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November 9, 2009 Coding for Cerebral Infarction For The Record Vol. 21 No. 21 P. 24 A cerebral infarction (ICD-9-CM code 434.91), also called a stroke or cerebrovascular accident (CVA), occurs when the blood supply to a part of the brain is slowed or interrupted and brain tissue is deprived of oxygen and nutrients, causing cells to die. Major risk factors include hypertension, smoking, and elevated cholesterol levels, but prompt treatment can decrease the complications and damage. There are two major types of stroke: ischemic and hemorrhagic. (Code assignment may change based on stroke type.) During an ischemic stroke, not enough blood reaches the brain because arteries are blocked or narrowed. Common ischemic strokes include thrombotic stroke (434.01), or the formation of a blood clot in an artery that supplies blood to the brain, and embolic stroke (434.11), which occurs when the blood clot breaks off and travels through the bloodstream to a vessel that feeds the brain. Atrial fibrillation is a common cause of embolic strokes. If the CVA is caused by an occlusion, narrowing, or stenosis of a precerebral artery, a code from category 433 is assigned. Common precerebral arteries include the basilar, carotid, and vertebral. The fifth digit of 1 is assigned to show that the occlusion/stenosis caused the CVA. The physician must document that the stroke occurred as a result of the occlusion or stenosis before the fifth digit of 1 can be assigned. The infarction is of the artery specified and for the current episode of care (AHA Coding Clinic for ICD-9-CM, 1995, second quarter, pages 14-15). A hemorrhagic stroke occurs when a blood vessel in the brain leaks or ruptures. Common types include intracerebral (431), subarachnoid (430), extradural/epidural (432.0), and subdural hemorrhages (432.1). Common stroke symptoms include the loss of balance or coordination; dizziness; slurred speech; aphasia; paralysis, numbness, or weakness on one side of the body; blurred, double, or blackened vision; and sudden, severe headache. It is appropriate to code residuals from a new CVA when the residual is still present at the time of discharge (AHA Coding Clinic for ICD-9-CM, 1989, second quarter, page 8). A transient ischemic attack (TIA) is a temporary interruption of the blood flow to the brain. The signs and symptoms are the same as a stroke but last for a shorter period of time, usually minutes to 24 hours, with no residual effects. Because it is difficult to decipher whether someone is experiencing a TIA or a CVA, the physician’s initial impression may well be TIA vs. CVA. For a CVA/infarct, the coder should review the medical record for neurological deficits lasting longer than 24 hours, a CT scan showing a new area of infarction or hemorrhage, and a discharge order to rehabilitation where there is no other rationale for rehab. Final code assignment is based on physician documentation, so if there is conflicting or vague documentation, query the physician for clarification. TIA defaults to code 435.9. If the physician links a patient’s TIA to a specific precerebral artery, assign the more specific diagnosis code (eg, 433.10, TIA due to carotid stenosis). Reversible ischemic neurologic deficit (RIND) describes a CVA in which deficits such as hemiplegia, dysphagia, and slurred speech last longer than those associated with a TIA and may persist for as long as six months but will eventually resolve. A RIND may show up as a slight perfusion defect on a perfusion MRI but may not be evident at all on most imaging studies. RIND is classified to code 434.91. Treatment for an ischemic stroke involves clot-busting drugs such as tissue plasminogen activator (tPA). tPA (99.10) needs to be administered within three hours of symptom onset. Since tPA is contraindicated in hemorrhagic strokes, a CT scan is done immediately to rule it out. tPA may significantly improve symptoms, causing the physician to document “aborted CVA.” According to coding directives, an aborted CVA is assigned to code 434.91. Since tPA must be administered quickly, it is usually given at a community hospital emergency department (ED). The patient is then transferred to a larger facility’s stroke center, which can provide the level of services required by the increased severity of these cases. So the facility providing the tPA administration in its ED doesn’t receive increased diagnosis-related group (DRG) reimbursement because the patient is transferred before being admitted. The receiving facility is not allowed to receive reimbursement for the tPA because it was administered at another facility. Code V45.88 is assigned as a secondary diagnosis in this instance to identify whether a patient received tPA prior to admission to the receiving facility. At this time, code V45.88 does not affect Medicare-severity DRG assignment, but it is important to capture as a secondary diagnosis when appropriate. Strokes can also be treated surgically with carotid endarterectomy (38.12), angioplasty and stents (00.62 and 00.65 or 00.61 and 00.63/00.64), aneurysm clipping (39.51), or coiling, or aneurysm embolizations (39.72, 39.75, or 39.76). Coding and sequencing for cerebral infarction 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 4,000 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.	4	4	0	0	4	0.853533	4	1,398
Last month, we discussed OB/GYN coding as part of our ICD-10 Quick Tips blog series. This week, we will continue our discussion of OB/GYN coding and focus on coding of multiple gestations. In our past life (ICD-9!) we did not have too many options to capture this data, but ICD-10 certainly took care of that for us! We now have new coding concepts to address and apply, so let’s take a look at one of the biggest changes involving multiple gestation coding. Once again, I want to start with some basic information which is critical for understanding this concept of coding. The first thing we must understand is the th ree different types of multiple gestations: - Monoamniotic/monochromic (mo/mo): Mo/mo twins share the same amniotic sac and share the same placenta within the uterus. These multiples are always identical, but have two separate umbilical cords. - Monoamniotic/diamniotic (mono/di): Mono/di twins generally have two amniotic sacs (a fetus in each sac) yet share the same placenta and have separate umbilical cords. These multiples are also identical. - Dichorionic/diamniotic (di/di): This is the most common form of multiples. These type of twins usually have two amniotic sacs and two placentas. Di/di twins are commonly referred to as fraternal twins. This type of multiple rarely produces identicals. To identify the fetus in a multiple gestation that is affected by the condition being coded. These are the applicable seventh characters: - The seventh character 0 is for single gestations and multiple gestations where the affected fetus is unspecified. - Seventh characters 1 through 9 are for cases of multiple gestations to identify the fetus for which the code applies. - 0 – not applicable or unspecified (also used for single pregnancies) - 1 – Fetus 1 - 2 – Fetus 2 - 3 – Fetus 3 - 4 – Fetus 4 - 5 – Fetus 5 - 9 – Other Fetus - A code from category O30, Multiple gestation must also be assigned when assigning these codes Therefore, if the physician is caring for a pregnant woman with the baby in breech presentation, you would report the appropriate seventh character from 1 through 9 to specify fetus 1, fetus 2, etc. - For example - Mary, pregnant with twins, is close to her due date and the physician noticed that fetus 2 is in breech position. Report code 032.1xx2 (maternal care for breech presentation, fetus 2). - Another example - Joan, pregnant with her first baby (single gestation), is ready to deliver but the baby is in breech position. Report 032.1xx0 (maternal care for breech presentation, not applicable). Physicians often document twins as fetus A and fetus B. However, the fetal extensions in chapter 15, Pregnancy, childbirth and the puerperium, for codes related to complications of multiple gestation (e.g., O31, O32, etc.) refer to fetus 1, fetus 2, and so on. For the purposes of selecting the seventh character for these codes, it is appropriate to assume that fetus A is fetus 1 and B is 2, etc. There you have it folks! Hope you found this short and sweet summary of coding multiple gestations in ICD-10!	4	7	0	0	2	0.692129	2	735
Hearing loss: perceptions and solutions; Hearing loss can be dealt with effectively to improve a resident's quality of life. Communication difficulties are not the only problems associated with hearing impairment. Hearing loss can lead to depression, social isolation, stress, and functional problems, such as impaired balance. Hearing loss and dementia have several symptoms in common, such as confusion, withdrawal, irritability, disorientation, and inappropriate responses, that can lead to a diagnosis of a more severe cognitive impairment than is truly the case. When furnished with hearing amplification, residents with dementia score better on cognitive screening tests than those without amplification. (3) When a proper screening program is in place and assistive listening devices are used, continuing decreases in quality of life and functional abilities can be stabilized. Although there is no universal protocol for screening hearing in nursing home residents, helpful assessment tools do exist. The Hearing Handicap Inventory for the Elderly is a widely used screening questionnaire. This 10-item questionnaire assesses the emotional and social impacts of hearing loss on residents. Answers are given in a "Yes," "No," or "Sometimes" format and then scored accordingly. Scoring and interpretation instructions are provided (see table). If a resident fails the screening, a full audiologic evaluation performed by a state-licensed, American Speech-Language-Hearing Association (ASHA)--certified audiologist is recommended. A comprehensive audiologic exam is considered the standard method for determining the type and severity of hearing loss and to rule out middle-ear pathology. In addition, it provides essential information in determining candidacy for hearing aids, assistive listening devices (ALDs), and aural rehabilitation. Medicare Part B covers hearing evaluations (CPT code 92557) when they are deemed medically necessary, such as to rule out a middle-ear pathology as a cause for a decrease in hearing. Otoscopic ear examination should be performed in conjunction with an audio-logic evaluation to exclude other treatable causes of hearing loss, including cerumen (earwax) impaction, ear infections, and tympanic membrane perforations. In fact, cerumen impaction is one of the most common causes of hearing loss in the elderly and can be attributed to a hearing loss of up to 40 decibels. (4) Aural rehabilitation and amplification should be offered to residents once they have been qualified as candidates for these services. Aural rehabilitation must be deemed medically necessary to be a covered service under Medicare. Medical necessity is determined by the recommendations of an audiologist and speech-language pathologist, and depends on determination that a hearing aid or an ALD in itself would not "sufficiently meet the patient's functional communication needs." (5) This type of speech-language therapy is reimbursable under CPT code 92507 which, under Medicare, is described as the "treatment of speech, language, voice communication, and/or auditory processing disorder." Hearing aids are the most commonly used amplification for the hearing-impaired. It has been reported, however, that only one-fifth of all residents who could benefit from hearing aids actually own them. (6) The most common reasons cited for this are residents' anxiety about hearing aid maintenance and care, and cost. Other issues with hearing aids, such as problems with insertion, cleaning, changing batteries, using volume controls accurately, and turning hearing aids on and off, can indeed be overwhelming, and residents may decide that their hearing "isn't that bad" after all. According to ConsumerAffairs.com, the average cost of a pair of hearing aids in 2004 was $2,300. (7) Cost can be prohibitive for the elderly, who might rely strictly on Medicare and Medigap to meet their healthcare needs. In fact, of the 10 standard Medigap plans available, not one covers the cost of hearing aids. A few commercial insurance companies reimburse for hearing aids, but coverage varies greatly. Medicaid coverage for hearing aids also varies greatly, depending on the state. Other Amplification Options Assistive technology can play an important role in the hearing healthcare of residents who are unable to handle or afford hearing aids. Assistive technology falls into two main categories: alerting devices and ALDs. Alerting devices can help the hearing-impaired perceive environmental sounds, such as those made by a doorbell, telephone, or fire alarm. These devices rely typically on flashing lights or vibration to communicate. They provide an important service to those who want to maintain their independence and still ensure their safety. ALDs help to address communication problems by amplifying sounds and are typically stand-alone devices; i.e., no hearing aids are required. There are many ALD options available, including telephone amplifying devices, TV listening systems, and personal listening systems. Amplified telephones increase the volume of sound emanating from a telephone handset. These generally have adjustable volume and tone controls for personal listening preference and to help make it easier to hear difficult voices (i.e., women's and children's voices); they are usually hearing aid--compatible. Special amplifying devices are available that can be attached to an existing telephone to serve the same purpose. TV listening systems typically use infrared technology to send sound from a transmitter plugged into the television to a headset receiver with an independent volume control. (It's no wonder that they are commonly referred to as "marriage savers.") Personal listening systems are perhaps the most useful to nursing home residents. These systems are inexpensive compared with hearing aids and can be much easier to handle. Personal amplifiers are handheld, battery-operated devices that are perfect for one-on-one conversation or even watching television. Most personal amplifiers are hardwired, meaning that a microphone is attached to a receiver by a wire. An example of a personal amplifier is the Pocketalker Pro by Williams Sound. It comes with several headset options, a carrying case, and a microphone extension cord for a television. It operates on two AA batteries (with optional recharger) and comes standard with a five-year warranty. There are times, however, when the resident or facility needs a less expensive option. In our practice, we recommend the Turbo Ear to fill this need. The Turbo Ear comes standard with in-the-ear headphones (other options may be available) and uses one AAA battery. The Turbo Ear does not provide as much amplification as the Pocketalker, but it can be quite helpful when trying to communicate with a hearing-impaired resident who has budget constraints. Other personal amplifying systems are available. An audiologist should be consulted to help select the most appropriate device for the individual patient. Hearing loss affects every aspect of a resident's life. It can greatly deteriorate quality of life and have a negative impact on independence. Nursing homes and long-term care facilities can help improve their resident's lives by using the specialized skills of speech-language pathologists and audiologists. Hearing impairment can easily be identified with a well-implemented screening process and improved with the help of an aural rehabilitation program that employs the use of assistive technology. Amanda D. Nichols is Business Manager for Southeastern Hearing Services, a private audiology practice based in Tuscaloosa, Alabama. Its clients include more than 100 nursing homes in Alabama, Mississippi, and Arkansas. For further information, phone (205) 391-9876 or visit www.forhearing.com. To send your comments to the author and editors, e-mail [email protected]. Note: The author's mention of specific products in this article should not be taken as an endorsement by Nursing Homes/Long Term Care Management. 1. Cruikshanks KJ, Wiley TL, Tweed TS, et al. Prevalence of hearing loss in older adults in Beaver Dam, Wisconsin. The Epidemiology of Hearing Loss Study. American Journal of Epidemiology 1998;148:879-86. 2. JonesA. The National Nursing Home Survey: 1999 summary. National Center for Health Statistics, Centers for Disease Control and Prevention, Department of Health and Human Services. Vital and Health Statistics 2002;13(152). Available at: www.cdc.gov/nchs/data/series/sr_13/sr13_152.pdf. 3. Weinstein BE, Amsel L. Hearing loss and senile dementia in the institutionalized elderly. Clinical Gerontologist 1986;4:3-15. 4. Lewis-Cullinan C, Janken JK. Effect of cerumen removal on the hearing ability of geriatric patients. Journal of Advanced Nursing 1990;15:594-600. 5. CMS Manual System: Pub 100-02 Medicare Benefit Policy, Transmittal 36, Change Request 3648. Centers for Medicare & Medicaid Services, Department of Health and Human Services. June 24, 2005. Available at: www.cms.gov/Transmittals/downloads/R36BP.pdf. 6. Popelka MM, Cruickshanks KJ, Wiley TL, et al. Low prevalence of hearing aid use among older adults with hearing loss: The Epidemiology of Hearing Loss Study. Journal of the American Geriatrics Society. 1998;46:1075-8. 7. Allen J. Hearing aids becoming easier & cheaper to buy. ConsumerAffairs.com; June 18, 2004. Available at: www.consumeraffairs.com/health/hearing/hearing_aids_01.html. American Speech-Language-Hearing Association, www.asha.org Better Hearing Institute, www.betterhearing.org Centers for Medicare & Medicaid Services, www.cms.hhs.gov HITEC Group, Ltd., www.hitec.com Williams Sound Corp., www.willisamssound.com Table. Hearing Handicap Inventory for the Elderly--Short Version. Instructions: Answer Yes, No, or Sometimes for each question. Do not skip a question if you avoid a situation because of hearing problems. If you use hearing aids or assistive devices, answer according to the way you hear without amplification. Scoring: No = 0; Sometimes = 2; Yes = 4. Interpretation of Scoring: 0-8 = no handicap; 10-24 = mild to moderate handicap; 26-40 = severe handicap. 1. Does a hearing problem cause you to feel embarrassed when you meet new people? 2. Does a hearing problem cause you to feel frustrated when talking to members of your family? 3. Do you have difficulty hearing when someone speaks in a whisper? 4. Do you feel handicapped by a hearing impairment? 5. Does a hearing problem cause you difficulty when visiting friends, relatives, or neighbors? 6. Does a hearing problem cause you to attend religious services less often than you would like? 7. Does a hearing problem cause you to have arguments with family members? 8. Does a hearing problem cause you difficulty when listening to TV or radio? 9. Do you feel that any difficulty with your hearing limits or hampers your personal or social life? 10. Does a hearing problem cause you difficulty when in a restaurant with relatives or friends? Source: Ventry IM, Weinstein BE. Identification of elderly people with hearing problems. American Speech-Language-Hearing Association 1983;25:37-42. \|Printer friendly Cite/link Email Feedback\| \|Author:\|\|Nichols, Amanda D.\| \|Date:\|\|Oct 1, 2006\| \|Previous Article:\|\|Keeping an ethical perspective on end-of-life issues: caregivers can't necessarily look to paperwork for answers for respecting dying residents'...\| \|Next Article:\|\|Weighing in on weight loss: in the elderly, unintentional weight loss sends a serious signal.\|	2	6	4	0	0	0.526557	4	2,445
What is ICD-10? ICD-10 is the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD), a medical classification by the WHO. ICD-10 codes hold critical information about abnormal findings, complaints, diseases, epidemiology, external causes of injury, managing health, treating conditions, signs and symptoms, and social circumstances. There are more than 14,400 different codes in ICD-10 which can be further expanded to over 16,000 codes by using optional sub-classifications. The U.S. Department of Health & Human Services (HHS) has designated ICD-10 as a code set under the Health Insurance Portability & Accountability Act (HIPAA) and it will be required for use by physicians and others in the health care industry beginning October 1, 2015. It will replace all ICD-9 code sets. Thus, for any healthcare service that occurs on or after October 1, 2015, providers must use ICD-10 codes. This mandate applies to healthcare reimbursement, research, and reporting services. CMS has stated that they will offer no grace period and no additional delays for the transition. Benefits of ICD-10 The U.S. has been using ICD-9 since 1979, and it is not sufficiently robust to serve the healthcare needs of the future. The content has limited data about patients’ medical conditions and hospital inpatient procedures, the number of available codes is limited, and the coding structure is too restrictive. Most developed countries have already made the transition to ICD-10 code sets, so the U.S. cannot compare U.S. morbidity diagnosis data at the international level. ICD-10 code sets will enhance the quality of data for: - Tracking public health conditions (complications, anatomical location) - Improved data for epidemiological research (severity of illness, co-morbidities) - Measuring outcomes and care provided to patients - Making clinical decisions - Identifying fraud and abuse - Designing payment systems/processing claims Through expanded categories and diagnosis codes, ICD-10 will foster a more accurate reporting system that will result in better clinical decision support. It also provides better data for measuring and tracking health care utilization and the quality of patient care. The granularity of ICD-10-is vastly improved over ICD-9 and will enable greater specificity in identifying health conditions. - The greater level of detail in the new code sets includes laterality, severity, and complexity of disease conditions, which will enable more precise identification and tracking of specific conditions. - Revised terminology and disease classification to be more consistent with new technology and current clinical practice. - Injuries, poisonings and external causes are much more detailed in ICD-10-CM. The codes include the severity of injuries, and how and where injuries happened. Extensions are also used to provide additional information for many injury codes. - Pregnancy trimester is designated for ICD-10-CM codes in the pregnancy, delivery and puerperium chapter. - Postoperative codes are expanded and now distinguish between intraoperative and post-procedural complications. - There are new concepts that did not exist in ICD-9-CM, such as under dosing, blood type, the Glasgow Coma Scale, and alcohol level. Key differences between ICD-9 and ICD-10 codes \|Comparison of Diagnosis Code Sets\| \|3-5 Characters in length\|\|3-7 Characters in length\| \|First character may be alpha or numeric, characters 2-5 are numeric\|\|Character 1 is alpha; Characters 2 and 3 are numeric; characters 4-7 are alpha or numeric\| \|Less specificity\|\|Greater specificity\| \|Laterality not specified\|\|Laterality specified (e.g. left versus right)\| \|Limited space for new codes\|\|Flexibility to add new codes\| \|ICD-10-CM Code Structure\| \|Characters 1 through 3 – Category\| \|Characters 4 through 6 – Etiology, anatomic site, severity, or other clinical detail\| \|Character 7 – Extension\| \|ICD-10-CM Code Detail\| \|S52 Fracture of the forearm\| \|S52.3 Fracture of the shaft of the radius\| \|S52.32 Transverse fracture of the shaft of the radius\| \|S52.321 Displaced transverse fracture of the shaft of the right radius\| \|S52.321A Displaced transverse fracture of the shaft of the right radius,initial encounter for closed fracture\| How to prepare for ICD-10 The transition to ICD-10 is expected to be much more disruptive for physicians than previous HIPAA mandates, as they must adjust their documentation and other processes. Unlike previous HIPAA mandates where physicians could lean heavily on other partners, such as billing services, vendors, and clearinghouses, use of the new codes will require a much deeper level of involvement by the physicians themselves.	4	6	0	0	2	0.676347	2	1,044
5 Common Causes and ICD 10 Code of Palpitations If you feel like your heart is beating too fast or too hard, skipping a beat or even fluttering, you have palpitations. ICD-10 code for palpitations is R00. ICD is known as the standard diagnostic tool which is used in clinical care and research to define diseases. It includes monitoring of the incidence and prevalence of diseases. The ICD-10 code for palpitations is in Chapter 18, Section R00-R09. You can check your heart palpitations in your chest, throat or neck. Palpitation occurs by certain condition that is usually not serious or harmful. In rare cases, the fast heart beat can be a sign of a more serious heart condition too. Some common reasons why a person experience heart palpitations can include the following. - Anxiety and Stress Normally, when a person is stressed out or nervous, his brain releases hormones which can cause the heart to pound. So, it is clear that being anxious or stressed can bring about heart palpitations. Another strong emotion such as fear can absolutely trigger palpitations too. People often ignore the amount of fluids that their bodies need. Losing too much fluids or nor drinking enough fluid can lead to severe dehydration. In fact, dehydration can lower your blood pressure. This can bring you to experience palpitations. - Strenuous Physical Activity A person who engages in strenuous physical activity may experience heart palpitations after or before the exercise but they are rare during the workout. Your heart rate increases during physical activity but the palpitations diminish. In contrast, the palpitations may return once the workout is done and the heart slows down gradually. - Stimulants Like Caffeine Caffeine is one of stimulants that can affect your heart if you consuming it too much or having it at the wrong time. It is can affect your brain and muscles as well. Other stimulants such as nicotine, alcohol, illegal street drugs can lead you to have palpitations too. - Certain Meals Something that we eat always creates an effect, either good or bad. Consuming heavy meals which are high in fats or sugar are though as triggers to palpitations. Others believe that foods with high levels of nitrates or sodium are also the triggers. In this case, it is about all about food sensitivities. So, it may be not same between one another. It is better for you to identify your food sensitivity.	3	2	0	0	4	0.988205	4	519
What the Anesthesiologist Should Know before the Operative Procedure During uterine curettage, an instrument is used to scrape or suction the uterine lining to diagnose and/or treat abnormal bleeding or to remove products of conception. If not already dilated, the cervix must first be opened mechanically or chemically. The indication for the dilation and curettage is an important concern for the anesthesiologist. An acute hemorrhage situation requiring an emergent or urgent dilation and curettage requires additional setup and has higher risks, while a diagnostic elective procedure typically has lower risks. Therefore, it is important for the anesthesiologist to know the indication for the procedure. The complications associated with this procedure, which consist primarily of bleeding and uterine perforation, occur at a frequency of approximately 1-2%. In order to maximize the diagnostic and therapeutic yield and minimize risk, Dilation and Curettage (D & C) or Dilation and Evacuation (D & E) can be substituted by non-invasive procedures (such as transvaginal ultrasound) when appropriate, or augmented with more directed techniques, such as hysteroscopy and/or polypectomy. The causes of uterine bleeding leading to curettage include: 1) Pregnancy-related issues, such as miscarriage, retained products of conception, or therapeutic abortion. 2) Non-pregnancy-related issues, such as investigation of fibroids or polyps or hyperplastic uterine linings. 1. What is the urgency of the surgery? What is the risk of delay in order to obtain additional preoperative information? D & Cs or D & Es are elective, outpatient procedures if there is no major bleeding and/or if the procedure is done for diagnostic purposes. Emergent: If the patient is having active and ongoing bleeding resulting in subjective symptoms, such as lightheadedness or palpitations, or is showing objective signs of significant hypovolemia, such as hypotension or tachycardia, then the D & C should be performed as soon as possible. Delaying curettage may result in exsanguination. Practitioners should be prepared for major resuscitation that includes crystalloids, colloids, and blood products (in some cases, uncrossed-matched RBCs) as needed. Depending on the source of bleeding, the procedure may need to be converted to a laparoscopy or laparotomy. Urgent: Patients with chronic bleeding are often evaluated first by imaging (e.g. ultrasound) to inform the decision of whether or not to proceed with D & C. There is typically time for these patients to undergo a more thorough preoperative evaluation and for blood to be typed and crossed, if needed. Elective: Patients with intermittent, abnormal vaginal bleeding, uterine fibroids, or polyps may undergo D & C as an elective procedure. These procedures are typically used to determine the cause of bleeding and, in some cases, the benign or malignant nature of a uterine growth. These patients can undergo pre-operative testing based on the presence or absence of co-morbidities. 2. Preoperative evaluation During the preoperative evaluation, it is important to assess the pregnancy status of the patient, as dilatation and curettage is contraindicated in patient with a viable and desired intrauterine pregnancy. Medically unstable conditions warranting further evaluation include major cardiac or pulmonary disease or clotting disorders. Patients with pelvic infections are at risk for bacteremia and perforation as a result of the fragile uterine tissue. In general, cardiac testing is unnecessary for asymptomatic patients. Delaying surgery may be indicated if the patient is pregnant and this is not a pregnancy-related D & C or if the procedure is elective and the patient is unstable because of comorbid illness. The patient should be optimized prior to proceeding with surgery, if feasible, if she had cardiac issues, such as unstable angina, and if significant intra-operative bleeding is expected. Patients with severe hip arthritis can be difficult or impossible to position in stirrups (i.e. lithotomy), thus limiting the feasibility of these procedures. Patients with pre-existing cardiac, gastrointestinal, or pulmonary issues may benefit from regional or paracervical blocks. It would be important to evaluate these patients preoperatively for coagulation disorders or infection near the block site. 3. What are the implications of co-existing disease on perioperative care? Patients with acute or chronic bleeding should have a baseline CBC. If bleeding has been significant (>=1.5 liters acutely, or multiple recent bleeds), then consider a DIC screen. b. Cardiovascular system Acute ongoing hemorrhage may exacerbate underlying cardiac ischemia, further necessitating prompt resuscitation and identification of the underlying cause of bleeding. Baseline coronary artery disease or cardiac dysfunction Goals of management: If the patient’s pain and bleeding are well controlled, then the D & C or D & E should lead to minimal hemodynamic derangement. However, inadequate anesthesia and major hemorrhage can precipitate ischemia through increased utilization and decreased availability of oxygen. Patients with a significant smoking history, chronic bronchitis, or baseline oxygen requirements should be identified preoperatively. Patients with acute or chronic alcohol use can have increased risk for aspiration and more colonization with pathologic bacteria in their airway. Unless an acute COPD exacerbation is suspected, additional preoperative testing is rarely indicated. Perioperative Risk Reduction Strategies These targeted patients should continue their ongoing medication regimens, assuming they are optimized. Patients with COPD may benefit from short term preoperative inhaled or systemic corticosteroids. Anesthetic techniques that avoid instrumenting the airway, such as a paracervical block with sedation or neuraxial anesthetics, are preferable to general anesthesia. Patients with a history of smoking or excessive alcohol consumption should be advised to practice smoking and alcohol cessation at least 4-8 weeks prior to surgery. Reactive Airway Disease (i.e., Asthma) The status and severity of the patient’s disease should be assessed, including identifying common triggers, the response to bronchodilators, history of recent hospitalizations, prior steroid therapy, or intubations for exacerbations. Perioperative Risk Reduction Strategies Ideally, patients would not undergo a procedure during an asthma or COPD exacerbation, but rather they would first be medically optimized. If the procedure is emergent, the anesthetic technique of choice would be to allow the patient to breathe spontaneously and avoid instrumentation of the airway (e.g. paracervical block with sedation/MAC or spinal). If general anesthesia is necessary, then initial use of a volatile agent to aid in bronchodilation, decreased to 0.5 MAC after induction to promote uterine contraction post-procedure, would be beneficial. Preoperative and intraoperative treatment with inhaled bronchodilator therapy may also benefit these patients. In situations with excessive bleeding, carboprost (Hemabate) should be avoided or used cautiously as it can cause bronchospasm in susceptible individuals. Alternative uterotonic agents such as oxytocin, methergine, or misoprostol should be used instead. Active respiratory therapy is advisable. As per ASA guidelines, patients undergoing non-urgent or emergent D & C should be NPO for 6-8 hours for solid food and 2 hours for clear liquids prior to the procedure. Those with symptomatic reflux should be identified, and should undergo light sedation that preserves airway reflexes (+ paracervical block or neuraxial anesthetic) or rapid sequence induction with general endotracheal anesthesia after H2 blocker therapy. g. Additional systems/conditions which may be of concern in a patient undergoing this procedure and are relevant for the anesthetic plan (e.g., musculoskeletal in orthopedic procedures, hematologic in a cancer patient) Patients with a history of or active cervical or uterine cancer should be evaluated preoperatively and managed carefully as heavy bleeding or perforation can occur. The anesthesiologist should be prepared with proper IV access and blood products on standby. 4. What are the patient's medications and how should they be managed in the perioperative period? h. Are there medications commonly seen in patients undergoing this procedure and for which should there be greater concern? If patients are taking anti-coagulants or anti-platelet agents, they should consult with their physicians at least a week prior to surgery for further instructions, as some of these medications have an extremely long half-life. i. What should be recommended with regard to continuation of medications taken chronically? consult with multidisciplinary team j. How To modify care for patients with known allergies – k. Latex allergy- If the patient has a sensitivity to latex (e.g., rash from gloves, underwear.) versus anaphylactic reaction, prepare the operating room with latex-free products. In case of anaphylaxis, epinephrine, IV H1, H2 blockers and steroids, and rescue airway equipment should be readily available. Diagnostic dilation and curettage (Endometrial biopsy): No antibiotics Elective suction curettage abortion: Antibiotic prophylaxis is indicated. Optimal antibiotic agents and dosages vary. One of the most effective and least expensive regimens is Doxycycline. l. Does the patient have any antibiotic allergies? m. Does the patient have a history of allergy to anesthesia? Malignant hyperthermia (MH) Avoid all trigger agents, such as succinylcholine and inhalational agents. Insure MH cart available: Clean machine according to individual anesthesia machine protocol. Use regional technique or paracervical block if possible. These are not considered to be MH triggering agents, and therefore can be used in patients at risk for malignant hyperthermia. It is important to ask patients if they are allergic to local anesthetics or sunscreen containing PABA (relevant for ester local anesthetics) before administering local anesthetic. 5. What laboratory tests should be obtained and has everything been reviewed? For young healthy patients not at risk of significant bleeding, no pre-operative labs are needed unless there is significant hemorrhage. Intraoperative Management: What are the options for anesthetic management and how to determine the best technique? The anesthetic options for dilation and curettage include conscious sedation or MAC (monitored anesthesia care) +/- paracervical block, neuraxial, and general anesthesia. The optimal anesthetic choice depends on the patient and: a) the degree of hemorrhage/hemodynamic stability, b) the patient and provider preference, c) and cervical dilation, which may affect the feasibility of doing a paracervical block. The Cochrane Database Review (2009) examined 17 studies, including over 1,855 participants, regarding cervical dilation and uterine intervention with paracervical block when compared with no treatment, placebo, and other regional anesthesia, systemic sedation, or GA. Some studies reported that women experienced severe pain (mean scores of 7-/10) during uterine intervention, irrespective of the analgesia technique used. No technique provided reliable pain control. The available evidence fails to show whether paracervical block is inferior, equivalent to, or superior to alternative analgesia techniques in terms of efficacy and safety for women undergoing uterine interventions. a. Regional anesthesia Regional anesthesia, including Paracervical block (+/- sedation), +/- intrauterine local anesthetic and neuraxial (+/- sedation) have been reported for D & C and D & E. Benefits: anecdotally, patients typically feel the least discomfort. Drawbacks: low, but non-zero, risk of post-dural puncture headache (PDPH) and transient radicular irritation (TRI) in setting of outpatient procedure and lithotomy position. Consider using hyperbaric bupivacaine 0.75% (1-1.5 ccs) with fentanyl (10-20 mics) or, if less than 1 hour of procedure time is anticipated, mepivacaine 1.5% (45-60 mg) with preservative-free dextrose (approximately 1 cc) or chloroprocaine 40-60mg. Recovery time varies and the patient may have to recover in hospital before being discharged. 2. Peripheral Nerve Block e.g., paracervical (consider Nesacaine 1%) Benefits: less invasive and better analgesia than sedation alone. Drawbacks: reports of pain regardless of the agent used if paracervical block is done without sedation. Benefits: less invasive. Some investigations have shown that 5 cc’s of 2% lidocaine can be as effective as paracervical block or po NSAID. As with paracervical block, use in conjunction with conscious sedation for best results. b. General Anesthesia Benefits: secured airway, anecdotally more reliable pain management, and less intra-op patient movement. Drawbacks: potential airway issues or increased risk of aspiration if patient is beyond the first trimester of pregnancy or recently post-partum. Increased risk of postoperative nausea and vomiting. c. Monitored Anesthesia Care D & C is often done under sedation or Monitored Anesthesia Care (MAC) with paracervical block. There are many analgesia and anesthetic agents that can be used in bolus dosing or as continuous infusions (e.g., Fentanyl and Versed, Propofol and Remifentanil). In one randomized, controlled trial, propofol (target concentration of 5 mics/ml) was recommended for D & C when administered with Fentanyl 1 mic/kg and N02 (66%) as compared with 4 and 6 mics/cc. Close monitoring and appropriate respiratory management were deemed necessary for safe administration. Benefits include that it takes the patient less time to wake up when compared with general anesthesia, potentially less need to instrument the airway, if the patient continues to breath spontaneously, and the avoidance of post-dural puncture headache. Drawbacks include the risk of respiratory depression, which could lead to depressed airway reflexes, aspiration, and/or apnea, the potential for patient movement, increasing the chance of uterine perforation, and a greater chance of inadequate pain relief when compared to neuraxial or general anesthesia. 6. What is the author's preferred method of anesthesia technique and why? When obstetric providers expect that the procedure will be straightforward (that is, there is no molar pregnancy or malplacentation) for first trimester incomplete or therapeutic abortions or the removal of retained products of conception, then our anesthetic of choice is a paracervical block placed by the surgeons (using 1% Nesacaine) and MAC. We use various combinations of anesthetics for sedation during the MAC, including bolus fentanyl and versed or propofol and remifentanil infusions. For second trimester D & Es, our anesthetic of choice is typically either spinal or general (endotracheal) anesthesia, and occasionally MAC plus paracervical block The MAC with paracervical block option requires careful case selection (e.g., absence of symptomatic reflux in the patient, anticipation of a straightforward procedure). If significant bleeding has occurred or is expected, or if the patient is hemodynamically unstable, then we proceed with resuscitation and general endotracheal anesthesia. If the uterus needs to be evacuated urgently, but the patient has recently ingested food other than clear liquids or has an active upper respiratory infection, we will proceed with a spinal anesthetic with light-to-moderate sedation if no contraindications, such as coagulopathy or hemodynamic instability, exist. If there are no contraindications and no objections by the surgical team, interoperative ketorolac 30mg is given IV for postoperative pain control. Patients are continued on NSAIDs postoperatively on an as-needed basis for pain control. What prophylactic antibiotics should be administered? According to the ACOG guidelines, despite the lack of data, antibiotic prophylaxis is indicated for elective and missed suction curettage abortion. Although the optimal antibiotic regimen is unclear, Doxycycline (100 mg prior to the procedure and 200 mg post-procedure) was shown in a meta-analysis to be effective and inexpensive. In a prospective, randomized, controlled trial, antibiotic prophylaxis showed no benefit before the treatment of incomplete abortion. What do I need to know about the surgical technique to optimize my anesthetic care? Will there be manual dilation of the cervix? In general, dilation is painful and requires a significant degree of anesthesia (i.e., a functional paracervical block, spinal, or general anesthesia). Will this be a first or second trimester gestation? In general, second trimester D & Es are more complex and are less conducive to MAC. What can I do intraoperatively to assist the surgeon and optimize patient care? During manual dilation of the cervix and active curettage, it is important that the patient not move her hips or lower extremities, as movement can increase the risk of uterine perforation. As such, the patient should either be conscious and able to control her own body or sedated enough to restrict movement (e.g., during a GET). What are the most common intraoperative complications and how can they be avoided/treated? Attention to pre-op volume status and intra-op bleeding is essential. In the case of straight-forward first trimester missed Ab, the bleeding is often self-limited. Patients with chronic uterine bleeding or retained products of conception requiring D & E can often require significant resuscitation, including blood products such as PRBCs, FFP, platelets, and Cryoprecipitate, if bleeding is severe. As with any change in patient status, suspected uterine perforation should prompt direct and specific communication between the surgery, nursing, and anesthesia teams. Minor perforation can have little to no effect on the patient’s intra-op course, while major perforation can require urgent laparotomy and precipitate significant hemorrhage. Uterine perforation is of higher likelihood in procedures done to treat uterine bleeding as opposed to diagnostic dilatation and curettage. Risk of perforation is also increased in pregnancy. Amniotic Fluid Embolus (AFE) has been reported in pregnancy-related D & E. Therapy involves supportive care; in cases of cardiac or respiratory collapse, cardiopulmonary bypass or ECMO have been employed in some isolated cases. In general, morbidity and mortality is high with AFE. Patients who have outpatient procedures in the lithotomy position under spinal anesthesia have an increased incidence of Transient Radicular Irritation (TRI). b. If the patient is intubated, are there any special criteria for extubation? If there has been significant hemorrhage and resuscitation, it is important to assess tissue swelling and airway swelling before extubation. c. Postoperative management What analgesic modalities can I implement? If not otherwise contraindicated, NSAIDS (e.g., Toradol) +/- opioids are particularly useful for post-D & E pain management, given the high incidence of uterine cramping. What level bed acuity is appropriate? Unless there has been significant hemorrhage, D & E is often done as an outpatient procedure. Those patients who have required significant resuscitation may need to be in an inpatient setting overnight; in this case, the patient’s underlying health status and degree of hemodynamic stability post-procedure can be used to decide whether she needs a monitored bed (e.g. step-down Unit or ICU). What are common postoperative complications, and ways to prevent and treat them? To prevent post-operative bleeding, patients will sometimes be given intra-operative uterotonic agents as well as resuscitation with crystalloids or blood products as needed. Those with suspected uterine perforation are often treated with antibiotics. The development of TRI after spinal anesthetic is typically a relatively benign and self-limited event. What's the Evidence? “Antibiotic Prophylaxis for Gynecologic Procedures”. Obstetrics and Gynecology. vol. 113. 2009. pp. 1180-1189. (This document summarizes the recommendations for first and second line prophylaxis [including exclusion criteria] for D & E and other gynecologic procedures.) Agostini, A, Provansal, M. “Comparison of ropivacaine and lidocaine for paracervical block during surgical abortion”. Contraception. vol. 77. 2008. pp. 382-385. (In this randomized, double-blind study, intraoperative pain was better, although still elevated, when ropivacaine was used for paracervical block compared with lidocaine. Postoperative pain was not different between the two groups.) Api, O, Ergen, B. “Comparison of oral nonsteroidal analgesic and intrauterine local anesthetic for pain relief in uterine fractional curettage: a randomized, double-blind, placebo-controlled trial”. Am J Obstet Gynecol. vol. 203. 2010. pp. 28 e21-27. (Either intrauterine lidocaine (5 cc's 2% lidocaine) or oral dexketoprofen were effective in relieving fractional curettage-related pain, although a combination of the two medications did not demonstrate a clinically relevant increase in analgesia.) Castillo, T, Avellanal, M. “Bolus application of remifentanil with propofol for dilatation and curettage”. Eur J Anaesthesiol. vol. 21. 2004. pp. 408-411. (The most favorable intra-op anesthetic conditions and post-operative recovery times were found with Remifentanil 1.5 mic/ kg(-1) i.v. with propofol 2 mg kg(-1) i.v. and 60% nitrous oxide in oxygen.) Fox, M. C, Hayes, J. L.. “Cervical preparation for second-trimester surgical abortion prior to 20 weeks of gestation”. Contraception. vol. 76. 2007. pp. 486-495. (These clinical guidelines explore the role of cervical preparation for D & E prior to 20 weeks’ gestation, specifically addressing the available osmotic dilators.) Mankowski, J. L, Kingston, J. “Paracervical compared with intracervical lidocaine for suction curettage: a randomized controlled trial”. Obstet Gynecol. vol. 113. 2009. pp. 1052-1057. (According to this investigation, either of these techniques, coupled with conscious sedation, provides effective and acceptable analgesia for first trimester suction curettage.) Rattanachaiyanont, M, Leerasiri, P. “Effectiveness of intrauterine anesthesia for pain relief during fractional curettage”. Obstet Gynecol. vol. 106. 2005. pp. 533-539. (This randomized, double-blind, controlled study showed that the addition of intrauterine anesthesia (in this case 5ml 2%lidocaine in addition to the paracervical block) further reduced pain during D & C without increasing side effects.) Sotiriadis, A, Makrydimas, G. “Expectant, medical, or surgical management of first-trimester miscarriage: a meta-analysis”. Obstet Gynecol. vol. 105. 2005. pp. 1104-1113. (Complete evacuation of the uterus was more common if surgical management was undertaken than if there was medical management of first trimester or incomplete miscarriage. Expectant management had very variable success rates.) Tangsiriwatthana, T, Sangkomkamhang, U. S. “Paracervical local anaesthesia for cervical dilatation and uterine intervention”. Cochrane Database Syst Rev. 2009. pp. CD005056(The Cochrane Database Review (2009) examined 17 studies, including over 1,855 participants, regarding cervical dilation and uterine intervention with paracervical block when compared with no treatment, placebo, and other regional anesthesia, systemic sedation, or GA. Some studies reported that women experienced severe pain (mean scores of 7-/10) during uterine intervention, irrespective of the analgesia technique used. No technique provided reliable pain control.) Tuncalp, O, Gulmezoglu, A. M. “Surgical procedures for evacuating incomplete miscarriage”. Cochrane Database Syst Rev. vol. 9. 2010. pp. CD001993(This paper indicates that serious complications (e.g. uterine perforation and other morbidity) were rare, but the trial sample sizes were not large enough to evaluate small or moderate differences.) Uerpairojkit, K, Urusopone, P. “A randomized controlled study of three targets of propofol plasma concentration in patients undergoing uterine dilation and curettage”. J Obstet Gynaecol Res. vol. 29. 2003. pp. 79-83. (The authors conclude that a target propofol concentration of 5 mics/ml in conjunction with Fentanyl 1mic/kg and nitrous oxide 66% minimized patient movement, hypotension, and respiratory depression during D & C.) Silvanus, MT, Groeben, H, Peters, J. “Corticosteroids and inhaled salbutamol in patients with reversible airway obstruction markedly decrease the incidence of bronchospasm after tracheal intubation”. Anesthesiology. vol. 100. 2004. pp. 1052-7. Warner, MA, Offord, KP, Warner, ME, Lennon, RL, Conover, MA, Jansson-Schumacher, U. “Role of preoperative cessation of smoking and other factors in postoperative pulmonary complications: a blinded prospective study of coronary artery bypass patients”. Mayo Clin Proc. vol. 64. 1989. pp. 609-616. Nelson, G, Altman, AD, Nick, A, Meyer, LA. “Guidelines for pre- and intra-operative care in gynecologic/oncology surgery: Enhanced Recovery After Surgery (ERAS) Society recommendations – Part I”. Gynecologic Oncology. vol. 140. 2016. pp. 313-322. 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. - What the Anesthesiologist Should Know before the Operative Procedure - 1. What is the urgency of the surgery? - What is the risk of delay in order to obtain additional preoperative information? - 2. Preoperative evaluation - 3. What are the implications of co-existing disease on perioperative care? - b. Cardiovascular system - c. Pulmonary - d. Renal-GI: - e. Neurologic: - f. Endocrine: - g. Additional systems/conditions which may be of concern in a patient undergoing this procedure and are relevant for the anesthetic plan (e.g., musculoskeletal in orthopedic procedures, hematologic in a cancer patient) - 4. What are the patient's medications and how should they be managed in the perioperative period? - h. Are there medications commonly seen in patients undergoing this procedure and for which should there be greater concern? - i. What should be recommended with regard to continuation of medications taken chronically? - j. How To modify care for patients with known allergies - - k. Latex allergy- If the patient has a sensitivity to latex (e.g., rash from gloves, underwear.) versus anaphylactic reaction, prepare the operating room with latex-free products. - l. Does the patient have any antibiotic allergies? - m. Does the patient have a history of allergy to anesthesia? - 5. What laboratory tests should be obtained and has everything been reviewed? - Intraoperative Management: What are the options for anesthetic management and how to determine the best technique? - 6. What is the author's preferred method of anesthesia technique and why? - What prophylactic antibiotics should be administered? - What do I need to know about the surgical technique to optimize my anesthetic care? - Will there be manual dilation of the cervix? - Will this be a first or second trimester gestation? - What can I do intraoperatively to assist the surgeon and optimize patient care? - What are the most common intraoperative complications and how can they be avoided/treated? - Uterine Perforation - Cardiac/Pulmonary Complications - a. Neurologic - b. If the patient is intubated, are there any special criteria for extubation? - c. Postoperative management	2	10	0	0	1	0.753257	1	6,297
Pulmonary edema is fluid accumulation in the tissue and air spaces of the lungs. It leads to impaired gas exchange and may cause respiratory failure. It is due to either failure of the left ventricle of the heart to remove blood adequately from the pulmonary circulation (cardiogenic pulmonary edema), or an injury to the lung parenchyma or vasculature of the lung (noncardiogenic pulmonary edema). Treatment is focused on three aspects: firstly improving respiratory function, secondly, treating the underlying cause, and thirdly avoiding further damage to the lung. Pulmonary edema, especially acute, can lead to fatal respiratory distress or cardiac arrest due to hypoxia. It is a cardinal feature of congestive heart failure. The term edema is from the Greek οἴδημα (oídēma, "swelling"), from οἰδέω (oidéō, "I swell"). \|Pulmonary edema with small pleural effusions on both sides.\| \|Classification and external resources\| \|Specialty\|\|Cardiology, critical care medicine\| \|eMedicine\|\|article/157452 article/300813, article/360932\| Signs and symptomsEdit The most common symptom of pulmonary edema is difficulty breathing, but may include other symptoms such as coughing up blood (classically seen as pink, frothy sputum), excessive sweating, anxiety, and pale skin. Shortness of breath can manifest as orthopnea (inability to lie down flat due to breathlessness) and/or paroxysmal nocturnal dyspnea (episodes of severe sudden breathlessness at night). These are common presenting symptoms of chronic pulmonary edema due to left ventricular failure. The development of pulmonary edema may be associated with symptoms and signs of "fluid overload"; this is a non-specific term to describe the manifestations of left ventricular failure on the rest of the body and includes peripheral edema (swelling of the legs, in general, of the "pitting" variety, wherein the skin is slow to return to normal when pressed upon), raised jugular venous pressure and hepatomegaly, where the liver is enlarged and may be tender or even pulsatile. Other signs include end-inspiratory crackles (sounds heard at the end of a deep breath) on auscultation and the presence of a third heart sound. Classically it is cardiogenic (left ventricular) but fluid may also accumulate due to damage to the lung. This damage may be direct injury or injury mediated by high pressures within the pulmonary circulation. When directly or indirectly caused by increased left ventricular pressure pulmonary edema may form when mean pulmonary pressure rises from the normal of 15 mmHg to above 25 mmHg. Broadly, the causes of pulmonary edema can be divided into cardiogenic and non-cardiogenic. By convention cardiogenic refers to left ventricular causes. - Congestive heart failure which is due to the heart's inability to pump the blood out of the pulmonary circulation at a sufficient rate resulting in elevation in wedge pressure and pulmonary edema – this may be due to left ventricular failure, arrhythmias, or fluid overload, e.g., from kidney failure or intravenous therapy. - Hypertensive crisis can cause pulmonary edema as the elevation in blood pressure and increased afterload on the left ventricle hinders forward flow and causes the elevation in wedge pressure and subsequent pulmonary edema. - Negative pressure pulmonary edema in which a significant negative pressure in the chest (such as from an inhalation against an upper airway obstruction) ruptures capillaries and floods the alveoli. - Neurogenic causes (seizures, head trauma, strangulation, electrocution). - Acute respiratory distress syndrome Injury to the lung may also cause pulmonary edema through injury to the vasculature and parenchyma of the lung. The acute lung injury-acute respiratory distress syndrome (ALI-ARDS) covers many of these causes, but they may include: - Inhalation of hot or toxic gases - Pulmonary contusion, i.e., high-energy trauma (e.g. vehicle accidents) - Aspiration, e.g., gastric fluid - Reexpansion, i.e. post large volume thoracocentesis, resolution of pneumothorax, post decortication, removal of endobronchial obstruction, effectively a form of negative pressure pulmonary oedema. - Reperfusion injury, i.e. postpulmonary thromboendartectomy or lung transplantation - Swimming induced pulmonary edema also known as immersion pulmonary edema - Transfusion Associated Circulatory Overload (TACO) occurs when multiple blood transfusions or blood-products (plasma, platelets, etc.) are transfused over a short period of time. - Transfusion associated Acute Lung Injury (TRALI) is a specific type of blood-product transfusion injury that occurs when the donors plasma contained antibodies against the donor, such as anti-HLA or anti-neutrophil antibodies. - Severe infection or inflammation which may be local or systemic. This is the classical form of ALI-ARDS. Some causes of pulmonary edema are less well characterised and arguably represent specific instances of the broader classifications above. Flash pulmonary edemaEdit Flash pulmonary edema (FPE), is rapid onset pulmonary edema. It is most often precipitated by acute myocardial infarction or mitral regurgitation, but can be caused by aortic regurgitation, heart failure, or almost any cause of elevated left ventricular filling pressures. Treatment of FPE should be directed at the underlying cause, but the mainstays are ensuring adequate oxygenation, diuresis, and decrease of pulmonary circulation pressures. Recurrence of FPE is thought to be associated with hypertension and may signify renal artery stenosis. Prevention of recurrence is based on managing hypertension, coronary artery disease, renovascular hypertension, and heart failure. There is no one single test for confirming that breathlessness is caused by pulmonary edema; indeed, in many cases, the cause of shortness of breath is probably multifactorial. Low oxygen saturation and disturbed arterial blood gas readings support the proposed diagnosis by suggesting a pulmonary shunt. Chest X-ray will show fluid in the alveolar walls, Kerley B lines, increased vascular shadowing in a classical batwing peri-hilum pattern, upper lobe diversion (increased blood flow to the superior parts of the lung), and possibly pleural effusions. In contrast, patchy alveolar infiltrates are more typically associated with noncardiogenic edema Lung ultrasound, employed by a healthcare provider at the point of care, is also a useful tool to diagnose pulmonary edema; not only is it accurate, but it may quantify the degree of lung water, track changes over time, and differentiate between cardiogenic and non-cardiogenic edema. Especially in the case of cardiogenic pulmonary edema, urgent echocardiography may strengthen the diagnosis by demonstrating impaired left ventricular function, high central venous pressures and high pulmonary artery pressures. Blood tests are performed for electrolytes (sodium, potassium) and markers of renal function (creatinine, urea). Liver enzymes, inflammatory markers (usually C-reactive protein) and a complete blood count as well as coagulation studies (PT, aPTT) are also typically requested. B-type natriuretic peptide (BNP) is available in many hospitals, sometimes even as a point-of-care test. Low levels of BNP (<100 pg/ml) suggest a cardiac cause is unlikely. In those with underlying heart disease, effective control of congestive symptoms prevents pulmonary edema. Dexamethasone is in widespread use for the prevention of high altitude pulmonary edema. Sildenafil is used as a preventive treatment for altitude-induced pulmonary edema and pulmonary hypertension, the mechanism of action is via phosphodiesterase inhibition which raises cGMP, resulting in pulmonary arterial vasodilation and inhibition of smooth muscle cell proliferation. While this effect has only recently been discovered, sildenafil is already becoming an accepted treatment for this condition, in particular in situations where the standard treatment of rapid descent has been delayed for some reason. The initial management of pulmonary edema, irrespective of the type or cause, is supporting vital functions. Therefore, if the level of consciousness is decreased it may be required to proceed to tracheal intubation and mechanical ventilation to prevent airway compromise. Hypoxia (abnormally low oxygen levels) may require supplementary oxygen, but if this is insufficient then again mechanical ventilation may be required to prevent complications. Treatment of the underlying cause is the next priority; pulmonary edema secondary to infection, for instance, would require the administration of appropriate antibiotics. Cardiogenic pulmonary edemaEdit Acute cardiogenic pulmonary edema often responds rapidly to medical treatment. Positioning upright may relieve symptoms. Loop diuretics such as furosemide or bumetanide are administered, often together with morphine or diamorphine to reduce respiratory distress. Both diuretics and morphine may have vasodilator effects, but specific vasodilators may be used (particularly intravenous glyceryl trinitrate or ISDN) provided the blood pressure is adequate. Continuous positive airway pressure and bilevel positive airway pressure (BIPAP/NIPPV) has been demonstrated to reduce the need of mechanical ventilation in people with severe cardiogenic pulmonary edema, and may reduce mortality. It is possible for cardiogenic pulmonary edema to occur together with cardiogenic shock, in which the cardiac output is insufficient to sustain an adequate blood pressure. This can be treated with inotropic agents or by intra-aortic balloon pump, but this is regarded as temporary treatment while the underlying cause is addressed. - "pulmonary edema" at Dorland's Medical Dictionary - Ware LB, Matthay MA (December 2005). "Clinical practice. Acute pulmonary edema". N. Engl. J. Med. 353 (26): 2788–96. doi:10.1056/NEJMcp052699. PMID 16382065. - What Is Pulmonary Hypertension? From Diseases and Conditions Index (DCI). National Heart, Lung, and Blood Institute. Last updated September 2008. Retrieved on 6 April 2009. - Chapter 41, page 210 in: Cardiology secrets By Olivia Vynn Adair Edition: 2, illustrated Published by Elsevier Health Sciences, 2001 ISBN 1-56053-420-6, ISBN 978-1-56053-420-4 - Papaioannou, V.; Terzi, I.; Dragoumanis, C.; Pneumatikos, I. (2009). "Negative-pressure acute tracheobronchial hemorrhage and pulmonary edema". Journal of Anesthesia. 23 (3): 417–420. doi:10.1007/s00540-009-0757-0. - O'Leary, R.; McKinlay, J. (2011). "Neurogenic pulmonary oedema". Continuing Education in Anaesthesia, Critical Care & Pain. 11 (3): 87–92. doi:10.1093/bjaceaccp/mkr006. - 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 . PMID 23957905. - Hampson NB, Dunford RG (1997). "Pulmonary edema of scuba divers". Undersea Hyperb Med. 24 (1): 29–33. PMID 9068153. Retrieved 2008-09-04. - Cochard G, Arvieux J, Lacour JM, Madouas G, Mongredien H, Arvieux CC (2005). "Pulmonary edema in scuba divers: recurrence and fatal outcome". Undersea Hyperb Med. 32 (1): 39–44. PMID 15796313. Retrieved 2008-09-04. - "Adverse Reactions". Professional Education. 2016-06-02. Retrieved 2016-12-03. - "Transfusion-related acute lung injury (TRALI)". Professional Education. 2016-06-17. Retrieved 2016-12-03. - Luks AM (2008). "Do we have a "best practice" for treating high altitude pulmonary edema?". High Alt. Med. Biol. 9 (2): 111–4. doi:10.1089/ham.2008.1017. PMID 18578641. - Bates, M (2007). "High altitude pulmonary edema". Altitude Physiology Expeditions. Retrieved 2008-09-04. - White J, Gray M, Fisher M (1989). Atrax Robustus IPCS InChem - Kramer K, Kirkman P, Kitzman D, Little WC. Flash pulmonary edema: association with hypertension and recurrence despite coronary revascularization. Am Heart J. 2000 Sep;140(3):451–5. doi:10.1067/mhj.2000.108828. PMID 10966547. - Pickering TG, Herman L, Devereux RB, Sotelo JE, James GD, Sos TA, Silane MF, Laragh JH. Recurrent pulmonary oedema in hypertension due to bilateral renal artery stenosis: treatment by angioplasty or surgical revascularisation. Lancet. 1988;332(8610):551–2. doi:10.1016/S0140-6736(88)92668-2. PMID 2900930. - 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. - Richalet JP, Gratadour P, Robach P, et al. (2005). "Sildenafil inhibits altitude-induced hypoxemia and pulmonary hypertension". Am. J. Respir. Crit. Care Med. 171 (3): 275–81. doi:10.1164/rccm.200406-804OC. PMID 15516532. - Perimenis P (2005). "Sildenafil for the treatment of altitude-induced hypoxaemia". Expert Opin Pharmacother. 6 (5): 835–7. doi:10.1517/14656522.214.171.1245. PMID 15934909. - Clark, Michael; Kumar, Parveen J. (2009). Kumar and Clark's clinical medicine. St. Louis, Mo: Elsevier Saunders. p. 783. ISBN 0-7020-2993-9. - Fagenholz PJ, Gutman JA, Murray AF, Harris NS (2007). "Treatment of high altitude pulmonary edema at 4240 m in Nepal". High Alt. Med. Biol. 8 (2): 139–46. doi:10.1089/ham.2007.3055. PMID 17584008. - Cleland JG, Yassin AS, Khadjooi K (2010). "Acute heart failure: focusing on acute cardiogenic pulmonary oedema". Clin Med. 10 (1): 59–64. doi:10.7861/clinmedicine.10-1-59. PMID 20408310. - Vital FM, Ladeira MT, Atallah AN (2013). "Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema". Cochrane Database Syst Rev. 5: CD005351. doi:10.1002/14651858.CD005351.pub3. PMID 23728654. - HeartFailureMatters.org Animation showing How Heart Failure causes Fluid Accumulation – Created by the European Heart Failure Association	2	15	2	1	0	0.952429	3	3,557
When you have a child or children with autism, you probably spend more time with doctors and therapists than most other families. First, there’s the search for a diagnosis, then there are potential treatments, not to mention the other conditions—such as ADHD or gastrointestinal issues—sometimes associated with ASD. All this means you’ve almost certainly come into contact with the ICD-10-CM. What does this string of letters and numbers mean, and how does it connect to autism? In this article, we’ll explore the ICD and how it impacts autism diagnosis. What is the ICD-10-CM index? The ICD-10-CM index is a version of the International Classification of Diseases, a tool created by the World Health Organization. It’s essentially a list of diseases, disorders, and other health conditions, all of which are categorized and labeled with a code made up of letters and numbers. The ICD got its start as the International Statistical Institute’s International List of Causes of Death in 1893. Eventually, the World Health Organization took over its maintenance, and it was expanded to include all conditions, not just fatal ones. Every country that is a member of WHO must use the ICD to compile national death and disease statistics. Member countries currently use the tenth edition of the ICD, called ICD-10. The International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) is a version created for use in the United States. The U.S. uses the ICD-10-CM to diagnose conditions and record patient information, and it uses the standard ICD-10 to classify data from death certificates. ICD-10 came into effect globally in 1990, but the United States didn’t begin using it for mortality information until 1999 and didn’t fully transition to the ICD-10-CM until 2015. That’s why some websites will list what tenth revision codes are equivalent to those from its predecessor, the ICD-9—although there aren’t exact matches, since the transition to the tenth edition added about 55,000 new codes. These codes have important purposes in the medical world. On a larger scale, public health officials use the data to conduct research and keep track of trends. For patients and caregivers, codes are usually used in hospital billing and insurance claims. How is autism classified in the ICD-10-CM Index? Autism is labeled with the code F84.0. It is a “billable code,” meaning it’s detailed enough to constitute a medical diagnosis. It falls under the section for mental and behavioral disorders (codes F00 through F99), the subsection of pervasive and specific developmental disorders (F80 through F89), and the smaller subsection of pervasive developmental disorders (F84). The ICD defines a pervasive developmental disorder as “severe distortions in the development of many basic psychological functions that are not normal for any stage in development.” F84 itself is a non-billable code, so it can’t be entered into any system as a diagnosis, but every code that falls under it (F84.0 through F84.9) can. Click here to find out more Looking at F84.0 autistic disorder The description of F84.0 autistic disorder in the ICD is basically the same as other descriptions of autism—children with ASD will have difficulties with social interaction, language and communication skills, and repetitive behavior that become evident in early childhood, particularly before the age of three. An ICD code may have “inclusion terms,” which are other conditions the code can be used for. Often, the inclusion terms are just synonyms of the primary one. In the case of code F84.0, the inclusion terms are autism spectrum disorder, infantile autism, infantile psychosis, and Kanner’s syndrome. The ICD also has Type 1 Excludes Notes, which indicate when two codes should never be diagnosed alongside each other. In this case, autism and asperger’s syndrome are considered to be mutually exclusive (a position not taken by all diagnostic authorities, as we’ll see later). Asperger’s syndrome is called code F84.5 instead of code F84.0. The difference, according to the ICD, is that children with asperger’s don’t have the language and cognitive impairments that can be found in other autism spectrum disorders. ICD coding allows professionals to include an additional code in their diagnosis, so they can further specify the disorder or identify any associated medical condition such as an intellectual disability. In that case, the patient would be coded for F84.0 autistic disorder as well as a code between F70-F79, which represent mild, moderate, severe, and unspecified intellectual disabilities. Autism in the ICD-9 American children diagnosed with autism before 2015, when the ICD-9 phased out, may have received the code 299.0 or 299.1. Code 299.0 indicated “autistic disorder, current or active state” and 299.1 indicated “autistic disorder, residual state,” meaning the patient used to meet the criteria for an ASD diagnosis but no longer does. People with ASD in a residual state may still have symptoms found in autism, but not enough to maintain the diagnosis. Either way, both codes now fall under F84.0 autistic disorder. Is the ICD-10-CM Index related to the DSM V? The DSM V is the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, published by the American Psychiatric Association. It has been in effect since 2013. Unlike the ICD, it only covers mental conditions. But they have similar purposes in providing a shared, consistent set of terms and diagnostic criteria for health care professionals. Because they’re created by two separate organizations, there are some discrepancies between the two manuals. For example, in the ICD-10, childhood disintegrative disorder, asperger’s syndrome, and pervasive developmental disorder-not otherwise specified each has its own code separate from autism. The American Psychiatric Association, however, collapsed each of these diagnoses under autism spectrum disorder. That said, the indexes have very similar definitions of ASD. Both emphasize repetitive behavior, struggles with social interaction and communication, and the appearance of symptoms in early childhood. The main difference between the two is that DSM-V codes can not be submitted for insurance claims. They are only useful for identification and diagnosis. If an insurance claim is submitted in the United States without an ICD code, it will be rejected. Clearly, the ICD-10-CM is important for anyone with long-term medical diagnoses. As research is done and advances are made, the ICD will continue to change how we understand and classify conditions. In fact, the ICD-11 is already on its way—WHO member countries will be allowed to implement it in 2022, though the United States isn’t expected to fully adopt it until the latter end of the decade. Autism has a new code in the ICD-11: 6A02, now called “autism spectrum disorder” instead of “autistic disorder”. There is a new range of codes from 6A02.0 to 6A02.5, indicating whether the individual has impaired intellectual development or functional language. ICD-11 has also followed the DSM-V’s lead in including asperger’s syndrome under ASD. We don’t know when ICD-11 will reach the U.S., or what, if any, modifications will be made to it. Either way, this article has hopefully helped you understand its purpose. Whether ASD is known as code F84.0, 6A02, 299.0, or something else in the future, autistic people and their loved ones represent a vibrant, supportive community. Autism Speaks. (n.d.). DSM-5 and Autism: Frequently Asked Questions. Autism Speaks. https://www.autismspeaks.org/dsm-5-and-autism-frequently-asked-questions Bielby, J. (2020, May 4). ICD-10, ICD-10-CM, & ICD-10-PCS. A.R. Dykes. https://guides.library.kumc.edu/icd10 Boyd, N. (n.d.). Diagnostic Codes: DSM-5 vs ICD-10. KASA. https://kasa-solutions.com/diagnostic-codes-dsm-5-vs-icd-10/ Holman, T. (2018, October). ICD-10-CM (Clinical Modification). TechTarget. https://searchhealthit.techtarget.com/definition/ICD-10-CM World Health Organization. (2021). International Statistical Classification of Diseases and Related Health Problems (ICD). World Health Organization. https://www.who.int/standards/classifications/classification-of-diseases World Health Organization. (2021). 2021 ICD-10-CM CODE F84.0. ICD List. https://icdlist.com/icd-10/F84.0 World Health Organization. (2021, May). 6A02 Autism spectrum disorder. ICD-11 for Mortality and Morbidity Statistics. https://icd.who.int/browse11/l-m/en#/http%3a%2f%2fid.who.int%2ficd%2fentity%2f437815624	4	2	0	0	21	0.612953	21	2,049
Skip to content Broadly speaking, injury is physical harm or damage to the body. It may be intentional or unintentional. If intentional, it may be self-inflicted (for example, suicide) or inflicted by another (for example, assault and homicide). The harm can be caused by any of the following things: • an external force (such as a collision with an object) • energy (heat, electricity, etc.) • external or internal contact with a harmful substance (poisoning, etc.) • the absence of an essential element (such as oxygen or heat) . Normally, only harmful effects occurring over a short time are considered injury. (The term ‘injury' is used generally in reference to those conditions classified within the ICD group ‘external causes of morbidity and mortality' - V01 to Y98). Assessing the total impact of injury is difficult. The vast majority of injuries do not result in hospitalisation or death and there are little systematic data on them other than those collected as part of large-scale population health surveys (such as the periodic National Health Surveys conducted by the Australian Bureau of Statistics). Thus, the vast majority of injuries are not recorded in routine data collections, and may not be brought to the attention of health policy-makers and program managers. For injuries that are serious enough to be recorded in the routine data collections or are identified by specific studies, there are some issues with their classification. The classification of injury has generally followed the World Health Organization's International Classification of Diseases (ICD), which includes particular attention to the external cause and intention of the injury. The 10th revision of the World Health Organization's International Classification of Diseases (ICD) is now applied in Australia to deaths and (in the somewhat more extensive ‘Australian Modification') to hospitalisation . The ICD-10 classification codes injuries in terms of their nature (for example, fracture of the vault of the skull) and the external cause of the injury (for example, assault by blunt instrument) . Because it is more useful for preventive purposes, most reporting of injury is in terms of external causes, the broad categories of which are as follows: • accidents - transport accidents (including motor-vehicle accidents) and other external causes of accidental injury (falls, burns, accidental poisoning, etc.) • intentional self-harm (including suicide) • assault (including homicide) • events of undetermined intent • legal interventions and operations of war • complications of medical and surgical care • sequelae of external causes of morbidity and mortality • supplementary factors related to causes of morbidity and mortality classified elsewhere.(this coding provides for factors like alcohol involvement, including blood alcohol levels if known). The ICD categories are useful for broad epidemiological studies, but have serious limitations for detailed investigations for injury prevention. Many Indigenous injuries fall into categories in which there is little detail (for example, falls). In addition, it is apparent that culture affects the way in which information about an injury-causing event is described to investigators and clinicians, and the way this is interpreted through coding . An example is the uncertainty over how traditional Indigenous punishment practices should be coded - depending upon the perspective taken, they could be recorded as an accident, a legal intervention, or violence. The magnitude of a problem can be assessed, but a detailed understanding of the causes cannot be obtained using the ICD system . Attempting to address these issues, Weeramanthri and Plumber proposed an alternative system to the ICD for the classification of cause of death. Their system emphasises the underlying rather than the direct cause of death, and the ICD classifications were replaced with the following categories: Land (diseases of the physical environment), Body (so-called ‘lifestyle diseases'), Spirit (diseases of poverty and cultural dislocation, including injury deaths), and Smoking-related. The authors calculated proportional mortality ratios and presented the results of a mortality analysis based on these ratios at feedback sessions and a workshop. No formal evaluation of this process was conducted, but informal feedback suggested that health information presented in this way was relevant and useful to the participating communities, and resonated more with the participants' world view. The development of injury-prevention projects and programs depends on a solid understanding of the various factors contributing to specific injuries. Reflecting the great diversity of injuries - and the diversity of disciplines and backgrounds among involved in injury prevention - approaches investigating these factors range from the traditional epidemiological single-risk-factor approach to broad sociological methods. The ecological model proposed in the World Report on Violence and Health provides one way of conceptualising the types of factors that need to be considered in the development of injury-prevention strategies . With a particular focus on violence, this model involves four levels: There are, of course, other ways of conceptualising the factors contributing to injury. Regardless of which classification scheme is used, however, it is important that the scope is wide enough to ensure that the analysis of ‘causes' will reveal most of the factors that need to be taken into account in the development of preventive strategies. This broad ecological approach to seeking causal factors is well established in the field of justice, being a feature of the work of the Royal Commission into Aboriginal Deaths and Custody , and also in the area of self-inflicted injury. It is a feature also of an analysis of road injuries in South Australia , but does not appear to be as widely used in the more traditional injury-prevention literature. Overall, however, the understanding of contributory factors is weak for most areas of injury, including injury among Indigenous people . Information facilitating the analysis of risk factors and mechanisms of injury is relatively scarce and varies across the specific topic areas considered. Most studies that have sought to identify risk factors have failed to explore the interplay of risk factors (for example, young males' alcohol consumption, risk-taking, and exposure to hazardous environments) . If we are to understand how these factors influence each other, more longitudinal, in-depth research is required. Such research, with greater collaboration between fields of study, should also help us identify the point in the chain of events that can offer the greatest opportunity for intervention. © Australian Indigenous HealthInfoNet 2013 This product, excluding the Australian Indigenous HealthInfoNet logo, artwork, and any material owned by a third party or protected by a trademark, has been released under a Creative Commons BY-NC-ND 3.0 (CC BY-NC-ND 3.0) licence. Excluded material owned by third parties may include, for example, design and layout, images obtained under licence from third parties and signatures.	2	2	0	0	2	0.69668	2	1,374
