http://www.c-r-y.org.uk/long_qt_syndrome.htm - The Ramon Brugada Senior Foundation - la Sindrome di Brugada	2	15	4	0	0	0.859691	4	3,475
How To Correctly Code Your EMG Studies To Maximize Your Reimbursement ? Needle EMG is the recording and study of electrical activity of muscles using a needle electrode. Neurologists use EMGs to test the electrical activity of a skeletal muscle to provide a medical diagnosis on a patient. Although these are common procedures but coding them incorrectly can not only cause billing problems but often lead to audits. The Centers for Medicare & Medicaid Services (CMS) outlines clearly its recommendations for EMG billing in the Federal Register (issue of October 31, 1997, Vol. 62, No. 211, page 59090), which covers some common questions like how many muscles should/need to be studied per limb in order to use the limb EMG codes or which code should be used when performing a limited study of a specific muscle and whether it can be used multiple times. Here are some tips which can clarify EMG billing confusions and help in maximizing your EMG reimbursements: 1. When choosing an EMG code, count the limbs and identify the specific muscles the physician has tested. The first set of EMG CPT codes 95860-95864 are used on the basis of this analysis. To report these codes, the physician must evaluate extremity muscles innervated by three nerves (for example, radial, ulnar, median, tibial, peroneal or femoral but not sub-branches) And a minimum of five muscles studied per limb. For example: If a physician performs EMG test on a patient’s right leg and meets the minimum testing requirements (five muscles innervated by three nerves each), then he should report CPT 95860. A single unit of 95860, 95861, 95863 or 95864 includes all muscles of five or more tested in a particular extremity(ies). In other words, one should report only a single unit of 95860-95864 per session: You cannot bill additional units for more than five muscles per extremity. CPT 95865 is used for needle examination of the larynx and CPT 95866 is used for needle examination of the hemidiaphragm. If fewer than five muscles are tested then CPT 95870 (Needle electromyography; limited study of muscles in one extremity or non-limb (axial) muscles (unilateral or bilateral), other than thoracic paraspinal, cranial nerve supplied muscles or sphincters) should be used. 2. The next set of CPT codes are 95867-95868 which describes the EMG study of muscles supplied by the cranial nerve, either unilaterally or bilaterally. If the answer to your question is yes, then CPT 95867 (Needle electromyography; cranial nerve supplied muscle[s], unilateral) OR CPT 95868 (Needle electromyography; cranial nerve supplied muscles, bilateral) should be used depending upon the test performed by the physician. For example: A physician monitors the RLN (Recurrent Laryngeal Nerve) during a total thyroidectomy, he should assign the CPT 95868 for a bilateral EMG. It is important to note that Codes 95867 and 95868 should not be reported together, nor should modifier -50 (bilateral procedure) be attached to CPT 95868. 3. Are studies performed on thoracic paraspinals other then those at T1 and T2? Then one must report CPT 95869 (Needle electromyography; thoracic paraspinal muscles). Code 95869 is exclusively used to study thoracic paraspinal muscles between T3 and T11. One unit can be billed, despite the number of levels studied or whether unilateral or bilateral. 95869 cannot be reported with 95860-95864 if only the T1 and/or T2 levels are studied with an upper extremity. This code should be used if the examinations are confined to distal muscles only, such as intrinsic foot or hand muscles. 4. Is the study performed on fewer than five muscles per extremity, then CPT 95870 should be used. This code should only be used when the muscles tested do not fit more appropriately under any other CPT code. Code 95870 can be billed at one unit per extremity (one limb, arm or leg), when fewer than five muscles are examined. For example: If a physician tests 3 muscles on the right arm and 4 muscles on the left arm, then code 95870 can be reported twice. This code can also be used for examining non-limb (axial) muscles (e.g. intercostal, abdominal wall, cervical and lumbar paraspinal muscles (unilateral or bilateral)) regardless of the number of level tested. However, it should not be billed when the paraspinal muscles corresponding to extremity are tested, and when the extremity codes 95860, 95861, 95863, or 95864 are reported. 5. The last in row is code 95872 which is (Needle electromyography using single fiber electrode, with quantitative measurement of jitter, blocking and/or fiber density, any/all sites of each muscle studied). This code should be used when a physician studies the action potentials (APs) from individual muscle fibers. One should report one unit of 95872 for each muscle the physician tests. The physician will generally test at least two muscles (one test serves as a “control”), so you will report a minimum of two units of service. When reporting CPT 95872, the physician must document the muscle(s) tested and the test results. Keep these tips handy when coding and billing EMG studies. As always, please consult your payer guidelines and state regulations for any specific rules. For recent changes in Nerve Conduction Study Codes 2013, please visit our latest blog post Recent Changes to Nerve Conduction Codes Was this helpful ? Help spread the word. Posted by SMBS Team	4	11	36	0	2	0.657881	38	1,283
Diagnosis Code J84.117 Information for Medical Professionals The diagnosis code J84.117 is grouped in the following Diagnostic Related Group(s) (MS-DRG V34.0) - 196 - INTERSTITIAL LUNG DISEASE WITH MCC - 197 - INTERSTITIAL LUNG DISEASE WITH CC - 198 - INTERSTITIAL LUNG DISEASE WITHOUT CC/MCC Convert to ICD-9 General Equivalence Map The ICD-10 and ICD-9 GEMs are used to facilitate linking between the diagnosis codes in ICD-9-CM and the new ICD-10-CM code set. The GEMs are the raw material from which providers, health information vendors and payers can derive specific applied mappings to meet their needs. - 516.37 - Desquamatv interst pneu - Desquamative interstitial pneumonia Information for Patients Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and scarring make it hard to get enough oxygen. The scarring is called pulmonary fibrosis. Breathing in dust or other particles in the air is responsible for some types of interstitial lung diseases. Specific types include - Black lung disease among coal miners, from inhaling coal dust - Farmer's lung, from inhaling farm dust - Asbestosis, from inhaling asbestos fibers - Siderosis, from inhaling iron from mines or welding fumes - Silicosis, from inhaling silica dust Other causes include autoimmune diseases or occupational exposures to molds, gases, or fumes. Some types of interstitial lung disease have no known cause. Treatment depends on the type of exposure and the stage of the disease. It may involve medicines, oxygen therapy, or a lung transplant in severe cases. - Hypersensitivity pneumonitis (Medical Encyclopedia) - Interstitial lung disease (Medical Encyclopedia) - Interstitial lung disease - adults - discharge (Medical Encyclopedia) - Pulmonary function tests (Medical Encyclopedia) Also called: Bronchopneumonia Pneumonia is an infection in one or both of the lungs. Many germs, such as bacteria, viruses, and fungi, can cause pneumonia. You can also get pneumonia by inhaling a liquid or chemical. People most at risk are older than 65 or younger than 2 years of age, or already have health problems. Symptoms of pneumonia vary from mild to severe. See your doctor promptly if you - Have a high fever - Have shaking chills - Have a cough with phlegm that doesn't improve or gets worse - Develop shortness of breath with normal daily activities - Have chest pain when you breathe or cough - Feel suddenly worse after a cold or the flu Your doctor will use your medical history, a physical exam, and lab tests to diagnose pneumonia. Treatment depends on what kind you have. If bacteria are the cause, antibiotics should help. If you have viral pneumonia, your doctor may prescribe an antiviral medicine to treat it. Preventing pneumonia is always better than treating it. Vaccines are available to prevent pneumococcal pneumonia and the flu. Other preventive measures include washing your hands frequently and not smoking. NIH: National Heart, Lung, and Blood Institute - Aspiration pneumonia (Medical Encyclopedia) - Atypical pneumonia (Medical Encyclopedia) - Hospital-acquired pneumonia (Medical Encyclopedia) - Mycoplasma pneumonia (Medical Encyclopedia) - Pneumonia (Medical Encyclopedia) - Pneumonia - adults - discharge (Medical Encyclopedia) - Pneumonia - children - community acquired (Medical Encyclopedia) - Pneumonia - children - discharge (Medical Encyclopedia) - Viral pneumonia (Medical Encyclopedia) Idiopathic pulmonary fibrosis Idiopathic pulmonary fibrosis is a chronic, progressive lung disease. This condition causes scar tissue (fibrosis) to build up in the lungs, which makes the lungs unable to transport oxygen into the bloodstream effectively. The disease usually affects people between the ages of 50 and 70.The most common signs and symptoms of idiopathic pulmonary fibrosis are shortness of breath and a persistent dry, hacking cough. Many affected individuals also experience a loss of appetite and gradual weight loss. Some people with idiopathic pulmonary fibrosis develop widened and rounded tips of the fingers and toes (clubbing) resulting from a shortage of oxygen. These features are relatively nonspecific; not everyone with these health problems has idiopathic pulmonary fibrosis. Other respiratory diseases, some of which are less serious, can cause similar signs and symptoms.In people with idiopathic pulmonary fibrosis, scarring of the lungs increases over time until the lungs can no longer provide enough oxygen to the body's organs and tissues. Some people with idiopathic pulmonary fibrosis develop other serious lung conditions, including lung cancer, blood clots in the lungs (pulmonary emboli), pneumonia, or high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension). Most affected individuals survive 3 to 5 years after their diagnosis. However, the course of the disease is highly variable; some affected people become seriously ill within a few months, while others may live with the disease for a decade or longer.In most cases, idiopathic pulmonary fibrosis occurs in only one person in a family. These cases are described as sporadic. However, a small percentage of people with this disease have at least one other affected family member. When idiopathic pulmonary fibrosis occurs in multiple members of the same family, it is known as familial pulmonary fibrosis.	4	8	0	0	2	0.813179	2	1,195
Post-traumatic Stress Disorder Post-traumatic stress disorder ("PTSD"), Complex PTSD and Acute Stress Reaction are stress-induced psychological conditions that can occur after traumatic experiences; They are natural emotional reactions to a deeply shocking and disturbing experiences. They are normal reactions to an abnormal situation. The main difference between the two conditions is that in Acute Stress Reaction, the reactive symptoms are more immediate and less enduring than they are for PTSD. Definition of PTSD Post-traumatic Stress Disorder is the name given to a range of symptoms a person may develop in response to a deeply shocking, disturbing experience outside the normal range of human experience. The condition is classified in the American Psychiatric Association's Diagnostic and Statistical Manual, DSM-5, and in the international equivalent manual, the World Health Organization's ICD-10. For a clinical diagnosis, a patient must meet the diagnostic criteria in the DSM or ICD manuals. In both manuals, the basic requirement for diagnosis is that the patient must have been exposed to a stressor, and must then display certain psychological and behavioural symptoms relating to the trauma. Post-traumatic Stress Disorder is within a spectrum of trauma and stress-related disorders. Another condition in the spectrum is "Acute Stress Reaction", a condition that usually begins very soon after exposure to a exceptional physical or mental stress and which subsides within hours or days. Making a Diagnosis For a doctor or mental health professional to make a diagnosis of ptsd or any other condition, the patient's experiences and symptoms must meet criteria set out in manuals. The American Psychiatric Association currently uses the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) as its classification and diagnostic tool. Europe and the rest of the world rely on the World Health Organisation's International Statistical Classification of Diseases and Related Health Problems (ICD), currently at revision 10, with revision 11 due in 2018. So far as PTSD is concerned, these manuals set out the symptoms of PTSD along with a description of the trauma a patient would need to have experienced, to obtain a diagnosis of PTSD. The less pervasive condition of Acute Stress Reaction (in ICD) or Acute Stress Disorder (in DSM) has its diagnostic criteria set out in the same manuals. ICD-10 Diagnostic Criteria for Post Traumatic Stress Disorder (PTSD) "Arises as a delayed or protracted response to a stressful event or situation (of either brief or long duration) of an exceptionally threatening or catastrophic nature, which is likely to cause pervasive distress in almost anyone. Predisposing factors, such as personality traits (e.g. compulsive, asthenic) or previous history of neurotic illness, may lower the threshold for the development of the syndrome or aggravate its course, but they are neither necessary nor sufficient to explain its occurrence. Typical features include episodes of repeated reliving of the trauma in intrusive memories ("flashbacks"), dreams or nightmares, occurring against the persisting background of a sense of "numbness" and emotional blunting, detachment from other people, unresponsiveness to surroundings, anhedonia, and avoidance of activities and situations reminiscent of the trauma. There is usually a state of autonomic hyperarousal with hypervigilance, an enhanced startle reaction, and insomnia. Anxiety and depression are commonly associated with the above symptoms and signs, and suicidal ideation is not infrequent. The onset follows the trauma with a latency period that may range from a few weeks to months. The course is fluctuating but recovery can be expected in the majority of cases. In a small proportion of cases the condition may follow a chronic course over many years, with eventual transition to an enduring personality change (F62.0). Diagnostic Criteria A. Exposure to a stressful event or situation (either short or long lasting) of exceptionally threatening or catastrophic nature, which is likely to cause pervasive distress in almost anyone. B. Persistent remembering or "reliving" the stressor by intrusive flash backs, vivid memories, recurring dreams, or by experiencing distress when exposed to circumstances resembling or associated with the stressor. C. Actual or preferred avoidance of circumstances resembling or associated with the stressor (not present before exposure to the stressor). D. Either (1) or (2): (1) Inability to recall, either partially or completely, some important aspects of the period of exposure to the stressor (2) Persistent symptoms of increased psychological sensitivity and arousal (not present before exposure to the stressor) shown by any two of the following: a) difficulty in falling or staying asleep; b) irritability or outbursts of anger; c) difficulty in concentrating; e) exaggerated startle response E. Criteria B, C (For some purposes, onset delayed more than six months may be included but this should be clearly specified separately.) In earlier revisions of DSM and ICD, the nature of the trauma for PTSD had to be a single, major, life threatening event. Tim Field wrote that this was because (a) most of the research on PTSD had been undertaken with people who had suffered a threat to life (eg combat veterans, especially from Vietnam, victims of accident, disaster, and acts of violence), and (b) it was thought that PTSD could not be a result of "normal" events such as bereavement, business failure, interpersonal conflict, bullying, harassment, stalking, marital disharmony, working for the emergency services, etc. In DSM-IV the requirement was eased although most mental health practitioners continued to interpret diagnostic criterion A1 as applying only to a single major life-threatening event. The current revision, DSM-V, holds that the patient must either:- Directly experience the traumatic event(s) Witness, in person, the event(s) as it occurred to others Learn that the traumatic event(s) occurred to a close family member or friend Experience repeated or extreme exposure to aversive details of the traumatic event(s); albeit that exposure through tv, radio, movies or images is not counted. A further change in DSM-V is the reclassification of PTSD to a new chapter, "Trauma- and Stressor-Related Disorders". ICD-10 defines the stressor as "Exposure to a stressful event or situation (either short or long lasting) of exceptionally threatening or catastrophic nature, which is likely to cause pervasive distress in almost anyone." It is possible for a patient to have the symptoms of PTSD, but to have experienced a trauma that falls outside the criteria set out in either manual. In such a case, strictly spealing, a psychiatrist would not be able to make a complete PTSD diagnosis. However, for years, it has been argued that "complex PTSD" is a valid term for a condition where the trauma has not been a single event. It appears that ICD-11 will finally address this anomaly. ICD-11 (due for publication in 2018), has proposed two related diagnoses, posttraumatic stress disorder (PTSD) and complex PTSD within the spectrum of trauma and stress-related disorders. This is an important development, showing recognition by the profession that PTSD symptoms (which this article has not yet touched upon) can arise from "sustained exposure to repeat or multiple types of traumatic stressors (e.g., childhood abuse, domestic violence, genocide campaigns, torture)." [Evidence for proposed ICD-11 PTSD and complex PTSD: a latent profile analysis] The ICD-10 diagnostic criteria for Acute Stress Reaction is in the professional reference area of patient.info, as is this excellent article on PTSD which includes information on predisposing factors and treatments. Patient.info also provides a less technical article on Acute Stress Reaction and one on PTSD, by the Royal College of Psychiatrists. Each article links to further, professional references on the conditions. Causes of PTSD PTSD resulting from accident, disaster, war, terrorism, torture, kidnap, etc has been extensively studied and literature is available elsewhere. The first written reference to PTSD symptoms comes from the sixth century BC; Post Traumatic Stress Disorder is nothing new. This section of Bully OnLine focuses on PTSD and Complex PTSD resulting from bullying, primarily in the workplace, however anyone interested in PTSD (however caused) may find this page enlightening. Most of the information on this page and web site is relevant to other types of bullying, eg at school, in relationships (including domestic violence), by families, by neighbours or landlords, in the care of elderly, young or disadvantaged people, in the armed services, etc. Bullying is behind harassment, discrimination, prejudice and persecution, therefore targets of repeated sexual harassment or racial discrimination or religious or ethnic persecution will also identify with the symptoms. The insight about bullying on this web site is therefore also relevant to more serious issues including physical abuse, repeated verbal abuse, sexual abuse, violent crime, kidnap, abduction, rape, war, terrorism, torture, and denial and abuse of human rights. Those exploring Contact Experience may also find this page helpful. CAUTION: Some medical practitioners would agree with the information on this page, others would not. Beware of self diagnosis! PTSD and bullying ICD-10 demonstrates recognition by the WHO that PTSD can result from an accumulation of many incidents which, in isolation are not life-threatening, but which as a whole creates a trauma that is similar in severity to a more serious single trauma that threatens life, serious injury and so on. ICD-11 is expected to further broaden the criteria for the trauma and, from that, classify conditions as PTSD and complex PTSD PTSD can potentially arise from any prolonged period of negative stress in which certain factors are present, which may include any of captivity, lack of means of escape, entrapment, repeated violation of boundaries, betrayal, rejection, bewilderment, confusion, and - crucially - lack of control, loss of control and disempowerment. It is the overwhelming nature of the events and the inability (helplessness, lack of knowledge, lack of support etc) of the person trying to deal with those events that collectively form the trauma that can lead to PTSD. Situations that can create these stresses include bullying, harassment, abuse, domestic violence, stalking, long-term caring for a disabled relative, unresolved grief, mounting debt, contact experience, etc. Those working in regular traumatic situations, eg the emergency services and armed services, through repeated exposure to horrific scenes, are also prone to developing PTSD. The ever present risk to armed services personnel working in war zones, of being killed or seriously injured, is a readily understandable source of extreme stress. A key stressor is the aspect of captivity, i.e. a perceived or actual inability to escape the situation. Despite some people's assertions to the contrary, situations of domestic abuse and workplace abuse can be extremely difficult to get out of. In the latter case there are several reasons, including the financial effect of losing the present job along with the unavailability of replacement jobs with comparable income and status. A very real concern to the target is the likely inability to get a job reference, given their bully's influence, as well as the prospect of having a previously untarnished disciplinary and/or attendance record ruined by the effects of being bullied. All these things, along with the hope that the bullying will stop before things get really silly, tend to prevent the target from following friends' advice to "just leave". Society's Attitude to PTSD In World War One, armed forces personnel faced threats of being labelled with "cowardice" and "lack of moral fibre" (LMF) if they gave in to the symptoms of PTSD. Then, 306 British and Commonwealth soldiers were shot as "cowards" and "deserters" on the orders of General Haig in an act which today would be treated as a war crime - see a separate page on this injustice. Even now, 40 years after the introduction of the UK's Health and Safety at Work Act, many employers pay little or no attention to the harm caused by bullying and harassment occurring in their workplaces. Uninformed adages still abound: "It's something you have to put up with" or "Bullying toughens you up" or "He's gone mad". Thankfully, one does not hear the same being openly said to targets of repeated sexual abuse or domestic violence, even though they are all forms of bullying. Employers that use bullying as a substitute for leadership and management, and therefore not only tolerate but rely upon bullying for their existence, typically pounce upon any stress related illness in a bullied employee as a sign of mental weakness, discrediting any allegation they may have made, blaming the victim for their situation and, according to their records, absolving the bully and employer of any responsibility. Mapping the health effects of bullying onto PTSD Workplace Bullying can result in symptoms of Post Traumatic Stress Disorder. How does a typical workplace bullying experience and its effects relate to the ICD-10 criteria for diagnosing PTSD? A. The prolonged (chronic) negative stress resulting from bullying has lead to threat of loss of job, career, health, livelihood, often also resulting in threat to marriage and family life. The family are the unseen victims of bullying. A.1.One of the key symptoms of prolonged negative stress is reactive depression; this causes the balance of the mind to be disturbed, leading first to thoughts of, then attempts at, and ultimately, suicide. A.2.The target of bullying may be unaware that they are being bullied, and even when they do realise (there's usually a moment of enlightenment as the person realises that the criticisms and tactics of control etc are invalid), they often cannot bring themselves to believe they are dealing with a disordered personality who lacks a conscience and does not share the same moral values as themselves. Naivety is the great enemy. The target of bullying is bewildered, confused, frightened, angry - and after enlightenment, very angry. For an answer to the question Why me? click here. B.1. The target of bullying experiences regular intrusive violent visualisations and replays of events and conversations; often, the endings of these replays are altered in favour of the target. B.2. Sleeplessness, nightmares and replays are a common feature of being bullied. B.3. The events are constantly relived; night-time and sleep do not bring relief as it becomes impossible to switch the brain off. Such sleep as is achieved is non-restorative and people wake up as tired, and often more tired, than when they went to bed. B.4. Fear, horror, chronic anxiety, and panic attacks are triggered by any reminder of the experience, eg receiving threatening letters from the bully, the employer, or personnel about disciplinary hearings etc. B.5. Panic attacks, palpitations, sweating, trembling, ditto. Criteria B4 and B5 manifest themselves as immediate physical and mental paralysis in response to any reminder of the bullying or prospect of having to take action against the bully. C. Physical numbness (toes, fingertips, lips) is common, as is emotional numbness (especially inability to feel joy). Sufferers report that their spark has gone out and, even years later, find they just cannot get motivated about anything. C.1. The target of bullying tries harder and harder to avoid saying or doing anything which reminds them of the horror of the bullying. C.2. Work, especially in the person's chosen field becomes difficult, often impossible, to undertake; the place of work holds such horrific memories that it becomes impossible to set foot on the premises; many targets of bullying avoid the street where the workplace is located. C.3. Almost all callers to the UK National Workplace Bullying Advice Line report impaired memory; this may be partly due to suppressing horrific memories, and partly due to damage to the hippocampus, an area of the brain linked to learning and memory (see John O'Brien's paper below) C.4. the person becomes obsessed with resolving the bullying experience which takes over their life, eclipsing and excluding almost every other interest. C.5. Feelings of withdrawal and isolation are common; the person just wants to be on their own and solitude is sought. C.6. Emotional numbness, including inability to feel joy (anhedonia) and deadening of loving feelings towards others are commonly reported. One fears never being able to feel love again. C.7. The target of bullying becomes very gloomy and senses a foreshortened career - usually with justification. Many targets of bullying ultimately give up their career; in the professions, severe psychiatric injury, severely impaired health, refusal by the bully and the employer to give a satisfactory reference, and many other reasons, conspire to bar the person from continuance in their chosen career. D.1. Sleep becomes almost impossible, despite the constant fatigue; such sleep as is obtained tends to be unsatisfying, unrefreshing and non-restorative. On waking, the person often feels more tired than when they went to bed. Depressive feelings are worst early in the morning. Feelings of vulnerability may be heightened overnight. D.2. The person has an extremely short fuse and is often permanently irritated, especially by small insignificant events. The person frequently visualises a violent solution, eg arranging an accident for, or murdering the bully; the resultant feelings of guilt tend to hinder progress in recovery. D.3. Concentration is impaired to the point of precluding preparation for legal action, study, work, or search for work. D.4. The person is on constant alert because their fight or flight mechanism has become permanently activated. D.5. The person has become hypersensitized and now unwittingly and inappropriately perceives almost any remark as critical. E. Recovery from a bullying experience is measured in years. Some people never fully recover. F. For many, social life ceases and work becomes impossible; the overwhelming need to earn a living combined with the inability to work deepens the trauma. Common symptoms of PTSD and Complex PTSD that sufferers report experiencing - hypervigilance (feels like but is not paranoia) - exaggerated startle response - sudden angry or violent outbursts - flashbacks, nightmares, intrusive recollections, replays, violent visualisations - sleep disturbance - exhaustion and chronic fatigue - reactive depression - feelings of detachment - avoidance behaviours - nervousness, anxiety - phobias about specific daily routines, events or objects - irrational or impulsive behaviour - loss of interest - loss of ambition - anhedonia (inability to feel joy and pleasure) - poor concentration - impaired memory - joint pains, muscle pains - emotional numbness - physical numbness - low self-esteem - an overwhelming sense of injustice and a strong desire to do something about it Associated symptoms of Complex PTSD Survivor guilt: survivors of disasters often experience abnormally high levels of guilt for having survived, especially when others - including family, friends or fellow passengers - have died. Survivor guilt manifests itself in a feeling of "I should have died too". In bullying, levels of guilt are also abnormally raised. The survivor of workplace bullying may have develop an intense albeit unrealistic desire to work with their employer (or, by now, their former employer) to eliminate bullying from their workplace. Many survivors of bullying cannot gain further employment and are thus forced into self-employment; excessive guilt may then preclude the individual from negotiating fair rates of remuneration, or asking for money for services rendered. The person may also find themselves being abnormally and inappropriately generous and giving in business and other situations. Shame, embarrassment, guilt, and fear are encouraged by the bully, for this is how all abusers - including child sex abusers - control and silence their victims. Marital disharmony: the target of bullying becomes obsessed with understanding and resolving what is happening and the experience takes over their life; partners become confused, irritated, bewildered, frightened and angry; separation and divorce are common outcomes. The word "breakdown" is often used to describe the mental collapse of someone who has been under intolerable strain. There is usually an (inappropriate) inference of "mental illness". All these are lay terms and mean different things to different people. I define two types of breakdown: - Nervous breakdown or mental breakdown is a consequence of mental illness - Stress breakdown is a psychiatric injury, which is a normal reaction to an abnormal situation The two types of breakdown are distinct and should not be confused. A stress breakdown is a natural and normal conclusion to a period of prolonged negative stress; the body is saying "I'm not designed to operate under these conditions of prolonged negative stress so I am going to do something dramatic to ensure that you reduce or eliminate the stress otherwise your body may suffer irreparable damage; you must take action now". A stress breakdown is often predictable days - sometimes weeks - in advance as the person's fear, fragility, obsessiveness, hypervigilance and hypersensitivity combine to evolve into paranoia (as evidenced by increasingly bizarre talk of conspiracy or MI6). If this happens, a stress breakdown is only days or even hours away and the person needs urgent medical help. The risk of suicide at this point is heightened. Often the cause of negative stress in an organisation can be traced to the behaviour of one individual. The profile of this individual is on the serial bully page. I believe bullying is the main - but least recognised - cause of negative stress in the workplace today. To see the effects of prolonged negative stress on the body click here. The person who suffers a stress breakdown is often treated as if they have had a mental breakdown; they are sent to a psychiatrist, prescribed drugs used to treat mental illness, and may be encouraged - sometimes coerced or sectioned - into becoming a patient in a psychiatric hospital. The sudden transition from professional working environment to a ward containing schizophrenics, drug addicts and other people with genuine long-term mental health problems adds to rather than alleviates the trauma. Words like "psychiatrist", "psychiatric unit" etc are often translated by work colleagues, friends, and sometimes family into "nutcase", "shrink", "funny farm", "loony" and other inappropriate epithets. The bully encourages this, often ensuring that the employee's personnel record contains a reference to the person's "mental health problems". Sometimes, the bully produces their own amateur diagnosis of mental illness - but this is more likely to be a projection of the bully's own state of mind and should be regarded as such. During the First World War, British soldiers suffering PTSD and stress breakdown were labelled as "cowards" and "deserters". During the Second World War, soldiers suffering PTSD and stress breakdowns were again vilified with these labels; Royal Air Force personnel were labelled as "lacking moral fibre" and their papers stamped "LMF". It's noticeable that those administrators and top brass enforcing this labelling were themselves always situated a safe distance from the fighting; see the section on projection. The person who is being bullied often thinks they are going mad, and may be encouraged in this belief by those who do not have that person's best interests at heart. They are not going mad; PTSD is an injury, not an illness. Sometimes, the term "psychosis" is applied to mental illness, and the term "neurosis" to psychiatric injury. The main difference is that a psychotic person is unaware they have a mental problem, whereas the neurotic person is aware - often acutely. The serial bully's lack of insight into their behaviour and its effect on others has the hallmarks of a psychosis, although this obliviousness would appear to be a choice rather than a condition. With targets of bullying, I prefer to avoid the words "neurosis" and "neurotic", which for non-medical people have derogatory connotations. Hypersensitivity and hypervigilance are likely to cause the person suffering PTSD to react unfavourably to the use of these words, possibly perceiving that they, the target, are being blamed for their circumstances. A frequent diagnosis of stress breakdown is "brief reactive psychosis", especially if paranoia and suicidal thoughts predominate. However, a key difference between mental breakdown and stress breakdown is that a person undergoing a stress breakdown will be intermittently lucid, often alternating seamlessly between paranoia and seeking information about their paranoia and other symptoms. The person is also likely to be talking about resolving their work situation (which is the cause of their problems), planning legal action against the bully and the employer, wanting to talk to their union rep and solicitor, etc. A stress breakdown is a transformational experience which, with the right support, can ultimately enrich the experiencer's life. However, completing the transformation can be a long and sometimes painful process. The Western response - to hospitalise and medicalize the experience, thus hindering the process - may be well-intentioned, but may lessen the value and effectiveness of the transformation. How would you feel if, rather than a breakdown, you viewed it as a breakthrough? How would you feel if it was suggested to you that the reason for a stress breakdown is to awaken you to your mission in life and to enable you to discover the reason why you have incarnated on this planet? How would it change your view of things if it was also suggested to you that a stress breakdown reconfigures your brain to enable you to embark on the path that will culminate in the achievement of your mission? [More \| More] Differences between mental illness and psychiatric injury The person who is being bullied will eventually say something like "I think I'm being paranoid..."; however they are correctly identifying hypervigilance, a symptom of PTSD, but using the popular but misunderstood word paranoia. The differences between hypervigilance and paranoia make a good starting point for identifying the differences between mental illness and psychiatric injury. \|paranoia is an aspect of a mental illness, where the cause is thought to be internal, eg a minor variation in the balance of brain chemistry\|\|is a response to an external event (violence, accident, disaster, violation, intrusion, bullying, etc) and therefore an injury\| \|paranoia tends to endure and to not get better of its own accord\|\|wears off (gets better), albeit slowly, when the person is out of and away from the situation which was the cause\| \|the paranoiac will not admit to feeling paranoid, as they cannot see their paranoia\|\|the hypervigilant person is acutely aware of their hypervigilance, and will easily articulate their fear, albeit using the incorrect but popularised word "paranoia"\| \|sometimes responds to drug treatment\|\|drugs are not viewed favourably by hypervigilant people, except in extreme circumstances, and then only briefly; often drugs have no effect, or can make things worse, sometimes interfering with the body's own healing process\| \|There is no objectively rational, plausible explanation or evidence of the cause of paranoid fears of\| \|The paranoid person's fears are based on something that does not exist, and therefore cannot be supported by evidence. The beliefs may be clearly irrational or implausible, although a sincere listener may be convinced initially that there is a cause for concern. The paranoid person will likely have an unswerving belief that what they are saying is irrefutably true, but will resist inquiries for evidence to demonstrate the truth of their beliefs, and shun the person making such inquiries.\|\|There is an objectively rational, plausible explanation and/or evidence to justify a hypervigilant person's concerns, even if those concerns may seem exaggerated to someone who has not been through/is not going through the same experience.