* To whom correspondence should be addressed. Received May 17, 2001; Revision received July 10, 2001 Cadherins are a family of membrane receptors that mediate calcium-dependent homophilic cell-cell adhesion. Cadherins play a key role in the regulation of organ and tissue development during embryogenesis. In adult organisms, these proteins are responsible for formation of stable cell-cell junctions and maintenance of normal tissue structure. Disruption in expression or function of cadherins may cause uncontrolled cell migration and proliferation during tumor development. This review focuses on the structure and physiological functions of classical cadherins. KEY WORDS: cadherins, cell-cell adhesion, morphogenesis, signaling, oncogenesis STRUCTURE OF CLASSICAL CADHERINS The majority of members of the cadherin superfamily are transmembrane glycoproteins that pass the membrane only once. The N- and C-termini of the cadherin protein chain are located outside and inside the cell, respectively (Fig. 1). The extracellular portion of the cadherin molecule consists of a varying number of so-called cadherin domains that are highly homologous to each other. Each domain is comprised of approximately 110 amino acid residues . Classical cadherins contain five cadherin domains that are commonly designated as EC1-EC5 (beginning with the N-terminus of the molecule). The conformation of the cadherin molecule is stable only in the presence of Ca2+, whose binding with the extracellular portion of the polypeptide chain is prerequisite for cadherin-mediated cell-cell adhesion. Calcium-binding sites consisting of short highly conserved amino acid sequences are located between neighboring extracellular repeats . The cytoplasmic domain of classical cadherins is associated with the cytoplasmic proteins catenins, which, in turn, serve as intermediate linkers between the cadherins and actin filaments [10-12]. It is this cadherin-catenin complex that is required for providing normal cell-cell adhesion. In principle, extracellular cadherin domains per se are capable of homophilic recognition and binding. It was shown that cells that express mutant cadherins lacking the cytoplasmic domains can bind with substrate covered with purified cadherin ectodomains. However, in this case adhesion is much weaker than in the case of cells bearing full-size cadherins [11, 13, 14]. These data indicate that the formation of stable cell-cell junctions depends on the presence in the cadherin molecule of functionally active cytoplasmic domain and association of the latter with the cytoskeleton. As mentioned above, cadherins mediate homophilic adhesion: during co-culturing of different types of cells, those cells first aggregate that bear identical cadherins on their surfaces . Similar dependence between cell sorting in the developing tissues and expression of different cadherins in them is observed during embryogenesis . The extracellular domains (primarily, the N-terminal domain EC1) play a key role in homophilic recognition between two cadherin molecules. It was shown that cells expressing chimerical E-cadherin, in which the EC1 domain was substituted with EC1 domain of P-cadherin, did not recognize the cells bearing native E-cadherin and aggregated with the P-cadherin-expressing cells . The site responsible for homophilic recognition contains 40 amino acid residues located in the C-terminal region of EC1. Blashchuk et al. assumed that sequence His-Ala-Val located in the C-terminal region of domain EC1 plays a key role in the interaction between cadherins because synthetic peptides containing this sequence effectively blocked mouse embryo blastomere assembling (a process that is mediated by cadherins). However, later it was shown that homophilic recognition also requires the presence of other regions located in the N-terminal domain. In addition, it was discovered that the sequence His-Ala-Val is contained only in the molecule of classical cadherins of type I that involves E- (epithelial), N- (neural), P- (placental), VE- (vascular endothelial), and R- (retinal) cadherins. The corresponding regions of type II classical cadherins that involve recently discovered cadherins designated by numbers 5-12 contain other amino acid residues [9, 10]. Type I and II cadherins also differ from each other in some amino acid residues. Fig. 1. Structure of classical cadherins and their interaction with cytoplasmic proteins . It should be noted that some cadherins can also mediate weak heterophilic interactions. In particular, E- and N-cadherin can bind with the integrin alphaEbeta7 and receptor for fibroblast growth factor [20, 21], respectively. The role of the four other cadherin repeats (EC2-4) in the cell-cell interaction remains obscure. Possibly, only EC1 domain directly participate in homophilic binding, whereas the remaining domains act as spacers providing the required distance between the junction and cell surface. Nevertheless, they are required for cadherin-dependent adhesion: in the absence of other extracellular domains, the N-terminal domain alone cannot maintain functional binding or adhesive activity . Numerous data that has accumulated to date show that the extracellular cadherin fragments exist in the form of stable parallel lateral dimers. Lateral dimers were revealed by X-ray analysis of N-cadherin EC1 domains and E-cadherin fragments including EC1 and EC2 domains . The existence of dimers was also shown for the whole extracellular fragment of C-cadherin . In the same experiments, it was also shown that the ability of C-cadherin monomers to aggregate significantly decreases compared to the dimers. To date, the mechanism of dimer formation is poorly understood. Apparently, N-cadherin dimers are stabilized by the hydrophobic interactions between the monomers , whereas in the case of EC1-EC2 fragment of E-cadherin dimeric structure is maintained by Ca2+ . It is still unclear why dimers exert higher activity than monomers during cell-cell interaction. Two main views on this phenomenon exist. The first hypothesis proposes that dimers are bivalent, which increases their avidity. The second hypothesis implies that dimer formation is associated with the occurrence of a unique site ensuring homophilic binding, which is absent from the monomers. The mechanism of interaction of cadherin dimers located on the membranes of different cells has been also the subject of much controversy. Based on the results of X-ray analysis of NCD1, Shapiro et al. proposed the existence of a zipper-like self-assembling structure. This molecular zipper model (Fig. 2) logically explains the mechanism whereby numerous weak bonds can ensure highly efficient binding in the cell layer. However, some authors believe that cadherin zipper is an in vitro artifact and suggest an alternative hypothesis that was formulated based on the results of electron microscopic analysis of adhesive zone preparations obtained by the freeze-fracture method . Separate protein cylinders extending from one cell surface to another and binding with the similar structures on the neighboring cell are seen on the images. According to the second model, cadherin molecules (dimers or oligomers) act as discrete units and do not form zipper-like ordered structures on the cell surface . Fig. 2. Two models of cadherin molecular organization in adhesive junctions. The molecular zipper model based on the results of X-ray analysis of N-cadherin EC1 domain is shown on the left. The model of cylindrical oligomers based on the results of electron microscopy of zonula adherens preparations obtained by the freeze-fracture method is shown on the right . The conclusion that cadherin complexes interact with the cytoskeleton was first made based on the data that cadherins cannot be extracted with non-ionic detergents that effectively solubilized other membrane proteins [13, 25, 26]. It was shown later that the major cytoplasmic proteins associated with the cytoplasmic domain of cadherins and participating in cell adhesion are alpha- and beta-catenins, which mediate the interaction between the cadherins and actin cytoskeleton [11, 13, 25, 27-30]. The catenin-binding site was mapped on E-cadherin. It is located at the distance of 56 amino acid residues from the C-terminus of the molecule [25, 31]. Biochemical analysis with the use of purified catenins and recombinant cytoplasmic domain of cadherins [32, 33] and expression of beta-catenin deletion mutants [34-36] showed that beta-catenin directly binds to the cytoplasmic cadherin fragment and serves as a linker for alpha-catenin attachment. The crucial role of the cytoplasmic domain of cadherin (and the catenin-binding site, in particular) is corroborated by numerous experiments. It was shown that deletion of the cytoplasmic domain or the catenin-binding site suppresses stable cadherin-mediated adhesion of cultured cells [11, 13]. Alternatively, overexpression of the catenin-binding site in the cultured cells , Xenopus laevis embryos , or in the intestinal cells of transgenic mice also entails disruption of cell-cell junctions. Such unusual, at first glance, result (at least, in the case of Xenopus laevis) can be, apparently, explained by competition of the expressed catenin-binding site with the endogenous cadherin for catenin binding. The evidence for participation of alpha-catenin in cell adhesion was obtained on lung carcinoma cell culture that does not contain alpha-catenin and aggregates with each other very weakly despite the presence of cadherins on the cell surface. However, transfection with alpha-catenin cDNA restores cadherin-mediated adhesion in these cells [27, 29]. Rim et al. showed that alpha-catenin directly binds to actin filaments both in vitro and in vivo in the cultured cells. The actin-binding protein alpha-actinin contained in adhesive junctions apparently also interacts with alpha-catenin . Participation of beta-catenin in cell adhesion was confirmed in experiments on Drosophila embryos using mutation analysis of protein armadillo, a homolog of beta-catenin . beta-Catenin is attached to the cytoplasmic domain of cadherin via its central region containing so-called armadillo repeats [34, 36]. These repeats (40 amino acid resides each) were first described in protein armadillo in Drosophila [40, 41]. alpha-Catenin binds to the N-terminus of beta-catenin [32, 34-36]. The role of a linker between cadherin and alpha-catenin is apparently the only function of beta-catenin in cell adhesion. It was shown that a chimerical molecule where the cytoplasmic domain of E-cadherin is substituted with alpha-catenin ensures cell adhesion in the absence of beta-catenin as successfully as the whole protein complex . Plakoglobin (gamma-catenin) sometimes substitutes beta-catenin in the cadherin-catenin complex . However, its physiological role is not completely understood. Plakoglobin is the major component of the desmosomes , where it is associated with the desmosomal cadherins [44, 45]. The high extent of homology of plakoglobin to beta-catenin and armadillo [26, 46] implies that these proteins may have similar functions. However, mouse embryo cells lacking beta-catenin due to genetic recombination aggregate very weakly and readily dissociate despite the presence of plakoglobin in them . This is indicative of inability of plakoglobin to completely substitute for beta-catenin in cell adhesion. Deletion of the plakoglobin gene, which was also caused by homologous recombination, entails lethal changes in the heart structure and early death of the embryos, presumably due to disruptions in desmosomal junction formation . Other cytoplasmic proteins directly associated with cadherin are tyrosine phosphatases [49, 50] and the substrate for src-kinase p120cas [51-53]. Interestingly, the level of cadherin expression in the cell may affect catenin expression. Transfection of L-cells with E-, N-, or P-cadherin cDNA results in a significant increase in the catenin content without changing the catenin mRNA content. Hence, the presence of cadherins regulates catenin expression at the post-translation level . It was also reported that cadherin cytoplasmic domain may mediate adhesion independently of catenins. Chimerical cadherin molecules in which cadherin cytoplasmic domain was substituted for the analogous domain of desmoglein-3 (one of desmosomal cadherins) that cannot bind catenins, mediates cadherin-dependent adhesion in the cultured cells . Thus, association with catenins is not the only way of participation of the intracellular cadherin domain in cell-cell adhesion. CELL-CELL JUNCTIONS CONTAINING CADHERINS Immunohistochemical analysis of tissues and cultured cells shows that cadherins most often are constituents of cell-cell adhesive junctions (Fig. 3). This type of junctions involves autotypic junctions between the layers of the same glial cell in the axon myelin sheath ; adhesive junctions in synapses, where cadherins link pre- and postsynaptic membranes in the regions adjacent to the neurotransmitter secretion areas [57, 58]; the intermediate disks between the cardiomyocytes ; and some other. The best-known type of cell-cell adhesive junctions is zonula adherens located at the apico-lateral border of the epithelial layer a little lower than the tight junctions. Actin bunches attached to the adhesive junctions girding the cell on the cytoplasmic side are located parallel to the membrane surface and form a united contracting network in the epithelial layer. Assembling of the belt-like zonula adherens is apparently the basis for the occurrence of the epithelial morphology of the cell layer [60-63]. During morphogenesis, folding of the epithelial layers into tubes is often attained by contraction of actin filaments contained in the zonula adherens, which is associated with narrowing the apical end of each cell in the apical layer and results in the cell layer bending [64, 65]. Besides cadherins and catenins, adhesive junctions contain numerous proteins (such as vinculin, ezrin, moesin, and radixin), protein components of the actin cytoskeleton, and integral membrane proteins (e.g., epidermal growth factor receptor, EGF) . Genetic studies on Drosophila revealed other components required for adhesive junction assembly. In particular, the genes whose mutations lead to disruptions in the course of zonula adherens assembling were identified in studies on Drosophila embryos. They involve the gene of beta-catenin homolog, armadillo, which is completely consistent with the view on the key role of this protein in cadherin-mediated adhesion [30, 67], as well as the genes crumb and stardust [67-69]. It was shown that gene crumb encodes the integral membrane protein that is required for epithelization of the ectodermic cells. In mutant individuals with inactive crumb gene normal cadherin-catenin complexes are expressed on the cell surface; however, their distribution is chaotic, leading to disruption in formation of mature zonula adherens in the epithelium [68-70]. Fig. 3. Cell-cell junctions formed by cadherins: a) epithelial zonula adherens; b) intermediate disks between the cardiomyocytes; c) adhesive junctions restricting the area of neurotransmitter secretion in the synapse; d) autotypic junctions between the glial cell layers in axon myelin sheath . It should be noted that in many cells cadherins can mediate adhesion without formation of morphologically pronounced adhesive junctions. Even in the epithelium of some organs, where cell-cell adhesion depends on E-cadherin, zonula adherens is absent . Cadherin-mediated adhesion without cadherin accumulation in the adhesive junctions was also described for blastomeres , nerve ridge cells , and fibroblasts transfected with different types of cadherins . REGULATION OF CADHERIN ACTIVITY Cadherin-mediated adhesion can be regulated by a variety of extracellular signals, including growth factors [72-74], peptide hormones [75, 76], signals from gap junctions , and cholinergic receptor agonists . In response to these external stimuli, different signals are generated in the cell, of which protein phosphorylation is, apparently, the most important for the regulation of cadherin function . Protein kinase C (PKC) participates in the activation of E-cadherin-dependent mouse embryo cell compacting, which was demonstrated with the use of a combination of pharmacological agonists and antagonists. Embryo compacting is accelerated by the addition of PKC-stimulating agents (e.g., phorbol ester and diacylglycerol) and inhibited by PKC-blocking agents , the PKC effect being blocked by the addition of anti-E-cadherin antibodies. However, it was not determined which PKC-mediated way is activated in this case. Using a similar experimental approach, a potential inhibitory effect of tyrosine phosphorylation on cadherin function was shown. Several scientific groups discovered that enhancement of tyrosine phosphorylation (transfection with v-src or incubation of the cells with pervanadate) weakens cadherin-mediated cell-cell adhesion. Components of the cadherin-catenin complex (primarily beta-catenin) undergo tyrosine phosphorylation in response to v-src transfection and incubation with pervanadate [80-82]. Attenuation of adhesion in these experiments was blocked by herbimicin, which is also indicative of participation of tyrosine phosphorylation in the regulation of cadherin activity. It was also shown that v-src can affect cadherin-mediated adhesion irrespective of beta-catenin . The authors of this work used mutant E-cadherin that could directly bind with the C-terminal fragment of alpha-catenin and induce adhesion without the participation of beta-catenin. However, in this case transfection with v-src also significantly inhibited cell-cell adhesion. Other data confirming the effect of tyrosine phosphorylation on cadherin-dependent adhesion are known. Tyrosine phosphorylation of beta-catenin is observed when cells are treated with hepatocyte growth factor (HGF) and EGF (agents that can induce dissociation of epithelial cells) . Tyrosine kinases or their substrates can associate with the cadherin-catenin complex. It is known that p120cas, a member of the armadillo protein family, is a substrate for both src kinases and receptor tyrosine kinases . It was shown that p120cas directly binds to the distal part of the cytoplasmic domain of E-cadherin, forming a whole complex with cadherin and beta-catenin or plakoglobin [52, 53, 84, 85]. Activation of the Erb-2/Neu receptor tyrosine kinase in the epithelial cells causes disassembling of the cell-cell junctions formed by E-cadherin, which results in the loss of the epithelial phenotype by the cells . EGF receptor tyrosine kinase also can bind to the cadherin-catenin complex . In addition, it was shown that cadherin-catenin complex can interact with receptor-dependent tyrosine phosphatases [49, 50, 88]. Cadherin function may also be affected by cell-cell communication via gap junctions. Inhibition of cell-cell communication by expression of the chimerical protein connexin 32/connexin 43 inhibitor (a protein that forms gap junctions) in Xenopus embryo cells leads to blastomere separation. A similar effect is observed when mutant cadherin is expressed in the embryo cells. This phenotype can be corrected by coexpression of connexin 37 that is insensitive to the inhibitor . Similarly, cell-cell junction assembling in Novikov hepatoma cells is suppressed by anti-connexin and anti-cadherin antibodies . The mechanism of signal transduction mediated by the gap junctions remains obscure. It is assumed that in this case cadherin-dependent adhesion and cell-cell junction assembling may be regulated via temporal increase in the concentration of Ca2+ and other small signal molecules (such as cyclic nucleotides or inositol phosphate) penetrating through the gap junctions and activating the intracellular processes that affect cadherin activity. The strength of cell-cell interactions can be affected both by modulating cadherin activity and changing their expression level in the cell. It was demonstrated that an increase in cadherin content enhances cell adhesion [7, 90, 91]. It was also shown that cadherin expression in cultured cells is regulated by growth factors and peptide hormones [72, 73, 75, 76]. Another mechanism of regulation of cadherin activity is changing the extent of clustering of cadherin molecules in the junction area. As was mentioned above, lateral clustering of cadherin molecules can significantly affect the strength of cell-cell interaction. Changes in the extent of clustering can mediate rapid changes in cell adhesion strength. For example, mouse embryo blastomere compacting is associated with E-cadherin redistribution in the region of cell-cell junctions without any change in protein expression . CADHERINS AND SIGNALING To date, numerous data indicate that cell adhesion receptors can affect cell form, motility, and growth not only due to mechanical attachment of the cells to each other or to the substrate, but also by activating internal signaling . Some papers report that many effects of cadherin on cell behavior are rapid and apparently caused by a series of short-term signals rather than by assembling stable long-term cell-cell junctions [4, 6, 94]. However, until recently only indirect evidence of cadherin ability to induce the production of secondary messengers in the cell have been known. For instance, it was shown that axon outgrowth stimulated by N-cadherin is associated with changes in the cytoplasmic Ca2+ concentration and activation of G-proteins and tyrosine kinases. However, it was not clear whether these signals result from the direct interaction of N-cadherin molecules [95, 96]. Because different signal molecules (such as proteins belonging to the non-receptor src kinase family as well as some membrane receptors and phosphatases) were found in the cell-cell junctions of epithelial cells [49, 97, 98], it was suggested that these molecules can mediate cadherin-dependent signaling. Data on the direct effect of cadherins on the signal processes appeared only during the last two years. It was shown that inter-cadherin junctions in cultured fibroblasts induced oscillations in the cytoplasmic Ca2+ concentration, antibodies raised against the first domain EC1 mimicking this effect. The oscillations occurred in the regions of cell-cell interactions and coincided in time with translocation of actin and other cytoplasmic proteins into the adhesive complexes . N-Cadherin can regulate axon outgrowth by direct interaction with the EGF receptor, thereby activating the cascade of mitogen-activated protein kinases (MAPK) . The experiments on cultured keratinocytes showed that adhesive junction formation leads to a rapid activation of MAPK-dependent signaling and that this effect is mediated by E-cadherin. In addition, E-cadherin can stimulate MAPK by ligand-independent activation of EGF receptors . It also activates Cdc42, a low-molecular-weight GTPase belonging to the Rho family, which regulates the cytoskeleton structure . For a long time beta-catenin, whose signal activity is well known, was considered as a candidate for the role of a messenger of signal transduction from cadherins, with which it is associated. beta-Catenin and its homolog armadillo from Drosophila are components of Wnt/wingless signal pathway that plays a key role in embryogenesis [102-104]. Recent data, however, indicate that the interaction between beta-catenin and cadherins is not prerequisite for manifestation of its signal activity. It was also shown that beta-catenin function as a cadherin partner during adhesive junction formation is not directly associated with its signal function in the cytoplasm and/or nucleus, where it affects transcription of genes by interacting with specific transcription factors [36, 105-111]. Free beta-catenin content in the cytoplasm is regulated by the protein product of the APC (adenomatous polyposis coli) gene. Formation of the complex between these two proteins is a signal for beta-catenin degradation. Conversely, triggering the Wnt signal pathway results in beta-catenin stabilization, its accumulation in the cytoplasm, and binding to the transcriptional factor Tcf, which, in turn, stimulates transcription of some genes. On the other hand, although the adhesive and signal functions of beta-catenin are separated, the formation of cell-cell junctions can apparently indirectly affect beta-catenin-dependent signaling. It was shown that overexpression of cadherins in the embryos of Xenopus laevis and Drosophila inhibited signal transduction via beta-catenin/armadillo [106, 112]. In Xenopus embryos, the inhibition is due to beta-catenin binding with C-cadherin on the inner surface of the cell membrane. As this takes places, beta-catenin is removed from its cytoplasmic pool, becoming inaccessible for participating in signaling. Thus, cadherins can regulate beta-catenin signaling activity by changing its distribution in the cell. It cannot be ruled out, however, that cadherins indirectly contribute to signaling regulation. Approaching of the membranes of the neighboring cells during adhesive junction formation may enable the interaction of membrane receptors and their membrane-bound ligands on the neighboring cells and activate juxtacrine signaling. This hypothesis is corroborated by data on association of some signal molecules with the cadherin-catenin complexes and on high concentration of tyrosine kinase substrates in the regions of adhesive junctions. The group of juxtacrine receptors described to date involves notch, delta, sevenless, and bride-of-sevenless (boss) receptors participating in Drosophila embryogenesis [113, 114] and associated with the membrane form of tumor necrosis factor (TNF) and transforming growth factor (TGFalpha) . It is tenable to assume that signaling via such receptors depends on the proximity of the surface of adjacent cells and, respectively, on formation of inter-cadherin junctions. This hypothesis is confirmed by the fact that expression of cadherins in the fibroblasts entails communication enhancement via gap junctions . THE ROLE OF CADHERINS IN MORPHOGENESIS The formation of tissues and organs during embryogenesis is determined by a number of processes coordinated in time and space, such as cell aggregation, polarization, differentiation, and migration. Because cell-cell and cell-nuclear matrix adhesive junctions play a key role in all these events, adhesion receptors are often called morphoregulatory molecules. One such adhesion-dependent processes is selective cell segregation. This phenomenon was discovered as early as in the 1950s. In classical works in embryology, it was shown that suspended cells from different amphibian blastophylla are capable of homotypic reaggregation to form junctions only with similar cells in correspondence with their histogenetic origin . Later it was discovered that this homotypic aggregation is based on selective expression of specific adhesion molecules on different subpopulations of cells. The role of cadherins in this process was revealed by Nose et al. . The L-cells were transfected with cDNA of either E- or P-cadherin. The suspensions were then mixed in vitro and analyzed for cluster formation. Under these conditions, highly selective adhesion between cells expressing cadherins of the same type was observed. Another morphogenetic process in which cadherins play a key role is cell condensing (i.e., transition of cell population from dispersed state to condensed solid formation). An example of such condensing is blastomere assembling at the early stages of embryogenesis. E-Cadherin plays a crucial role in cell condensing in mouse embryo morula: the embryo structure is disrupted as a result of treatment of the cells with blocking anti-E-cadherin antibodies, introduction of antisense nucleotides to E-cadherin mRNA into the cell, and in transgenic mice defective by the gene encoding this protein [118-123]. Injection of antisense nucleotides into Xenopus laevis oocytes, which decreases expression of EP-cadherin (a Xenopus laevis protein homologous to E- and P-cadherins), significantly attenuates adhesion between the blastomeres and entails disruption of the embryo structure . Numerous studies performed both in intact embryos and cultured cells revealed significant correlation between epithelization of mesenchymal cells and expression of specific cadherins in them. During somite development, mesenchymal cells comprising its future wall are polarized and temporarily form epithelium-like structures, the expression of N-cadherin in them significantly increasing [64, 65, 125]. Transfection of cultured mesenchymal cells with cDNA of different cadherins results in their epithelization [13, 126-128], whereas inhibition of cell-cell interactions by anti-cadherin antibodies leads to the loss of epithelial phenotype by the cells and stimulates cell motility and invasiveness [129-131]. One of the most vivid examples of participation of cadherins in morphogenesis is their role in the central nervous system development. At different stages of embryogenesis and in different structural layers, neuroepithelial tissues express more than 20 different cadherins involved in all key events of neurogenesis, beginning from selective aggregation of the cells at the earliest stages of embryo development and finishing with the formation of synapses [132-137]. Cadherins play a key role during neuroectoderm sorting and neural tube formation. It was also shown that before segregation of the neuroectoderm from the ectoblast in neurula, a coordinated decrease in the expression of E-cadherin and increase in that of N-cadherin occurs in the cells of future neuroectoderm. It is believed that it is N-cadherin that is responsible for selective cell uniting in the neural plate [64, 65, 138]. Interestingly, normal neural tube is formed in transgenic mice defective in the N-cadherin gene. Apparently, in this case N-cadherin is functionally substituted with other adhesion molecules (presumably, cadherin-6) . It is known that the coordinated change in the cell shape induced by microfilament contraction in zonula adherens underlies neural tube folding and other morphogenetic processes that require change in the shape of the epithelial layers [64, 65]. Further development of the neural tube involves its segregation to separate regions due to local expression of different cadherins. For example, selective distribution of E- and R-cadherins, cadherin-6, and cadherin-8 in different regions of embryonic brain is observed [135, 136, 140, 141]. The possibility of selective segregation of nerve cells that express cadherins of the same type was demonstrated in vitro. In vivo such segregation of the neural tube to segments apparently prevents the migration of nerve cells between adjacent regions of the developing brain . Normal expression of cadherins is required for neurite outgrowth activating and regulating. The expression of dominant-negative functionally inactive N-cadherin in developing frog retina blocks the axon and dendrite outgrowth. Those axons that are still formed are usually shorter and often do not have growth cones . In the experiments in vitro, it was shown that growth and migration of axons change during neuron culturing on the substrates containing recombinant cadherins. In particular, recombinant N-cadherin enhances adhesion of axons to the substrate and enables their projecting in the direction of higher concentrations of the recombinant protein. Similar growth stimulation is observed when the neurons are cultured on the monolayer of cells transfected with N-cadherin cDNA [8, 95, 143-146]. Such effect on axon projecting is apparently due to the interaction of N-cadherin with FGF receptor with subsequent MAPK activation . By contrast, another member of the cadherin family, T-cadherin, inhibits axon outgrowth [137, 147]. Thus, the coordinated action of different cadherins and other adhesion receptors expressed on the axon membrane and surrounding tissues ensure navigation of axon projecting to the peripheral targets. Cadherins also play a key role in setting and stabilization of junctions between the neurons and formation of neural nets and neuromuscular junctions [148-153]. In mouse postnatal brain, cadherins of the same type are expressed in functionally related regions (e.g., in the thalamus nucleus and related cortex regions ). During chick eye development N-cadherin stabilizes the junctions between the axon termini and their targets. Formation of a branched net of neural termini in the retina may be blocked by injecting anti-N-cadherin antibodies . It was shown that in synapses cadherins anchor the pre- and postsynaptic membranes, bordering the area of neurotransmitter secretion [57, 58]. E-Cadherin is also present in the myelin sheath of nerves, where it forms autotypic adhesion junctions between the plasma membrane layers of the same Schwann cell (Fig. 3). CADHERINS AND ONCOGENESIS The ability of tumor cells for uncontrolled growth, migration, invasion into surrounding tissues, and metastasizing is often associated with disruption of cell-cell and cell-extracellular matrix junctions [156, 157]. For this reason, special attention is currently paid to identification and characterization of cell adhesion receptors involved in tumor development. With regard for the role of cadherins in cell-cell adhesion, maintenance of tissue structure, and regulation of epithelial cell phenotype, it was assumed that the disruption of cadherin-dependent cell-cell interactions in the epithelium may cause attenuation of cell-cell junctions, loss of epithelial phenotype, enhancement of cell motility, removal of contact suppression of growth, and, as a result, uncontrolled proliferation and invasion of tumor cells . The majority of studies in this area focus on the role of E-cadherin in malignant cell transformation. In many works, it has been shown that E-cadherin expression is decreased or absent from different carcinomas (esophagus, stomach, or breast) [159-162]. Abnormal distribution of E-cadherin in tumor cells was often observed (it was absent from the regions of adhesion junctions). It should be noted that E-cadherin expression was most often decreased in the undifferentiated aggressive carcinomas that have high invasive potential . Similar results were obtained on cultured cells. Frixen et al. also reported that carcinoma cell lines with the epithelial noninvasive phenotype expressed E-cadherin, whereas the latter was absent from the cells with the fibroblastoid phenotype. Navarro et al. revealed reciprocal dependence between the amount of E-cadherin expressed on the cell surface of different carcinomas and the ability of these cells for invasion. Malignant transformation of MDCK epithelial cells (which are noninvasive in normal state) as a result of injection of Harvey and Maloney sarcoma virus to the cell culture is accompanied by a decrease in E-cadherin expression on the cell surface. A similar change of MDCK cell phenotype from noninvasive for invasive is also observed after disruption of cell-cell junctions in the presence of anti-E-cadherin antibodies . Conversely, transfection of the carcinoma cells with E-cadherin cDNA restores normal cell phenotype, decreases invasiveness and migration, and suppresses tumor growth [163-165]. The few studies on the role of P-cadherin in oncogenesis also revealed a correlation between decreased expression of this protein and the invasiveness of lung carcinomas and melanomas . Unexpected results were obtained when studying the effect of N-cadherin on tumor cells. It was discovered that expression of this protein is significantly enhanced in invasive undifferentiated breast carcinoma cells . It was also shown that an increase in N-cadherin expression in the carcinoma cells simultaneously with the decrease in E- and P-cadherin expression changes the phenotype from epithelial to mesenchymal . Transfection of MCF-7 carcinoma cells with N-cadherin cDNA significantly enhances the invasiveness and stimulates metastasis development despite the presence of E-cadherin in these cells . Such an opposite effect of cell-cell adhesion mediated by E- and N-cadherins on cell behavior may be due to the ability of E-cadherin to form stable cell-cell junctions that prevent cell migration, whereas N-cadherin can form labile junctions required for such dynamic processes as axon projecting or migration and invasion of tumor cells . Other components of cadherin complexes (primarily catenins) can also affect the growth and migration of transformed cells. As was mentioned above (see Cadherins and Signaling), normal expression of free beta-catenin in the cytoplasm is maintained by the oncosuppressing protein APC that binds with excessive beta-catenin and activates its degradation . In patients with hereditary polyposis, who are predisposed to intestine cancer, mutations in the APC gene or directly in beta-catenin gene are often observed. As a result of these mutations, the APC protein lacks its ability to regulate beta-catenin level in the cytoplasm, which leads to uncontrolled activation of the Tcf transcription factor by beta-catenin and development of intestine tumors . T-CADHERIN IS AN ATYPICAL MEMBER OF THE CADHERIN FAMILY T-Cadherin (truncated) (or H-cadherin (heart), or cadherin-13) is one of the most unusual members of the cadherin superfamily. Although its N-terminal domain EC1 does not contain the His-Ala-Val sequence, its extracellular part comprised of five cadherin repeats is very similar in structure to the classical cadherins. A unique feature of this protein is the absence of both the transmembrane and cytoplasmic domains. It is anchored in the membrane via glycosylphosphatidylinositol (GPI) that attaches to the mature protein after cleavage its C-terminal sequence during processing in the endoplasmic reticulum . Despite the absence of the cytoplasmic domain, T-cadherin can mediate any weak homophilic adhesion of the suspended cells . The mechanisms of formation of cell-cell junctions via T-cadherin and classical cadherins are apparently significantly different because the majority of cadherins ensure adhesion only when they contain the cytoplasmic domain that mediates their binding with the cytoskeleton [11, 13]. Another unusual property of T-cadherin is simultaneous expression on the cell surface of its two forms (the mature protein and partially processed precursor containing an uncleaved propeptide, whose function remains obscure) . T-Cadherin was first discovered in chick nervous system [137, 175]. Later its human homolog called cadherin-13 was identified . The only physiological function of T-cadherin established so far is its participation in the regulation of neuron growth during embryogenesis. During formation of chick embryo hind limbs, the outgrowing axons avoid those regions where T-cadherin is expressed . Neuron culturing on substrate containing recombinant T-cadherin significantly inhibits axon growth . Contact suppression of axon growth as a result of homophilic binding between T-cadherin molecules located on the axon membrane and surrounding mesenchymal tissues is apparently a navigating mechanism whereby the direction of nerve fiber growth is determined. Numerous recent data indicate that malignant tumor development is associated with the changes in T-cadherin expression. The loss of chromosome 16q24 locus containing T-cadherin gene correlates with the development of pancreas, lung, stomach, and ovary cancers [177-182]. The transfection of tumor cells with T-cadherin cDNA entails a decrease in the proliferative and invasive activities both in vitro and in vivo as a result of challenging the mice with tumorigenic cell lines as well as the loss of cancer cell sensitivity to the action of growth factors . The mechanisms of T-cadherin effect on cell adhesion and proliferative activity are still unknown. It cannot be ruled out that the maintenance of mechanical junctions between the cells is not the main function of this protein. It is most likely that it serves as a signal receptor, a sensor that allows the cell to sense its environment. This hypothesis is corroborated by the data on T-cadherin distribution in the membrane: in the polarized intestinal cells it is located on the apical part of the cell rather than in the adhesive junctions on the basolateral cell surface . It has long being known that many other GPI proteins may activate intracellular signaling [186-188]. The absence of the cytoplasmic domain in these proteins implies the presence of a membrane adapter protein. Owing to the interaction with the latter, the signal can be relayed across the membrane from the GPI proteins into the cell. We showed that, similar to other GPI proteins, T-cadherin is located on the cell surface in special plasma membrane domains (caveolae and lipid rafts) , which also contain other signal molecules (such as G-proteins, src kinases, rasproteins, and transmembrane receptors of growth factors ). It cannot be excluded that some of these molecules may serve as messengers during activation of T-cadherin-dependent signaling. In our laboratory, the main attention is focused on investigation of the role that T-cadherin plays in the cardiovascular system function. Cell adhesion molecules play a crucial role in the maintenance of normal structure of vascular walls. The development of different pathologies (such as atherosclerosis and restenosis after balloon angioplasty and atherectomy) is characterized by enhanced migration, proliferation, and phenotypic modulation of the endothelial cells, which is often associated with disruption of cell-cell and cell-extracellular matrix junctions [191, 192]. The expression and functions of T-cadherin in the cardiovascular system have not been studied before. We performed a comparative study of T-cadherin expression in different human organs and tissues. The results show that T-cadherin content is maximal in the aorta, carotid, iliac, and kidney arteries, and in heart. In aorta wall, T-cadherin is contained in the endothelial and smooth muscle cells and pericytes. Its expression in the smooth muscle cells depends on the cell phenotype and proliferative activity [193-195] and increases in sclerotic lesion of vascular walls . Preliminary studies performed on the model of balloon catheterization of rat carotid artery indicate that T-cadherin expression in smooth muscle cells increases in restenosis. The content of this protein is also elevated in the endothelium isolated from tumor vasculature . In addition, anti-T-cadherin antibodies can affect the phenotype, adhesion, and motility of the endothelial cells in vitro (our unpublished data). With regard for these data, it is likely that T-cadherin plays a key role in the regulation of cell phenotype, migration, and growth, as well as in maintenance of vascular wall structure. Study of the interaction of heterophilic interactions between T-cadherin and blood plasma lipoproteins is also of great interest. Originally, the work of our group was aimed toward searching for the receptors that mediate the hormone-like effect of low-density lipoproteins on the systems of intracellular signaling in smooth muscle cells in human vasculature [197, 198]. On the surface of membranes of aorta smooth muscle cells, we discovered two unusual lipoprotein-binding proteins with molecular weight of 105 and 130 kD. The characteristics of these proteins are indicative of their participation in lipoprotein-dependent signaling [199, 200]. After isolation of these receptors from human aorta medium and determination of their amino acid sequence, we discovered that the 105-kD protein is mature T-cadherin , whereas the 130-kD protein is its partially processed precursor . It is known that increased lipoprotein content in blood plasma is a risk factor of development of vascular pathologies based on increased proliferation and migration of smooth muscle cells. 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Attention Deficit Hyperactivity Disorder (ADHD), including the different types and who gets them. - Bipolar Disorder Facts about bipolar disorder, including different types and symptoms. - ADHD Attention Deficit Hyperactivity Disorder (ADHD), including the different types and who gets them. - Adult ADHD Facts about attention deficit hyperactivity disorder (ADHD) in adults. - Alzheimer's Disease Facts about Alzheimer’s Disease, including the symptoms and stages. - Autism Spectrum Disorder Get the facts about Autism Spectrum Disorder (ASD). - Chronic Pain Facts about chronic pain, including body parts most commonly affected. - Clinical Depression Clinical depression facts; symptoms & other depressive disorders. - Depression Facts about depression, including the symptoms of the condition. - Diabetic Neuropathy Facts about diabetic neuropathy, including the symptoms and doctors. - Epilepsy Facts about epilepsy, including different types, symptoms and causes. - View All Care Guides Prepare for your next visit with our extensive library of Care Guides Dr. James R Wright III has the following 2 specialties A psychiatrist is a doctor with specific training in the diagnosis and treatment of mental illness. He or she can not only provide the counseling necessary to both diagnose and treat a patient, but can also prescribe medication when needed. In some cases, a psychiatrist will only provide the medication and the counseling will be provided by another healthcare specialist, like a certified counselor or psychologist. Like other doctors, psychiatrists employ diagnostic tools like CT scans and MRI in order to observe the structure and function of a patient's brain. Once a diagnosis is made, these specialists may use behavior or cognitive therapy in order to address the patient's condition, or a multitude of other types of therapy, in conjunction with or in place of medication. A neurologist is a physician who diagnoses and treats disorders of the nervous system which is comprised of the brain, spinal cord and nerves. These doctors do not perform surgery, but refer patients to neurological surgeons when they determine that surgical intervention is necessary. Some of the conditions that neurologists diagnose and treat are epilepsy, aneurysms, hydrocephalus, Parkinson's disease, multiple sclerosis, stroke, spinal disc herniation, and spinal disease. In addition to using diagnostic tests like MRI, CT scans, EEG and EMG, neurologists also employ neurological testing to gauge muscle strength and movement, balance, reflexes, sensation, memory, speech, and other cognitive abilities. Dr. James R Wright III has the following 15 expertise - Mood Disorders - Sleep Disorders - Erectile Dysfunction (ED) - Obsessive-Compulsive Disorder (OCD) - Anxiety Disorders - Closed Head Injuries - Personality Disorder - Attention Deficit Disorder (ADD) / Attention Deficit Hyperactivity Disorder (ADHD) - Mental Illness - Depressive Disorder - Attention-Deficit/Hyperactivity Disorder (ADHD) - Bipolar Disorder Dr. James R Wright III is Board Certified in 1 specialty See the board certifications this doctor has received. Board certifications provide confidence that this doctor meets the nationally recognized standards for education, knowledge and experience. Showing 5 of 97 He fell asleep while I was talking to him. I feel like he never listened to me because his eyes wouldn't meet mine. He was looking my way but I had to repeat things several times. The staff-disorganized, forgot to answer faxes from my pharmacy which led me to going to the ER. They NEVER answer the phone. They have been rude to my husband and I by informing us that if we didn't pay a 25.00 balance that my appt would be canceled, I would be fired as a patient & my account would go to their collection agency. Wow! My husband called on the weekend and his answering service tried contacting Dr. Wright and he never returned any of my calls. I was suicidal and in a dark place. Beware. I felt like a number in the last couple of years. Ive been a patient for 2 years. I was seeing Jeanete who represented herself as a nurse practitioner. After many visits & always feeling like she would throw medication at me, I did some research. She's not even a nurse practitioner as her cards, door & staff says she is. THIS IS AGAINST THE LAW to misrepresent herself! I saw other patient charts laying around. Front desk staff named Tanya, should be fired. She was rude to me several times I called. She refused my refill & I had an appt within the week. I had major withdrawals and almost took a handful of pills because I didn't want to live once I started feeling the withdrawal of NOT having my medication. jeanete gave me her cell # but would never respond to my texts.She spent our appts cussing and complaining about the office staff. All of their old staff is gone and they were the ones who were caring. The new staff is awful. I started with the doctor & he was the most unresponsive man I've ever met. DO NOT GO! Patients' Choice Award (2009, 2010, 2018) Patients' Choice recognition reflects the difference a particular physician has made in the lives of his/her patients. The honor is bestowed to physicians who have received near perfect scores, as voted by patients. On-Time Doctor Award (2014) Vitals On-Time + Promptness Award recognizes doctors with consistent high ratings for timeliness of appointments. The honor is granted based on a physician's overall and promptness scores. Compassionate Doctor Recognition (2011) Compassionate Doctor certification is granted to physicians who treat their patients with the utmost kindness. The honor is granted based on a physician's overall and bedside manner scores. 43 Years Experience The University Of Texas School Of Medicine At San Antonio Graduated in 1975 University Of Texas Health Science Center Dr. James R Wright III accepts the following insurance providers. BCBS Blue Card - BCBS Blue Card PPO - BCBS TX Blue Advantage HMO - BCBS TX BlueChoice - BCBS TX HMO Blue Texas - CIGNA HMO - CIGNA LocalPlus - CIGNA Open Access Plus - CIGNA PPO - First Health PPO - Multiplan PPO - PHCS PPO Locations & DirectionsJames Robert Wright Iii Md, 14340 Torrey Chase Blvd Ste 325, Houston, TX Dr. James R Wright III is similar to the following 3 Doctors near Houston, TX.	2	6	1	0	0	0.966536	1	1,359
Get the facts about attention deficit hyperactivity disorder (ADHD) in adults, including the different types and symptoms of each. - Bipolar Disorder Facts about bipolar disorder, including different types and symptoms. - ADHD Attention Deficit Hyperactivity Disorder (ADHD), including the different types and who gets them. - Adult ADHD Facts about attention deficit hyperactivity disorder (ADHD) in adults. - Alzheimer's Disease Facts about Alzheimer’s Disease, including the symptoms and stages. - Autism Spectrum Disorder Get the facts about Autism Spectrum Disorder (ASD). - Chronic Pain Facts about chronic pain, including body parts most commonly affected. - Clinical Depression Clinical depression facts; symptoms & other depressive disorders. - Depression Facts about depression, including the symptoms of the condition. - Diabetic Neuropathy Facts about diabetic neuropathy, including the symptoms and doctors. - Epilepsy Facts about epilepsy, including different types, symptoms and causes. - View All Care Guides Prepare for your next visit with our extensive library of Care Guides Dr. Luke P Peris has the following 2 specialties A psychiatrist is a doctor with specific training in the diagnosis and treatment of mental illness. He or she can not only provide the counseling necessary to both diagnose and treat a patient, but can also prescribe medication when needed. In some cases, a psychiatrist will only provide the medication and the counseling will be provided by another healthcare specialist, like a certified counselor or psychologist. Like other doctors, psychiatrists employ diagnostic tools like CT scans and MRI in order to observe the structure and function of a patient's brain. Once a diagnosis is made, these specialists may use behavior or cognitive therapy in order to address the patient's condition, or a multitude of other types of therapy, in conjunction with or in place of medication. A neurologist is a physician who diagnoses and treats disorders of the nervous system which is comprised of the brain, spinal cord and nerves. These doctors do not perform surgery, but refer patients to neurological surgeons when they determine that surgical intervention is necessary. Some of the conditions that neurologists diagnose and treat are epilepsy, aneurysms, hydrocephalus, Parkinson's disease, multiple sclerosis, stroke, spinal disc herniation, and spinal disease. In addition to using diagnostic tests like MRI, CT scans, EEG and EMG, neurologists also employ neurological testing to gauge muscle strength and movement, balance, reflexes, sensation, memory, speech, and other cognitive abilities. Dr. Luke P Peris has the following 12 expertise - Personality Disorder - Sleep Disorders - Attention Deficit Disorder (ADD) / Attention Deficit Hyperactivity Disorder (ADHD) - Bipolar Disorder - Attention-Deficit/Hyperactivity Disorder (ADHD) - Depressive Disorder - Manic Depressive Disorder - Mental Illness - Mood Disorders Dr. Luke P Peris has 0 board certified specialties Showing 5 of 25 I was referred to Dr Peris when I moved to Dallas. I had been medicated off and on for 15 years before him and never felt well. I saw Dr Peris for 9 years until I moved. He was the best Psychiatrist I have been to. He had me take a med combo that worked promptly. He is on time, easy to schedule a last minute appointment,and he also returns phone calls within hours. Even on weekends. In all honesty, I picked Dr. Peris because his office is across the street from my job. But I lucked out. Getting an appointment is easy, especially compared to some places I have gone. His office manager, Eleanor, is awesome. She takes care of everything, is well organized and always calls to remind me of appointments. I am never left waiting for long periods of time. And Dr. Peris himself is pretty great. I've had doctors where they literally saw me for 5 minutes before handing me a refill and pushing me out the door, still holding my list of concerns that I had wanted to discuss. Dr. Peris doesn't do that. If you have a laundry list of things to discuss, then he has the time to discuss them with you. He is knowledgeable about a large spectrum of topics. He is kind and considerate. Even if I change jobs, I won't change doctors. We have been appreciative patients of Dr Peris for 3 years. I have found him to be respectful, helpful, and caring. His approach is supportive and conservative. One of his strengths is that he really does know his meds and the many ways they can be used well. Words cannot express our thankfulness for Dr Peris. I've been to great psychiatrists, and I've been to terrible ones. Dr. Peris is the very best. He's also a therapist, so he isn't solely focused on doling out medication. He understands the value of combining therapy, diet, exercise, etc. with drug therapy. His office administrator, Eleanor, is also wonderful. A friend referred him to me, and I've since referred him to several other people. In the six years I've been seeing him I've never left his office dissatisfied. On-Time Doctor Award (2016, 2017, 2018) Vitals On-Time + Promptness Award recognizes doctors with consistent high ratings for timeliness of appointments. The honor is granted based on a physician's overall and promptness scores. Compassionate Doctor Recognition (2015, 2016, 2017, 2018) Compassionate Doctor certification is granted to physicians who treat their patients with the utmost kindness. The honor is granted based on a physician's overall and bedside manner scores. Patients' Choice Award (2016, 2017, 2018) Patients' Choice recognition reflects the difference a particular physician has made in the lives of his/her patients. The honor is bestowed to physicians who have received near perfect scores, as voted by patients. 34 Years Experience University Of Oklahoma College Of Medicine Graduated in 1984 Nassau University Medical Center Dr. Luke P Peris accepts the following insurance providers. - Aetna Managed Choice POS Open Access BCBS Blue Card - BCBS Blue Card PPO - BCBS TX Blue Advantage HMO - BCBS TX BlueChoice - BCBS TX HMO Blue Texas - CIGNA HMO - CIGNA LocalPlus - CIGNA Open Access Plus - CIGNA PPO - Multiplan PPO Locations & DirectionsLuke Prakash Peris Md, 14800 Quorum Dr Ste 465, Dallas, TX Dr. Luke P Peris is similar to the following 3 Doctors near Dallas, TX.	2	9	1	0	0	0.956358	1	1,382
- 1 Disease Entity - 2 Diagnosis - 3 Management - 4 References Round hole of retina without detachment ICD-10 H33.32 (non-billable); retinal breaks without detachment ICD-10 H33.3 (billable) An atrophic retinal hole is a break in the retina not associated with vitreoretinal traction. Etiology and Risk Factors Idiopathic atrophic retinal hole is the most common presentation. There are no generally accepted risk factors for this condition but lesions have been cited more often in younger myopic patients. It has been estimated about 5% of the general population has atrophic holes. Atrophic holes often present in the peripheral (temporal or superior) retina. There appears to be no sex predilection. Atrophic retinal holes are full thickness retina breaks often existing in the peripheral retina. They are the result of atrophic changes/thinning within the sensory retina that is not induced by vitreous adhesions. Often, these lesions are found in association with lattice degeneration. The incidence of this association has been reported as high as 43%. Retinal holes are the result of chronic atrophy of the sensory retina. These lesions often take a round or oval shape. It has been postulated that the pathogenesis of this lesion stems from an atrophic pigmented chorioretinopathy that is associated with retinal vessel sclerosis and a disturbance of the overlying vitreous. As the blood supply to the retina is shut down, the retinal tissue subsequently dies in conjunction with degeneration of the surrounding vitreous. This pathology precludes traction of the vitreous to the underlying sensory retina. There are no preventative measures to the development of atrophic retinal holes. This is a clinical diagnosis based on history and clinical exam, including slit lamp and dilated fundus examination. Patients with atrophic retinal holes generally present for routine ocular examinations. This type of lesion is generally an incidental finding. Some patients may present with a complaint of photopsias (flashing lights) or other visual disturbance if associated with a symptomatic posterior vitreous detachment. Slit lamp examination with special attention to the peripheral fundus is important in the evaluation of this disorder. An indirect ophthalmologic examination with scleral depression may be required to indentify retinal holes adjacent to the ora serrata. Careful attention should be used when examining myopic patients and those patients with lattice degeneration due to the increased incidence in these populations. Retinal holes are full thickness breaks in the sensory retina. They may be surrounded by pigmentation, especially if chronic and embedded withing a patch of lattice degeneration. As mentioned prior, they take a round or oval shape and lack a "tag" that is seen with a classic horseshoe tear. Subretinal fluid may accompany these lesions. Subretinal fluid, if present, may involve up to 360 degrees of the lesion's edge and spread slowly under the surrounding retina resulting in either a symptomatic or asymptomatic retinal detachment. Atrophic holes are asymptomatic in a majority of patients. If associated with a retinal detachment patients may experience visual symptoms such as photopsias, floaters, or loss of visual field. The diagnosis of an atrophic retinal hole is a clinical one. There are no studies currently used to diagnose or classify this type of retinal pathology. To differentiate this lesion from an operculated retinal hole, a clinician needs to look for an isolated detachment of the sensory retina adherent to the overlying vitreous without traction to the edges of the retinal hole. The absence of vitreoretinal traction, round/oval shape, and a free retinal flap will also assist in differentiating this lesion from a horseshoe retinal tear. Atrophic retinal holes are diagnosed during routine clinical examination. Depending on how far into the peripheral retina the lesions are located a clinician has the option of using either direct or indirect ophthalmoscopy. Scleral depression is sometimes needed to fully assess the pathology. Direct ophthalmolscopy utilizes a slit lamp for the examination and the choice of either a non contact 78 or 90 diopter lens (various other similar lenses are available) versus a Goldmann triple mirror contact lens. The 78 and 90 diopter lens provides an image of the retina which is best for viewing the posterior pole and mid periphery of the fundus. A skilled physician can often times manipulate the slit lamp and provide patient direction which allows for a good view of the peripheral fundus. The Goldmann triple mirror lens is designed specifically to allow for a broader view of the fundus to include the posterior pole and extend out to the ora serrata and ciliary body. Other wide angle contact lenses can be used as well. Widefield funduscopic photography (e.g., Optos) can be beneficial in documenting atrophic retinal holes. No laboratory tests are indicated in cases of atrophic retinal holes. The clinical appearance of atrophic retinal holes is very characteristic. Despite this there are several possible diagnoses that should be considered which include horseshoe retinal tear, lattice degeneration, operculated retinal hole, snailtrack degeneration, and retinoschisis. Sometimes round area of normal retina when surrounded by white without pressure may appear like a retinal hole on clinical examination. There is no mandatory therapy for this condition in general. According to the Preferred Practice Patterns set forth by the American Academy of Ophthalmology, treatment is rarely recommended for atrophic retinal holes. Some studies suggest that prophylactic laserpexy may be considered for eyes with retinal holes when there are active symptoms, when there is accompanying subretinal fluid, or when a retinal detachment already exists in the patient’s fellow eye. There is currently no medical therapy required for this condition. Medical follow up See above. Return and retinal detachment precautions should be carefully discussed with these patients, especially since many of them have concurrent myopia and lattice degeneration which increase the risk of a retinal detachment. Surgical procedures (laserpexy) are rarely recommended for this condition. See above. However, if there is documented progression of subretinal fluid around the hole, most retina specialists will recommend barricade laser. When atrophic holes are the primary cause of macula off/ macula threatening retinal detachment in young, phakic patients without a posterior vitreous detachment present, scleral buckling may be preferred over vitrectomy. Surgery (buckling or vitrectomy) should also be considered in retinal detachment approaching the arcade, though laser delimitation may also be an option. The prognosis for atrophic retinal holes is good. There is a low risk of retinal detachments in patient with round holes, and the incidence of atrophic holes in the general population is low as well. - Kanski, Jack. Clinical Ophthalmology 5th edition. Butterworth-Heinemann; 2003:359-371 - Preferred Practice Patterns: Posterior Vitreous Detachment, Retinal Breaks, and Lattice Degeneration. AAO 2008 - Byer N. Subclinical Retinal Detachment Resulting from Asymptomatic Retinal Breaks. Ophthalmology 2001; 108:1499-1504 - Gonzales C,Gupta A, Schwartz S,et al.The fellow eye of patients with phakic rhegmatogenous retinal detachment from atrophic holes of lattice degeneration without posterior vitreous detachment. Br J Ophthalmol 2004 88: 1400-1402 - Michaelson I. Role of a Distinctive Choroido-retinal Lesion in the Pathogenesis of Retinal Hole: A Clinical and Pathological Report. Br J Ophthalmol 1956 40: 527-535 - Sigelman J. Vitreous Base Classification of Retinal Tears: Clinical Application. Surv Ophthalmol 25:59-74, 1980	2	9	0	0	2	0.412606	2	1,688
I'm a provider You will be redirected to myBlue. Would you like to continue? Please wait while you are redirected. DESCRIPTIONColonoscopy is a visual examination of the lining of the colon (large intestine, large bowel) with a fiberoptic endoscope. It is inserted through the anus and rectum and advanced through the large intestine under direct vision, using the scope's optical system. Instruments and tools can be passed through the scope, for taking samples (biopsies). This procedure may be performed in the outpatient setting. Flexible sigmoidoscopy is a visual examination of the rectum and lower colon called the sigmoid colon. A sigmoidoscope, long flexible tube with fiber optics, is passed through the anus and rectum into the sigmoid colon. Instruments and tools can be passed through the scope, for taking samples (biopsies). This procedure may be performed in the outpatient setting. Virtual colonoscopy, also known as computed tomography (CT) colonography, is an imaging technique of the colon involving thin-section helical CT to generate high-resolution 2-dimensional axial images of the colon. Three-dimensional images, which resemble the endoluminal images obtained with conventional endoscopic colonoscopy, are then reconstructed off line. Virtual colonoscopy has been investigated as an alternative to conventional endoscopic colonoscopy, specifically as an alternative screening technique for colon cancer. While virtual colonoscopy requires a full bowel preparation, similar to conventional colonoscopy, no sedation is required, and the examination is less time consuming. However, gas insufflation of the intestine, which may be uncomfortable to the patient, and interpretation of the images is described as difficult and time consuming. POLICYFor Coding Guidelines see the Monitored Anesthesia Care during Gastrointestinal Endoscopy Policy. Screening (asymptomatic individuals) colonoscopy, fecal occult blood test (FOBT) and sigmoidoscopy will be allowed under the following guidelines: Beginning at age 50, both men and women should follow ONE of the screening options below: A digital rectal examination (DRE) should be performed at the time of EACH screening sigmoidoscopy or colonoscopy.High Risk People should begin colorectal cancer screening earlier and/or undergo screening more often if they have any of the following colorectal cancer risk factors. Frequency should be determined by the ordering physician: Inflammatory Bowel Disease Most patients do not require colonoscopy for initial diagnosis, unless clinical sigmoidoscopy and radiological studies fail to secure diagnosis. Multiple biopsies are helpful when it is clinically necessary to distinguish between ulcerative colitis and Crohn's. Screening colonoscopy for follow-up of inflammatory bowel disease is usually not covered except for cancer surveillance in chronic ulcerative colitis. Abnormal Exam (Symptomatic individuals) Colonoscopy is considered medically necessary under the following circumstances:Unexplained bleeding Flexible sigmoidoscopy in the ambulatory or office-setting is considered medically necessary under the following circumstances: Computed tomography (CT) colonography, commonly referred to as virtual colonoscopy, may be considered medically necessary in patients for whom a conventional colonoscopy is indicated but who are unable to undergo conventional colonoscopy for medical reasons or in patients with an incomplete conventional colonoscopy because of colonic stenosis or obstruction. Except as noted in the policy statement above, CT colonography is considered not medically necessary for the purposes of colon cancer screening because the clinical outcomes with this screening strategy have not been shown to be superior to other approaches including optical colonoscopy. 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. Computed tomography (CT) colonography should be performed with a minimum 16-row detector CT scanner. Contraindications to conventional colonoscopy may include continuous anticoagulation therapy or high anesthesia risk. POLICY HISTORY2/1998: Approved by Medical Policy Advisory Committee (MPAC) 3/1999: Updated to reflect national standards 2/2001: Reviewed by MPAC; Virtual colonoscopy considered investigational. Healthy you guidelines will be aligned to be consistent with the American Cancer Society recommendations for early colorectal cancer detection. 5/23/2001: Code reference section revised; ICD-9 diagnosis code 235.2 and 239.0 deleted 11/14/2001: Colonoscopy and flexible sigmoidoscopy description revised under the "Description" section. 2/13/2002: Investigational definition added 3/20/2002: Revised verbiage of familial syndromes for clarity 3/26/2002: Healthy You guideline for barium enema deleted; G0121 added to non-covered 3/27/2002: Healthy You guidelines moved to Policy Exceptions 4/18/2002: Type of Service and Place of Service deleted 6/12/2002: ICD-9 diagnosis codes 235.2 and 239.0 added 7/23/2002: Policy section revised, Policy Exceptions deleted 7/30/2002: Prior authorization deleted 8/22/2002: CPT codes 44390-44397, 45332-45345, 45382-45387 deleted; ICD-9 procedure codes 45.42-45.43 deleted; ICD-9 diagnosis codes 555.9, 787.99, 799.8 deleted; ICD-9 diagnosis codes 557.1- 557.9 added; ICD-9 diagnosis code 564.89 description revised and one deleted; ICD-9 diagnosis code 556.9 is covered and non-covered depending on the description 12/11/2002: HCPCS G0102 added 11/18/2004: Reviewed by MPAC, CT colonography (“virtual colonoscopy”) remains investigational, policy title “Colonoscopy and Flexible Sigmoidoscopy” renamed “Colonoscopy, Flexible Sigmoidoscopy, and CT Colonography,” Description section updated to be consistent with BCBSA policy # 6.01.32, Sources updated 4/12/2005: Code Reference section updated, CPT code 44390, 44392, 44393, 44394, 45307, 45332, 45333, 45338, 45339, 45383, 45384, 45385 added covered codes, ICD-9 procedure code 45.42, 45.43, 98.03, 98.04 added covered codes, ICD-9 diagnosis 560.89 added covered codes, ICD-9 diagnosis codes 578.1 description revised covered codes, HCPCS G0102 deleted covered codes, HCPCS G0328 added covered codes, HCPCS 0066T, 0067T added non-covered codes, ICD-9 diagnosis code 556.9, 562.11, 562.13, 567.9, 569.49, 569.83, V72.83 deleted non-covered codes 3/13/2006: Coding updated. CPT4 2006 revisions added to policy 3/21/2006: Policy reviewed, no changes 09/13/2006: Coding updated. ICD9 2006 revisions added to policy 12/27/2006: Code Reference section updated per the 2007 CPT/HCPCS revisions 12/17/2007: Coding updated. CPT/HCPCS 2008 revisions added to policy 7/8/2008: Anesthesia Coding Policy hyperlink added 9/15/2008: Code reference section updated per the annual ICD-9 updates effective 10-1-2008 9/29/2009: Code reference section updated. New ICD-9 diagnosis code 569.71 added to covered table. HCPC code G0107 deleted from covered table due to code was deleted as of 12-31-06. 04/12/2010: Policy Statement revised to include CT Colonography may be considered medically necessary in patients with medical reasons. Code Reference Section updated revised to identify deleted codes S0605, 0066T and 0067T. Added new CPT Code 74261 and 74262 to the Covered Codes Table and CPT Code 74263 to Non-Covered Codes Table. 07/12/2012: Policy reviewed; no changes to policy statement. Removed S0605, 0066T, and 0067T from the Code Reference section as these codes have been deleted. 05/08/2013: Policy reviewed; no changes. 12/31/2014: Code Reference section updated to revise the description of the following CPT codes: 44388, 44390, 44392, 45330, 45332, 45333, 45378, 45379, 45384, and 45385. Effective 1/1/15. Added the following new 2015 CPT codes: 44401, 44402, 44403, 44404, 44405, 44406, 44407, 44408, 45346, 45347, 45349, 45350, 45388, 45389, 45390, 45393, 45398, and 45399. Added the following new 2015 HCPCS codes to the Code Reference section: G6019, G6020, G6022, G6023, G6024, G6025. SOURCE(S)Hayes Medical Technology Directory American Society of Gastroendoscopy (ASGE) consensus statement, "The Appropriate Use of Gastrointestinal Endoscopy" Guidelines for Clinical Applications by the ASGE; Publication Nos. 1009 and 1013 1986. United States Preventive Services Task Force (USPSTF) 1996 recommendation American Cancer Society, Colon and Rectum Cancer Resource Center recommendations for early colorectal cancer detection TEC Assessment Program, Volume 19, No. 6, July 2004 Blue Cross Blue Shield association policy #6.01.32 CODE REFERENCEThis is not intended to be a comprehensive list of codes. Note that some codes may be variable and coverage will be based on the clinical indication for the service. For Coding Guidelines see the Anesthesia Coding Policy . This may not be a comprehensive list of procedure codes applicable to this policy. The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document. This may not be a comprehensive list of procedure codes applicable to this policy.	4	16	8	9	2	0.620639	19	2,304
We were going to write about ICD-10 anyway, but a recent article in The Wall Street Journal (subscription required) beat us to it. But first, what is ICD-10? Those of you who may not be fluent in Medispeak deserve a 60 second explanation. “ICD” is the abbreviation for the International Classification of Diseases. It’s a tabulated and coded compendium of the various things that can go wrong with people and cause morbidity and mortality. The idea of categorizing and classifying illness is an old one, and the first iteration of the ICD was published as the International List of Causes of Death in 1893. Just as we have universal classifications of plants, animals, fungi, bacteria and everything else, the purpose of the ICD is supposed to be to help people organize information so that we can better understand the world and improve our lives. The ICD is, for example, used to compile information on the causes of death and disability. It’s used to find and track epidemics of diseases, compare the distribution of illnesses to geographic locations and match resource use to specific diseases. The invention of computers marked an enormous change in the use of the ICD; their ability to process and tabulate enormous numbers of codes simultaneously made it easy and painless ask increasingly detailed – and even esoteric – questions, as long as enough data was available in enough detail. Want to know if there’s a relationship between smoking and cancer? An analysis of ICD codes could tell us that. And there is one other important use for ICD coding; the federal government and private health insurers require that the appropriate ICD codes be included as a component of each and every medical claim submitted for payment. The World Health Organization (WHO) took over responsibility for maintaining and updating the ICD in 1948, and it’s been through many versions since then. ICD-10 is, as the name implies, the tenth version to be published, and the WHO released it in 1994. One of the big changes between ICD-10 and ICD-9 is the ability to add lots of new diagnoses. ICD-9 codes consisted of up to five numbers. Theoretically this allows it to represent up to 100,000 different diseases and conditions. In contrast, ICD-10 is represented by a combination of up to seven letters or numbers, giving it the ability to code for over 78 billion different conditions. Despite this, the WHO version of ICD-10 is relatively manageable and consists of only 16,000 different codes. Here in the United States, the medical community is generally still using ICD-9, but because of its legal jurisdiction over all aspects of medical information under the Health Insurance Portability and Accountability Act of 1996 (HIPAA), the federal government has the power to require that every physician, medical facility and provider in the country use whatever version of the ICD it mandates. Eager to keep America’s healthcare system in line with the rest of the world, the federal government decreed that all U.S. healthcare providers must switch over to ICD-10 by October 1, 2013. Hey, what could be wrong with that? Lots, if you leave the implementation of the code set to be used up to a bunch of people with a penchant toward the academic and the bureaucratic. You see, every country is free to modify WHO’s version of the ICD to meet its own particular needs. Canada has its own version called ICD-10-CA. Australia uses ICD-10-AM, while Germany uses ICD-10-GM. So the committee that the Department of Health and Human Services (HHS) set up to adapt ICD-10 for domestic use felt free to add lots of new codes to the U.S. version. Some 85,000 of these were created for to represent procedures done in the hospital, a subset called ICD-10-PCS. But while U.S. clinicians only had to deal with 16,000 diagnostic codes in ICD-9, HHS packed the ICD-10 diagnostic set with some 70,000 codes and called it ICD-10-CM. In total, American healthcare providers are now required to accommodate up to 155,000 new codes for billing and documentation purposes into their businesses. The recent article in the Wall Street Journal tells the story: “Indeed, health plans may never again wonder where a patient got hurt. There are codes for injuries in opera houses, art galleries, squash courts and nine locations in and around a mobile home, from the bathroom to the bedroom. Some doctors aren’t sure they need quite that much detail. ‘Really? Bathroom versus bedroom?’ says Brian Bachelder, a family physician in Akron, Ohio. ‘What difference does it make?’… Some codes could seem downright insulting: R46.1 is ‘bizarre personal appearance,’ while R46.0 is ‘very low level of personal hygiene.’ It’s not clear how many klutzes want to notify their insurers that a doctor visit was a W22.02XA, ‘walked into lamppost, initial encounter’ (or, for that matter, a W22.02XD, ‘walked into lamppost, subsequent encounter’). Why are there codes for injuries received while sewing, ironing, playing a brass instrument, crocheting, doing handcrafts, or knitting—but not while shopping, wonders Rhonda Buckholtz, who does ICD-10 training for the American Academy of Professional Coders, a credentialing organization. Code V91.07XA, which involves a ‘burn due to water-skis on fire,’ is another mystery she ponders: ‘Is it work-related?’ she asks. ‘Is it a trick skier jumping through hoops of fire? How does it happen?’” Much of the new system is based on a World Health Organization code set in use in many countries for more than a decade. Still, the American version, developed by the Centers for Disease Control and Prevention and the Centers for Medicare and Medicaid Services, is considerably more fine-grained. Y93.J4: A code for injuries received while playing brass instruments. The WHO, for instance, didn’t see the need for 72 codes about injuries tied to birds. But American doctors whose patients run afoul of a duck, macaw, parrot, goose, turkey or chicken will be able to select from nine codes for each animal, notes George Alex, an official at the Advisory Board Co., a health-care research firm. There are 312 animal codes in all, he says, compared to nine in the international version. There are separate codes for “bitten by turtle” and “struck by turtle.” Of course for the really curious even these codes still don’t tell the full story for those struck by turtles. Were they struck vertically as the turtle fell from the sky, horizontally as a turtle was hurled at them, or bowled over by a turtle sprinting at top speed? And while the Wall Street Journal stops there, let us assure you that it’s not for lack of content. Take a look at this: V9540XA Unspecified spacecraft accident injuring occupant, initial encounter V9541XA Spacecraft crash injuring occupant, initial encounter V9542XA Forced landing of spacecraft injuring occupant, initial encounter V9543XA Spacecraft collision injuring occupant, initial encounter V9544XA Spacecraft fire injuring occupant, initial encounter V9545XA Spacecraft explosion injuring occupant, initial encounter V9549XA Other spacecraft accident injuring occupant, initial encounter Someone, somewhere in the HHS ICD committee is far more interested in space travel than the lowly problems of the average Medicare recipient. And lest anyone be concerned that the ICD-10-PCS system is any less rigorous in its specificity, never fear. “’You have millions of transactions flowing in the health-care system and this is an opportunity to mess them all up,’ says Jeremy Delinsky, chief technology officer for athenahealth Inc., which provides billing services to doctors. Medicare officials say they believe many big insurers and hospital systems are making preparations, but there may be some issues with smaller ones that won’t be ready. With the move to ICD-10, the one code for suturing an artery will become 195 codes, designating every single artery, among other variables, according to OptumInsight, a unit of UnitedHealth Group Inc. A single code for a badly healed fracture could now translate to 2,595 different codes, the firm calculates. Each signals information including what bone was broken, as well as which side of the body it was on.” Predictably, the people that created the U.S. version of ICD-10 claim that it’s all needed, and that they got lots of input from real, live doctors. Well, sort of. Here’s the HHS response to the “myth” that it was developed “without clinical input”: “The development of ICD-10-CM/PCS involved significant clinical input. A number of medical specialty societies contributed to the development of the coding systems.” Any doctor these days can tell you that few “medical societies” have anything in common with practicing physicians these days, except that they stick up clinicians for membership dues and fees for mandated certification and continuing medical education. But really, why did someone go to all of this trouble to find out if patients were “struck by orcas” multiple times and frankly, why should we care? Let’s return to planet Earth for a minute and think about these codes and how they’re used to deliver or improve healthcare services in real life. Let’s say that we have a patient in front of us in the clinic or the emergency room. Do we need to know the patient’s ICD-10 codes? Well, no. Seriously, we don’t. What we’re really like to know are the patient’s past and current diagnoses and treatments. We don’t need the ICD code for that unless that’s the specific method used to store the information. We could really manage just as well with a simple list of these things spelled out in plain English or medical terms. In fact, that method has worked successfully for hundreds of years. If someone wishes to represent those pieces of information by one code or another it’s all well and good, but no doctor on Earth really thinks in terms of their patient manifesting a “W5801XA”. Instead, he just wants to know that they were bitten by damned alligator. But if doctors don’t care about this, then who does? How about epidemiologists and medical researchers? There is no question that having large amounts of accurate coded data readily and rapidly available for computer processing would come in handy for medical epidemiologists and researchers who are trying to track down epidemics and public health hazards. But the value of this information is limited by two competing factors: detail and reliability. In a situation in which one is relying on others to collect information as a byproduct of their normal activities, the speed and accuracy of collection will be inversely related to the amount of detail we are asking them to describe. “You were struck by a bird? What kind of bird? A brown bird. How big was it? What other markings did it have? What color was its beak?” It’s easy to understand that the more detail we request, the less abundant and accurate the information will become as a result of two factors. The first is the ability of the patient to recall the details. The second is the limited time, patience and energy of the clinician asked to compile and code the information. Under these circumstances, asking for more and more data rapidly becomes a double-edged sword. If we demand high levels of detail, there is good reason to question its accuracy. If we’re not holding a gun to each doctor’s head, more and more of the data will be coded as such-and-such an injury, “unspecified”. Even so, it’s hard to imagine that the needs of a relatively few epidemiologists and researchers is sufficient to justify the unbelievably expensive and complex disruption that switching to HHS’ version of ICD-10 is going to entail. When all is said and done, we’re talking about an investment of literally hundreds of billions of dollars. Every single piece of medical record, billing and accounting software in the industry has to be re-programmed, and none of the programming is the same as that already being done for the versions of ICD-10 used by WHO or any other country. Every medical encounter form in every medical clinic has to be changed. Every clinician and every biller needs to learn the new codes. Sure, no one is likely to need all of them, but the sheer number and complexity of them is daunting. So who the heck would want to create such a system, and why? There are really only two possible suspects: medical voyeurs and those who stand to benefit from increasing the complexity (and ultimate cost) of the U.S. healthcare system. Medical voyeurism is self-explanatory. Somewhere in America, there is always going to a substantial group of people – be they academics, bureaucrats or tabloid journalists – who get a thrill out of being able to peek into the statistics and write articles about the number of people mauled by Macaws or put into the hospital when their water skis somehow burst into flame. It is a big mistake to underestimate the power and influence of people who wish to collect and analyze data, simply on the off chance that there might be something interesting in it. But who could possibly benefit from making coding more complex? The answer is simple: health insurers, especially the federal government itself. As we’ve extensively documented many times before, the RBRVS-based medical payment system invented at the behest of Congress and used by virtually all public and private U.S. insurers is a travesty of the first order. In its current form it is hopelessly complex, prone to abuse by criminals and payers alike, inefficient and expense. Both the ICD and CPT system represent major components of this system. But while proponents of ICD-10 claim that the increasing levels increasing level of detail provided will make it easier to ensure “quality and affordability”, the reality is that increasing levels of complexity always increase rather than decrease the potential for abuse by payers and criminals alike. There is no scam that cannot be perpetrated and hidden more easily in a complex system than in simpler one, especially by insurers intent on requiring that every “i” be dotted and “t” crossed before paying providers for their services. As it is, public and private insurers both play games with reporting requirements and paperwork to avoid meeting their financial obligations. In a recent post, Dr. Rich over at The Covert Rationing Blog accurately describes how Medicare uses the process of physician certification and re-certification as an excuse for denying payments owed for medical services legitimately provided in good faith. Medical billing is already an arms race between the billing software used to submit claims based upon elaborate coding algorithms designed to maximize payments, and equally sophisticated software designed to deny payment. All ICD-10 is going to do is take this to the next level, further impoverishing real healthcare in the process. Insurers will ask for more detailed codes in order to justify payment, and considerable expense will be generated in providing them. For patients, providers, businesses and taxpayers, it’s a no-win situation. In January of 2011, President Obama pledged to reduce the amount of regulation sandbagging the U.S. economy, and “ordered a government-wide review of regulations, both old and new, in a broad push to curtail rules that retard job creation and economic growth.” Frankly, the wholesale simplification of ICD-10 would be a good place to start.	3	6	0	0	6	0.662699	6	3,419
Alpha Galactosidase B Deficiency - Schindler disease Schindler Disease is one of seven identified Glycoprotein storage diseases. These inherited diseases are part of a larger group of disorders called Lysosomal storage diseases. Lysosomes are membrane-bound compartments found in the cells of the body. These compartments contain enzymes, which are responsible for the breakdown of many different oligosaccharides (long sugar chains.) These sugar chains are continuously made and broken down in our bodies, and this process is necessary for the appropriate mental and physical development. Each enzyme in the lysosome is responsible for a certain step in the breakdown of the sugar chains. When an enzyme is not working, it leads to the build up of the sugar chains in the lysosome. In Schindler Disease, the specific enzyme that is absent is called alpha-N-acetylgalactosaminidase (previously known as alpha-galactosidase B.) The build up of oligosaccharide sugars that is caused, is gradual and interferes with the correct function of the cell. ItThis build up is gradual and eventually leads to the clinical features of Schindler Disease. Features may progress in severity over time. In Schindler Disease, the specific enzyme that is absent is called alpha-N- acetylgalactosaminidase (previously known as alpha-galactosidase B.) (1) Genetic: Gene map locus 22q11 - NAGA encodes the lysosomal enzyme alpha-N-acetylgalactosaminidase, which cleaves alpha-N-acetylgalactosaminyl moieties from glycoconjugates. Mutations in NAGA have been identified as the cause of Schindler disease types I and II (type II also known as Kanzaki disease). Diagnosis of Schindler disease is based on the symptoms the individual has, as well as the age the symptoms began. A urine test, blood test, or skin sample (biopsy) may help confirm the diagnosis. In Schindler disease, the blood or skin sample will show decreased activity of alpha-NAGA. Teleangiectasia (widening of groups of blood vessels which causes skin redness), excess urinary sialylglycoaminoacids, warty discolorations on skin, mildly coarse facial features, mild intellectual impairment, edema/lymphedema, loss of previously acquired physical skills, loss of previously acquired mental abilities, progressive neurological symptoms (seizures) Supportive - no treatment for underlying disorder, multidisciplinary approach (Peadiatrics, Neurology, Ophthalmology, Orthopedics), Genetic counselling (normal sib of an affected patient has a 67% risk of being a carrier). June 11, 2008 Alternative titles; symbolsALPHA-GALACTOSIDASE B; GALBGene map locus 22q11 Alpha-N-acetylgalactosaminidase (EC 126.96.36.199) is a lysosomal glycohydrolase that cleaves alpha-N-acetylgalactosaminyl moieties from glycoconjugates. Wang et al. (1990) isolated a full-length 2.2-kb NAGA cDNA and a genomic cosmid clone containing the entire NAGA gene from a human fibroblast cDNA library. The cDNA encodes a 411-amino acid protein with a 17-residue signal peptide and 6 putative N-glycosylation sites. Northern blot analysis detected 2 mRNA transcripts of 3.6 and 2.2 kb. Sequence analysis revealed striking similarities between the NAGA gene and exons 1-6 of the alpha-galactosidase A gene (GLA; 300644), suggesting that the 2 genes evolved by duplication and divergence from a common ancestral locus. Wang and Desnick (1991) also pointed to remarkable amino acid identity between the NAGA and GLA genes. Wang et al. (1998) isolated the mouse Naga cDNA from a fibroblast cDNA library and found that the deduced human and mouse proteins share 81.9% sequence identity. Wang and Desnick (1991) determined that the NAGA gene contains 9 exons. De Groot et al. (1978) assigned the human N-acetyl-alpha-D-galactosaminidase gene to chromosome 22 by human-rodent somatic cell hybridization. The authors suggested that 'alpha-NAGA' was a more appropriate designation for this enzyme than alpha-galactosidase B. In human-rodent cell hybrids, Geurts van Kessel et al. (1979, 1980) studied chronic myeloid leukemia cells to determine the site of the break on 22q relative to markers assigned to chromosomes 22 and 9. Alpha-NAGA remained with the Ph-1 chromosome, whereas the aconitase gene (ACO2; 100850) went with chromosome 9. Alpha-NAGA was located to band 22q11 and ACO2 was located between it and 22qter. Wang et al. (1994) generated a mouse model of Schindler disease by targeted disruption of the Naga gene. Naga-null mice appeared clinically normal, survived into adulthood, and were fertile. Consistent with the human disease, the mice had no Naga activity and showed lysosomal pathology, including vacuolated peripheral lymphocytes. Desnick and Schindler (2001) reported that Naga-null mice developed widespread lysosomal storage of abnormal material in the central nervous system and other organs, as well as focal axonal swellings or spheroids in the brain and spinal cord. In the 2 German boys first described with Schindler disease (609241) (11,12:van Diggelen et al., 1987, 1988), Wang et al. (1990) identified a homozygous 973G-A transition in exon 8 of the NAGA gene, resulting in a glu325-to-lys (E325K) substitution. Keulemans et al. (1996) identified a distant affected relative of the 2 boys who had the E325K homozygous mutation. The boys had approximately 1% residual NAGA activity. Bakker et al. (2001) reported homozygosity for the E325K mutation in a 3-year-old Moroccan boy with alpha-NAGA deficiency. He was born of consanguineous parents. The proband and his 7-year-old healthy brother had undetectable alpha-NAGA activity in leukocytes and a profound deficiency in fibroblasts. The parents had alpha-NAGA activity consistent with heterozygosity. Mutation analysis revealed homozygosity for the E325K mutation in the proband and his healthy brother, whereas a third sib and both parents were heterozygous. The family demonstrated the extreme clinical heterogeneity of alpha-NAGA deficiency, as the homozygous brother at the age of 7 years showed no clinical or neurologic symptoms. In a Japanese woman with disseminated angiokeratoma (609242) reported by Kanzaki et al. (1989), Wang et al. (1990, 1994) identified a homozygous 985C-T transition in the NAGA gene, resulting in an arg329-to-trp (R329W) substitution. The base substitution was confirmed by hybridization of PCR-amplified genomic DNA from family members with allele-specific oligonucleotides. Wang et al. (1994) showed that in transiently expressed COS-1 cells, both the infantile-onset E325K (104170.0001) and the adult-onset R329W precursors were processed to the mature form; however, the E325K mutant polypeptide was more rapidly degraded than the R329W subunit, thereby providing a basis for the distinctly different infantile- and adult-onset phenotypes. Keulemans et al. (1996) showed by PCR and sequence analysis that the Spanish brother and sister with manifestations of Kanzaki disease (609242) described by Chabas et al. (1994) were homozygous for a 5371G-T transversion in exon 5 of the NAGA gene (numbering according to Yamauchi et al., 1990), resulting in a glu193-to-ter (E193X) substitution, premature truncation, and complete loss of the NAGA protein. In a Dutch girl with type III NAGA deficiency (609241) reported by de Jong et al. (1994), Keulemans et al. (1996) identified compound heterozygosity for 2 mutations in the NAGA gene: E325K (104170.0001) and a 4969C-G transversion in exon 4 (numbering according to Yamauchi et al., 1990), resulting in a ser160-to-cys (S160C) substitution. The same genotype was found in the clinically unaffected 3-year-old brother of the proband, and the authors suggested that the brother might be a preclinical case of NAGA deficiency; the brother's twin sister did not have the genotype. Residual enzyme activity in the proband was approximately 4% of controls. The S160C allele was not identified in 80 Dutch control alleles. In a Japanese woman with Kanzaki disease (609242), Kodama et al. (2001) identified a homozygous 986G-A transition in the NAGA gene, resulting in an arg329-to-gln (R329Q) substitution. The patient had angiokeratoma corporis diffusum, Meniere syndrome, and no mental retardation. Her parents were consanguineous. PubMed ID : 2243144 Kniffin - updated : 5/11/2005 Cassandra L. Kniffin - updated : 4/6/2005 Cassandra L. Kniffin - reorganized : 4/1/2005 Cassandra L. Kniffin - updated : 3/8/2005 Michael B. Petersen - updated : 8/21/2001 Iosif W. Lurie - updated : 7/10/1996 Victor A. McKusick : 6/4/1986 carol : 3/28/2007 Blood group B glycosphingolipids in deficiency (Fabry disease): influence of secretor status. Ledvinova J, Poupetova H, Hanackova A, Pisacka M, Elleder M. Institute of Inherited Metabolic Diseases, First Faculty of Medicine, Charles University, Prague, Czech Republic. Defect in degradation of blood group B-immunoactive glycosphingolipids in Fabry disease (deficiency of lysosomal alpha-galactosidase EC 188.8.131.52) has been studied using highly sensitive and specific TLC-immunostaining analysis of urinary sediments and tonsillar tissues of blood group B patients and healthy controls, secretors and nonsecretors. The B glycolipid antigens with hexasaccharide chains were consistently found increased (25- to 100-fold) in the urinary sediments of three Fabry patients, blood group B or AB secretors. Conversely, they were absent in the urinary sediment of one blood group B nonsecretor patient. In normal secretors, B glycosphingolipids were present only in traces. Moreover, significant increase in B glycolipid antigens (8-fold) was found in the tonsillar tissue of a Fabry patient blood group B secretor. We conclude that the secretor status is responsible for increased concentration of blood group B glycosphingolipids in both urinary cells and tonsils in alpha-galactosidase deficiency. The quantity of stored B-immunoactive glycosphingolipids, however, is much lower than that of the mainly accumulated glycosphingolipid Gb(3)Cer. The results clearly indicate that active or silent Se gene, which controls synthesis of B-antigen precursors, is responsible for notable difference in B-glycosphingolipids expression in Fabry patients - secretors and nonsecretors. Whether this novel aspect may be of prognostic significance, remains to be established. PMID: 9106497 [PubMed - indexed for MEDLINE] Defects in degradation of blood group A and B glycosphingolipids in Schindler and Fabry diseases. Asfaw B, Ledvinova J, Dobrovolny R, Bakker HD, Desnick RJ, van Diggelen OP, de Jong JG, Kanzaki T, Chabas A, Maire I, Conzelmann E, Schindler D. Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, 128 08 Prague, Czech Republic. [email protected] Skin fibroblast cultures from patients with inherited lysosomal enzymopathies, alpha-N-acetylgalactosaminidase (alpha-NAGA) and alpha-galactosidase A deficiencies (Schindler and Fabry disease, respectively), and from normal controls were used to study in situ degradation of blood group A and B glycosphingolipids. Glycosphingolipids A-6-2 (GalNAc (alpha 1-->3)[Fuc alpha 1-->2]Gal(beta1-->4)GlcNAc(beta 1-->3)Gal(beta 1--> 4)Glc (beta 1-->1')Cer, IV(2)-alpha-fucosyl-IV(3)-alpha-N-acetylgalactosaminylneolactotetraosylceramide), B-6-2 (Gal(alpha 1-->3)[Fuc alpha 1--> 2] Gal (beta 1-->4)GlcNAc(beta 1-->3)Gal(beta 1-->4)Glc(beta 1-->1')Cer, IV(2)- alpha-fucosyl-IV(3)-alpha-galactosylneolactotetraosylceramide), and globoside (GalNAc(beta 1-->3)Gal(alpha 1-->4)Gal(beta 1-->4)Glc(beta 1-->1') Cer, globotetraosylceramide) were tritium labeled in their ceramide moiety and used as natural substrates. The degradation rate of glycolipid A-6-2 was very low in fibroblasts of all the alpha-NAGA-deficient patients (less than 7% of controls), despite very heterogeneous clinical pictures, ruling out different residual enzyme activities as an explanation for the clinical heterogeneity. Strongly elevated urinary excretion of blood group A glycolipids was detected in one patient with blood group A, secretor status (five times higher than upper limit of controls), in support of the notion that blood group A-active glycolipids may contribute as storage compounds in blood group A patients. When glycolipid B-6-2 was fed to alpha-galactosidase A-deficient cells, the degradation rate was surprisingly high (50% of controls), while that of globotriaosylceramide was reduced to less than 15% of control average, presumably reflecting differences in the lysosomal enzymology of polar glycolipids versus less-polar ones. Relatively high-degree degradation of substrates with alpha-D-Galactosyl moieties hints at a possible contribution of other enzymes. PMID: 12091494 [PubMed - indexed for MEDLINE] Schindler disease: the molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes an infantile Wang AM, Schindler D, Desnick R. Division of Medical and Molecular Genetics, Mount Sinai School of Medicine, New York 10029. Schindler disease is a recently recognized infantile neuroaxonal dystrophy resulting from the deficient activity of the lysosomal hydrolase, alpha-N-acetylgalctosaminidase (alpha-GalNAc). The recent isolation and expression of the full-length cDNA encoding alpha-GalNAc facilitated the identification of the molecular lesions in the affected brothers from family D, the first cases described with this autosomal recessive disease. Southern and Northern hybridization analyses of DNA and RNA from the affected homozygotes revealed a grossly normal alpha-GalNAc gene structure and normal transcript sizes and amounts. Therefore, the alpha-GalNAc transcript from an affected homozygote was reverse-transcribed, amplified by the polymerase chain reaction (PCR), and sequenced. A single G to A transition at nucleotide 973 was detected in multiple subclones containing the PCR products. This point mutation resulted in a glutamic acid to lysine substitution in residue 325 (E325K) of the alpha-GalNAc polypeptide. The base substitution was confirmed by dot blot hybridization analyses of PCR-amplified genomic DNA from family members with allele-specific oligonucleotides. Furthermore, transient expression of an alpha-GalNAc construct containing the E325K mutation resulted in the expression of an immunoreactive polypeptide which had no detectable alpha-GalNAc activity. PMID: 2243144 [PubMed - indexed for MEDLINE] Schindler Disease is a rare inherited metabolic disorder characterized by a deficiency of the lysosomal enzyme alpha-N-acetylgalactosaminidase (alpha-NAGA). The disorder belongs to a group of diseases known as lysosomal storage disorders. Lysosomes function as the primary digestive units within cells. Enzymes within lysosomes break down or digest particular nutrients, such as certain fats and carbohydrates. In individuals with Schindler Disease, deficiency of the alpha-NAGA enzyme leads to an abnormal accumulation of certain complex compounds (glycosphingolipids) in many tissues of the body. There are two forms of Schindler Disease. The classical form of the disorder, known as Schindler Disease, Type I, has an infantile onset. Affected individuals appear to develop normally until approximately 1 year of age, when they begin to lose previously acquired skills that require the coordination of physical and mental activities (developmental regression). Additional neurological and neuromuscular symptoms may become apparent, including diminished muscle tone (hypotonia) and weakness; involuntary, rapid eye movements (nystagmus); visual impairment; and episodes of uncontrolled electrical activity in the brain (seizures). With continuing disease progression, affected children typically develop restricted movements of certain muscles due to progressively increased muscle rigidity, severe mental retardation, hearing and visual impairment, and a lack of response to stimuli in the environment. Schindler Disease, Type II, which is also known as Kanzaki Disease, is the adult-onset form of the disorder. Associated symptoms may not become apparent until the second or third decade of life. In this milder form of the disease, symptoms may include the development of clusters of wart-like discolorations on the skin (angiokeratomas); permanent widening of groups of blood vessels (telangiectasia), causing redness of the skin in affected areas; relative coarsening of facial features; and mild intellectual impairment. The progressive neurological degeneration characteristically seen in the infantile form of the disease has not occurred in association with Schindler Disease, Type II. Both forms of Schindler Disease are inherited as autosomal recessive traits. According to investigators, different changes (mutations) of the same gene are responsible for the infantile- and adult-onset forms of the disease. The gene has been mapped to the long arm (q) of chromosome 22 (22q11). Organizations related to Schindler Disease 5223 Brookfield LaneCLIMB (Children Living with Inherited Metabolic Diseases) Sylvania OH 43560-1809 Phone #: 419-885-1497 800 #: -- Home page: N/A Crewe Intl CW2 6BG Phone #: 44 -870- 7700 325 800 #: -- 3210 Batavia Ave, Baltimore, MD, 21214 Baltimore MD 21214 Phone #: 410-254-4903 800 #: N/A PO Box 5801 Bethesda MD 20824 Phone #: 301-496-5751 800 #: 800-352-9424 National Lipid Diseases Foundation 1201 Corbin StreetNational Tay-Sachs and Allied Diseases Association, Inc. Elizabeth NJ 07201 Phone #: 908-527-8000 800 #: 800-527-8005 Home page: N/A 2001 Beacon StreetVaincre Les Maladies Lysosomales Boston MA 02135 Phone #: 617-277-4463 800 #: 800-906-8723 9 Place du 19 Mars 1962, Evry Cedex None 91035 Phone #: 016-091-7500 800 #: -- Schindler disease - Webmd Schindler disease - Pedbase.org Schindler Disease - Developmental Disorders of the Lymphatics Classification and Codes: ICD 10 code - E74.2 N-ACETYL-ALPHA-D-GALACTOSAMINIDASE; NAGA 104170 SCHINDLER DISEASE, TYPE I 609241 KANZAKI DISEASE 609242 Join us as we work for lymphedema patients everywhere: Advocates for Lymphedema Dedicated to be an advocacy group for lymphedema patients. Working towards education, legal reform, changing insurance practices, promoting research, reaching for a cure. Lymphedema People / Advocates for Lymphedema For information about Lymphedema For Information about Lymphedema Complications For Lymphedema Personal Stories For information about How to Treat a Lymphedema Wound For information about Lymphedema Treatment For information about Exercises for Lymphedema For information on Infections Associated with Lymphedema For information on Lymphedema in Children Lymphedema People - Support Groups The time has come for families, parents, caregivers to have a support group of their own. Support group for parents, families and caregivers of chilren with lymphedema. Sharing information on coping, diagnosis, treatment and prognosis. Sponsored by Lymphedema People. No matter how you spell it, this is another very little understood and totally frustrating conditions out there. This will be a support group for those suffering with lipedema/lipodema. A place for information, sharing experiences, exploring treatment options and coping. Come join, be a part of the family! MEN WITH LYMPHEDEMA If you are a man with lymphedema; a man with a loved one with lymphedema who you are to help and understand come join us and discover what it is to be the instead of the sufferer of lymphedema. Support group for parents, patients, children who suffer from all forms of lymphangiectasia. This condition is caused by dilation of the lymphatics. It can affect the intestinal tract, lungs and other critical body areas. Disorders Support Group @ Yahoo Groups While we have a number of support groups for lymphedema... there is nothing out there for other lymphatic disorders. Because we have one of the most comprehensive information sites on all lymphatic disorders, I thought perhaps, it is time that one be offered. Information and support for rare and unusual disorders affecting the lymph system. Includes lymphangiomas, lymphatic malformations, telangiectasia, hennekam's syndrome, distichiasis, Figueroa syndrome, ptosis syndrome, plus many more. Extensive database of information available through sister site Lymphedema People. Lymphedema People New Wiki Pages Have you seen our new “Wiki” yet? Listed below are just a sample of the more than 140 pages now listed in our Wiki section. We are also on hundred more. Come and take a not for Lymphedema People Online Support Groups Lymphatic Drainage (MLD) and Complex Decongestive Therapy (CDT) Associated with Lymphedema How to Treat a Infections Associated with Lymphe dema para-aortic lymph node dissection (EPLND) Needle Biopsy - Fine Needle Aspiration Lymphedema Gene VEGFC Lymphedema Gene SOX18 Home page: Lymphedema People Page Updated: Dec. 14, 2011	2	26	3	0	2	0.784926	5	5,353
Below are answer to some of the most frequently asked and searched questions regarding cerebral palsy. - What is Cerebral Palsy? - Is Cerebral Palsy a Disease? - Is Cerebral Palsy Infectious or Contagious? - What Causes Cerebral Palsy? - What are the Different Types of Cerebral Palsy? - How Common is Cerebral Palsy? - How Long do People Live With Cerebral Palsy? - What is the ICD-10 Code for Cerebral Palsy? - When is Cerebral Palsy Diagnosed? - How to Prevent Cerebral Palsy? - How is Cerebral Palsy Treated? Cerebral palsy is disorder someone is born with in which their brain has been damaged and they are not able to control and coordinate normal movement of muscles in certain areas of their body. Cerebral palsy is primarily a physical movement disorder but it can also involve mental impairment. Cerebral palsy comes in different forms and individual cases range from mild to very severe. No. Cerebral palsy is not really a disease like cancer or AIDS. Instead cerebral palsy is a permanent disability caused by injury to the brain before or during childbirth. Cerebral palsy is not contagious and is not related to a virus or bacteria. No. Cerebral palsy is a disorder that is caused by physical injury to the brain during fetal gestation or birth and not by exposure to any virus or bacteria. Cerebral palsy is not any more infectious than a broken leg or a concussion. Cerebral palsy is the result of injury or damage to the developing brain of a fetus or newborn baby. The "injury" to the brain that triggers cerebral palsy is related to oxygen deprivation. Cells in the brain need a continuous circulation of oxygen or they will rapidly start to decay and die. When the brain of a fetus or infant is deprived of oxygen it quickly causes neurologic damage and the brain ends up developing abnormally. The end result is an impaired brain that is not able to exercise normal control and coordination over body movement. There are a number of different conditions or events during pregnancy or childbirth which can potentially disrupt oxygen to the brain and lead to cerebral palsy. When hypoxic brain damage occurs during fetal gestation (pregnancy) potential causes can include maternal infections such as chorioamnionitis and prenatal asphyxiation from complications involving the placenta or umbilical cord. Oxygen deprivation during labor and delivery is the more common cause of CP and can result from a number of events or complications during childbirth. When CP is the result of something that happens during delivery, medical error is frequently involved. For more detailed information on the specific events and complications that often result in cerebral palsy visit our page on Causes of Cerebral Palsy. Cerebral palsy is actually not just one single disorder but actually a grouping of several different movement disorders that are caused by the same type of injury to the brain. The different movement disorders under the cerebral palsy umbrella have been categorized into 3 separate CP subtypes: - Spastic: spastic CP is the predominant cerebral palsy subtype. Over 75% percent of all cerebral palsy cases are classified as spastic. People with spastic CP primarily suffer from hypertonia which is excessive muscle rigidity which blocks normal movements. When someone has spastic CP their brain transmits conflicting movement signals to muscle groups in the body. Instead of signaling one group of muscles to engage while opposing muscles disengage, the person's brain signals both muscles to engage simultaneously. This contradictory message from the brain causes muscles to oppose each other and essentially freeze up instead of moving fluidly. The resulting rigidity prevents normal body movement in the affected area. Spastic CP cases are divided into subcategories depending on what area of the body is disabled by the muscle lock-out. Diplegia = lower body. Hemiplegia = upper body. Quadriplegia = entire body. - Dyskinetic / Athetoid: dyskinetic or athetiod cerebral palsy (also called dyskinesia) is the second most common subtype of CP, accounting for somewhere between 5-10% of all cases. People with this type of cerebral palsy suffer from 3 types of involuntary muscle movements: athetosis (slow contortion or twisting of the arms and legs); dystonia (repetitive contracting or twisting when attempting to move); and chorea (rapid irregular movements like crazy dancing). Dyskinetic CP is not limited to specific areas of the body and affects all muscles. - Ataxic: ataxic CP is the rarest subtype and accounts for less than 5% of all cerebral palsy cases. Ataxic cerebral palsy causes severe hypotonia which is the medical term for lack of muscle tone (floppy muscles). Children with ataxic CP will often display a rag-doll appearance because of the lack of muscle rigidity. Ataxic CP also makes it very difficult to execute fine motor movements such as writing. Cerebral palsy is the most common type of physical movement disability in the United States. Current estimates suggest that about 1 million people are currently living with cerebral palsy in U.S. However, the chances of having a baby with cerebral palsy are still comparatively low. For every 1,000 newly delivered babies only 5 will be born with some type of cerebral palsy - which is .005%. This equates to around 10,000 new cerebral palsy babies annually. Visit our page on cerebral palsy facts and statistics for more information about CP occurrence rates and demographics. Fortunately cerebral palsy is not a disorder than directly decreases or limits a child's expected life span. For starters, cerebral palsy is not a progressive condition meaning it is not a disorder that gradually gets worse and worse over time. The brain injury that triggers cerebral palsy is an isolated occurrence. Once the damage to the brain occurs it doesn't spread to other parts of the brain. Cerebral palsy impacts a child's ability to move normally but it does not necessarily impair the normal functioning or longevity of their body. In fact, most children with mild to moderate cases of cerebral palsy can be expected to live just as long as any normal child. The only caveat to this is that some children with very severe cases of cerebral palsy may be more prone to accidental events that could statistically shorten their life span. For example, some kids with cerebral palsy have difficult chewing and swallowing food. This increases their risk of choking accidents. It also may lead to problems with malnourishment. Either of these secondary effects of CP can potentially reduce life expectancy. For additional information on the how long people with cerebral palsy live visit on page on Life Expectancy with Cerebral Palsy. The ICD-10 code for cerebral palsy is G80.9. This may seem like an odd entry on this cerebral palsy FAQ list, but the ICD code for cerebral palsy is actually one of the most frequently searched internet phrases for CP. The International Classification of Diseases (ICD) is a globally recognized standard for coding and classification of health and mortality statistics. Health insurance companies, hospitals, and healthcare providers use the ICD codes for insurance billing and reimbursement purposes. The ICD-10 is the most current version which went into effect in 2018. Most cases of cerebral palsy are diagnosed within the first 18 months after birth. However, mild cases of cerebral palsy may take significantly longer to diagnose because the physical symptoms are more subtle. Milder cases of cerebral palsy often do not get diagnosed until the child is 3-4 or even older. Diagnosis is usually made by the child's pediatrician based on clinical symptoms and failure to meet certain developmental milestones (e.g., sitting up by 6 months, walking by 18 months, etc.). Once cerebral palsy is suspected based on clinical symptoms, the assumptive diagnosis is usually confirmed with diagnostic imaging tests like a CT scan. For more information about the clinical symptoms of cerebral palsy visit our page on Cerebral Palsy Symptoms. Cerebral palsy is the result of neurologic damage during pregnancy or childbirth, usually from oxygen deprivation. The best way to prevent or decrease the risk of having a baby with cerebral palsy is to get the best possible prenatal medical care and the best possible care during labor and delivery. Most cases of cerebral palsy are actually the result of preventable medical errors by doctors, nurses or hospital staff. One of the sad aspects of cerebral palsy is that there is no "cure" for the disorder. Once the brain injury that causes cerebral palsy occurs there is no way to medically repair or reverse the damage. Treatment options for cerebral palsy are generally aimed at alleviating the various symptoms of the disorder and helping children manage and adapt to their disability. A typical treatment plan for cerebral palsy will involve a combination of: - Medications: various prescription medication are used to alleviate movement problems, limit secondary symptoms like seizures, reduce pain and/or make other problematic CP symptoms easier to handle. For example, muscle relaxants like Baclofen or Valium are commonly prescribed to kids with spastic CP who suffer from excess muscle stiffness. Drugs called anticholinergics are used to help control the random, involuntary movements that occur in people with dyskinetic CP. - Physical Therapy: physical therapy is the foundation of treatment for almost all children with cerebral palsy. Regularly physical therapy can help children with cerebral palsy train and manage their muscles around the limitations of their disability. Physical therapy has proven to be very effective at increasing the physical abilities of people with CP. Physical therapy can enable a child to do things like get themselves dress or walk independently which can have a dramatic impact of overall quality of life. - Occupation Therapy: occupational therapy is a more targeted variation of physical therapy. While physical therapy works on improvement of macro muscle functions and skills, occupational therapy focuses closer in on the enhancement of micro muscle movements and fine motor skills. The goal of occupational therapy is to teach children with cerebral palsy to do things like writing, typing, buttoning a shirt, etc. For more information about the various treatment options available for children and adults with different types of cerebral palsy, visit our page on Cerebral Palsy Treatment Options. Cerebral palsy is strongly linked to medical malpractice because the reality is that a large percentage of CP cases are undeniably the result of medical errors or negligent medical care during pregnancy or in the labor and delivery room. The consequences of having a child with cerebral palsy can be devastating, both economically and emotionally. When these consequences are the result of a mistake by doctors or hospitals parents have every right to get financial compensation. If you have a child with cerebral palsy and you suspect that it may be the result of medical malpractice, the cerebral palsy lawyers at Miller & Zois can help you. Call us at 800-553-8082 or request an online consultation.	2	5	0	0	2	0.935367	2	2,284
Part 1: Sepsis Series \| What is Sepsis? Kim Carrier RHIT, CDIP, CCS, CCS-P Director of Coding Quality Assurance AHIMA Approved ICD-10-CM/PCS Trainer This is part 1 in a series focused on coding of sepsis. Sepsis remains one of the most common diagnoses reported, but is also one of the most common found in denials. In this series, we will learn what sepsis is or causes of sepsis, how to sequence the diagnosis in ICD-10-CM, what are the clinical indicators for sepsis, is a query necessary before reporting the diagnosis of sepsis, and how to prevent denials on sepsis records. What is Sepsis? Sepsis is a common diagnosis in the United States and it is estimated that between one and three million Americans are diagnosed each year with this condition. Of these, about 22 percent will die on average. Sepsis is defined as a very serious medical condition and is the overwhelming response to infection. Sepsis progresses rapidly once it has begun and leads to organ damage. In the more serious cases of sepsis, one or more of the patient’s organs will fail. In the worse cases, the patient will develop septic shock, and when that occurs multiple organs will fail and the patient may find it very difficult to recover. What Causes Sepsis? Bacteria is the most common cause of sepsis, but it can also be due to fungus or a virus. When this occurs the patient’s blood culture will oftentimes be positive for the causative organism. However, a negative blood culture does not negate the diagnosis of sepsis. When the blood culture is negative, the physician is using other clinical findings of the patient to make the diagnosis of sepsis. The most common clinical findings that are used by physicians to make this diagnosis are: - High fever or low temperature (usually >100.4 F (38 C) or hypothermia <96.8 (36C) - Tachycardia (usually HR over 90) - Confirmed or suspected localized infection - Decreased mental status - Tachypnea (usually respiratory rate over 20) - Chills due to fall in body temperature - Elevated white count (more than what is seen with just a localized infection usually less than 4,000 or greater than 12,000) Keep in mind that there are a plethora of clinical indicators, according if Sepsis-1, Sepsis-2 or Sepsis-3 criteria are used. The number of sepsis cases in the United States increase each year. This is felt to be due to the aging population, increase in antibiotic resistance, and more people diagnosed with conditions that create a weaker immune system. Anyone of any age can develop sepsis, but it is more prevalent in the older population. How is Sepsis Coded? Coding the diagnosis of sepsis is a very difficult task for coders since coders see incomplete and contradictory documentation within many of the hospital records. There are many codes in ICD-10-CM for reporting the diagnosis of sepsis depending on the organism or cause. Many times, queries are needed for clarification prior to final coding of the hospital record. We will learn more on querying for sepsis as this series progresses. The most common sepsis code reported in the United States is A41.9 (Sepsis, unspecified organism). When this is reported, the patient’s blood culture was negative for any causative organism. We will also be looking at sequencing of the diagnosis of sepsis in Part 2 of this series. Please be on the lookout for this next part. ICD-10-CM Official Guidelines for Coding and Reporting FY 2020 Coding Clinic for ICD-10-CM/PCS, First Quarter 2018: Page 16 Coding Clinic, Second Quarter 2000 Page: 5 The information contained in this coding advice is valid at the time of posting. Viewers are encouraged to research subsequent official guidance in the areas associated with the topic as they can change rapidly. In the previous three parts of this four-part series, we discussed the new ICD-10-CM diagnosis code changes, ICD-10-PCS procedure code changes and FY2021 IPPS changes. In this last Part 4 of the series, we will review the NTAP procedure codes and reimbursement add-on payments for FY2021. In the previous two parts of this four part series, we discussed the new ICD-10-CM diagnosis code changes and ICD-10-PC procedure code changes. In this session we will review the major IPPS changes for FY2021. This is Part 2 of a 4 part series on the FY2021 ICD-10 Code and IPPS changes. In this part, the ICD-10-PCS procedure codes are presented. For FY2021 ICD-10-PCS there are 78,115 total codes (FY2020 total was 77,571); 556 new codes (734 new last year in FY2020)… This is Part 1 of a 4 part series on the FY2021 changes to ICD-10 and the IPPS. In this part, we discuss some of the new ICD-10-CM diagnosis changes. Here is the breakdown: 72,616 total ICD-10-CM codes for FY2021; 490 new codes (2020 had 273 new codes); 58 deleted codes (2020 had 21 deleted codes); 47 revised codes (2020 had 30 revised codes) Acute pulmonary edema is the rapid accumulation of fluid within the tissue and space around the air sacs of the lung (lung interstitium). When this fluid collects in the air sacs in the lungs it is difficult to breathe. Acute pulmonary edema occurs suddenly and is life threatening. “Client S” is a small, not-for-profit, 40 bed micro-hospital in the Southeast. HIA performed a 65-record review this year for Client S and found an opportunity with 15 of them. 9 had an increased reimbursement with a total of $43,228 found. The coma scale codes (R40.2-) can be used in conjunction with traumatic brain injury codes, acute cerebrovascular disease or sequelae of cerebrovascular disease codes. These codes are primarily for use by trauma registries, but they may be used in any setting where this information is collected. The coma scale may also be used to assess the status of the central nervous system for other non-trauma conditions, such as monitoring patients in the intensive care unit regardless of medical condition. In the past, there had been an Excludes1 note at I46.- Cardiac arrest that excluded R57.0, Cardiac shock. HIA had also received a letter from AHA on a case in the past that had stated that only I46.- Cardiac arrest would be coded if both were documented. In addition, the Third Quarter Coding Clinic page 26 had a similar case that asked if both could be coded, and AHA had instructed that only I46.9, cardiac arrest, cause unspecified would be coded if both were documented and that the CDC would be looking at possible revision to the Excludes1 note. A higher CMI corresponds to increased consumption of resources and increased cost of patient care, resulting in increased reimbursement to the facility from government and private payers, like CMS. We know that documentation directly impacts coding. Lately we have seen several cases where the endarterectomy was assigned along with the coronary artery bypass (CABG) procedure when being performed on the same vessel to facilitate the CABG. A coronary artery endarterectomy is not always performed during a CABG procedure, so when it is performed it becomes confusing as to whether to code it separately or not. Assign code Z20.828, “Contact with and (suspected) exposure to other viral communicable diseases” for all patients who are tested for COVID-19 and the results are negative, regardless of symptoms, no symptoms, exposure or not as we are in a pandemic. The Centers for Medicare & Medicaid Services (CMS) announced new procedure codes for treatments of COVID-19 – effective as of August 1, 2020. Among the new codes are Section X New Technology codes for the introduction or infusion of therapeutics including Remdesivir, Sarilumab, Tocilizumab, transfusion of convalescent plasma, as well as introduction of any other or new therapeutic substances for the treatment of COVID-19. One common element in many value-based programs is risk adjustment using Hierarchical Condition Categories (HCCs) to create a Risk Adjustment Factor (RAF) score. This method ranks diagnoses into categories that represent conditions with similar cost patterns. Why are so many AKI records being denied? It’s hard to give one answer for why so many AKI records are being denied lately, but most appear to be due to the multiple sets of criteria available for use in determining if a patient has AKI, as well as physician documentation. As stated in Part 3 of this series, there are three main criteria/classifications used to diagnose AKI. In previous parts of this series we looked at the definitions of AKI/ARF, causes, coding and sequencing, and the common clinical indicators that patients present with that are diagnosed with this condition. In Part 4, we will look at the documentation that should be present to report the diagnosis without fear of denial, as well as when a query is needed to clarify the diagnosis. If the facility does a COVID-19 test, and test is negative, do I need a diagnosis code. The answer is yes, you will report a Z-code. The Z-code depends on the record documentation and circumstances of testing. For any patient receiving a COVID-19 test, if negative, there MUST e a Z-code to describe why the test was taken. (Test negative for COVID-19 and MD does not override negative results). In the first parts of this series we looked at definitions of AKI/ARF, causes, coding and sequencing. In Part 3, we will look at what clinical indicators would possibly be present to support the diagnosis of AKI/ARF. The FY2021 IPPS Proposed Rule is out and here are some highlights from it regarding ICD-10 Code proposals. We will know if these changes are permanent after the public comment period is over on July 10, 2020 and CMS prepares the Final Rule, usually out by August 1. As discussed in Part 1 of this series, AKI/ARF is a common diagnosis that coders see daily. In Part 2, we are going to focus on the different types/specificity of AKI/ARF. We’ll learn what they mean, as well as how to code the diagnosis. This is part 1 in a series focused on coding of acute kidney injury (AKI) and/or acute renal failure (ARF). AKI/ARF is reported often, but is also one of the most common diagnosis found in denials. With the proliferation of COVID-19 cases, we thought we would put together a quick reference listing of some of the common scenarios that coders have asked about. As with all coding, coders should follow Official Guidelines for Coding and Reporting and the COVD-19 Frequently Asked Questions document by the AHA. Effective March 1, Medicare will pay physicians for telehealth services at the same rate as in-person visits for all diagnoses, not just services related to COVID-19. This great for providers whose patients are reluctant to visit the office. The biggest reasons why some hospital systems are moving to single path coding is to eliminate duplicative processes and to optimize productivity. In addition, costs are reduced when only one coder “touches” the record and completes both types of coding. The US government and public-health officials are urging consumers to utilize telemedicine for remote treatment, fill prescriptions and get medical attention during the new coronavirus pandemic. The goal is to keep people with symptoms at home and to practice social distancing if their condition doesn’t warrant more intensive hospital care. Coronavirus: Tips for working from home. Companies around the world have told their employees to stay home and work remotely. Whether you’re a new to this concept or a work from home veteran, here’s some tips to staying productive from our #HIAfamily. This is the final part of a three part series in which we address how coders can better interact with Clinical Documentation Improvement (CDI) professionals. In this part, we provide an actual example of an effective communication response to CDI. This is part two of a three part series in which we address how coders can better interact with Clinical Documentation Improvement (CDI) professionals. In this part, we discuss mismatches and how to best go about resolving them. In part three we will provide a case example of best practice interaction. This is part one of a three part series in which we address how coders can better interact with Clinical Documentation Integrity (CDI) professionals. Many times these departments are separate and the remote environment makes it difficult to interact efficiently between the two departments. In part one, we will discuss the history and objectives of CDI so the coder has a better understanding of CDI’s role. One reason that coders should report chronic conditions (including history and status codes) on outpatient records is the HCC’s—Hierarchical Condition Categories. The quick and easy explanation of what HCC’s are is each HCC is mapped to certain ICD-10-CM codes or code ranges. HCC coding is designed to estimate future health care costs for patients.	4	18	0	0	6	0.720492	6	2,921
Clinical Anaesthesia Answers Question 1: FFFTF Malignant hyperthermia (MH) is a rare autosomal dominant condition. If this patient’s biological father had MH his risk is likely to be 50%. The responsible gene mutation is on chromosome 19 in the majority of patients, resulting in three abnormal isoforms of the ryanodine receptors in muscle (plasma cholinesterase is coded for on chromosome 3). Up to 15 relevant mutations at chromosome 19 have been identified and point mutations may occur, resulting in cases with no relevant family history. The abnormality results in an abnormal ryanodine calcium channel in muscle that allows excessive calcium to move from the endoplasmic reticulum into the cytoplasm, with uncontrolled muscle contraction. Dantrolene is used to treat MH by uncoupling the excitation contraction process and blocking the ryanodine calcium channel. MH may develop after exposure to triggering agents, with some reports up to 12 hours post exposure, and can occur after previous uneventful general anaesthetics. Question 2: TTFFT In children a cuffed tube is not always used, in order to prevent tracheal stenosis; an uncuffed tube can provide a secure airway due to the anatomical variation in children. A method of detecting CO2 will confirm placement, but continuous capnography is not the only available method; in prehospital practice a colorimetric device is used. Question 3: TFFFT The Third National Audit Project of the Royal College of Anaesthetists (NAP3) investigated the major complications following central neuraxial block. Staphylococcus aureus was found to be the most common organism associated with epidural abscesses. The majority of complications following perioperative central neuraxial block (CNB) occurred with epidurals. Vertebral canal haematoma commonly presents with symptoms of leg weakness. In NAP3 weak legs were a universal symptom in cases of vertebral canal haematoma, but back pain was rare. The incidence of permanent injury after adult perioperative epidural was 8.2–17.4 per 100 000. The incidence of paraplegia and death following CNB was found to be 0.7–1.8 per 100 000. Question 4: FTTFT Cyanotic heart disease is a group of illnesses in which the deoxygenated blood travels to the systemic circulation without entering the pulmonary circulation (right to left shunt). In coarctation of the aorta there is no alteration of the normal flow but rather stenosis in the descending thoracic aorta. Tetralogy of Fallot is characterized by right ventricular outflow obstruction, VSD, aortic root over-riding a high VSD and RV hypertrophy. Thus the blood is shunted from the right ventricle to the aorta. After birth the pulmonary vascular resistance (PVR) drops below the SVR making any shunt through ASD or VSD almost always a left to right shunt. Only when complicated with severe pulmonary hypertension (Eisenmenger’s syndrome) does the reversal of shunt occur leading to cyanosis in conditions with isolated septal defects. One metabolic equivalent (MET) is equivalent to 3.5 ml.kg–1.min–1 oxygen consumption and represents the oxygen consumption of an adult at rest. Patients should be able to perform more than 4 METS to undertake major surgery, which correlates clinically to being able to climb at least one flight of stairs. MET values of activities range from 0.9 (sleeping) to 23 (running at 22.5 km.h–1). Question 6: FFFFF Myasthenic syndrome is a diagnosis related to myasthenia gravis (MG), also known as Eaton–Lambert syndrome. There are some important features of myasthenic syndrome distinguishing it from MG. There is decreased release of acetylcholine from the presynaptic nerve terminal, as opposed to IgG autoantibodies directed at the postsynaptic acetylcholine receptor seen in MG. Muscle weakness in myasthenic syndrome predominantly affects the proximal muscles, as opposed to the generalized pattern often with ocular and bulbar muscle involvement seen in MG. Weakness in MG is typically worse on exertion and improves with rest and the opposite pattern is true in myasthenic syndrome, with electromyography showing an increase in power on titanic stimulation. Patients with myasthenic syndrome show an increased sensitivity to both depolarizing and non-depolarizing muscle relaxants. In MG there is increased sensitivity to non-depolarizing muscle relaxants, but a relative resistance to suxamethonium, with up to twice the normal dose being required. Acetylcholinesterase inhibitors (such as neostigmine and more commonly pydridostigmine) are a mainstay in the pharmacological treatment of MG, but result only in slight improvement in muscle weakness in myasthenic syndrome. Other features of myasthenic syndrome not seen in MG include autonomic system disturbance and the depression or absence of tendon reflexes. Question 7: TTTFF Postherpetic neuralgia (PHN) is the term used to describe the painful aftermath of herpes zoster (HZ) infection, also known as shingles. The diagnosis is given to patients who still have pain three months or more following HZ. It is the reactivation of varicella zoster virus (VZV) that gives rise to HZ and it remains in a latent state in spinal and cranial sensory ganglia until reactivation. Although most people are immune due to childhood vaccination or exposure to wild-type virus, immunity may be decreased – by disease or immune suppression – and reactivation occur. Risk factors include: Older age (it is rare below 50 years) Acute pain and rash severity Dermatomal pain before rash appears Most patients experience a painful vesicular eruption in a single dermatome that settles within three months. However, approximately 20% will develop PHN. The pain is intense and described as burning, throbbing, stabbing or shooting. It can be continuous or intermittent, and patients often experience allodynia and hypersensitivity. The pain can be very debilitating and lead to depression and social isolation. Some measures that are part of good intensive care practice also apply to the management of the potential heart-beating donor, but there are additional measures shown to increase the viability and number of transplantable organs. Endocrine dysfunction following brainstem death can contribute to organ failure and hence hormone replacement may help preserve homeostasis. The hormones commonly replaced are insulin, methylprednisolone and triiodothyronine. The rationale for using these hormones is: insulin for treating hyperglycaemia, methylprednisolone to counter the cytokine-driven inflammatory response and thyroid hormones to improve the function of transplanted hearts in the recipient. Donor lungs are susceptible to fluid overload and so considerations may include the measurement of left-sided filling pressures and avoiding a CVP of >6 mmHg (without PEEP), which may worsen the alveolar–arterial oxygen gradient. The use of lung protective ventilation, including a positive end expiratory pressure of 5–10 cmH2O, can be effective in treating pulmonary oedema and preventing alveolar collapse. Hypotension is initially managed with volume loading because potential donors often are often relatively vasodilated, but where vasopressor support is required vasopressin is the first-line agent. In septic patients doses of vasopressin >2.5 U.h−1 are associated with adverse outcomes, including cardiac arrest. Question 9: FFTTF The Rule of Nines is a quick method used to estimate medium to large-sized burns in adults (it is not accurate in children). The body is divided into areas of 9% TBSA (see Table 5.9.1). \|Head (front and back)\|\|= 9%\| \|Anterior chest\|\|= 18%\| \|Each arm\|\|= 9%\| \|Each leg\|\|= 18%\| For small burns (generally < 5% TBSA) the palmer surface method can be used. In this method the surface of the patient’s palm, including the fingers, is estimated to be approximately 0.8–1% of TBSA and can be used to estimate the burn area. Bariatric surgery has been sanctioned by NICE as a recommended treatment for obesity, and has been shown to cause a maintainable reduction in weight of more than 50% in some cases. Laparoscopic techniques have a lower morbidity and mortality in the short term; this is thought to be due to differences in wound healing and postoperative pain causing problems with respiratory function. According to studies by Brodsky et al., raised BMI in isolation is not an indicator of difficult intubation, but raised BMI with other signs such as a Mallampati score of >3 is an indication of a potentially difficult airway. The incidence of OSA in obese patients is approximately 5%, but a history of daytime somnolence, apnoeic periods or snoring should be sought, as preoperative CPAP/BiPAP may be helpful. Due to excess limb weight and positioning, nerve injuries are more common in the obese. Suxamethonium dose should be based upon actual body weight due to increased plasma cholinesterase activity. Question 11: TTTFF RCOA guidelines require a number of features specific to paediatric day surgery. A PICU on site is not essential unless infants with chronic lung disease are undergoing surgery. Ex-premature neonates should not undergo day-case anaesthesia unless over 60 weeks post conception and medically fit. Play specialists are not obligatory, but suitable paediatric facilities must be available. Question 12: FTFTT There are several bedside tests that may predict difficult intubation: The inability to protrude the mandibular incisors A sternomental distance less than 12 cm A thyromental distance less than 6 cm Mallampati score 3 or 4 The presence of buck teeth Limited ability to extend the neck Previous radiotherapy to the head and neck can cause formation of fibrotic tissue and reduced mobility of tissues, causing difficulty at intubation. Previous tracheostomy formation or prolonged intubation may result in scarring and tracheal stenosis. The presence of numerous congenital syndromes, including Pierre Robin, Treacher Collins and Goldenhar syndrome, plus mucopolysaccharide disorders such as Hurler’s and Hunter’s syndromes, are associated with difficult intubation. The presence of a high-arched palate is seen in Marfan’s and Down’s syndromes and may complicate intubation. Question 13: TFFTF Thoracic paravertebral blocks provide an ipsilateral somatic and sympathetic nerve block similar to a unilateral epidural block, especially useful for breast surgery, thoracotomy, in patients with rib fractures or open cholecystectomy. The thoracic paravertebral space is a wedge-shaped area that lies on either side of the vertebral column defined by: Parietal pleura anterolaterally The vertebral body, intervertebral disc and intervertebral foramen medially The superior costotransverse ligament posteriorly The space is continuous with the intercostal space laterally, epidural space medially and contralateral paravertebral space via the prevertebral fascia. As the nerves emerge from intervertebral foramina, they transverse through the paravertebral space where they may be blocked by local anaesthetics, thereby blocking dorsal and ventral rami and hence the sympathetic chain. The block can be inserted with ultrasound guidance, but more commonly is performed using a landmark technique. C7 is the most prominent cervical spinous process, whilst the lower tip of the scapula lines up with T7. Complications of paravertebral blocks include infection, haematoma, local anaesthetic toxicity, nerve injury and, rarely, total spinal anaesthesia and paravertebral muscle pain (resembling muscle spasm mainly in young muscular men, especially when larger gauge Tuohy needles are used). There is no good evidence to support one inotrope over another in cardiogenic shock. Dobutamine is used frequently, not only because of its positive inotropic effect, but also as a peripheral vasodilator, reducing the afterload against a failing heart. In this case the BP is significantly low and will be made worse by dobutamine. Adrenaline is a potent vasopressor through its action on the α1-receptor, which will support the SVR in this situation. In diastolic dysfunction the cardiac output is dependent on venous return and filling pressure, which will be reduced by dobutamine due to vasodilatation. IABP can be quite helpful in patients with ischaemic cardiogenic shock who are expected to be on multiple inotropes. It will improve the coronary perfusion during diastole and reduce the afterload during systole. Noradrenaline is not routinely used as a first-line agent in these cases. Raised lactate in this case is due to pump failure that is unlikely to be helped by noradrenaline. However, it can be added later on if the low BP proved to be resistant to either adrenaline or dopamine as a single agent. Question 15: TFFTT Acute fatty liver of pregnancy is a serious condition affecting approximately 5 in every 100 000 pregnancies and has a significant maternal mortality and morbidity. The maternal mortality rate is now in the region of 10–20%, having been over 85% when the disease was first identified. It often presents later in pregnancy (after 30 weeks). Common signs and symptoms include jaundice, abdominal pain, altered mental state, nausea and acute renal impairment. The features of pre-eclampsia are present in a significant proportion of patients and it can be difficult to differentiate clinically and biochemically from HELLP syndrome. There is a higher incidence of AFLP in first pregnancies, multiple pregnancies and when the fetus is male (3:1 M:F). Radiological appearances can be normal and liver biopsy remains the gold standard test; it is, however, often contraindicated due to an underlying coagulopathy. There are risks and benefits of both general and regional anaesthesia and both have been used safely, provided none of the usual contraindications are present. CPET is a very useful test in assessing patients for lung resection. It is not needed for all patients. In those patients with poor predicted lung function as well as unexplained poor functional capacity it is indicated. If the peak VO2 is above 20 ml.kg–1.min–1 they can usually have resection up to pneumonectomy . The ability to climb two flights correlates with a VO2 max of approximately 12 ml.kg–1.min–1. The anaerobic threshold is approximately 55% of VO2 max in untrained individuals but rises to >80% in trained athletes. Question 17: FTTFT Sickle cell disease is an inherited haemoglobinopathy resulting from a mutation on chromosome 11. The mutation causes a pathological amino-acid substitution of valine for glutamic acid on the β-globin chain of haemoglobin A. This substitution produces haemoglobin S, which is inherently unstable and can adopt the notorious ‘sickle’ appearance under certain conditions. The Sickledex® test is a sickle solubility test and is used in emergency situations as a rapid screening test. It detects haemoglobin S levels greater then 10%, but is unable to differentiate between homozygous (sickle cell disease) and heterozygous (sickle cell trait) conditions. Haemoglobin electrophoresis is the definite distinguishing test. Sickle cell trait has been shown in numerous studies to confer strong protection against Plasmodium falciparum malaria. The protective mechanisms are not fully understood. However, proposed mechanisms include a reduction in parasite growth and enhanced removal of parasitized cells through acquired or innate immune systems. Question 18: FTFTT The tongue is large and the larynx is situated more anteriorly and cephalad (C3–C4). The epiglottis is large and U-shaped. The cricoid cartilage is the narrowest part of the upper airway and a small decrease in diameter caused by oedema or stricture formation following prolonged tracheal intubation may lead to airway obstruction. Tidal volume is fixed and ventilatory frequency needs to be increased to increase minute ventilation. Ventilation is mainly diaphragmatic and there are fewer type I muscle fibres, so infants fatigue earlier. FRC is less than the closing capacity owing to the low elastic recoil of the chest wall. This, along with the high metabolic requirement, predisposes them to hypoxia. Question 19: FFTFF Recognition of malignant hyperpyrexia (MH) is key: the AAGBI guidance from 2011 suggests unexplained increase in heart rate and end tidal CO2, alongside increased oxygen requirement, and possibly late-onset temperature rises, should prompt recognition of MH. Volatile anaesthesia should be discontinued and anaesthesia maintained via intravenous agents. The patient should be ventilated with 100% oxygen via a clean circuit and preferably via a dedicated anaesthetic machine that has not been in contact with volatile anaesthetic agents. While hyperventilation may help control respiratory acidosis, it alone is not adequate management. Close liaison with the surgical team is vital – explain that there is an anaesthetic emergency and that completion of surgery should be expedited, or, if feasible, surgery abandoned. In this case, conversion to an open procedure may be warranted depending on surgical experience/expertise. The recommended bolus dose is now 2.5 mg.kg–1 of dantrolene with further 1 mg.kg–1 boluses up to 10 mg.kg–1 . Active cooling measures need to be taken, but using ice is likely to cause peripheral vasoconstriction that is counterproductive and should be avoided. Question 21: TFTFF In 2015/16, 33% of renal transplants in the UK were from living donors. Under UK guidelines both a consultant surgeon and consultant anaesthetist should be present during the donor nephrectomy. As long as the renal function tests and urine production are normal, hypertension is not a contraindication to being a living donor. Diabetes mellitus is a contraindication to donating, but those with impaired glucose tolerance may be considered if fasting glucose is <7.0 mmol.l–1, oral glucose tolerance test is <7.8 mmol.l–1 and BMI is <30 with no family history of diabetes. As a nephrectomy is considered a clean procedure, routine antibiotic prophylaxis is not required. Unless there are specific patient concerns, routine use of invasive monitoring is not necessary. Question 22: FTFTF During intrauterine life, the passage of deoxygenated blood from the pulmonary artery through the ductus arteriosus (DA) into the aorta stimulates release of prostaglandin E2 (PG E2). This in turn helps to keep the DA patent. At birth, with the first breath, the flow reverses, with oxygenated blood passing from the aorta to the pulmonary artery due to changes in pressure in both circulations. This will lead to closure of the DA. In conditions where the deoxygenated blood bypasses the pulmonary circulation, such as tetralogy of Fallot, transposition of the great arteries and pulmonary stenosis, keeping the DA patent is very useful to allow the blood flow to the pulmonary circulation to improve oxygenation. Question 23: FTFTF The safe dose of lignocaine is 3 mg.kg–1 plain and 7 mg.kg–1 with adrenaline. The safe dose for bupivacaine/levobupivacaine is 2 mg.kg–1 (max of 150 mg) regardless of whether adrenaline is in the mixture. Prilocaine is safe at 6 mg.kg–1 and 9 mg.kg–1 with adrenaline. A 10 ml dose of prilocaine 2% contains 200 mg, which is within the safe dose for a 60 kg patient. However, it will be inappropriate for this operation as the spinal will be unnecessarily high and the duration of action will be very short for the procedure mentioned. The use of adrenaline is contraindicated near end arteries, e.g. ring blocks or penile blocks. Intraoperative neurophysiological monitoring is commonly used to test the integrity of spinal cord functions in scoliosis surgery. Somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) monitor the response of the spinal cord distally in response to a stimulus applied proximally. SSEPs are applied at a peripheral nerve and detected using epidural or scalp electrodes. MEPs are applied using scalp electrodes to the motor cortex and subsequently detected using epidural electrodes or compound muscle action potentials (CMAPs). To negate background noise, multiple signals applied over 2–3 minutes are averaged. Neuromuscular blocking drugs prevent CMAPs, but may help reduce background noise when detecting SSEPs. SSEPs and MEPs are depressed by volatile agents, nitrous oxide and propofol, but opioids have little effect. To identify neurological injury, as opposed to drug-induced changes in SSEPs and MEPs, it is important to achieve steady state anaesthesia with minimal changes in the drugs administered after induction. Changes in physiological parameters such as reductions in blood pressure and temperature may also depress signals. If changes thought to be due to neurological injury are detected (reduced amplitude, increased latency or loss of waveform), a ‘wake-up test’ to clinically assess the integrity of the relevant pathways is necessary. Question 25: FTTTF Overall estimated incidence of awareness under general anaesthesia is 1:19 000. This varies in different settings: with neuromuscular blockade (NMB), the incidence increases to 1:8000 and without NMB it is 1:136 000. The main risk factors identified are: Drug factors: neuromuscular blockade, thiopental, total intravenous anaesthesia techniques Patient factors: female gender, age (younger adults, but not children), obesity, previous accidental awareness under general anaesthesia and possibly difficult airway management Subspecialties: obstetric, cardiac, thoracic, neurosurgical Organizational factors: emergencies, out of hours operating, junior anaesthetists ASA grade, physical status, race and use of nitrous oxide are not risk factors for accidental awareness under general anaesthesia. Question 26: FFFTF Guillain–Barré syndrome (GBS) is an acute demyelinating polyneuropathy characterized by ascending motor weakness preferentially affecting the proximal skeletal muscles. GBS is often preceded by limb paraesthesia, back pain and in more than half of patients a bacterial or viral illness, commonly a gastrointestinal or respiratory tract infection. The commonest responsible pathogen is Campylobacter jejuni, but others that have been implicated include Epstein–Barr virus, Mycoplasma pneumoniae and cytomegalovirus. Autonomic disturbance is common in GBS and this may manifest at any stage as arrhythmias, wide fluctuations in blood pressure and pulse, urinary retention, ileus and excessive sweating. A quarter of patients with GBS will require ventilatory support. A vital capacity of <20 ml.kg–1 is an indication for intubation and ventilation; other indications include maximal inspiratory pressure of <30 cmH2O, maximal expiratory pressure of <40 cmH2O or a decrease in any of these three parameters by >30%. Treatment modalities include those that are supportive therapies, e.g. ventilatory support and physiotherapy, as well as specific therapies to reduce the inflammatory process, e.g. corticosteroids, intravenous immunoglobulin and plasmapheresis, which may reduce the severity and duration of the illness. The underlying pathophysiology in acromegaly is the hypersecretion of growth hormone from the anterior pituitary gland. Patients with acromegaly may present with a number of systemic manifestations that are of concern to anaesthetists, including changes to the airway, respiratory and cardiovascular systems, some of which are detailed here. Macrognathia, macroglossia and excess soft tissue may make laryngoscopy and tracheal intubation more difficult. Soft tissue enlargement of the upper airway results in up to 70% of patients having significant obstructive sleep apnoea. Soft tissue overgrowth peripherally results in an increased risk of nerve entrapment syndromes necessitating meticulous attention to patient positioning. Cardiovascular changes in acromegaly can include refractory hypertension with left ventricular hypertrophy, ischaemic heart disease, arrhythmias, heart block, cardiomyopathy, and biventricular dysfunction. The onset of acromegaly is typically insidious, with patients often presenting in middle age with advanced features. The hypersecretion of other anterior pituitary hormones can occur alongside acromegaly or as part of other conditions, one of which is Cushing’s disease, attributed to the hypersecretion of ACTH from a pituitary corticotroph adenoma. Physical features associated specifically with Cushing’s disease include exophthalmos secondary to retro-orbital fat deposits, as well as cervical/supraclavicular fat pads making central venous cannulation more difficult. Question 28: FTFFT Myotonic dystrophy is an autosomal dominant disease and the most common of the dystonias, the others being myotonia congenita and paramyotonia. It has an incidence of approximately 1 in 20 000, typically presenting in the second or third decade of life with death occurring in the fifth or sixth decade. Stimulation of skeletal muscle is followed by persistent contraction, disease progression is characterized by progressive muscle atrophy (skeletal, cardiac and smooth). The other important systemic manifestations include cardiorespiratory complications some of which are discussed here, but also CNS and endocrine dysfunction. Bulbar palsy increases the risk of aspiration, and respiratory deterioration can occur due to progressive depression of central respiratory drive, as well as weakness of the respiratory musculature. Cardiovascular complications include cardiomyopathy, atrioventricular block, arrhythmias and mitral valve prolapse (occurs in 20% of patients). Factors in the conduct of anaesthesia can trigger persistent muscle contraction; potential triggers include the use of suxamethonium, reversal with neostigmine and hypothermia. Regional anaesthesia does not prevent muscle contraction, but local anaesthetic injected directly into muscles may help. Other strategies to avoid troublesome spasms that have been effective in some cases include the use of IV quinine and a slow bolus of IV phenytoin (3–5 mg.kg–1 ). Cerebral palsy (CP) is a group of neurological disorders characterized