\| \|paranoia is often seen in conjunction with other symptoms of mental illness, but not in conjunction with symptoms of PTSD\|\|hypervigilance is seen in conjunction with other symptoms of PTSD, but not in conjunction with symptoms of mental illness\| \|the paranoiac is convinced of their plausibility\|\|the hypervigilant person is aware of how implausible their experience sounds and often doesn't want to believe it themselves (disbelief and denial)\| \|the paranoiac feels persecuted by a person or persons unknown (eg "they're out to get me")\|\|the hypervigilant person is hypersensitized but is often aware of the inappropriateness of their heightened sensitivity, and can identify the person responsible for their psychiatric injury\| \|sense of persecution\|\|heightened sense of vulnerability to victimisation\| \|the sense of persecution felt by the paranoiac is a delusion, for usually no-one is out to get them\|\|the hypervigilant person's sense of threat is well-founded, for the serial bully is out to get rid of them and has often coerced others into assisting, eg through mobbing; the hypervigilant person often cannot (and refuses to) see that the serial bully is doing everything possible to get rid of them\| \|the paranoiac is on constant alert because they know someone is out to get them\|\|the hypervigilant person is on alert in case there is danger\| \|the paranoiac is certain of their belief and their behaviour and expects others to share that certainty\|\|the hypervigilant person cannot bring themselves to believe that the bully cannot and will not see the effect their behaviour is having; they cling naively to the mistaken belief that the bully will recognise their wrongdoing and apologise\| Other differences between mental illness and psychiatric injury include: \|the cause often cannot be identified\|\|the cause is easily identifiable and verifiable, but denied by those who are accountable\| \|the person may be incoherent or what they say doesn't make sense\|\|the person is often articulate but prevented from articulation by being traumatised\| \|the person may appear to be obsessed\|\|the person is obsessive, especially in relation to identifying the cause of their injury and both dealing with the cause and effecting their recovery\| \|the person is oblivious to their behaviour and the effect it has on others\|\|the person is in a state of acute self-awareness and aware of their state, but often unable to explain it\| \|the depression is a clinical or endogenous depression\|\|the depression is reactive; the chemistry is different to endogenous depression\| \|there may be a history of depression in the family\|\|there is very often no history of depression in the individual or their family\| \|the person has usually exhibited mental health problems before\|\|often there is no history of mental health problems\| \|may respond inappropriately to the needs and concerns of others\|\|responds empathically to the needs and concerns of others, despite their own injury\| \|displays a certitude about themselves, their circumstances and their actions\|\|is often highly sceptical about their condition and circumstances and is in a state of disbelief and bewilderment which they will easily and often articulate ("I can't believe this is happening to me" and "Why me?" )\| \|may suffer a persecution complex\|\|may experience an unusually heightened sense of vulnerability to possible victimisation (ie hypervigilance)\| \|suicidal thoughts are the result of despair, dejection and hopelessness\|\|suicidal thoughts are often a logical and carefully thought-out solution or conclusion\| \|exhibits despair\|\|is driven by the anger of injustice\| \|often doesn't look forward to each new day\|\|looks forward to each new day as an opportunity to fight for justice\| \|is often ready to give in or admit defeat\|\|refuses to be beaten, refuses to give up\| Common features of Complex PTSD from bullying People suffering Complex PTSD as a result of bullying report consistent symptoms which further help to characterise psychiatric injury and differentiate it from mental illness. These include: - Fatigue with symptoms of or similar to Chronic Fatigue Syndrome (formerly ME) An anger of injustice stimulated to an excessive degree (sometimes but improperly attracting the words "manic" instead of motivated, "obsessive" instead of focused, and "angry" instead of "passionate", especially from those with something to fear) - An overwhelming desire for acknowledgement, understanding, recognition and validation of their experience - A simultaneous and paradoxical unwillingness to talk about the bullying or abuse - A lack of desire for revenge, but a strong motivation for justice - A tendency to oscillate between conciliation (forgiveness) and anger (revenge) with objectivity being the main casualty - Extreme fragility, where formerly the person was of a strong, stable character - Numbness, both physical (toes, fingertips, and lips) and emotional (inability to feel love and joy) - Hyperawareness and an acute sense of time passing, seasons changing, and distances travelled - An enhanced environmental awareness, often on a planetary scale - An appreciation of the need to adopt a healthier diet, possibly reducing or eliminating meat - especially red meat - Willingness to try complementary medicine and alternative, holistic therapies, etc - A constant feeling that one has to justify everything one says and does - A constant need to prove oneself, even when surrounded by good, positive people - An unusually strong sense of vulnerability, victimisation or possible victimisation, often wrongly diagnosed as "persecution" - Occasional violent intrusive visualisations - Feelings of worthlessness, rejection, a sense of being unwanted, unlikeable and unlovable - A feeling of being small, insignificant, and invisible - An overwhelming sense of betrayal, and a consequent inability and unwillingness to trust anyone, even those close to you - In contrast to the chronic fatigue, depression etc, occasional false dawns with sudden bursts of energy accompanied by a feeling of "I'm better!", only to be followed by a full resurgence of symptoms a day or two later - Excessive guilt - when the cause of PTSD is bullying, the guilt expresses itself in forms distinct from "survivor guilt"; it comes out as: - an initial reluctance to take action against the bully and report him/her knowing that he/she could lose his/her job - later, this reluctance gives way to a strong urge to take action against the bully so that others, especially successors, don't have to suffer a similar fate - reluctance to feel happiness and joy because one's sense of other people's suffering throughout the world is heightened - a proneness to identifying with other people's suffering - a heightened sense of unworthiness, undeservingness and non-entitlement (some might call this shame) - a heightened sense of indebtedness, beholdenness and undue obligation - a reluctance to earn or accept money because one's sense of poverty and injustice throughout the world is heightened - an unwillingness to take ill-health retirement because the person doesn't want to believe they are sufficiently unwell to merit it - an unwillingness to draw sickness, incapacity or unemployment benefit to which the person is entitled - an unusually strong desire to educate the employer and help the employer introduce an anti-bullying ethos, usually proportional to the employer's lack of interest in anti-bullying measures - a desire to help others, often overwhelming and bordering on obsession, and to be available for others at any time regardless of the cost to oneself - an unusually high inclination to feel sorry for other people who are under stress, including those in a position of authority, even those who are not fulfilling the duties and obligations of their position (which may include the bully) but who are continuing to enjoy salary for remaining in post [hint: to overcome this tendency, every time you start to feel sorry for someone, say to yourself "sometimes, when you jump in and rescue someone, you deny them the opportunity to learn and grow"] The fatigue is understandable when you realise that in bullying, the target's fight or flight mechanism eventually becomes activated from Sunday evening (at the thought of facing the bully at work on Monday morning) through to the following Saturday morning (phew - weekend at last!). The fight or flight mechanism is designed to be operational only briefly and intermittently; in the heightened state of alert, the body consumes abnormally high levels of energy. If this state becomes semi-permanent, the body's physical, mental and emotional batteries are drained dry. Whilst the weekend theoretically is a time for the batteries to recharge, this doesn't happen, because: - the person is by now obsessed with the situation (or rather, resolving the situation), cannot switch off, may be unable to sleep, and probably has nightmares, flashbacks and replays; - sleep is non-restorative and unrefreshing - one goes to sleep tired and wakes up tired - this type of experience plays havoc with the immune system; when the fight or flight system is eventually switched off, the immune system is impaired such that the person is open to viruses which they would under normal circumstances fight off; the person then spends each weekend with a cold, cough, flu, glandular fever, laryngitis, ear infection etc so the body's batteries never have an opportunity to recharge. When activated, the body's fight or flight response results in the digestive, immune and reproductive systems being placed on standby. It's no coincidence that people experiencing constant abuse, harassment and bullying report malfunctions related to these systems (loss of appetite, constant infections, flatulence, irritable bowel syndrome, loss of libido, impotence, etc). The body becomes awash with cortisol which in high prolonged doses is toxic to brain cells. Cortisol kills off neuroreceptors in the hippocampus, an area of the brain linked with learning and memory. The hippocampus is also the control centre for the fight or flight response, thus the ability to control the fight or flight mechanism itself becomes impaired. Most survivors of bullying experience symptoms of Chronic Fatigue Syndrome - see health page for details. In law, gaining compensation for psychiatric injury is a long arduous process which can take years. As years have passed, legal precedents have been made and then reversed with case after life-changing case. The Tim Field Foundation is not in a position to maintain up-to-date information on bullying as it relates to personal injury law. Please contact a personal injury specialist for advice or, if you believe you have been subjected to criminal abuse, report it to the Police. One of the factors that make it so difficult to win a compensation claim for pyschiatric injury is that the respondent to the claim can, and is highly likely to have the claimant examined by a psychiatrist of their choosing, who will dismiss the notion of post-traumatic stress disorder and claim, instead, testify that the claimant has some other underlying mental illness. Incidence of PTSD and Complex PTSD The number of people suffering PTSD is unknown but David Kinchin estimates in his book Post Traumatic Stress Disorder: the invisible injury that at any time around 1% of the population are experiencing PTSD. This figure is only for PTSD resulting from traditional causes such as accident, violence or disaster. The incidence of Complex PTSD is unknown; with estimates of the number of people being bullied at work in the UK ranging from 1 in 8 (IPD, November 1996) to 1 in 2 (Staffordshire University Business School, 1994). Post Traumatic Stress Disorder: the invisible injury, 2005 edition, David Kinchin Supporting Children with Post-traumatic Stress Disorder: a practical guide for teachers and professionals, David Kinchin and Erica Brown Stress and employer liability, Earnshaw & Cooper, IPD, 1996 Why zebras don't get ulcers: an updated guide to stress, stress-related diseases, and coping, Robert M Sapolsky The Body Bears the Burden: Trauma, Dissociation and Disease, Robert C Scaer, MD Recovering damages for psychiatric injury, M Napier & K Wheat Understanding stress breakdown, Dr William Wilkie, Millennium Books, 1995 Understanding stress, V Sutherland & C Cooper, Chapman and Hall Trauma and transformation: growing in the aftermath of suffering, R Tedeschi & L Calhoun, Sage, 1996 The Railway Man, Eric Lomax (a poignant story of undiagnosed PTSD from World War II) National Center for PTSD articles: Dave Baldwin's trauma information pages contain comprehensive links. Post-Traumatic Stress Disorder is covered on the Mental Health Network Information on Falsification of Type (Dr Carl Gustav Jung's description for an individual whose most developed and/or used skills were outside one’s area of greatest natural preference) and PASS (Prolonged Adaption Stress Syndrome) is at http://www.benziger.org/articles/physfalsoftype.php Gillian Kelly, barrister at law, looks at the development of Post Traumatic Stress Disorder and the legal recognition thereof on her web site	2	8	0	0	1	0.686093	1	8,482
Uncovering the Diagnosis and Procedure Code Creation Process There’s no escaping discussions about the Novel Coronavirus (COVID-19, as it’s also called). Every aspect of life has been touched by the spread of it. The respiratory illness COVID-19 was first identified in 2019 in Wuhan, Hubei Province, China. Since then, it’s spread internationally. What isn’t widely discussed by the general population is a seemingly small detail that has a significant impact upon the medical community—the necessity of virus response to include the creation of new diagnosis and procedure codes. There are several codes that must be created not only to address a new disease through diagnosis but also through testing. Some of the codes are as follows: - ICD-10-CM, which stands for International Classification of Diseases, Tenth Revision, Clinical Modification, is the standard for reporting diseases and health conditions - ICD-procedure codes document procedures, such as testing for a condition or the administration of a vaccine or treatment - ICD-diagnostic codes are used to document inpatient and outpatient diagnoses - CPT codes are used to document outpatient procedures, such as those shared above Note that new procedure codes are needed to document the testing for a disease. Then, at a later date, if a vaccine or procedure is created to treat the disease, another new procedure code is created for that. While there is a standard process in place for when and how codes are released, COVID-19 is a unique situation, triggering the creation of a new code outside the normal process. In this post, we provide a high-level overview of why we need these codes. We also discuss how they are created under normal circumstances as well as during an unexpected outbreak, such as the one we’re experiencing today. Why We Need Diagnosis and Procedure Codes As stated by the World Health Organization (WHO), diagnosis and procedure codes allow for: - easy storage, retrieval and analysis of health information for evidence-based decision-making - sharing and comparing health information between hospitals, regions, settings, and countries - data comparisons in the same location across different time periods. Every time a patient goes to the doctor, the encounter is memorialized using the set of diagnosis and procedure codes identified above, which correspond to what happened during that visit. By using specific codes for encounters, physicians have a normalized way of reporting what happens in their practices. There are thousands upon thousands of codes, each intended to document the specific diagnoses and procedures that occur in healthcare settings around the world. Codes are also important for billing and reimbursement, as physician encounters are billed based on what codes are present on the claim corresponding to the encounter. This is how insurers understand what they are paying for when their covered patients go to the doctor. How Diagnosis and Procedure Codes are Typically Released New ICD and DRG codes are created every year by CMS. They are typically released in the fall, with an announcement at the beginning of Q3. This allows for healthcare providers to prepare and plan for any changes to come. Codes then typically go into effect October 1, the beginning of Q4 of that year. CPT codes are maintained by the American Medical Association and are released biannually due to new technologies and innovations being implemented to treat diseases. Applications for new or revised CPT codes can be submitted by certain parties to be reviewed by the 17-member CPT Editorial Panel. The Panel meets three times a year and addresses nearly 350 topics per year, involving 3,000+ votes on individual items. New/revised code approvals are then referred to the RVS (Relative Value Scale) Update Committee (RUC), which will conduct a survey of Qualified Health Plans (QHP) from certain medical specialties that provide the service or procedure. Category I CPT codes are updated annually and are effective January 1st of each year. Category II CPT codes are released three times yearly (March, July, November) and become effective three months after release. Category III codes are released either January 1st or July 1st and become effective six month after date of release. While it's helpful to understand how codes are released, it's also important to keep in mind that codes are also regularly revised and retired. Organizations need to revisit codes and their product line definitions often for this reason, especially when looking at trends over time. How COVID-19 is Unique While new codes are released on a regular basis, in the face of an emergency, a special meeting is held to specifically address the immediate need for an interim code. In emergency cases, CMS and AMA reserve the right to create new codes outside of the regularly scheduled updates. This process was first seen in action with the creation of emergency code U070 to document e-cigarette, or vaping, product use and associated lung injury. Interim diagnosis coding protocols are used, consisting of suggested primary and secondary diagnoses until an official code is effective with the regular release schedule. The interim protocols give different scenarios of disease progression and characteristics to specify which primary and secondary diagnoses to code. In the case of COVID-19, the January 30, 2020 declaration by the WHO of a public health emergency of international concern led to the scheduling of an emergency meeting of the World Health Organization Family of International Classifications (WHOFIC) Network Classification and Statistics Advisory Committee (CSAC). They convened in January to discuss the creation of a specific code for the new coronavirus. What we know about the ICD-10-CM diagnosis code for COVID-19 at this time, as shared by the American Academy of Family Physicians (AAFP), is stated below. There was no specific code for COVID-19 in the U.S. until March 18th, when the CDC announced via a webcast meeting that the new code would be implemented on April 1st, instead of the usual October 1st date, citing ‘timely data collection needs’. The World Health Organization (WHO) has already added code U07.1 (2019-nCoV acute respiratory disease) to the international ICD-10, and the U.S. version (ICD-10-CM) will be implemented on April 1st. When ICD-11 is released in October, COVID is expected to become RA01.0 and U07.1 will return to be reserved for emergency diseases. The CDC published the following interim guidance prior to March 18th that provides insight to the April 1st update: - For a diagnosis of COVID-19, report the code for the patient condition that is related to the COVID-19 (e.g., J12.89, "Other viral pneumonia") and B97.29, "Other coronavirus as the cause of diseases classified elsewhere." - For suspected COVID-19, not confirmed or ruled out at the encounter, report codes for the presenting signs and symptoms. Do not report a code for coronavirus when this diagnosis is not stated in the medical record. - For known exposure to COVID-19 (without diagnosis of COVID-19), report Z20.828, "Contact with and (suspected) exposure to other viral communicable diseases." - For suspected exposure to COVID-19 that is ruled out after evaluation, report Z03.818, "Encounter for observation for suspected exposure to other biological agents ruled out." The American Health Information Management Association shared that full addenda information regarding the new code and the final code title was presented at the ICD-10 Coordination and Maintenance Committee meeting that was held on March 17–18. When attempting to understand the full impact of an illness, accurately and consistently diagnosing it becomes paramount. In order to aggregate information quickly, that consistency becomes even more important. The main way that can take place is with the formation of diagnosis and procedure coding, which provide a way to tag encounters in the data that meet the specifics for the illness at hand. In these times of uncertainty, when many things are unknown, our international system of diagnosis and procedure coding provides one area of formality that we can look to for tracking how a new disease is impacting patients. Know too, that the team at Stratasan is still hard at work on your behalf. We’re ready to support your efforts to address specific issues that may arise at this time. Here are a few ways we can help: - Redefining patient and physician needs after a pandemic - Addressing the challenges of an ever-changing healthcare landscape - Implementing the best working from home habits to control your safety AND sanity (read more about that, here) Please reach out and schedule a time to talk, if there’s anything we can do to help.	4	2	0	0	5	0.734226	5	1,818