by varying degrees of motor, sensory and intellectual impairment. CP is the most common cause (60%) of motor impairment in childhood. Two-thirds of patients will have some degree of impaired intellectual and cognitive function. Up to 50% of patients have either focal or generalized forms of epilepsy. There is an increased risk of aspiration pneumonitis and consequently chronic lung scarring because of swallowing difficulties, oesophageal dysmotility, abnormal lower oesophageal sphincter tone and spinal deformity, which lead to gastro-oesophageal reflux. In the long term, truncal muscle spasticity can lead to scoliosis, restrictive lung defects, pulmonary hypertension, and ultimately cor pulmonale and respiratory failure. Succinylcholine is not contraindicated in patients with CP. Non-depolarizing neuromuscular blocking agents are less potent and have a shorter duration of action in patients with CP owing to the upregulation of ACh receptors. Many anaesthetists choose to perform a rapid sequence induction to secure the airway in patients with reflux, but there is no evidence to suggest that this is any safer than a gas induction with the patient inclined at a 20–30° head-up tilt. A gas induction is often the only option in the ‘veinless’ uncooperative patient. Question 30: TFFTF The dose requirement for induction agents is reduced in the elderly. A contracted blood volume coupled with reduced protein binding lead to a higher free-drug concentration. Prolongation of arm–brain circulation time dictates that induction agents should be administered more slowly. Failure to do this leads to inadvertent overdose, often with marked cardiorespiratory side effects. Virtually all opioids, IV agents and benzodiazepines exhibit an age-related increase in their elimination half-life, resulting in a prolonged duration of action. This is attributable to an increased volume of distribution for lipophilic drugs because of the increase in body lipid content in the elderly, and a reduction in organ-based elimination. The MAC value of all inhalational anaesthetic agents is reduced by 20–40% from young adult values. Although ageing is associated with a reduction in muscle mass, the development of extrajunctional cholinergic receptors offsets the reduction in the expected dosage of neuromuscular blocking agents required to produce acceptable intubating conditions. However, the time of onset and the duration of action are both prolonged because of a reduction in cardiac output and reduced metabolism. Ageing is associated with a reduction in the carotid baroreceptor response to a fall in blood pressure. Both IV and inhalational anaesthetic agents further impair this response, and also depress cardiac and vascular smooth muscle contractility. The choice of inhalational anaesthetic has no influence on the risk of POCD, but it has been suggested that propofol via TIVA may be associated with a lower incidence. Operating frequency range – the higher the frequency, the better the discrimination of fine detail, but the lower the penetration Width of scanned tissue field – dependent on size of the probe Linear probes have a flat face and give a parallel-sided scan field approximately 1 mm thick. They generally operate at frequencies between 5 and 18 MHz. Hockey-stick probes are smaller and often used in paediatrics. Curvilinear probes have a curved face giving a fan-shaped scan field. They operate at lower frequencies, typically 2–5 MHz. Gain control adjusts brightness. More sophisticated machines employ time gain compensation. Question 32: FTFFF Migraine is more likely to affect females and commonly presents in the second or third decade. It is can occur with (30%) or without (70%) aura. It has a throbbing, pulsating quality and can be associated with nausea, vomiting, fatigue, confusion, photophobia and phonophobia. It is not commonly associated with focal neurological abnormality. Acute treatment includes simple oral analgesics, plus antiemetics or rectal diclofenac. The triptans are also used in the acute management, whereas pizotifen is used in the prophylactic management of migraine. Generally, opioids are not considered useful for migraine. In this case the patient is presenting with sudden onset headache with focal neurology and so neuroimaging should be considered, despite her history of migraine. Question 33: TTTTT Many different patient positions are utilized in neurosurgery, including all of those mentioned in the question. In the majority of patients, pressure- and positioning-related injuries are avoidable if due diligence is taken in patient positioning. Damage to the common peroneal nerve (a branch of the sciatic nerve) can occur in the lateral position, resulting in foot drop. This nerve is particularly vulnerable because of its superficial course as it wraps laterally around the fibular head. In the prone position the upper limbs are slightly flexed, then abducted and externally rotated; this should be done simultaneously in both arms. The brachial plexus is at risk in this position and particular care should be taken to ensure that chest supports do not impinge on the axilla. Venous air embolism is a well-recognized complication of the sitting position, the pathophysiology of which relates to the potential for air entrainment into dural venous sinuses that are relatively non-collapsible. The lateral position carries the highest risk of ocular complications in both the dependent and non-dependent eye, the most of common of which is corneal abrasion. A head ring or horseshoe headrest if malpositioned can result in direct pressure on the globe, causing ischaemic optic neuropathy. The Lund–Browder chart is an accurate tool commonly used to measure percentage burns in children and adults (Table 5.34.1). As opposed to the Rule of Nines, the Lund–Browder chart compensates for the changes in body proportions in the head, thighs and legs that occur with age, the head (front and back) making up 17% of total body surface area (TBSA) in a one-year-old child compared with only 7% in an adult. It has been noted that the Lund–Browder chart does not take into account obesity, breast size, pregnancy status and amputated body parts, all of which may affect the calculated body surface area. \|Half of head\|\|9.5\|\|8.5\|\|6.5\|\|5.5\|\|4.5\|\|3.5\| \|Half of one thigh\|\|2.75\|\|3.25\|\|4\|\|4.5\|\|4.5\|\|4.75\| \|Half of one lower leg\|\|2.5\|\|2.5\|\|2.75\|\|3\|\|3.25\|\|3.5\| The neck (1%), perineum (1%), arms (10% each), torso (13% each side), buttocks (2.5% each) and feet (3.5% each) are the same %TBSA, regardless of age. Question 35: FTTFF Laparoscopy involves the insufflation of the peritoneum with CO2. This gas is chosen because it is more blood soluble than nitrogen, so it is less likely to cause air embolism, as it is rapidly absorbed if inadvertent intravascular injection takes place. The diaphragmatic irritation causes irritation of the phrenic nerve (roots C3–C5), which have a shoulder dermatomal distribution. Raised ICP (caused by either intracranial neoplasm, head trauma or hydrocephalus), hypovolaemia and severe valvular or ischaemic heart disease are all relative contraindications to laparoscopy. Insufflation pressures are typically up to 20 mmHg, as above this point the physiological responses to pneumoperitoneum can cause a severe fall in cardiac output leading to cardiac arrest. There are some reports of laparoscopy being combined with epidural or spinal anaesthesia, however a block to T4 is required and this does not obliterate the referred diaphragmatic pain. Question 36: FTTTF Tuberculous meningitis is associated with turbid or opalescent CSF, very high protein (>2 g.l–1), low glucose and lymphocytes. Mumps meningitis may be associated with low glucose in 20% of cases. Partially treated bacterial meningitis may be associated with lymphocytes rather that neutrophils, the more classic picture in bacterial infection. CSF glucose is two-thirds or higher of the serum level and CSF pressure is 6–15 cmH2O. Question 38: FFTFT Water and other clear, non-carbonated drinks, including tea and coffee without milk – two hours Breast milk – four hours Food, drinks containing milk, carbonated drinks – six hours In patients in whom you suspect gastric emptying may be abnormal, consideration should be given to performing a rapid sequence induction and securing the airway with an endotracheal tube. Question 39: FFTFF In isolated left anterior fascicular block the QRS width is normal: a maximum of 0.12 s. The only finding is that of left axis deviation. In left posterior fascicular block, right axis deviation is present without signs of right ventricular hypertrophy. Left anterior fascicular block is more common than posterior fascicular block; the fascicle has a dual blood supply. The definition of trifascicular block is more contentious than that of bifascicular block. It is commonly taken to mean the presence of bifascicular block, that is right bundle branch block with co-existent left hemifascicular block, with co-existent first-degree atrioventricular block. Question 40: FTFTF In order to standardize the description of permanent pacing and defibrillation systems, a five-letter international classification system is accepted.The first three letters are always stated and describe the antibradycardia functions.The last two letters are additional functions and not always stated if absent. For example, VVI00 describes a pacemaker that: V: Paces the ventricle (the chamber paced; can be A – atrial, V – ventricle, D – dual, 0 – none) V: Senses in the ventricle (the chamber sensed; can be A – atrial, V – ventricle, D – dual, 0 – none) I: Is inhibited by sensed activity (the response to a sensed beat; can be 0 – none, T – triggered, I – inhibited, D – dual) 0: Is not programmable (programmability; can be 0 – none, P – simple, M – multiprogrammability, C – communicating, R – rate responsiveness) 0: Doesn’t have antitachycardia functions (antitachycardia function; can be 0 – none, D – dual, P – pace, S – shock) Amniotic fluid embolism (AFE) is a rare (1:50 000) disorder with a mortality of around 20–40%. It was once thought to have a mortality of around 80%, but better identification and management have reduced this to the current levels. It is thought to be an immune-mediated response rather than a direct embolic effect. There is no pathognomonic test and diagnosis is based on clinical signs. It can present atypically with symptoms ranging from a sense of feeling generally unwell to cardiac arrest; it is possible that it could present with an isolated coagulopathy. Management is predominantly supportive and the early involvement of critical care teams is essential to provide the best chance of survival and recovery. Known risk factors include: Maternal age >35 Induction of labour Instrumental or operative delivery Question 42: FTFTF For lobectomy, the calculation uses the number of bronchopulmonary segments removed compared with the total number, 19, in both lungs. Although previous guidelines used absolute values of FEV1, 1.5 litres for lobectomy and 2 litres for pneumonectomy, this may lead to false interpretations. For preoperative assessment these values (FEV1, DLCO) should always be expressed as a percentage of predicted volumes corrected for age, sex and height. A ppoFEV1 <30% is not an absolute contraindication for lung resection. The patient can be offered lung resection if they accept the risk involved and potential impact on lifestyle, such as dyspnoea. Question 43: FFFFF Question 45: FFFFF Anaphylaxis is a type 1, IgE-mediated hypersensitivity reaction. Type 2 hypersensitivity reactions are cytotoxic immune-mediated reactions via IgG or IgM antibodies reacting to the presence of antigens. Type 3 immune-complex-mediated reactions involving antigen/antibody complexes cause activation of complement and neutrophils resulting in tissue damage – a more gradual process. Type 4 hypersensitivity reactions are delayed reactions resulting from antigen-specific T cells causing a macrophage-driven response. Anaphylaxis can occur in anyone, but atopic individuals are more prone. The commonest presentation, particularly under anaesthesia, is cardiovascular collapse and respiratory compromise secondary to bronchospasm. Rash is a non-specific sign and may be delayed, or difficult to ascertain under anaesthesia. Epipens deliver a dose a 0.3 ml of 1 in 1000 adrenaline. Current ALS guidelines recommend 0.5 ml 1 in 1000 adrenaline IM or in the case of adults 50 μg IV boluses if competent in the IV administration of adrenaline. As the quaternary ammonium group is commonly found in other drugs, food products and cosmetics, previous exposure to neuromuscular blockers is not necessary. Question 46: TFTFT The majority of complications are secondary to improper pressure point protection or prolonged positioning. Abdominal compartment syndrome has been described in patients who have had prone positioning; it is important to allow free movement of abdominal contents both to prevent this and allow for easier ventilation. Visual loss is as a result of external orbital pressure. Question 47: FFFTF In the UK, conscious sedation is defined as ‘a technique in which the use of a drug or drugs produces a state of depression of the central nervous system enabling treatment to be carried out, but during which verbal contact with the patient is maintained throughout the period of sedation’. The ASA classifies sedation into three levels: Minimal sedation: drug-induced state where the patient responds normally to verbal commands. Cognitive function and physical co-ordination can be impaired, but airway reflexes, and ventilatory and cardiovascular functions, are maintained Moderate sedation: patients respond purposefully to verbal stimuli, which may be accompanied with light tactile stimulation. This equates to conscious sedation Deep sedation: patients respond only to repeated or painful stimulation; can be associated with significant ventilatory depression Benzodiazepines can be up to eight times more potent when given after an opioid, therefore when they are to be used in combination, the opioid should be administered first and the benzodiazepine titrated carefully after the peak effect of the opioid is seen. The elimination half-life of midazolam is 1.5–3.5 hours. It is almost completely metabolized in the liver to hydroxylated derivatives that are conjugated to glucuronides, these are then excreted in the urine, thus renal impairment has little effect. The AAGBI recommends that continuous capnography should be used for all patients undergoing moderate or deep sedation, and should be available in areas where these patients are recovered. It is appropriate to deliver oxygen, usually via nasal cannula, to all sedated patients from the administration of the sedatives until they are ready for discharge from recovery. • β-adrenergic drugs • Epidermal growth factor • Male gender • Ethnicity (Caucasian) • Genetic predisposition Question 49: FTTTF Question 50: TFFFT When oxygen demand exceeds supply, muscle cells begin generating ATP anaerobically. This process produces lactic acid, which is buffered by bicarbonate and results in an increase in CO2. The VO2 at the point this occurs is called the anaerobic threshold. Therefore the anaerobic threshold will not vary with patient motivation, but the peak VO2 will only reach as high as the effort the patient puts into the test. Anaerobic threshold only reduces slightly with increased age, but will be reduced in proportion to the degree of organ impairment. An anaerobic threshold of at least 11 ml.kg–1.min–1 is required to safely undertake significant surgery. Question 51: TFTTT Complex regional pain syndrome (CRPS) usually develops after trauma to a limb. The predominant symptom is pain, but it is also associated with sensory, autonomic, motor, skin and bone changes. For a diagnosis of CRPS to be made the patient must meet the Budapest Diagnostic Criteria (Table 5.51.1). All the following statements must be met: The patient has continuing pain that is disproportionate to the inciting event The patient has at least one sign in two or more of the categories below The patient reports at least one symptom in three or more of the categories below No other diagnosis can better explain the signs and symptoms \|1 ‘Sensory’\|\|Allodynia (pain to light touch and/or temperature sensation and/or deep somatic pressure and/or joint movement) and/or hyperalgesia (to pinprick)\| \|2 ‘Vasomotor’\|\|Temperature asymmetry (>1 °C if counted as a sign) and/or skin colour changes and/or skin colour asymmetry\| \|3 ‘Sudomotor/oedema’\|\|Oedema and/or sweating changes and/or sweating asymmetry\| \|4 ‘Motor/trophic’\|\|Decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair/nail/skin)\| Hypoaesthesia is not part of the diagnostic criteria. Epilepsy is defined as two or more epileptic seizures with no immediately identifiable cause. The clinical manifestations of seizures are extremely variable and can range from behavioural disturbance to life-threatening and unremitting convulsions. Investigations to determine the cause for a patient presenting with seizures include electroencephalography (EEG) as well as imaging modalities including CT, MRI, SPECT and PET scans. Patients with established epilepsy show abnormal epileptiform activity in up to 50% of cases, but interestingly this is also apparent in 4% of patients without epilepsy. It may be necessary to administer anticonvulsant drugs perioperativly, particularly if the risk of further seizures is high or the seizures are particularly poorly controlled. Of the commonly used drugs sodium valproate, phenytoin and levetiracetam are available in intravenous forms. Status epilepticus (SE) is defined as continuous seizure activity lasting 30 minutes or intermittent seizures for this period without regaining consciousness. SE carries a mortality of 25% and has systemic complications that include respiratory failure, pulmonary oedema, disseminated intravascular coagulopathy, myocardial ischaemia, arrhythmias, cerebral hypoxia and central venous thrombosis (not an exhaustive list). The prompt management of SE is therefore crucial; lorazepam 0.1 mg.kg–1 is commonly recommended as a first-line agent. • Burn centre – This level of in-patient burn care is for the highest level of injury complexity and offers a separately staffed, geographically discrete ward. The service is staffed to the highest level of critical care and has immediate operating theatre access. • Burn unit – This level of in-patient care is for the moderate level of injury complexity and offers a separately staffed, discrete ward. • Burn facility – This level of in-patient care equates to a standard plastic surgical ward for the care of non-complex burn injuries. Question 54: FFTTT Carcinoid tumours are neuroendocrine tumours that secrete a large amount of vasoactive peptides such as serotonin, dopamine, corticotrophin, histamine, substance P, neurotensins, kallikrein and prostaglandins. The clinical features of carcinoid crisis are due to the intravascular release of these hormones. If the primary tumour is found in the gut (as in 67.5% of cases), the vasoactive hormones are metabolized by the liver so rarely cause systemic effects. For this reason, frequent or severe attacks of flushing, hypotension and bronchospasm are thought to be due to hepatic metastases or non-GI tumours (e.g. bronchopulmonary). These hormones, when released into the venous system, cause right-sided (tricuspid and pulmonary) valvular lesions and fibrous thickening of the endocardium. Left-sided lesions are rare and usually signify right to left shunting or bronchial carcinoid. Cardiac complications are associated with an increase in perioperative complications. Tyrosine-containing foods may precipitate an attack due to tumour metabolism, as may histamine-releasing drugs such as atracurium and morphine. Noradrenaline has been shown to activate kallikrein in tumours and may lead to synthesis and release of bradykinin, resulting paradoxically in vasodilatation and worsening hypotension. Question 55: TFTTT NICE guidelines recommend ceftriaxone as first-line therapy (unless calcium-containing solutions are used, in which case cefotaxime should be used). Neuroimaging is indicated if there is suspicion of raised ICP, an alternative intracranial diagnosis is suspected, focal neurological signs are present or on expert recommendation. In the UK, suspected or proven meningitis is a notifiable disease. Young children may present subtle features suggesting raised ICP, as well as bradycardia, hypertension, reduced conscious level, unilateral pupillary dilatation, tense fontanelles, nausea and vomiting, and papilloedema. NICE recommend considering intubation if shock persists after more than 40 ml.kg–1. Question 56: TTFFT Wilson’s criteria comprise five components: obesity, restricted jaw movement, receding mandible, the presence of buckteeth and reduced neck movement. Each variable receives a score between zero and two. A total score greater than two is predictive of a difficult intubation. Previous difficult intubation and a reduced thyromental distance are predictive of difficult intubation, but do not form part of Wilson’s criteria. Ultrasound-guided regional blocks provide faster sensory onset and improved success rates when compared to landmark-based techniques. There is no current evidence to suggest that ultrasound use in regional anaesthesia reduces the incidence of neurological complications. However, there is a reduction in the incidence of vascular puncture and haematoma when undertaking regional anaesthesia using ultrasound guidance. There is level 1a evidence to confirm that phrenic nerve blockade is almost always seen with higher-volume (20 ml or more) local anaesthetic use during brachial plexus block. Ultrasound guidance allows practitioners to use low volumes. Question 58: FTTFF The Goldman Cardiac Risk Index is a multifactorial index of cardiac risk in non-cardiac surgery (Table 5.58.1). It was developed in 1977 from retrospective data on 1001 patients undergoing non-cardiac surgery to identify patients at risk from major perioperative cardiovascular complications. The score is made up from nine independent risk factors, which have different weightings: 1. Third heart sound/elevated JVP – 11 2. MI in last six months – 10 3. Rhythm other than sinus – 7 4. Ventricular ectopics (>5 per minute) – 7 5. Age >70 – 5 6. Emergency operation – 4 7. Significant aortic stenosis – 3 8. Poor medical condition of patient or bedridden – 3 9. Abdominal or thoracic operations – 3 \|Class\|\|Score\|\|Complication risk (%)\| Overall the index has high specificity, but low sensitivity. The index was revised in 1999 by Lee, known as the Revised Cardiac Risk Index, based on six independent variables (chronic kidney disease, ischaemic heart disease, heart failure, cerebrovascular disease, insulin-dependent diabetes, intraperitoneal/thoracic surgery). This has been further superseded by the American College of Surgeons Risk Calculator (2014). Adrenaline has both inotropic and chronotropic effects, resulting in an increased cardiac workload. This will eventually increase the oxygen consumption, resulting in lactic acidosis. Adrenaline also enhances hepatic gylcogenolysis and glycolysis whilst reducing pyruvate utilization, leading to lactic acid production. The increased heart rate in this scenario gives a clue that the patient may be helped by a reduction in the adrenaline infusion rate. Starting vasopressin or increasing the rate of noradrenaline will not add any benefit as both MAP and urine output are adequate. Dopamine will further increase the heart rate and oxygen consumption. Question 60: FTTFT Cardiac disease remains a significant cause of maternal morbidity and mortality. Predominant causes of cardiac death are sudden adult death syndrome, myocardial infarction, aortic dissection and cardiomyopathy. It is the greatest cause of indirect and overall maternal death. Infarction is the fourth biggest cause of death (behind the others listed above). Cardiomyopathy can be difficult to diagnose, as its symptoms may be seen normally in later pregnancy – shortness of breath, swelling, tachycardia and reduced exercise tolerance. Dilated cardiomyopathy has a significantly worse prognosis than hypertrophic due to the additional stress of pregnancy and labour producing a high risk of left ventricular decompensation. Peripartum cardiomyopathy can present late and should be considered in any patient with symptoms of cardiac failure up to six months post delivery. Aortic dissection is still a leading cause of death, with most of those occurring involving the ascending aorta. Dissection should be excluded in any patient with severe chest pain and investigation with CT, MRI or USS is appropriate. Question 61: TFFTF Thalassaemias have an autosomal recessive pattern of inheritance. Cooley’s anaemia is the homozygous, major clinical phenotype of β-thalassaemia. It results in a profound anaemia requiring multiple blood transfusions. Bart’s hydrops fetalis syndrome is the most severe form of α-thalassaemia, where there is no functional α-allele. This results in formation of haemoglobin-Bart’s (four γ-chains). Haemoglobin-Bart’s has a very high affinity for oxygen, resulting in very little tissue oxygen delivery. Bart’s hydrops fetalis syndrome usually results in intrauterine or early neonatal death, as well as serious maternal risks. A difficult laryngoscopy must be anticipated as a consequence of facial changes (for example, maxillary hypertrophy) from marrow hyperplasia. Haemolysis may be precipitated by oxidant drugs, including: Cyanotic heart disease is due to venous blood entering the systemic circulation, having bypassed the lung. The blood that is pumped out to the body is low in oxygen. Heart defects like tetralogy of Fallot, transposition of the great arteries, truncus arteriosus, Ebstein’s anomaly and coarctation of aorta can cause cyanosis. Tetralogy of Fallot is the most common congenital cyanotic heart disease. The classic form includes four defects, i.e. large VSD, pulmonary stenosis, right ventricular hypertrophy and an over-riding aorta. Question 63: TTFTT Malignant hyperpyrexia (MH) is a rare autosomal dominant condition. The incidence is approximated at 1:200000, resulting from abnormal ryanodine receptors. Release of calcium through faulty channels results in sustained muscle contraction. This results in muscle cell damage, with the release of potassium, myoglobin and creatinine kinase. These patients are therefore at significant risk of acute renal failure and may need renal replacement therapy. With increased metabolism, temperature and carbon dioxide production, it would seem logical to expect cutaneous vasodilatation. However, catecholamine surges result in vasoconstriction initially. Increased metabolic demands of muscle result in diversion of cardiac output from cutaneous vasculature beds to muscle mass. Disseminated intravascular coagulation is a recognized complication of malignant hyperpyrexia and there are case reports of compartment syndrome associated with confirmed cases of malignant hyperthermia. Question 64: TTFTT There tends to be some unintended movement of the COETT during change in position and this may lead to carinal stimulation or endobronchial intubation, which in turn can lead to atelectasis. Redistribution of blood within the lower limbs can lead to fluid overload in susceptible patients. Prolonged positioning is a risk factor for the development of VTE and compartment syndrome of the lower limbs; the sole use of foot stirrups versus combined calf and foot supports shows no difference in the risk. Alopecia can develop in any position with the potential for ischemia of the scalp. There is little risk of pressure on the orbit due to the position (although the risk of damage from the improper use of a facemask or lack of protective measures for the eye can be a cause of damage in any position). Question 65: FTFFF Low-frequency jet ventilation (LFJV) was first described in 1967 by Douglas Sanders. His technique allowed continuous patient ventilation alongside unrestricted surgical access to the airway via an open rigid bronchoscope. LFJV is delivered via a handheld device, such as a Sanders injector or a Manujet, through a short rigid narrow cannula. It can be used in conjunction with rigid bronchoscopes or laryngoscopes for short surgical procedures, and also has an important role in emergency airway management via a cricothyroidotomy cannula. LFJV uses a high-pressure oxygen source and the entrainment of air via the Venturi principle, so the delivered tidal volume is the sum of the injected and entrained volumes. A jet frequency of between 8 and 20 min–1 is normally appropriate; this allows time for both chest wall expansion and passive recoil. The upper airway must be patent to allow adequate exhalation of gases to prevent air-trapping and barotrauma. Capnography cannot easily be used, therefore the best way to assess adequacy of ventilation is to observe the chest wall for expansion and perform arterial blood gas analysis. When using LFJV for surgical procedures, inhalation agents cannot be delivered, hence anaesthesia is maintained with TIVA. Achondroplasia is associated with a large tongue and mandible, stenosis of the foramen magnum, limited neck extension and increased incidence of atlantoaxial instability. Hurler’s and Hunter’s syndromes are both hereditary, progressive mucopolysaccharidoses, characterized by progressive generalized infiltration and thickening of the soft tissues. They are associated with extremely difficult airways for a number of reasons: macroglossia, tonsillar and adenoidal hypertrophy, narrowing of the nasal passages, short immobile neck, TMJ involvement, cervical spine instability, and supraglottic and infraglottic soft tissue thickening. Beckwith–Wiedemann syndrome is the most common overgrowth syndrome in infancy, it describes the combination of macroglossia, macrosomia (birth weight and length greater than the 90th percentile), mid-line abdominal wall defects, ear creases or pits, and neonatal hypoglycaemia. Goldenhar syndrome (oculo-auriculo-vertebral dysplasia) is characterized by a wide range of congenital anomalies, including micrognathia, facial asymmetry and hypoplasia, vertebral anomalies causing limited neck movement and ear malformations with hearing loss. Other anomalies of the oral cavity sometimes seen include a high arch or cleft palate and abnormalities of the tongue. Question 67: TTTFF This preterm baby suffers from severe respiratory distress syndrome. The preterm labour is mostly due to infection, secondary to prolonged rupture of membranes. Hence antibiotics should be given in this case. Investigations that would help to confirm the diagnosis include a chest radiograph, which usually shows symmetrical reticulogranular shadowing and excludes pulmonary hypoplasia, and an echocardiogram is essential to determine if there is pulmonary hypertension leading to the higher FiO2 requirement. Pulmonary maturity can be assessed by measuring the lecithin-to-sphingomyelin ratio from baby’s pharynx or stomach. Increasing PEEP and the use of high-frequency oscillation are recognized measures to improve oxygenation rather than increasing FiO2 for longer periods, leading to oxygen toxicity. Surfactant therapy is usually used as prophylaxis to the preterm within the first hour of birth. This leads to significant reduction in pneumothorax, bronchopulmonary dysplasia and mortality. Question 68: TFFFF Packed red cells may be stored for up to 35 days with SAGM (saline adenine glucose mannitol). Platelets can be stored for up to five days at room temperature (20–24 °C) and up to seven days with bacterial screening. They must be continually agitated to prevent clumping. Storage is limited to five days due to the risk of bacterial contamination. Platelets are labelled with ABO and rhesus type. ABO compatibility is preferred, but in adults ABO-incompatible platelets can be used due to the small volume of plasma containing antibodies. Cross-matching is not required because a platelet unit contains only 2–5 ml of red cells. This small red cell volume is capable of creating immunization of the Rh-D antigen and therefore Rh compatibility is required for all Rh-negative children and Rh-negative mothers of childbearing age to prevent the formation of anti-D antibodies. The aim of electroconvulsant therapy (ECT) is to produce a generalized seizure lasting between 15 and 120 seconds. First described in 1938, during the first three decades of its use anaesthesia was not employed, but now a general anaesthetic with paralysis is obligatory. The cardiovascular response to ECT begins with an initial parasympathetic discharge that can result in bradycardia and hypotension. This is followed by a sympathetic response that can involve cardiac arrhythmias. Myocardial ischaemia is a risk due to a combination of increased myocardial oxygen consumption and reduced myocardial oxygen supply. Common induction agents include propofol and etomidate. Propofol is associated with quicker emergence, whereas etomidate produces the longest seizure duration and may reduce the seizure threshold. Neuromuscular blocking agents reduce the risk of serious injury due to muscular convulsions. Suxamethonium is the most commonly used agent, usually at a dose of 0.5 mg.kg–1 . Larger doses are sometimes required, for example in cases of osteoporosis or severe cachexia. Question 70: FFTFF The patient is describing the typical symptoms of trigeminal neuralgia (TN). It is defined as a sudden, usually unilateral, brief stabbing recurrent pain in the distribution of one or more branches of the trigeminal nerve. TN is usually subdivided into idiopathic and secondary categories. Idiopathic TN has no obvious cause other than vascular compression. Secondary TN occurs as a result of a structural lesion such as multiple sclerosis. The diagnosis of TN can often be made on the basis of the history alone. To image the trigeminal ganglion and surrounding vessels, MRI and angiography are employed. The superior cerebellar artery is the more likely vessel to be compressing the trigeminal nerve. However, not all patients with idiopathic TN have obvious neurovascular contact, which has led to the development of other theories regarding its pathophysiology. Carbamazepine is widely used in the management of TN and with some success. Gabapentin and the lidocaine plaster are also management options, but are not generally first line. Acyclovir is used in the management of acute herpes zoster. Question 71: TFFFT See explanation for Question 28. Myasthenia gravis (MG) is an autoimmune disease characterized by worsening muscle weakness. In its early stages the muscle weakness may affect the ocular muscles alone, but as the disease progresses the effects on skeletal muscle are more pronounced and eventually this may lead to respiratory failure. The pathophysiology is attributed to autoantibodies specific for the postjunctional acetylcholine receptor, reducing the number of functional receptors and preventing normal neuromuscular transmission. There are a number of markers of disease severity that are predictive of the need for postoperative ventilation and these include: duration >6 years, pyridostigmine dose >750 mg.day–1, preoperative vital capacity of <2.9 l and co-existing chronic respiratory disease. MG sufferers are very sensitive to the effect of non-depolarizing muscle relaxants (NDMRs) and so a tenth of the usual dose is recommended for intubation and subsequent maintenance doses. Myasthenic patients are, however, resistant to the effect of suxamethonium and so a slightly increased dose (1.5 mg.kg–1 ) is usually needed for rapid sequence induction. Reversal of NDMRs with a normal dose of neostigmine is possible, but its use carries the risk of precipitating a cholinergic crisis. The avoidance of NDMRs or the use of atracurium (spontaneously broken down) is therefore preferable to reversal using neostigmine. A number of different devices can be used to monitor intracranial pressure; examples include the extradural fibreoptic probe, subarachnoid screw and external ventricular drain. These devices measure intracranial pressure, but some can be used to calculate other indices, including compliance or pressure/volume index and to drain CSF. The intracranial pressure waveform is similar to the trace produced by an arterial line, since it corresponds to the pressure changes in large intracerebral vessels, as well as varying with respiration, reflecting changes in central venous pressure. The three main waveforms observed are as follows. ‘A’ waves are also known as plateau waves (amplitude 50–100 mmHg, lasting 5–20 min). These represent severely reduced compliance and are most commonly associated with tumours and cerebral vasodilatation. ‘B’ waves (amplitude <50 mmHg, occur with a frequency of one per minute) are associated with changes in respiration and are less useful clinically. A variation of ‘B’ waves known as ‘ramp’ waves is associated with hydrocephalus. ‘C’ waves (amplitude <20 mmHg, frequency of 4–8 per minute) are not useful clinically and relate to normal physiology: blood pressure and vasomotor tone. Parameters vary according to the pathology identified, but a sustained rise in intracranial pressure of >20 mmHg for 30 minutes usually warrants active management. Question 74: TFTFT The moorLD12-BI is a laser Doppler blood-flow imaging system used for the non-invasive mapping of blood flow in an area of skin that has been burnt. NICE guidance supports its use to guide treatment decisions for patients in whom there is uncertainty about the depth and healing potential of burn wounds that have been assessed by experienced healthcare clinicians. It uses a low-power laser beam that scans the burn area and using Doppler frequency shift calculations displays the blood flow as a colour coded blood-flow image and a colour video image of the burn wound. Healing potential results based on the blood-flow image are calculated and reported in three categories: less than 14 days, 14–21 days and more than 21 days. In burn wounds of intermediate (also known as indeterminate) depth the moorLD12-BI can be used to demonstrate which areas of any burn wound require surgical treatment and which do not, enabling decisions about surgery to be made earlier and for surgery to be avoided in some patients. It has been shown to have a higher accuracy than clinical assessment, with a variety of criteria, including the ability to predict wound healing in 14–21 days. Pulmonary hypertension (PH) is defined as a mean pulmonary arterial pressure over 25 mmHg at rest with a wedge pressure <12 mmHg; moderate PH is said to occur when the PA pressure is >35 mmHg. The key to safely anaesthetizing these patients is to maintain coronary perfusion pressure by ensuring a normal or near normal SVR, avoiding a loss of right ventricular preload, avoiding high PEEP, hypoxia, hypercarbia, acidosis, hypothermia and pain – all conditions which will increase pulmonary vascular resistance. Due to their inodilator properties, which may decrease SVR, milrinone and dobutamine are not recommended for use in PH. Central neuraxial anaesthesia can be safely used in PH, as long as attention is paid to minimizing the cardiovascular effects of these techniques. There are no α1-receptors in the pulmonary circulation. Ketamine may raise pulmonary vascular resistance, but its safe use has been reported in the literature. Question 76: TTFFF A thyroid storm is a hypermetabolic crisis that may occur in thyroid disease or be precipitated by drugs, radioiodine or surgery. Mortality may be as high as 30%. Management includes resuscitation and cooling. Specific therapy includes: Propranolol, which reduces effects via β-blockade and reduction in T4 to T3 conversion Hydrocortisone, which treats relative adrenal insufficiency and blocks T4 to T3 conversion Lugol’s solution, which delivers high concentrations of iodine, which suppresses thyroid hormone synthesis via the Wolff–Chaikov effect (not the Jod–Basedow mechanism). Amiodarone has a high iodine content and can be a precipitant of a thyroid crisis, so should be used with great caution. Paracetamol can be used as an antipyretic, but NSAIDs can displace bound thyroid hormone and should be avoided. Question 77: TTFFT The systemic effects of cigarette smoke are widespread, owing to the different chemicals contained therein. In the respiratory system, airway reactivity is increased, predisposing to laryngospasm and bronchospasm. There is a greater production of airway secretions compared to non-smokers, and combined with impaired ciliary function, results in mucous plugging and sputum retention. Smokers are at risk of developing COPD and lung cancer. In the cardiovascular system, nicotine acts to increase heart rate, systemic vascular resistance and blood pressure. Prolonged exposure to cigarette smoke increases the risk of developing ischaemic heart disease and peripheral vascular disease. In the presence of carboxyhaemoglobin, the oxyhaemoglobin dissociation curve is shifted to the left, resulting in impaired release of oxygen to the tissues and the risk of hypoxia. Hepatic enzymes can be induced by cigarette smoking; this may result in lower levels of drugs than might otherwise be anticipated. Smoking reduces the risk of postoperative nausea and vomiting. The mechanism by which this occurs is uncertain. Question 78: TFFFF Atrial fibrillation with a spontaneously slow ventricular response is an indication for pacemaker insertion. The pressing need for surgery must be balanced against the risk of compromise to the cardiovascular system if a pacemaker is not inserted preoperatively and an alternative mechanism of pacing, such as transcutaneous pacing, should be available. Patients who receive β-blockers as part of their routine management of atrial fibrillation should take these on the morning of surgery. The risk of developing a rapid ventricular response in the perioperative period outweighs that of hypotension intraoperatively, which is usually relatively straightforward to manage with vasoconstrictors or chronotropic agents. Digoxin doses should be reduced by a third when an oral dose is converted to intravenous. It is not essential to measure digoxin levels on the day of surgery in patients who have been established on digoxin long term without a recent dose change; adequate rate control and an ECG without concerning features of toxicity are acceptable. Patients undergoing elective surgery are able to take their routine medications – unless contraindicated – with a small amount of water. There is no need to routinely convert oral medications to intravenous formulations. Interscalene block provides reliable anaesthesia and analgesia for procedures (open and arthroscopic) involving the shoulder joint, lateral two-thirds of the clavicle and proximal humerus. It effectively blocks the proximal nerve roots, distal cervical plexus (supraclavicular nerves) and important nerves such as the suprascapular, which exit proximally from the plexus. A sterile high-frequency (10–13 MHz) probe is used to scan the neck transversely between the level of the cricoid cartilage and supraclavicular fossa until an optimal view of the hypoechoic round images of C5 and C6 nerve roots or upper trunk is obtained. There is level 1a evidence to confirm that phrenic nerve blockade is almost always seen with traditional high volume (20 ml or more) blocks, including continuous infusions for postoperative analgesia. Question 80: FTTFT The liver is the principle organ in the body for drug metabolism. The phases of metabolism are typically split into two and aim to make the drug easier to excrete. Phase 1 reactions are non-synthetic and involve formation of a new or modified functional group, or cleavage (commonly oxidation, reduction, hydrolysis or hydration). Phase 2 reactions are synthetic and involve conjugation with endogenous hydrophilic groups to increase solubility and hence renal excretion (e.g. glucuronide, sulfate, glycine). Benzodiazepines undergo oxidation in the liver, whilst morphine undergoes glucuronidation (the most common phase 2 reaction). Morphine is metabolised to morphine-3- (inactive) and morphine-6-glucoronides (active). Cytochrome enzymes function as electron transfer agents and are found in many tissues including the liver, gut and kidneys. They are proteins containing haem as a co-factor. The term P450 is from the spectrophotometric wavelength absorption maxima for the enzyme in the reduced state complexed with carbon monoxide (450 nm). These enzymes are typically found on the inner mitochondrial membrane or in the endoplasmic reticulum, and are generally terminal oxidase enzymes in electron transfer chains. Cytochrome P450 enzymes are the major enzymes involved in drug metabolism. They are also important in hormone synthesis and breakdown. Sepsis and its related complications remain the most common cause of death in the ICU. Oxygen utilization rather than delivery is the main problem. Normally, antioxidant defences act to protect the mitochondria against the production of reactive oxygen species (ROS). In sepsis this mechanism is overwhelmed by the increased production of ROS and nitric oxide. This results in an oxidative stress and mitochondrial damage leading to impaired ATP production. Although antioxidants have shown some promising results in the laboratory, there is still little evidence to support their regular use in humans. Question 82: TTTFF It is becoming more common for women with spinal cord injuries to go through labour. The level of lesion involved can have a significant effect upon potential complications and labour management. Lesions above T5 have a reasonable likelihood of autonomic dysreflexia being present and this can cause severe cardiovascular instability, commonly causing hypotension, headaches and bradycardia. In extreme cases cardiac arrest is possible. Labour can be a trigger for this instability and therefore a pre-emptive epidural can be used to protect against it. The instability can continue for up to 48 hours post delivery so the epidural should continue into the postdelivery period. Suxamethonium should be avoided for up to one year post injury to prevent a hyperkalaemic response to its use, although this is controversial and many clinicians would avoid suxamethonium altogether. Question 83: TTTTT Since the majority of pulmonary resection patients have a smoking history, they already have one risk factor for coronary artery disease. Surgical risk estimate is a broad approximation of 30-day risk of cardiovascular death and myocardial infarction that takes into account only the specific surgical intervention, without considering the patient’s co-morbidities. Intrathoracic, non-major surgeries are considered as intermediate-risk procedures, whereas pneumonectomy is considered a high-risk procedure. The surgical stress increases myocardial oxygen demand. Surgery also causes alterations in the balance between prothrombotic and fibrinolytic factors, potentially resulting in increased coronary thrombogenicity. CT angiography has a high sensitivity for coronary stenosis, but is less specific. Thus, a patient with a normal CT coronary angiogram can proceed to surgery. Question 84: FTTFT The parathyroid glands lie within close anatomical proximity to the thyroid gland. As such, the parathyroid glands may be accidently damaged during thyroid surgery. Transient hypocalcaemia may present 36 hours postoperatively in 20% of patients having undergone thyroidectomy for large multinodular goitre. Permanent hypocalcaemia is rare. Hypocalcaemia may present with: Trousseau’s sign – carpopedal spasm (may be caused by non-invasive blood pressure cuff inflation) Chvostek’s sign – facial twitch or spasm upon tapping over the facial nerve at the parotid gland Prolonged QT interval Treatment with calcium replacement should commence immediately. The route of calcium replacement depends upon serum calcium concentration: Serum calcium >2 mmol.l–1 – oral calcium replacement Serum calcium <2 mmol.l–1 – intravenous calcium with, e.g. 10 ml of 10% calcium gluconate. A calcium infusion may be required in severe cases Question 86: TFTTT Laparoscopic surgery reduces venous return. Insufflation can cause marked vagal stimulation resulting in bradycardia; coupled with reduced venous return in a dehydrated elective patient, this can result in marked hypotension. Insufflation should therefore be gradual with intra-abdominal pressures limited to 20 mmHg. Trochar introduction to the abdominal cavity may also result in vascular injury, resulting in rapid hypovolaemia. Anaphylaxis should be amongst the differentials – cardiovascular collapse is a common initial presenting feature of anaphylaxis under general anaesthesia. Air embolism is a risk with laparoscopic surgery, especially in the presence of venous injury. However, as CO2 is a relatively soluble gas, any gas embolism should be short-lived – which is the reason it is the gas of choice when creating a pneumoperitoneum in laparoscopic surgery. Too small a blood pressure cuff would cause falsely high blood pressure readings at the extremes of blood pressure. Question 87: TTFFF Awareness is most often associated with emergency situations or patients with a higher ASA grade due to the higher risk of haemodynamic instability. Patients with chronic alcohol and opiate use are more likely to be aware compared to those with acute intake. Patients with TIVA are not proven to have higher rates of awareness. Question 88: FFFTF – 10 N of pressure to the cricoid while the patient is awake and 30 N once consciousness has been lost – That during initial tracheal intubation (Plan A), no more than three attempts should be made at intubation – That a second dose of muscle relaxant should not be administered During anaesthesia, oxygen consumption in a healthy adult stays relatively constant at approximately 250 ml.min–1. During a RSI, haemoglobin is not important as an oxygen store, but as an oxygen transporter, therefore anaemia will only cause a small decrease in the time taken to reach critical hypoxia. However, if the FRC is reduced, anaemia will have a more significant effect on the time taken for desaturation to occur. The most commonly used irrigation fluid is glycine 1.5% in water, which is hypotonic, with an osmolality of 220 mmol.l–1. Irrigation fluid is normally absorbed at a rate of approximately 20 ml.min–1, although absorption can be much greater. The rate of absorption depends on the infusion pressure of the irrigation fluid and the venous pressure within the patient; therefore, the pressure of the irrigation must be kept to the minimum that still allows adequate flow (it should never be at a height of greater than 100 cm). TURP syndrome is the result of large amounts of irrigation fluid being absorbed through open venous sinuses, which causes fluid overload and hyponatraemia. TURP syndrome is more common in procedures lasting over an hour, when the prostate weighs more than 50 g, when the patient is hypovolaemic/hypotensive (as this creates a greater pressure gradient for absorption) and when high irrigation pressures are used. Question 90: TTFTT The patency of the ductus arteriosus (DA) depends on the high concentration of prostaglandin E2. Acidosis and low arterial pO2 are the two main stimuli for PG E2 release. In pulmonary hypertension, the blood flows from the pulmonary trunk to the aorta before reaching the lung (deoxygenated blood), leading to release of PG E2, maintaining the DA open. Question 91: TTTTF Local anaesthetic toxicity depends on the volume of the drug injected, as well as the absorption rate and the site of injection. Intercostal blocks have the highest rate of absorption after intravenous, then caudal, paracervical, epidural, brachial, sciatic and subcutaneous. Signs of LA toxicity depend on the plasma concentration of the individual agent used. For example: bupivacaine concentration of 2–4 μg.ml–1 and lignocaine level of 10–12 μg.ml–1 can initiate the CNS excitatory stage of LA toxicity. Circumoral numbness and tingling are the first signs of toxicity, followed by respiratory then cardiovascular signs and symptoms. Blood samples should be taken to diagnose the plasma levels of the drug used, yet not as a first line of action. First stop the injection, then deal with the collapsed patient in an ABC manner. The appropriate action is 100% O2, with constant CVS monitoring and supportive treatment. Candidates would be advised to familiarize themselves with the AAGBI guidelines regarding the use of intralipid. Cardiopulmonary exercise (CPET) testing requires appropriate monitoring as listed and two members of staff, one to instruct and look after the patient and the other to watch the monitoring screen and run the test. The equipment includes a static cycle and a metabolic cart containing a gas analyzer to enable breath-by-breath measurement of oxygen consumption (VO2) and carbon dioxide production (VCO2). The duration of exercise is between 6 and 10 minutes. Question 93: TFFFT The sciatic nerve is formed from the nerve roots L4 to S3. The two components of the nerve (tibial and common peroneal) diverge approximately 4 to 10 cm above the popliteal crease to separately continue their paths into the lower leg. Blocking the sciatic nerve will provide anaesthesia of the leg below the knee with the exception of the medial strip of skin, which is innervated by the saphenous nerve. The inferior or Raj approach to the sciatic nerve requires the patient to lie supine with the knee flexed to 90°. A line is drawn connecting the greater trochanter to the ischial tuberosity and needle insertion is at the halfway point in the groove between the hamstring and the adductor muscles. The sciatic nerve is usually found at a depth between 40 and 80 mm. Adrenaline is not advised because of the risk of ischaemia of the sciatic nerve. Question 94: FFFTF \|Patch\|\|Drug delivery μg.h–1\|\|Oral morphine mg per 24 h\| \|Patch\|\|Drug delivery μg.h–1\|\|Oral morphine mg per 24 h\| Chlorhexidine gluconate was developed in the UK in the 1950s. It is a cationic, bisbiguanide molecule that is used widely for skin decontamination prior to procedures. It has good activity against Gram-positive bacteria, somewhat less activity against Gram-negative bacteria and fungi, and is minimally active against mycobacteria. It is not sporicidal and because chlorhexidine is a cationic molecule, its activity can be reduced by natural soaps, various inorganic anions, non-ionic surfactants and hand creams containing anionic emulsifying agents. For skin preparation prior to central neuraxial block, a 0.5% chlorhexidine preparation is recommended. The antimicrobial activity of chlorhexidine is not seriously affected by the presence of organic material, including blood. Care must be taken to avoid contact with the eyes, as concentrations of 1% or greater can cause conjunctivitis. Chlorhexidine is also ototoxic and direct contact with brain tissue or meninges should be avoided. Question 98: TFFFF Standard ET tubes can be used to isolate one lung in an emergency, and in conjunction with either bronchial blockers (or unconventionally, Fogarty or Foley catheters), or pulmonary artery catheters in paediatrics, put down an ET tube. However, for elective surgery this is not recommended, and an appropriately sized double lumen tube should be used. The dependent (lowermost) lung is the lung that is being ventilated, so clamping its pulmonary artery will dramatically worsen hypoxia. Left-sided double lumen tubes are most commonly used so that the right upper lobe is not accidentally occluded. Malpositioned ET tubes have been implicated in 30% of deaths in oesophagectomies. The double lumen tube is rotated 90° on passing through the vocal cords. Question 99: FFFFF A low intrinsic thyroid function blunts responses to inotropes and vasopressors – however, cardiovascular responses are variably affected and cautious initiation is recommended. Thyroid imaging is not essential, measurement of thyroid function is. Patients are typically hyponatraemic due to reduced cardiac output and altered renal handling of sodium and water. Lack of thyroid hormone leads to reduced cardiac index, reduced contractility and relative bradycardia. Steroid replacement should be considered for these patients, as there is a risk of concomitant Addison’s being made worse with thyroid hormone administration or pituitary failure being the cause. Passive rewarming is recommended, but aggressive active rewarming can lead to vasodilatation and worsening hypotension. It is important to note the presence of fistulae; intravenous access and blood pressure cuffs should be sited away from any active fistulae. Patients who are dialysis dependent may be fluid restricted. This needs to be taken into account when planning perioperative fluid management. It is therefore also important to note the volume status of the patient and when they are normally dialyzed, including the date and time of their last session and when they should next be dialyzed. Elective surgery should usually be planned for the day between dialysis sessions. Patients with renal disease are at risk of developing peripheral neuropathy. This should be documented preoperatively, particularly if peripheral nerve blockade is planned, and care taken when positioning the patient to ensure no further nerve damage occurs perioperatively. Question 101: TFFFT Regional blocks in children are usually performed after general anaesthesia has been administered. Calculated maximum allowable dose is based on patient ideal body weight (IBW). Estimating the IBW has particular relevance to the high BMI child. As the structures of interest in the paediatric patient are relatively superficial, a higher-frequency probe will be more suitable. Penile block performed using the landmark approach has reported failure rates of 4–8%. Systemic absorption of local anaesthetic when performing ilioinguinal and iliohypogastric blocks is higher after ultrasound guidance when compared to a landmark approach, and careful attention needs to be paid to avoid local anaesthetic toxicity. Question 102: FTFFF The commonest cause for liver transplant is posthepatitis C cirrhosis, though acute liver failure, e.g. post paracetamol overdose, will be prioritized for transplantation. Most cases involve the transplantation of a whole adult liver from a non-living donor and removing the diseased organ (orthotopic transplant). Portions of adult livers can be used in paediatrics and split livers allow one liver to be used for two patients. In living-donor liver transplantation, a portion of a healthy liver is transplanted from the donor to the patient. Venovenous bypass can be used to allow venous return from the lower part of the body whilst the liver is being removed and the transplant implanted. Reperfusion syndrome post reperfusion of the liver graft will cause massive cytokine release and typically is accompanied by a small drop in patient temperature. The anhepatic phase and need for massive transfusion are also reasons for further intraoperative hypothermia. Typically hypocalcaemia is more common during the anhepatic phase as a result of chelation with unmetabolized citrate. Hepatic artery thrombosis is a real concern in the first few days post transplantation, but occurs in 0.5–5% of patients. Thrombectomy can be attempted, but retransplantation may be needed. Question 103: TTTTF In June 2012, a panel of experts announced a new definition and severity classification system for ARDS. It is known as the ‘Berlin Definition’ and aims to simplify the diagnosis of ARDS and clarify the ambiguity of the old definition. Acute lung injury (ALI) does not exist anymore, but rather three degrees of severity according to the paO2/FiO2 ratio. Patients with a ratio of 200–300 would now have ‘mild ARDS’ rather than ALI. The severity of hypoxaemia predicts the mortality; being measured at 45% for severe ARDS with a paO2/FiO2 <100. The old definition did not define the ‘acute onset’, which caused confusion in cases of acute on chronic hypoxaemia. Patients with heart failure can still develop ARDS and hence there is no more need to exclude a raised PCWP. However, if there is no obvious cause for ARDS, heart failure shold be excluded as a cause of bilateral lung opacities and pulmonary oedema. The need for high PEEP predicts neither mortality nor clinical outcome. Cardiac arrests in the pregnant population are increasing in frequency and have a current incidence of around 1:30 000 pregnancies. This increase is probably caused by the increasing ages and morbidities of women now going through pregnancy. Perimortem caesarean section (PMCS) is now widely considered to be the best chance for a successful resuscitation of the mother, but should aim to be performed within 5 minutes of any arrest. This is, however, difficult to achieve practically. If PMCS is performed it should be done so where the woman is being treated and ideally not involve moving her to theatre. Cardiac arrests occur for a variety of reasons and can occur ‘out of the blue’ during an otherwise apparently normal pregnancy and labour. There is no change to standard ALS protocols for the defibrillation of patients. Question 105: TFFTT Age <75 years FEV1 between 15 and 35% of predicted paCO2 <55 mmHg (7.3 kPa) Prednisone requirement <20 mg.day–1 PAPsys <50 mmHg An ideal anatomical precondition for LVRS is a lack of homogeneity of the lung structure, where normal lung tissue and severely destroyed, over-distended tissue are present in the same lung. If it is homogeneous and the FEV1 is <20% there is high morbidity and mortality. Question 106: FTFTT There are five subtypes of atlantoaxial subluxation that may result from rheumatoid disease. Anterior subluxation is the most common and can affect up to 80% of patients. It results from the C1 vertebra moving anteriorly on the C2 vertebra. The transverse ligament and apical ligaments are destroyed as a consequence, risking spinal cord compression by the odontoid peg. Anterior subluxation is made worse by neck flexion, whereas posterior subluxation (affecting less than 5% of patients) is made worse by neck extension. In posterior subluxation, destruction of the odontoid peg may cause posterior movement of the C1 vertebra on the C2 vertebra. Vertical subluxation affects between 10 and 20% of patients and results from the destruction of the lateral masses of the C1 and C2 vertebrae. The cervicomedullary junction is then compressed by subluxation of the odontoid peg through the foramen magnum. Other subtypes of atlantoaxial subluxation include lateral⁄rotatory (affecting 5–10% of patients) and subaxial (rare). Speed of induction with inhalational agents is increased with high inspired concentration, increased alveolar ventilation, small FRC, low blood–gas partition coefficient, low cardiac output and second gas effect. Second gas effect: administration of rapidly absorbed gas, such as nitrous oxide, given in high concentration together with a volatile agent of lower solubility produces an increasing alveolar concentration of the second agent thus promoting its absorption. Question 108: FFTFT All the volatile anaesthetic agents and suxamethonium are known to cause malignant hyperpyrexia (MH) in susceptible individuals. Nitrous oxide, however, does not, but should be used through a clean circuit, ideally via an anaesthetic machine reserved solely for MH patients. Ketamine and etomidate are safe to use. Patients are referred to the specialist centre in Leeds for fresh muscle biopsy that is exposed to halothane and caffeine. In susceptible patients muscle contraction occurs at lower concentrations than normal. Question 109: TFFTF A disposable four-electrode sensor is placed on the forehead. The frontal EEG signal is converted by an algorithm to a dimensionless index of the depth of anaesthesia. A reading between 0 and 100 is produced; zero represents no electrical activity, 100 being awake. The manufacturers recommend a number between 40 and 60. BIS monitors are not validated for use in paediatrics, especially in those below the age of one, despite data suggesting EEG patterns in those over five are similar to adults. Question 110: FFTFT The most commonly used irrigation fluid in the UK is 1.5% glycine solution in water. The ideal irrigation fluid for use during TURP is clear, electrically non-conductive, non-haemolytic, non-toxic, sterile, not metabolized and cheap. No fluid that fulfils all these criteria exists; other irrigation fluids include mannitol 5% and sorbitol 3.5%. Glycine is an inhibitory neurotransmitter, it is metabolized in the liver and kidneys by oxidative deamination to glyoxylic acid and ammonia. Question 111: FTTFF The ductus arteriosus normally closes spontaneously at 24 hours (90% by 60 hours). Isolated PDA should always be treated. Treatment options depend on the size of the PDA. Small PDA can be treated by indomethacin to prevent infective endocarditis. Moderate PDA could be treated by device occlusion via catheterization to prevent pulmonary vascular disease. Very large PDA is treated by ligation through left thoracotomy, to treat heart failure. Left to right shunts lead to heart failure due to sequestration, while right to left shunts lead to cyanosis due to bypassing the pulmonary circulation. Fresh frozen plasma (FFP) must be transfused to an ABO-compatible donor due to the presence of antibodies in the plasma. The usual FFP starting dose is 10–15 ml.kg–1. For children up to the age of 16 born after 1995 it is obtained from the USA to reduce the risk of transmitting variant Creutzfeldt–Jakob disease. The FFP is also treated with methylene blue to inactivate viruses within the transfusion. Question 113: FTFFF The coeliac plexus is the main junction for autonomic nerves supplying the upper abdominal organs and consists of bilateral coeliac ganglia with a network of interconnecting fibres. The greater (T5–T10), lesser (T9–T11) and least (T11–T12) splanchnic nerves provide the major contributions to the plexus with input from the vagus and phrenic nerves also. The plexus lies anterior to the aorta on either side of the body of L1 and posterior to the pancreas. Alcohol is usually preferred to phenol for coeliac plexus block due its greater ability to diffuse through tissues. Diarrhoea and hypotension are common side effects and damage to the L1 nerve root may occur. Paraplegia, either through direct trauma or spasm of the artery of Adamkiewicz, has been quoted as 1 in 683 in one large case study. Question 114: FTFFF Intraoperative sedation and general anaesthesia using a scalp block for analgesia or regional anaesthesia as the sole technique are the anaesthetic options for an awake craniotomy. The term ‘awake craniotomy’ can be misleading, since varying levels of sedation or anaesthesia may be used during the procedure. The patient is always fully awake for the process of ‘cortical mapping’, during which lesion resection takes place, in order to minimize the risk of damage to the eloquent cortex. Patient selection is vital to the success of this surgery; absolute contraindications include patient refusal, inability to lie still and lack of cooperation, e.g. acute confusion. Relative contraindications include an inability to lie flat, having a cough, anxiety, a language barrier and learning difficulties. In order to anaesthestize the scalp, six nerves need to be blocked bilaterally, these are the supratrochlear, supraorbital, zygomaticotemporal, auriculotemporal, and the lesser and greater occipital nerves. The greater auricular nerve and third occipital nerve may need to be blocked in some patients, making a total of eight on each side at most. To block the greater auricular nerve, local anaesthetic is injected approximately 2 cm posterior to the auricle at the level of the tragus. \|Nomenclature\|\|Traditional nomenclature\|\|Depth\|\|Clinical features\| \|Superficial\|\|First degree\|\|Epidermis\|\|Painful, blanchable\| \|Superficial–dermal\|\|Second degree\|\|Through epidermis to upper layers of dermis\|\|Painful, blisters, blanchable, hair follicles present\| \|Deep-dermal\|\|Second degree\|\|Into deep dermis but not entire dermis\|\|± Pain, does not blanch, some hair follicles present\| \|Full thickness\|\|Third/fourth degree\|\|Extends to subcutaneous tissue\|\|Painless, black eschar, no hair follicles\| Question 116: FFTTT The key message is to not make any assumptions about what is acceptable, and clarify exactly what each individual will accept in the way of treatment. Some Jehovah’s Witnesses will accept cell salvage, but not all. The AAGBI has produced guidance on good practice and mandates that consultant surgeons and anaesthetists should be directly involved in the care of these patients. In an emergency, anaesthetists are obligated to treat Jehovah’s Witnesses, but this is not true for elective surgery. However, they must refer Jehovah’s Witnesses to a colleague who is willing to anaesthetize them. AAGBI guidance makes provision for Jehovah’s Witnesses to change their advance directive under regional anaesthesia. Tranexamic acid may be used to decrease bleeding. Question 117: TFFFF AAGBI day-case guidelines state specific cut-offs for age and BMI are not appropriate in assessing patients for day-case surgery suitability. Asthma, obesity and epilepsy may be well suited to the principles of regional anaesthesia and short-acting techniques, as well as minimal disruption to daily routine. Oral intake should be able to resume within a few hours. Question 118: TTFTF In advanced renal disease, gastric emptying is delayed, residual volume is greater and pH lowered. This increases the risk of aspiration and a rapid sequence induction may be considered where a history of reflux is elucidated. Platelet count is usually normal, however platelet function may be impaired with decreased adhesiveness and aggregation. Standard tests of coagulation are often normal, however bleeding time may be prolonged. Atracurium is often considered to be the muscle relaxant of choice in patients with severe renal disease owing to its termination of action by Hoffman degradation. However its duration of action may still be altered in renal disease owing to the alteration in ion concentrations such as magnesium, which can prolong the duration of block. So it is recommended, as for all patients, that neuromuscular monitoring is utilized to ensure adequate reversal prior to emergence and extubation. Patients with renal dysfunction are likely to be relatively fluid overloaded and hypoalbuminaemic. Hypoproteinaemic states result in an increased fraction of free drug within the plasma and thus a higher concentration of free drug with heavily protein-bound drugs. Hyperkalaemia is a common electrolyte abnormality seen in renal dysfunction. The evidence for a reduction in thromboembolic complications comes mainly from the orthopaedic literature. Studies in abdominal surgery have shown only a non-significant trend towards reduction of thromboembolic complications. Epidural anaesthetic blocks afferent nociceptive input and reduces pain and sensitization. This reduces the incidence of chronic postsurgical pain. The reduced stress response occurring with a regional technique results in less postoperative immunocompromise with consequent reduced potential for the spread of micrometastases at the time of surgery. When epidural analgesia is used intraoperatively in abdominal surgeries, it reduces the depth of anaesthesia required and hence would have a beneficial effect in reducing postoperative cognitive dysfunction. The debate on whether intrathecal blocks are safer when performed on awake or anaesthetized patients in unresolved. Available evidence is low-level and conflicting. Question 120: FTFFF Cardioplegia can be either blood- or crystalloid-based and typically has 20 mmol.l–1 potassium, 16 mmol.l–1 magnesium and procaine. Rapid infusion of approximately 1 l renders the heart asystolic. Cold cardioplegia at 4 °C provides further myocardial protection again ischaemia. Cardioplegia is instilled into the ascending aorta (as long as the aortic valve is competent) with a cross clamp on the aorta distal to the cardioplegia cannula, and runs into the coronaries. If the aortic valve is incompetent, the cardioplegia can be instilled directly into the coronaries or can be retrograde instilled via the coronary sinus. The aim is for the cold, hyperkalaemic solution to cause depolarization and arrest in diastole, which is a relaxed state and, therefore, at a cellular level, metabolically less active. On cardiopulmonary bypass, the blood is typically pumped through roller pumps which provide non-pulsatile flow. Pulsatile flow may be more physiological, but is more expensive to produce and has shown little benefit (ECMO circuits typically use centrifugal pumps). As blood comes in contact with a large prothrombotic surface in the bypass circuit, it is essential that the patient is fully heparinized, aiming for an ACT >400 s, prior to going on to cardiopulmonary bypass. Question 121: FTTFT Enteral feeding is more physiological and hence should be considered before parenteral feeding. Whilst it is almost impossible to overfeed using the enteral route, overfeeding is more common with the parenteral route. Enteral feed protects the gut against bacterial translocation and hence may reduce the risk of hospital-acquired infection. Postpyloric feeding should only be considered if gastric absorption is problematic. Although early feeding is advocated for its benefits, it is certainly better to underfeed than overfeed. It is not advisable to attempt to match the calculated caloric requirement. Aiming for a high caloric intake during the acute phase of critical illness may be associated with a less favourable outcome. Diabetes is increasing in incidence in the general population and there is also a corresponding increase in gestational diabetes. Risk factors for gestational diabetes include BMI over 30 (therefore routinely screened for), first-degree relative with diabetes or certain ethnic subgroups (South Asian, Black Caribbean). With pre-existing diabetes, management should ideally commence preconception to ensure the risks of pregnancy-associated diabetes are reduced. Risks include increases in miscarriage, pre-eclampsia, stillbirth and birth trauma. Whilst the manufacturers of oral hypoglycaemic agents suggest avoiding their use in pregnancy for safety purposes, NICE guidelines recommend they are used and believe them to have an appropriate safety record (Clinical Guideline 63). During labour, blood glucose should be maintained between 4 and 7 mmol.l–1. Where this is not possible or if the patient is a Type I diabetic, insulin and dextrose should be used. Whilst there is an increase in larger babies and an associated risk of birth trauma and obstetric interventions being required, epidurals are not specifically recommended to women with diabetes. Question 123: FFTFF Hypoxic pulmonary vasoconstriction (HPV) is a reflex contraction of vascular smooth muscle in the pulmonary circulation in response to low regional partial pressure of oxygen (paO2). Animal studies show that at low doses almitrine enhances HPV by a vasoconstrictor effect specific to pulmonary arteries. Iron attenuates HPV and also greatly reduces the enhanced response normally seen after prolonged hypoxic exposure. The common intravenous anesthetic agents show no inhibition of HPV. Question 124: TFFFF An advance directive made in the presence of a witness is a legally binding document. The patient must be over 18 years of age and have capacity at the time of writing. Patients are encouraged to carry a copy of their advance directive, as well as keeping copies with their general practitioner, family and friends. The directive must specify the decision applied to a specific treatment if the individual’s life is at risk and if any of these conditions are not met, the directive may be invalid. A doctor who knowingly breaches the terms of the directive may face criminal charges and referral to the General Medical Council. In an emergency where the patient cannot express their own wishes, an advance directive should be obtained as soon as possible. However, where such a directive cannot be obtained, life-saving treatment should not be withheld. The views of family and friends may be sought where possible, but no individual can refuse treatment on behalf of a patient. Involvement of the hospital legal team and Jehovah’s Witness liaison, and documentation of all discussions and decisions are paramount in such situations. Cleft lip and palate (CLP) is one of the commonest congenital deformities. Two-thirds involve the lip with or without the palate and the remainder the palate alone. Cleft lip is unilateral in 80% of cases and occurs on the left in over 70% of cases. CLP is more common in males. Chronic rhinorrhoea is common due to food reflux into the nasal passages and may present with recurrent URTI. Snoring, apnoea during feeds or protacted feeding time may indicate chronic airway obstruction. Difficult mask ventilation is unusual. Difficult laryngoscopy and intubation are strongly associated with retrognathia and bilateral cleft lip, due to protruding maxilla. Nasopharyngeal airways are effective and well tolerated and should be inserted in patients with high risk of postoperative airway complications before emergence. Avoid an oropharyngeal airway due to risk of disrupting the surgical repair. Question 126: TTFFT Suxamethonium apnoea occurs due to abnormal levels of functional plasma cholinesterase, coded for on chromosome 3. Plasma cholinesterase may be present, but not functional. In E1f:E1f there is reduced or no activity of plasma cholinesterase. In 1957 Kalow and Genest described mixing plasma with benzoylcholine and measuring the light emitted. They established that normal plasma and benzoylcholine emitted light at a specific wavelength. Dibucaine inhibits this reaction, and the percentage inhibition by a set amount of dibucaine compared to a reference value is known as the dibucaine number. Normal is 80 and reduced values reflect lack of functional plasma cholinesterase in plasma samples. Low dibucaine number is therefore a reflection of plasma cholinesterase abnormality. The risks of transfusing blood products outweigh the benefits. Given time, the neuromuscular block will reverse. Fresh frozen plasma should only be given in emergency situations following consultation with a consultant haematologist. Methotrexate is a cause of acquired plasma cholinesterase deficiency. Question 127: FTFTT 1. Preoperative (up to an hour prior to arriving in theatre suite) 3. Postoperative (up to 24 hours after entry to recovery area) Core temperature should be measured preoperatively and warming devices should be employed if temperature falls below 36 °C. NICE guidelines on perioperative hypothermia suggest groups at high risk of inadvertent hypothermia include patients with: ASA grade ≥II Preoperative temperature <36 °C Combined general and regional anaesthesia Undergoing major or intermediate surgery At risk of cardiovascular complications The trachea divides into the left and right main bronchi at the level of approximately T5. The right main bronchus is wider, shorter (approximately 2.5 cm) and more vertically angled when compared with the left. The right main bronchus gives off the right upper lobe bronchus (which divides into the apical, anterior and posterior segments), the right middle lobe bronchus (which divides into the lateral and medial lobes), and the bronchus of the apical segment of the lower lobe (which divides into superior, anterior basal and lateral basal). The lower lobe bronchus continues downwards giving off the medial, anterior, lateral and posterior basal segments. The left main bronchus is longer (approximately 5 cm), narrower and more obliquely angled than the right. The left main bronchus gives off the left upper lobe bronchus, this divides into the superior division (which divides into the apical, posterior and anterior segments) and the lingular bronchus (divides into superior lingular and inferior lingular segments). The left lower lobe bronchus gives off the apical, anterior basal, medial basal (although can arise with the anterior basal), lateral basal and posterior basal. Question 129: FTFFT This neonate’s most likely diagnosis is tetralogy of Fallot. This is due to the presence of cyanosis (secondary to an over-riding aorta), a murmur over the pulmonary area (suggesting a right ventricular outflow tract obstruction) and evidence of right ventricular hypertrophy on the ECG. The degree of the right ventricular outflow obstruction (RVOT) will dictate the speed of onset of his cyanosis. Within 72 hours 90% of all PDAs will close, leading to significant cyanosis in cases of severe RVOT obstruction. Treatment should aim to improve pulmonary blood flow. This could be achieved medically by prostaglandin infusion until a more definitive shunt is established surgically. In the modified Blalock–Taussig operation, an anastomosis is established between the subclavian and the ipsilateral pulmonary artery. Question 130: TFTTF Wrong site surgery Retained foreign object post procedure Mis-selection of a strong potassium-containing solution Wrong route administration of medication Overdose of insulin due to abbreviations or incorrect device Overdose of methotrexate for non-cancer treatment Mis-selection of high-strength midazolam during conscious sedation Falls from poorly restricted windows Chest or neck entrapment in bedrails Transfusion or transplantation of ABO-incompatible blood components or organs Misplaced naso- or orogastric tubes Scalding of patients Wrong site surgery includes a surgical intervention performed on the wrong patient or the wrong site. It includes wrong level spinal surgery and wrong site block unless being undertaken as a pain control procedure. Retention of a foreign body post procedure does not include items inserted before the procedure that are not subject to the formal counting/checking process, such as a throat pack inserted in the anaesthetic room. Misplacement of naso- or orogastric tube itself is not a never event; however, failing to recognize misplacement and administering feed down a misplaced tube is.	2	43	0	0	1	0.824053	1	24,125
\|MP 7.01.25\|\|Spinal Cord Stimulation\| \|Original Policy Date \|Last Review Status/Date Reviewed with literature search/1:2013 \|Return to Medical Policy Index\| Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract. Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage. Medical technology is constantly changing, and we reserve the right to review and update our policies periodically. Spinal cord stimulation (SCS) delivers low voltage electrical stimulation to the dorsal columns of the spinal cord to block the sensation of pain. Spinal cord stimulation devices have a radiofrequency receiver that is surgically implanted and a power source (battery) that is either implanted or worn externally. Spinal cord stimulation (SCS) devices consist of several components: 1) the lead that delivers the electrical stimulation to the spinal cord; 2) an extension wire that conducts the electrical stimulation from the power source to the lead; and 3) a power source that generates the electrical stimulation. The lead may incorporate from 4 to 8 electrodes, with 8 electrodes more commonly used for complex pain patterns, such as bilateral pain or pain extending from the limbs to the trunk. There are two basic types of power source. In one type, the power source (battery) can be surgically implanted. In the other, a radiofrequency receiver is implanted, and the power source is worn externally with an antenna over the receiver. Totally implantable systems are most commonly used. Spinal cord stimulation has been used in a wide variety of chronic refractory pain conditions, including pain associated with cancer, failed back pain syndromes, arachnoiditis, and complex regional pain syndrome (CRPS) (i.e., chronic reflex sympathetic dystrophy). There has also been interest in spinal cord stimulation as a treatment of critical limb ischemia, primarily in patients who are poor candidates for revascularization and in patients with refractory chest pain. The neurophysiology of pain relief after spinal cord stimulation is uncertain but may be related to either activation of an inhibitory system or blockage of facilitative circuits. The patient’s pain distribution pattern dictates at what level in the spinal cord the stimulation lead is placed. The pain pattern may influence the type of device used; for example, a lead with 8 electrodes may be selected for those with complex pain patterns or bilateral pain. Implantation of the spinal cord stimulator is typically a 2-step process. Initially, the electrode is temporarily implanted in the epidural space, allowing a trial period of stimulation. Once treatment effectiveness is confirmed (defined as at least 50% reduction in pain), the electrodes and radio-receiver/transducer are permanently implanted. Successful spinal cord stimulation may require extensive programming of the neurostimulators to identify the optimal electrode combinations and stimulation channels. Computer-controlled programs are often used to assist the physician in studying the millions of programming options when complex systems are used. A number of total implanted spinal cord stimulators have received U.S. Food and Drug Administration (FDA) premarket approval (PMA). The Cordis programmable neurostimulator from Cordis, Corp. was approved in 1981, and the Itrel(R) manufactured by Medtronic was approved in 1984. In April 2004, Advanced Bionics received PMA for its Precision Spinal Cord Stimulator as an aid in management of chronic, intractable trunk and limb pain. All are fully implanted devices. Spinal cord stimulation may be considered medically necessary for the treatment of severe and chronic pain of the trunk or limbs that is refractory to all other pain therapies, when performed according to policy guidelines. Spinal cord stimulation is considered investigational as a treatment of critical limb ischemia as a technique to forestall amputation and as a treatment for refractory angina pectoris. Patient selection focuses on determining whether or not the patient is refractory to other types of treatment. The following considerations may apply. - The treatment is used only as a last resort; other treatment modalities (pharmacological, surgical, psychological, or physical, if applicable) have been tried and failed or are judged to be unsuitable or contraindicated; - Pain is neuropathic in nature; i.e., resulting from actual damage to the peripheral nerves. Common indications include, but are not limited to failed back syndrome, complex regional pain syndrome (i.e., reflex sympathetic dystrophy), arachnoiditis, radiculopathies, phantom limb/stump pain, peripheral neuropathy. Spinal cord stimulation is generally not effective in treating nociceptive pain (resulting from irritation, not damage to the nerves) and central deafferentation pain (related to CNS damage from a stroke or spinal cord injury). - No serious untreated drug habituation exists; - Demonstration of at least 50% pain relief with a temporarily implanted electrode precedes permanent implantation; - All the facilities, equipment, and professional and support personnel required for the proper diagnosis, treatment, and follow-up of the patient are available. BlueCard/National Account Issues Patients with chronic refractory pain may be managed through case management programs. State or federal mandates (e.g., FEP) may dictate that all devices approved by the U.S. Food and Drug Administration (FDA) may not be considered investigational. Therefore, FDA-approved devices may be assessed on the basis of their medical necessity. This policy was originally created in 1996 and was updated regularly with searches of the MEDLINE database. The most recent literature search was performed for the period December 2009 through November 2011. Following is a summary of the key literature to date: Chronic trunk or limb pain In 2009, a systematic review of randomized controlled trials (RCTs) and observational studies of spinal cord stimulation (SCS) in post-lumbar surgery syndrome was undertaken by Frey et al. (1) Primary outcome measures were short term (< 1 year) and long-term (> 1 year) pain relief, and secondary measures were improvement in functional status, psychological status, return to work, and reduction in opioid intake. The authors caution that the paucity and heterogeneity of the literature are limitations of the review. Using U.S Preventive Services Task Force quality ratings, the authors found Level II-1 evidence (from well-designed controlled trials without randomization) or II-2 evidence (from well-designed cohort or case-control analytic studies, preferably from more than one center or research group) for clinical use of the treatment on a long term-basis. Also in 2009, Simpson and colleagues performed a systematic review of the literature to obtain clinical and cost-effectiveness data for SCS in adults with chronic neuropathic or ischemic pain with inadequate response to medical or surgical treatment other than SCS. (2) Trials for failed back surgery syndrome and complex regional pain syndrome type I suggested that SCS was more effective than conventional medical management (CMM) or reoperation in reducing pain. The authors concluded “evidence from CLI [critical limb ischaemia] trials suggests that SCS was more effective than CMM in reducing the use of analgesics up to 6 months, but not at 18 months. Although there was significant pain relief achieved, there was no significant difference between groups in terms of pain relief, for SCS versus CMM or analgesics treatment. SCS had similar limb survival rates to CMM, or analgesics treatment, or prostaglandin E1. SCS and CMM were similarly effective in improving HRQoL (health-related quality of life).” Representative RCTs on spinal cord stimulation for treating pain are described below: A multicenter randomized trial by Kumar and colleagues (the PROCESS study) compared SCS (plus conventional medical management) with medical management alone in 100 patients with failed back surgery syndrome. (3) Leg pain relief (> 50%) at 6 months was observed in 24 (48%) SCS-treated patients and in 4 (9%) controls, with an average leg pain visual analogue scale (VAS) score of 40 in the SCS group and 67 in the conventional management control group. Between 6 and 12 months, 5 (10%) patients in the SCS group and 32 (73%) patients in the control group crossed over to the other condition. Of the 84 patients who were implanted with a stimulator over the 12 months of the study, 27 (32%) experienced device-related complications. In 2008, Kemler and colleagues reported 5-year outcomes from a randomized trial of 54 patients with complex regional pain syndrome (CRPS) (4) Twenty-four of the 36 patients assigned to SCS and physical therapy were implanted with a permanent stimulator after successful test stimulation; 18 patients were assigned to physical therapy alone. Five-year follow-up showed a 2.5-cm change in VAS pain score in the SCS group (n =20) and a 1.0-cm change for the control group (n =13). Pain relief at 5 years was not significantly different between the groups; 19 (95%) patients reported that for the same result they would undergo the treatment again. Ten (42%) patients underwent reoperation due to complications. Conclusions: The evidence on SCS for treatment of chronic limb or trunk pain consists of a number of small RCTs that include patients with refractory pain due to conditions such as failed back surgery and complex regional pain syndrome. These studies are heterogenous in terms of patient populations and outcomes, but generally report an improvement in pain and a reduction in requirement for medications. Because these patients have few other options, this evidence suggests that SCS is a reasonable treatment option. Critical limb ischemia Critical limb ischemia is described as pain at rest or the presence of ischemic limb lesions. If the patient is not a suitable candidate for limb revascularization (typically due to insufficient distal runoff), it is estimated that amputation will be required in 60–80% of these patients within 1 year. SCS has been investigated in this small subset of patients as a technique to relieve pain and decrease the incidence of amputation. A systematic review from the Cochrane group on the use of spinal cord stimulation in peripheral vascular diseases was updated in 2005. Included were 6 European studies of generally good quality with a total of 444 patients. (5) None of the studies were blinded. At 12 months’ follow-up, limb salvage improved by 11% compared with any form of conservative treatment with a number needed to treat (NNT) of 9. The SCS patients required significantly less analgesics, and more patients reached Fontaine stage II than in the conservative group. There was no difference in ulcer healing. The overall risk of complications or additional SCS treatment was 17%, with a number needed to harm (NNH) of 6. The report concludes that there is evidence to favor SCS over standard conservative treatment to improve salvage and clinical situation in patients with critical leg ischemia but that “the benefits of SCS against the possible harm of relatively mild complications and costs must be considered.” Analysis of data and cost calculations from a randomized trial with 120 patients previously published in 1999 by Klomp and colleagues (6) showed that the difference in amputation rate at 12 months when SCS was provided in addition to best medical care was no longer present at 24 months, and there was no difference in survival rate at 24 months. (7) In 2009, Klomp and colleagues published a meta-analysis of 5 randomized trials on spinal cord stimulation for prevention of amputations in patients with critical limb ischemia. (8) They found insufficient evidence that SCS is more efficacious than best medical treatment alone. They also conducted additional analyses of data from their 1999 RCT to identify factors associated with a better or worse prognosis. They found that patients with ischemic skin lesions had a higher risk of amputation compared to patients with other risk factors. There were no significant interactions between this or any other prognostic factor. The analyses did not identify any subgroup of patients who might benefit from SCS. Conclusions: A number of small RCTs of SCS versus usual care have been completed on patients with critical limb ischemia. These studies report that SCS reduces pain, but the impact on limb amputations is less certain. Some studies have shown a small improvement in amputation rates, but others have not. This evidence is not sufficient to determine whether SCS improves outcomes for patients with critical limb ischemia. Refractory angina pectoris Spinal cord stimulation has been used for treatment of refractory angina in Europe for 20 years, and much of the literature on SCS comes from European centers. Several systematic reviews have recently been published. In 2009, Taylor et al. included seven RCTs in a systematic review of SCS in the treatment of refractory angina. (9) The authors noted that trials were small and varied considerably in quality. They concluded that “compared to a ‘no stimulation’ control, there was some evidence of improvement in all outcomes following SCS implantation with significant gains observed in pooled exercise capacity and health related quality of life”; however, “further high quality RCT and cost effectiveness evidence is needed before SCS can be accepted as a routine treatment for refractory angina.” In 2008, a systematic review of the literature based on the Swedish Council on Technology Assessment in Health Care report on spinal cord stimulation in severe angina pectoris was published. (10) Seven controlled studies (5 of them randomized), 2 follow-up reports, and a preliminary report, as well as 2 non-randomized studies determined to be of medium-to-high quality were included in the review. The largest RCT included 104 subjects and compared SCS and coronary artery bypass graft (CABG) in patients accepted for CABG and who were considered to have only symptomatic indication (i.e., no prognostic benefit) for CABG, according to the American College of Cardiology/American Heart Association guidelines, to run an increased risk of surgical complications, and to be unsuitable for percutaneous transluminal coronary angioplasty. Between-group differences on nitrate consumption, anginal attack frequency, and self-estimated treatment effect were not statistically significant at the 6-month follow-up. (11) At the 5-year follow-up, significantly fewer patients in the CABG group were taking long-acting nitrates, and between-group differences on quality of life and mortality were not significant. (12) Other studies included in the Swedish systematic review include one by McNab et al., which compared SCS and PMR in a study with 68 subjects. (Note: PMR is currently considered investigational through Medical Policy Reference Manual review.) Thirty subjects in each group completed a 12-month follow-up, and differences on mean total exercise time and mean time to angina were not significant. Eleven in the SCS group and 10 in the PMR group had no angina during exercise. (13) The remaining RCTs included in the systematic review included 25 or fewer subjects. Several RCTs were published after the systematic review but had limitations, such as small sample size and short follow-up. In 2012, Zipes and colleagues published an industry-sponsored, single-blind, multicenter trial with sites in the United States and Canada. (14) This study, however, was terminated early. The Data and Safety Monitoring Board recommended that the study be terminated for futility after the interim analysis. A total of 118 patients with severe angina despite maximal medical treatment were enrolled in the study. Of these, 71 patients (60%) underwent SCS implantation with the Intrel III neurostimulator (Medtronic). The remaining 47 patients were found not to meet eligibility criteria post-enrollment or there were other issues e.g., withdrawal of consent. The investigators had originally been planning to randomize up to 310 patients, but enrollment was slow. Implantation was successful in 68 patients; this group was randomized to high-stimulation (n=32) or a low-stimulation control (n=36). The low-stimulation control was designed so that patients would feel paresthesia, but the effect of stimulation would be sub-therapeutic. The primary outcome was a composite variable of major adverse cardiac events (MACE), which included death from any cause, acute myocardial infarction (MI), or revascularization through 6 months. Fifty-eight of 68 patients (85%) contributed data to the 6-month analysis; analysis was by intention-to-treat. The proportion of patients experiencing MACE at 6 months did not differ significantly between groups (12.6% in the high-stimulation group and 14.6% in the low-stimulation group; p=0.81). The sample size of this study was small, and it may have been underpowered for clinically meaningful differences. A small 2011 RCT from Italy randomly assigned 25 patients to 1 of 3 treatment groups: SCS with standard levels of stimulation (n=10), SCS with low-level stimulation (75% to 80% of the sensory threshold) (n=7), or very low-intensity SCS (n=8). (15) Thus, patients in groups 2 and 3 were unable to feel sensation during stimulation. After a protocol adjustment at 1 month, patients in the very low-intensity group were re-randomized to one of the other groups after which there were 13 patients in the standard stimulation group and 12 patients in the low-level stimulation group. At the 3-month follow-up (2 months after re-randomization), there were statistically significant between-group differences in 1 of 12 outcome variables. There were a median of 22 angina episodes in the standard stimulation group and 10 in the low-level stimulation group (p=0.002). Non-significant variables included use of nitroglycerin, quality of life (VAS), Canadian Cardiovascular Society angina class, exercise-induced angina, and 5 sub-scales of the Seattle angina questionnaire. Conclusions: Numerous small RCTs have evaluated SCS as a treatment for refractory angina. While some studies have reported benefit, the majority have not. In two of the larger, more recent RCTs that enrolled more than 100 patients, there was no benefit on the primary outcomes. Overall, this evidence is mixed and not sufficient to allow conclusions on whether health outcomes are improved. Potential adverse effects Whereas RCTs are useful for evaluating efficacy, observational studies can provide data on the likelihood of potential complications. In 2010, Mekhail and colleagues published a retrospective review of 707 patients treated with SCS between 2000 and 2005. (16) The patients’ diagnoses included CRPS (n=345, 49%), failed back surgery syndrome (n=235, 33%), peripheral vascular disease (n=20, 3%), visceral pain in the chest, abdomen, or pelvis (n=37, 5%), and peripheral neuropathy (n=70, 10%). There was a mean follow-up of 3 years (range 3 months to 7 years). A total of 527 of the 707 (36%) eventually underwent permanent implantation of an SCS device. Hardware-related complications included lead migration in 119 of 527 (23%) cases, lead connection failure in 50 (9.5%) cases, and lead break in 33 (6%) cases. Revisions or replacements were done to correct the hardware problems. The authors noted that rates of hardware failure have decreased in recent years due to advances in SCS technology. Documented infection occurred in 32 of 527 (6%) patients with implants; there were 22 cases of deep infection, and 18 patients had documented abscesses. There was not a significant difference in the infection rate by diagnosis. All cases of infection were managed by device removal. In 2012, Lanza and colleagues reviewed observational studies on SCS in patients with refractory angina pectoris. (17) The authors identified 16 studies with a total of 1,204 patients (although they noted that patients may have been included in more than one report). The most frequently reported complications were lead issues i.e., electrode dislodgement or fracture requiring repositioning, or internal programmable generator (IPG) failure during substitution. Lead issues were reported by 10 studies with a total of 450 patients. In these studies, 55 cases of lead or IPG failure were reported. No fatalities related to SCS treatment were reported. Ongoing Clinical Trials Effect of Spinal Cord Stimulation in Painful Diabetic Polyneuropathy (NCT01162993) (18): This RCT compared SCS treatment to usual care (optimal medication treatment) in patients with painful diabetic polyneuropathy in the lower limbs. Eligibility includes pain for more than 12 months and previous unsuccessful medication treatment. The primary outcome is pain intensity, and secondary endpoints include quality of life and blood glucose control. The study is sponsored by Maastricht University in the Netherlands. The expected study completion date is December 2012. Spinal Cord Stimulation For Heart Failure (NCT01362725) (19): This is an observational study that will include approximately 20 patients with heart failure. Patients will be followed for 6 months. Primary outcomes include intra- and post-procedure adverse events, exercise capacity and functional ability, left ventricular structure and function, inflammatory condition, and quality-of-life. In patients with refractory trunk or limb pain, the available evidence is mixed and limited by heterogeneity. Systematic reviews have found support for the use of spinal cord stimulation to treat refractory trunk or limb pain, and patients who have failed all other treatment modalities have very limited options. Therefore, spinal cord stimulation for chronic refractory pain of the trunk or limbs may be considered medically necessary when criteria are met. For patients with critical limb ischemia, the available evidence supports a decrease in pain with a short-term decrease in limb amputations following treatment with SCS. Complications include the need for operative repositioning procedures. There is a lack of evidence for improvement in pain and limb salvage at longer endpoints, which is a crucial factor when considering a permanently implanted device. Thus, spinal cord stimulation for critical limb ischemia to reduce limb amputation is considered investigational. For patients with refractory angina pectoris, the available evidence consists of case series and small controlled trials with methodologic limitations and limited follow-up and is not sufficient to conclude that SCS improves health outcomes. Thus, spinal cord stimulation for patients with refractory angina pectoris is considered investigational. Practice Guidelines and Position Statements In 2012, the Special Interest Group of the Canadian Pain Society published a guideline on interventions for neuropathic pain. (20) The guideline stated that clinicians should consider offering a trial of SCS to patients with failed back syndrome and complex regional pain syndrome who are not surgical candidates and who have failed conservative evidence-based treatments. (Recommendation based on good evidence with moderate certainty, Grade B strength of recommendation). The guideline also stated that clinicians should consider offering a trial of SCS to patients with traumatic neuropathy and brachial plexopathy who are not surgical candidates and have failed conservative evidence-based treatments. (Recommendation based on fair evidence with moderate certainty, Grade C strength of recommendation). In 2009, the American Society of Interventional Pain Physicians updated their evidence-based guidelines for interventional techniques in the management of chronic spinal pain. (21) The guideline states that, based on Guyatt et al.’s (2006) criteria, the recommendation for spinal cord stimulation is “1B or 1C/strong recommendation for clinical use on a long-term basis” (1B is defined as ‘strong recommendation, moderate quality evidence’ and 1C as ‘strong recommendation, low-quality or very low-quality evidence’). In October 2008, the National Institute for Health and Clinical Excellence (NICE) issued a guideline on spinal cord stimulation for chronic pain of neuropathic or ischemic origin. (22) The guideline stated that SCS is recommended as a treatment option for adults with chronic pain of neuropathic origin who continue to experience chronic pain (measuring at least 50 mm on a 0–100 mm VAS) for at least 6 months despite appropriate conventional medical management, and who have had a successful trial of stimulation as part of an assessment by a specialist team. An evidence-based guideline from the American Society of Interventional Pain Physicians found the evidence for SCS in failed back surgery syndrome and complex regional pain syndrome strong for short-term relief and moderate for long-term relief. (23) Reported complications with SCS ranged from infection, hematoma, nerve damage, lack of appropriate paresthesia coverage, paralysis, nerve injury, and death. Medicare National Coverage According to Medicare policy, the implantation of central nervous system stimulators may be covered as therapies for the relief of chronic intractable pain, subject to the following conditions: - The implantation of the stimulator is used only as a late resort (if not a last resort) for patients with chronic intractable pain; - With respect to item a, other treatment modalities (pharmacological, surgical, physical, or psychological therapies) have been tried and did not prove satisfactory, or are judged to be unsuitable or contraindicated for the given patient; - Patients have undergone careful screening, evaluation, and diagnosis by a multidisciplinary team prior to implantation. (Such screening must include psychological, as well as physical evaluation.); - All the facilities, equipment, and professional and support personnel required for the proper diagnosis, treatment training, and follow-up of the patient (including that required to satisfy item c) must be available; and - Demonstration of pain relief with a temporarily implanted electrode precedes permanent implantation. (24) Frey ME, Manchikanti L, Benyamin RM et al. Spinal cord stimulation for patients with failed back surgery syndrome: a systematic review. Pain Physician 2009; 12(2):379-97. Simpson EL, Duenas A, Holmes MW et al. Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin: systematic review and economic evaluation. Health Technol Assess 2009; 13(17):iii, ix-x, 1-154. Kumar K, Taylor RS, Jacques L et al. Spinal cord stimulation versus conventional medical management for neuropathic pain: a multicentre randomised controlled trial in patients with failed back surgery syndrome. Pain 2007; 132(1-2):179-88. Kemler MA, de Vet HC, Barendse GA et al. Effect of spinal cord stimulation for chronic complex regional pain syndrome Type I: five-year final follow-up of patients in a randomized controlled trial. J Neurosurg 2008; 108(2):292-8. Ubbink DT, Vermeulen H. Spinal cord stimulation for non-reconstructable chronic critical leg ischaemia. Cochrane Database Syst Rev 2005; (3):CD004001. Klomp HM, Spincemaille GH, Steyerberg EW et al. Spinal-cord stimulation in critical limb ischaemia: a randomised trial. ESES Study Group. Lancet 1999; 353(9158):1040-4. Klomp HM, Steyerberg EW, van Urk H et al. Spinal cord stimulation is not cost-effective for non-surgical management of critical limb ischaemia. Eur J Vasc Endovasc Surg 2006; 31(5):500-8. Klomp HM, Steyerberg EW, Habbema JD et al. What is the evidence on efficacy of spinal cord stimulation in (subgroups of) patients with critical limb ischemia? Ann Vasc Surg 2009; 23(3):355-63. Taylor RS, De Vries J, Buchser E et al. Spinal cord stimulation in the treatment of refractory angina: systematic review and meta-analysis of randomised controlled trials. BMC Cardiovasc Disord 2009; 9:13. Borjesson M, Andrell P, Lundberg D et al. Spinal cord stimulation in severe angina pectoris--a systematic review based on the Swedish Council on Technology assessment in health care report on long-standing pain. Pain 2008; 140(3):501-8. Mannheimer C, Eliasson T, Augustinsson LE et al. Electrical stimulation versus coronary artery bypass surgery in severe angina pectoris: the ESBY study. Circulation 1998; 97(12):1157-63. Ekre O, Eliasson T, Norrsell H et al. Long-term effects of spinal cord stimulation and coronary artery bypass grafting on quality of life and survival in the ESBY study. Eur Heart J 2002; 23(24):1938-45. McNab D, Khan SN, Sharples LD et al. An open label, single-centre, randomized trial of spinal cord stimulation vs. percutaneous myocardial laser revascularization in patients with refractory angina pectoris: the SPiRiT trial. Eur Heart J 2006; 27(9):1048-53. Zipes DP, Svorkdal N, Berman D et al. Spinal cord stimulation therapy for patients with refractory angina who are not candidates for revascularization. Neuromodulation 2012; 15(6):550-9. Lanza GA, Grimaldi R, Greco S et al. Spinal cord stimulation for the treatment of refractory angina pectoris: a multicenter randomized single-blind study (the SCS-ITA trial). Pain 2011; 152(1):45-52. Mekhail NA, Mathews M, Nageeb F et al. Retrospective review of 707 cases of spinal cord stimulation: indications and complications. Pain Pract 2011; 11(2):148-53. Lanza GA, Barone L, Di Monaco A. Effect of spinal cord stimulation in patients with refractory angina: evidence from observational studies. Neuromodulation 2012; 15(6):542-9. Sponsored by Maastricht University. Effect of Spinal Cord Stimulation in Painful Diabetic Polyneuropathy (NCT01162993). Available online at: www.clinicaltrials.gov. Last accessed November, 2012. Sponsored by St. Jude Medical. Spinal Cord Stimulation For Heart Failure (NCT01362725). Available online at: www.clinicaltrials.gov. Last accessed November, 2012. Mailis A, Taenzer P. Evidence-based guideline for neuropathic pain interventional treatments: spinal cord stimulation, intravenous infusions, epidural injections and nerve blocks. Pain Res Manag 2012; 17(3):150-8. American Society of Interventional Pain Physicians. Comprehensive evidence-based guidelines for interventional techniques in the management of chronic spinal pain. Available online at: www.guideline.gov. Last accessed November, 2012. National Institute for Health and Clinical Excellence (NICE). Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin. NICE Technology Appraisal Guidance 159. October 2008. . Available online at: http://guidance.nice.org.uk/TA159. Last accessed November, 2012. Boswell MV, Trescot AM, Datta S et al. Interventional techniques: evidence-based practice guidelines in the management of chronic spinal pain. Pain Physician 2007; 10(1):7-111. Centers for Medicare and Medicaid Services (CMS). National Coverage Determination for Electrical Nerve Stimulators (160.7). Available online at: http://www.cms.hhs.gov. Last accessed November, 2011. \|CPT\|\|63650\|\|Percutaneous implantation of neurostimulator electrode array; epidural\| \|63655\|\|Laminectomy for implantation of neurostimulator electrode plate/paddle; epidural\| \|63661\|\|Removal of spinal neurostimulator electrode percutaneous array(s), including fluoroscopy, when performed (new code 1/1/10)\| \|63662\|\|Removal of spinal neurostimulator electrode plate/paddle(s) placed via laminotomy or laminectomy (new code 1/1/10)\| \|63663\|\|Revision including replacement, when performed, of spinal neurostimulator electrode percutaneous array(s), including fluoroscopy, when performed (new code 1/1/10)\| \|63664\|\|Revision including replacement, when performed, of spinal neurostimulator electrode plate/paddle(s) placed via laminotomy or laminectomy, including fluoroscopy, when performed (new code 1/1/10)\| \|63685\|\|Insertion or replacement of spinal neurostimulator pulse generator or receiver, direct or inductive coupling\| \|63688\|\|Revision or removal of implanted spinal neurostimulator pulse generator or receiver\| \|95970, 95971, 95972, 95973\|\|Neurostimulator programming and analysis code range\| \|ICD-9 Procedure\|\|03.93\|\|Insertion or replacement of spinal neurostimulator\| \|03.94\|\|Removal of spinal neurostimulator lead(s)\| \|86.05\|\|Incision with removal of foreign body or device from skin and subcutaneous tissue (used to report removal of a neurostimulator pulse generator)\| \|86.94\|\|Insertion or replacement of single array neurostimulator pulse generator, not specified as rechargeable\| \|86.95\|\|Insertion or replacement of dual array neurostimulator pulse generator, not specified as rechargeable\| \|86.97\|\|Insertion or replacement of single array rechargeable neurostimulator pulse generator (new code effective 10/1/05)\| \|86.98\|\|Insertion or replacement of dual array rechargeable neurostimulator pulse generation (new code effective 10/1/05)\| \|ICD-9 Diagnosis\|\|See “Pain” in ICD-9 diagnosis index\| \|HCPCS\|\|L8680\|\|Implantable neurostimulator electrode, each (new code effective 1/1/06)\| \|L8685\|\|Implantable neurostimulator pulse generator, single array, rechargeable, includes extension (new code effective 1/1/06)\| \|L8686\|\|Implantable neurostimulator pulse generator, single array, nonrechargeable, includes extension (new code effective 1/1/06)\| \|L8687\|\|Implantable neurostimulator pulse generator, dual array, rechargeable, includes extension (new code effective 1/1/06)\| \|L8688\|\|Implantable neurostimulator pulse generator, dual array, nonrechargeable, includes extension (new code effective 1/1/06)\| \|ICD-10-CM (effective 10/1/14)\|\|This list is a representative list of severe and chronic pain of the trunk and limbs diagnosis codes.\| \|G56.40 -G56.42\|\|Causalgia of upper limb code range\| \|G57.70 -G57.72\|\|Causalgia of lower limb code range\| \|G89.21 -G89.8\|\|Chronic pain, not elsewhere classified, code range\| \|G89.4\|\|Chronic pain syndrome\| \|G90.50 -G90.59\|\|Complex regional pain syndrome I (CRPS I), code range\| \|M25.50 -M25.579\|\|Pain in joint, code range\| \|M54.10 -M54.18\|\|Radiculopathy, code range\| \|M54.30 -M54.32\|\|Sciatica, code range\| \|M54.40 -M54.42\|\|Lumbago with sciatica, code range\| \|M54.5\|\|Low back pain\| \|M54.6\|\|Pain in thoracic spine\| \|M54.81, M54.89\|\|Other dorsalgia codes\| \|M79.60 -M79.676\|\|Pain in limb, hand, foot, fingers and toes code range\| \|ICD-10-PCS (effective 10/1/14)\|\|ICD-10-PCS codes are only used for inpatient services.\| \|Surgical, central nervous system, insertion, spinal canal, neurostimulator lead, code by approach\| \|00HV0MZ, 00HV3MZ, 00HV4MZ\|\|Surgical, central nervous system, insertion, spinal cord, neurostimulator lead, code by approach\| \|00WU0MZ, 00WU3MZ, 00WU4MZ\|\|Surgical, central nervous system, removal, spinal canal, neurostimulator lead, code by approach\| \|00PV0MZ, 00PV3MZ, 00PV4MZ\|\|Surgical, central nervous system, removal, spinal cord, neurostimulator lead, code by approach\| \|00WU0MZ, 00WU3MZ, 00WU4MZ\|\|Surgical, central nervous system, revision, spinal canal, neurostimulator lead, code by approach\| \|00WV0MZ, 00WV3MZ, 00WV4MZ\|\|Surgical, central nervous system, revision, spinal cord, neurostimulator lead, code by approach\| \|0JH60M6, 0JH60M7, 0JH60M8, 0JH60M9, 0JH63M6, 0JH63M7, 0JH63M8, 0JH63M9, 0JH70M6, 0JH70M7, 0JH70M8, 0JH70M9, 0JH73M6, 0JH73M7, 0JH73M8, 0JH73M9, 0JH80M6, 0JH80M7, 0JH80M8, 0JH80M9, 0JH83M6, 0JH83M7, 0JH83M8, 0JH83M9\|\|Surgical, subcutaneous tissue and fascia, insertion, stimulator generator, code by body part, approach, number of arrays and whether rechargeable or not\| \|0JPT0MZ, 0JPT3MZ\|\|Surgical, subcutaneous tissue and fascia, removal, subcutaneous tissue and fascia, trunk, stimulator generator, code by approach (there aren’t ICD-10-PCS codes for removal of stimulator generator from other body parts)\| \|Type of Service\|\|Surgical\| \|Place of Service\|\|Inpatient/Outpatient\| Electrical Nerve Stimulation, Spinal Spinal Cord Stimulation Stimulation, Electrical, Spinal Cord \|03/31/96\|\|Add to Surgery section\|\|New policy\| \|04/01/98\|\|Replace policy\|\|Policy cross-referenced to No. 7.01.63\| \|07/10/98\|\|Replace policy\|\|Policy updated and revised\| \|11/15/98\|\|Coding update\|\|1999 CPT coding release\| \|04/29/03\|\|Replace policy\|\|Policy updated; new policy statement added, stating that spinal cord stimulation is investigational as a treatment of critical limb ischemia\| \|11/9/04\|\|Replace policy\|\|Policy updated; no change to policy statement. Coding updated\| \|08/17/05\|\|Replace policy\|\|Policy updated with literature search and coding updated; no change to policy statement\| \|12/14/05\|\|Replace policy – coding update only\|\|Coding updated\| \|12/12/06\|\|Replace policy\|\|Policy updated with literature search; no change to policy statement; reference numbers 7 – 9 added\| \|03/13/08\|\|Replace policy\|\|Policy updated with literature search; references 10 – 13 added; no change to policy statements\| \|01/08/09\|\|Replace policy\|\|Policy updated with literature search; references 14–25 added. Use in refractory angina added as investigational indication.\| \|01/14/10\|\|Replace policy\|\|Policy updated with literature search; reference numbers 26-29 added; no change to policy statements\| \|01/13/11\|\|Replace policy\|\|Policy updated with literature search. Rationale extensively reqritten; references numbers 15 and 16 added, other references reordered or removed. No change to policy statements.\| \|1/12/12\|\|Replace policy\|\|Policy updated with literature search. Reference numbers 16, 17 and 18 added, other references reordered or removed. No change to policy statements\| \|1/10/13\|\|Replace policy\|\|Policy updated with literature search. Reference numbers 14, 17, 19 and 20 added; other references reordered or removed. No change to policy statements.\|	2	47	2	2	2	0.447495	6	8,738
Medicare Program Description and Legislative History The following are brief summaries of complex subjects as of November 1, 2010. They should be used only as overviews and general guides to the Medicare and Medicaid programs. The views expressed herein do not necessarily reflect the policies or legal positions of the Centers for Medicare & Medicaid Services (CMS) or the Department of Health and Human Services (HHS). These summaries do not render any legal, accounting, or other professional advice, nor are they intended to explain fully all of the provisions or exclusions of the relevant laws, regulations, and rulings of the Medicare and Medicaid programs. Original sources of authority should be researched and utilized.1 Title XVIII of the Social Security Act, designated "Health Insurance for the Aged and Disabled," is commonly known as Medicare. As part of the Social Security Amendments of 1965, the Medicare legislation established a health insurance program for aged persons to complement the retirement, survivors, and disability insurance benefits under Title II of the Social Security Act. When first implemented in 1966, Medicare covered most persons aged 65 or older. In 1973, the following groups also became eligible for Medicare benefits: persons entitled to Social Security or Railroad Retirement disability cash benefits for at least 24 months, most persons with end-stage renal disease (ESRD), and certain otherwise noncovered aged persons who elect to pay a premium for Medicare coverage. Beginning in July 2001, persons with Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease) are allowed to waive the 24-month waiting period. Beginning March 30, 2010, individuals in the vicinity of Libby, Montana who are diagnosed with an asbestos-related condition are Medicare-eligible. Medicare eligibility could also apply to individuals in other areas who are diagnosed with a medical condition caused by exposure to a public health hazard for which a future public health emergency declaration is made under the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (Public Law 96-510). This very broad description of Medicare eligibility is expanded in the next section. Medicare originally consisted of two parts: Hospital Insurance (HI), also known as Part A, and Supplementary Medical Insurance (SMI), which in the past was also known simply as Part B. Part A helps pay for inpatient hospital, home health agency, skilled nursing facility, and hospice care. Part A is provided free of premiums to most eligible people; certain otherwise ineligible people may voluntarily pay a monthly premium for coverage. Part B helps pay for physician, outpatient hospital, home health agency, and other services. To be covered by Part B, all eligible people must pay a monthly premium. A third part of Medicare, sometimes known as Part C, is the Medicare Advantage program, which was established as the Medicare+Choice program by the Balanced Budget Act of 1997 (Public Law 105-33) and subsequently renamed and modified by the Medicare Prescription Drug, Improvement, and Modernization Act (MMA) of 2003 (Public Law 108-173). The Medicare Advantage program expands beneficiaries' options for participation in private-sector health care plans. The MMA also established a fourth part of Medicare, known as Part D, to help pay for prescription drugs not otherwise covered by Part A or Part B. Part D initially provided access to prescription drug discount cards, on a voluntary basis and at limited cost to all enrollees (except those entitled to Medicaid drug coverage) and, for low-income beneficiaries, transitional limited financial assistance for purchasing prescription drugs and a subsidized enrollment fee for the discount cards. This temporary plan began in mid-2004 and phased out during 2006. In 2006 and later, Part D provides subsidized access to prescription drug insurance coverage on a voluntary basis for all beneficiaries upon payment of a premium, with premium and cost-sharing subsidies for low-income enrollees. Part D activities are handled within the SMI trust fund but in an account separate from Part B. It should thus be noted that the traditional treatment of "SMI" and "Part B" as synonymous is no longer accurate, since SMI now consists of Parts B and D. The purpose of the two separate accounts within the SMI trust fund is to ensure that funds from one part are not used to finance the other. When Medicare began on July 1, 1966, approximately 19 million people enrolled. In 2010, over 47 million are enrolled in one or both of Parts A and B of the Medicare program, and over 11 million of them have chosen to participate in a Medicare Advantage plan. Entitlement and Coverage Part A is generally provided automatically and free of premiums to persons aged 65 or older who are eligible for Social Security or Railroad Retirement benefits, whether they have claimed these monthly cash benefits or not. Also, workers and their spouses with a sufficient period of Medicare-only coverage in federal, state, or local government employment are eligible beginning at age 65. Similarly, individuals who have been entitled to Social Security or Railroad Retirement disability benefits for at least 24 months, and government employees with Medicare-only coverage who have been disabled for more than 29 months, are entitled to Part A benefits. (As noted previously, the waiting period is waived for persons with Lou Gehrig's Disease, and certain persons in the Libby, Montana vicinity who are diagnosed with asbestos-related conditions are Medicare-eligible. It should also be noted that, over the years, there have been certain liberalizations made to both the waiting period requirement and the limit on earnings allowed for entitlement to Medicare coverage based on disability.) Part A coverage is also provided to insured workers with ESRD (and to insured workers' spouses and children with ESRD), as well as to some otherwise ineligible aged and disabled beneficiaries who voluntarily pay a monthly premium for their coverage. In 2009, Part A provided protection against the costs of hospital and specific other medical care to about 46 million people (over 38 million aged and almost 8 million disabled enrollees). Part A benefit payments totaled $239.3 billion in 2009. The following health care services are covered under Part A: - Inpatient hospital care. Coverage includes costs of a semiprivate room, meals, regular nursing services, operating and recovery rooms, intensive care, inpatient prescription drugs, laboratory tests, X-rays, psychiatric hospitals, inpatient rehabilitation, and long-term care hospitalization when medically necessary, as well as all other medically necessary services and supplies provided in the hospital. An initial deductible payment is required of beneficiaries who are admitted to a hospital, plus copayments for all hospital days following day 60 within a benefit period (described later). - Skilled nursing facility (SNF) care. Coverage is provided by Part A only if it follows within 30 days (generally) a hospitalization of 3 days or more and is certified as medically necessary. Covered services are similar to those for inpatient hospital care, and include rehabilitation services and appliances. The number of SNF days provided under Medicare is limited to 100 days per benefit period (described later), with a copayment required for days 21 through 100. Part A does not cover nursing facility care if the patient does not require skilled nursing or skilled rehabilitation services. Home health agency (HHA) care (covered by Parts A and B). The Balanced Budget Act transferred from Part A to Part B those home health services furnished on or after January 1, 1998, that are unassociated with a hospital or SNF stay. Part A will continue to cover the first 100 visits following a 3-day hospital stay or a SNF stay; Part B covers any visits thereafter. Home health care under Parts A and B has no copayment and no deductible. HHA care, including care provided by a home health aide, may be furnished part time by an HHA in the residence of a homebound beneficiary, if intermittent or part-time skilled nursing and/or certain other therapy or rehabilitation care is necessary. Certain medical supplies and durable medical equipment may also be provided, although beneficiaries must pay a 20 percent coinsurance for durable medical equipment, as required under Part B of Medicare. There must be a plan of treatment and periodic review by a physician. Full-time nursing care, food, blood, and drugs are not provided as HHA services. - Hospice care. Coverage is provided for services to terminally ill persons with life expectancies of 6 months or less who elect to forgo the standard Medicare benefits for treatment of their illness and to receive only hospice care for it. Such care includes pain relief, supportive medical and social services, physical therapy, nursing services, and symptom management. However, if a hospice patient requires treatment for a condition that is not related to the terminal illness, Medicare will pay for all covered services necessary for that condition. The Medicare beneficiary pays no deductible for the hospice program but does pay small coinsurance amounts for drugs and inpatient respite care. An important Part A component is the benefit period, which starts when the beneficiary first enters a hospital and ends when there has been a break of at least 60 consecutive days since inpatient hospital or skilled nursing care was provided. There is no limit to the number of benefit periods covered by Part A during a beneficiary's lifetime; however, inpatient hospital care is normally limited to 90 days during a benefit period, and copayment requirements (detailed later) apply for days 61 through 90. If a beneficiary exhausts the 90 days of inpatient hospital care available in a benefit period, the beneficiary can elect to use days of Medicare coverage from a nonrenewable "lifetime reserve" of up to 60 (total) additional days of inpatient hospital care. Copayments are also required for such additional days. All citizens (and certain legal aliens) aged 65 or older, and all disabled persons entitled to coverage under Part A, are eligible to enroll in Part B on a voluntary basis by payment of a monthly premium. Almost all persons entitled to Part A choose to enroll in Part B. In 2009, Part B provided protection against the costs of physician and other medical services to about 43 million people (36 million aged and 7 million disabled enrollees). Part B benefits totaled $202.6 billion in 2009. Part B covers certain medical services and supplies, including the following: - Physicians' and surgeons' services, including some covered services furnished by chiropractors, podiatrists, dentists, and optometrists; - Services provided by Medicare-approved practitioners who are not physicians, including certified registered nurse anesthetists, clinical psychologists, clinical social workers (other than in a hospital or SNF), physician assistants, and nurse practitioners and clinical nurse specialists in collaboration with a physician; - Services in an emergency room, outpatient clinic, or ambulatory surgical center, including same-day surgery; - Home health care not covered under Part A; - Laboratory tests, X-rays, and other diagnostic radiology services; - Certain preventive care services and screening tests; - Most physical and occupational therapy and speech pathology services; - Comprehensive outpatient rehabilitation facility services, and mental health care in a partial hospitalization psychiatric program, if a physician certifies that inpatient treatment would be required without it; - Radiation therapy; renal (kidney) dialysis and transplants; heart, lung, heart-lung, liver, pancreas, and bone marrow transplants; and, as of April 2001, intestinal transplants; - Approved durable medical equipment for home use, such as oxygen equipment and wheelchairs, prosthetic devices, and surgical dressings, splints, casts, and braces; - Drugs and biologicals that are not usually self-administered, such as hepatitis B vaccines and immunosuppressive drugs (certain self-administered anticancer drugs are covered); - Certain services specific to people with diabetes; - Ambulance services, when other methods of transportation are contraindicated; and - Rural health clinic and federally qualified health center services, including some telemedicine services. To be covered, all services must be either medically necessary or one of several prescribed preventive benefits. Part B services are generally subject to a deductible and coinsurance (see next section). Certain medical services and related care are subject to special payment rules, including deductibles (for blood), maximum approved amounts (for Medicare-approved physical, speech, or occupational therapy services performed in settings other than hospitals), and higher cost-sharing requirements (such as those for certain outpatient hospital services). The preceding description of Part B-covered services should be used only as a general guide, due to the wide range of services covered under Part B and the quite specific rules and regulations that apply. Medicare Parts A and B, as described above, constitute the original fee-for-service Medicare program. Medicare Part C, also known as Medicare Advantage, is an alternative to traditional Medicare. Although all Medicare beneficiaries can receive their benefits through the traditional fee-for-service program, most beneficiaries enrolled in both Part A and Part B can choose to participate in a Medicare Advantage plan instead. Medicare Advantage plans are offered by private companies and organizations and are required to provide at least those services covered by Parts A and B, except hospice services. These plans may (and in certain situations must) provide extra benefits (such as vision or hearing) or reduce cost sharing or premiums. The primary Medicare Advantage plans are: - Local coordinated care plans (LCCPs), including health maintenance organizations (HMOs), provider-sponsored organizations, local preferred provider organizations (PPOs), and other certified coordinated care plans and entities that meet the standards set forth in the law. Generally, each plan has a network of participating providers. Enrollees may be required to use these providers or, alternatively, may be allowed to go outside the network but pay higher cost-sharing fees for doing so. - Regional PPO plans, which began in 2006 and offer coverage to one of 26 defined regions. Like local PPOs, regional PPOs have networks of participating providers, and enrollees must use these providers or pay higher cost-sharing fees. However, regional PPOs are required to provide beneficiary financial protection in the form of limits on out-of-pocket cost sharing, and there are specific provisions to encourage regional PPO plans to participate in Medicare. - Private fee-for-service (PFFS) plans, which were not required to have networks of participating providers through 2010. Beginning in 2011, this will still be the case for PFFS plans in "network areas" (usually counties) with fewer than two network-based LCCPs and/or regional PPOs, and members will be able to use any Medicare provider willing to accept the plan's payment. However, for PFFS plans in network areas with two or more network-based LCCPs and/or regional PPOs, provider networks will be mandatory, and members may be required to use these participating providers. - Special Needs Plans, which are restricted to beneficiaries who are dually eligible for Medicare and Medicaid, live in long-term care institutions, or have certain severe and disabling conditions. For individuals entitled to Part A or enrolled in Part B (except those entitled to Medicaid drug coverage), the new Part D initially provided access to prescription drug discount cards, at a cost of no more than $30 annually, on a voluntary basis. For low-income beneficiaries, Part D initially provided transitional financial assistance of up to $600 per year for purchasing prescription drugs, plus a subsidized enrollment fee for the discount cards. This temporary plan began in mid-2004 and phased out in 2006. Beginning in 2006, Part D provides subsidized access to prescription drug insurance coverage on a voluntary basis, upon payment of a premium, to individuals entitled to Part A or enrolled in Part B, with premium and cost-sharing subsidies for low-income enrollees. Beneficiaries may enroll in either a stand-alone prescription drug plan (PDP) or an integrated Medicare Advantage plan that offers Part D coverage. Enrollment began in late 2005. In 2009, Part D provided protection against the costs of prescription drugs to about 33 million people. Part D benefits totaled $60.5 billion in 2009. Part D coverage includes most FDA-approved prescription drugs and biologicals. (The specific drugs currently covered in Parts A and B remain covered there.) However, plans may set up formularies for their prescription drug coverage, subject to certain statutory standards. Part D coverage can consist of either standard coverage (defined later) or an alternative design that provides the same actuarial value. For an additional premium, plans may also offer supplemental coverage exceeding the value of basic coverage. It should be noted that some health care services are not covered by any portion of Medicare. Noncovered services include long-term nursing care, custodial care, and certain other health care needs, such as dentures and dental care, eyeglasses, and hearing aids. These services are not a part of the Medicare program, unless they are a part of a private health plan under the Medicare Advantage program. Program Financing, Beneficiary Liabilities, and Payments to Providers All financial operations for Medicare are handled through two trust funds, one for Hospital Insurance (HI, Part A) and one for Supplementary Medical Insurance (SMI, Parts B and D). These trust funds, which are special accounts in the U.S. Treasury, are credited with all receipts and charged with all expenditures for benefits and administrative costs. The trust funds cannot be used for any other purpose. Assets not needed for the payment of costs are invested in special Treasury securities. The following sections describe Medicare's financing provisions, beneficiary cost-sharing requirements, and the basis for determining Medicare reimbursements to health care providers. The HI trust fund is financed primarily through a mandatory payroll tax. Almost all employees and self-employed workers in the United States work in employment covered by Part A and pay taxes to support the cost of benefits for aged and disabled beneficiaries. The Part A tax rate is 1.45 percent of earnings, to be paid by each employee and a matching amount by the employer for each employee, and 2.90 percent for self-employed persons. Beginning in 1994, this tax is paid on all covered wages and self-employment income without limit. (Prior to 1994, the tax applied only up to a specified maximum amount of earnings.) Beginning in 2013, an additional Part A payroll tax of 0.9 percent will be collected on earned income in excess of $200,000 (for those filing income tax singly) and $250,000 (for those filing jointly; the earnings thresholds are not indexed). The Part A tax rate is specified in the Social Security Act and cannot be changed without legislation. Part A also receives income from the following sources: (1) a portion of the income taxes levied on Social Security benefits paid to high-income beneficiaries, (2) premiums from certain persons who are not otherwise eligible and choose to enroll voluntarily, (3) reimbursements from the general fund of the U.S. Treasury for the cost of providing Part A coverage to certain aged persons who retired when Part A began and thus were unable to earn sufficient quarters of coverage (and those federal retirees similarly unable to earn sufficient quarters of Medicare-qualified federal employment), (4) interest earnings on its invested assets, and (5) other small miscellaneous income sources. The taxes paid each year are used mainly to pay benefits for current beneficiaries. The SMI trust fund differs fundamentally from the HI trust fund with regard to the nature of its financing. As previously noted, SMI is now composed of two parts, Part B and Part D, each with its own separate account within the SMI trust fund. The nature of the financing for both parts of SMI is similar, in that both parts are primarily financed by contributions from the general fund of the U.S. Treasury and (to a much lesser degree) by beneficiary premiums. For Part B, the contributions from the general fund of the U.S. Treasury are the largest source of income, since beneficiary premiums are generally set at a level that covers 25 percent of the average expenditures for aged beneficiaries. The standard Part B premium rate will be $115.40 per beneficiary per month in 2011. There are, however, three provisions that can alter the premium rate for certain enrollees (and the third will reduce the premium for most enrollees in 2011). First, penalties for late enrollment (that is, enrollment after an individual's initial enrollment period) may apply, subject to certain statutory criteria. Second, beginning in 2007, beneficiaries whose income is above certain thresholds are required to pay an income-related monthly adjustment amount, in addition to their standard monthly premium. Finally, a "hold-harmless" provision, which prohibits increases in the standard Part B premium from exceeding the dollar amount of an individual's Social Security cost-of-living adjustment, lowers the premium rate for most individuals who have their premiums deducted from their Social Security checks. Under this provision, the Part B premium for 2010 remained at the 2009 amount of $96.40 for about 73 percent of Part B enrollees because the Social Security cost-of-living adjustment was 0 percent for 2010. Higher premium amounts ($110.50 or more) were in effect for about 27 percent of Part B enrollees, all of whom were ineligible for protection under the "hold-harmless" provision. (Those not protected included most new enrollees during the year; enrollees with high incomes who were subject to the income-related monthly adjustment amount; and enrollees—such as certain federal, state, and local government retirees—who did not have their Part B premium withheld from a Social Security check. Also not protected were dual Medicare-Medicaid beneficiaries whose premiums were paid by state Medicaid programs.) The increase in the standard Part B premium rate, from $96.40 to $110.50, was higher than it otherwise would have been because the cost of adequately funding Part B was spread across a minority of enrollees, rather than across all of them. For 2011, the Social Security cost-of-living adjustment is again 0 percent. Hence, under the "hold-harmless" provision, most enrollees will continue to pay the same $96.40 or $110.50 Part B premium amount in 2011 that they paid in 2010, with the majority of those enrollees paying $96.40. The standard premium rate of $115.40 will be in effect only for those enrollees who are not eligible for protection under the "hold-harmless" provision. As in 2010, in order for Part B to be adequately funded in 2011, the 2011 contingency margin had to be increased to account for this situation, and, as a result, a larger-than-usual premium increase will again be borne by a minority of Part B enrollees. It must be noted that the above description of Part B premium amounts for 2011 is accurate as of November 1, 2010. It is possible that Congress will override the increase in the standard Part B premium for 2011. The 2011 Part B income-related monthly adjustment amounts and total monthly premium amounts to be paid by beneficiaries, according to income level and filing status, are shown in the following table. \|Beneficiaries who file individual tax returns and are single individuals, heads of households, qualifying widow(er)s with dependent children, or married individuals who lived apart from their spouse for the entire taxable year and file separately\| \|Less than or equal to $85,000\|\|0\|\|96.40, 110.50, or 115.40 (see text)\| \|Greater than $85,000 and less than or equal to $107,000\|\|46.10\|\|161.50\| \|Greater than $107,000 and less than or equal to $160,000\|\|115.30\|\|230.70\| \|Greater than $160,000 and less than or equal to $214,000\|\|184.50\|\|299.90\| \|Greater than $214,000\|\|253.70\|\|369.10\| \|Beneficiaries who file joint tax returns\| \|Less than or equal to $170,000\|\|0\|\|96.40, 110.50, 115.40 (see text)\| \|Greater than $170,000 and less than or equal to $214,000\|\|46.10\|\|161.50\| \|Greater than $214,000 and less than or equal to $320,000\|\|115.30\|\|230.70\| \|Greater than $320,000 and less than or equal to $428,000\|\|184.50\|\|299.90\| \|Greater than $428,000\|\|253.70\|\|369.10\| \|Beneficiaries who are married and lived with their spouse at any time during the year but file separate tax returns\| \|Less than or equal to $85,000\|\|0\|\|96.40, 110.50, 115.40 (see text)\| \|Greater than $85,000 and less than or equal to $129,000\|\|184.50\|\|299.90\| \|Greater than $129,000\|\|253.70\|\|369.10\| For Part D, as with Part B, general fund contributions account for the largest source of income, since Part D beneficiary premiums are to represent, on average, 25.5 percent of the cost of standard coverage. The Part D base beneficiary premium for 2011 will be $32.34. The actual Part D premiums paid by individual beneficiaries equal the base beneficiary premium adjusted by a number of factors. In practice, premiums vary significantly from one Part D plan to another and seldom equal the base beneficiary premium. As of this writing, it is estimated that the average monthly premium for basic Part D coverage, which reflects the specific plan-by-plan premiums and the estimated number of beneficiaries in each plan, will be about $30 in 2011. Penalties for late enrollment may apply. (Late enrollment penalties do not apply to enrollees who have maintained creditable prescription drug coverage.) Beneficiaries meeting certain low-income and limited-resources requirements pay substantially reduced premiums or no premiums at all (and are not subject to late enrollment penalties). Beginning in 2011, beneficiaries with income above certain thresholds will be required to pay an income-related monthly adjustment amount, in addition to their monthly premium. The 2011 Part D income-related monthly adjustment amounts to be paid by beneficiaries, according to income level and filing status, are shown in the following table. \|Beneficiaries who file individual tax returns and are single individuals, heads of households, qualifying widow(er)s with dependent children, or married individuals who lived apart from their spouse for the entire taxable year and file separately\| \|Less than or equal to $85,000\|\|0\| \|Greater than $85,000 and less than or equal to $107,000\|\|12.00\| \|Greater than $107,000 and less than or equal to $160,000\|\|31.10\| \|Greater than $160,000 and less than or equal to $214,000\|\|50.10\| \|Greater than $214,000\|\|69.10\| \|Beneficiaries who file joint tax returns\| \|Less than or equal to $170,000\|\|0\| \|Greater than $170,000 and less than or equal to $214,000\|\|12.00\| \|Greater than $214,000 and less than or equal to $320,000\|\|31.10\| \|Greater than $320,000 and less than or equal to $428,000\|\|50.10\| \|Greater than $428,000\|\|69.10\| \|Beneficiaries who are married and lived with their spouse at any time during the year but file separate tax returns\| \|Less than or equal to $85,000\|\|0\| \|Greater than $85,000 and less than or equal to $129,000\|\|50.10\| \|Greater than $129,000\|\|69.10\| In addition to contributions from the general fund of the U.S. Treasury and beneficiary premiums, Part D also receives payments from the states. With the availability of prescription drug coverage and low-income subsidies under Part D, Medicaid is no longer the primary payer for prescription drugs for Medicaid beneficiaries who also have Medicare, and states are required to defray a portion of Part D expenditures for those beneficiaries. During the Part D transitional period that began in mid-2004 and phased out during 2006, the general fund of the U.S. Treasury financed the transitional assistance benefit for low-income beneficiaries. Funds were transferred to, and paid from, a Transitional Assistance account within the SMI trust fund. The SMI trust fund also receives income from interest earnings on its invested assets, as well as a small amount of miscellaneous income. It is important to note that beneficiary premiums and general fund payments for Parts B and D are redetermined annually and separately. Payments to Medicare Advantage plans are financed from both the HI trust fund and the Part B account within the SMI trust fund in proportion to the relative weights of Part A and Part B benefits to the total benefits paid by the Medicare program. Beneficiary Payment Liabilities Fee-for-service beneficiaries are responsible for charges not covered by the Medicare program and for various cost-sharing aspects of Parts A and B. These liabilities may be paid (1) by the Medicare beneficiary; (2) by a third party, such as an employer-sponsored retiree health plan or private Medigap insurance; or (3) by Medicaid, if the person is eligible. The term "Medigap" is used to mean private health insurance that pays, within limits, most of the health care service charges not covered by Parts A or B of Medicare. These policies, which must meet federally imposed standards, are offered by Blue Cross and Blue Shield and various commercial health insurance companies. In Medicare Advantage plans, the beneficiary's payment share is based on the cost-sharing structure of the specific plan selected by the beneficiary, since each plan has its own requirements. Most plans have lower deductibles and coinsurance than are required of fee-for-service beneficiaries. Such beneficiaries, in general, pay the monthly Part B premium. However, some Medicare Advantage plans may pay part or all of the Part B premium for their enrollees as an added benefit. Depending on the plan, enrollees may also pay an additional premium for certain extra benefits provided (or, in a small number of cases, for certain Medicare-covered services). For hospital care covered under Part A, a beneficiary's fee-for-service payment share includes a one-time deductible amount at the beginning of each benefit period ($1,132 in 2011). This deductible covers the beneficiary's part of the first 60 days of each spell of inpatient hospital care. If continued inpatient care is needed beyond the 60 days, additional coinsurance payments ($283 per day in 2011) are required through the 90th day of a benefit period. Each Part A beneficiary also has a "lifetime reserve" of 60 additional hospital days that may be used when the covered days within a benefit period have been exhausted. Lifetime reserve days may be used only once, and coinsurance payments ($566 per day in 2011) are required. For skilled nursing care covered under Part A, Medicare fully covers the first 20 days of SNF care in a benefit period. But for days 21 through 100, a copayment ($141.50 per day in 2011) is required from the beneficiary. After 100 days per benefit period, Medicare pays nothing for SNF care. Home health care requires no deductible or coinsurance payment by the beneficiary. In any Part A service, the beneficiary is responsible for fees to cover the first 3 pints or units of nonreplaced blood per calendar year. The beneficiary has the option of paying the fee or of having the blood replaced. There are no premiums for most people covered by Part A. Eligibility is generally earned through the work experience of the beneficiary or of the beneficiary's spouse. However, most aged people who are otherwise ineligible for premium-free Part A coverage can enroll voluntarily by paying a monthly premium, if they also enroll in Part B. For people with fewer than 30 quarters of coverage as defined by the Social Security Administration (SSA), the Part A monthly premium rate will be $450 in 2011; for those with 30 to 39 quarters of coverage, the rate will be reduced to $248. Penalties for late enrollment may apply. Voluntary coverage upon payment of the Part A premium, with or without enrolling in Part B, is also available to disabled individuals for whom coverage has ceased because earnings are in excess of those allowed. The Part B beneficiary's payment share includes the following: one annual deductible ($162 in 2011), the monthly premiums, the coinsurance payments for Part B services (usually 20 percent of the remaining allowed charges with certain exceptions noted below), a deductible for blood, certain charges above the Medicare-allowed charge (for claims not on assignment), and payment for any services not covered by Medicare. For outpatient mental health services, the beneficiary is currently liable for 50 percent of the approved charges, but this percentage is to phase down to 20 percent over the 5-year period 2010–2014. For services reimbursed under the outpatient hospital prospective payment system, coinsurance percentages vary by service and currently fall in the range of 20 percent to 50 percent. There are no deductibles or coinsurance for certain services, such as clinical lab tests, HHA services, and some preventive care services (including an initial, "Welcome to Medicare" preventive physical examination and, beginning in 2011, an annual wellness visit to develop or update a prevention plan). For the standard Part D benefit design, there is an initial deductible ($310 in 2011). After meeting the deductible, the beneficiary pays 25 percent of the remaining costs, up to an initial coverage limit ($2,840 in 2011). The coverage gap starts after an individual's drug costs reach the initial coverage limit and stops when the beneficiary incurs a certain threshold of out-of-pocket costs ($4,550 in 2011). Previously, beneficiaries had to pay the full cost of their prescription drugs while in this coverage gap. However, under the Patient Protection and Affordable Care Act (Public Law 111-148) as amended by the Health Care and Education Reconciliation Act of 2010 (Public Law 111-152)—collectively referred to as the Affordable Care Act—beneficiaries (excluding those low-income enrollees eligible for cost-sharing subsidies) who entered the coverage gap in 2010 received a $250 rebate, and, starting in 2011, these beneficiaries will receive a 50-percent discount on covered brand-name prescription drugs. Additionally, reductions in beneficiary cost sharing in the coverage gap will phase in for generic drug costs beginning in 2011 and for brand-name prescription drug costs beginning in 2013; by 2020, the coverage gap will be fully phased out, with beneficiaries responsible for 25 percent of their prescription drug costs. (The 2011 out-of-pocket threshold of $4,550 is equivalent to total covered drug costs ranging from $6,447.50 to $6,719.03, depending on the percentage of brand-name versus generic drugs used by the beneficiary while in the coverage gap.) For costs incurred after reaching the out-of-pocket threshold, catastrophic coverage is provided, which requires enrollees to pay the greater of 5 percent coinsurance or a small defined copayment amount ($2.50 in 2011 for generic or preferred multisource drugs, and $6.30 in 2011 for other drugs). The benefit parameters are indexed annually to the growth in average per capita Part D costs. Beneficiaries meeting certain low-income and limited-resources requirements pay substantially reduced cost-sharing amounts. In determining out-of-pocket costs, only those amounts actually paid by the enrollee or another individual (and not reimbursed through insurance) are counted; the exceptions to this "true out-of-pocket" provision are cost-sharing assistance from the low-income subsidies provided under Part D and from State Pharmacy Assistance programs and, starting in 2011, the 50-percent discount on brand-name drugs purchased by enrollees in the Part D coverage gap. Many Part D plans offer alternative coverage that differs from the standard coverage described above. In fact, the majority of beneficiaries are not enrolled in the standard benefit design but rather in plans with low or no deductibles, flat payments for covered drugs, and, in some cases, additional partial coverage in the coverage gap. The monthly premiums required for Part D coverage are described in the previous section. Payments to Providers Before 1983, Part A payments to providers were made on a reasonable cost basis. Medicare payments for most inpatient hospital services are now made under a reimbursement mechanism known as the prospective payment system (PPS). Under the PPS for acute inpatient hospitals, each stay is categorized into a diagnosis-related group (DRG). Each DRG has a specific predetermined amount associated with it, which serves as the basis for payment. A number of adjustments are applied to the DRG's specific predetermined amount to calculate the payment for each stay. In some cases the payment the hospital receives is less than the hospital's actual cost for providing Part A–covered inpatient hospital services for the stay; in other cases it is more. The hospital absorbs the loss or makes a profit. Certain payment adjustments exist for extraordinarily costly inpatient hospital stays and other situations. Payments for skilled nursing care, home health care, inpatient rehabilitation hospital care, long-term care hospitals, inpatient psychiatric hospitals, and hospice are made under separate prospective payment systems. For nonphysician Part B services, home health care is reimbursed under the same prospective payment system as Part A, most hospital outpatient services are reimbursed on a separate prospective payment system, and most payments for clinical laboratory and ambulance services are based on fee schedules. A fee schedule is a comprehensive listing of maximum fees used to pay providers. Most durable medical equipment has also been paid on a fee schedule in recent years but is to be paid based on a competitive bidding process in some areas beginning January 1, 2011. This competitive bidding process will be expanded to all areas within the next several years. In general, the prospective payment systems and fee schedules used for Part A and non-physician Part B services are increased each year either by indices related to the "market basket" of goods and services that the provider must purchase or by indices related to the Consumer Price Index (CPI). These indices vary by type of provider. The Affordable Care Act mandates that these payment updates be decreased in all future years, in some cases by stipulated amounts during 2010–2019, and in all cases by the growth in economywide productivity, during this 10-year period and afterward. It is likely that the lower payment increases will not be viable in the long range. The best available evidence indicates that most health care providers cannot improve their productivity to this degree because of the labor-intensive nature of most of these services. For Part B, before 1992, physicians were paid on the basis of reasonable charge. This amount was initially defined as the lowest of (1) the physician's actual charge, (2) the physician's customary charge, or (3) the prevailing charge for similar services in that locality. Since January 1992, allowed charges have been defined as the lesser of (1) the submitted charges or (2) the amount determined by a fee schedule based on a relative value scale (RVS). In practice, most allowed charges are based on the fee schedule, which is supposed to be updated each year by a Sustainable Growth Rate (SGR) system prescribed in the law. However, over the past 8 years, the SGR system would have required significant fee reductions for physicians, and Congress has passed a series of bills to override the reductions. If a doctor or supplier agrees to accept the Medicare-approved rate as payment in full ("takes assignment"), then payments provided must be considered as payments in full for that service. The provider may not request any added payments (beyond the initial annual deductible and coinsurance) from the beneficiary or insurer. If the provider does not take assignment, the beneficiary will be charged for the excess (which may be paid by Medigap insurance). Limits now exist on the excess that doctors or suppliers can charge. Physicians are "participating physicians" if they agree before the beginning of the year to accept assignment for all Medicare services they furnish during the year. Since beneficiaries in the original Medicare fee-for-service program may select their doctors, they can choose participating physicians. Medicare Advantage plans and their precursors have generally been paid on a capitation basis, meaning that a fixed, predetermined amount per month per member is paid to the plan, without regard to the actual number and nature of services used by the members. The specific mechanisms to determine the payment amounts have changed over the years. In 2006, Medicare began paying capitated payment rates to plans based on a competitive bidding process. For Part D, each month for each plan member, Medicare pays stand-alone PDPs and