January 17, 2011 Coding for Heart Disease For The Record Vol. 23 No. 1 P. 27 Heart disease is a general term that involves a wide range of diseases affecting the heart and blood vessels, including the following: • coronary artery disease (CAD) (ICD-9-CM category 414); • arrhythmias (category 427); • congenital heart defects (categories 745 to 746); • cardiomyopathy (category 425); • heart infections such as pericarditis (categories 420 and 423), myocarditis (category 422 or 429.0), and endocarditis (categories 421 and 424); and • valvular heart disease (category 424). The term “heart disease” is often used interchangeably with the term “cardiovascular disease,” which refers to conditions that can narrow or block the blood vessels and may lead to myocardial infarction, chest pain, angina, or stroke. Symptoms depend on the type of heart disease. Common CAD symptoms include the following: • Stable angina (413.9) is predictable, is brought on by exertion, and diminishes after resting and nitroglycerin is administered. • Unstable angina (411.1) is a change in the usual pattern of angina, such as being more frequent, more severe, lasting longer, or occurring at rest. • Chest pain (786.50) other than angina can have many other possible underlying causes. Chest pain that begins suddenly or lasts only a few seconds is less likely to be angina. • shortness of breath with exertion. • fast heartbeat. • increased perspiration. • pain, numbness, weakness, or coldness in arms or legs. Chest pain is often the first indicator of CAD. The chest pain may be described as pressure, tightness, heaviness, squeezing, or burning. In addition, it may radiate to the left arm (most common), left shoulder, neck, lower jaw, midback, or right arm. Pressing on the chest wall does not cause the pain. Chest pain that is related to CAD may be termed angina pectoris. If, after careful study, a physician determines a patient’s underlying cause of chest pain to be angina and the patient has a documented history of CAD, then CAD will be sequenced as the principal diagnosis followed by the appropriate code for the angina (AHA Coding Clinic for ICD-9-CM, 2001, third quarter, page 15). CAD, the most prevalent type of heart disease, occurs when the coronary arteries become narrowed or blocked by plaque. Atherosclerosis is the most common cause of CAD and is characterized by a progressive buildup of plaque that causes less blood flow to the heart muscle, resulting in angina pectoris. If the blockage is complete, it leads to an acute myocardial infarction or sudden cardiac death. The ICD-9-CM diagnosis codes for CAD are classified to subcategory 414.0x. The fifth-digit subclassification identifies the location of the disease (eg, native vessel, bypass graft) and whether it has occurred in a transplanted heart. The appropriate code assignment will depend on the documentation, and it may be appropriate to assign more than one code from subcategory 414.0. If a patient has CAD and there is no past history of bypass surgery, then it is appropriate to assign code 414.01 to identify the CAD is in the native artery (AHA Coding Clinic for ICD-9-CM, 1997, third quarter, page 15). Code 996.03, Mechanical complication due to coronary artery bypass graft, should not be assigned for a diagnosis of coronary artery graft occlusion due to atherosclerosis. Assign a code from 414.0x instead (AHA Coding Clinic for ICD-9-CM, 1995, second quarter, page 17). Common symptoms of arrhythmias include tachycardia (fast heartbeat), bradycardia (slow heartbeat), palpitations or skipped beats, fluttering in the chest, chest pain or discomfort, shortness of breath, lightheadedness, dizziness, weakness or fatigue, syncope or near syncope, paleness, and sweating. A heart arrhythmia may not cause any symptoms and may be identified only during a regular routine exam. Common symptoms of congenital heart defects include cyanosis; swelling in the legs, abdomen, or area around the eyes; shortness of breath; easily tiring during exercise or activity; fluid in the heart or the lungs; and swelling in the hands, ankles, or feet. Common symptoms of cardiomyopathy include shortness of breath, swelling of the lower extremities, abdominal distention due to fluid, fatigue, irregular heart rhythm, dizziness, lightheadedness, and fainting. Common symptoms of heart infections include fever, shortness of breath, weakness or fatigue, swelling in the legs or the abdomen, arrhythmia, cough, and skin rashes. Common symptoms of valvular heart disease include fatigue, shortness of breath, irregular heartbeat or murmur, swollen feet or ankles, chest pain, and syncope. Tests to diagnose heart disease may include blood tests, chest x-ray, electrocardiogram, holter monitoring (ambulatory electrocardiography monitoring), heart biopsy, stress test, cardiac catheterization with coronary angiography, coronary MRI, cardiac CT, scan, and echocardiogram. Coding and sequencing for heart disease are dependent on the physician documentation in the medical record and application of the Official Coding Guidelines for inpatient care. Also, use specific AHA Coding Clinic for ICD-9-CM and American Medical Association CPT Assistant references to ensure complete and accurate coding. — This information was prepared by Audrey Howard, RHIA, of 3M Consulting Services. 3M Consulting Services is a business of 3M Health Information Systems, a supplier of coding and classification systems to more than 5,000 healthcare providers. The company and its representatives do not assume any responsibility for reimbursement decisions or claims denials made by providers or payers as the result of the misuse of this coding information. More information about 3M Health Information Systems is available at www.3mhis.com or by calling 800-367-2447. Coding CAD in ICD-10 Editor’s Note: As we flipped the calendar to 2011, the deadline for ICD-10 implementation crept that much closer. To give coding departments a better idea of what the transition will be like, For The Record is expanding its popular Coding and Transcription column to include a sidebar that maps the ICD-9 codes to their more advanced counterparts. The idea is to give readers a stronger sense of what’s in store in the near future. Documentation specificity under the ICD-10-CM system for coronary artery disease (CAD) with and without angina is crucial for accurate classification of these disease processes. Combination codes including CAD with and without angina will exist under the new coding system. Unstable angina is classified to code I20.0. It includes accelerated angina, crescendo angina, de novo effort angina, intermediate coronary syndrome, preinfarction syndrome, and worsening effort angina. The combination codes for CAD with and without angina are in category I25 (chronic ischemic heart disease). I25.10, Arteriosclerotic heart disease (ASHD) of native coronary artery without angina pectoris; I25.11, ASHD of native coronary artery with angina pectoris, with further breakdown in I25.11 to specify the types of angina, including unstable angina pectoris, angina pectoris with documented spasm, other forms of angina pectoris, and unspecified angina pectoris. The I25.7 subcategory further breaks down CAD of coronary artery bypass graft (CABG) arteries and veins with angina pectoris. The I25.8 subcategory further breaks down CAD of CABG arteries and veins without angina pectoris. If a patient has both ASHD/CAD and angina, a causal relationship can be assumed, according to the ICD-10-CM Official Guidelines for Coding and Reporting. — Donna M. Smith, RHIA, is a senior consultant for 3M Health Information Systems.	4	8	0	0	6	0.941245	6	1,785
- Lung cancer Lung cancer Classification and external resources Cross section of a human lung. The white area in the upper lobe is cancer; the black areas are discoloration due to smoking. ICD-10 C33-C34 ICD-9 162 DiseasesDB 7616 MedlinePlus 007194 eMedicine med/1333 med/1336 emerg/335 radio/807 radio/405 radio/406 MeSH D002283 Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary lung cancers, are carcinomas that derive from epithelial cells. Worldwide, lung cancer is the most common cause of cancer-related death in men and women, and is responsible for 1.3 million deaths annually, as of 2004. The most common symptoms are shortness of breath, coughing (including coughing up blood), and weight loss. The main types of lung cancer are small-cell lung cancer (SCLC), also called oat cell cancer, and non-small-cell lung cancer (NSCLC). The most common cause of lung cancer is long-term exposure to tobacco smoke. Nonsmokers account for 15% of lung cancer cases, and these cases are often attributed to a combination of genetic factors, radon gas, asbestos, and air pollution including secondhand smoke. Lung cancer may be seen on chest radiograph and computed tomography (CT scan). The diagnosis is confirmed with a biopsy. This is usually performed by bronchoscopy or CT-guided biopsy. Treatment and prognosis depend on the histological type of cancer, the stage (degree of spread), and the patient's general wellbeing, measured by performance status. Common treatments include surgery, chemotherapy, and radiotherapy. NSCLC is sometimes treated with surgery, whereas SCLC usually responds better to chemotherapy and radiation therapy. This is partly because SCLC often spreads quite early, and these treatments are generally better at getting to cancer cells that have spread to other parts of the body. - 1 Signs and symptoms - 2 Causes - 3 Pathogenesis - 4 Diagnosis - 5 Prevention - 6 Treatment - 7 Prognosis - 8 Epidemiology - 9 History - 10 References - 11 External links Signs and symptoms - dyspnea (shortness of breath) - hemoptysis (coughing up blood) - chronic coughing or change in regular coughing pattern - chest pain or pain in the abdomen - cachexia (weight loss), fatigue, and loss of appetite - dysphonia (hoarse voice) - clubbing of the fingernails (uncommon) - dysphagia (difficulty swallowing). If the cancer grows in the airway, it may obstruct airflow, causing breathing difficulties. The obstruction can lead to accumulation of secretions behind the blockage, and predispose to pneumonia. Many lung cancers have a rich blood supply. The surface of the cancer may be fragile, leading to bleeding from the cancer into the airway. This blood may subsequently be coughed up. Depending on the type of tumor, so-called paraneoplastic phenomena may initially attract attention to the disease. In lung cancer, these phenomena may include Lambert-Eaton myasthenic syndrome (muscle weakness due to auto-antibodies), hypercalcemia, or syndrome of inappropriate antidiuretic hormone (SIADH). Tumors in the top (apex) of the lung, known as Pancoast tumors, may invade the local part of the sympathetic nervous system, leading to changed sweating patterns and eye muscle problems (a combination known as Horner's syndrome) as well as muscle weakness in the hands due to invasion of the brachial plexus. Many of the symptoms of lung cancer (bone pain, fever, and weight loss) are nonspecific; in the elderly, these may be attributed to comorbid illness. In many patients, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention. Common sites of metastasis include the brain, bone, adrenal glands, contralateral (opposite) lung, liver, pericardium, and kidneys. About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest radiograph. The main causes of any cancer include carcinogens (such as those in tobacco smoke), ionizing radiation, and viral infection. This exposure causes cumulative changes to the DNA in the tissue lining the bronchi of the lungs (the bronchial epithelium). As more tissue becomes damaged, eventually a cancer develops. Smoking, particularly of cigarettes, is by far the main contributor to lung cancer. Cigarette smoke contains over 60 known carcinogens, including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene. Additionally, nicotine appears to depress the immune response to malignant growths in exposed tissue. Across the developed world, 91% of lung cancer deaths in men during the year 2000 were attributed to smoking (71% for women). In the United States, smoking is estimated to account for 87% of lung cancer cases (90% in men and 85% in women). Among male smokers, the lifetime risk of developing lung cancer is 17.2%; among female smokers, the risk is 11.6%. This risk is significantly lower in nonsmokers: 1.3% in men and 1.4% in women. Women who smoke (former smokers and current smokers) and take hormone therapy are at a much higher risk of dying of lung cancer. In a study by Chlebowski et al. published in 2009, the women taking hormones were about 60% more likely to die of lung cancer than the women taking a placebo. Not surprisingly, the risk was highest for current smokers, followed by past smokers, and lowest for those who have never smoked. Among the women who smoked (former or current smokers), 3.4% of those taking hormone therapy died of lung cancer compared to 2.3% for women taking the placebo. The time a person smokes (as well as rate of smoking) increases the person's chance of developing lung cancer. If a person stops smoking, this chance steadily decreases as damage to the lungs is repaired and contaminant particles are gradually removed. In addition, there is evidence that lung cancer in never-smokers has a better prognosis than in smokers, and that patients who smoke at the time of diagnosis have shorter survival times than those who have quit. Passive smoking—the inhalation of smoke from another's smoking—is a cause of lung cancer in nonsmokers. A passive smoker can be classified as someone living or working with a smoker. Studies from the U.S., Europe, the UK, and Australia have consistently shown a significant increase in relative risk among those exposed to passive smoke. Recent investigation of sidestream smoke suggests that it is more dangerous than direct smoke inhalation. 10–15% of lung cancer patients have never smoked. That means between 20,000 to 30,000 never-smokers are diagnosed with lung cancer in the United States each year. Because of the five-year survival rate, each year in the U.S. more never-smokers die of lung cancer than do patients of leukemia, ovarian cancer, or AIDS. Radon is a colorless and odorless gas generated by the breakdown of radioactive radium, which in turn is the decay product of uranium, found in the Earth's crust. The radiation decay products ionize genetic material, causing mutations that sometimes turn cancerous. Radon exposure is the second major cause of lung cancer in the general population, after smoking with the risk increasing 8–16% for every 100 Bq/m³ increase in the radon concentration. Radon gas levels vary by locality and the composition of the underlying soil and rocks. For example, in areas such as Cornwall in the UK (which has granite as substrata), radon gas is a major problem, and buildings have to be force-ventilated with fans to lower radon gas concentrations. The United States Environmental Protection Agency (EPA) estimates that one in 15 homes in the U.S. has radon levels above the recommended guideline of 4 picocuries per liter (pCi/L) (148 Bq/m³). Iowa has the highest average radon concentration in the United States; studies performed there have demonstrated a 50% increased lung cancer risk, with prolonged radon exposure above the EPA's action level of 4 pCi/L. Asbestos can cause a variety of lung diseases, including lung cancer. There is a synergistic effect between tobacco smoking and asbestos in the formation of lung cancer. In the UK, asbestos accounts for 2–3% of male lung cancer deaths. Asbestos can also cause cancer of the pleura, called mesothelioma (which is different from lung cancer). Viruses are known to cause lung cancer in animals, and recent evidence suggests similar potential in humans. Implicated viruses include human papillomavirus, JC virus, simian virus 40 (SV40), BK virus, and cytomegalovirus. These viruses may affect the cell cycle and inhibit apoptosis, allowing uncontrolled cell division. Studies of the American Cancer Society cohort directly link the exposure to particulate matter with lung cancer. For example, if the concentration of particles in the air increases by only 1%, the risk of developing a lung cancer increases by 14%. Further, it has been established that particle size matters, as ultrafine particles penetrate further into the lungs. Similar to many other cancers, lung cancer is initiated by activation of oncogenes or inactivation of tumor suppressor genes. Oncogenes are genes that are believed to make people more susceptible to cancer. Proto-oncogenes are believed to turn into oncogenes when exposed to particular carcinogens. Mutations in the K-ras proto-oncogene are responsible for 10–30% of lung adenocarcinomas. The epidermal growth factor receptor (EGFR) regulates cell proliferation, apoptosis, angiogenesis, and tumor invasion. Mutations and amplification of EGFR are common in non-small-cell lung cancer and provide the basis for treatment with EGFR-inhibitors. Her2/neu is affected less frequently. Chromosomal damage can lead to loss of heterozygosity. This can cause inactivation of tumor suppressor genes. Damage to chromosomes 3p, 5q, 13q, and 17p are particularly common in small-cell lung carcinoma. The p53 tumor suppressor gene, located on chromosome 17p, is affected in 60-75% of cases. Other genes that are often mutated or amplified are c-MET, NKX2-1, LKB1, PIK3CA, and BRAF. Several genetic polymorphisms are associated with lung cancer. These include polymorphisms in genes coding for interleukin-1, cytochrome P450, apoptosis promoters such as caspase-8, and DNA repair molecules such as XRCC1. People with these polymorphisms are more likely to develop lung cancer after exposure to carcinogens. Performing a chest radiograph is the first step if a patient reports symptoms that may suggest lung cancer. This may reveal an obvious mass, widening of the mediastinum (suggestive of spread to lymph nodes there), atelectasis (collapse), consolidation (pneumonia), or pleural effusion. If there are no radiographic findings but the suspicion is high (such as a heavy smoker with blood-stained sputum), bronchoscopy and/or a CT scan may provide the necessary information. Bronchoscopy or CT-guided biopsy is often used to identify the tumor type. Abnormal findings in cells ("atypia") in sputum are associated with an increased risk of lung cancer. Sputum cytologic examination combined with other screening examinations may have a role in the early detection of lung cancer. The differential diagnosis for patients who present with abnormalities on chest radiograph includes lung cancer as well as nonmalignant diseases. These include infectious causes such as tuberculosis or pneumonia, or inflammatory conditions such as sarcoidosis. These diseases can result in mediastinal lymphadenopathy or lung nodules, and sometimes mimic lung cancers. Lung cancer can also be an incidental finding: a solitary pulmonary nodule (also called a coin lesion) on a chest radiograph or CT scan taken for an unrelated reason. The definitive diagnosis of lung cancer and its classification (described above) is based on examination of the suspicious tissue under the microscope by a pathologist. Lung cancers are classified according to histological type. This classification has important implications for clinical management and prognosis of the disease. The vast majority of lung cancers are carcinomas—malignancies that arise from epithelial cells. The two most prevalent histological types of lung carcinoma, categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope, are non-small-cell and small-cell lung carcinoma. The non-small-cell type is the most prevalent by far (see accompanying table). Frequency of histological types of lung cancer Histological type Frequency (%) Non-small-cell lung carcinoma 80.4 Small-cell lung carcinoma 16.8 Carcinoid 0.8 Sarcoma 0.1 Unspecified lung cancer 1.9 Cancer found outside of the lung may be determined to have arisen within the lung, as lung cancers that metastasize, i.e. spread, often retain a cell marker profile that allow a pathologist to say, with a good deal of certainty, that the tumor arose from the lung, i.e. is a primary lung cancer. Primary lung cancers of adenocarcinoma histology typically have nuclear immunostaining with TTF-1. Non-small-cell lung carcinoma The non-small-cell lung carcinomas (NSCLC) are grouped together because their prognosis and management are similar. There are three main sub-types: squamous cell lung carcinoma, adenocarcinoma, and large-cell lung carcinoma. Sub-types of non-small-cell lung cancer in smokers and never-smokers Histological sub-type Frequency of non-small-cell lung cancers (%) Smokers Never-smokers Squamous cell lung carcinoma 42 33 Adenocarcinoma Adenocarcinoma (not otherwise specified) 39 35 Bronchioloalveolar carcinoma 4 10 Carcinoid 7 16 Other 8 6 Accounting for 25% of lung cancers, squamous cell lung carcinoma usually starts near a central bronchus. A hollow cavity and associated necrosis are commonly found at the center of the tumor. Well-differentiated squamous cell lung cancers often grow more slowly than other cancer types. Adenocarcinoma accounts for 40% of non-small-cell lung cancers. It usually originates in peripheral lung tissue. Most cases of adenocarcinoma are associated with smoking; however, among people who have never smoked ("never-smokers"), adenocarcinoma is the most common form of lung cancer. A subtype of adenocarcinoma, the bronchioloalveolar carcinoma, is more common in female never-smokers, and may have different responses to treatment. Small-cell lung carcinoma Small-cell lung carcinoma (SCLC) is less common. It was formerly referred to as "oat-cell" carcinoma. Most cases arise in the larger airways (primary and secondary bronchi) and grow rapidly, becoming quite large. The small cells contain dense neurosecretory granules (vesicles containing neuroendocrine hormones), which give this tumor an endocrine/paraneoplastic syndrome association. While initially more sensitive to chemotherapy and radiation, it is often metastatic at presentation, and ultimately carries a worse prognosis. Small-cell lung cancers have long been dichotomously staged into limited and extensive stage disease. This type of lung cancer is strongly associated with smoking. Lung cancers are highly heterogeneous malignancies, with tumors