the prescription drug portions of Medicare Advantage plans their risk-adjusted bid, minus the enrollee premium. Plans also receive payments representing premiums and cost-sharing amounts for certain low-income beneficiaries for whom these items are reduced or waived. Under the reinsurance provision, plans receive payments for 80 percent of costs in the catastrophic coverage category. To help them gain experience with the Medicare population, Part D plans are protected by a system of "risk corridors" that allow Medicare to assist with unexpected costs and to share in unexpected savings. The risk corridors became less protective after 2007. Under Part D, Medicare provides certain subsidies to employer and union PDPs that continue to offer coverage to Medicare retirees and meet specific criteria in doing so. These retiree drug subsidy (RDS) payments are tax-exempt, but under the Affordable Care Act, they will be taxable beginning in 2013. Medicare's Part A and Part B fee-for-service claims are processed by nongovernment organizations or agencies that contract to serve as the fiscal agent between providers and the federal government. These claims processors are known as intermediaries and carriers. They apply the Medicare coverage rules to determine the appropriateness of claims. Medicare intermediaries process Part A claims for institutional services, including inpatient hospital claims, SNFs, HHAs, and hospice services. They also process outpatient hospital claims for Part B. Examples of intermediaries are Blue Cross and Blue Shield (which utilize their plans in various states) and other commercial insurance companies. Intermediaries' responsibilities include: - Determining costs and reimbursement amounts, - Maintaining records, - Establishing controls, - Safeguarding against fraud and abuse or excess use, - Conducting reviews and audits, - Making the payments to providers for services, and - Assisting both providers and beneficiaries as needed. Medicare carriers handle Part B claims for services by physicians and medical suppliers. Examples of carriers are the Blue Shield plans in a state and various commercial insurance companies. Carriers' responsibilities include: - Determining charges allowed by Medicare, - Maintaining quality-of-performance records, - Assisting in fraud and abuse investigations, - Assisting both suppliers and beneficiaries as needed, and - Making payments to physicians and suppliers for services that are covered under Part B. Claims for services provided by Medicare Advantage plans (that is, claims under Part C) are processed by the plans themselves. Part D plans are responsible for processing their claims, akin to Part C. However, because of the "true out-of-pocket" provision discussed previously, the Centers for Medicare & Medicaid Services (CMS) has contracted the services of a facilitator, who works with CMS, Part D drug plans (stand-alone PDPs and the prescription drug portions of Medicare Advantage plans), and carriers of supplemental drug coverage to coordinate benefit payments and track the sources of cost-sharing payments. Claims under Part D also have to be submitted by the plans to CMS, so that certain payments based on actual experience (such as payments for low-income cost-sharing and premium subsidies, reinsurance, and risk corridors) can be determined. Because of its size and complexity, Medicare is vulnerable to improper payments, ranging from inadvertent errors to outright fraud and abuse. Although providers are responsible for submitting accurate claims, and intermediaries and carriers are responsible for ensuring that only such claims are paid, there are additional groups whose duties include the prevention, reduction, and recovery of improper payments. Quality improvement organizations (QIOs, formerly called peer review organizations or PROs) are groups of practicing health care professionals who are paid by the federal government to improve the effectiveness, efficiency, economy, and quality of services delivered to Medicare beneficiaries. One function of QIOs is to ensure that Medicare pays only for services and goods that are reasonable and necessary and that are provided in the most appropriate setting. The ongoing effort to address improper payments intensified after enactment of the Health Insurance Portability and Accountability Act (HIPAA) of 1996 (Public Law 104-191), which created the Medicare Integrity Program (MIP). The MIP provides CMS with dedicated funds to identify and combat improper payments, including those caused by fraud and abuse, and, for the first time, allows CMS to award contracts competitively with entities other than carriers and intermediaries to conduct these activities. MIP funds are used for (1) audits of cost reports, which are financial documents that hospitals and other institutions are required to submit annually to CMS; (2) medical reviews of claims to determine whether services provided are medically reasonable and necessary; (3) determinations of whether Medicare or other insurance sources have primary responsibility for payment; (4) identification and investigation of potential fraud cases; and (5) education to inform providers about appropriate billing procedures. In addition to creating the MIP, HIPAA established a fund to provide resources for the Department of Justice—including the Federal Bureau of Investigation—and the Office of Inspector General (OIG) within the Department of Health and Human Services (HHS) to investigate and prosecute health care fraud and abuse. The Deficit Reduction Act (DRA) of 2005 (Public Law 109-171) established and funded the Medicare-Medicaid Data Match Program, which is designed to identify improper billing and utilization patterns by matching Medicare and Medicaid claims information. As is the case under the MIP, CMS can contract with third parties. The funds also can be used (1) to coordinate actions by CMS, the states, the Attorney General, and the HHS OIG to prevent improper Medicaid and Medicare expenditures and (2) to increase the effectiveness and efficiency of both Medicare and Medicaid through cost avoidance, savings, and the recoupment of fraudulent, wasteful, or abusive expenditures. The Affordable Care Act includes many provisions intended to improve the accuracy of payments and to link those payments to quality and efficiency in the Medicare program. One of the most important provisions establishes the Center for Medicare and Medicaid Innovation (CMI) in CMS to test innovative payment and service delivery models, with the goal of reducing Medicare, Medicaid, and the Children's Health Insurance Program (CHIP) expenditures while preserving or enhancing quality of care. HHS has the overall responsibility for administration of the Medicare program. Within HHS, responsibility for administering Medicare rests with CMS. The Social Security Administration (SSA) assists, however, by initially determining an individual's Medicare entitlement, by withholding Part B premiums from the Social Security benefit checks of most beneficiaries, and by maintaining Medicare data on the Master Beneficiary Record, which is SSA's primary record of beneficiaries. The MMA requires SSA to undertake a number of additional Medicare-related responsibilities, including making low-income subsidy determinations under Part D, notifying individuals of the availability of Part D subsidies, withholding Part D premiums from monthly Social Security cash benefits for beneficiaries who request such an arrangement, and, for 2007 and later, determining the individual's Part B premium if the Part B income-related monthly adjustment applies. For 2011 and later, the Affordable Care Act will also require SSA to determine the individual's Part D premium if the Part D income-related monthly adjustment applies. The Internal Revenue Service (IRS) in the Department of the Treasury collects the Part A payroll taxes from workers and their employers. IRS data, in the form of income tax returns, play a role in determining which Part D enrollees are eligible for low-income subsidies (and to what degree) and which Part B and Part D enrollees are subject to the income-related monthly adjustment amounts in their premiums (and to what degree). A Medicare Board of Trustees, composed of two appointed members of the public and four members who serve by virtue of their positions in the federal government, oversees the financial operations of the HI and SMI trust funds. The Secretary of the Treasury is the managing trustee. Each year, around the first day of April, the Board of Trustees reports to Congress on the financial and actuarial status of the Medicare trust funds. State agencies (usually state health departments under agreements with CMS) identify, survey, and inspect provider and supplier facilities and institutions wishing to participate in the Medicare program. In consultation with CMS, these agencies then certify the facilities that are qualified. Medicare Financial Status Medicare is the largest health care insurance program—and the second-largest social insurance program—in the United States. Medicare is also complex, and it faces a number of financial challenges in both the short term and the long term. These challenges include: - The solvency of the HI trust fund, which fails the Medicare Board of Trustees' test of short-range financial adequacy, as annual expenditures are projected to exceed annual assets within 10 years. - The long-range health of the HI trust fund, as the trust fund fails the Trustees' long-range test of close actuarial balance. - The rapid growth projected for SMI costs as a percent of Gross Domestic Product. (The Part B and Part D accounts in the SMI trust fund are automatically in financial balance—in both the short range and the long range—since premiums and general revenue financing rates are reset each year to match estimated costs.) - The Part B premium situation in 2010 and 2011, whereby about one-quarter of Part B enrollees are subject to above-average premium increases while the other three-quarters are not subject to a premium increase at all (because of the zero-percent cost-of-living increase for Social Security benefits and the "hold-harmless" provision for Part B, discussed above). - The substantial reductions in Part B physician payment rates required under the Sustainable Growth Rate system in current law. In recent years, Congress has consistently passed legislation that overrides the reductions (also discussed above). - The likelihood that the lower payment rate updates to most categories of Medicare providers for 2011 and later, as mandated by the Affordable Care Act, will not be viable in the long range (also discussed above). A detailed description of these issues is beyond the scope of this summary. For more information, see the Medicare Trustees Report (https://www.cms.gov/ReportsTrustFunds/). The Medicare program covers 95 percent of our nation's aged population, as well as many people who receive Social Security disability benefits. In 2009, Part A covered almost 46 million enrollees with benefit payments of $239.3 billion, Part B covered almost 43 million enrollees with benefit payments of $202.6 billion, and Part D covered over 33 million enrollees with benefit payments of $60.5 billion. Administrative costs in 2009 were about 1.3 percent, 1.5 percent, and 0.5 percent of expenditures for Part A, Part B, and Part D, respectively. Total expenditures for Medicare in 2009 were $509.0 billion. Medicare: History of Provisions This section is a summary of selected Medicare provisions, based on general interest, as of November 1, 2010. It should be used only as a broad overview of the history of the provisions of the Medicare program. This section does not render any legal, accounting, or other professional advice and is not intended to explain fully all the provisions and exclusions of the relevant laws, regulations, and rulings of the Medicare program. Original sources of authority should be researched and utilized. Entitlement to Medicare Part A (also known as Hospital Insurance, or HI) Benefits 1965. Individual aged 65 or older entitled to monthly benefits under the Social Security or Railroad Retirement program, or aged 65 before 1968, or 3 quarters of coverage (QC) after 1965 and before attainment of age 65. 1967. Three QC for each year after 1966 and before attainment of age 65. 1972. Disabled individual, under age 65, entitled to disability benefits for 24 consecutive months under the Social Security or Railroad Retirement program (excludes spouses and children of disabled individuals). Individual under age 65 who has end-stage renal disease (ESRD) and who is either fully or currently insured, or is entitled to monthly benefits under the Social Security or Railroad Retirement program, or is the spouse or dependent child of such an insured individual or beneficiary. Entitlement begins on the first day of the third month following the initiation of a course of renal dialysis and ends with the 12th month following the month in which either the dialysis terminates or the individual has a renal transplant. Individual aged 65 or older enrolled in the Part B program who is not otherwise entitled to HI benefits, upon voluntary participation with payment of HI premium. 1980. Individual who would be entitled to monthly benefits under the Social Security or Railroad Retirement program if application were made. Disabled individual under age 65 entitled to disability benefits for at least 24 months, not necessarily consecutive, under the Social Security or Railroad Retirement program. Coverage extended for up to 36 months for disabled individuals whose disability continues but whose monthly benefit ceased because they engaged in substantial gainful activity. Second waiting period eliminated if a former disabled-worker beneficiary becomes entitled again within 5 years (7 years for disabled widows and widowers and disabled children aged 18 or older). 1982. Federal employees covered under HI on the basis of QC for earnings as federal employees or on the basis of deemed QC for earnings as federal employees before 1983. 1983. Employees of nonprofit organizations, effective January 1, 1984. 1986. Mandatory coverage for state and local government employees not covered under Social Security and hired after March 31, 1986. 1987. Second waiting period eliminated if a former disabled beneficiary becomes entitled again (no time limit). 1989. Disabled individuals under age 65 who are no longer entitled to Social Security disability benefits because their earnings exceeded the substantial gainful activity level have the option to purchase Medicare coverage by paying the HI and Supplementary Medical Insurance (SMI) Part B premiums. 2000. The 24-month waiting period (otherwise required for an individual to establish Medicare eligibility on the basis of a disability) is waived for persons with amyotrophic lateral sclerosis, effective July 1, 2001. The entitlement to Medicare begins with the first month of the Social Security Administration's determination of eligibility for Disability Insurance benefits. 2010. Individuals in the vicinity of Libby, Montana who are diagnosed with an asbestos-related condition are Medicare-eligible beginning March 30, 2010. Medicare eligibility could also apply to individuals in other areas who are diagnosed with a medical condition caused by exposure to a public health hazard for which a future public health emergency is declared under the Comprehensive Environmental Response, Compensation, and Liability Act of 1980. Entitlement to Medicare Part B (also known as Supplementary Medical Insurance Part B Account, or SMI Part B) Benefits 1965. U.S. resident (citizen or lawfully admitted alien with 5 years continuous residence) aged 65 or older or any individual entitled to HI benefits, upon voluntary participation with payment of Part B premium. 1972. Individual under age 65 entitled to HI benefits, upon voluntary participation with payment of Part B premium. Entitlement to Medicare Part D (also known as Supplementary Medical Insurance Part D Account, or SMI Part D) Benefits 2003. For temporary Medicare-endorsed prescription drug discount card program (as a prelude to the new Part D prescription drug program), individual entitled or enrolled under Part A or enrolled in Part B, except those enrolled in Medicaid and entitled to Medicaid outpatient drug coverage, upon voluntary participation with payment of up to $30 annual enrollment fee. Under a Transitional Assistance provision, a drug card-eligible beneficiary whose income does not exceed 135 percent of the federal poverty level and does not have third-party prescription drug coverage is entitled to further benefits. Enrollment begins in May 2004, access to discounts begins in June 2004, and program phases out as drug benefit becomes available in 2006 (see next entry). Beginning January 1, 2006, individual entitled to benefits under Part A or enrolled under Part B, upon voluntary enrollment (including payment of Part D premium, if applicable) in either a stand-alone PDP or an integrated Medicare Advantage plan that offers Part D coverage in its benefit package. Under Part A 1965. In each benefit period, inpatient hospital services, 90 days. Includes semiprivate accommodations, operating room, hospital equipment (including renal dialysis), laboratory tests and X-ray, drugs, dressings, general nursing services, and services of interns and residents in medical osteopathic or dentistry training. Inpatient psychiatric hospital care limited to 190-day lifetime maximum. Outpatient hospital diagnostic services. Post-hospital extended-care services, 100 days (including physical, occupational, and speech therapy). Post-hospital home health services, 100 visits. Deductible and coinsurance provisions (see Table 2.C1). 1967. Lifetime reserve of 60 additional days of inpatient hospital services. Outpatient hospital diagnostic services transferred to SMI. 1972. Services of interns and residents in podiatry training. 1980. Unlimited home health visits in a year. Requirement for prior hospitalization eliminated. Home health services provided for up to 4 days a week and up to 21 consecutive days. Alcohol detoxification facility services. 1981. Part A coinsurance is based on the deductible for the calendar year in which services are received rather than the deductible in effect at the time the beneficiary's spell of illness began, starting in 1982. Alcohol detoxification facility services eliminated. 1982. Beneficiaries expected to live 6 months or less may elect to receive hospice care benefits instead of other Medicare benefits. May elect maximum of two 90-day and one 30-day hospice care periods, effective November 1, 1983, to October 1, 1986. 1984. For durable medical equipment provided by home health agencies, the payment amount is reduced from 100 percent of costs to 80 percent of reasonable charges. 1986. Set the Part A deductible for 1987 at $520 with resulting increases in cost sharing. Increased the Part A deductible annually by the applicable percentage increase in the hospital prospective payment rates. Hospice care benefit (enacted in 1982) made permanent. 1987. Specifies in law that to be eligible for home health care, a Medicare beneficiary must have a restricted ability to leave the home, requiring the assistance of another or the aid of a supportive device (such as crutches, a cane, a wheelchair, or a walker). 1988. Enrollee pays annual hospital deductible (set at $560 for 1989) and Medicare pays balance of covered charges, regardless of the number of days of hospitalization (except for psychiatric hospital care, which is still limited by 190-day lifetime maximum). The number of days in a skilled nursing facility (SNF) changed to 150 per year. Deletes the requirement for a prior hospital stay of 3 or more consecutive days. Expands home health care to provide care for less than 7 days per week and up to 38 consecutive days. Hospice care extended beyond 210 days when beneficiary is certified as terminally ill. All 1988 provisions became effective January 1, 1989. 1989. The spell of illness and benefit period coverage of laws before 1988 return to the determination of inpatient hospital benefits in 1990 and later. After the deductible is paid in benefit period, Medicare pays 100 percent of covered costs for the first 60 days of inpatient hospital care. Coinsurance applies for the next 30 days in a benefit period. The requirement for a prior hospital stay of 3 or more consecutive days is reinstated for SNF services. Coverage returns to 100 days post-hospital care per spell of illness with a daily coinsurance rate in effect for days 21 through 100. Home health services return to a limit of 21 consecutive days of care. Provision providing for home health care for fewer than 7 days per week continued due to a court decision. Hospice care is returned to a lifetime limit of 210 days. 1990. Hospice care is extended beyond 210 days when beneficiary is certified as terminally ill. 1997. Home health services not associated with a hospital or SNF stay for individuals enrolled in both HI and SMI are transferred from the HI program to the SMI program, effective January 1998. The HI program will continue to cover the first 100 visits following a hospital stay of at least 3 consecutive days or an SNF stay. The cost to the SMI trust fund of the transferred services will phase in over a 6-year period (that is, the HI trust fund will transfer funds to the SMI trust fund during that period). Limits on the number of hours and days that home health care can be provided have been clarified. Part-time now defined as skilled nursing and home health aide services (combined) furnished any number of days per week, for less than 8 hours per day and 28 or fewer hours per week. Intermittent now defined as skilled nursing care provided for fewer than 7 days each week, or less than 8 hours each day (combined) for 21 days or less. Hospice benefit periods are restructured to include two 90-day periods, followed by an unlimited number of 60-day periods. Medicare coverage provided for a number of prevention initiatives, most of which are covered under SMI program. HI program affected mainly by two of the initiatives: (1) annual prostate cancer screening for male beneficiaries aged 50 or older, effective January 1, 2000, and (2) colorectal screening procedures, including fecal-occult blood tests and flexible sigmoidoscopies, for beneficiaries aged 50 or older, colonoscopy for beneficiaries at high risk for colorectal cancer, and other procedures, including screening barium enemas under certain circumstances. 2000. The homebound criterion for home health services is clarified to specify that beneficiaries who require home health services may attend adult day care for therapeutic, psychosocial, or medical treatment and still remain eligible for the home health benefit. Homebound beneficiaries may also attend religious services without being disqualified from receiving home health benefits. Screening colonoscopies are covered for all beneficiaries, not just for those at high risk, beginning July 1, 2001. For persons not at high risk, a screening colonoscopy is covered 10 years after a previous one, or 4 years after a screening flexible sigmoidoscopy. (See 1997.) Under Part B 1965. Physician and surgeon services. In-hospital services of anesthesiologists, pathologists, radiologists, and psychiatrists. Limited dental services. Home health services, 100 visits in calendar year. Other medical services including various diagnostic tests, limited ambulance services, prosthetic devices, rental of durable medical equipment used at home (including equipment for dialysis), and supplies used for fractures. For deductible and coinsurance provisions, see Table 2.C1. Beginning in 1966, the beneficiary pays a $50 deductible, with a 3-month carryover provision. 1967. Outpatient hospital diagnostic services transferred from HI. Includes physical therapy services in a facility. Purchase of durable medical equipment. 1972. Physical therapy services furnished by a therapist in his or her office or individual's home (calendar year limit of $100). Chiropractor services (limited to manual manipulation of the spine). Outpatient services include speech pathology services furnished in, or under arrangements with, a facility or agency. Services of a doctor of optometry in furnishing prosthetic lenses. Beginning in 1973, the beneficiary pays a $60 deductible. 1977. Services in rural health clinics. 1980. Home health services. Deductible applicable to home health services is eliminated, effective July 1, 1981. Facility costs of certain surgical procedures performed in freestanding ambulatory surgical centers. Increase in annual limit for outpatient therapy from $100 to $500. Recognizes comprehensive outpatient rehabilitation facilities as Medicare providers. 1981. Beginning in 1982, the beneficiary pays a $75 deductible, with the carryover provision eliminated. 1984. Hepatitis B and pneumococcal vaccines and blood clotting factors and necessary supplies are included as Part B benefits. Debridement of mycotic toenails is limited. For outpatient physical therapy services, includes services of a podiatrist. For outpatient ambulatory surgery, includes services of a dentist and podiatrist furnished in his or her office. 1986. Includes vision care services furnished by an optometrist. For occupational therapy services, includes services furnished in an SNF (when Part A coverage has been exhausted), in a clinic, rehabilitation agency, public health agency, or by an independently practicing therapist. Includes outpatient (in addition to previously covered inpatient) immunosuppressive drugs for 1 year after covered transplant. Includes occupational therapy services provided in certain delivery settings. For ambulatory surgical procedures performed in ambulatory surgical centers, hospital outpatient departments, and certain physician offices, the Part B coinsurance and deductible are no longer waived. 1987. Increases the maximum payment for mental health services and includes outpatient mental health services provided by ambulatory hospital-based or hospital-affiliated programs under the supervision of a physician. Services provided by clinical social workers when furnished by risk-sharing HMOs and competitive medical plans, physician assistants in rural health manpower shortage areas, clinical psychologists in rural health clinics and community mental health centers, and certified nurse midwives. Coverage of outpatient immunosuppressive drugs (see 1986) is broadened and clarified to include prescription drugs used in immunosuppressive therapy. Specifies in law that to be eligible for home health care, a Medicare beneficiary must have a restricted ability to leave the home, requiring the assistance of another or the aid of a supportive device (such as crutches, a cane, a wheelchair, or a walker). 1988. Beginning January 1, 1990, the beneficiary pays a $75 deductible and 20 percent coinsurance, but once out-of-pocket expenses for the deductible and coinsurance exceed $1,370, Medicare pays 100 percent of allowable charges for remainder of year. Beginning in 1991, Medicare pays 50 percent of the cost of outpatient prescription drugs above $600. When fully implemented in 1993, Medicare will pay 80 percent of prescription drug costs above a deductible that assumes that 16.8 percent of Part B enrollees will exceed the deductible. Certain prescription drugs administered in an outpatient or home setting, including immunosuppressive drugs (previously covered for 1 year after a covered transplant), home intravenous drugs, and certain others, will be covered in 1990 under a new prescription drug provision. 1989. Provisions enacted in 1988 and to begin in 1990 and 1991 are repealed, and benefits are restored to levels in effect before January 1, 1989. Limits on mental health benefits eliminated in 1990. Coverage extended to services of clinical psychologists and social workers. The annual payment limits of $500 per beneficiary for outpatient physical therapy services and outpatient occupational therapy services, each, are raised to $750 for 1990 and later. (See 1980.) 1990. Beginning in 1991, routine mammography screenings are covered. The Part B deductible is set at $100 in 1991 and subsequent years. Beginning in 1992, physicians' services are reimbursed on a fee-schedule basis. 1993. Includes coverage of oral, self-administered anticancer drugs. Lengthens the coverage period for immunosuppressive drugs after a transplant to 18 months in 1995, 24 months in 1996, 30 months in 1997, and 36 months thereafter. (See 1986.) The annual payment limits of $750 per beneficiary for outpatient physical therapy services and outpatient occupational therapy services, each, are raised to $900 for 1994 and later. (See 1989.) 1997. Home health services not associated with a hospital or SNF stay for individuals enrolled in both HI and SMI are transferred from the HI program to the SMI program, effective January 1998. The HI program will continue to cover the first 100 visits following a hospital stay of at least 3 consecutive days or an SNF stay. The cost to the SMI trust fund of the transferred services will phase in over a 6-year period, while the cost of the home health services will phase into the SMI premium over 7 years. Coverage provided for a number of prevention initiatives, including (1) annual screening mammograms for female beneficiaries aged 40 or older, with SMI deductible waived; (2) screening pap smear and pelvic exam (including clinical breast exam) every 3 years or annually for beneficiaries at higher risk, with SMI deductible waived; (3) annual prostate cancer screening for male beneficiaries aged 50 or older, effective January 1, 2000; (4) colorectal screening procedures, including fecal occult blood tests and flexible sigmoidoscopies, for beneficiaries aged 50 or older, colonoscopy for beneficiaries at high risk for colorectal cancer, and other procedures, including screening barium enemas under certain circumstances; (5) diabetes outpatient self-management training in nonhospital-based programs (previously covered in hospital-based programs only) and blood glucose monitors and testing strips for all diabetics (previously provided for insulin-dependent diabetics only), effective July 1, 1998; (6) procedures to identify bone mass, detect bone loss, or determine bone quality for certain qualified beneficiaries, at frequencies determined by the secretary of Health and Human Services, effective July 1, 1998. Beginning January 1999, an annual beneficiary limit of $1,500 will apply to all outpatient physical therapy services, except for services furnished by a hospital outpatient department. A separate $1,500 limit will also apply to outpatient occupational therapy services, except for services furnished by hospital outpatient departments. Beginning with 2002, these caps will be increased by the percentage increase in the Medical Economic Index. (See 1993.) 1999. The coverage period for immunosuppressive drugs after a transplant is lengthened to 44 months, for individuals who exhaust their 36 months of coverage in 2000. For those exhausting their 36 months of coverage in 2001, at least 8 more months will be covered. (The secretary of Health and Human Services will specify the increase, if any, beyond 8 months.) For those exhausting their 36 months of coverage in 2002, 2003, or 2004, the number of additional months may be more or fewer than 8. (The secretary will specify the increase for each of these years.) (See 1993.) The annual payment limits of $1,500 per beneficiary for outpatient physical therapy services and outpatient occupational therapy services, each, for services furnished by independent practitioners (that is, not by a hospital outpatient department) are suspended for 2000 and 2001. (See 1997.) 2000. Coverage for screening pap smears and pelvic exams (including a clinical breast exam) is provided every 2 years (increased from every 3 years) beginning July 1, 2001. (Annual coverage continues for beneficiaries at higher risk, and SMI deductible continues to be waived.) (See 1997.) Annual coverage of glaucoma screenings is provided for certain high-risk beneficiaries, effective January 1, 2002. Screening colonoscopies are covered for all beneficiaries, not just for those at high risk, beginning July 1, 2001. For persons not at high risk, a screening colonoscopy is covered 10 years after a previous one, or 4 years after a screening flexible sigmoidoscopy. (See 1997.) Coverage is provided for medical nutrition therapy services under certain circumstances for beneficiaries who have diabetes or a renal disease, effective January 1, 2002. The amount of a beneficiary's copayment for a procedure in a hospital outpatient department is limited, beginning April 1, 2001, to the hospital inpatient deductible applicable for that year. Also, the secretary of Health and Human Services must reduce the effective copayment rate for outpatient services to a maximum rate of 57 percent in 2001 (for services received after April 1), 55 percent in 2002 and 2003, 50 percent in 2004, 45 percent in 2005, and 40 percent in 2006 and later. Time and budget limitations are removed on the coverage of immunosuppressive drugs, making coverage of these drugs a permanent benefit for beneficiaries who have received a covered organ transplant. (See 1999.) The annual payment limits of $1,500 per beneficiary for outpatient physical therapy services and outpatient occupational therapy services, each, for services provided by independent practitioners (that is, not by a hospital outpatient department), which were suspended for 2000 and 2001, are also suspended for 2002. (See 1999.) The homebound criterion for home health services is clarified to specify that beneficiaries who require home health services may attend adult day care for therapeutic, psychosocial, or medical treatment and still remain eligible for the home health benefit. Homebound beneficiaries may also attend religious services without being disqualified from receiving home health benefits. 2003. The Part B deductible remains at $100 through 2004 and increases to $110 in 2005. Beginning in 2006, it will be increased each year by the annual percentage increase in the Part B aged actuarial rate. A one-time, initial preventive physical exam is covered within 6 months of a beneficiary's first coverage under Part B, beginning January 1, 2005, for beneficiaries whose Part B coverage begins on or after that date. Certain screening blood tests are covered for the early detection of cardiovascular disease and abnormalities associated with elevated risk for such disease, including certain tests for cholesterol and other lipid or triglyceride levels, effective January 1, 2005, under frequency standards to be established (but not to exceed once every 2 years). Diabetes screening tests, including a fasting plasma glucose test and other such tests determined appropriate by the secretary of Health and Human Services, are covered for beneficiaries at risk for diabetes, beginning January 1, 2005, under frequency standards to be established (but not to exceed two times per year). 2005. The colorectal screening benefit (see 1997 and 2000) is exempt from the Part B deductible, effective January 2007. Exceptions to the financial limits on therapy services not provided by a hospital outpatient department are allowed for services furnished in 2006, if such services are determined to be medically necessary. (See 1997, 1999, and 2000.) 2006. Exceptions to the financial limits on nonhospital therapy services when deemed medically appropriate are extended through December 31, 2007. (See 2005.) 2007. Exceptions to the financial limits on nonhospital therapy services when deemed medically appropriate are extended through July 1, 2008. (See 2005 and 2006). 2008. For outpatient mental health services, the percentage of approved charges for which the beneficiary is liable phases down from 50 percent to 20 percent, over the 5-year period 2010–2014. For the one-time, initial preventive examination (see 2003), the Part B deductible is waived, the eligibility period is extended from 6 months to 1 year after enrollment in Part B, measurement of body mass index is covered, and, upon agreement with the beneficiary, end-of-life planning is covered. Effective January 1, 2009. Exceptions to the financial limits on nonhospital therapy services when deemed medically appropriate are extended through December 31, 2009. (See 2005, 2006, and 2007.) 2009. Exceptions to the financial limits on nonhospital therapy services when deemed medically appropriate are extended through March 31, 2010. (See 2005, 2006, 2007, and 2008.) 2010. An annual wellness visit to develop or update a personalized prevention plan is covered, with no beneficiary cost sharing, effective January 1, 2011. Beneficiary cost sharing is eliminated for preventive services recommended with a grade of A or B by the U.S. Preventive Services Task Force, and the Part B deductible is waived for colorectal cancer screening tests, both effective January 1, 2011. Exceptions to the financial limits on nonhospital therapy services when deemed medically appropriate are extended through December 31, 2010. (See 2005, 2006, 2007, 2008, and 2009.) Under Parts A and B 1965. Requires that Medicare be secondary payer to benefits provided by liability insurance policies or under no-fault insurance. 1981. Requires that Medicare be secondary payer to employer-based group health plans for beneficiaries entitled to Medicare solely on the basis of end-stage renal disease (ESRD) for up to 12 months. 1982. For workers and their spouses aged 65 to 69, Medicare is the secondary payer when benefits are provided under an employer-based group health plan (applicable to employers with 20 or more employees who sponsor or contribute to the group plan). Health maintenance organizations (HMOs) will be authorized as providers of benefits. The secretary of Health and Human Services must certify the prospective payment mechanism for HMOs before implementation. 1984. Medicare secondary-payer provisions are extended to spouses aged 65 to 69 of workers under age 65 whose employer-based group health plan covers such spouses. For HMOs, includes medical and other health services furnished by clinical psychologists. 1985. Provides payment for liver transplant services. 1986. Extends the working-age, secondary-payer provision to cover workers and their spouses beyond age 69. For HMOs that offered organ transplants as a basic health service on April 15, 1985, such services may be offered from October 1, 1985, through April 1, 1988. For disabled individuals who are covered by employer-based health plans (with at least 100 employees), Medicare is the secondary payer, effective for the period from 1987 to 1991. 1987. Requires HMOs and competitive medical plans that cease to contract with Medicare to provide or arrange supplemental coverage of benefits related to preexisting conditions for the lesser of 6 months or the duration of an exclusion period. Specifies in law that to be eligible for home health care, a Medicare beneficiary must have a restricted ability to leave the home, requiring the assistance of another or the aid of a supportive device (such as crutches, a cane, a wheelchair, or a walker). Clarifies that the secondary-payer provision for disabled individuals covered under employer-based health plans for employers with at least 500 employees applies to employers who are government entities. 1990. Requires that Medicare be the secondary payer to employer-based group health plans for beneficiaries entitled to Medicare solely on the basis of ESRD for up to 18 months (extended from 12 months), effective February 1, 1991, to January 1, 1996. The secondary-payer provision for disabled beneficiaries covered under large employer plans (see 1986) is effective through September 30, 1995. 1993. The secondary-payer provision for disabled beneficiaries covered under large employer plans is effective through September 30, 1998. The secondary-payer provision for beneficiaries with ESRD applies to all beneficiaries with end-stage renal disease, not only those entitled to Medicare solely on the basis of ESRD. The extension to include the first 18 months of an individual's entitlement on the basis of ESRD is effective through September 30, 1998. 1996. The Medicare Integrity Program (MIP) is created, providing dedicated funds to identify and combat improper payments, including those caused by fraud and abuse, and, for the first time, allowing for contracts to be awarded competitively to entities other than carriers and intermediaries to conduct these activities. 1997. Established an expanded set of options for the delivery of health care under Medicare, referred to as Medicare+Choice (and also known as "Medicare Part C"). All Medicare beneficiaries can receive their Medicare benefits through the original fee-for-service program. In addition, most beneficiaries can choose instead to receive their Medicare benefits through one of the following Medicare+Choice plans: (1) coordinated care plans (such as HMOs, provider-sponsored organizations, and PPOs), (2) Medical Savings Account (MSA)/High Deductible plans (through a demonstration available for up to 390,000 beneficiaries), or (3) private fee-for-service plans. Except for MSA plans, all Medicare+Choice plans are required to provide the current Medicare benefit package (excluding hospice services) and any additional health services required under the adjusted community rate (ACR) process. MSA plans provide Medicare benefits after a single high deductible is met, and enrollees receive an annual deposit in their medical savings account. Transition rules for current Medicare HMO program also provided. (See also HMO provision of 1982.) The provision making Medicare the secondary payer for disabled beneficiaries covered under large employer plans, previously scheduled to expire September 30, 1998, made permanent. The provision making Medicare the secondary payer for the first 12 months of entitlement because of ESRD, which had been extended on a temporary basis (through September 30, 1998) to include the first 18 months of entitlement, has been extended, permanently, to include the first 30 months of entitlement on the basis of ESRD. 2003. Medicare+Choice is renamed Medicare Advantage. (It is still sometimes referred to as "Medicare Part C.") As before, beneficiaries enrolled in both Part A and Part B can receive their Medicare benefits through the original fee-for-service program; most can opt instead to use a Medicare Advantage plan in their area. Medicare Advantage plans include (1) Medicare Managed Care plans (like HMOs), (2) Medicare Preferred Provider Organization plans (PPOs), (3) Private Fee-for-Service plans, and (4) Medicare Specialty plans (available in some areas to provide Medicare benefits for certain people with special needs, such as beneficiaries in institutions). Beginning in 2006, Medicare Advantage plan choices will be expanded to include regional PPOs. Participating regional PPOs will be required to serve an entire region (10 to 50 regions are to be established), and there are provisions to encourage plan participation. Regional PPOs must have a single deductible for benefits under Parts A and B, and they must include catastrophic limits for out-of-pocket expenditures. Beginning in 2006, the adjusted community rate (ACR) process for determining plan payments is replaced by a competitive bidding process. (Historical reference points to this item include the Medicare+Choice provision of 1997 and the HMO provision of 1982, both of which are displayed in this section.) 2007. Group health plans are required to provide information identifying situations in which the plan is, or has been, primary to Medicare, effective January 2009. Effective June 2009, liability insurance, no-fault insurance, and workers' compensation plans must submit specific information to enable appropriate determinations concerning coordination of benefits and any applicable recovery claims. Under Part D 2003. Under temporary Medicare-endorsed prescription drug discount card program, for eligible beneficiaries voluntarily enrolling and paying up to $30 annually, discounts on certain prescription drugs, as specified by card sponsors. Under Transitional Assistance provision, eligible beneficiaries whose incomes do not exceed 135 percent of the federal poverty level and do not have third-party prescription drug coverage are eligible for (1) financial assistance of up to $600 per year for purchasing prescription drugs and (2) a subsidized enrollment fee under the temporary Medicare-endorsed prescription drug discount card program. Enrollment begins in May 2004, access to discounts begins in June 2004, and program phases out as drug benefit becomes available in 2006 (see next entry). Beginning January 1, 2006, upon voluntary enrollment in either a stand-alone PDP or an integrated Medicare Advantage plan that offers Part D coverage in its benefit, subsidized prescription drug coverage. Most FDA-approved drugs and biologicals are covered. However, plans may set up formularies for their drug coverage, subject to certain statutory standards. (Drugs currently covered in Parts A and B remain covered there.) Part D coverage can consist of either standard coverage or an alternative design that provides the same actuarial value. (For an additional premium, plans may also offer supplemental coverage exceeding the value of basic coverage.) Standard Part D coverage is defined for 2006 as having a $250 deductible, with 25 percent coinsurance (or other actuarially equivalent amounts) for drug costs above the deductible and below the initial coverage limit of $2,250. The beneficiary is then responsible for all costs until the $3,600 out-of-pocket limit (which is equivalent to total drug costs of $5,100) is reached. For higher costs, there is catastrophic coverage; it requires enrollees to pay the greater of 5 percent coinsurance or a small copay ($2 for generic or preferred multisource brand and $5 for other drugs). After 2006, these benefit parameters are indexed to the growth in per capita Part D spending (see Table 2.C1). In determining out-of-pocket costs, only those amounts actually paid by the enrollee or another individual (and not reimbursed through insurance) are counted; the exception is cost-sharing assistance from Medicare's low-income subsidies (certain beneficiaries with low incomes and modest assets will be eligible for certain subsidies that eliminate or reduce their Part D premiums, cost-sharing, or both) and from State Pharmacy Assistance Programs. A beneficiary premium, representing 25.5 percent of the cost of basic coverage on average, is required (except for certain low-income beneficiaries, as previously mentioned, who may pay a reduced or no premium). For PDPs and the drug portion of Medicare Advantage plans, the premium will be determined by a bid process; each plan's premium will be 25.5 percent of the national weighted average plus or minus the difference between the plan's bid and the average. To help them gain experience with the Medicare population, plans will be protected by a system of risk corridors, which allow Part D to assist with unexpected costs and to share in unexpected savings; after 2007, the risk corridors became less protective. To encourage employer and union plans to continue prescription drug coverage to Medicare retirees, subsidies to these plans are authorized; the plan must meet or exceed the value of standard Part D coverage, and the subsidy pays 28 percent of the allowable costs associated with enrollee prescription drug costs between a specified cost threshold ($250 in 2006, indexed thereafter) and a specified cost limit ($5,000 in 2006, indexed thereafter). 2008. Part D plans are required to include two classes of drugs in their formularies: (1) benzodiazepines and (2) for the treatment of epilepsy, cancer, or chronic mental disorder, barbiturates. Effective January 1, 2013. 2010. Beneficiaries who enter the coverage gap in 2010 receive a $250 rebate and, starting in 2011, beneficiaries receive a 50-percent discount on covered brand-name prescription drugs. (The dollar value of this discount counts toward out-of-pocket spending, even though the beneficiary does not incur the cost.) Additionally, reductions in beneficiary cost sharing for both brand-name and generic drugs during the coverage gap are to be phased in beginning in 2011, such that by 2020, the coverage gap will be closed, and beneficiaries will be responsible for 25 percent of their prescription drug costs. Retiree drug subsidies paid to employers and unions that provide continued prescription drug coverage to Medicare retirees (and meet specific criteria in doing so) are taxable beginning in 2013. Hospital Insurance Taxes See Table 2.A3. 2010. Beginning in 2013, an additional Part A payroll tax of 0.9 percent is collected on earned income exceeding $200,000 (for those filing income tax singly) and $250,000 (for those filing jointly). The earnings thresholds are not indexed. Appropriations from General Revenues 1965. For HI costs attributable to transitionally insured beneficiaries. For HI costs attributable to noncontributory wage credits granted for military service prior to 1957 (see Table 2.A2). For the Part B program, an amount equal to participant premiums. 1972. For cost of Part B not met by enrollee premiums. 1982. For HI costs attributable to beneficiaries having transitional entitlement based on Medicare-qualified federal employment. 1983. For HI taxes on noncontributory wage credits granted for military service (a) from the inception of HI program through 1983 and (b) on a current basis, annually, beginning in 1984 (see Table 2.A2). 2002. Eliminated for HI taxes on noncontributory wage credits granted for military service on a current basis, for all years after calendar year 2001 (see Table 2.A2). 2003. For Part D costs not met by enrollee premiums or otherwise, beginning in January 2006. (That is, transfers from general revenues [plus smaller income sources, particularly the payments from states described below] will pay for (1) the 74.5 percent subsidy to PDPs and the prescription drug portion of Medicare Advantage plans [which remains after enrollee premiums of 25.5 percent, on average], in the form of a direct subsidy and reinsurance, and (2) for other Part D costs, such as low-income subsidies and subsidies to employers who provide qualifying drug coverage to their Medicare-eligible retirees.) Beginning January 2007, for Part B beneficiaries meeting certain income thresholds and thus paying income-related adjustment amounts in addition to their standard Part B premiums (see "Medicare Financing, Participant Premiums, 2003"), the per capita general revenue appropriations to Part B (see 1965 and 1972) are supposed to be reduced accordingly. 2010. Beginning January 2011, for Part D beneficiaries meeting certain income thresholds and thus paying income-related adjustment amounts in addition to their Part D premiums (see "Medicare Financing, Participant Premiums, 2010"), the per capita general revenue appropriations to Part D (see 2003) are supposed to be reduced accordingly. See Table 2.C1. 1965. Part B enrollee premium rate (originally $3 per month) to be established annually such that it will pay one-half of program costs. 1972. Part B enrollee premium rate increase limited to rate of increase in OASDI cash benefits. HI premium (originally $33 per month) to be established annually. Only individuals not otherwise entitled to HI but desiring voluntary participation need to pay the HI premium. 1983. Part B enrollee premiums for July 1983 to December 31, 1983, frozen at premium level of June 30, 1983. Premiums for January 1, 1984, to December 31, 1985, set to cover 25 percent of aged program costs. 1984. Part B enrollee premiums for January 1, 1986, to December 31, 1987, will be set to cover 25 percent of aged program costs. Increases in the Part B premium may not exceed the dollar amount of the Social Security cost-of-living adjustment. For calculating the amount of Part B premium surcharge for individuals aged 65–70 not previously enrolled in Part B, the number of years an individual did not enroll because of coverage by employer group health insurance will not be taken into account. 1985. Extends through calendar year 1988 the requirement that Part B premiums be set to cover 25 percent of aged program costs and that increases in the Part B premium may not exceed the dollar amount of the Social Security cost-of-living adjustment. Premium-paying individuals who do not purchase Part A coverage within a specific time after becoming eligible because of age are subject to a 10 percent penalty for each 12 months they are late in enrolling. There is a cutoff on the length of time these individuals will have to pay an enrollment penalty. The 10 percent premium penalty would be limited to twice the number of years enrollment was delayed. Therefore, if enrollment was delayed 1 year, the penalty would be assessed for 2 years. Individuals in this category and already enrolled will have the length of time the higher premium was paid credited to them. 1987. Extends through calendar year 1989 the provisions requiring that the Part B premium be set to cover 25 percent of aged program costs, prohibiting any increase in the premium if there is no Social Security cost-of-living adjustment, and continuing to hold beneficiaries harmless from Social Security check reductions as a result of a premium increase. 1988. Increases in the Part B premium may not exceed the dollar amount of the Social Security cost-of-living adjustments for 1989 and beyond. 1989. Extends through calendar year 1990 the requirement that Part B premiums be set to cover 25 percent of aged program costs. 1990. The Part B premium is set at $29.90 in 1991, $31.80 in 1992, $36.60 in 1993, $41.10 in 1994, and $46.10 in 1995. 1993. Part B enrollee premiums for January 1, 1996, to December 31, 1998, will be set to cover 25 percent of aged program costs. 1997. The Part B premium is permanently set at 25 percent of program costs. 2003. Beginning January 2007, the Part B premium is increased for beneficiaries meeting certain income thresholds. (Beneficiaries with modified adjusted gross incomes under $80,000 will continue to pay premiums that are 25 percent of twice the actuarial rate. Actuarial rate is defined as one-half of the Part B expected monthly cost per enrollee. For beneficiaries with incomes greater than $80,000 and less than or equal to $100,000, the applicable percentage is 35 percent; for those with incomes greater than $100,000 and less than or equal to $150,000, the percentage is 50 percent; for incomes greater than $150,000 and less than or equal to $200,000, the percentage is 65 percent; and for incomes greater than $200,000, the percentage is 80 percent. For married couples who file joint tax returns, the income thresholds are doubled. For beneficiaries who are married and lived with their spouses at any time during the taxable year but who file separate tax returns from their spouses, with incomes greater than $80,000 and less than or equal to $120,000, the percentage is 65 percent; with incomes greater than $120,000, the percentage is 80 percent. These thresholds are to be updated each calendar year by the Consumer Price Index (CPI). There is a 5-year adjustment period for this provision as well; that is, the amount of premium above 25 percent of twice the actuarial rate is phased in—at 20, 40, 60, 80, and 100 percent for 2007 to 2011 and later, respectively.) For military retirees, their spouses (including eligible divorced spouses and widows and widowers), and dependent children who enroll(ed) in Part B during the period from 2001 to 2004, the late enrollment penalty imposed on beneficiaries who do not enroll in Part B upon becoming eligible for Medicare is waived for premium payments for January 2004 and later. (Also, a special enrollment period for these beneficiaries is to begin as soon as possible and end December 31, 2004.) For Part D, beginning in January 2006, a beneficiary premium, representing 25.5 percent of the cost of basic coverage on average, is required (except for certain low-income beneficiaries who may pay a reduced or no premium). For PDPs and the drug portion of Medicare Advantage plans, the premium will be determined by a bid process; each plan's premium will be 25.5 percent of the national weighted average plus or minus the difference between the plan's bid and the average. A late enrollment penalty will apply for certain beneficiaries who fail to enroll at the first opportunity and who do not maintain creditable coverage elsewhere (external prescription drug coverage, such as through a retiree group health plan that meets or exceeds the actuarial value of standard Part D coverage). 2005. The phase-in of the income-related Part B premium (see 2003) is shortened from 5 years to 3 years, beginning January 1, 2007. (That is, the amount of premium above 25 percent of twice the actuarial rate is phased in at 1/3 for 2007, 2/3 for 2008, and 3/3 for 2009 and later.) For beneficiaries who are volunteering outside the United States through a 12-month or longer program sponsored by a tax-exempt organization and who have other health insurance, the late enrollment penalties imposed on beneficiaries who do not enroll in Part B upon becoming eligible for Medicare are waived, effective January 2007, and a special enrollment period for these beneficiaries is established. 2008. The policy waiving the late enrollment penalty for Part D enrollees who meet certain low-income and limited-resources requirements is codified into statute. (The policy was in effect through 2008 and the law is effective beginning January 1, 2009.) 2010. The income thresholds used to calculate Part B income-related premiums are frozen at 2010 levels for 2011 through 2019. Beginning in January 2011, Part D enrollees whose income exceeds certain thresholds are required to pay higher Part D premiums. The income thresholds and premium adjustments are to be set in the same manner as those under Part B (including the use of frozen thresholds in 2011–2019). Income from Taxation of OASDI Benefits 1993. The additional income tax revenues resulting from the increase in the taxable percentage applicable to OASDI benefits (an increase from 50 percent to 85 percent, see Table 2.A31) are transferred to the HI trust fund. Payment from States 2003. Beginning in January 2006, with the availability of drug coverage and low-income subsidies under Part D, Medicaid will no longer be primary payer for full-benefit dual eligibles, and states are required to make payments to defray a portion of the Part D drug expenditures for these beneficiaries. States pay 90 percent of the estimated costs for 2006, phasing down over a 10-year period to 75 percent for 2015 and later. 1981. See Table 2.A6. 1983. See Table 2.A6. CONTACT: Barbara S. Klees (410) 786-6388 or [email protected]. 1 These summaries were prepared by Barbara S. Klees, Christian J. Wolfe, and Catherine A. Curtis, Office of the Actuary, Centers for Medicare & Medicaid Services, 7500 Security Blvd., Baltimore, MD 21244. The authors wish to express their gratitude to Mary Onnis Waid, who originated these summaries and diligently prepared them for many years before her retirement.	2	65	1	0	1	0.62229	2	20,392
- Fertilization Movie) Note though there can be subtle differences in the fertilization process which occurs naturally within the body or through reproductive technologies outside the body, the overall product in both cases is a diplod zygote. — “UNSW Embryology- Week 1 Fertilization”, embryology.med.unsw.edu.au - fertilization (reproduction), union of a spermatozoal nucleus, of paternal origin, with an egg nucleus, of maternal origin, to form the primary nucleus of an embryo. In all organisms the essence of fertilization is, in fact, the fusion of the. — “fertilization (reproduction) -- Britannica Online Encyclopedia”, - Fertilization Fertilization. Before she actually starts growing, you'll set the stage. Last week an increase in the amount of estrogen and progesterone coursing through your bloodstream prompted your uterus to form a lush, blood-rich lining of. — “Fertilization \| BabyCenter”, - Its the process of fertilization from where it begins. Before ovulation, mucus is These two nuclei then move to form a set of chromosomes, this them is the fertilized egg or zygote. — “human fertilization”, - In Vitro Fertilization is a process during which egg cells, which have been harvested In Vitro Fertilization is a process during which egg cells, which. — “In Vitro Fertilization”, - fertilization n. The act or process of initiating biological reproduction by insemination or pollination. — “fertilization: Definition from ”, - For fertilization in humans See: Human fertilization If fertilization takes place, the sperm usually meet the ovum in the fallopian tube, requiring the sperm. — “Fertilization - Psychology Wiki”, - After fertilization, a period of 14 days that follows is referred to as the pre-embryonic period. The process of in vitro fertilization (IVF) is widely considered to be a marvel of modern reproductive science. — “Fertilization - Topic - Associated Content from Yahoo!”, - Definition of fertilization in the Medical Dictionary. fertilization explanation. Information about fertilization in Free online English dictionary. What is fertilization? Meaning of fertilization medical term. What does fertilization mean?. — “fertilization - definition of fertilization in the Medical”, medical- - If fertilization does not take place, this ovum gets released in the mentrual phase. When is fertilization and pregnancy most likely to occur? Fertilization of an egg can. — “Fertilization”, - Get information, facts, and pictures about fertilization at . Make research projects and school reports about fertilization easy with credible articles from our FREE, online encyclopedia and dictionary. — “fertilization Facts, information, pictures \| ”, - In *ual reproduction, fertilization involves the donation of genes from two parents which results in the production of offspring with a mix of inherited genes. — “ual Reproduction: Fertilization”, - Scientific article describing fertilization, the union of an ovum and sperm usually occurring in the development of an embryo. — “Fertilisation (Conception) - Wikipedia”, - Definition and other additional information on Fertilization from Biology- dictionary. — “Fertilization - definition from Biology-”, biology- - Fertilization is more a chain of events than a single, isolated phenomenon. Fertilization by more than one sperm - polyspermy - almost inevitably leads to early embryonic death. — “Fertilization”, vivo.colostate.edu - Normally, an egg and sperm are fertilized inside a womans body. If the doctor thinks the chance of fertilization is low, the laboratory staff may directly inject the sperm into the egg. — “In vitro fertilization (IVF)”, - Fertilization. Learn about Fertilization on . Get information and videos on Fertilization including articles on wiki, vitro, miraculously and more!. — “Fertilization \| Answerbag”, - While the cost of in vitro fertilization is high, it's the last hope of conceiving a child for many couples. The average cost for one cycle of in vitro fertilization is around $12,400. Typically, this includes lab screenings for both parents, your ultrasound. — “Cost of In Vitro Fertilization - LoveToKnow Pregnancy”, - The process of In Vitro fertilization has been very popular despite it being a debatable issue for many. — “Fertilization - Pregnancy Fertilization - Pregnancy”, pregnancy- - Fertilization definition, an act, process, or instance of fertilizing. fertilization (fûr'tl-ĭ-zā'shən) Pronunciation Key. The process by which two gametes (reproductive cells having a single, haploid set of chromosomes) fuse to become a zygote, which develops into a new organism. — “Fertilization \| Define Fertilization at ”, - The egg can be fertilized for about 24 hours after ovulation. The fertilized egg (called a zygote) continues to divide as it passes slowly through the fallopian tube to the uterus where its next job is to attach. — “Pregnancy and conception”, - Definition of fertilization in the Online Dictionary. Meaning of fertilization. Pronunciation of fertilization. Translations of fertilization. fertilization synonyms, fertilization antonyms. Information about fertilization in the free online. — “fertilization - definition of fertilization by the Free”, related images for fertilization - Monosomy Fertilization CTI view large image Structural - Cement Fertilization GIF - fertilization big png - Our technician applying a granular fertilizer - Is an embryo or fetus a human When does it become a human at fertilization - A intermediate scale of disturbances are maintaining maximum biodiversity - FERTILIZATION jpg - Our fertilization crews come prepared to handle any kind of weed - Strategic Project Forest Fertilization 002 jpg - 我々と米国ベイラー医科大学の共同研究において排卵過程の卵丘細胞を材料としたマイクロアレイ解析により初期免疫に関わる因子が排卵 - potatoes and cord jpg 22 May 2009 08 57 58k Crick and Watson jpg 22 May 2009 08 16 46k fertilization diagra > 22 May 2009 08 06 52k from person to gene jpg 22 May 2009 07 57 57k - fertilization services jpg - DRGNTOY GIF 14 Feb 2009 23 27 252K Image gif ELYSIANO GIF 14 Feb 2009 23 27 113K Image gif Fertilization gif 14 Feb 2009 23 27 202K Image gif - fertilizationf jpg - menstrual cycle This animation from the CD Audio Important describes the late events in the menstrual cycle Zygote Formation If sperm are present in the oviduct at the time of ovulation fertilization takes place in the oviduct Zygotes form as a result of fertilization In fertilization the - fertilization 5 jpg - binge feed your grass Fertilizing over a period of time keeps your grass consistent As with most things overdoing it can be as harmful as doing without - the gamonts of Monocystis lumbrici have released their isogametes which are actively fusing in this view 400x - Экстракорпоральное оплодотворение ЭКО - Back to Overview - Our technician applying a granular fertilizer - Normal Fertilization CTI view large image - the soil for absorption by the root system Plant leaves are very effective at absorbing nutrients and making them available for plant growth Using Foliar Fertilizers in the Organic Garden While it s not a substitute for building a healthy fertile garden soil foliar fertilization is a great supplement for providing an extra boost to your plants in the midst of the growing - Crazy 015 - Fertilization Site - Posted by Kate Stravinskas at 11 01 00 AM \| 0 Comment s Do you want a healthy and beautiful green lawn this fall With Greenview s Zero Phosphate Fall Fertilizer you ll get the lawn you always wanted while being eco friendly Phosphorous - cell to make wouldn t you say Here s a diagrammatic look at the cellular events that take place in the ovule as an egg cell is differentiated The journey of the pollen tube is shown here And here s another drawing that might help Compare these with the beautiful photo in the book of a germinating pollen grain Everything fitting together OK A look at how one - Fertilization 1 - GCMGA2369 101 Lawn Fertilization GIF - or featured on its web site To Print Program Right click anywhere within the outline of the program and select Print or Print Picture from the drop down or pop up window that appears SEE ALSO Grow The Perfect Lawn - Trisomy Fertilization CTI view large image - Raspberry Fertilization To use any of the clipart images above including the thumbnail image in the top left corner just click and drag the picture to your desktop You may also control click Mac or right click - Information from the Virginia Cooperative Extension seminar can be viewed and downloaded by clicking on the image below Forest Lakes Neighborhood Watch - A property that subscribes to our 6 Step Fertilization Program - 1 55 N Fertilization Considerations for Cotton Nitrogen fertilization should be considered in irrigated fields making good progress Figure 1 link to figure shows a typical N uptake curve for cotton and corresponding crop development stages Suggestions for applications of approximate percentages of total N are also shown A one - Fertilization 2006 acrylic on canvas 30 x 40 SOLD - Strategic Project Forest Fertilization 022 jpg related videos for fertilization - Invitro Fertilization - A couple's story Linda and Nils had been trying for years to have a baby. They finally tried Invitro Fertilization, or IVF, and the results were doubly as gratifying! Robert Edwards won the 2010 Nobel Prize in medicine co-founding in-vitro fertilization technique. - Experts Say In Vitro Fertilization Could Lead To Eugenics Benedict XVI recalled that while scientific advances in genetics have helped improve the diagnosis of diseases, they have also presented new challenges. Benedict XVI "It is necessary to reiterate that any discrimination carried out by any power against persons, populations or ethnic groups on the basis of real or presumed genetics factors is an attack against all humanity. He spoke to scientists, theologians and philosophers participating in an international congress on genetics in Rome organized by the Pontifical Academy for Life. For three days, experts from around the world studied "The New Frontiers of Genetics and the Risks of Eugenics." The discussion focused on studying the practices of genetics that lead to considering that some unhealthy embryos are less useful than healthy ones and must be eliminated. Msgr. Rino Fisichella The word eugenics seemed to be a word that pertained to the past but in fact its still valid because an eugenic mentality is growing and perhaps the greatest dangers is that although the term is not used, the mentality that not all people have the same dignity is being assumed. The participants were especially alarmed by the selection of embryos during in vitro fertilization because it eliminates those who have genetic diseases like cystic fibrosis or Down syndrome. Msgr. Ignacio Carrasco The case of children with Down syndrome. Today those children practically are no longer born because they eliminate the problem of Down syndrome by ... - About In Vitro Fertilization In vitro fertilization requires stimulating the female with hormones, mixing the eggs and sperm outside the body and implanting them back into the female to hopefully conceive. Understand this method of reproduction suitable for infertile couples with helpful information from a practicing ob-gyn in this free video on getting pregnant. Expert: Lisa Gibbons Bio: Lisa Gibbons is an OB/GYN at Cascadia Women's Clinic in Vancouver, Washington. - Plant Reproduction: Plant Fertilization () *CLICK HERE for RELATED CONTENT Plant Breeding - FREE NEWSLETTERS - - IVF In Vitro Fertilization Birth - The Creation of Life(: Logan Thomas was created 11-17-05 by way of IVF (Invertrofertilzation or a test tube baby) He is a miricle for us all that's for sure! To see him being a four cell embryo too clapping hands now is some thing words can't explain! My song I added to it was written a long time ago and was not intended for this video, but it seems to almost fit? I hope you enjoy and stay subscribed to more of my videos to come. Peace outy! TAMMpON - Sea Urchin Fertilization Fertilization of eggs of the sea urchin species Strongylocentrotus purpuratus and formation and elevation of the fertilization membrane. Real time. View full screen. - In Vitro Fertilization in Mexico Mexico is a popular destination for people looking for low cost in vitro fertilization abroad. IVF (also known as Assisted reproductive technology; ART; Test-tube baby procedure) usually requires a trip of two weeks. Low cost IVF destinations abroad include Mexico, Turkey, India & Jordan. IVF steps involve : Stimulation, Egg retrieval, Insemination and Fertilization, Embryo culture, Embryo transfer. In vitro fertilization costs in Mexico should also consider the cost of travel and a long stay. Fertility treatment in mexico at reputed clinics has good success rates. Cheap IVF clinics in Mexico do not always equate to poor quality. Mexico has Affordable IVF price due to lower drug costs & other medical expenses. Beach resorts of Manzanillo, Mazatlan and Puerto Vallarta are very near to the location of this Mexico ivf clinic. - News Update: In Vitro Fertilization Developer Wins Nobel Prize The Nobel Foundation has announced the first in 6 awards that recognize outstanding cultural and scientific advances. Monday's prize announcement was for Physiology or Medicine. SOT: ""...the Nobel Prize in Physiology or Medicine 2010 to Robert Edwards for the development of in vitro fertilization."" The English biologist, along with his partner Patrick Steptoe who would have shared the prize if he were still alive, spent more than 20 years working to get eggs and sperm to mature and unite outside the body. They made the discovery 30 years ago. Today, 1-2% of all births in the US are a result of the revolutionary IVF method. The treatment has seen the conception of around 4 million babies since the first test tube baby, Louise Brown, in 1978. The procedure, which was originally met with much controversy because of the moral implications of intervening in the creation of a human being, is now more widely accepted and has helped hopeful parents overcome infertility. The Nobel Foundation will award prizes everyday this week, with the final announcement next Monday. The organization will recognize outstanding individuals in physics, chemistry, literature, the economic sciences and peace. - In Vitro Fertilization? What is the relevant biblical wisdom regarding the complex ethical decisions surrounding in vitro fertilization? Is it an open handed issue or is IVF to always be avoided by Christians?Pastor Mark Driscoll answers this question as part of a live "Ask Anything" session in which audience members SMS questions to the pulpit to be answered in real time. This question was answered in the broader context of a sermon entitled "Is Birth Control a Sin?" which can be found at - In Vitro Fertilization at UAB: One Couple's Success Story In Vitro Fertilization helped Jennifer and Gregg Fleming start a family. Infertility specialists at UAB discuss the benefits of coming to UAB for infertility treatment. - Sea Urchin Fertilization This video shows the process of fertilization in a sea urchin. This video is from: Essential Cell Biology, 3rd Edition Alberts, Bray, Hopkin, Johnson, Lewis, Raff, Roberts, & Walter ISBN: 978-0-8153-4129-1 - FRIED OR FERTILIZED- Yung Humma ft Flynt Flossy and Whatchyamacallit Download on iTunes NOW!! JOIN TURQUOISE JEEP ON FACEBOOK . FOLLOW ON TWITTER Newly signed Hip Hop sensation YUNG HUMMA debuts with his new hit single and dance phenomenon "FRIED OR FERTILIZED" featuring FLYNT FLOSSY and WHATCHYAMACALLIT DIR: G.WINTERS (c)TURQUOISE JEEP RECORDS 2010 - 3D sperm fertilization project 3D models of (sperm, fallopian tubes, white blood cell hehe) used in a particle system. An overuse of 2-headed and 2-tailed sperm is used for fun. Also after reading a sidenote that some white blood cells can kill sperm setups a cool lil' animation that probably rarely happens in real life. Original music had Wagner's Ride of the Valkyries as the music but had to swap that out, and this track was pretty darn cool anyway :) - In Vitro Fertilization IVF Superior ART is an infertility treatment center with recognized expertise specializing in a method to diagnose embryos with chromosomal and single genes disorders in order to provide solutions for couples with infertility and repeated miscarriage or those who gave birth to children with inherit disease, such as beta thalassemia or genetic abnormality like Robertsonian translocation. In the old days, as there was no treatment to the problems, the couples had to take all the risk of getting pregnant and repeated miscarriage. But today, thanks to the Assisted Reproduction Technology, Superior ART is capable of helping couples to get through such problems. Why Superior ART? Thats because at Superior ART, we have available the expertise and advanced technology to diagnose genetic health of the embryos and select those without any genetic diseases to be transferred to the uterus. There was a case of a couple who experienced problems of repeated miscarriage due to genetic abnormality of Robertsonian translocation. They received IVF treatment and PGD in which genetic material from the embryos is tested to see if they carry the genetic disease. Then only embryos not affected by the disease are transferred to the mothers womb. At the end, they achieved a pregnancy and gave birth to very healthy twin girls. - How To Fertilize Bermuda Grass Lawns Learn tips on how to properly fertilize Bermuda grass lawns. From the Southwest Yard & Garden series. - In-Vitro Fertilization (IVF) 101 (Pregnancy Health Guru) It's expensive and invasive--but if you are trying to get pregnant, it often works. Here is the real deal with IVF. More Videos on Infertility: - Fertilization: A Sweet Love Story This is my video for Professor Talbot's CBNS 169 class on the fertilization process. It took me a couple of trial and error ideas to finally get it right with using only candy. CBNS 169 Winter 09 Professor Talbot TA: John Ta Section 22 I'd like to give a special thanks to few people who made this happen: My mom, who helped me with the sorting of the Skittles (which is harder than it sounds) and endured my frustration with this project. Robert Hassaballa who helped me pick out the candy to use in the project (and also helped out with "getting rid" of the candy I didn't need). And Mina Youssef for helping me out with the idea. Some of the candy I used was skittles, starburst, gushers, fruit by the foot, reeses, twizzlers, and airheads. - Human Fertilization the animation of human fertilization - Human Fertilization.FECUNDACION OR .co..Blog Name"AALOJAMIENTO INTERNACIONAL".-Fertilization occurs when spermatozoa travels up into the uterus, an a spermatozoon encounters an egg. Pregnancy occurs as a result of the fertilization of an ovum by sperm. - Health Matters: Fertility and In Vitro Fertilization (IVF) In the US today, over 6 million people are affected by infertility. What should be the most joyous time in a couple's life can often become the most difficult. This complex issue requires the latest medical technology with the equally important need for empathetic care. To help couples on this journey, Dr. Granet is joined by a nationally recognized expert, Arlene Morales, MD, Fertility Specialists Medical Group, as she talks about the latest fertility treatments and what the best options are given the situation. Series: "Health Matters" [9/2007] [Health and Medicine] [Show ID: 12319] - In Vitro Fertilization (IVF) -- Greenville and Spartanburg, S In this video, Dr. John Nichols explains the In Vitro fertilization procedure. At our Greenville and Spartanburg, SC fertility centers, IVF is one of many advanced infertility treatments. For more information, visit - Biology 1A - Lecture 32: Fertilization and embryogenesis General Biology Lecture - Fertilization & Fetal Development Video on the development of the fetus from an embryo - InVitro Fertilization IVF This video explans the basics of IVF using Family Guy's Stewie! This is an assignment for cbns 169. - Fertilizing Dahlias Fertilization - In Vitro Fertilization (IVF) - Kurena's Treatment Story Kurena's tests revealed that she had thyroid tumors in addition to polycystic ovarian syndrome (PCOS). Treating these conditions involved removing the tumors, ovarian drilling, and follicular reduction. During this process, our doctors extracted, froze, and stored ten eggs at our Atlanta, Georgia, office for use in in vitro fertilization (IVF). A few months later, Kurena was pregnant. For more information about in vitro fertilization,please visit us at Georgia Reproductive Specialists Atlanta, GA Phone 404-975-0466 Fax: 404-843-0812 2 Office Locations: 5445 Meridian Mark Road Suite 270 Atlanta, GA 30342 3400-C Old Milton Parkway Suite 475 Alpharetta, GA 30005 - Catholic Church Attacks 'In Vitro Fertilization' in Poland November 28, 2009 on Russia Today - The Roman Catholic Church has lambasted the use of in vitro fertilization (IVF), and has taken steps to have it banned altogether, while for some families it is the only way to have children in Poland. via - - Day 1 (Fertilisation check) The next day, whether "classic" IVF or ICSI has been performed, fertilization is confirmed by observing 2 pro-nuclei (one containing half the number of chromosomes from the mother, the other containing the other half from the father). - Ancient technologies of seed fertilization with John Burke John Burke, an expert on ancient technologies of seed fertilization, is the author of the book Seed of Knowledge Stone of Plenty: Undertstanding the Lost Technologies of the Megalith-Builders with Kaj Halberg - Fertilized Human Eggs are Child ...with Bacon too Fertilized Human Egg Story: College Student Study Story: How bacon is made: Thanks a ton for watch, don't forget to subscribe :) Connect With Me http http - BONSAI-EASY NEW METHOD-PART 4-REPOTTING, FERTILIZING THIS IS PART FOUR OF "ADVENTURES IN BONSAI." THIS EPISODE COVERS REPOTTING A ROOT-BOUND MING TREE, FERTILIZATION, AND TOOLS THAT I USE IN CARING FOR MY BONSAI. TO LEARN MORE ABOUT THE BASIC STARTING OF A BONSAI USING THE NEW EASY METHOD OF SPHAGNUM MOSS AS A SUBSTRATE, SEE PARTS 1 AND 2. FOR AN UPDATE ON THE TREE WORKED ON IN PARTS 1 1ND 2, SEE PART 3.(May, 2008- showing traditional bonsai at the Morikami Museum. It's just a silent look at their trees, but it is inspiring)("Morikami Bonsai Gardens May 2008").(PLEASE VIEW PART 12 ABOUT THE WARNING ON HANDLING SPHAGNUM MOSS BEFORE YOU WORK WITH SPHAGNUM MOSS). Videographer-Carol L. - In vitro Fertilization (IVF) W09 CBNS 169 Video Project by Xiaowei Ma: "In vitro Fertilization." In vitro fertilization (IVF) is one of the best known assisted reproductive technologies that will help couples experiencing infertility problems. This video briefly describes the procedures, costs, probabilities, benefits, and results involved in IVF. Enjoy! - Fertility In Vitro Fertilization (IVF) ... Gifted Journeys ... By GloZell Straight and Gay coulples can have children. Wendie Wilson from Gifted Journeys chats with good friend GloZell about when to have kids... and more! - Fertilization CBNS 169 The process of Fertilization! The music that I originally had for this video was completely different from what you hear now...there was a bit of a problem with youtube's copyright issue... a special shout out to my sister and to my friend kevin for helping with all the technical difficulties! =) enjoy! - In Vitro Fertilization IVF Infertility Treatment Georgia Reproductive Specialists ()provides the latest in assisted reproductive technologies such as in vitro fertilization (IVF), ICSI, preimplantation genetic diagnosis (PGD)blastocyst transfer, egg donation, embryo cryopreservation, ovulation induction and insemination to couples with infertility problems due to endometriosis, polycystic ovary syndrome (PCOS), male factor, fallopian tube obstruction, uterine fibroids and age related issues. GRS offers convenienently located offices in Alpharetta, Northside and Decatur. For more information visit us online at , call 404-843-2229 or simply attend a free educational seminar "IVF AFTER HOURS" held monthly at our Northside office. - In Vitro Fertilization Pioneer, Robert Edwards, Awarded Nobel Prize Read the Transcript: This year's first Nobel Prize was awarded to Robert Edwards for his work developing the in-vitro fertilization method that led to the birth of the world's first "test-tube baby." - Sea urchin fertilization This is a movie of sea urchin egg fertilization (species: Lytechinus variegatus). Note that you can see the sperm fertilizing each egg, including both the head and the tail. Also note the formation of a fertilization cone around the sperm after initial contact with the egg. Sperm binding initiates a series of intracellular signaling events that result in the elevation of the fertilization envelope (clear membrane surrounding the fertilized egg). The fertilization envelope prevents the egg from being fertilized by more than one sperm (a fatal event) and protects the developing embryo during early development. It takes about 1-2 minutes for the fertilization envelope to rise completely after sperm binding. - Human embryology/** education: Fertilization and Implantation animation Implantation is a very hard subject for many students to grasp so I made this animation. Hope it helps- by Nhan Do BGM: Beyoncé Single Ladies (Put A Ring On It) from the album Single Ladies (Put A Ring On It) (C) 2008 SONY BMG MUSIC ENTERTAINMENT ^ buy her album _______________________ ... - Double Fertilization in Flowering Plants Double fertilization in flowering plants involves the fusion of two sperm cell nuclei of the male gametophyte with two cell nuclei of female gametophyte. One sperm fuses with the haploid egg cell to form the zygote; the other sperm unites with the diploid central cell to form a triploid cell that will develop to an endosperm. twitter about fertilization Blogs & Forum blogs and forums about fertilization “After tubal ligation, what are your options for conceiving again? Tubal ligation reversal can reopen the fallopian tubes. But, if your tubes were cut or burned there will not be enough tube to put back together. If it has been more than 10” — Tubal Ligation Reversal or IVF? - Our Blog, “Subscribe to the Andy Blog and receive an email notifications to alert you of a new post. Invitro Fertilization - All I know about IVF. News about IVF. Medical” — The Andy Blog: Invitro Fertilization Archives, .mx “Life Training Institute Blog. Persuasively Communicating the Pro-Life claiming the capacity to interrupt the fertilization process and not redefine the new” — Life Training Institute Blog: Lee & George on Fertilization, lti- “Henrik Falck's blog. reinventing web 3.0. Self-fertilization, or: web and the reason I figured I'd write this blog post at all: In their reception they had” — Self-fertilization, or: web 3.0, or: Mixi, or: One of those, “Following the SRI guidelines (see Fertilization Blog Entry), we hoped to replace chemical fertilizers with application of organic where the manure was piled before it was spread over the field (see picture in Fertilization Blog Entry)” — Yellowing of Fields, “Blog. fertilization. Share. Print. Email a Friend. Facebook. Mark as Favorite. Blog: rights, down syndrome, fertilization, john mccain, kristi burton,” — All Blog Posts - Blog - Eternal Perspective Ministries, “Plant It Landscape is a quality landscape designer, architect and contractor. We also provide fertilization services. This landscaping company proudly Thanks for stopping by our Sarasota Landscape and Fertilization Blog. We look forwarding to hearing from you! As a reminder, we certainly welcome” — Sarasota Landscape Company – Designer Architect Contractor, “Tubal Reversal Blog in vitro fertilization' Tubal Reversal After 40 : This blog is to share observations, experiences, and thoughts about tubal ligation reversal developed over the 30 years I have been performing” — Blog Posts Tagged In Vitro Fertilization - Part 2, tubal- “Read our IVF Procedures Blog for more information! The risks of retrieval involve ZIFT is a procedure that involves an oocyte retrieval followed by in vitro fertilization” — Pacific Fertility Center Los Angeles California,	2	29	2	0	1	0.465073	3	6,796