containing more than one subtype being very common. Currently, the most widely recognized and utilized lung cancer classification system is the 4th revision of the Histological Typing of Lung and Pleural Tumours, published in 2004 as a cooperative effort by the World Health Organization and the International Association for the Study of Lung Cancer. It recognizes numerous other distinct histopathological entities of non-small-cell lung carcinoma, organized into several additional subtypes, including sarcomatoid carcinoma, salivary gland tumors, carcinoid tumor, and adenosquamous carcinoma. The latter subtype includes tumors containing at least 10% each of adenocarcinoma and squamous cell carcinoma. When a tumor is found to contain a mixture of both small-cell carcinoma and non-small-cell carcinoma, it is classified as a variant of small-cell carcinoma and called a combined small-cell carcinoma. Combined small-cell carcinoma is the only currently recognized variant of small-cell carcinoma. The lung is a common place for metastasis of tumors from other parts of the body. Secondary cancers are classified by the site of origin; e.g., breast cancer that has spread to the lung is called breast cancer. Metastases often have a characteristic round appearance on chest radiograph. Solitary round lung nodules are not infrequently of an uncertain etiology and may prompt a lung biopsy. In children, the majority of lung cancers are secondary. Lung cancer staging is an assessment of the degree of spread of the cancer from its original source. In most studies, it is the most important factor affecting the prognosis and potential treatment of lung cancer. Staging varies for the two major cell types of lung cancer (non-small cell lung carcinoma and small cell lung carcinoma). It is normally done prior to attempts at curative therapy, and usually consists of an extensive battery of tests, to include physical examination, laboratory tests, imaging studies, and/or biopsies and other invasive procedures (such as mediastinoscopy). Non-small cell lung carcinoma is usually staged from IA ("one A"; best prognosis) to IV ("four"; worst prognosis). Small cell lung carcinoma has traditionally been classified as limited stage (confined to one half of the chest and within the scope of a single tolerable radiotherapy field) or extensive stage (more widespread disease). For both NSCLC and SCLC, there are two general types of staging evaluations: Clinical Staging: evaluated prior to definitive surgery, and typically based on the results of physical examination, imaging studies, and pertinent laboratory findings. Does not necessarily involve a pathologist. Pathological Staging: usually evaluated either intra- or post-operatively, and based on the combined results of surgical and clinical findings. Prevention is the most cost-effective means of fighting lung cancer. While in most countries industrial and domestic carcinogens have been identified and banned, tobacco smoking is still widespread. Eliminating tobacco smoking is a primary goal in the prevention of lung cancer, and smoking cessation is an important preventive tool in this process. Of utmost importance are prevention programs that target the young. In 1998 the Master Settlement Agreement entitled 46 states in the USA to an annual payout from the tobacco companies. Between the settlement money and tobacco taxes, each state's public health department funds their prevention programs, although none of the states are living up to the Center for Disease Control's recommended amount by spending 15 percent of tobacco taxes and settlement revenues on these prevention efforts. Policy interventions to decrease passive smoking in public areas such as restaurants and workplaces have become more common in many Western countries, with California taking a lead in banning smoking in public establishments in 1998. Ireland played a similar role in Europe in 2004, followed by Italy and Norway in 2005, Scotland as well as several others in 2006, England in 2007, France in 2008 and Turkey in 2009. New Zealand has banned smoking in public places as of 2004. The state of Bhutan has had a complete smoking ban since 2005. In many countries, pressure groups are campaigning for similar bans. In 2007, Chandigarh became the first city in India to become smoke-free. India introduced a total ban on smoking in public places on 2 October 2008. The long-term use of supplemental multivitamins—such as vitamin C, vitamin E, and folate—does not reduce the risk of lung cancer. Indeed long-term intake of high doses of vitamin E supplements may even increase the risk of lung cancer. However, eating at least five servings of fruits and vegetables per day and following a diet that conforms to the American Cancer Society's guidelines may help lower risk. The World Health Organization has called for governments to institute a total ban on tobacco advertising to prevent young people from taking up smoking. They assess that such bans have reduced tobacco consumption by 16% where already instituted. Screening refers to the use of medical tests to detect disease in asymptomatic people. Possible screening tests for lung cancer include chest radiograph, or computed tomography (CT). As of December 2009, screening programs for lung cancer have not demonstrated any benefit. Treatment for lung cancer depends on the cancer's specific cell type, how far it has spread, and the patient's performance status. Common treatments include palliative care, surgery, chemotherapy, and radiation therapy. If investigations confirm lung cancer, CT scan and often positron emission tomography (PET) are used to determine whether the disease is localized and amenable to surgery or whether it has spread to the point where it cannot be cured surgically. Blood tests and spirometry (lung function testing) are also necessary to assess whether the patient is well enough to be operated on. If spirometry reveals poor respiratory reserve (often due to chronic obstructive pulmonary disease), surgery may be contraindicated. Surgery for lung cancer has an operative death rate of about 4.4%, depending on the patient's lung function and other risk factors. In non-small-cell lung carcinoma, surgery is usually only an option if the cancer is limited to one lung, up to stage IIIA. This is assessed with medical imaging (computed tomography, positron emission tomography). A sufficient preoperative respiratory reserve must be present to allow adequate lung function after the tissue is removed. Procedures include wedge resection (removal of part of a lobe), segmentectomy (removal of an anatomic division of a particular lobe of the lung), lobectomy (one lobe), bilobectomy (two lobes), or pneumonectomy (whole lung). In patients with adequate respiratory reserve, lobectomy is the preferred option, as this minimizes the chance of local recurrence. If the patient does not have enough functional lung for this, wedge resection may be performed. Radioactive iodine brachytherapy at the margins of wedge excision may reduce recurrence to that of lobectomy. Video-assisted thoracoscopic surgery and VATS lobectomy have allowed for minimally invasive approaches to lung cancer surgery that may have the advantages of quicker recovery, shorter hospital stay and diminished hospital costs. Early studies suggested that small-cell lung carcinoma (SCLC) fared better when treated with chemotherapy and/or radiation than when treated surgically. While this approach to treating SCLC remains the current standard of care, the role of surgery in SCLC is being reconsidered, recent reviews indicating that surgery might improve outcomes when added to chemotherapy and radiation in early stage SCLC and combined forms of SCLC and NSCLC. Radiotherapy is often given together with chemotherapy, and may be used with curative intent in patients with non-small-cell lung carcinoma who are not eligible for surgery. This form of high intensity radiotherapy is called radical radiotherapy. A refinement of this technique is continuous hyperfractionated accelerated radiotherapy (CHART), in which a high dose of radiotherapy is given in a short time period. For small-cell lung carcinoma cases that are potentially curable, chest radiation is often recommended in addition to chemotherapy. The use of adjuvant thoracic radiotherapy following curative intent surgery for non-small-cell lung carcinoma is not well established and is controversial. Benefits, if any, may only be limited to those in whom the tumor has spread to the mediastinal lymph nodes. For both non-small-cell lung carcinoma and small-cell lung carcinoma patients, smaller doses of radiation to the chest may be used for symptom control (palliative radiotherapy). Unlike other treatments, it is possible to deliver palliative radiotherapy without confirming the histological diagnosis of lung cancer. Brachytherapy (localized radiotherapy) may be given directly inside the airway when cancer affects a short section of bronchus. It is used when inoperable lung cancer causes blockage of a large airway. Patients with limited-stage small-cell lung carcinoma are usually given prophylactic cranial irradiation (PCI). This is a type of radiotherapy to the brain, used to reduce the risk of metastasis. More recently, PCI has also been shown to be beneficial in those with extensive small-cell lung cancer. In patients whose cancer has improved following a course of chemotherapy, PCI has been shown to reduce the cumulative risk of brain metastases within one year from 40.4% to 14.6%. Recent improvements in targeting and imaging have led to the development of extracranial stereotactic radiation in the treatment of early-stage lung cancer. In this form of radiation therapy, very high doses are delivered in a small number of sessions using stereotactic targeting techniques. Its use is primarily in patients who are not surgical candidates due to medical comorbidities. The chemotherapy regimen depends on the tumor type. Small-cell lung carcinoma Even if relatively early stage, small-cell lung carcinoma is treated primarily with chemotherapy and radiation. In small-cell lung carcinoma, cisplatin and etoposide are most commonly used. Combinations with carboplatin, gemcitabine, paclitaxel, vinorelbine, topotecan, and irinotecan are also used. Celecoxib showed a potential signal of response in a small study. Non-small-cell lung carcinoma Primary chemotherapy is also given in advanced and metastatic non-small-cell lung carcinoma. Testing for the molecular genetic subtype of non-small-cell lung cancer may be of assistance in selecting the most appropriate initial therapy For example, mutation of the epidermal growth factor receptor gene may predict whether initial treatment with a specific inhibitor or with chemotherapy is more advantageous. Advanced non-small-cell lung carcinoma is often treated with cisplatin or carboplatin, in combination with gemcitabine, paclitaxel, docetaxel, etoposide, or vinorelbine. Bevacizumab improves results in non-squamous cancers treated with paclitaxel and carboplatin in patients less than 70 years old who have reasonable general performance status. Pemetrexed has been approved for use in non-small-cell lung cancer. For adenocarcinoma and large-cell lung cancer, cisplatin with pemetrexed was more beneficial than cisplatin and gemcitabine; squamous cancer had the opposite results. As a consequence, subtyping of non-small lung cancer histology has become more important. The U.S. Food and Drug Administration (FDA) approved erlotinib (Tarceva) for the treatment of locally advanced or metastatic non-small cell lung cancer that has failed at least one prior chemotherapy regimen, and has also approved its use as maintenance treatment in locally advanced or metastatic non-small cell lung cancer that has not progressed after four cycles of platinum-based first-line chemotherapy. The U.S. Food and Drug Administration approved crizotinib (Xalkori) to treat certain late-stage (locally advanced or metastatic) non-small cell lung cancers that express the abnormal anaplastic lymphoma kinase (ALK) gene. In advanced non-small-cell lung cancer there are several approaches for continuing treatment after an initial response to therapy. Switch maintenance changes to different medications than the initial therapy and can use pemetrexed, erlotinib, and docetaxel, although pemetrexed is only used in non-squamous NSCLC. Adjuvant chemotherapy refers to the use of chemotherapy after apparently curative surgery to improve the outcome. In non-small-cell lung cancer, samples are taken during surgery of nearby lymph nodes. If these samples contain cancer, the patient has stage II or III disease. In this situation, adjuvant chemotherapy may improve survival by up to 15%. Standard practice has often been to offer platinum-based chemotherapy (including either cisplatin or carboplatin). However, the benefit of platinum-based adjuvant chemotherapy was confined to patients who had tumors with low ERCC1 (excision repair cross-complementing 1) activity. Adjuvant chemotherapy for patients with stage IB cancer is controversial, as clinical trials have not clearly demonstrated a survival benefit. Trials of preoperative chemotherapy (neoadjuvant chemotherapy) in resectable non-small-cell lung carcinoma have been inconclusive. Radiofrequency ablation should currently be considered an investigational technique in the treatment of bronchogenic carcinoma. It is done by inserting a small heat probe into the tumor to kill the tumor cells. In a 2010 study of patients with metastatic non–small-cell lung cancer, early palliative care led to significant improvements in both quality of life and mood. As compared with patients receiving standard care, patients receiving early palliative care had less aggressive care at the end of life but longer survival" (increased by 3 months). Other studies in advanced cancer also found benefit from palliative care, or found hospice involvement to be beneficial. These approaches allow additional discussion of treatment options and provide opportunities to arrive at well-considered decisions and may avoid unhelpful but expensive care at the end of life. Chemotherapy may be combined with palliative care in the treatment of the non-small-cell lung cancer. In advanced NSCLC, a 1994 meta-analysis found that appropriate chemotherapy improved average survival over supportive care alone, as well as improving quality of life. With adequate physical fitness, maintaining chemotherapy during lung cancer palliation offers a 1.5 to 3 months prolongation of survival, symptomatic relief and an improvement in quality of life, with better results seen with modern agents. Since 2008, the NSCLC Meta-Analyses Collaborative Group has recommended that if the recipient wants and can tolerate treatment then chemotherapy should be considered in advanced NSCLC. Prognostic factors in non-small-cell lung cancer include presence or absence of pulmonary symptoms, tumor size, cell type (histology), degree of spread (stage) and metastases to multiple lymph nodes, and vascular invasion. For patients with inoperable disease, prognosis is adversely affected by poor performance status and weight loss of more than 10%. Prognostic factors in small-cell lung cancer include performance status, gender, stage of disease, and involvement of the central nervous system or liver at the time of diagnosis. For non-small-cell lung carcinoma (NSCLC), prognosis is generally poor. Following complete surgical resection of stage IA disease, five-year survival is 67%. With stage IB disease, five-year survival is 57%. The five-year survival rate of patients with stage IV NSCLC is about 1%. For small-cell lung carcinoma, prognosis is also generally poor. The overall five-year survival for patients with SCLC is about 5%. Patients with extensive-stage SCLC have an average five-year survival rate of less than 1%. The median survival time for limited-stage disease is 20 months, with a five-year survival rate of 20%. Worldwide, lung cancer is the most common cancer in terms of both incidence and mortality (1.1 million new cases per year and 0.95 million deaths in males and 0.51 million new cases per year and 0.43 million deaths in females). The highest rates are in Europe and North America. The population segment most likely to develop lung cancer is over-fifties who have a history of smoking. Lung cancer is the second most commonly occurring form of cancer in most Western countries, and it is the leading cancer-related cause of death. In contrast to the mortality rate in men, which began declining more than 20 years ago, women's lung cancer mortality rates have been rising over the last decades, and are just recently beginning to stabilize. The evolution of "Big Tobacco" plays a significant role in the smoking culture. Tobacco companies have focused their efforts since the 1970s at marketing their product toward women and girls, especially with "light" and "low-tar" cigarettes. Among lifetime nonsmokers, men have higher age-standardized lung cancer death rates than women. Not all cases of lung cancer are due to smoking, but the role of passive smoking is increasingly being recognized as a risk factor for lung cancer—leading to policy interventions to decrease undesired exposure of nonsmokers to others' tobacco smoke. Emissions from automobiles, factories, and power plants also pose potential risks. Eastern Europe has the highest lung cancer mortality among men, while northern Europe and the U.S. have the highest mortality among women. In the United States, black men and women have a higher incidence. Lung cancer incidence is currently less common in developing countries. With increased smoking in developing countries, the incidence is expected to increase in the next few years, notably in China and India. Lung cancer incidence (by country) has an inverse correlation with sunlight and UVB exposure. One possible explanation is a preventive effect of vitamin D, which is produced in the skin on exposure to sunlight. From the 1950s, the incidence of lung adenocarcinoma started to rise relative to other types of lung cancer. This is partly due to the introduction of filter cigarettes. The use of filters removes larger particles from tobacco smoke, thus reducing deposition in larger airways. However the smoker has to inhale more deeply to receive the same amount of nicotine, increasing particle deposition in small airways where adenocarcinoma tends to arise. The incidence of lung adenocarcinoma in the U.S. has fallen since 1999. This may be due to reduction in environmental air pollution. However, in some developing countries like India, there has been little change in the epidemiology with squamous cell carcinoma continuing to be the predominant histological type. An absence of change in the type of tobacco smoking or the pattern of tobacco consumption in the population could be one of the possible reasons. Lung cancer was uncommon before the advent of cigarette smoking; it was not even recognized as a distinct disease until 1761. Different aspects of lung cancer were described further in 1810. Malignant lung tumors made up only 1% of all cancers seen at autopsy in 1878, but had risen to 10–15% by the early 1900s. Case reports in the medical literature numbered only 374 worldwide in 1912, but a review of autopsies showed that the incidence of lung cancer had increased from 0.3% in 1852 to 5.66% in 1952. In Germany in 1929, physician Fritz Lickint recognized the link between smoking and lung cancer, which led to an aggressive antismoking campaign. The British Doctors Study, published in the 1950s, was the first solid epidemiological evidence of the link between lung cancer and smoking. As a result, in 1964 the Surgeon General of the United States recommended that smokers should stop smoking. The connection with radon gas was first recognized among miners in the Ore Mountains near Schneeberg, Saxony. Silver has been mined there since 1470, and these mines are rich in uranium, with its accompanying radium and radon gas. Miners developed a disproportionate amount of lung disease, eventually recognized as lung cancer in the 1870s. An estimated 75% of former miners died from lung cancer. Despite this discovery, mining continued into the 1950s, due to the USSR's demand for uranium. The first successful pneumonectomy for lung cancer was performed in 1933. Palliative radiotherapy has been used since the 1940s. Radical radiotherapy, initially used in the 1950s, was an attempt to use larger radiation doses in patients with relatively early stage lung cancer but who were otherwise unfit for surgery. In 1997, continuous hyperfractionated accelerated radiotherapy (CHART) was seen as an improvement over conventional radical radiotherapy. With small-cell lung carcinoma, initial attempts in the 1960s at surgical resection and radical radiotherapy were unsuccessful. In the 1970s, successful chemotherapy regimens were developed. - ^ WHO (February 2006). "Cancer". World Health Organization. http://www.who.int/mediacentre/factsheets/fs297/en/. Retrieved 2007-06-25. - ^ a b c d e f Minna, JD; Schiller JH (2008). Harrison's Principles of Internal Medicine (17th ed.). McGraw-Hill. pp. 551–562. ISBN 0-07-146633-9. - ^ a b c "Lung Carcinoma: Tumors of the Lungs". Merck Manual Professional Edition, Online edition. http://www.merck.com/mmpe/sec05/ch062/ch062b.html#sec05-ch062-ch062b-1405. Retrieved 2007-08-15. - ^ Thun, MJ; Hannan LM, Adams-Campbell LL et al. (2008). Adami, Hans-Olov. ed. "Lung Cancer Occurrence in Never-Smokers: An Analysis of 13 Cohorts and 22 Cancer Registry Studies". PLoS Medicine 5 (9): e185. doi:10.1371/journal.pmed.0050185. PMC 2531137. PMID 18788891. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2531137. - ^ Gorlova, OY; Weng SF, Zhang Y et al. (July 2007). "Aggregation of cancer among relatives of never-smoking lung cancer patients". International Journal of Cancer 121 (1): 111–118. doi:10.1002/ijc.22615. PMID 17304511. - ^ Hackshaw, AK; Law MR, Wald NJ (1997-10-18). "The accumulated evidence on lung cancer and environmental tobacco smoke". British Medical Journal 315 (7114): 980–988. PMC 2127653. PMID 9365295. http://www.bmj.com/cgi/content/full/315/7114/980. - ^ a b Catelinois O, Rogel A, Laurier D, et al. (September 2006). "Lung Cancer Attributable to Indoor Radon Exposure in France: Impact of the Risk Models and Uncertainty Analysis". Environ. Health Perspect. 114 (9): 1361–6. doi:10.1289/ehp.9070. PMC 1570096. PMID 16966089. http://www.ehponline.org/members/2006/9070/9070.html. - ^ a b O'Reilly, KM; Mclaughlin AM, Beckett WS, Sime PJ (March 2007). "Asbestos-related lung disease". American Family Physician 75 (5): 683–688. PMID 17375514. http://www.aafp.org/afp/20070301/683.html. - ^ a b Kabir, Z; Bennett K, Clancy L (February 2007). "Lung cancer and urban air-pollution in dublin: a temporal association?". Irish Medical Journal 100 (2): 367–369. PMID 17432813. - ^ Coyle, YM; Minahjuddin AT, Hynan LS, Minna JD (September 2006). "An ecological study of the association of metal air pollutants with lung cancer incidence in Texas". Journal of Thoracic Oncology 1 (7): 654–661. doi:10.1097/01243894-200609000-00009. PMID 17409932. - ^ a b Chiu, HF; Cheng MH, Tsai SS et al. (December 2006). "Outdoor air pollution and female lung cancer in Taiwan". Inhalation Toxicology 18 (13): 1025–1031. doi:10.1080/08958370600904561. PMID 16966302. - ^ Carmona, RH (2006-06-27). "The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General". U.S. Department of Health and Human Services. http://www.surgeongeneral.gov/library/secondhandsmoke. "Secondhand smoke exposure causes disease and premature death in children and adults who do not smoke." - ^ "Tobacco Smoke and Involuntary Smoking" (PDF). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans (WHO International Agency for Research on Cancer) 83. 2002. http://monographs.iarc.fr/ENG/Monographs/vol83/volume83.pdf. "There is sufficient evidence that involuntary smoking (exposure to secondhand or 'environmental' tobacco smoke) causes lung cancer in humans. [...] Involuntary smoking (exposure to secondhand or 'environmental' tobacco smoke) is carcinogenic to humans (Group 1)." - ^ a b c d e f Vaporciyan, AA; Nesbitt JC, Lee JS et al. (2000). Cancer Medicine. B C Decker. pp. 1227–1292. ISBN 1-55009-113-1. - ^ Hamilton, W; Peters TJ, Round A, Sharp D (December 2005). "What are the clinical features of lung cancer before the diagnosis is made? A population based case-control study". Thorax (BMJ Publishing Group) 60 (12): 1059–1065. doi:10.1136/thx.2005.045880. PMC 1747254. PMID 16227326. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1747254. - ^ Honnorat, J; Antoine JC (May 2007). "Paraneoplastic neurological syndromes". Orphanet Journal of Rare Diseases (BioMed Central) 2 (1): 22. doi:10.1186/1750-1172-2-22. PMC 1868710. PMID 17480225. http://www.ojrd.com/content/2/1/22. - ^ Jones, DR; Detterbeck FC (July 1998). "Pancoast tumors of the lung". Current Opinion in Pulmonary Medicine 4 (4): 191–197. doi:10.1097/00063198-199807000-00001. PMID 10813231. - ^ Greene, Frederick L. (2002). AJCC cancer staging manual. Berlin: Springer-Verlag. ISBN 0-387-95271-3. - ^ Biesalski, HK; Bueno de Mesquita B, Chesson A et al. (1998). "European Consensus Statement on Lung Cancer: risk factors and prevention. Lung Cancer Panel". CA Cancer J Clin (Smoking is the major risk factor, accounting for about 90% of lung cancer incidence.) 48 (3): 167–176; discussion 164–166. doi:10.3322/canjclin.48.3.167. PMID 9594919. http://caonline.amcancersoc.org/cgi/pmidlookup?view=long&pmid=9594919. - ^ Hecht, S (October 2003). "Tobacco carcinogens, their biomarkers and tobacco-induced cancer". Nature Reviews. Cancer (Nature Publishing Group) 3 (10): 733–744. doi:10.1038/nrc1190. PMID 14570033. http://www.nature.com/nrc/journal/v3/n10/abs/nrc1190_fs.html. - ^ Sopori, M (May 2002). "Effects of cigarette smoke on the immune system". Nature Reviews. Immunology 2 (5): 372–7. doi:10.1038/nri803. PMID 12033743. - ^ Peto, R; Lopez AD, Boreham J et al. (2006). Mortality from smoking in developed countries 1950–2000: Indirect estimates from National Vital Statistics. Oxford University Press. ISBN 0-19-262535-7. http://www.ctsu.ox.ac.uk/~tobacco/. - ^ Samet, JM; Wiggins CL, Humble CG, Pathak DR (May 1988). "Cigarette smoking and lung cancer in New Mexico". American Review of Respiratory Disease 137 (5): 1110–1113. PMID 3264122. - ^ Villeneuve, PJ; Mao Y (November 1994). "Lifetime probability of developing lung cancer, by smoking status, Canada". Canadian Journal of Public Health 85 (6): 385–388. PMID 7895211. - ^ Chlebowski RT et al (2009). "Non-small cell lung cancer and estrogen plus progestin use in postmenopausal women in the Women's Health Initiative randomized clinical trial". Journal of Clinical Oncology 27 (155): CRA1500. - ^ US Department of Health and Human Services (1990-09-30). "The Health Benefits of Smoking Cessation: a Report of the Surgeon General" (PDF). Centers for Disease Control (CDC), Office on Smoking and Health.. pp. vi, 130, 148, 152, 155, 164, 166. http://profiles.nlm.nih.gov/NN/B/B/C/T/_/nnbbct.pdf. Retrieved 2007-11-18. - ^ Nordquist, LT; Simon GR, Cantor A et al. (August 2004). "Improved survival in never-smokers vs current smokers with primary adenocarcinoma of the lung". Chest (American College of Chest Physicians) 126 (2): 347–351. doi:10.1378/chest.126.2.347. PMID 15302716. http://www.chestjournal.org/cgi/content/full/126/2/347. - ^ Tammemagi, CM; Neslund-Dudas C, Simoff M, Kvale P (January 2004). "Smoking and lung cancer survival: the role of comorbidity and treatment". Chest (American College of Chest Physicians) 125 (1): 27–37. doi:10.1378/chest.125.1.27. PMID 14718417. http://www.chestjournal.org/cgi/content/full/125/1/27. - ^ Centers for Disease Control (CDC) (December 1986). "1986 Surgeon General's report: the health consequences of involuntary smoking". MMWR. Morbidity and mortality weekly report (CDC) 35 (50): 769–70. PMID 3097495. http://www.cdc.gov/mmwr/preview/mmwrhtml/00000837.htm. Retrieved 2007-08-10. * National Research Council (1986). Environmental tobacco smoke: measuring exposures and assessing health effects. National Academy Press. ISBN 0-309-07456-8. http://www.nap.edu/catalog.php?record_id=943#toc. * EPA (1992). Respiratory health effects of passive smoking: lung cancer and other disorders. EPA. http://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=2835. Retrieved 2007-08-10. * California Environmental Protection Agency (1997). "Health effects of exposure to environmental tobacco smoke. California Environmental Protection Agency". Tobacco Control 6 (4): 346–353. doi:10.1136/tc.6.4.346. PMC 1759599. PMID 9583639. http://www.druglibrary.org/schaffer/tobacco/caets/ets-main.htm. * CDC (December 2001). "State-specific prevalence of current cigarette smoking among adults, and policies and attitudes about secondhand smoke—United States, 2000". Morbidity and Mortality Weekly Report (Atlanta, Georgia: CDC) 50 (49): 1101–1106. PMID 11794619. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5049a1.htm. * Alberg, AJ; Samet JM (January 2003). "Epidemiology of lung cancer". Chest (American College of Chest Physicians) 123 (S1): 21S–49S. doi:10.1378/chest.123.1_suppl.21S. PMID 12527563. http://www.chestjournal.org/cgi/content/full/123/1_suppl/21S. - ^ Boffetta, P; Agudo A, Ahrens W et al. (October 1998). "Multicenter case-control study of exposure to environmental tobacco smoke and lung cancer in Europe". Journal of the National Cancer Institute (Oxford University Press) 90 (19): 1440–1450. doi:10.1093/jnci/90.19.1440. PMID 9776409. http://jnci.oxfordjournals.org/cgi/reprint/90/19/1440. [dead link] - ^ "Report of the Scientific Committee on Tobacco and Health". Department of Health. March 1998. http://www.archive.official-documents.co.uk/document/doh/tobacco/contents.htm. Retrieved 2007-07-09. * Hackshaw, AK (June 1998). "Lung cancer and passive smoking". Statistical Methods in Medical Research 7 (2): 119–136. doi:10.1191/096228098675091404. PMID 9654638. - ^ National Health and Medical Research Council (April 1994). The health effects and regulation of passive smoking. Australian Government Publishing Service. Archived from the original on September 29, 2007. http://web.archive.org/web/20070929025344/http://www.obpr.gov.au/publications/submission/healthef/index.html. Retrieved 2007-08-10. - ^ Schick, S; Glantz S (December 2005). "Philip Morris toxicological experiments with fresh sidestream smoke: more toxic than mainstream smoke". Tobacco Control 14 (6): 396–404. doi:10.1136/tc.2005.011288. PMC 1748121. PMID 16319363. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1748121. - ^ Thun, M.J., S.J. Henley, D Burns, et al., Lung cancer death rates in lifelong nonsmokers. J. Natl Cancer Inst, 2006. 98: p.691. - ^ Sun, S., J.H. Schiller and A.F. Gazdar, Lung cancer in never-smokers: A different disease. Nat Rev Cancer, 2007. 7: p.778-90. - ^ Schmid K, Kuwert T, Drexler H (March 2010). "Radon in Indoor Spaces: An Underestimated Risk Factor for Lung Cancer in Environmental Medicine". Dtsch Arztebl Int 107 (11): 181–6. doi:10.3238/arztebl.2010.0181. PMC 2853156. PMID 20386676. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2853156. - ^ EPA (October 2006). "Radiation information: radon". EPA. http://www.epa.gov/rpdweb00/radionuclides/radon.html. Retrieved 2007-08-11. - ^ Field, RW; Steck DJ, Smith BJ et al. (1 June 2000). "Residential radon gas exposure and lung cancer: the Iowa Radon Lung Cancer Study". American Journal of Epidemiology (Oxford Journals) 151 (11): 1091–1102. PMID 10873134. http://aje.oxfordjournals.org/cgi/reprint/151/11/1091. - ^ EPA (June 2000). "Iowa Radon Lung Cancer Study". EPA. http://www.epa.gov/radon/iowastudy.html. Retrieved 2007-08-11. [dead link] - ^ Darnton, AJ; McElvenny DM, Hodgson JT (January 2006). "Estimating the number of asbestos-related lung cancer deaths in Great Britain from 1980 to 2000". Annals of Occupational Hygiene 50 (1): 29–38. doi:10.1093/annhyg/mei038. PMID 16126764. http://annhyg.oxfordjournals.org/cgi/content/full/50/1/29. - ^ Leroux, C; Girard N, Cottin V et al. (March–April 2007). "Jaagsiekte Sheep Retrovirus (JSRV): from virus to lung cancer in sheep". Veterinary Research 38 (2): 211–228. doi:10.1051/vetres:2006060. PMID 17257570. - ^ Palmarini, M; Fan H (November 2001). "Retrovirus-induced ovine pulmonary adenocarcinoma, an animal model for lung cancer". Journal of the National Cancer Institute (Oxford University Press) 93 (21): 1603–1614. doi:10.1093/jnci/93.21.1603. PMID 11698564. http://jnci.oxfordjournals.org/cgi/content/full/93/21/1603. - ^ Cheng, YW; Chiou HL, Sheu GT et al. (1 April 2001). "The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women". Cancer Research (American Association for Cancer Research) 61 (7): 2799–2803. PMID 11306446. http://cancerres.aacrjournals.org/cgi/content/full/61/7/2799. - ^ Zheng, H; Aziz HA, Nakanishi Y et al. (May 2007). "Oncogenic role of JC virus in lung cancer". Journal of Pathology 212 (3): 306–315. doi:10.1002/path.2188. PMID 17534844. - ^ Giuliani, L; Jaxmar T, Casadio C et al. (September 2007). "Detection of oncogenic viruses (SV40, BKV, JCV, HCMV, HPV) and p53 codon 72 polymorphism in lung carcinoma". Lung Cancer 57 (3): 273–281. doi:10.1016/j.lungcan.2007.02.019. PMID 17400331. - ^ Pope, CA 3rd; Burnett RT, Thun MJ, Calle EE, Krewski D, Ito K, Thurston GD (2002). "Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution". Journal of the American Medical Association 287 (9): 1132–1141. doi:10.1001/jama.287.9.1132. PMID 11879110. http://jama.ama-assn.org/cgi/content/full/287/9/1132. - ^ Krewski D, Burnett R, Jerrett M, Pope CA, Rainham D, Calle E, Thurston G, Thun M (2005 Jul 9-23). "Mortality and long-term exposure to ambient air pollution: ongoing analyses based on the American Cancer Society cohort". J Toxicol Environ Health A 68 (13–14): 1093–109. doi:10.1080/15287390590935941. PMID 16024490. - ^ Valavanidis A, Fiotakis K, Vlachogianni T (2008 Oct-Dec). "Airborne particulate matter and human health: toxicological assessment and importance of size and composition of particles for oxidative damage and carcinogenic mechanisms". J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 26 (4): 339–62. doi:10.1080/10590500802494538. PMID 19034792. - ^ Fong, KM; Sekido Y, Gazdar AF, Minna JD (October 2003). "Lung cancer • 9: Molecular biology of lung cancer: clinical implications". Thorax (BMJ Publishing Group Ltd.) 58 (10): 892–900. doi:10.1136/thorax.58.10.892. PMC 1746489. PMID 14514947. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1746489. - ^ Salgia, R; Skarin AT (March 1998). "Molecular abnormalities in lung cancer". Journal of Clinical Oncology 16 (3): 1207–1217. PMID 9508209. - ^ a b c d Herbst, RS; Heymach JV, Lippman SM (September 2008). "Molecular origins of cancer: lung cancer". N Engl J Med 359 (13): 1367–1380. doi:10.1056/NEJMra0802714. PMID 18815398. http://content.nejm.org/cgi/content/full/359/13/1367. - ^ Aviel-Ronen, S; Blackhall FH, Shepherd FA, Tsao MS (July 2006). "K-ras mutations in non-small-cell lung carcinoma: a review". Clinical Lung Cancer (Cancer Information Group) 8 (1): 30–38. doi:10.3816/CLC.2006.n.030. PMID 16870043. - ^ Devereux, TR; Taylor JA, Barrett JC (March 1996). "Molecular mechanisms of lung cancer. Interaction of environmental and genetic factors". Chest (American College of Chest Physicians) 109 (Suppl 3): 14S–19S. doi:10.1378/chest.109.3_Supplement.14S. PMID 8598134. - ^ Engels, EA; Wu X, Gu J et al. (July 2007). "Systematic evaluation of genetic variants in the inflammation pathway and risk of lung cancer". Cancer Research (American Association for Cancer Research) 67 (13): 6520–6527. doi:10.1158/0008-5472.CAN-07-0370. PMID 17596594. - ^ Wenzlaff, AS; Cote ML, Bock CH et al. (December 2005). "CYP1A1 and CYP1B1 polymorphisms and risk of lung cancer among never smokers: a population-based study". Carcinogenesis (Oxford University Press) 26 (12): 2207–2212. doi:10.1093/carcin/bgi191. PMID 16051642. - ^ Son, JW; Kang HK, Chae MH et al. (September 2006). "Polymorphisms in the caspase-8 gene and the risk of lung cancer". Cancer Genetics and Cytogenetics 169 (2): 121–127. doi:10.1016/j.cancergencyto.2006.04.001. PMID 16938569. - ^ Yin, J; Vogel U, Ma Y et al. (May 2007). "The DNA repair gene XRCC1 and genetic susceptibility of lung cancer in a northeastern Chinese population". Lung Cancer 56 (2): 153–160. doi:10.1016/j.lungcan.2006.12.012. PMID 17316890. - ^ Tomoda K, Ohkoshi T, Hirota K, et al. (February 2009). "Preparation and properties of inhalable nanocomposite particles for treatment of lung cancer". Colloids and Surfaces B: Biointerfaces 71 (2): 177–82. doi:10.1016/j.colsurfb.2009.02.001. PMID 19264458. http://linkinghub.elsevier.com/retrieve/pii/S0927-7765(09)00055-1. - ^ Fan, YG; Hu P, Jiang Y, et al. (March 2009). "Association between sputum atypia and lung cancer risk in an occupational cohort in yunnan, china". Chest 135 (3): 778–85. doi:10.1378/chest.08-1469. PMID 19265088. - ^ a b Travis, WD; Travis LB, Devesa SS (January 1995). "Lung cancer". Cancer 75 (Suppl. 1): 191–202. doi:10.1002/1097-0142(19950101)75:1+<191::AID-CNCR2820751307>3.0.CO;2-Y. PMID 8000996. - ^ Morandi, U; Casali C, Rossi G (2006). "Bronchial typical carcinoid tumors". Seminars in Thoracic and Cardiovascular Surgery 18 (3): 191–198. doi:10.1053/j.semtcvs.2006.08.005. PMID 17185178. - ^ Etienne-Mastroianni, B; Falchero L, Chalabreysse L et al. (December 2002). "Primary sarcomas of the lung: a clinicopathologic study of 12 cases". Lung Cancer 38 (3): 283–289. doi:10.1016/S0169-5002(02)00303-3. PMID 12445750. - ^ Tan D, Zander DS (2008). "Immunohistochemistry for Assessment of Pulmonary and Pleural Neoplasms: A Review and Update". Int J Clin Exp Pathol 1 (1): 19–31. PMC 2480532. PMID 18784820. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2480532. - ^ Park SY, Kim BH, Kim JH, Lee S, Kang GH (October 2007). [1561:POIMHD2.0.CO;2 "Panels of immunohistochemical markers help determine primary sites of metastatic adenocarcinoma"]. Arch. Pathol. Lab. Med. 131 (10): 1561–7. doi:10.1043/1543-2165(2007)131[1561:POIMHD]2.0.CO;2. ISSN 1543-2165. PMID 17922593. http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2007)131[1561:POIMHD]2.0.CO;2. - ^ Bryant, A; Cerfolio RJ (July 2007). "Differences in epidemiology, histology, and survival between cigarette smokers and never-smokers who develop non-small cell lung cancer". Chest 132 (1): 198–192. doi:10.1378/chest.07-0442. PMID 17573517. http://www.chestjournal.org/cgi/content/full/132/1/185. - ^ Smokers defined as current or former smoker of more than 1 year of duration. Reference: - Table 2 in: Kenfield SA, Wei EK, Stampfer MJ, Rosner BA, Colditz GA (2008). "Comparison of Aspects of Smoking Among Four Histologic Types of Lung Cancer". Tob Control 17 (3): 198–204. doi:10.1136/tc.2007.022582. PMC 3044470. PMID 18390646. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3044470. - ^ a b Travis WD. Pathology of lung cancer. Clin Chest Med 2002;23:65-81 - ^ Subramanian, J; Govindan R (February 2007). "Lung cancer in never smokers: a review". Journal of Clinical Oncology (American Society of Clinical Oncology) 25 (5): 561–570. doi:10.1200/JCO.2006.06.8015. PMID 17290066. - ^ Raz, DJ; He B, Rosell R, Jablons DM (March 2006). "Bronchioloalveolar carcinoma: a review". Clinical Lung Cancer 7 (5): 313–322. doi:10.3816/CLC.2006.n.012. PMID 16640802. - ^ Lung cancer - small cell Medline Plus. Retrieved 5 February 2010. - ^ a b Collins, LG; Haines C, Perkel R, Enck RE (January 2007). "Lung cancer: diagnosis and management". American Family Physician (American Academy of Family Physicians) 75 (1): 56–63. PMID 17225705. http://www.aafp.org/afp/20070101/56.html. - ^ Rosti, G; Bevilacqua G, Bidoli P et al. (March 2006). "Small cell lung cancer". Annals of Oncology 17 (Suppl. 2): 5–10. doi:10.1093/annonc/mdj910. PMID 16608983. http://annonc.oxfordjournals.org/cgi/reprint/17/suppl_2/ii5. - ^ Barbone, F; Bovenzi M, Cavallieri F, Stanta G (December 1997). "Cigarette smoking and histologic type of lung cancer in men" (PDF). Chest (American College of Chest Physicians) 112 (6): 1474–1479. doi:10.1378/chest.112.6.1474. PMID 9404741. http://www.chestjournal.org/cgi/reprint/112/6/1474. - ^ Roggli VL, Vollmer RT, Greenberg SD, McGavran MH, Spjut HJ, Yesner R. Lung cancer heterogeneity: a blinded and randomized study of 100 consecutive cases. Hum Pathol 1985; 16: 569-79. - ^ a b Dishop MK, Kuruvilla S (July 2008). "Primary and metastatic lung tumors in the pediatric population: a review and 25-year experience at a large children's hospital". Arch. Pathol. Lab. Med. 132 (7): 1079–103. doi:10.1043/1543-2165(2008)132[1079:PAMLTI]2.0.CO;2. ISSN 1543-2165. PMID 18605764. http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=1079. - ^ Seo, JB; Im JG, Goo JM et al. (1 March 2001). "Atypical pulmonary metastases: spectrum of radiologic findings". Radiographics 21 (2): 403–417. PMID 11259704. http://radiographics.rsnajnls.org/cgi/content/full/21/2/403. - ^ Mountain, CF; Libfluffz HI, Hermes KE (2003). A Handbook for Staging, Imaging, and Lymph Node Classification. Charles P Young. http://www.ctsnet.org/book/mountain/index.html. Retrieved 2007-09-01. - ^ Vineis, P; Hoek G, Krzyzanowski M et al. (February 2007). "Lung cancers attributable to environmental tobacco smoke and air pollution in non-smokers in different European countries: a prospective study". Environmental Health (BioMed Central) 6: 7. doi:10.1186/1476-069X-6-7. PMC 1803768. PMID 17302981. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1803768. - ^ a b "A Decade of Broken Promises: The 1998 State Tobacco Settlement Ten Years Later" (PDF). Campaign for Tobacco-Free Kids. http://www.tobaccofreekids.org/reports/settlements/2009/fullreport.pdf. Retrieved 2008-12-03. - ^ Pandey, G (February 2005). "Bhutan's smokers face public ban". BBC. http://news.bbc.co.uk/2/hi/south_asia/4305715.stm. Retrieved 2007-09-07. - ^ Gray, N (February 2003). "A global approach to tobacco policy". Lung Cancer (BioMed Central) 39 (2): 113–117. doi:10.1016/S0169-5002(02)00456-7. PMID 12581561. - ^ Slatore, CG; Littman AJ, Au DH, Satia JA, White E (2008). "Long-Term Use of Supplemental Multivitamins, Vitamin C, Vitamin E, and Folate Does Not Reduce the Risk of Lung Cancer". American Journal of Respiratory and Critical Care Medicine 177 (5): 524–30. doi:10.1164/rccm.200709-1398OC. PMC 2258445. PMID 17989343. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2258445. - ^ Kushi LH, Byers T, Doyle C, Bandera EV, McCullough M, McTiernan A, et al. (2006). "American cancer society guidelines on nutrition and physical activity for cancer prevention: Reducing the risk of cancer with healthy food choices and physical activity". CA: A Cancer Journal for Clinicians 56 (5): 254–81. doi:10.3322/canjclin.56.5.254. - ^ "UN health agency calls for total ban on tobacco advertising to protect young" (Press release). United Nations News service. 30 May 2008. http://www.un.org/apps/news/story.asp?NewsID=26857. - ^ van Klaveren RJ, Oudkerk M, Prokop M, et al. (December 2009). "Management of lung nodules detected by volume CT scanning". N. Engl. J. Med. 361 (23): 2221–9. doi:10.1056/NEJMoa0906085. PMID 19955524. - ^ Gohagan, JK; Marcus PM, Fagerstrom RM et al. (January 2005). "Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer". Lung Cancer 47 (1): 9–15. doi:10.1016/j.lungcan.2004.06.007. PMID 15603850. - ^ a b Temel JS, Greer JA, Muzikansky A, et al. (August 2010). "Early palliative care for patients with metastatic non-small-cell lung cancer". N. Engl. J. Med. 363 (8): 733–42. doi:10.1056/NEJMoa1000678. PMID 20818875. http://www.nejm.org/doi/full/10.1056/NEJMoa1000678. - ^ Schiller JH, Vidaver RM, Novello S, Brahmer J, Monroe L (2007). "Living with a Diagnosis of Lung Cancer". [National Lung Cancer Partnership]. http://www.nationallungcancerpartnership.org/index.cfm?page=treatment. Retrieved 2008-12-01. - ^ Strand, TE; Rostad H, Damhuis RA, Norstein J (June 2007). "Risk factors for 30‐day mortality after resection of lung cancer and prediction of their magnitude". Thorax (BMJ Publishing Group) 62 (11): 991–7. doi:10.1136/thx.2007.079145. PMC 2117132. PMID 17573442. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2117132. - ^ El-Sherif, A; Gooding WE, Santos R et al. (August 2006). "Outcomes of sublobar resection versus lobectomy for stage I non-small cell lung cancer: a 13-year analysis". Annals of Thoracic Surgery 82 (2): 408–415. doi:10.1016/j.athoracsur.2006.02.029. PMID 16863738. - ^ Fernando, HC; Santos RS, Benfield JR et al. (February 2005). "Lobar and sublobar resection with and without brachytherapy for small stage IA non-small cell lung cancer". Journal of Thoracic and Cardiovascular Surgery 129 (2): 261–267. doi:10.1016/j.jtcvs.2004.09.025. PMID 15678034. - ^ Casali G, Walker WS (March 2009). "Video-assisted thoracic surgery lobectomy: can we afford it?". Eur J Cardiothorac Surg 35 (3): 423–8. doi:10.1016/j.ejcts.2008.11.008. PMID 19136272. - ^ Lennox SC, Flavell G, Pollock DJ, Thompson VC, Wilkins JL (November 1968). "Results of resection for oat-cell carcinoma of the lung". Lancet 2 (7575): 925–7. doi:10.1016/S0140-6736(68)91163-X. PMID 4176258. - ^ Fox W, Scadding JG (July 1973). "Medical Research Council comparative trial of surgery and radiotherapy for primary treatment of small-celled or oat-celled carcinoma of bronchus. Ten-year follow-up". Lancet 2 (7820): 63–5. doi:10.1016/S0140-6736(73)93260-1. PMID 4123619. - ^ Simon GR, Turrisi A (September 2007). "Management of small cell lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition)". Chest 132 (3 Suppl): 324S–339S. doi:10.1378/chest.07-1385. PMID 17873178. http://chestjournal.chestpubs.org/content/132/3_suppl/324S.long. - ^ Yang SC (October 2010). "Reversing the surgical stigma for small-cell lung cancer". Oncology (Williston Park, N.Y.) 24 (11): 1042–3. PMID 21155455. - ^ Hage R, Elbers JR, Brutel de la Rivière A, van den Bosch JM (June 1998). "Surgery for combined type small cell lung carcinoma". Thorax 53 (6): 450–3. doi:10.1136/thx.53.6.450. PMC 1745233. PMID 9713442. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1745233. - ^ Arriagada, R; Goldstraw P, Le Chevalier T (2002). Oxford Textbook of Oncology (2nd ed.). Oxford University Press. p. 2094. ISBN 0-19-262926-3. - ^ a b Saunders, M; Dische S, Barrett A et al. (July 1997). "Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small-cell lung cancer: a randomised multicentre trial". Lancet (Elsevier) 350 (9072): 161–165. doi:10.1016/S0140-6736(97)06305-8. PMID 9250182. - ^ Wagner, H (January 1998). "Radiation therapy in the management of limited small cell lung cancer: when, where, and how much?". Chest (American College of Chest Physicians) 113 (Suppl. 1): 92S–100S. doi:10.1378/chest.113.1_Supplement.92S. PMID 9438697. http://www.chestjournal.org/cgi/reprint/113/1/92S. [dead link] - ^ PORT Meta-analysis Trialists Group (2005). Rydzewska, Larysa. ed. "Postoperative radiotherapy for non-small cell lung cancer". Cochrane database of systematic reviews (Online) (2): CD002142. doi:10.1002/14651858.CD002142.pub2. PMID 15846628. http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD002142/frame.html. - ^ Lally, BE; Zelterman D, Colasanto JM et al. (July 2006). "Postoperative Radiotherapy for Stage II or III Non–Small-Cell Lung Cancer Using the Surveillance, Epidemiology, and End Results Database". Journal of Clinical Oncology (John Wiley & Sons) 24 (19): 2998–3006. doi:10.1200/JCO.2005.04.6110. PMID 16769986. http://jco.ascopubs.org/cgi/content/full/24/19/2998. - ^ Raben, A; Mychalczak B (October 1997). "Brachytherapy for non-small cell lung cancer and selected neoplasms of the chest". Chest (American College of Chest Physicians) 112 (Suppl. 4): 276S–286S. doi:10.1378/chest.112.4_Supplement.276S. PMID 9337304. http://www.chestjournal.org/cgi/reprint/112/4_Supplement/276S. - ^ Celebioglu, B; Gurkan OU, Erdogan S et al. (November 2002). "High dose rate endobronchial brachytherapy effectively palliates symptoms due to inoperable lung cancer". Japanese Journal of Clinical Oncology (Oxford University Press) 32 (11): 443–448. doi:10.1093/jjco/hyf102. PMID 12499415. http://jjco.oxfordjournals.org/cgi/content/full/32/11/443. - ^ Ng, M; Chong J, Milner A et al. (June 2007). "Tolerability of accelerated chest irradiation and impact on survival of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer: review of a single institution's experience". Journal of Thoracic Oncology (International Association for the Study of Lung Cancer) 2 (6): 506–513. doi:10.1097/JTO.0b013e318060095b. PMID 17545845. - ^ Slotman, B; Faivre-Finn C, Kramer G et al. (August 2007). "Prophylactic cranial irradiation in extensive small-cell lung cancer". New England Journal of Medicine 357 (7): 664–672. doi:10.1056/NEJMoa071780. PMID 17699816. http://content.nejm.org/cgi/content/full/357/7/664. - ^ Hof, H; Muenter M, Oetzel D et al. (July 2007). "Stereotactic single-dose radiotherapy (radiosurgery) of early stage nonsmall-cell lung cancer (NSCLC)". Cancer (Wiley InterScience) 110 (1): 148–155. doi:10.1002/cncr.22763. PMID 17516437. http://www3.interscience.wiley.com/cgi-bin/fulltext/114265991/PDFSTART. - ^ Hann CL, Rudin CM (2008-11-30). "Management of small-cell lung cancer: incremental changes but hope for the future". Oncology (Williston Park) 22 (13): 1486–92. PMID 19133604. - ^ Murray, N; Turrisi AT (March 2006). "A review of first-line treatment for small-cell lung cancer". Journal of Thoracic Oncology 1 (3): 270–278. PMID 17409868. - ^ Azim, HA; Ganti AK (March 2007). "Treatment options for relapsed small-cell lung cancer". Anticancer drugs 18 (3): 255–261. doi:10.1097/CAD.0b013e328011a547. PMID 17264756. - ^ MacCallum, C; Gillenwater HH (July 2006). "Second-line treatment of small-cell lung cancer". Current Oncology Reports 8 (4): 258–264. doi:10.1007/s11912-006-0030-8. PMID 17254525. - ^ Araujo AM, Mendez JC, Coelho AL, et al. (March 2009). "Phase II Study of Celecoxib with Cisplatin Plus Etoposide in Extensive-Stage Small Cell Lung Cancer". Cancer Invest. 27 (4): 391–6. doi:10.1080/07357900802232756. PMID 19266367. http://www.informaworld.com/openurl?genre=article&doi=10.1080/07357900802232756&magic=pubmed%7C%7C1B69BA326FFE69C3F0A8F227DF8201D0. - ^ Aggarwal C et al. (2010). "Biomarkers with predictive and prognostic function in non-small cell lung cancer: ready for prime time?". J Natl Compr Canc Netw 8: 822–32. - ^ Rosell, R; Moran, T; Queralt, C; Porta, R; Cardenal, F; Camps, C; Majem, M; Lopez-Vivanco, G et al. (2009). "Screening for epidermal growth factor receptor mutations in lung cancer". N Engl J Med 361 (10): 958–67. doi:10.1056/NEJMoa0904554. PMID 19692684. - ^ Mok TS et al. (2009). "Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma". N Engl J Med 361 (10): 947–57. doi:10.1056/NEJMoa0810699. PMID 19692680. - ^ Clegg, A; Scott DA, Hewitson P et al. (January 2002). "Clinical and cost effectiveness of paclitaxel, docetaxel, gemcitabine, and vinorelbine in non-small cell lung cancer: a systematic review". Thorax (BMJ Publishing Group) 57 (1): 20–28. doi:10.1136/thorax.57.1.20. PMC 1746188. PMID 11809985. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1746188. - ^ Sandler A, Gray R, Perry MC, et al. (2006). "Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer". N Engl J Med 355 (24): 2542–50. doi:10.1056/NEJMoa061884. PMID 17167137. - ^ Fuld AD, Dragnev KH, Rigas JR (June 2010). "Pemetrexed in advanced non-small-cell lung cancer". Expert Opin Pharmacother 11 (8): 1387–402. doi:10.1517/14656566.2010.482560. PMID 20446853. - ^ Scagliotti GV, Parikh P, von Pawel J, et al. (July 2008). "Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer". J. Clin. Oncol. 26 (21): 3543–51. doi:10.1200/JCO.2007.15.0375. PMID 18506025. - ^ Rossi A, Maione P, Bareschino MA, et al. (2010). "The emerging role of histology in the choice of first-line treatment of advanced non-small cell lung cancer: implication in the clinical decision-making". Curr. Med. Chem. 17 (11): 1030–8. doi:10.2174/092986710790820589. PMID 20156162. - ^ http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021743s14s16lbl.pdf - ^ a b http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm209058.htm - ^ FDA approves Xalkori with companion diagnostic for a type of late-stage lung cancer. U.S. Food and Drug Administration. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm269856.htm - ^ West HL, Franklin WA, McCoy J, et al. (2006). "Gefitinib therapy in advanced brochoalveolar carcinoma. Southwest Oncology Group study S0126". J Clin Oncol 24 (12): 1807–13. doi:10.1200/JCO.2005.04.9890. PMID 16622257. - ^ Miller VA, Riely GJ, Zakowski MF, et al. (2008). "Molecular characteristics of bronchoalveolar carcinoma and adenocarcinoma, brochoalveolar carcinoma subtype, predict response to erlotinib". J Clin Oncol 26 (9): 1472–8. doi:10.1200/JCO.2007.13.0062. PMID 18349398. - ^ Eaton KD, Martins RG (2010 Jul). "Maintenance chemotherapy in non-small cell lung cancer". J Natl Compr Canc Netw 8 (7): 815–21. PMID 20679540. - ^ Ciuleanu T, Brodowicz T, Zielinski C, et al. (2009). "Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study". The Lancet 374 (9699): 1432–40. doi:10.1016/S0140-6736(09)61497-5. PMID 19767093. - ^ Cappuzzo F, Ciuleanu T, Stelmakh L, et al. (2010). "Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study". Lancet Oncol 11 (6): 521–9. doi:10.1016/S1470-2045(10)70112-1. PMID 20493771. - ^ Fidias PM, Dakhil SR, Lyss AP, et al. (2009). "Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer". J Clin Oncol 27 (4): 591–8. doi:10.1200/JCO.2008.17.1405. PMID 19075278. - ^ Rossi A, Ricciardi S, Maione P, de Marinis F, Gridelli C (2009). "Pemetrexed in the treatment of advanced non-squamous lung cancer". Lung Cancer 66 (2): 141–9. doi:10.1016/j.lungcan.2009.06.006. PMID 19577816. - ^ Winton, T; Livingston R, Johnson D, et al. (June 2005). "Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer". New England Journal of Medicine (Massachusetts Medical Society) 352 (25): 2589–2597. doi:10.1056/NEJMoa043623. PMID 15972865. "Adjuvant vinorelbine plus cisplatin has an acceptable level of toxicity and prolongs disease-free and overall survival among patients with completely resected early-stage non-small-cell lung cancer." - ^ Douillard, JY; Rosell R, De Lena M et al. (September 2006). "Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial". Lancet Oncology (Elsevier) 7 (9): 719–727. doi:10.1016/S1470-2045(06)70804-X. PMID 16945766. - ^ Tsuboi, M; Ohira T, Saji H et al. (April 2007). "The present status of postoperative adjuvant chemotherapy for completely resected non-small cell lung cancer" (PDF). Annals of Thoracic and Cardiovascular Surgery 13 (2): 73–77. PMID 17505412. http://www.atcs.jp/pdf/2007_13_2/73.pdf. - ^ Olaussen KA, Dunant A, Fouret P, et al: DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 2006;355:983-991 - ^ Horn, L; Sandler AB, Putnam JB Jr, Johnson DH (May 2007). "The rationale for adjuvant chemotherapy in stage I non-small cell lung cancer". Journal of Thoracic Oncology 2 (5): 377–383. doi:10.1097/01.JTO.0000268669.64625.bb. PMID 17473651. - ^ Wakelee, HA; Schiller JH, Gandara DR (July 2006). "Current status of adjuvant chemotherapy for stage IB non-small-cell lung cancer: implications for the New Intergroup Trial". Clinical Lung Cancer (Cancer Information Group) 8 (1): 18–21. doi:10.3816/CLC.2006.n.028. PMID 16870041. - ^ BMJ (December 2005). Clinical evidence concise : the international resource of the best available evidence for effective health care.. London: BMJ Publishing Group. pp. 486–488. ISBN 1-905545-00-2. ISSN 1475-9225. - ^ Simon, CJ; Dupuy DE, DiPetrillo TA et al. (April 2007). "Pulmonary radiofrequency ablation: long-term safety and efficacy in 153 patients". Radiology 243 (1): 268–275. doi:10.1148/radiol.2431060088. PMID 17392258. - ^ Bakitas M, Lyons KD, Hegel MT, et al. (August 2009). "Effects of a palliative care intervention on clinical outcomes in patients with advanced cancer: the Project ENABLE II randomized controlled trial". JAMA 302 (7): 741–9. doi:10.1001/jama.2009.1198. PMID 19690306. - ^ Connor SR, Pyenson B, Fitch K, Spence C, Iwasaki K (March 2007). "Comparing hospice and nonhospice patient survival among patients who die within a three-year window". J Pain Symptom Manage 33 (3): 238–46. doi:10.1016/j.jpainsymman.2006.10.010. PMID 17349493. - ^ Kelley AS, Meier DE (August 2010). "Palliative care--a shifting paradigm". N. Engl. J. Med. 363 (8): 781–2. doi:10.1056/NEJMe1004139. PMID 20818881. - ^ a b Prince-Paul M (April 2009). "When hospice is the best option: an opportunity to redefine goals". Oncology (Williston Park, N.Y.) 23 (4 Suppl Nurse Ed): 13–7. PMID 19856592. - ^ Marino P, Pampallona S, Preatoni A, Cantoni A, Invernizzi F (September 1994). "Chemotherapy vs supportive care in advanced non-small-cell lung cancer. Results of a meta-analysis of the literature". Chest 106 (3): 861–5. doi:10.1378/chest.106.3.861. PMID 7521815. - ^ Souquet PJ, Chauvin F, Boissel JP, Bernard JP (April 1995). "Meta-analysis of randomised trials of systemic chemotherapy versus supportive treatment in non-resectable non-small cell lung cancer". Lung Cancer 12 Suppl 1: S147–54. doi:10.1016/0169-5002(95)00430-9. PMID 7551923. - ^ Sörenson S, Glimelius B, Nygren P (2001). "A systematic overview of chemotherapy effects in non-small cell lung cancer". Acta Oncol 40 (2–3): 327–39. PMID 11441939. - ^ Clegg A, Scott DA, Sidhu M, Hewitson P, Waugh N (2001). "A rapid and systematic review of the clinical effectiveness and cost-effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine in non-small-cell lung cancer". Health Technol Assess 5 (32): 1–195. PMID 12065068. - ^ NSCLC Meta-Analyses Collaborative Group (October 2008). "Chemotherapy in Addition to Supportive Care Improves Survival in Advanced Non–Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data From 16 Randomized Controlled Trials". J. Clin. Oncol. 26 (28): 4617–25. doi:10.1200/JCO.2008.17.7162. PMC 2653127. PMID 18678835. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2653127. - ^ Non-Small Cell Lung Cancer Collaborative Group (2010). Burdett, Sarah. ed. "Chemotherapy and supportive care versus supportive care alone for advanced non-small cell lung cancer". Cochrane Database of Systematic Reviews (5): CD007309. doi:10.1002/14651858.CD007309.pub2. PMID 20464750. - ^ "Non-Small Cell Lung Cancer Treatment". PDQ for Health Professionals. National Cancer Institute. http://www.cancer.gov/cancertopics/pdq/treatment/non-small-cell-lung/HealthProfessional/page2. Retrieved 2008-11-22. - ^ "-Small Cell Lung Cancer Treatment". PDQ for Health Professionals. National Cancer Institute. http://www.cancer.gov/cancertopics/pdq/treatment/small-cell-lung/healthprofessional. Retrieved 2008-11-22. - ^ Mountain, CF (1997). "Revisions in the international system for staging lung cancer" (PDF). Chest (American College of Chest Physicians) 111 (6): 1710–1717. doi:10.1378/chest.111.6.1710. PMID 9187198. http://www.chestjournal.org/cgi/reprint/111/6/1710. - ^ SEER data (SEER.cancer.gov) Median Age of Cancer Patients at Diagnosis 2002-2003 - ^ SEER data (SEER.cancer.gov) Median Age of Cancer Patients at Death 2002-2006 - ^ "WHO Disease and injury country estimates". World Health Organization. 2009. http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html. Retrieved November 11, 2009. - ^ Jemal, A; Bray, F, Center, MM, Ferlay, J, Ward, E, Forman, D (2011-02-04). "Global cancer statistics". CA: a cancer journal for clinicians 61 (2): 69–90. doi:10.3322/caac.20107. PMID 21296855. - ^ "Commonly diagnosed cancers worldwide". Cancer Research UK. April 2005. http://info.cancerresearchuk.org/cancerstats/geographic/world/commoncancers/. Retrieved 2008-01-11. - ^ Jemal, A., R.C. Tiwari, T. Murray, A. Ghafoor, A. Samuels, El. Ward, E.J. Feuer, and M.J. Thun, Cancer statistics, 2004. CA Cancer J Clin, 2004. 54(1): p.8-29. - ^ Lum, KL; Polansky JR, Jackler RK, Glantz SA (October 2008). "Signed, sealed and delivered: "big tobacco" in Hollywood, 1927–1951". Tobacco Control 17 (5): 313–323. doi:10.1136/tc.2008.025445. PMC 2602591. PMID 18818225. http://tobaccocontrol.bmj.com/cgi/content/full/17/5/313. - ^ "Deadly in Pink". Tobaccofreekids.org. http://www.tobaccofreekids.org/reports/women/. Retrieved 2010-09-26. - ^ Parent, ME; Rousseau MC, Boffetta P et al. (January 2007). "Exposure to diesel and gasoline engine emissions and the risk of lung cancer". American Journal of Epidemiology 165 (1): 53–62. doi:10.1093/aje/kwj343. PMID 17062632. - ^ National Cancer Institute; SEER stat fact sheets: Lung and Bronchus. Surveillance Epidemiology and End Results. 2010 - ^ "Gender in lung cancer and smoking research" (PDF). World Health Organization. 2004. http://www.who.int/gender/documents/en/lungcancerlow.pdf. Retrieved 2007-05-26. - ^ Liu, BQ; Peto R, Chen ZM et al. (1998-11-21). "Emerging tobacco hazards in China: 1. Retrospective proportional mortality study of one million deaths". British Medical Journal 317 (7170): 1411–1422. PMC 28719. PMID 9822393. http://www.bmj.com/cgi/content/full/317/7170/1411. - ^ Behera, D; Balamugesh T (2004). "Lung cancer in India" (PDF). Indian Journal of Chest Diseases and Allied Sciences 46 (4): 269–281. PMID 15515828. http://www.vpci.org.in/upload/Journals/pic130.pdf#page=27. - ^ Mohr, SB; Garland CF, Gorham ED et al. (2008). "Could ultraviolet B irradiance and vitamin D be associated with lower incidence rates of lung cancer?". Journal of Epidemiology and Community Health 62 (1): 69–74. doi:10.1136/jech.2006.052571. PMID 18079336. - ^ a b Chen, F; Bina WF, Cole P (April 2007). "Declining incidence rate of lung adenocarcinoma in the United States". Chest 131 (4): 1000–1005. doi:10.1378/chest.06-1695. PMID 17426202. http://www.chestjournal.org/cgi/content/full/131/4/1000. - ^ Charloux, A; Quoix E, Wolkove N et al. (February 1997). "The increasing incidence of lung adenocarcinoma: reality or artefact? A review of the epidemiology of lung adenocarcinoma". International Journal of Epidemiology 26 (1): 14–23. doi:10.1093/ije/26.1.14. PMID 9126499. http://ije.oxfordjournals.org/cgi/reprint/26/1/14. - ^ Singh N, Aggarwal AN, Gupta D, et al. Unchanging clinico-epidemiological profile of lung cancer in North India over three decades. Cancer Epidemiol 2010; 34(1): 101-104 - ^ Rawat J, Sindhwani G, Gaur D, et al. Clinico-pathological profile of lung cancer in Uttarakhand. Lung India. 