In recent years, several studies have shed light into the processes that regulate epidermal specification and homeostasis. embryonic stem cells to the ectoderm lineage. The human being ectoderm cell signature identified in this scholarly study contains several genes expressed in ectodermal and epithelial tissues. Significantly, these genetics are connected with pores and skin disorders and ectodermal problems also, offering a system pertaining to understanding the biology of human being skin keratinocyte advancement below homeostatic and unhealthy conditions. Intro The pores and skin acts as a protecting obstacle that establishes an organisms first line of defense against external aggressions such as UV light, microbial pathogens, hazardous substances, mechanical stress, and loss of internal bodily fluids [1, 2]. These essential functions are mediated by the epidermis, the outmost layer of the skin, which establishes a tight barrier by creating a stratified epithelium that is separated from the dermis by a basement membrane. During development, the epidermis derives from the primitive ectoderm, a single layer of epithelial cells that differentiates into epidermal basal keratinocytes [1C3]. These actively proliferating cells can symmetrically divide to laterally expand epidermal growth and asymmetrically divide to form the upper, mature squamous layers of the skin epithelium. Cells within the upmost epidermal layer are sloughed from the skin surface and are continually replaced by differentiating basal keratinocytes moving outward. During embryogenesis, cells of the surface ectoderm, which cover the entire embryo, express the intermediate filaments Keratin 8 (K8) and K18. Around embryonic day 8.5 a few of these cells become committed to an epidermal keratinocyte fate which is marked by a transition in the expression of K8/K18 to K5 and K14 [1, 2, 4, 5]. The E5/E14 positive basal coating cells initiate a system of stratification and ultimately go through port difference to type the adult adult pores and skin, a procedure that requires the expression of the transcription keratinocyte and element gun G63. The molecular systems that regulate skin formation pursuing stratification possess been the concentrate of many research but the systems that control the preliminary dedication of surface area ectoderm to the skin family tree during embryogenesis stay elusive. Our previous work Rebastinib shed light into these earlier stages by identifying an unappreciated step during keratinocyte specification . This stage is characterized by the expression of P63 in pre-epidermal keratinocytes prior to K14 expression in fully committed epidermal keratinocytes . Furthermore, impairing -secretase related pathways utilizing N-[In-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) in human being embryonic come cells (hESCs) or by genetically Rebastinib removing presenilin 1 and 2 in the developing murine pores and skin promotes G63 phrase . In latest years hESCs possess been used as a model for the scholarly research of family tree standards and difference. Protocols for difference of hESCs into keratinocyte lineages possess been created and demonstrated to become capable to generate surface area ectoderm cells [6C9]. These protocols possess also been demonstrated to imitate the developing measures that happen during regular murine surface area ectoderm advancement (6). Consequently, these difference protocols can become utilized to determine book molecular systems that regulate the changeover Rebastinib of the surface area ectoderm towards an skin destiny. Since our earlier research proven that hESCs treated with DAPT improved the development of GP3A skin progenitors, we utilized this -secretase inhibitor as a medicinal device to recognize essential government bodies of non-neural ectoderm standards using RNA sequencing. Our RNA sequencing display screen uncovers a brand-new transcriptional gene personal linked with early non-neural ectoderm advancement and with skin standards of hESCs. Strategies and Components Individual embryonic control cell lifestyle L1 hESC cells were obtained from WiCell . The cells had been cultured on matrigel (BD Biosciences) in mTESR1 moderate (Control Cell Technology) at 37C, 5% O2 Rebastinib and 5% Company2 and passaged every 5C6 times using dispase (Control Cell Technology). Ectoderm specification of hESCs was performed according to described protocols previously. Rebastinib Quickly, hESC colonies had been incubated for 3 times with 0.5 nM of human. With the rapidly expanding field of tissue engineering, surgeons have been eager to apply these principles to craniofacial surgery. cytokine stimuli for tissue engineering driven strategies to address the clinical needs in skeletal and soft tissue reconstruction. to address a tissue RGS21 defect or tissue Mesaconine manufacture dysfunction. More recently, excitement has surrounded the use of pluripotent and multipotent cells types when utilizing tissue engineering technologies. Though these pluiripotent or stem cells are attractive, it is usually crucial that physicians and surgeons understand the cell type they are using, assess whether it is usually the optimal cell type to address the clinical need, and most importantly, understand the risks of such therapies before using them clinically. Furthermore, craniofacial surgeons must understand methods of cell delivery using different scaffold designs. In this review we will discuss the current clinical need for skeletal and soft tissue engineering faced by craniofacial surgeons and subsequently we will explore current cell types and scaffold designs being employed for tissue engineering treatment options. We will conclude by discussing ways to enhance the vascularity of tissue engineered constructs Mesaconine manufacture as this will ultimately allow for a definitive repair. Clinical need for stem cell therapy in Craniofacial Surgery Craniofacial surgery is usually particularly suited to tissue engineering as Mesaconine manufacture significant progress has been made in adipose and osseous tissue induction. With regards to soft tissue needs, craniofacial surgeons are faced with the aesthetic challenges of facial rejuvenation such as malar and lip augmentation which currently rely on the use of synthetic fillers such as hyaluronic acid and fat transfer. Similarly, reconstructive needs for soft tissue contour such as in patients suffering from Parry-Romberg syndrome and HIV related lipoatrophy are addressed with a number of treatment options. Autologous lipoinjection has become recently popularized and been shown to provide excellent outcomes, however, even in the best hands, lipotransfer does not provide a self-renewing population of cells.(2, 3) Thus, recent efforts by Yoshimura to enhance transferred adipose tissue with adipose derived stromal cells (ASCs) offer a promising application of stem cell therapy.(4C7) A second medical bioburden faced by craniofacial surgeons is the need for bone alternative. The craniofacial skeleton provides structural stability and mastication puts load bearing stress on several craniofacial bones. There are over 500,000 bone grafts performed annually, of which 6% are for craniofacial indications.(8, 9) Bone is a responsive, highly vascularized tissue that responds to local stress and strain. Bone consists of three different cell types (osteocytes, osteoblasts, and osteoclasts) which are surrounded by a matrix composed of hydroxyapatite, collagens, glycoproteins, proteoglycans and sialoproteins.(10, Mesaconine manufacture 11) With regards to the pediatric population, cleft palate represents an area where bony tissue regeneration to address the alveolar ridge and enable subsequent tooth eruption and midface development would greatly benefit from tissue engineered bone. Autogenous bone grafts, often harvested from the iliac crest have become the current platinum standard to treat the alveolar cleft, however, such tissues are painful to harvest, and can be complicated by hematoma, infection and resorption. In patients of all ages above 2 years old, a time when the calvarium can no longer regenerate on its own, calvarial defects also represent a significant reconstructive challenge. Whether from congenital malformations, trauma or cancer extirpation, the loss of bone in the craniofacial skeleton has significant structural and functional consequences. Current treatments for such skeletal defects include nonvascularized bone grafting, which are at risk of resorption, and the use of alloplastic materials which are wrought with contamination, extrusion and mechanical failure. Thus, the development and clinical introduction of a biomimetic, osteoconductive scaffold would greatly benefit surgeons treating patients with osseous defects of the craniofacial skeleton. Cancer resections and trauma can also often lead to maxillary and mandibular bony defects. Current approaches of bone grafting using nonvascularized as well as vascularized bone grafts such as those harvested from the fibula and scapula are often employed. Though vascularized grafts undergo less resorption, they often create large secondary defects and are available in a limited supply. When autologous transplantation is usually not possible, allogenic and xenogenic bone grafts have been employed, however, these substitutes are constrained in their osteogenicity, stability and. Cardiomyocytes (CMs) derived from individual pluripotent control cells (hPSCs) possess a great potential for regenerative medication. (qRT-PCR), TF-specific immunofluorescence evaluation, and movement cytometry. Tests TF combos in our strategy uncovered that (BGM) had been most effective for cardiac forwards coding in individual activated pluripotent control cell lines and individual Ha sido cells as well. Removal of decreased development of CM-like cells somewhat, whereas exhaustion of or removed cardiomyogenesis. Each of these TFs by itself got no inductive impact. In addition, we possess observed awareness of buy 179461-52-0 CM development to cell thickness results, which features the requirement for careful evaluation when interpreting TF-directed family tree induction. In overview, this is certainly the initial record on TF-induced cardiomyogenesis of hPSCs applying a transient, nonintegrating technique of cell transfection. Launch Myocardial infarction and various other cardiovascular system disorders can stimulate serious, permanent reduction of useful cardiomyocytes (CMs) and decreased center function. Eventually, this may business lead to center failing with extremely limited treatment choices at present. CMs extracted from individual pluripotent control cells (hPSCs), including individual embryonic control cells (hESCs) and individual activated pluripotent control cells (hiPSCs), possess a high potential for the advancement of innovative regenerative remedies for infected minds. They also represent a individual cell supply for the advancement of even more predictive medication breakthrough discovery and medication protection assays . Furthermore, patient-specific hiPSC-derived CMs possess been set up as a tool for buy 179461-52-0 in vitro Igfbp1 disease modeling recently. It provides, for example, been confirmed that buy 179461-52-0 the anticipated prolongation of the actions potential length quality of sufferers with long-QT symptoms was effectively emulated in patient-specific hiPSC-derived CMs [2C4]. Nevertheless, a single of the primary obstructions in generating CMs from hPSCs is the relatively inefficient and shifting difference performance . Many techniques have got been researched to better control the difference procedure and to improve CM produces from hPSCs, including the relatives pricey supplements of development elements or particular effector elements . In addition, the overexpression of one or multiple transcription elements (TFs) known to play significant jobs in center advancement was examined. An in situ research confirmed the ectopic induction of defeating cardiac tissues in preformed mouse mesoderm outdoors the center field by the mixed phrase of . Eventually, lentiviral-delivered TFs had been stated to induce immediate transdifferentiation of mouse cardiac and tail-tip fibroblasts into useful CMs in vitro and in vivo [8,9]. Despite their thrilling scientific effects, the efficiency of such immediate conversion experiments is talked about in the field controversially. Relating to PSCs, forwards development provides been confirmed upon constitutive overexpression of and in mouse Ha sido cells applying embryoid body (EB)-activated difference . Many lately, a 4-aspect drink, including and just. However, we possess also noticed an influence of the (general and regional) cell thickness on cardiomyogenesis contacting for a important evaluation of reviews on the subject. Strategies and Components Vector structure To generate phrase vectors, TF cDNAs had been cloned by RT-PCR or received from ImaGenes (Bremen, Indonesia), cloned into pCAGGS2 under the control of the CMV booster (CMVieE)/poultry beta-actin marketer (positivity in few cells (data not really proven). FIG. 2. Efficient transcription aspect (TF) phrase from bicistronic transfection vectors. (A) Schematic display of bicistronic transfection vectors development particular TFs combined to fluorescence reporters via an inner ribosome admittance site … The 5th aspect examined in our research was (encoded on an specific plasmid without news reporter gene coupling; Fig. 2C) with all feasible double-TF combos in the present research (Fig. 3E and forward). At initial, nevertheless, anti-and and induce formation of CM-marker-expressing clusters Previous reports have shown an impact of TF overexpression on cardiomyogenic induction of pluripotent cells upon combining different factors. Here, we have tested individual TF candidates as well as combinations of 2 or 3, whereby buy 179461-52-0 was always included in our 3 factor cocktails. After electroporation, cells were seeded as a subconfluent monolayer on gelatin-coated dishes and cultured in a feeder cell-conditioned medium for 2 days to allow for recovery (Fig. 4A). The medium was then replaced by a fully defined serum-free medium (bSF [18,19]) for another 12 days of culture. Figure 4C depicts the morphology of hCBiPS2 as colonies on murine feeder cells on day 0, on day 2 postelectroporation, and as confluent monolayer formed buy 179461-52-0 over time in a bSF medium (day 14). Starting with 0.33106 electroporated cells per well of a 12-well dish, about 67% vital cells were retrieved on day 2 (Fig. 4B, 0.220.12106 TF-transfected cells and 0.210.11106 reporter plasmid-receiving controls). The cell number increased by about 3-fold at day 14 after electroporation, resulting in 0.690.39106 of TF-transfected cells (0.710.35106 cells in control transfections). To test the formation of CMs, immunofluorescence staining specific to the sarcomeric protein cardiac Troponin T ((BGM) yielded a considerable number of (BGT), recently reported to induce ectopic beating cardiac cells in mouse embryos .. Growth necrosis factor-related apoptosis-inducing ligand (Path), delivered while a membrane-bound molecule expressed on the surface area of adenovirus-transduced Compact disc34+ cells (Compact disc34-Path+), was analyzed for its apoptotic activity in vitro on 12 breasts tumor cell lines representing estrogen receptor-positive, HER2+ and triple-negative (TN) subtypes and for its impact on growth development, vascularization, necrosis, and lung metastasis occurrence in Jerk/SCID rodents xenografted with the TN breasts tumor collection MDA-MB-231. in vitro cytotoxicity tests demonstrated that Compact disc34-Path+ cells selectively targeted Compact disc44+/Compact disc24?/low cells. Although in vivo treatment with Compact disc34-Path+ cells do not really business lead to growth development inhibition, treated rodents uncovered considerably bigger areas of necrosis linked with harm of growth vasculature than do control rodents. Furthermore, lung area from MDA-MD-231 tumor-bearing rodents were free of charge of metastases in Pracinostat 12 completely?days after the last shot of Compact disc34-Trek+ cells, whereas metastases were present in all control mouse lung area. An anti-metastatic impact of CD34-Trek+ cells was noticed in a super model tiffany livingston of experimental lung metastases also. The relationship between in vitro susceptibility to membrane-bound growth and Trek control cell content material, with Compact disc34-Trek+ cell-induced inhibition of the metastatic procedure jointly, factors to the picky concentrating on of cancers control cells by Compact disc34-equipped cells and the potential worth of such cells in eliminating growth control cells before the onset of overt metastases. Electronic ancillary materials The online edition of this content (doi:10.1007/h10549-012-2281-4) contains supplementary materials, which is obtainable to authorized users. and symbolize the longest and shortest diameters, respectively. At 12?times after the last treatment, all rodents in test 1 and 5 of 11 of each group in test 2 were killed. After one week in the staying 6 rodents per group tumors had been surgically eliminated and pets had been murdered 18?times later on. Lung area from rodents in test 2 had been examined for the existence of metastases. The anti-metastatic impact of Compact disc34-Path+ cells was also looked into in an fresh metastasis model. Eight-week-old feminine NOD/SCID mice we were injected.v. with 1??106 MDA-MB-231 cells followed 4?h by Pracinostat i later.v. shot with Compact disc34-Trek+ cells (1??106?cells/mouse; 4 rodents), Compact disc34+ cells (1??106?cells/mouse; 4 rodents), or PBS (4 rodents). At time 31 post-injection, rodents were killed and the true amount of pulmonary metastases was estimated. Lung and Growth histology and immunohistochemistry Formalin-fixed, paraffin-embedded growth nodules had been sectioned at 4?m, dewaxed, hydrated, and stained with hematoxylin and eosin or processed for immunohistochemistry with mouse anti-mouse Compact disc31 antibody (PECAM-1, duplicate Chemical-11; 1:50, Santa claus Cruz Biotechnology, California, USA) after antigen retrieval in 1?millimeter EDTA at 95?C for 30?minutes or with monoclonal mouse anti-human Compact disc45 antibody (imitations 2B11?+?PD7/26; 1:100, Dako) after antigen retrieval in citrate barrier, 6 pH.0, in 95?C for 6?minutes. Growth necrosis was discovered using TdT-mediated dUTP nick-end-labeling (TUNEL) yellowing (Roche, Milano, Italia, European union) relating to the producers guidelines. Positive indicators had been exposed by 3,3-diaminobenzidine yellowing, and growth areas had been counterstained before evaluation by light microscopy. To imagine lung metastases, 4-meters formalin-fixed, paraffin-embedded lung areas had been dewaxed, hydrated, and discolored with hematoxylin and eosin or prepared for immunohistochemistry with mouse anti-human vimentin (duplicate Sixth is v9; 1:400, Dako) after antigen retrieval with citrate barrier, pH 6.0, in 95?C for 6?minutes. For each mouse, mean quantity and size of lung metastases had been examined in 3 microscopic areas (3.0??3.0?millimeter2) randomly selected in each histological section. Metastases size indicated in meters was determined using ImageJ software program by perseverance of the longest size using the range club as guide. Evaluation of tarnished areas After TUNEL yellowing, tissues areas had been obtained at 20??zoom with an auto high-resolution scanning device (dotSlide Program, Olympus, Tokyo, Asia) and grouped according to nonoverlapping crimson, green, and blue (RGB) pictures in TIFF structure (last quality, 3.125?-pixels/meters). Pictures had been examined using the open up supply image resolution software program ImageJ (http://rsb.info.nih.gov/ij/). Routines for picture evaluation had been coded in ImageJ macro vocabulary and performed on RGB pictures without additional treatment. For each fresh condition, three tissues areas from each growth nodule had been examined. Pictures had been initial treated for sound decrease using a average filtration system with a 1.5?-pixel radius. Necrotic and total tissues areas had been analyzed using different filtration system beliefs under immediate individual guidance. Dark areas in last binary pictures had been quantified relating to pixel matters to get a percentage of necrotic areas indicated as: 100??(necrotic area/total tissue area). Growth vasculature was examined in Compact disc31-discolored areas obtained at 400??zoom and using Aperio ImageScope sixth is v220.127.116.112 in 2??zoom in Pracinostat vimentin-stained areas. Statistical evaluation Statistical evaluation was performed with the record package deal Prism 5 (GraphPad Software program, San Diego, California, USA). In all in vitro tests, variations between neglected and treated cells in apoptotic response had been examined using the unpaired (2-tailed) College students check. The relationship between the percentage of Compact disc44+/Compact disc24?/low cells and mTRAIL level of sensitivity was evaluated by Pearsons Chi-squared check and the correlation between Path receptor expression and mTRAIL level of sensitivity, by Fisherman precise check. Variations in areas of necrosis and in mean quantity of lung metastases between the two fresh mouse organizations had been Rabbit Polyclonal to RREB1 examined using the unpaired (2-tailed) College students check. Variations had been regarded as significant at represents the mean percentage of Compact disc44+/Compact disc24?/low in … Results of Compact disc34-Trek+ on MDA-MD-231 subcutaneous xenograft tumors MDA-MB-231 cells, which had been delicate to mTRAIL in vitro and are capable to metastasize. Objective To detect the radiosensitivity of intratumour quiescent (Queen) cells unlabelled with pimonidazole to accelerated co2 ion beams and the boron neutron catch response (BNCR). postponed assay or a reduce in rays dosage price, was even more obviously noticed among the Queen than total cells. These noticeable changes in radiosensitivity were suppressed subsequent co2 ion gleam and neutron beam-only irradiaton. In the BNCR, the make use of of a 10B-pet carrier, l-status of tumor cells especially. Nevertheless, the Queen cell people in solid tumours provides hardly ever been proven to end up being completely hypoxic . In fact, the size of the HF of Queen cell populations in SCC VII squamous She cell carcinomas, incorporated in the hind hip and legs of C3L/He rodents and with a size of 1 cm, was 55.1 6.2% (mean regular mistake) . Therefore, this worth was considerably much less than 100%, suggesting that the Queen cell human population unquestionably contains oxygenated tumor cells. A few years ago, the common recognition of hypoxic cells in both cells and cell ethnicities became feasible using pimonidazole (a replaced 2-nitroimidazole) and a mouse immunoglobulin (Ig)G1 monoclonal antibody (MAb1) to steady covalent adducts created through reductive service of pimonidazole in hypoxic cells . Right here, we attempted to selectively detect the response of the pimonidazole-unlabelled and most likely oxygenated cell portion of the Queen cell human population. To accomplish this we mixed our technique for selectively discovering the response of Queen cells in solid tumours with the technique for discovering cell and cells hypoxia using pimonidazole and MAb1 to pimonidazole. High-linear energy transfer (Allow) rays including neutrons is definitely even more effective than low-LET Times- or -rays at causing natural harm. High-LET rays displays a higher comparable natural performance (RBE) worth for cell eliminating, a decreased air impact and a decreased dependence on the cell routine [2,5], producing it excellent to low-LET light in the treatment of cancerous tumours possibly. Reactor thermal and epithermal neutron beams obtainable at our start acquired been also proven to possess a considerably higher RBE worth than -sun rays in irradiated tumor cells . Owing to a picky physical dosage distribution and improved natural harm in focus on tumours, particle light therapy with protons or large ions provides obtained raising curiosity world-wide, and many scientific companies are taking into consideration presenting light therapy with billed contaminants. Nevertheless, nearly all reviews on the natural advantages of billed particle beams are structured on results just on total tumor cell populations as a entire using cell civilizations or solid tumours [1,5]. Intensity-modulated radiotherapy and stereotactic irradiation possess become common as brand-new radiotherapy methods for the treatment of malignancies. These methods frequently need exact placing of individuals and much longer publicity instances in a solitary treatment program [6,7]. Prolongation of irradiation period may induce undesirable rays results and evokes main concern related to the dose-rate impact. Therefore, there is definitely a want to explain the impact of ARRY334543 a decrease in dosage price on the radiosensitivity of tumours in response to particle rays. Strategies Rodents and tumours Un4 lymphoma cells (Cell Source Middle for the Biomedical Study Company of Advancement, Ageing and Tumor, Tohoku College or university, Asia) made from C57BM/6J rodents had been preserved in RPMI 1640 moderate supplemented with 12.5% foetal bovine serum. The position of the Un4 tumour cells was the outrageous type . Cells were collected from developing civilizations and approximately 1 exponentially.0105 tumour cells were inoculated subcutaneously into the still left hind hip and legs of 9-week-old syngeneic female C57BL/6J mice ARRY334543 (Japan Animal Co. Ltd, Osaka, Asia). 14 times after the inoculation, the tumours, 1 cm in size around, had been utilized for irradiation in this scholarly research, and the physical body fat of the tumour-bearing rodents was 22.12.3 g. Rodents had been taken care of regarding to the Suggestions for Managing of Lab Pets for Biomedical Analysis, created by the Panel on Protection Managing Rules for Lab Pet Tests. Labelling with 5-bromo-2-deoxyuridine 9 times after the tumor inoculation, mini-osmotic pushes ARRY334543 (Durect Company, Cupertino, California) comprising 5-bromo-2-deoxyuridine (BrdU) blended in physical saline (250 mg ml?1) were incorporated subcutaneously to enable the labelling of all G cells more than a 5-day time period . The percentage of branded cells after constant labelling with BrdU was 66.13.8% and level at. Self-reactive B cells are tolerized at several stages of B-cell differentiation and advancement, including the premature B-cell stage (central tolerance) and the germinal middle (GC) B-cell stage, and B-cell tolerance involves several mechanisms such as deletion, anergy, and receptor editing. cells. Flaws in self-tolerance trigger lupus-like disease with creation of anti-nuclear antibodies preferentially, most likely credited to the existence of a huge potential B-cell repertoire reactive to nucleic acids and the existence of nucleic acid-induced account activation systems in several resistant cells, including T cells and dendritic cells. A feed-forward cycle constructed of anti-nuclear antibodies created by T cells and type 1 interferons secreted from nucleic acid-activated dendritic cells has a essential function in the advancement of systemic lupus erythematosus. IFN blockade 41. Hence, IFN as well as IFN I may play a function in the pathogenesis of individual SLE as well as mouse versions. Regulations of central patience and clonal anergy by apoptosis and phosphatases Self-reactive T cells generated in bone fragments marrow by arbitrary Ig Sixth is v gene rearrangements are tolerized by central patience such as removal, receptor and anergy editing. It is certainly set up that Bim currently, a pro-apoptotic member of the Bcl-2 family members, has a essential function in the removal and anergy of self-reactive T cells produced in bone fragments marrow by regulating apoptosis 42C 44. Self-reactive T cells in Bim ?/? autoantibody-transgenic rodents obviously get away from both removal and anergy 42, 43. Bim is definitely needed for BCR ligation-induced B-cell apoptosis that shows up to become included in the removal of self-reactive M cells 42. Bim is definitely also included in early loss of life of anergic M cells as they are much less delicate to success signaling generated by BAFF 43 that induce B-cell success by reducing Bim appearance 45. Therefore, Bim-mediated apoptosis takes on a important part in both the removal and anergy of self-reactive M cells. Infringement of anergy and removal in self-reactive Bim ?/? C cells might lead to the advancement of lupus-like disease in Bim ?/? rodents 46. The lipid phosphatase Boat-1 and the non-receptor type proteins tyrosine phosphatases (PTPs) SHP-1 and LYB/PEP regulate B-cell patience and the advancement of autoimmune illnesses 47, 48. A latest research by Getahun et al. 48 showed that inducible removal of either SHP-1 or Boat-1 reverses anergy of DNA-reactive C cells and enables natural difference of these self-reactive C cells to SBI-0206965 manufacture plasma cells. This result obviously signifies that anergy of self-reactive C cells is normally reversible and that both SHP-1 and Boat-1 are needed for maintenance of anergy. C cell-specific removal of Boat-1 or SHP-1 causes serious lupus-like disease with autoantibody creation 12, 13, recommending that a useful problem in M cells triggered by removal of SHP-1 or Vessel-1 is definitely adequate to abrogate B-cell threshold and to develop autoimmune disease. In M cells, both SHP-1 and Vessel-1 adversely regulate signaling through BCR. Vessel-1 dephosphorylates phosphatidyl inositol 3,4,5-triphosphate (PI(3,4,5)G3), needed for phosphatidyl inositol 3-kinase (PI-3E)-mediated service of AKT, which in switch activates different signaling substances, including mechanistic focus on of rapamycin (mTOR), and manages cell service procedures, including rate of metabolism, expansion, and cytoskeletal adjustments 49. The PI-3E path as well as the nuclear factor-kappa M (NF-B) path takes on a important part in BCR and BAFF-R signaling for B-cell success and service 50, 51. Therefore, Boat-1 inhibits B-cell success and account activation by regulating the PI-3K path. SHP-1 dephosphorylates proximal BCR signaling elements such as Ig/Ig and SLP-65/BLNK 52 needed for BCR signaling, including the PI-3T path. Both Boat-1 and SHP-1 include SH2 fields, and their account activation needs holding of these SH2 fields to tyrosine-phosphorylated protein. When BCR interacts with antigens, BCR-associated tyrosine kinases such as Lyn and Syk phosphorylate several cytoplasmic signaling molecules 53. Lyn phosphorylates B-cell co-receptors also, including Compact disc19, Compact disc22, PIR-B, and Compact disc72. Upon phosphorylation, Compact disc19 employees and activates SBI-0206965 manufacture PI-3T. In comparison, various other co-receptors such as Compact disc22, PIR-B, and Compact disc72 hire SHP-1 at the phosphorylated immuno-receptor tyrosine-based inhibition motifs (ITIMs) in their cytoplasmic locations and activate SHP-1 54 ( Amount 2). Although completely phosphorylated immuno-receptor tyrosine-based account activation motifs (ITAMs) in Ig/Ig get the tyrosine kinase Syk, these ITAMs are partly phosphorylated in anergic self-reactive M cells. The partly phosphorylated ITAMs Itga9 get and activate Vessel-1 rather of Syk 47. Most likely still SBI-0206965 manufacture to pay SBI-0206965 manufacture to constant connection of BCR with self-antigens in self-reactive M cells, both SHP-1 and Vessel-1 are constitutively triggered in anergic M cells and play a important part in the maintenance of anergy by controlling the PI-3E/AKT. Background We previously showed that a VLDL- and LDL-rich mix of human native lipoproteins induces a set of repressive epigenetic marks, i. regulation by native lipoproteins. Furthermore, we provide an example of DNMT1 acting as a de novo DNA methyltransferase independently of canonical de novo enzymes, and show proof of principle that de novo DNA methylation can occur independently of a functional Dicer/micro-RNA pathway in mammals. Background Atherosclerosis is characterised by the accumulation of lipids, extracellular matrix, smooth muscle, inflammatory and immune cells in the arterial wall . Diet-related and environment-related factors are pivotal determinants of atherosclerosis risk, thus epigenome remodelling by such factors has been proposed as an important underlying molecular mechanism for that disease . According to this view, environmental and nutritional risk factors might impose stable epigenetic “hits” during an individual’s lifetime that, possibly in synergy with other concomitant molecular changes, cause anti- or pro-atherogenic gene expression patterns [3,4]. Indeed, altered DNA methylation patterns have been detected in atherosclerosis [5-7]. Such changes may at least in part be caused by abnormal lipoprotein profiles, given their central role in atherogenesis . This idea is supported by our previous observation that a very low density- and low density lipoprotein (VLDL and LDL, respectively)-rich lipoprotein mix (VLR) induces global de novo DNA methylation in THP-1 human macrophages, in addition to other epigenetic modifications associated with non-permissive chromatin. The latter include loss of histone 4 acetylation and an increase in histone 4 lysine 20 hypermethylation . Furthermore, work by other groups showed that oxidised LDL (oxLDL) modulates promoter methylation of the estrogen receptor alpha and matrix metallopeptidase-2 and -9 genes in vascular smooth muscle cells [8,9]. The present work analysed the effects of lipoprotein-induced de novo DNA methylation on gene expression in THP-1 macrophages. Furthermore, it tested the involvement of individual DNA methyltransferase enzymes and known DNA methylation-mediating pathways. Our findings are discussed in the context of the current knowledge on the role of native lipoproteins in epigenetic gene regulation and inflammation. Methods Cell culture, lipoprotein isolation 648450-29-7 manufacture THP-1 monocytes were differentiated to macrophages as previously described . For Oil Red O staining and intracellular lipid determination, macrophages were processed as described . 648450-29-7 manufacture Human VLDL, LDL and high-density lipoprotein (HDL) were isolated and mixed to create the VLR mix (concentrations in g protein/ml: 68 VLDL, 32.1 LDL, 91.1 HDL) Mouse monoclonal to APOA4 that was used to stimulate THP-1 macrophages in serum-free conditions for 24 h as previously described . The rationale for VLR composition is outlined in and in brief is the following: 1) relative lipoprotein proportions reproduce a hyperlipidaemic profile similar to the one observed in APOE-null mice and in diabetic patients; 2) final absolute lipoprotein concentrations are ~10-fold lower than hyperlipidaemic levels to avoid cell toxicity; 3) triglyceride-rich lipoprotein levels in VLR were sufficient to induce intracellular lipid (Oil Red O-stained) droplets in our conditions (not shown) and increased intracellular triglyceride levels (additional file 1: Figure S1), suggesting that THP-1 macrophages exposed to VLR represented a model of lipid-loaded counterparts observed in hyperlipidaemic atherosclerosis . Each lipoprotein preparation represented a pool of a variable number of donors with unspecified lipidaemic status, obtained either in Malm?, Sweden (4 independent preparations) or Mexico City, Mexico (3 independent preparations), as specified in the Results section for each experiment. Lipoprotein preparations were stored at -80C for less than 6 648450-29-7 manufacture months and used within 3 days of thawing. Genome expression arrays Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays were hybridized with labelled total RNA extracted by using the RNeasy system (Qiagen), scanned with an Affymetrix GeneChip Scanner 3000 according to standard protocols at the microarray facility, Rigshospitalet, Copenhagen, Denmark. RNA integrity was checked by agarose electrophoresis at the source laboratory and again at the microarray facility. The dChip software (build April 15, 2005) was used for normalization and modelling using the PM-only model. Array data were deposited in the GEO database (http://www.ncbi.nlm.nih.gov/geo/) with accession numbers “type”:”entrez-geo”,”attrs”:”text”:”GSE9101″,”term_id”:”9101″GSE9101 and “type”:”entrez-geo”,”attrs”:”text”:”GSM230349″,”term_id”:”230349″GSM230349-“type”:”entrez-geo”,”attrs”:”text”:”GSM230360″,”term_id”:”230360″GSM230360. For pathway analysis, the BioCarta (http://www.biocarta.com) and. Banana cultivars may encounter chilling or freezing damage in a few of their cultivated areas, where outdoors banana can develop perfectly. most significant nutrient-rich plants, staple foods and ornamental vegetation cultivated in tropical and subtropical areas where temperature can be relatively high. non-etheless, considerable passions still leave in discovering banana cold-resistant genes and developing cool tolerant banana cultivars because of the chilling or freezing accidental injuries they might encounter at a few of their cultivated areas (Yang et al. 2012). Until now, however, zero effective technique offers however been developed to resolve the cool damage issue effectively. Crazy banana germplasm assets are loaded in China, where different studies have already been conducted within the last 20?years (Liu et al. 2007, 2012; Lai et al. 2007). Crazy banana varieties are more cool resistant than cultivated ones and can grow under relatively lower temps (Lai et al. 2007). The finding of beneficial crazy banana gene resources is definitely as a result of great usefulness for cold-resistance breeding of cultivated banana. Chilly acclimation can dramatically increase freezing tolerance of vegetation and is very important for extending their adaptation areas (Zhang et al. 2009). It was reported that sucrose can enhance chilly hardening of vegetation by regulating manifestation of cold-acclimation-associated genes such as (((and cold-acclimation related genes were rare due to the lack of sequence information. Wild banana is definitely widely distributed in all prefecture-level towns in Fujian Province, China (Lai et 630-93-3 manufacture al. 2007). Among numerous germplasm resources, a crazy banana human population recently found in Huanxi, Fuzhou City, China, was found to be very tolerant to chilly (Liu et al. 2012), making it very nice 630-93-3 manufacture gene resources for cold-resistant genes and germplasm resources for cold-tolerant banana breeding. The release of Malaysian crazy banana (and (the prospective gene of (and 6 (spp. The generated sequences were submitted to GenBank, and the related accession numbers were granted to “type”:”entrez-nucleotide”,”attrs”:”text”:”KC127685″,”term_id”:”448278879″,”term_text”:”KC127685″KC127685, “type”:”entrez-nucleotide”,”attrs”:”text”:”KC127686″,”term_id”:”448278881″,”term_text”:”KC127686″KC127686, “type”:”entrez-nucleotide”,”attrs”:”text”:”KC127687″,”term_id”:”448278883″,”term_text”:”KC127687″KC127687, “type”:”entrez-nucleotide”,”attrs”:”text”:”KC127688″,”term_id”:”448278885″,”term_text”:”KC127688″KC127688, “type”:”entrez-nucleotide”,”attrs”:”text”:”KC127689″,”term_id”:”448278887″,”term_text”:”KC127689″KC127689, “type”:”entrez-nucleotide”,”attrs”:”text”:”KC127690″,”term_id”:”448278889″,”term_text”:”KC127690″KC127690, “type”:”entrez-nucleotide”,”attrs”:”text”:”JX678611″,”term_id”:”421958220″,”term_text”:”JX678611″JX678611, “type”:”entrez-nucleotide”,”attrs”:”text”:”KC157569″,”term_id”:”449811522″,”term_text”:”KC157569″KC157569, “type”:”entrez-nucleotide”,”attrs”:”text”:”KC157570″,”term_id”:”449811524″,”term_text”:”KC157570″KC157570, 630-93-3 manufacture “type”:”entrez-nucleotide”,”attrs”:”text”:”KC157571″,”term_id”:”449811526″,”term_text”:”KC157571″KC157571, “type”:”entrez-nucleotide”,”attrs”:”text”:”KC157572″,”term_id”:”449811528″,”term_text”:”KC157572″KC157572, “type”:”entrez-nucleotide”,”attrs”:”text”:”KC157573″,”term_id”:”449811530″,”term_text”:”KC157573″KC157573 and “type”:”entrez-nucleotide”,”attrs”:”text”:”KC157574″,”term_id”:”449811532″,”term_text”:”KC157574″KC157574, respectively. Recognition, characterization and bioinformatic analysis of genes from cold-resistant crazy banana Huanxi Multiple-sequence BLAST search exposed that and experienced related ORF sequences that were 95.51?% identical to the of Malaysian wild banana (and 630-93-3 manufacture shared lower identity (only 76.58?%). These sequence variations may be due to variations between genes or varieties. Bioinformatics prediction result exposed that all the 6 were fundamental, hydrophilic, and unstable proteins possessing transmembrane domains with expected location in the nucleus or in membranes. Moreover, 21C26 phosphorylation sites were found in KIN10s (Table?1). Observed variations in the number and position of these phosphorylation sites suggest that some of their potential functions may be different. The KIN10s possessed 10C13 conserved domains, most of which were protein kinase domains (Additional file 1: Table?S1). Phylogenetic analysis 630-93-3 manufacture of KIN10 sequences generated the tree demonstrated in Additional file 2: Number?S1. Besides the Malaysian crazy banana KIN10, KIN10 and KIN10 showed the closest relationship with crazy banana Huanxi KIN10s. Table?1 Info of KIN10s, HOS1 and ICE1s proteins in crazy banana Huanxi Recognition, characterization and bioinformatic analysis of from cold-resistant crazy banana Huanxi The cDNA was 2926?bp very long and contained a 2904?bp ORF encoding 967 amino acids. Multiple-sequence BLAST assessment showed from Huanxi shared high similarity (93.95?%) with the Malaysian crazy banana (GSMUA_Ach1G14640_001). The major difference between the two varieties was the presence of a 140?bp insertion in the upstream region of the Huanxi. On the basis of bioinformatics prediction analysis, HOS1 was shown to be a nuclear-localized, hydrophilic unstable protein without transmission peptide. And 57 Ctsk phosphorylation sites and a specific ELYS-like conserved domain were found in HOS1 (Table?1). Phylogenetic analysis of HOS1 sequences generated the tree demonstrated in Additional file 3: Number?S3. Besides the Malaysian crazy banana HOS1, HOS1 showed the closest relationship with crazy banana Huanxi HOS1. Recognition, characterization and bioinformatic analysis of genes from cold-resistant crazy banana Huanxi Multiple-sequence BLAST search showed the cloned genes shared higher identity (97.52?%) with Malaysian crazy banana (GSMUA_Achr10 G18380_001) compared with and (92.08?%). A 75?bp sequence, which was almost exactly the same size while that of introns in Malaysian crazy banana, was missing from the middle region of Snow1-1CSnow1-4 in crazy banana Huanxi. Additional missing sequences in crazy banana Huanxi were a 16?bp sequence absent from your upstream region of and and a 19?bp sequence deleted from your termination codon region of and and were 9?bp longer in crazy banana Huanxi. Interestingly, compared with the Malaysian crazy banana of crazy banana Huanxi contained one more intron and one fewer exon and possessed two additional introns, which might be results of alternate splicing in development (Keren et al. 2010). Relating to bioinformatics prediction, the 1st four crazy banana Huanxi Snow1s encoded related numbers of amino acid residues, whereas the number of amino acid residues encoded by Snow1-5 and Snow1-6 was quite. Background Sofosbuvir and ledipasvir with or without ribavirin (RBV) regimens (SLR vs. 210 possibly relevant game titles and abstracts had been determined through the digital data source and manual queries. Of the 20 reports that were considered to be potentially relevant, seven met the study inclusion criteria. Thirteen potential trials were excluded for the following reasons: six included co-infected patients, five contained non-genotype 1 HCV contamination patients, and two failed to provide sufficient data on primary outcomes. Finally, seven RCTs 86639-52-3 manufacture involving genotype 1 HCV contamination patients were included in the meta-analysis (Fig.?1). The resulting analyses included 2601 participants, of which 1204 were in the SLR therapy group. The full text of all eligible RCTs was published between 2014 and 2015. Patients in the included trials were from the 86639-52-3 manufacture USA, New Zealand, France, Japan, and other countries and were aged mainly 50C60?years. The basic characteristics of the seven RCTs included in the meta-analysis are presented in Table?1. Fig.?1 Flowchart from the literature selection and search methods used Desk?1 Main characteristics from the research and sufferers signed up for this meta-analysis Quality Assessment The methodological quality from the included trials was assessed using the Jadad scale, and the full total email address details are proven in Desk?2. All of the included research got high methodological quality and have scored five or even more factors. The randomization treatment was reported in enough detail to make sure that it was suitable in four research, but had not been reported in three. Furthermore, all scholarly research attained an acceptable randomization concealment and blinded the procedure groupings effectively. Finally, five from the seven content reported the real amount and the reason why for just about any dropouts or treatment withdrawals. Desk?2 Evaluation of the grade of the KLRC1 antibody research contained in the meta-analysis SVR12 in the SL and SLR Groupings The meta-analysis of SVR12 in every sufferers receiving SLR and SL therapy is proven in Fig.?2. The SVR12 in genotype 1 HCV infections sufferers ranged from 70 to 100?%. The pooled data demonstrated that there is no statistically factor in the entire proportion of sufferers achieving SVR12 between your two groupings (RR?=?1.002, 95?% CI?=?0.988, 1.017, P?=?0.780, I 2?=?5.3?%). Fig.?2 Meta-analysis looking at the SVR12 price between your SLR and SL groupings Predicated on treatment history, the existence or lack of duration and 86639-52-3 manufacture cirrhosis of treatment, we performed subgroup analyses subsequently. Treatment-na?ve sufferers that received the SLR and SL regimens had an identical possibility of achieving SVR12 (RR?=?0.994, 95?% CI?=?0.975, 1.014, P?=?0.567, I 2?=?0.0?%). Equivalent observations had been manufactured in previously treated sufferers (RR?=?1.020, 95?% CI?=?0.990, 1.051, P?=?0.201, We 2?=?32.6?%). For the lack or existence of cirrhosis, the SLR program did not present an excellent SVR12 price in cirrhotic sufferers (RR?=?1.022, 95?% CI?=?0.955, 1.094, P?=?0.528, I2?=?70.9?%) or sufferers including people that have cirrhosis (RR?=?1.003, 95?% CI?=?0.990, 1.016, P?=?0.629, I 2?=?0.0?%). Taking into consideration the length 86639-52-3 manufacture of treatment, there is no statistically factor in the percentage SVR12 between your SLR and SL groupings in sufferers getting 12?weeks of treatment (RR?=?1.010, 95?% CI?=?0.989, 1.031, P?=?0.374, We 2?=?59.0?%) or sufferers getting 24?weeks of treatment (RR?=?1.010, 95?% CI?=?0.988, 1.025, P?=?0.496, I 2?=?44.6?%). Just SVR12 price among sufferers who received 8?weeks of SLR therapy was more 86639-52-3 manufacture advanced than that among sufferers who have received 8 statistically?weeks of SL therapy (RR?=?1.040, 95?% CI?=?1.001, 1.081, P?=?0.047, I 2?=?0.0?%). The info through the subgroup evaluation of treatment background, the lack or existence of cirrhosis, and duration of treatment are shown in Desk?3. Desk?3 Outcomes of subgroup analyses analyzing the difference in SVR12 predicated on treatment history, the existence or lack of cirrhosis, and duration of treatment in sufferers with HCV genotype 1 infection Relapse Prices in the SL and SLR Groupings Next, the relapse prices had been likened in patients that received the dual and triple therapy. Data revealed the fact that. History: Chlorogenic acid (CGA) or 5-caffeoylquinic acid was found out to be the dominant phenolic compound in leaves of (Zingiberaceae). tyrosinase inhibition and antibacterial properties. The entire fractionation process required only 6.5 hours using Rabbit Polyclonal to PTGER3. gravity flow. From 50 g of leaves the final yield of CGA draw out was 0.2 g (0.4%). The CGA content material from the standardised natural extract from leaves of (40%) can be 1.6 times that of commercial extracts from honeysuckle blossoms (25%). GSK461364 Summary: With high CGA content material the standardised natural draw out includes a great potential to become developed into practical food and additional health items. Leaves of varieties (Zingiberaceae) are high ginger vegetation of disturbed exotic forests. Inflorescences are borne on stalks protruding from the bottom or are located in the dirt level. The varying shades of pink and red flowers and bracts make sure they are extremely attractive plants. In Peninsular Malaysia a complete of 15 varieties continues to be recorded.[1 2 Vegetation of possess various traditional and industrial uses as meals condiment ornamentals and medication. The hearts of youthful shoots inflorescences and fruits from the torch ginger (Jack) R.M. Kantan or Smith are consumed by indigenous areas while condiment eaten natural or cooked. In Southeast Asia inflorescences of are widely cultivated as spices for GSK461364 meals flavouring so that as ornamentals. Fruits are accustomed to deal with earache while leaves are requested cleaning wounds traditionally. Leaves blended with other aromatic herbs in drinking water are utilized by post-partum ladies for bathing to eliminate GSK461364 body odour. Inside our previous study antioxidant properties in terms of total phenolic content (TPC) and ascorbic acid equivalent antioxidant capacity (AEAC) of leaves of 26 ginger species belonging to eight genera were screened. Results showed that leaves of had the strongest TPC and AEAC followed by species assessed leaves of had the highest values. Prompted by their outstanding antioxidant properties leaves of were analysed for phenolic constituents. Three caffeoylquinic acids (CQA) i.e. 3-CQA or neochlorogenic acid 5 or chlorogenic acid and methyl 5-CQA were reported for the first time in Zingiberaceae.[7 8 Three flavonoids namely isoquercitrin quercitrin and (+)-catechin GSK461364 were also isolated. Chlorogenic acid (CGA) is the dominant phenolic compound in leaves of (294 ± 53 mg CGA/100 g) was found to be significantly higher than flowers of Thunb. or Japanese honeysuckle (173 ± 13 mg CGA/100 g) the commercial source. CGA (5-CQA) is an ester of caffeic and quinic acids that is commonly found in coffee and in fruits such as prunes and plums.[9-11] CGA is one of the abundant polyphenols in the human diet and is the only CQA that is commercially available.[9 12 It is a natural antioxidant with commercial applications in medicine food and cosmetics. CGA is an antioxidant having two phenolic groups which are able to scavenge free radicals via proton transfer. It is also a bioactive compound with anti-inflammatory antitumor antimutagenic anticarcinogenic antidiabetic analgesic and antipyretic properties.[14-16] CGA protects against degenerative and age-related diseases in animals and contributes to the prevention of cardiovascular diseases in humans.[17 18 Consumption of CGA enriched instant coffee induced decrease in blood sugar absorption body fat and pounds in the torso. With this research a protocol to make a standardised herbal extract of CGA from leaves of is reported. Fractions had been analysed for CQA content material CGA content material total phenolic content material radical scavenging activity antibacterial activity and tyrosinase inhibition capability. Components AND Strategies Vegetable materials Leaves of had been gathered from Janda Baik in Pahang. The species is widely cultivated and can be easily identified as its leaves emit a characteristic pleasant sour scent when crushed. Voucher specimen of (EC14) was deposited at the herbarium of Forest Research Institute Malaysia. Leaf extraction Leaves of (50 g in triplicate) were freeze dried overnight at 0.125 mbar and -50°C and ground in a blender. Floor leaves had been extracted four instances with 500 ml of 30% ethanol for just one hour every time in orbital shaker. Crude draw out was filtered under suction as well as the solvent eliminated having a rotary evaporator (Eyela) at 50°C. For every batch residues had been weighed (4 g) and kept at -20°C for even more make use of. Fractionation with Diaion Horsepower-20 The 30% ethanol crude leaf draw out (in triplicate) was put through column chromatography. The draw out (4 g) was dissolved in 10 ml GSK461364 of 20% ethanol and chromatographed more than a 40 g Diaion Horsepower-20 (Supelco) column. Fractions had been eluted using.	2	34	8	0	5	0.407245	13	12,836
Kidney Transplant Dx. Coding By: Gouri Pathare MBBS, CPC Kidney transplantation is a treatment option for most patients with End Stage Renal Disease (ESRD). The procedure may be deceased-donor (cadaveric) or living-donor transplantation. Living-donor renal transplants may be genetically related (living-related) or non-related (living-unrelated) transplants. Diabetes mellitus, hypertension, cystic kidney disease, urologic conditions, and external causes such as trauma and toxins, all may cause kidney failure. When kidneys cease to filter wastes and extra fluid from the bloodstream, renal failure is considered to be permanent and consideration must be given to hemodialysis and/or kidney transplantation. A common complication of kidney transplant is rejection of the transplanted organ. The body’s immune system, or defense mechanism, recognizes that something foreign is in the body and tries to destroy it When post-organ transplant patients present for care, the coder should review medical record documentation to determine whether the patient has any complications of the transplanted organ. Consider 996.81 Complications of transplanted kidney versus V42.7. Kidney replaced by transplant. Assign V42.7 only if there is no complication of the kidney transplant. Code V42.7 is never used with 996.81. V codes are status codes used to classify certain conditions that may have an impact on the patient’s health status. It is appropriate to assign 996.81 when the kidney transplant is being rejected by the patient, or if there are any other complications or diseases that affect the function of the transplant. You must assign two codes to completely describe the impact on the transplanted kidney. For example, if the patient presents with acute kidney injury and has a history of kidney transplant, the function of the patient’s kidney is affected. Hence, the coder would assign 996.81 and 584.9 Acute kidney failure, unspecified. Physicians may document in the medical record that a kidney transplant recipient also has chronic kidney disease (CKD). The coder should not assume that this kidney disease is a complication of the transplant, unless the physician documents the link. A kidney transplant may not fully restore function to the kidney, and some residual kidney disease could be present. Without the link provided by the physician, coders should report V42.7 with an additional code for the CKD. Physicians may also document in the medical record of the post-kidney transplant recipient ESRD. Coders should pay special attention to this diagnosis because the physician may be indicating a past history of ESRD. The kidney transplantation was initially performed to improve the patient’s kidney function, and it would be unlikely that patient would still have ESRD. Physician clarification is required, as the addition of 585.6 End stage renal disease is a major complication/comorbidity, and can significantly affect the MS-DRG assignment. ICD 10 Coding for Kidney Transplant Kidney transplant status Z94.0 Patients who have undergone kidney transplant may still have some form of chronic kidney disease because the kidney transplant may not fully restore kidney function. Therefore, the presence of CKD alone does not constitute transplant complication. Assign the appropriate N18 code for the patient’s CKD and code Z94.0, kidney transplant status. Complications of kidney transplant T86.1 Unspecified complications of kidney transplant T86.10 Kidney transplant rejection T86.11 Kidney transplant failure T86.12 Kidney transplant infection T86.13 Use additional code to specify infection. Other complications of Kidney transplant T86.19. Gouri Pathare MBBS, CPC, is a practicing medical professional with nearly 30 years of experience as an independent private medical practitioner in Mumbai, India, and has worked as a clinical specialist training coders for Episource India Pvt, Ltd., a United States-based KPO company. She was lecturer in Anatomy in Government Medical College.	4	2	0	0	9	0.932209	9	860
* To whom correspondence should be addressed. Received May 17, 2001; Revision received July 10, 2001 Cadherins are a family of membrane receptors that mediate calcium-dependent homophilic cell-cell adhesion. Cadherins play a key role in the regulation of organ and tissue development during embryogenesis. In adult organisms, these proteins are responsible for formation of stable cell-cell junctions and maintenance of normal tissue structure. Disruption in expression or function of cadherins may cause uncontrolled cell migration and proliferation during tumor development. This review focuses on the structure and physiological functions of classical cadherins. KEY WORDS: cadherins, cell-cell adhesion, morphogenesis, signaling, oncogenesis STRUCTURE OF CLASSICAL CADHERINS The majority of members of the cadherin superfamily are transmembrane glycoproteins that pass the membrane only once. The N- and C-termini of the cadherin protein chain are located outside and inside the cell, respectively (Fig. 1). The extracellular portion of the cadherin molecule consists of a varying number of so-called cadherin domains that are highly homologous to each other. Each domain is comprised of approximately 110 amino acid residues . Classical cadherins contain five cadherin domains that are commonly designated as EC1-EC5 (beginning with the N-terminus of the molecule). The conformation of the cadherin molecule is stable only in the presence of Ca2+, whose binding with the extracellular portion of the polypeptide chain is prerequisite for cadherin-mediated cell-cell adhesion. Calcium-binding sites consisting of short highly conserved amino acid sequences are located between neighboring extracellular repeats . The cytoplasmic domain of classical cadherins is associated with the cytoplasmic proteins catenins, which, in turn, serve as intermediate linkers between the cadherins and actin filaments [10-12]. It is this cadherin-catenin complex that is required for providing normal cell-cell adhesion. In principle, extracellular cadherin domains per se are capable of homophilic recognition and binding. It was shown that cells that express mutant cadherins lacking the cytoplasmic domains can bind with substrate covered with purified cadherin ectodomains. However, in this case adhesion is much weaker than in the case of cells bearing full-size cadherins [11, 13, 14]. These data indicate that the formation of stable cell-cell junctions depends on the presence in the cadherin molecule of functionally active cytoplasmic domain and association of the latter with the cytoskeleton. As mentioned above, cadherins mediate homophilic adhesion: during co-culturing of different types of cells, those cells first aggregate that bear identical cadherins on their surfaces . Similar dependence between cell sorting in the developing tissues and expression of different cadherins in them is observed during embryogenesis . The extracellular domains (primarily, the N-terminal domain EC1) play a key role in homophilic recognition between two cadherin molecules. It was shown that cells expressing chimerical E-cadherin, in which the EC1 domain was substituted with EC1 domain of P-cadherin, did not recognize the cells bearing native E-cadherin and aggregated with the P-cadherin-expressing cells . The site responsible for homophilic recognition contains 40 amino acid residues located in the C-terminal region of EC1. Blashchuk et al. assumed that sequence His-Ala-Val located in the C-terminal region of domain EC1 plays a key role in the interaction between cadherins because synthetic peptides containing this sequence effectively blocked mouse embryo blastomere assembling (a process that is mediated by cadherins). However, later it was shown that homophilic recognition also requires the presence of other regions located in the N-terminal domain. In addition, it was discovered that the sequence His-Ala-Val is contained only in the molecule of classical cadherins of type I that involves E- (epithelial), N- (neural), P- (placental), VE- (vascular endothelial), and R- (retinal) cadherins. The corresponding regions of type II classical cadherins that involve recently discovered cadherins designated by numbers 5-12 contain other amino acid residues [9, 10]. Type I and II cadherins also differ from each other in some amino acid residues. Fig. 1. Structure of classical cadherins and their interaction with cytoplasmic proteins . It should be noted that some cadherins can also mediate weak heterophilic interactions. In particular, E- and N-cadherin can bind with the integrin alphaEbeta7 and receptor for fibroblast growth factor [20, 21], respectively. The role of the four other cadherin repeats (EC2-4) in the cell-cell interaction remains obscure. Possibly, only EC1 domain directly participate in homophilic binding, whereas the remaining domains act as spacers providing the required distance between the junction and cell surface. Nevertheless, they are required for cadherin-dependent adhesion: in the absence of other extracellular domains, the N-terminal domain alone cannot maintain functional binding or adhesive activity . Numerous data that has accumulated to date show that the extracellular cadherin fragments exist in the form of stable parallel lateral dimers. Lateral dimers were revealed by X-ray analysis of N-cadherin EC1 domains and E-cadherin fragments including EC1 and EC2 domains . The existence of dimers was also shown for the whole extracellular fragment of C-cadherin . In the same experiments, it was also shown that the ability of C-cadherin monomers to aggregate significantly decreases compared to the dimers. To date, the mechanism of dimer formation is poorly understood. Apparently, N-cadherin dimers are stabilized by the hydrophobic interactions between the monomers , whereas in the case of EC1-EC2 fragment of E-cadherin dimeric structure is maintained by Ca2+ . It is still unclear why dimers exert higher activity than monomers during cell-cell interaction. Two main views on this phenomenon exist. The first hypothesis proposes that dimers are bivalent, which increases their avidity. The second hypothesis implies that dimer formation is associated with the occurrence of a unique site ensuring homophilic binding, which is absent from the monomers. The mechanism of interaction of cadherin dimers located on the membranes of different cells has been also the subject of much controversy. Based on the results of X-ray analysis of NCD1, Shapiro et al. proposed the existence of a zipper-like self-assembling structure. This molecular zipper model (Fig. 2) logically explains the mechanism whereby numerous weak bonds can ensure highly efficient binding in the cell layer. However, some authors believe that cadherin zipper is an in vitro artifact and suggest an alternative hypothesis that was formulated based on the results of electron microscopic analysis of adhesive zone preparations obtained by the freeze-fracture method . Separate protein cylinders extending from one cell surface to another and binding with the similar structures on the neighboring cell are seen on the images. According to the second model, cadherin molecules (dimers or oligomers) act as discrete units and do not form zipper-like ordered structures on the cell surface . Fig. 2. Two models of cadherin molecular organization in adhesive junctions. The molecular zipper model based on the results of X-ray analysis of N-cadherin EC1 domain is shown on the left. The model of cylindrical oligomers based on the results of electron microscopy of zonula adherens preparations obtained by the freeze-fracture method is shown on the right . The conclusion that cadherin complexes interact with the cytoskeleton was first made based on the data that cadherins cannot be extracted with non-ionic detergents that effectively solubilized other membrane proteins [13, 25, 26]. It was shown later that the major cytoplasmic proteins associated with the cytoplasmic domain of cadherins and participating in cell adhesion are alpha- and beta-catenins, which mediate the interaction between the cadherins and actin cytoskeleton [11, 13, 25, 27-30]. The catenin-binding site was mapped on E-cadherin. It is located at the distance of 56 amino acid residues from the C-terminus of the molecule [25, 31]. Biochemical analysis with the use of purified catenins and recombinant cytoplasmic domain of cadherins [32, 33] and expression of beta-catenin deletion mutants [34-36] showed that beta-catenin directly binds to the cytoplasmic cadherin fragment and serves as a linker for alpha-catenin attachment. The crucial role of the cytoplasmic domain of cadherin (and the catenin-binding site, in particular) is corroborated by numerous experiments. It was shown that deletion of the cytoplasmic domain or the catenin-binding site suppresses stable cadherin-mediated adhesion of cultured cells [11, 13]. Alternatively, overexpression of the catenin-binding site in the cultured cells , Xenopus laevis embryos , or in the intestinal cells of transgenic mice also entails disruption of cell-cell junctions. Such unusual, at first glance, result (at least, in the case of Xenopus laevis) can be, apparently, explained by competition of the expressed catenin-binding site with the endogenous cadherin for catenin binding. The evidence for participation of alpha-catenin in cell adhesion was obtained on lung carcinoma cell culture that does not contain alpha-catenin and aggregates with each other very weakly despite the presence of cadherins on the cell surface. However, transfection with alpha-catenin cDNA restores cadherin-mediated adhesion in these cells [27, 29]. Rim et al. showed that alpha-catenin directly binds to actin filaments both in vitro and in vivo in the cultured cells. The actin-binding protein alpha-actinin contained in adhesive junctions apparently also interacts with alpha-catenin . Participation of beta-catenin in cell adhesion was confirmed in experiments on Drosophila embryos using mutation analysis of protein armadillo, a homolog of beta-catenin . beta-Catenin is attached to the cytoplasmic domain of cadherin via its central region containing so-called armadillo repeats [34, 36]. These repeats (40 amino acid resides each) were first described in protein armadillo in Drosophila [40, 41]. alpha-Catenin binds to the N-terminus of beta-catenin [32, 34-36]. The role of a linker between cadherin and alpha-catenin is apparently the only function of beta-catenin in cell adhesion. It was shown that a chimerical molecule where the cytoplasmic domain of E-cadherin is substituted with alpha-catenin ensures cell adhesion in the absence of beta-catenin as successfully as the whole protein complex . Plakoglobin (gamma-catenin) sometimes substitutes beta-catenin in the cadherin-catenin complex . However, its physiological role is not completely understood. Plakoglobin is the major component of the desmosomes , where it is associated with the desmosomal cadherins [44, 45]. The high extent of homology of plakoglobin to beta-catenin and armadillo [26, 46] implies that these proteins may have similar functions. However, mouse embryo cells lacking beta-catenin due to genetic recombination aggregate very weakly and readily dissociate despite the presence of plakoglobin in them . This is indicative of inability of plakoglobin to completely substitute for beta-catenin in cell adhesion. Deletion of the plakoglobin gene, which was also caused by homologous recombination, entails lethal changes in the heart structure and early death of the embryos, presumably due to disruptions in desmosomal junction formation . Other cytoplasmic proteins directly associated with cadherin are tyrosine phosphatases [49, 50] and the substrate for src-kinase p120cas [51-53]. Interestingly, the level of cadherin expression in the cell may affect catenin expression. Transfection of L-cells with E-, N-, or P-cadherin cDNA results in a significant increase in the catenin content without changing the catenin mRNA content. Hence, the presence of cadherins regulates catenin expression at the post-translation level . It was also reported that cadherin cytoplasmic domain may mediate adhesion independently of catenins. Chimerical cadherin molecules in which cadherin cytoplasmic domain was substituted for the analogous domain of desmoglein-3 (one of desmosomal cadherins) that cannot bind catenins, mediates cadherin-dependent adhesion in the cultured cells . Thus, association with catenins is not the only way of participation of the intracellular cadherin domain in cell-cell adhesion. CELL-CELL JUNCTIONS CONTAINING CADHERINS Immunohistochemical analysis of tissues and cultured cells shows that cadherins most often are constituents of cell-cell adhesive junctions (Fig. 3). This type of junctions involves autotypic junctions between the layers of the same glial cell in the axon myelin sheath ; adhesive junctions in synapses, where cadherins link pre- and postsynaptic membranes in the regions adjacent to the neurotransmitter secretion areas [57, 58]; the intermediate disks between the cardiomyocytes ; and some other. The best-known type of cell-cell adhesive junctions is zonula adherens located at the apico-lateral border of the epithelial layer a little lower than the tight junctions. Actin bunches attached to the adhesive junctions girding the cell on the cytoplasmic side are located parallel to the membrane surface and form a united contracting network in the epithelial layer. Assembling of the belt-like zonula adherens is apparently the basis for the occurrence of the epithelial morphology of the cell layer [60-63]. During morphogenesis, folding of the epithelial layers into tubes is often attained by contraction of actin filaments contained in the zonula adherens, which is associated with narrowing the apical end of each cell in the apical layer and results in the cell layer bending [64, 65]. Besides cadherins and catenins, adhesive junctions contain numerous proteins (such as vinculin, ezrin, moesin, and radixin), protein components of the actin cytoskeleton, and integral membrane proteins (e.g., epidermal growth factor receptor, EGF) . Genetic studies on Drosophila revealed other components required for adhesive junction assembly. In particular, the genes whose mutations lead to disruptions in the course of zonula adherens assembling were identified in studies on Drosophila embryos. They involve the gene of beta-catenin homolog, armadillo, which is completely consistent with the view on the key role of this protein in cadherin-mediated adhesion [30, 67], as well as the genes crumb and stardust [67-69]. It was shown that gene crumb encodes the integral membrane protein that is required for epithelization of the ectodermic cells. In mutant individuals with inactive crumb gene normal cadherin-catenin complexes are expressed on the cell surface; however, their distribution is chaotic, leading to disruption in formation of mature zonula adherens in the epithelium [68-70]. Fig. 3. Cell-cell junctions formed by cadherins: a) epithelial zonula adherens; b) intermediate disks between the cardiomyocytes; c) adhesive junctions restricting the area of neurotransmitter secretion in the synapse; d) autotypic junctions between the glial cell layers in axon myelin sheath . It should be noted that in many cells cadherins can mediate adhesion without formation of morphologically pronounced adhesive junctions. Even in the epithelium of some organs, where cell-cell adhesion depends on E-cadherin, zonula adherens is absent . Cadherin-mediated adhesion without cadherin accumulation in the adhesive junctions was also described for blastomeres , nerve ridge cells , and fibroblasts transfected with different types of cadherins . REGULATION OF CADHERIN ACTIVITY Cadherin-mediated adhesion can be regulated by a variety of extracellular signals, including growth factors [72-74], peptide hormones [75, 76], signals from gap junctions , and cholinergic receptor agonists . In response to these external stimuli, different signals are generated in the cell, of which protein phosphorylation is, apparently, the most important for the regulation of cadherin function . Protein kinase C (PKC) participates in the activation of E-cadherin-dependent mouse embryo cell compacting, which was demonstrated with the use of a combination of pharmacological agonists and antagonists. Embryo compacting is accelerated by the addition of PKC-stimulating agents (e.g., phorbol ester and diacylglycerol) and inhibited by PKC-blocking agents , the PKC effect being blocked by the addition of anti-E-cadherin antibodies. However, it was not determined which PKC-mediated way is activated in this case. Using a similar experimental approach, a potential inhibitory effect of tyrosine phosphorylation on cadherin function was shown. Several scientific groups discovered that enhancement of tyrosine phosphorylation (transfection with v-src or incubation of the cells with pervanadate) weakens