2009 Jul;26(3):74-6. - ^ Khan NA, Afroz F, Lone MM, et al. Profile of lung cancer in Kashmir, India: a five-year study.Indian J Chest Dis Allied Sci. 2006 Jul-Sep;48(3):187-90. - ^ Morgagni, Giovanni Battista (1761). De sedibus et causis morborum per anatomen indagatis. http://books.google.com/?id=A3IFAAAAQAAJ&printsec=frontcover&dq=editions:0gslDCsk4Fm2hLne. - ^ Bayle, Gaspard-Laurent (1810) (in French). Recherches sur la phtisie pulmonaire. Paris. - ^ a b Witschi, H (November 2001). "A short history of lung cancer". Toxicological Sciences 64 (1): 4–6. doi:10.1093/toxsci/64.1.4. PMID 11606795. http://toxsci.oxfordjournals.org/cgi/content/full/64/1/4. - ^ Adler, I (1912). Primary Malignant Growths of the Lungs and Bronchi. New York: Longmans, Green, and Company. OCLC 14783544. , cited in Spiro SG, Silvestri GA (2005). "One hundred years of lung cancer". American Journal of Respiratory and Critical Care Medicine 172 (5): 523–529. doi:10.1164/rccm.200504-531OE. PMID 15961694. - ^ Grannis, FW. "History of cigarette smoking and lung cancer". smokinglungs.com. Archived from the original on July 18, 2007. http://web.archive.org/web/20070718174754/http://www.smokinglungs.com/cighist.htm. Retrieved 2007-08-06. - ^ Proctor, R (2000). The Nazi War on Cancer. Princeton University Press. pp. 173–246. ISBN 0-691-00196-0. - ^ Doll, R; Hill AB (November 1956). "Lung Cancer and Other Causes of Death in Relation to Smoking". British Medical Journal 2 (5001): 1071–1081. doi:10.1136/bmj.2.5001.1071. PMC 2035864. PMID 13364389. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2035864. - ^ US Department of Health Education and Welfare (1964). "Smoking and health: report of the advisory committee to the Surgeon General of the Public Health Service" (PDF). Washington, DC: US Government Printing Office. http://profiles.nlm.nih.gov/NN/B/B/M/Q/_/nnbbmq.pdf. - ^ Pirozynski, M (December 2006). "100 years of Lung Cancer". Respiratory Medicine 100 (12): 2073–2084. doi:10.1016/j.rmed.2006.09.002. PMID 17056245. - ^ Greaves, M (2000). Cancer: the Evolutionary Legacy. Oxford University Press. pp. 196–197. ISBN 0-19-262835-6. - ^ Horn, L; Johnson DH (July 2008). "Evarts A. Graham and the first pneumonectomy for lung cancer". Journal of Clinical Oncology 26 (19): 3268–3275. doi:10.1200/JCO.2008.16.8260. PMID 18591561. http://jco.ascopubs.org/cgi/pdf_extract/26/19/3268. - ^ Edwards, AT (1946). "Carcinoma of the Bronchus". Thorax 1 (1): 1–25. doi:10.1136/thx.1.1.1. PMC 1018207. PMID 20986395. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1018207. - ^ Kabela, M (1956). "[Experience with radical irradiation of bronchial cancer]" (in German). Ceskoslovenská Onkológia 3 (2): 109–115. PMID 13383622. - ^ Lennox, SC; Flavell G, Pollock DJ et al. (November 1968). "Results of resection for oat-cell carcinoma of the lung". Lancet (Elsevier) 2 (7575): 925–927. doi:10.1016/S0140-6736(68)91163-X. PMID 4176258. - ^ Miller, AB; Fox W, Tall R (September 1969). "Five-year follow-up of the Medical Research Council comparative trial of surgery and radiotherapy for the primary treatment of small-celled or oat-celled carcinoma of the bronchus". Lancet (Elsevier) 2 (7619): 501–505. doi:10.1016/S0140-6736(69)90212-8. PMID 4184834. - ^ Cohen, M; Creaven PJ, Fossieck BE Jr et al. (1977). "Intensive chemotherapy of small cell bronchogenic carcinoma". Cancer Treatment Reports 61 (3): 349–354. PMID 194691. - Detailed guide: Lung cancer - small cell American Cancer Society - Detailed guide: Lung cancer - non-small cell American Cancer Society - 1957 Film on link between smoking and lung cancer Early video on smoking and lung cancer - Lung cancer tutorial ChestRadiology.net - Lung cancer at the Open Directory Project - LungCancer.org — free resources and support services - Lung cancer National Cancer Institute - Tobacco smoke and involuntary smoking, summary of data reported and evaluation (2004) IARC - Lung Cancer Articles & Information Stop smoking articles & information at National Institutes of Health - Medical Encyclopedia WebMD: Lung Cancer Health Center - Medical Encyclopedia MayoClinic: Lung cancer - Clinically reviewed lung cancer information for patients, from Cancer Research UK Tumors: Mediastinal tumors/Thoracic neoplasm/respiratory neoplasia (C30–C34/D14, 160–163/212.0–212.4) Upper RT Lower RTTracheal tumorLungNon-carcinomaBy location Pleura Wikimedia Foundation. 2010.	2	100	24	12	3	0.664776	39	23,626
This week, several national news organizations ran a story on a new CDC study which showed rural Americans were more likely to die from the top 5 causes of death than their urban counterparts. Per the study, “the five leading causes of death in the United States during 1999–2014 were heart disease, cancer, unintentional injury, chronic lower respiratory disease, and stroke”. While the report results shocked, the data upon which the conclusion is based is deeply flawed, containing a statistical error–an error which my investigation found to be contained in other far more critical HHS reports provided by mandate to the President and Congress. In short, the error result is a significant over-inflation of the mortality burden of heart disease in America while under-reporting the impact of venous thromboembolism. To understand the life-and-death implications of how one tiny error can cascade throughout the health system without question, first let’s clearly define what we mean by these two medical terms, both in lay terms and in statistical analysis. What is considered heart disease? When you hear the term ‘heart disease’, what do you think of? Heart attack and cardiac arrest, right? That’s also what our health agencies educate the public. From the NIH’s National Heart, Lung, and Blood Institute: “Coronary heart disease—often simply called heart disease—is the main form of heart disease. It is a disorder of the blood vessels of the heart that can lead to heart attack. A heart attack happens when an artery becomes blocked, preventing oxygen and nutrients from getting to the heart. Heart disease is one of several cardiovascular diseases, which are diseases of the heart and blood vessel system. Other cardiovascular diseases include stroke, high blood pressure, angina (chest pain), and rheumatic heart disease.” Clinical researchers define heart disease more precisely using the International Classification of Diseases, Tenth Revision (ICD-10), a system used by healthcare providers to code all diagnoses and procedures. All Health Insurance Portability and Accountability Act-covered entities are mandated by the U.S Department of Health and Human Services to use this classification system. It’s primary application is for billing and reimbursement purposes, but the data collected also provides epidemiological researchers a way to look for the incidence and distribution of specific medical conditions. Here’s how the CDC researchers in the referenced study used ICD-10 codes to define ‘heart disease’: Heart disease here is defined as ICD-10 codes: I00-I09, I11, I13, and I20–I51. The problem with this definition is that these ICD-10 codes capture far more than merely heart attack and cardiac arrest. For example, this range includes code I26, the code for pulmonary embolism. A pulmonary embolism (PE) is a blood clot in the lung. Per the NIH National Heart, Lung and Blood Institute: “PE most often is a complication of a condition called deep vein thrombosis (DVT). In DVT, blood clots form in the deep veins of the body—most often in the legs. These clots can break free, travel through the bloodstream to the lungs, and block an artery.” “If a blood clot is large, or if there are many clots, PE can cause death.” While a pulmonary embolism is a blood clot which lodges in a pulmonary artery of the lung to block blood flow, it’s etiology is venous. “A PE occurs when a blood clot breaks off from a DVT and travels through the blood stream, traversing the right atrium and right ventricle, and lodging in the lung.” Why is this distinction important? Because…. All blood clots are not equal Clots in arteries and clots in veins have different risk factors, treatments and risks for recurrence. They are therefore prevented in different ways. - Blood clots which form in arteries lead to: stroke, TIA (mini-stroke), heart attack (myocardial infarction), and peripheral arterial clots. - Blood clots which form in veins lead to: venous thromboembolism (VTE) which is a term used for both pulmonary embolism-PE (lung clot) and deep vein thrombosis-DVT (most commonly leg). VTE = DVT + PE. Why this matters: follow the money In practical terms, if you are a public health official and you want to design a program to prevent blood clots, you’ll need a very different educational tact for tackling heart attack and stroke (arterial clots) than you will deep vein thrombosis and pulmonary embolism (venous clots). Different causes = different prevention strategies. For a heart attack prevention program, you’d focus your educational outreach on risk factors such as cholesterol, blood pressure, obesity, and smoking. For VTE prevention, you’d focus education on risk factors such as hospitalization, cancer, pregnancy, oral contraceptive use and travel. Very different messages. Very different audiences to educate. Even though the CDC includes pulmonary embolism in the ICD-10 codes it pulls to define ‘heart disease’, in policy practice, PE is excluded from heart disease prevention efforts. The CDC has an entire division dedicated to heart disease and the prevention of heart attack and stroke–the Division for Heart Disease and Stroke Prevention. Absolutely no where will you find a single mention of pulmonary embolism on the Divisions’s website–no prevention information, no programs in place, no resources allocated. This exclusion simply reflects how most non-researchers think of what constitutes ‘heart disease’–it is heart attack and stroke, not deep vein thrombosis or pulmonary embolism. Yet because researchers do include pulmonary embolism in their statistical definitions of ‘heart disease’, their data over-inflates both the incidence and burden of true heart disease (heart attack and stroke) while downplaying the significance of PE and it’s underlying cause, DVT. The data makes heart disease look much bigger than it is which translates into a stronger policy case for tax-funded programs aimed at heart disease…which in practice are programs exclusively targeting heart attack and stroke. A widespread error in numerous reports used by the President, Congress, reporters and the public The flawed definition of ‘heart disease’ is not limited to this week’s small CDC report. The same definition appears in the 461 page benchmark report, Health, United States, 2015, “submitted by the Secretary of the Department of Health and Human Services to the President and the Congress of the United States in compliance with Section 308 of the Public Health Service Act”. This mandated report is compiled annually by the CDC to present national trends in health statistics. It’s data, provided by the CDC Center for Health Statistics, is often used to make the cases for many critical policy and funding decisions. This report, and the companion monthly vital statistics data update reports, do not present all causes of death, but rather only 113 select causes of death. VTE is not one of them, but heart disease is. Unfortunately, heart disease is also wrongly defined in these reports by including the ICD-10 codes for pulmonary embolism. To sum: The key reports provided to the President and Congress for the purpose of making critical health policy and funding decisions are flawed. It overstates the burden of heart disease and under-reports deadly, preventable pulmonary embolism. What are the true top 5 causes of death? Because pulmonary embolism is wrapped up in the statistical definition of ‘heart disease’, it does not get it’s own attribution as a ’cause of death’. If VTE were pulled out and reported separately, where might it rank? The CDC estimates upwards of 900,000 new VTE cases each year, with 300,000 deaths from pulmonary embolism. This would place VTE among the top 3 causes of death…more than AIDS, breast cancer and car accidents combined. VTE deaths in America even exceed (by 26 times more!) those due to firearm homicides which we hear more about, which the CDC places at 11,208. Even opiods–which just weeks ago in December 2016 both President Obama and CDC Director Thomas Freiden called ‘an epidemic’–kills far fewer persons at 52,000 Americans annually. Another implication: if you take away the pulmonary embolism cases from the ‘heart disease’ category, then cancer would move up the list as a cause of death, likely making it the true #1 cause of death among Americans rather than heart disease. Implication: A public health threat goes ignored That heart disease figures are over-stated might not be cause for alarm if VTE was being addressed in other meaningful ways. It isn’t. The CDC’s FY 2017 Congressional budget justification includes $87 million by name for two other thrombotic conditions, heart disease and stroke, there is no line-item specifically for VTE which by the CDC’s own mortality figures, kills more Americans annually than stroke While there is no line-item funding allocation for VTE as you find with other conditions and it’s not included in the mission of the Division for Heart Disease and Stroke Prevention, that is not to say there is not some effort to address VTE by the CDC within its budgetary constraints. Found within the CDC National Center on Birth Defects and Developmental Disabilities (NCBDDD) is a $4.5 million line-item titled “Public Health Approach to Blood Disorders”. It is from a portion of these funds and within this division that current CDC efforts to address VTE arise. Past efforts have included creating a Flickr album of patient stories and hosting a webinar for health care professionals. As a VTE survivor and thrombosis educator, I was pleased to contribute to both these educational efforts. However, despite good intentions to do the most possible with the available resources, we must admit that these are relatively low-impact, virtual based efforts when held in comparison to the more interventional-type methodologies employed to address other preventable medical conditions. For comparison, take a look at the national, hands-on network of programs the CDC has implemented for stroke. Impact on public perceptions and lives A consequence of the current flawed methodology is that it is difficult to advocate for what isn’t reported correctly. What is reported widely as the ‘top causes of death’ influences public perceptions and more importantly, it impacts where policymakers choose to focus limited public health funding. If we want to call VTE ‘heart disease’, fine, but then our public health agencies whose mission is to tackle heart disease should be utilizing their funds to develop VTE prevention programs. But to present a false picture to the public (and funding lawmakers) of the burdens of both heart disease and venous thromboembolism…well, that’s just plain wrong and people are dying as a result. How? Because funds are not being invested on conditions where they are truly most needed. Most VTE are preventable. Nearly a third of VTE result in death. The Agency for Healthcare Research and Quality (AHRQ) calls VTE “the most common preventable cause of hospital death”. There are effective prevention, diagnostic and treatment strategies. Yet, it is hard to argue that VTE is a serious problem which needs funding and dedicated efforts when it doesn’t even show up on on the most commonly utilized and widely distributed lists of causes of death and disability. I do not like to point out a problem without offering a solution. A 2008 Surgeon General Call to Action report found VTE was “a major public health problem, exacting a significant human and economic toll on the Nation”. The report found gaps existed in the systematic application of clinical knowledge and that the condition itself suffered from low public awareness….both ideal preconditions for a coordinated public health intervention to have impact. But we’re so far off from where we need to be that it is going to take funding attached to a Congressional mandate to create one. While we would like to ideally think that our public health agencies prioritize those medical conditions which pose the greatest threat to American’s morbidity and mortality, this is not the case. While there are effective strategies to prevent and treat VTE, it is a largely ignored public health concern. CDC is the agency charged with protecting the public health from preventable conditions. The problem with the current CDC approach to VTE is 2 fold: - VTE is not a blood disorder. It is also not heart disease. VTE is a cardiovascular event. There are identifiable risk factors for VTE–such as hospitalization, immobility, cancer, long-distance travel, oral contraceptives, pregnancy, advanced age. So it doesn’t fit neatly within the mission scope and skill set of an administrative unit at CDC which primarily addresses conditions acquired at birth, which is where the topic is languishing now. To capitalize on existing expertise and tap economies of scale, it should be addressed by the same administrative unit as the other 2 major thrombosis-related conditions–heart disease and stroke–within the National Center for Chronic Disease Prevention and Health Promotion. - Because VTE is not mentioned by name, with a line-item expressly for it, funds in the ‘Public Health Approach to Blood Disorders’ line can easily be diverted and utilized on non-VTE educational activities, which has been seen in past years. The only way to ensure funds are utilized for VTE is for it to have its own, clearly named line-item allocation. To clean up our health data and target VTE, the President and Congress need to: - Establish a task force (as has been done for other conditions) to review, consolidate and coordinate all US VTE efforts across federal agency stakeholders–CDC, CMS, AHRQ, NIH, FDA, HRSA, Veterans Affairs, Rural Health. Currently, efforts are siloed reflecting a lack of cross-agency collaboration. - Make a clearly named VTE line-item funding allocation. - Funds should carry the mandate that they can only be utilized for VTE, prohibiting the ability to divert funds towards other conditions. - A clear line of reporting and accountability should be implemented with attached funds to ensure results. - If it is determined that CDC should maintain responsibility for public health prevention of VTE, then a clearly named VTE line-item funding allocation must be made within the same CDC administrative unit that addresses other thrombotic conditions–the National Center for Chronic Disease Prevention and Health Promotion. If another agency is chosen, VTE should be paired with related thrombotic conditions to take advantage of existing expertise. If VTE is going to be statistically treated like heart disease, it should get the corresponding resources to go with it. - Establish a work group to review current health data reports and decide upon a consistent methodology for data definitions. I recognized the coding issue with pulmonary embolism because I know this condition very well, but it calls into question…could there be flaws in the definitions of other medical conditions? We have become such a data-driven system for decision making, we need to have confidence in the quality of the data. A thorough review and revision is in order. - Moy E, Garcia MC, Bastian B, et al. Leading Causes of Death in Nonmetropolitan and Metropolitan Areas — United States, 1999–2014. MMWR Surveill Summ 2017;66(No. SS-1):1–8. DOI: http://dx.doi.org/10.15585/mmwr.ss6601a1. I corresponded with the CDC study author, Dr. Enest Moy, who was promptly responsive, polite and helpful (emails copied below). He confirmed that indeed, the codes for pulmonary embolism are included in the statistical definition of heart disease. However I’m told the fix may be difficult and their data shows that even if PE were pulled out separately it would only account for 7,000-9,000 deaths which is far fewer than reported by other HHS agencies (CDC,AHRQ,CMS)and independent academic researchers funded by HHS (CDC,NIH) to study the epidemiology and incidence of VTE.(Significant CDC and NIH funded work in the field of modeling VTE incidence data has been led by Dr John Heit of the Mayo Clinic, see publication citation) Without digging further to understand the disparity, I cannot say for certain why different agencies have different death figures, but clearly not all these figures can be correct…the disparity is too wide. I suspect the difference may be due to how a cause of death is defined between various datasets. Additionally, death certificate data is notoriously inaccurate when it comes to pulmonary embolism. Again, I cannot say based upon the information at hand, but this makes a stronger case for my recommendation #3: that a consistent methodology is needed across federal health data reports. If we’re making policy and funding decisions based upon data, we need clean, trustworthy data. At the moment, I don’t have full confidence in the data I’ve seen. BW	2	9	1	0	4	0.970474	5	3,645

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