cadherin-mediated cell-cell adhesion. Components of the cadherin-catenin complex (primarily beta-catenin) undergo tyrosine phosphorylation in response to v-src transfection and incubation with pervanadate [80-82]. Attenuation of adhesion in these experiments was blocked by herbimicin, which is also indicative of participation of tyrosine phosphorylation in the regulation of cadherin activity. It was also shown that v-src can affect cadherin-mediated adhesion irrespective of beta-catenin . The authors of this work used mutant E-cadherin that could directly bind with the C-terminal fragment of alpha-catenin and induce adhesion without the participation of beta-catenin. However, in this case transfection with v-src also significantly inhibited cell-cell adhesion. Other data confirming the effect of tyrosine phosphorylation on cadherin-dependent adhesion are known. Tyrosine phosphorylation of beta-catenin is observed when cells are treated with hepatocyte growth factor (HGF) and EGF (agents that can induce dissociation of epithelial cells) . Tyrosine kinases or their substrates can associate with the cadherin-catenin complex. It is known that p120cas, a member of the armadillo protein family, is a substrate for both src kinases and receptor tyrosine kinases . It was shown that p120cas directly binds to the distal part of the cytoplasmic domain of E-cadherin, forming a whole complex with cadherin and beta-catenin or plakoglobin [52, 53, 84, 85]. Activation of the Erb-2/Neu receptor tyrosine kinase in the epithelial cells causes disassembling of the cell-cell junctions formed by E-cadherin, which results in the loss of the epithelial phenotype by the cells . EGF receptor tyrosine kinase also can bind to the cadherin-catenin complex . In addition, it was shown that cadherin-catenin complex can interact with receptor-dependent tyrosine phosphatases [49, 50, 88]. Cadherin function may also be affected by cell-cell communication via gap junctions. Inhibition of cell-cell communication by expression of the chimerical protein connexin 32/connexin 43 inhibitor (a protein that forms gap junctions) in Xenopus embryo cells leads to blastomere separation. A similar effect is observed when mutant cadherin is expressed in the embryo cells. This phenotype can be corrected by coexpression of connexin 37 that is insensitive to the inhibitor . Similarly, cell-cell junction assembling in Novikov hepatoma cells is suppressed by anti-connexin and anti-cadherin antibodies . The mechanism of signal transduction mediated by the gap junctions remains obscure. It is assumed that in this case cadherin-dependent adhesion and cell-cell junction assembling may be regulated via temporal increase in the concentration of Ca2+ and other small signal molecules (such as cyclic nucleotides or inositol phosphate) penetrating through the gap junctions and activating the intracellular processes that affect cadherin activity. The strength of cell-cell interactions can be affected both by modulating cadherin activity and changing their expression level in the cell. It was demonstrated that an increase in cadherin content enhances cell adhesion [7, 90, 91]. It was also shown that cadherin expression in cultured cells is regulated by growth factors and peptide hormones [72, 73, 75, 76]. Another mechanism of regulation of cadherin activity is changing the extent of clustering of cadherin molecules in the junction area. As was mentioned above, lateral clustering of cadherin molecules can significantly affect the strength of cell-cell interaction. Changes in the extent of clustering can mediate rapid changes in cell adhesion strength. For example, mouse embryo blastomere compacting is associated with E-cadherin redistribution in the region of cell-cell junctions without any change in protein expression . CADHERINS AND SIGNALING To date, numerous data indicate that cell adhesion receptors can affect cell form, motility, and growth not only due to mechanical attachment of the cells to each other or to the substrate, but also by activating internal signaling . Some papers report that many effects of cadherin on cell behavior are rapid and apparently caused by a series of short-term signals rather than by assembling stable long-term cell-cell junctions [4, 6, 94]. However, until recently only indirect evidence of cadherin ability to induce the production of secondary messengers in the cell have been known. For instance, it was shown that axon outgrowth stimulated by N-cadherin is associated with changes in the cytoplasmic Ca2+ concentration and activation of G-proteins and tyrosine kinases. However, it was not clear whether these signals result from the direct interaction of N-cadherin molecules [95, 96]. Because different signal molecules (such as proteins belonging to the non-receptor src kinase family as well as some membrane receptors and phosphatases) were found in the cell-cell junctions of epithelial cells [49, 97, 98], it was suggested that these molecules can mediate cadherin-dependent signaling. Data on the direct effect of cadherins on the signal processes appeared only during the last two years. It was shown that inter-cadherin junctions in cultured fibroblasts induced oscillations in the cytoplasmic Ca2+ concentration, antibodies raised against the first domain EC1 mimicking this effect. The oscillations occurred in the regions of cell-cell interactions and coincided in time with translocation of actin and other cytoplasmic proteins into the adhesive complexes . N-Cadherin can regulate axon outgrowth by direct interaction with the EGF receptor, thereby activating the cascade of mitogen-activated protein kinases (MAPK) . The experiments on cultured keratinocytes showed that adhesive junction formation leads to a rapid activation of MAPK-dependent signaling and that this effect is mediated by E-cadherin. In addition, E-cadherin can stimulate MAPK by ligand-independent activation of EGF receptors . It also activates Cdc42, a low-molecular-weight GTPase belonging to the Rho family, which regulates the cytoskeleton structure . For a long time beta-catenin, whose signal activity is well known, was considered as a candidate for the role of a messenger of signal transduction from cadherins, with which it is associated. beta-Catenin and its homolog armadillo from Drosophila are components of Wnt/wingless signal pathway that plays a key role in embryogenesis [102-104]. Recent data, however, indicate that the interaction between beta-catenin and cadherins is not prerequisite for manifestation of its signal activity. It was also shown that beta-catenin function as a cadherin partner during adhesive junction formation is not directly associated with its signal function in the cytoplasm and/or nucleus, where it affects transcription of genes by interacting with specific transcription factors [36, 105-111]. Free beta-catenin content in the cytoplasm is regulated by the protein product of the APC (adenomatous polyposis coli) gene. Formation of the complex between these two proteins is a signal for beta-catenin degradation. Conversely, triggering the Wnt signal pathway results in beta-catenin stabilization, its accumulation in the cytoplasm, and binding to the transcriptional factor Tcf, which, in turn, stimulates transcription of some genes. On the other hand, although the adhesive and signal functions of beta-catenin are separated, the formation of cell-cell junctions can apparently indirectly affect beta-catenin-dependent signaling. It was shown that overexpression of cadherins in the embryos of Xenopus laevis and Drosophila inhibited signal transduction via beta-catenin/armadillo [106, 112]. In Xenopus embryos, the inhibition is due to beta-catenin binding with C-cadherin on the inner surface of the cell membrane. As this takes places, beta-catenin is removed from its cytoplasmic pool, becoming inaccessible for participating in signaling. Thus, cadherins can regulate beta-catenin signaling activity by changing its distribution in the cell. It cannot be ruled out, however, that cadherins indirectly contribute to signaling regulation. Approaching of the membranes of the neighboring cells during adhesive junction formation may enable the interaction of membrane receptors and their membrane-bound ligands on the neighboring cells and activate juxtacrine signaling. This hypothesis is corroborated by data on association of some signal molecules with the cadherin-catenin complexes and on high concentration of tyrosine kinase substrates in the regions of adhesive junctions. The group of juxtacrine receptors described to date involves notch, delta, sevenless, and bride-of-sevenless (boss) receptors participating in Drosophila embryogenesis [113, 114] and associated with the membrane form of tumor necrosis factor (TNF) and transforming growth factor (TGFalpha) . It is tenable to assume that signaling via such receptors depends on the proximity of the surface of adjacent cells and, respectively, on formation of inter-cadherin junctions. This hypothesis is confirmed by the fact that expression of cadherins in the fibroblasts entails communication enhancement via gap junctions . THE ROLE OF CADHERINS IN MORPHOGENESIS The formation of tissues and organs during embryogenesis is determined by a number of processes coordinated in time and space, such as cell aggregation, polarization, differentiation, and migration. Because cell-cell and cell-nuclear matrix adhesive junctions play a key role in all these events, adhesion receptors are often called morphoregulatory molecules. One such adhesion-dependent processes is selective cell segregation. This phenomenon was discovered as early as in the 1950s. In classical works in embryology, it was shown that suspended cells from different amphibian blastophylla are capable of homotypic reaggregation to form junctions only with similar cells in correspondence with their histogenetic origin . Later it was discovered that this homotypic aggregation is based on selective expression of specific adhesion molecules on different subpopulations of cells. The role of cadherins in this process was revealed by Nose et al. . The L-cells were transfected with cDNA of either E- or P-cadherin. The suspensions were then mixed in vitro and analyzed for cluster formation. Under these conditions, highly selective adhesion between cells expressing cadherins of the same type was observed. Another morphogenetic process in which cadherins play a key role is cell condensing (i.e., transition of cell population from dispersed state to condensed solid formation). An example of such condensing is blastomere assembling at the early stages of embryogenesis. E-Cadherin plays a crucial role in cell condensing in mouse embryo morula: the embryo structure is disrupted as a result of treatment of the cells with blocking anti-E-cadherin antibodies, introduction of antisense nucleotides to E-cadherin mRNA into the cell, and in transgenic mice defective by the gene encoding this protein [118-123]. Injection of antisense nucleotides into Xenopus laevis oocytes, which decreases expression of EP-cadherin (a Xenopus laevis protein homologous to E- and P-cadherins), significantly attenuates adhesion between the blastomeres and entails disruption of the embryo structure . Numerous studies performed both in intact embryos and cultured cells revealed significant correlation between epithelization of mesenchymal cells and expression of specific cadherins in them. During somite development, mesenchymal cells comprising its future wall are polarized and temporarily form epithelium-like structures, the expression of N-cadherin in them significantly increasing [64, 65, 125]. Transfection of cultured mesenchymal cells with cDNA of different cadherins results in their epithelization [13, 126-128], whereas inhibition of cell-cell interactions by anti-cadherin antibodies leads to the loss of epithelial phenotype by the cells and stimulates cell motility and invasiveness [129-131]. One of the most vivid examples of participation of cadherins in morphogenesis is their role in the central nervous system development. At different stages of embryogenesis and in different structural layers, neuroepithelial tissues express more than 20 different cadherins involved in all key events of neurogenesis, beginning from selective aggregation of the cells at the earliest stages of embryo development and finishing with the formation of synapses [132-137]. Cadherins play a key role during neuroectoderm sorting and neural tube formation. It was also shown that before segregation of the neuroectoderm from the ectoblast in neurula, a coordinated decrease in the expression of E-cadherin and increase in that of N-cadherin occurs in the cells of future neuroectoderm. It is believed that it is N-cadherin that is responsible for selective cell uniting in the neural plate [64, 65, 138]. Interestingly, normal neural tube is formed in transgenic mice defective in the N-cadherin gene. Apparently, in this case N-cadherin is functionally substituted with other adhesion molecules (presumably, cadherin-6) . It is known that the coordinated change in the cell shape induced by microfilament contraction in zonula adherens underlies neural tube folding and other morphogenetic processes that require change in the shape of the epithelial layers [64, 65]. Further development of the neural tube involves its segregation to separate regions due to local expression of different cadherins. For example, selective distribution of E- and R-cadherins, cadherin-6, and cadherin-8 in different regions of embryonic brain is observed [135, 136, 140, 141]. The possibility of selective segregation of nerve cells that express cadherins of the same type was demonstrated in vitro. In vivo such segregation of the neural tube to segments apparently prevents the migration of nerve cells between adjacent regions of the developing brain . Normal expression of cadherins is required for neurite outgrowth activating and regulating. The expression of dominant-negative functionally inactive N-cadherin in developing frog retina blocks the axon and dendrite outgrowth. Those axons that are still formed are usually shorter and often do not have growth cones . In the experiments in vitro, it was shown that growth and migration of axons change during neuron culturing on the substrates containing recombinant cadherins. In particular, recombinant N-cadherin enhances adhesion of axons to the substrate and enables their projecting in the direction of higher concentrations of the recombinant protein. Similar growth stimulation is observed when the neurons are cultured on the monolayer of cells transfected with N-cadherin cDNA [8, 95, 143-146]. Such effect on axon projecting is apparently due to the interaction of N-cadherin with FGF receptor with subsequent MAPK activation . By contrast, another member of the cadherin family, T-cadherin, inhibits axon outgrowth [137, 147]. Thus, the coordinated action of different cadherins and other adhesion receptors expressed on the axon membrane and surrounding tissues ensure navigation of axon projecting to the peripheral targets. Cadherins also play a key role in setting and stabilization of junctions between the neurons and formation of neural nets and neuromuscular junctions [148-153]. In mouse postnatal brain, cadherins of the same type are expressed in functionally related regions (e.g., in the thalamus nucleus and related cortex regions ). During chick eye development N-cadherin stabilizes the junctions between the axon termini and their targets. Formation of a branched net of neural termini in the retina may be blocked by injecting anti-N-cadherin antibodies . It was shown that in synapses cadherins anchor the pre- and postsynaptic membranes, bordering the area of neurotransmitter secretion [57, 58]. E-Cadherin is also present in the myelin sheath of nerves, where it forms autotypic adhesion junctions between the plasma membrane layers of the same Schwann cell (Fig. 3). CADHERINS AND ONCOGENESIS The ability of tumor cells for uncontrolled growth, migration, invasion into surrounding tissues, and metastasizing is often associated with disruption of cell-cell and cell-extracellular matrix junctions [156, 157]. For this reason, special attention is currently paid to identification and characterization of cell adhesion receptors involved in tumor development. With regard for the role of cadherins in cell-cell adhesion, maintenance of tissue structure, and regulation of epithelial cell phenotype, it was assumed that the disruption of cadherin-dependent cell-cell interactions in the epithelium may cause attenuation of cell-cell junctions, loss of epithelial phenotype, enhancement of cell motility, removal of contact suppression of growth, and, as a result, uncontrolled proliferation and invasion of tumor cells . The majority of studies in this area focus on the role of E-cadherin in malignant cell transformation. In many works, it has been shown that E-cadherin expression is decreased or absent from different carcinomas (esophagus, stomach, or breast) [159-162]. Abnormal distribution of E-cadherin in tumor cells was often observed (it was absent from the regions of adhesion junctions). It should be noted that E-cadherin expression was most often decreased in the undifferentiated aggressive carcinomas that have high invasive potential . Similar results were obtained on cultured cells. Frixen et al. also reported that carcinoma cell lines with the epithelial noninvasive phenotype expressed E-cadherin, whereas the latter was absent from the cells with the fibroblastoid phenotype. Navarro et al. revealed reciprocal dependence between the amount of E-cadherin expressed on the cell surface of different carcinomas and the ability of these cells for invasion. Malignant transformation of MDCK epithelial cells (which are noninvasive in normal state) as a result of injection of Harvey and Maloney sarcoma virus to the cell culture is accompanied by a decrease in E-cadherin expression on the cell surface. A similar change of MDCK cell phenotype from noninvasive for invasive is also observed after disruption of cell-cell junctions in the presence of anti-E-cadherin antibodies . Conversely, transfection of the carcinoma cells with E-cadherin cDNA restores normal cell phenotype, decreases invasiveness and migration, and suppresses tumor growth [163-165]. The few studies on the role of P-cadherin in oncogenesis also revealed a correlation between decreased expression of this protein and the invasiveness of lung carcinomas and melanomas . Unexpected results were obtained when studying the effect of N-cadherin on tumor cells. It was discovered that expression of this protein is significantly enhanced in invasive undifferentiated breast carcinoma cells . It was also shown that an increase in N-cadherin expression in the carcinoma cells simultaneously with the decrease in E- and P-cadherin expression changes the phenotype from epithelial to mesenchymal . Transfection of MCF-7 carcinoma cells with N-cadherin cDNA significantly enhances the invasiveness and stimulates metastasis development despite the presence of E-cadherin in these cells . Such an opposite effect of cell-cell adhesion mediated by E- and N-cadherins on cell behavior may be due to the ability of E-cadherin to form stable cell-cell junctions that prevent cell migration, whereas N-cadherin can form labile junctions required for such dynamic processes as axon projecting or migration and invasion of tumor cells . Other components of cadherin complexes (primarily catenins) can also affect the growth and migration of transformed cells. As was mentioned above (see Cadherins and Signaling), normal expression of free beta-catenin in the cytoplasm is maintained by the oncosuppressing protein APC that binds with excessive beta-catenin and activates its degradation . In patients with hereditary polyposis, who are predisposed to intestine cancer, mutations in the APC gene or directly in beta-catenin gene are often observed. As a result of these mutations, the APC protein lacks its ability to regulate beta-catenin level in the cytoplasm, which leads to uncontrolled activation of the Tcf transcription factor by beta-catenin and development of intestine tumors . T-CADHERIN IS AN ATYPICAL MEMBER OF THE CADHERIN FAMILY T-Cadherin (truncated) (or H-cadherin (heart), or cadherin-13) is one of the most unusual members of the cadherin superfamily. Although its N-terminal domain EC1 does not contain the His-Ala-Val sequence, its extracellular part comprised of five cadherin repeats is very similar in structure to the classical cadherins. A unique feature of this protein is the absence of both the transmembrane and cytoplasmic domains. It is anchored in the membrane via glycosylphosphatidylinositol (GPI) that attaches to the mature protein after cleavage its C-terminal sequence during processing in the endoplasmic reticulum . Despite the absence of the cytoplasmic domain, T-cadherin can mediate any weak homophilic adhesion of the suspended cells . The mechanisms of formation of cell-cell junctions via T-cadherin and classical cadherins are apparently significantly different because the majority of cadherins ensure adhesion only when they contain the cytoplasmic domain that mediates their binding with the cytoskeleton [11, 13]. Another unusual property of T-cadherin is simultaneous expression on the cell surface of its two forms (the mature protein and partially processed precursor containing an uncleaved propeptide, whose function remains obscure) . T-Cadherin was first discovered in chick nervous system [137, 175]. Later its human homolog called cadherin-13 was identified . The only physiological function of T-cadherin established so far is its participation in the regulation of neuron growth during embryogenesis. During formation of chick embryo hind limbs, the outgrowing axons avoid those regions where T-cadherin is expressed . Neuron culturing on substrate containing recombinant T-cadherin significantly inhibits axon growth . Contact suppression of axon growth as a result of homophilic binding between T-cadherin molecules located on the axon membrane and surrounding mesenchymal tissues is apparently a navigating mechanism whereby the direction of nerve fiber growth is determined. Numerous recent data indicate that malignant tumor development is associated with the changes in T-cadherin expression. The loss of chromosome 16q24 locus containing T-cadherin gene correlates with the development of pancreas, lung, stomach, and ovary cancers [177-182]. The transfection of tumor cells with T-cadherin cDNA entails a decrease in the proliferative and invasive activities both in vitro and in vivo as a result of challenging the mice with tumorigenic cell lines as well as the loss of cancer cell sensitivity to the action of growth factors . The mechanisms of T-cadherin effect on cell adhesion and proliferative activity are still unknown. It cannot be ruled out that the maintenance of mechanical junctions between the cells is not the main function of this protein. It is most likely that it serves as a signal receptor, a sensor that allows the cell to sense its environment. This hypothesis is corroborated by the data on T-cadherin distribution in the membrane: in the polarized intestinal cells it is located on the apical part of the cell rather than in the adhesive junctions on the basolateral cell surface . It has long being known that many other GPI proteins may activate intracellular signaling [186-188]. The absence of the cytoplasmic domain in these proteins implies the presence of a membrane adapter protein. Owing to the interaction with the latter, the signal can be relayed across the membrane from the GPI proteins into the cell. We showed that, similar to other GPI proteins, T-cadherin is located on the cell surface in special plasma membrane domains (caveolae and lipid rafts) , which also contain other signal molecules (such as G-proteins, src kinases, rasproteins, and transmembrane receptors of growth factors ). It cannot be excluded that some of these molecules may serve as messengers during activation of T-cadherin-dependent signaling. In our laboratory, the main attention is focused on investigation of the role that T-cadherin plays in the cardiovascular system function. Cell adhesion molecules play a crucial role in the maintenance of normal structure of vascular walls. The development of different pathologies (such as atherosclerosis and restenosis after balloon angioplasty and atherectomy) is characterized by enhanced migration, proliferation, and phenotypic modulation of the endothelial cells, which is often associated with disruption of cell-cell and cell-extracellular matrix junctions [191, 192]. The expression and functions of T-cadherin in the cardiovascular system have not been studied before. We performed a comparative study of T-cadherin expression in different human organs and tissues. The results show that T-cadherin content is maximal in the aorta, carotid, iliac, and kidney arteries, and in heart. In aorta wall, T-cadherin is contained in the endothelial and smooth muscle cells and pericytes. Its expression in the smooth muscle cells depends on the cell phenotype and proliferative activity [193-195] and increases in sclerotic lesion of vascular walls . Preliminary studies performed on the model of balloon catheterization of rat carotid artery indicate that T-cadherin expression in smooth muscle cells increases in restenosis. The content of this protein is also elevated in the endothelium isolated from tumor vasculature . In addition, anti-T-cadherin antibodies can affect the phenotype, adhesion, and motility of the endothelial cells in vitro (our unpublished data). With regard for these data, it is likely that T-cadherin plays a key role in the regulation of cell phenotype, migration, and growth, as well as in maintenance of vascular wall structure. Study of the interaction of heterophilic interactions between T-cadherin and blood plasma lipoproteins is also of great interest. Originally, the work of our group was aimed toward searching for the receptors that mediate the hormone-like effect of low-density lipoproteins on the systems of intracellular signaling in smooth muscle cells in human vasculature [197, 198]. On the surface of membranes of aorta smooth muscle cells, we discovered two unusual lipoprotein-binding proteins with molecular weight of 105 and 130 kD. The characteristics of these proteins are indicative of their participation in lipoprotein-dependent signaling [199, 200]. After isolation of these receptors from human aorta medium and determination of their amino acid sequence, we discovered that the 105-kD protein is mature T-cadherin , whereas the 130-kD protein is its partially processed precursor . It is known that increased lipoprotein content in blood plasma is a risk factor of development of vascular pathologies based on increased proliferation and migration of smooth muscle cells. 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Managing Your Health Care Private Health Care Coverage Understanding Your Policy Tips on Fighting Back Appeals, Grievances, and Complaints Prescription Drugs Medigap and Long-Term Care Insurance Medical Billing Protecting Private Information Questions about COBRA and Continuation Coverage Government Programs and Assistance Glossary of Terms Protecting Private Information A number of federal laws and regulations restrict the ways that health plans, pharmacies, hospitals and other entities can use patients’ personal medical information. The most important of those laws is the Health Insurance Portability and Accountability Act of 1996, known as HIPAA. HIPAA is designed to provide a minimum standard of privacy protection for consumers across the United States, but it does not replace state laws that provide greater privacy protections. Most health care providers were first required to comply with the federal privacy standards in 2003. You may have noticed that your health care provider asks you to sign various notices and consent forms. Here is a summary of some of the key HIPAA provisions: Access to Medical Records: Under HIPAA, patients generally have the right to view and obtain copies of their medical records and request corrections if they identify errors and mistakes. Access to these records should be provided within 30 days, but the patient may be charged for the cost of copying and sending the records. The records should be provided in the form requested by the patient if it is readily producible in that form. Notice of Privacy Practices: Patients must be provided with a notice about their privacy rights and how their personal medical information may be used. Limits on Use of Personal Medical Information: HIPAA sets limits on how health plans and covered providers may use individually identifiable health information. It does not eliminate the sharing of such information, but it restricts the sharing to the minimum necessary to accomplish the intended purpose of the disclosure. Employees must be trained on privacy procedures and each covered entity must designate a privacy officer. Restrictions on Marketing: The final privacy rule sets some restrictions and limits on the use of patient information for marketing purposes. Unfortunately, it appears the HIPAA restrictions on marketing are fairly weak and may not curb many unfortunate marketing practices, such as health plans hiring telemarketers to contact patients to sell them more health plan services. Health Care Identity Theft: Because of concern about identity theft, Congress enacted the Fair and Accurate Credit Transaction (FACT) Act of 2003, which applies to financial institutions and other entities that accept payments over time. Under FACT, the Federal Trade Commission (FTC) has enacted a “Red Flag Rule” that requires covered entities, which can include health care companies that offer credit or deferred billing, to develop and implement a written identity theft prevention program. If you think that your private health information has been used for identity theft, you should contact the FTC as follows: Federal Trade Commission Identity Theft Clearinghouse 600 Pennsylvania Avenue NW Washington, D.C. 20580 The United States Department of Health and Human Services Office for Civil Rights (OCR) has primary jurisdiction to oversee and enforce HIPAA. To obtain further information or to file a complaint regarding the privacy practices of a health plan or provider, contact the OCR as follows: United States Department of Health & Human Services Office for Civil Rights, Midwest Region 233 North Michigan Avenue, Suite 240 Chicago, IL 60601-5519 Medical Information Bureau MIB Group, Inc. is an organization that compiles a central database of medical information. Approximately 430 insurance firms use the services of the MIB, primarily to obtain information about life insurance and individual health insurance policy applicants. You are entitled to a free medical record disclosure once a year. You can get a copy by calling the Medical Information Bureau toll-free at (866) 692-6901. For other questions or to correct your report, write to: MIB Group, Inc. 50 Braintree Hill Park, Suite 400 Braintree, MA 02184-8734 Minnesota has a number of state laws restricting the use and dissemination of personal health information by participants in the health care system. Some of these laws provide greater privacy protection than that granted under HIPAA. The general rule under Minnesota law is that a health care provider cannot share your health information with a third party unless you have given written consent or there is a law that authorizes the provider to share your information. Minnesota’s health privacy laws are complex, but the law requires providers to give patients notice of when a patient’s health records may be disclosed without the patient’s consent. This notice should be posted in the provider’s place of business or given to you. There are also government resources available to help you address your health privacy concerns. First, the Minnesota Department of Health regulates many health care facilities, such as hospitals and nursing homes, and health maintenance organizations (HMOs), such as Medica, Blue Plus, PreferredOne, and HealthPartners. If you believe that a health care facility or HMO may have violated your privacy rights, you can contact the Department of Health as follows: Minnesota Department of Health Managed Care Systems Section P.O. Box 64882 Saint Paul, MN 55164-0882 (651) 201-5100 or (800) 657-3916 Second, the Minnesota Department of Commerce regulates certain health plan companies and health insurance companies, such as Blue Cross Blue Shield of Minnesota. If you believe that an insurance company or health plan company may have violated your privacy rights, you can contact the Department of Commerce as follows: Minnesota Department of Commerce 85 7th Place East, Suite 280 St. Paul, MN 55101 (651) 539-1500 (local) (800) 657-3602 (Greater MN only) Finally, if your health privacy complaint involves an individual health care practitioner, or if you are otherwise unsure which state agency or board to contact about your concerns, you can contact the Attorney General’s Office at (651) 296-3353 (Twin Cities Calling Area) or (800) 657-3787 (Outside the Twin Cities) and we will assist you in identifying the proper regulatory agency.	2	9	5	0	0	0.731218	5	1,280
\|Page tools: Print Page Print All\| Mortality analysis primarily focuses on underlying causes of death. The underlying cause is the disease or condition which led directly to the death. These underlying causes are coded in accordance with the International Classification of Diseases – Version 10 (ICD-10). However, death certificates contain more information than just the underlying cause of death. The certificates also include significant diseases and/or conditions which led to or contributed to death (i.e. associated causes). Multiple cause of death statistics refer to both underlying and associated causes of death (see Causes of Death, Australia (cat. no. 3303.0) Glossary for further details). Multiple cause of death data have been compiled for Australia since 1997. Across the causes of death dataset, multiple cause data is particularly valuable in providing an insight into deaths which can be attributed to a number of concurrent disease processes. It enables the identification of patterns of association amongst conditions, links which may assist in targeting health interventions. This chapter focusses on multiple cause data for suicide deaths. From the outset, it is important to distinguish between the number of times a cause or group of causes appears on death records and the number of deaths where the cause (or group of causes) is mentioned. For example, if a death record contained three different codes from the range of codes belonging to Diseases of the circulatory system (I00-I99), then there are three causes (within the circulatory disease chapter), but only one death. Counts presented in this chapter reflect the number of suicide deaths where a particular multiple cause has been identified. Where more than one multiple cause has been identified for a particular death it may contribute to counts against more than one condition or group of conditions, but it will only contribute once to the total number of deaths. Care needs to be taken when analysing multiple cause of death data associated with suicide deaths. Data quality depends on the procedures being followed at every stage of collection and processing of statistical information. The quality of multiple cause of death data is particularly dependent on the contribution that doctors and coroners make when recording information about a death. When analysing multiple causes of death data, it is important to note that some conditions present at death will not be identified, effectively leading to under-reporting of associated causes and conditions. The extent to which under-reporting of multiple causes of death occurs is unknown and there may be differences in the likelihood of particular conditions being identified. Most suicide deaths are sudden or unexpected in nature. This, combined with a low median age at death, means that the likelihood of associated conditions being identified and recorded is also low. However, in some cases, mental health conditions, cancers or other terminal conditions may be viewed as a trigger or precursor to the suicide event. A secondary cause of death was recorded for only 22% of deaths from suicide between 2001 and 2010 compared to 96% for all deaths during the same period. The data presented in this chapter focuses only on the 22% of suicide deaths from 2001-2010 for which an associated cause was recorded. Care should be taken in making inferences about all suicide deaths based on this sub-group. SUICIDE DEATHS WITH MULTIPLE CAUSES Between 2001 and 2010, 22,526 deaths were registered where suicide was determined to be the underlying cause. Of these suicide deaths, 22% (4,932) were recorded with a multiple cause of death; that is, any condition, disease or injury which was involved in the morbid train of events leading to death (see Glossary for further details). This chapter focuses on data for these 4,932 suicide deaths with multiple causes recorded. Table 7.1 reports the number of suicide deaths by multiple cause by 10 year age groups. For instance, in Table 7.1, there were 340 suicide deaths of 15-24 year olds where the group of multiple causes Mental and behavioural disorders (F00-F99) was listed. The sub-categories of Mental and behavioural disorders (F00-F99) also include counts of suicide deaths. One death may be counted in more than one sub-category but can only contribute once at the broader level of the classification. Consequently, counts of suicide deaths at the sub-category level will add up to more than the total for this group of causes. The likelihood of a multiple cause of death being identified with a suicide increases with age. Only 19.6% of 15-24 year olds who died of suicide had a multiple cause identified, while this increased to 31.4% for individuals aged 75 years or older. It should be noted that this trend may reflect the tendency for a greater number of medical conditions to be present in advanced age. A Mental or behavioural disorder (F00-F99) was recorded for over half of all individuals who died from suicide and for whom a multiple cause was identified. The highest incidence of these disorders was observed in younger age groups: 58.6% of persons aged between 15 and 24 years and 61.6% of persons aged between 25 and 34 years. A Mental and behavioural disorder (F00-F99) was listed as a multiple causes for only 23.0% of individuals aged 75 years and over who died from suicide and for whom a multiple cause was identified. Within the category Mental and behavioural disorders (F00-F99), two disorders were most commonly associated with suicide: Mood disorders (F30-F39) and Mental and behavioural disorders due to psychoactive substance use (F10-F19). These disorders were also the most common Mental and behavioural disorders recorded with suicide across all age groups. Mood disorders (F30-39) were reported in 28.1% of all suicides where a multiple cause was identified, and occurred most often in suicides of 45-54 year olds (33.4%). Mental and behavioural disorders due to psychoactive substance use were recorded in 19.4% of all suicides where a multiple cause was identified, and were most prevalent for persons aged between 15 and 24 years and 25 and 34 years (30.0 and 30.2% of these age groups respectively). The prevalence of the main associated causes of death at the ICD-10 chapter level, for those suicide deaths where a multiple cause was identified, is shown in Figure 7.1. Footnote(s): (a) Includes ICD-10 codes X60-X84 and Y87.0. Care needs to be taken in interpreting figures relating to suicide. See Causes of Death, Australia, 2010 (cat. no. 3303.0) Explanatory Notes 98-101. (b) All causes of death data from 2006 onward are subject to a revisions process - once data for a reference year are 'final', they are no longer revised. Affected data in this graph are: 2006 (final) 2007 (final), 2008 (final), 2009 (revised), 2010 (preliminary). See Causes of Death, Australia, 2009 (cat. no. 3303.0) Technical Note and Explanatory Notes for further information. Source(s): Suicides, Australia All underlying causes with multiple causes of death Amongst all deaths where suicide was found to be the underlying cause, only 22% had an associated (multiple) cause of death, whereas for all underlying causes of death, 96% had associated causes. There were differences observed between the types of multiple causes of death associated with suicide and the multiple causes observed when all other underlying causes were considered. Table 7.3 presents the proportions of deaths with selected multiple causes for all underlying causes of death. For deaths due to any underlying cause, Diseases of the circulatory system (I00-I99, associated with 59.7% of deaths), Neoplasms (C00-D48, 35.0%) and Diseases of the respiratory system (J00-J99, 31.8%) were the most common diseases or conditions that contributed to death. Suicide deaths were most commonly associated with Mental and behavioural disorders (F00-F99, 50.2%), Diseases of the circulatory system (I00-I99, 19.4%), and Diseases of the respiratory system (J00-J99, 9.6%).	4	10	0	0	11	0.43013	11	1,680
Standard of Care: Greater Trochanteric Pain Syndrome ICD 9 Codes Myofascial pain syndrome — Comprehensive overview covers symptoms and treatment of myofascial pain. An estimated 26 million Americans have either fibromyalgia syndrome (FMS), myofascial pain syndrome (MPS), or both in the form of an FMS/MPS complex. The volume by Synapse: the functional membrane to membrane contact between one nerve cell and another nerve cell, receptor, or other cell. In most cases, impulses are carried Medical Coding \| ICD-9 Codes 2010 \| ICD-10 Codes: How Lyme disease MDGuidelines is the most trusted source of disability guidelines, disability durations, and return to work information on myofascial pain syndrome. The cause of this syndrome is currently unknown. Precipitating factors include injury and surgery, although there are documented cases that have no demonstrable 724.5 Backache, unspecified, Vertebrogenic (pain) syndrome NOS – ICD-9-CM Vol. 1 Diagnostic Codes – FindACode.com Icd 9 Code For Tmj Syndrome \| How To Stop Grinding Your Teeth Everything you need to know about pain syndrome icd 9 code, including the most common causes, symptoms and treatments. To diagnose myofascial pain syndrome, your doctor will ask if you have had a recent injury, where the pain is, how long you have had the pain, what makes it better or This page includes the following topics and synonyms: Myofascial Pain Syndrome. Fibromyalgia Myofascial Pain Syndrome – Fibromyalgia Information If you are asking what the ICD-9 (International Classification of Diseases, 9th edition) code for limb pain is, it would depend on which limb, as well as the cause of BRIGHAM AND WOMEN'S HOSPITAL Department of Rehabilitation Services Physical Therapy Standard of Care: Greater Trochanteric Pain Syndrome ICD 9 Codes: 726.5 From Wikipedia, the free encyclopedia Myofascial Pain Syndrome (or MPS) is a term used to describe one of the conditions characterized by chronic pain. Myofascial Pain Syndrome General Discussions at DailyStrength adj. Of or relating to the fascia surrounding and separating muscle tissue. Welcome to MedLink Neurology — the most comprehensive resource for neurology. See for yourself how valuable the leading neurology resource can be in your practice. Dr. Terry Chambers of Chambers Chiropractic and Acupuncture Offices, Martinsburg, WV 25403 discusses Myofascial Pain Syndrome Extremely persistent, intractable type of pain that can be quite debilitating and depressing to the sufferer. The pain may be localized to a particular part of the < Chapter Overview. Conditions Complaints List w/ ICD 9 Codes (From Physician’s ICD-9-CM 2007, Vol 1 2, condensed edition © 2006) A. Neurological Myofascial pain syndrome – Orthopaedic. Myofascial Pain . Myofascial pain refers to soft tissue pain usually arising from trauma, repetitive activities, or poor posture. Myofascial Pain Syndromes – Orthopaedic Web Links “May our spirit fill us with understanding of victory and defeat, the gift of collaboration, the wisdom to choose the right path, and opportunities to inspire hope.” Get the latest updates on ICD-10 Codes, ICD 9 Codes 2010, ICD-9-CM Codes, HCPCS Codes, Medical Coding, Modifier 59 E124 / The Journal of Manual Manipulative Therapy, 2006 The Journal of Manual Manipulative Therapy Vol. 14 No. 4 (2006), E124 – E171 Myofascial Trigger Points and Myofascial pain syndrome – LuMriX XML Solutions for Enterprises Free official medical coding data for 2008 ICD-9-CM diagnosis code 338.2 (2012 also), including ICD-9-CM coding notes, detailed description and associated index data. 338.4 Chronic pain syndrome, Chronic pain associated with significant psychosocial dysfunction – ICD-9-CM Vol. 1 Diagnostic Codes – FindACode.com Gout is a medical condition that usually presents with recurrent s of acute inflammatory arthritis (red, tender, hot, swollen joint). ^ Gout is a disease Fibromyalgia/Myofascial Pain Syndromes – Portsmouth,Va Everything you need to know about mechanical low back pain syndrome icd 9, including the most common causes, symptoms and treatments. Myofascial Pain Syndrome . Myofascial Pain Syndrome will vary in severity. For this reason, please take the time to read about the following information about can necrotizing fascitis,myofascial pain syndrome,and plantar fasciaitis all be related?I’m glad your daughter pulled though such a serious disease! Yes, I think si joint dysfunction icd 9 – Results for: si joint dysfunction icd 9 Myofascial pain syndrome (MPS), also known as chronic myofascial pain (CMP), is a syndrome characterized by chronic pain caused by multiple trigger points and fascial n MPD A subset of the TMJ pain dysfunction syndrome that presents with the triad of symptoms of unilateral pain in the muscles of mastication, c of the joint MDGuidelines is the most trusted source of clinical information on definition for myofascial pain syndrome. Myofascial pain syndrome icd 9 code Read about myofascial pain dysfunction syndrome treatment, diagnosis, symptoms (trigger points, chronic pain) and causes (tissue injury). Welcome ; Myofascial Release ; Testimonials ; Services and Prices ; Indy's Guests ; About Dr. Jeren ; Business Cards and Ads ; MFR in USA ; Sharings i haven't been 'diagnosed' or anything with this because for me it's because of magnesium deficiency, so i'm diagnosed deficient in magnesiu	4	9	1	0	0	0.66712	1	1,251
- Pulmonary hypertension Pulmonary arterial hypertension Classification and external resources The pulmonary artery receives blood (blue arrow) from the right ventricle of the heart; increased pressure on the artery can impair the function of the right ventricle ICD-10 I27.0, I27.2 ICD-9 416.0 DiseasesDB 10998 eMedicine med/1962 MeSH D006976 In medicine, pulmonary hypertension (PH) is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion. Pulmonary hypertension can be a severe disease with a markedly decreased exercise tolerance and heart failure. It was first identified by Dr. Ernst von Romberg in 1891. According to the most recent classification, it can be one of five different types: arterial, venous, hypoxic, thromboembolic or miscellaneous. - 1 Signs and symptoms - 2 Diagnosis - 3 Causes and classification - 4 Pathogenesis - 5 Epidemiology - 6 Treatment - 7 Prognosis - 8 See also - 9 References - 10 External links Signs and symptoms Because symptoms may develop very gradually, patients may delay seeing a physician for years. Common symptoms are shortness of breath, fatigue, non-productive cough, angina pectoris, fainting or syncope, peripheral edema (swelling around the ankles and feet), and rarely hemoptysis (coughing up blood). Pulmonary venous hypertension typically presents with shortness of breath while lying flat or sleeping (orthopnea or paroxysmal nocturnal dyspnea), while pulmonary arterial hypertension (PAH) typically does not. A detailed family history is established to determine whether the disease might be familial. A history of exposure to drugs such as cocaine, methamphetamine, alcohol leading to cirrhosis, and tobacco leading to emphysema are considered significant. A physical examination is performed to look for typical signs of pulmonary hypertension, including a loud S2 (pulmonic valve closure sound), (para)sternal heave, jugular venous distension, pedal edema, ascites, hepatojugular reflux, clubbing etc. Evidence of tricuspid insufficiency is also sought and, if present, is consistent with the presence of pulmonary hypertension. Because pulmonary hypertension can be of five major types, a series of tests must be performed to distinguish pulmonary arterial hypertension from venous, hypoxic, thromboembolic, or miscellaneous varieties. A physical examination is performed to look for typical signs of pulmonary hypertension. These include altered heart sounds, such as a widely split S2 or second heart sound, a loud P2 or pulmonic valve closure sound (part of the second heart sound), (para)sternal heave, possible S3 or third heart sound, and pulmonary regurgitation. Other signs include an elevated jugular venous pressure, peripheral edema (swelling of the ankles and feet), ascites (abdominal swelling due to the accumulation of fluid), hepatojugular reflux, and clubbing. Further procedures are required to confirm the presence of pulmonary hypertension and exclude other possible diagnoses. These generally include pulmonary function tests; blood tests to exclude HIV, autoimmune diseases, and liver disease; electrocardiography (ECG); arterial blood gas measurements; X-rays of the chest (followed by high-resolution CT scanning if interstitial lung disease is suspected); and ventilation-perfusion or V/Q scanning to exclude chronic thromboembolic pulmonary hypertension. Biopsy of the lung is usually not indicated unless the pulmonary hypertension is thought to be due to an underlying interstitial lung disease. But lung biopsies are fraught with risks of bleeding due to the high intrapulmonary blood pressure. Clinical improvement is often measured by a "six-minute walk test", i.e. the distance a patient can walk in six minutes. Stability and improvement in this measurement correlate with better survival. Blood BNP level is also being used now to follow progress of patients with pulmonary hypertension. Diagnosis of PAH requires the presence of pulmonary hypertension with two other conditions. Pulmonary artery occlusion pressure (PAOP or PCWP) must be less than 15 mm Hg (2000 Pa) and pulmonary vascular resistance (PVR) must be greater than 3 Wood units (240 dyn•s•cm−5 or 2.4 mN•s•cm−5). Although pulmonary arterial pressure can be estimated on the basis of echocardiography, pressure measurements with a Swan-Ganz catheter provides the most definite assessment. PAOP and PVR cannot be measured directly with echocardiography. Therefore diagnosis of PAH requires right-sided cardiac catheterization. A Swan-Ganz catheter can also measure the cardiac output, which is far more important in measuring disease severity than the pulmonary arterial pressure. Normal pulmonary arterial pressure in a person living at sea level has a mean value of 12–16 mm Hg (1600–2100 Pa). Pulmonary hypertension is present when mean pulmonary artery pressure exceeds 25 mm Hg (3300 Pa) at rest or 30 mm Hg (4000 Pa) with exercise. Mean pulmonary artery pressure (mPAP) should not be confused with systolic pulmonary artery pressure (sPAP), which is often reported on echocardiogram reports. A systolic pressure of 40 mm Hg typically implies a mean pressure of more than 25 mm Hg. Roughly, mPAP = 0.61•sPAP + 2. Causes and classification A 1973 meeting organized by the World Health Organization was the first to attempt classification of pulmonary hypertension. A distinction was made between primary and secondary PH, and primary PH was divided in the "arterial plexiform", "veno-occlusive" and "thromboembolic" forms. A second conference in 1998 at Évian-les-Bains also addressed the causes of secondary PH (i.e. those due to other medical conditions), and in 2003, the 3rd World Symposium on Pulmonary Arterial Hypertension was convened in Venice to modify the classification based on new understandings of disease mechanisms. The revised system developed by this group provides the current framework for understanding pulmonary hypertension. The system includes several improvements over the former 1998 Evian Classification system. Risk factor descriptions were updated, and the classification of congenital systemic-to pulmonary shunts was revised. A new classification of genetic factors in PH was recommended, but not implemented because available data were judged to be inadequate. The Venice 2003 Revised Classification system can be summarized as follows: - WHO Group I - Pulmonary arterial hypertension (PAH) - Idiopathic (IPAH) - Familial (FPAH) - Associated with other diseases (APAH): collagen vascular disease (e.g. scleroderma), congenital shunts between the systemic and pulmonary circulation, portal hypertension, HIV infection, drugs, toxins, or other diseases or disorders - Associated with venous or capillary disease - WHO Group II - Pulmonary hypertension associated with left heart disease - Atrial or ventricular disease - Valvular disease (e.g. mitral stenosis) - WHO Group III - Pulmonary hypertension associated with lung diseases and/or hypoxemia - WHO Group IV - Pulmonary hypertension due to chronic thrombotic and/or embolic disease - WHO Group V - Miscellaneous The classification does not include sickle cell disease, Human herpesvirus 8, also associated with Kaposi's sarcoma, has been demonstrated in patients with PAH, suggesting that this virus may play a role in its development. Recent studies have been unable to find an association between human herpesvirus 8 and idiopathic pulmonary arterial hypertension. Whatever the initial cause, pulmonary arterial hypertension (WHO Group I) involves the vasoconstriction or tightening of blood vessels connected to and within the lungs. This makes it harder for the heart to pump blood through the lungs, much as it is harder to make water flow through a narrow pipe as opposed to a wide one. Over time, the affected blood vessels become both stiffer and thicker, in a process known as fibrosis. This further increases the blood pressure within the lungs and impairs their blood flow. In addition, the increased workload of the heart causes hypertrophy of the right ventricle, making the heart less able to pump blood through the lungs, ultimately causing right heart failure (a condition known as cor pulmonale). As the blood flowing through the lungs decreases, the left side of the heart receives less blood. This blood may also carry less oxygen than normal. Therefore it becomes harder and harder for the left side of the heart to pump to supply sufficient oxygen to the rest of the body, especially during physical activity. Pathogenesis in pulmonary venous hypertension (WHO Group II) is completely different. There is no obstruction to blood flow in the lungs. Instead, the left heart fails to pump blood efficiently, leading to pooling of blood in the lungs. This causes pulmonary edema and pleural effusions. In hypoxic pulmonary hypertension (WHO Group III), the low levels of oxygen are thought to cause vasoconstriction or tightening of pulmonary arteries. This leads to a similar pathophysiology as pulmonary arterial hypertension. In chronic thromboembolic pulmonary hypertension (WHO Group IV), the blood vessels are blocked or narrowed with blood clots. Again, this leads to a similar pathophysiology as pulmonary arterial hypertension. IPAH is a rare disease with an incidence of about 2-3 per million per year and a prevalence of about 15 per million. Adult females are almost three times as likely to present with IPAH than adult males. The presentation of IPAH within children is more evenly split along gender lines. Other forms of PAH are far more common. In scleroderma the incidence has been estimated to be 6 to 60% of all patients, in rheumatoid arthritis up to 21%, in systemic lupus erythematosus 4 to 14%, in portal hypertension between 2 to 5%, in HIV about 0.5%, and in sickle cell disease ranging from 20 to 40%. Diet pills such as Fen-Phen produced an annual incidence of 25-50 per million per year. Pulmonary venous hypertension is exceedingly common, since it occurs in most patients symptomatic with congestive heart failure. Up to 4% of people who suffer a pulmonary embolism go on to develop chronic thromboembolic disease including pulmonary hypertension. Only about 1.1% of patients with COPD develop pulmonary hypertension with no other disease to explain the high pressure. Sleep apnea is usually associated with only very mild pulmonary hypertension, typically below the level of detection. On the other hand Pickwickian syndrome (obesity-hypoventilation syndrome) is very commonly associated with right heart failure due to pulmonary hypertension. Treatment is determined by whether the PH is arterial, venous, hypoxic, thromboembolic, or miscellaneous. Since pulmonary venous hypertension is synonymous with congestive heart failure, the treatment is to optimize left ventricular function by the use of diuretics, beta blockers, ACE inhibitors, etc., or to repair/replace the mitral valve or aortic valve. In PAH, lifestyle changes, digoxin, diuretics, oral anticoagulants, and oxygen therapy are considered conventional therapy, but have never been proven to be beneficial in a randomized, prospective manner. High dose calcium channel blockers are useful in only 5% of IPAH patients who are vasoreactive by Swan-Ganz catheter. Unfortunately, calcium channel blockers have been largely misused, being prescribed to many patients with non-vasoreactive PAH, leading to excess morbidity and mortality. The criteria for vasoreactivity have changed. Only those patients whose mean pulmonary artery pressure falls by more than 10 mm Hg to less than 40 mm Hg with an unchanged or increased cardiac output when challenged with adenosine, epoprostenol, or nitric oxide are considered vasoreactive. Of these, only half of the patients are responsive to calcium channel blockers in the long term. A number of agents has recently been introduced for primary and secondary PAH. The trials supporting the use of these agents have been relatively small, and the only measure consistently used to compare their effectivity is the "6 minute walk test". Many have no data on mortality benefit or time to progression. Many pathways are involved in the abnormal proliferation and contraction of the smooth muscle cells of the pulmonary arteries in patients with pulmonary arterial hypertension. Three of these pathways are important since they have been targeted with drugs — endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and prostacyclin derivatives. Because inexpensive generic drugs for this disease are not widely available, the World Health Organization does not include them in its model list of essential medicines. Prostacyclin (prostaglandin I2) is commonly considered the most effective treatment for PAH. Epoprostenol (synthetic prostacyclin, marketed as Flolan) is given via continuous infusion that requires a semi-permanent central venous catheter. This delivery system can cause sepsis and thrombosis. Flolan is unstable, and therefore has to be kept on ice during administration. Since it has a half-life of 3 to 5 minutes, the infusion has to be continuous (24/7), and interruption can be fatal. Other prostanoids have therefore been developed. Treprostinil (Remodulin) can be given intravenously or subcutaneously, but the subcutaneous form can be very painful. An increased risk of sepsis with intravenous Remodulin has been reported by the CDC. Iloprost (Ilomedin) is also used in Europe intravenously and has a longer half life. Iloprost (marketed as Ventavis) was the only inhaled form of prostacyclin approved for use in the US and Europe, until the inhaled form of treprostinil was approved by the FDA in July 2009 and is marketed under the trade name Tyvaso. The inhaled form of administration has the advantage of selective deposition in the lungs with less systemic side effects, however coughing and throat irritation commonly occur. Oral and inhaled forms of Remodulin are under development. Beraprost is an oral prostanoid available in South Korea and Japan. Endothelin receptor antagonists The dual (ETA and ETB) endothelin receptor antagonist bosentan (marketed as Tracleer) was approved in 2001. Sitaxentan, a selective endothelin receptor antagonist that blocks only the action of ETA, has been approved for use in Canada, Australia, and the European Union, to be marketed under the name Thelin. Sitaxentan has not been approved for marketing by the U.S. Food and Drug Administration (FDA). In 2010, Thelin was withdrawn by Pfizer due to severe side effects. A new trial to address the FDA's concerns will begin in 2008. A similar drug, ambrisentan is marketed as Letairis in U.S. by Gilead Sciences. In addition, another dual/nonselective endothelin antagonist, Actelion-1, from the makers of Tracleer, will enter clinical trials in 2008. Phosphodiesterase type 5 inhibitors The U.S. FDA approved Sildenafil, a selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5), for the treatment of PAH in 2005. It is marketed for PAH as Revatio. In 2009, they also approved Tadalafil, another PDE5 inhibitor, marketed under the name Adcirca. Activators of soluble guanylate cyclase Atrial septostomy is a surgical procedure that creates a communication between the right and left atria. It relieves pressure on the right side of the heart, but at the cost of lower oxygen levels in blood (hypoxia). Pulmonary thromboendarterectomy (PTE) is a surgical procedure that is used for chronic thromboembolic pulmonary hypertension. It is the surgical removal of an organized thrombus (clot) along with the lining of the pulmonary artery; it is a very difficult, major procedure that is currently performed in a few select centers. Case series show remarkable success in most patients. Treatment regimens for hypoxic and miscellaneous varieties of pulmonary hypertension have not been established. However, studies of several agents are currently enrolling patients. Many physicians will treat these diseases with the same medications as for PAH, until better options become available. Such treatment is called off-label use. Patients are normally monitored through commonly available tests such as: - pulse oximetry - arterial blood gas tests - chest X-rays - serial ECG tests - serial echocardiography - spirometry or more advanced lung function studies The NIH IPAH registry from the 1980s showed an untreated median survival of 2–3 years from time of diagnosis, with the cause of death usually being right ventricular failure (cor pulmonale). Although this figure is widely quoted, it is probably irrelevant today. Outcomes have changed dramatically over the last two decades. This may be because of newer drug therapy, better overall care, and earlier diagnosis (lead time bias). A recent outcome study of those patients who had started treatment with bosentan (Tracleer) showed that 89% patients were alive at 2 years. With multiple agents now available, combination therapy is increasingly used. Impact of these agents on survival is not known, since many of them have been developed only recently. It would not be unreasonable to expect median survival to extend past 10 years in the near future. - ^ von Romberg, Ernst (1891-1892). "Über Sklerose der Lungenarterie" (in German). Dtsch Arch Klin Med 48: 197–206. - ^ a b c d Simonneau G, Galiè N, Rubin LJ, et al. (June 2004). "Clinical classification of pulmonary hypertension". J. Am. Coll. Cardiol. 43 (12 Suppl S): 5S–12S. doi:10.1016/j.jacc.2004.02.037. PMID 15194173. http://content.onlinejacc.org/cgi/content/full/43/12_Suppl_S/5S. - ^ Hatano S, Strasser R (1975). Primary pulmonary hypertension. Geneva: World Health Organization. - ^ Rich S, Rubin LJ, Abenhail L et al. (1998). Executive summary from the World Symposium on Primary Pulmonary Hypertension (Evian, France, September 6–10, 1998). Geneva: The World Health Organization. Archived from the original on April 8, 2002. http://web.archive.org/web/20020408173726/http://www.who.int/ncd/cvd/pph.html. - ^ Gladwin MT, Sachdev V, Jison ML, et al. (2004). "Pulmonary hypertension as a risk factor for death in patients with sickle cell disease". N. Engl. J. Med. 350 (9): 886–95. doi:10.1056/NEJMoa035477. PMID 14985486. http://content.nejm.org/cgi/content/full/350/9/886. - ^ Cool CD, Rai PR, Yeager ME, et al. (2003). "Expression of human herpesvirus 8 in primary pulmonary hypertension". N. Engl. J. Med. 349 (12): 1113–22. doi:10.1056/NEJMoa035115. PMID 13679525. http://content.nejm.org/cgi/content/full/349/12/1113. - ^ Rudarakanchana, N; Trembath RC, Morrell NW (November 2001). "New insights into the pathogenesis and treatment of primary pulmonary hypertension". Thorax 56 (11): 888–890. doi:10.1136/thorax.56.11.888. PMC 1745964. PMID 11641516. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1745964. - ^ Barst RJ, McGoon M, Torbicki A, et al. (June 2004). "Diagnosis and differential assessment of pulmonary arterial hypertension". J. Am. Coll. Cardiol. 43 (12 Suppl S): 40S–47S. doi:10.1016/j.jacc.2004.02.032. PMID 15194177. - ^ Sitbon O, Humbert M, Jaïs X, et al. (June 2005). "Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension". Circulation 111 (23): 3105–11. doi:10.1161/CIRCULATIONAHA.104.488486. PMID 15939821. http://circ.ahajournals.org/cgi/content/short/111/23/3105. - ^ Torres F (2007). "Systematic review of randomised, double-blind clinical trials of oral agents conducted in patients with pulmonary arterial hypertension". Int. J. Clin. Pract. 61 (10): 1756–65. doi:10.1111/j.1742-1241.2007.01545.x. PMID 17877662. http://www.blackwell-synergy.com/doi/full/10.1111/j.1742-1241.2007.01545.x. - ^ "UPDATE 1-Encysive gets Canadian approval for hypertension drug". Reuters. 2008-05-30. http://www.reuters.com/article/governmentFilingsNews/idUSBNG28335020070530. Retrieved 2007-07-08. - ^ "U.S. Food and Drug Administration Approves Gilead's Letairis Treatment of Pulmonary Arterial Hypertension" (Press release). Gilead Sciences. 2007-06-15. http://www.gilead.com/wt/sec/pr_1016053. Retrieved 2007-06-16. - ^ "FDA approves Adcirca (tadalafil) tablets for pulmonary arterial hypertension" (Press release). 2009-05-26. http://www.news-medical.net/news/2009/05/26/FDA-approves-Adcirca-(tadalafil)-tablets-for-pulmonary-arterial-hypertension.aspx. Retrieved 2010-12-06. - ^ "2006 OPTN/SRTR Annual Report". US Scientific Registry of Transplant Recipients. 2006-05-01. http://www.ustransplant.org/annual_reports/current/113_surv-new_dh.htm. Retrieved 2007-03-28. - ^ McLaughlin VV, Sitbon O, Badesch DB, et al. (2005). "Survival with first-line bosentan in patients with primary pulmonary hypertension". Eur. Respir. J. 25 (2): 244–9. doi:10.1183/09031936.05.00054804. PMID 15684287. http://erj.ersjournals.com/cgi/content/full/25/2/244. - ^ Nauser TD, Stites SW (2001). "Diagnosis and treatment of pulmonary hypertension". Am Fam Physician 63 (9): 1789–98. PMID 11352291. http://www.aafp.org/afp/20010501/1789.html. - ^ Kelley's essentials of internal medicine. Hagerstwon, MD: Lippincott Williams & Wilkins. 2001. pp. 84. ISBN 0-7817-1937-2. - ^ Edward Benz; David Weatherall; David Warrell; Cox, Timothy J.; Firth, John B. (2005). Oxford textbook of medicine. Oxford [Oxfordshire]: Oxford University Press. pp. 1101. ISBN 0-19-856978-5. - ^ Kaufman, Matthew H.; Latha Stead; Feig, Robert (2007). First aid for the obstetrics & gynecology clerkship. New York: McGraw-Hill, Medical Pub. Division. pp. 100. ISBN 0-07-144874-8. - ^ Ghosh, Amit K. (2008). Mayo Clinic Internal Medicine Review: Eighth Edition (Mayo Clinic Internal Medicine Review). Informa Healthcare. pp. 55. ISBN 1-4200-8478-X. - ^ British Journal of Anaesthesia: "Primary pulmonary hypertension in pregnancy; a role for novel vasodilators" March 19, 2011 - Rubin LJ, Badesch DB (2005). "Evaluation and management of the patient with pulmonary arterial hypertension". Ann. Intern. Med. 143 (4): 282–92. PMID 16103472. http://www.annals.org/cgi/reprint/143/4/282. - The Merck Manual Home Edition: Pulmonary Hypertension - Pulmonary Hypertension Association - PH Central - the internet resource for Pulmonary Arterial Hypertension - Facts About Primary Pulmonary Hypertension from the National Heart, Lung, and Blood Institute (NHLBI) - Webcast: The Changing World of Pulmonary Arterial Hypertension Therapies - American College of CHEST Physicians - GeneReviews/NCBI/NIH/UW entry on Heritable Pulmonary Arterial Hypertension - OMIM entries on Heritable Pulmonary Arterial Hypertension 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 Pathology of respiratory system (J, 460–519), respiratory diseases Upper RT Common cold)Headvocal folds: Laryngopharyngeal reflux (LPR) · Vocal fold nodule · Vocal cord paresis · Vocal cord dysfunction Lower RT/lung disease (including LRTIs)acute: Acute bronchitischronic: COPD (Chronic bronchitis, Acute exacerbations of chronic bronchitis, Acute exacerbation of COPD, Emphysema) · Asthma (Status asthmaticus, Aspirin-induced, Exercise-induced) · BronchiectasisInterstitial/ restrictiveBy pathogenBy vector/routeBy distributionBroncho- · LobarOther Wikimedia Foundation. 2010. Look at other dictionaries: pulmonary hypertension — a condition in which there is raised blood pressure within the blood vessels supplying the lungs (the pulmonary artery blood pressure is normally much lower than the pressure within the aorta and its branches). Pulmonary hypertension may… … Medical dictionary pulmonary hypertension — a condition in which there is raised blood pressure within the blood vessels supplying the lungs (the pulmonary artery blood pressure is normally much lower than the pressure within the aorta and its branches). Pulmonary hypertension may… … The new mediacal dictionary Pulmonary Hypertension Association — The Pulmonary Hypertension Association (PHA) is a 501(c)(3) non profit support, education, advocacy and awareness association for pulmonary hypertension (PH). It provides information to the public about the illness and acts as a support group for … Wikipedia Гипертензия Легочная (Pulmonary Hypertension) — состояние, характеризующееся повышением кровяного давления внутри сосудов, по которым в легких циркулирует кровь (при этом кровяное давление в легочной артерии оказывается значительно ниже, чем давление крови внутри аорты и ее ответвлений).… … Медицинские термины chronic thromboembolic pulmonary hypertension — persistent pulmonary hypertension due to obstruction of a major pulmonary artery by an unresolved embolus … Medical dictionary persistent pulmonary hypertension of the newborn — a condition in newborns in which blood continues to flow through the foramen ovale and a patent ductus arteriosus, bypassing the lungs and resulting in hypoxemia. Called also persistent fetal circulation … Medical dictionary Hypertension artérielle pulmonaire — Classification et ressources externes L artère pulmonaire reçoit le sang (flèche bleue) du ventricule droit ; une augmentation de la pression dans cette artère peut altérer la fonction du ventricule dro … Wikipédia en Français Pulmonary embolism — Classification and external resources Chest spiral CT scan with radiocontrast agent showing multiple filling defects both at the bifurcation and in the pulmonary arteries. ICD 10 … Wikipedia Hypertension Artérielle Pulmonaire — Identifiée pour la première fois en 1891 par le Docteur Ernst Von Romberg, l hypertension artérielle pulmonaire (HTAP) correspond à un groupe de maladies d évolution progressive caractérisée par une élévation anormale de la pression sanguine au… … Wikipédia en Français Hypertension arterielle pulmonaire — Hypertension artérielle pulmonaire Identifiée pour la première fois en 1891 par le Docteur Ernst Von Romberg, l hypertension artérielle pulmonaire (HTAP) correspond à un groupe de maladies d évolution progressive caractérisée par une élévation… … Wikipédia en Français	2	25	4	0	3	0.969315	7	6,717
Medical misadventure is a vague term referring to an unexpected patient injury outside of the control of the physician — an ‘act of God,’ as some might call it. Misadventure can represent a countless number of nonspecific scenarios; errors in prescribed medication can be considered a ‘misadventure,’ for example. A related phrasing may be more commonly used: death by misadventure. This is a coroner’s term that originated in the UK to describe a death due to risk willingly incurred — a preventable death. Surrounding these mysterious mishaps is a murky gray area where it can be hard to objectively separate misadventures from the much more implicit and accusatory label of medical negligence — meaning the physician either made a poor choice that directly lead to patient harm or failed to treat the patient at all. To make matters more confusing, medical error bears an unfortunate similarity to both previously mentioned terms and is often used synonymously with misadventure — even though ‘error’ is technically more aligned with medical negligence. Medical error is when a preventable incident occurs due to an inaccurate diagnosis or treatment, or something of the like. Why are medical misadventures a serious problem in the U.S.? Research done at Johns Hopkins, based on death rate data over an eight-year period, claims that on average the U.S. sees more than 250,000 deaths per year due to medical error. This estimation ranks medical error as the third highest cause of death in America, despite respiratory disease having been originally reported as the third highest cause of death by the Centers for Disease Control and Prevention (CDC). Researchers involved in this study say that the CDC’s means of collecting healthcare statistics neglects to appropriately represent ‘medical error’ on death certificates. “Incidence rates for deaths directly attributable to medical care gone awry haven’t been recognized in any standardized method for collecting national statistics,” said one professor of surgery at the Johns Hopkins University School of Medicine. The major problem with the data the CDC currently uses for its mortality statistics is this: when the U.S. first adopted the International Classification of Diseases (ICD) billing system in 1949, decision-makers at the time failed to consider that medical errors might commonly result in patient death. This oversight resulted in a lapse in modern healthcare statistics. National mortality rates are being calculated based on billing codes that could not properly anticipate the prevalence or importance of medical misadventures. Furthermore, ICD billing codes were never intended to be used for statistics — their primary purpose was and still is payer reimbursement. Definitive Healthcare's Medical Claims database reflects this idea as well. The only ICD-10 codes related to medical misadventures are codes Y62–Y69, and can be found through secondary diagnoses records. Hospitals ranked by highest volume of medical misadventures Baptist Medical Center Jacksonville Sharp Memorial Hospital Sharp Grossmont Hospital Memorial Sloan Kettering Cancer Center Beth Israel Deaconess Medical Center Specialists Hospital Shreveport Hendrick Medical Center Fig. 1 Data from Definitive Healthcare’s Claims Analytics database. Annual Medicare Data is from the Centers for Medicare and Medicaid Services (CMS) Medicare Standard Analytical Files (SAFs). Data is from calendar year 2018 (most recent complete data available). Accessed May 2020. There are a few red flags with this data set. Firstly, if we suspect that approximately 250,000 patients die of misadventure per year, then why is the highest reported volume of misadventure by a provider on 60 total diagnoses? Lastly, why is the only code being used to report a misadventure Y658 (Other specified misadventures during surgical and medical care)? Properly reporting medical mishaps is not just about accountability. Top-ranked causes of death inform research priorities and funding in the U.S. If the CDC is inaccurately representing the severity and commonality of medical misadventures, then researchers will not be studying new techniques that could reduce relevant incidence rates. This is undoubtedly a problem in the U.S. healthcare system that deserves more attention. Want to learn more about medical misadventures and errors in the U.S. healthcare system? Good luck! Information is hard to come by on this topic. In the meantime, however, you can check out this Healthcare Insights list from a few years ago that also attempted to fill in some these anomalous blanks: Top Hospitals by ICD-10 Misadventure Diagnosis. ABOUT THE AUTHOR An English graduate and a tech nerd — I enjoy reading, writing, and getting involved with some technical nitty-gritty and design when time and opportunity allow for it. Some favorite books of mine ...	3	2	0	0	2	0.856457	2	991
2018 saw the release of the 11th edition of the International Classification of Diseases (ICD-11) by the World Health Organization.1 Here, substantial changes relative to ICD-10 were made to the criteria for post-traumatic stress disorder (PTSD). There are now a smaller number of core symptoms, with sleep and concentration difficulties removed, but functional impairment has been added. In addition, a new disorder — complex post-traumatic stress disorder (CPTSD) — has been defined. The criteria for CPTSD are the same as those for PTSD, but with the addition of disturbances in self-organization. Now, data from a study recently published in the Journal of Child Psychology and Psychiatry have shed light on the clinical utility of these revisions in the ICD-11. “Initial conceptualisations of CPTSD suggested it was most likely to occur as a response to repeated or severe trauma histories; as such, CPTSD won’t be commonly assessed following a single traumatic event”, explains corresponding author Dr Caitlin Hitchcock. “We felt that it was important to explore whether rates of CPTSD are indeed low in young people exposed to a single traumatic event, as the ICD-11 diagnostic criteria don’t actually list repeated trauma as being necessary for a CPTSD diagnosis”. To address this question, Hitchcock and colleagues analysed data collected from children and adolescents aged 8-17 years old,2 at 2-4 weeks and 9 weeks after attending hospital after experiencing a single traumatic event. They then calculated and compared the prevalence, specificity and predictive value of ICD-10 and ICD-11 PTSD criteria and CPTSD. First, they found that the ICD-11 criteria were more clinically conservative in diagnosing PTSD compared to the ICD-10 criteria (but not compared to the DSM-IV or -5 criteria). These findings suggest that the transition from ICD-10 to ICD-11 might reduce the number of young people deemed eligible for PTSD treatment if the service uses the ICD -11 PTSD diagnosis as an intake criterion. Second, they found that CPTSD following a single traumatic event was indeed uncommon. However, 90% of children with ICD-11 PTSD met at least one of the self-organization criteria for CPTSD, some as early as 2 weeks after a single traumatic event. “Although few young people met the criteria for CPTSD, we were interested to find that many of the participants with PTSD did endorse some CPTSD features, mainly interpersonal difficulties and affect dysregulation”, says Hitchcock. “It will be important for future research to further explore the nature of these symptoms”. Future evaluations of the ICD-11 with a larger and more varied sample are now warranted. Elliott, R., McKinnon, A., Dixon, C., Boyle, A., Murphy, F., Dahm, T., Travers-Hill, E., Mul, C-L., Archibald, S-J., Smith, P., Dalgleish, T., Meiser-Stedman, R. & Hitchcock, C. (2020), Prevalence and predictive value of ICD-11 posttraumatic stress disorder and Complex PTSD diagnoses in children and adolescents exposed to a single-event trauma. J. Child Psychol. Psychiatr. doi: 10.111/jcpp.13240. 1World Health Organization. (2018), International Classiﬁcation of Diseases, 11th edition (ICD-11). Geneva, Switzerland: WHO 2Meiser-Stedman, R. et al. (2017), Acute stress disorder and the transition to posttraumatic stress disorder in children and adolescents: Prevalence, course, prognosis, diagnostic suitability, and risk markers. Depress. Anxiety. 34: 348–355. doi: 10.1002/da.22602. Complex post-traumatic stress disorder: a diagnostic category introduced by the World Health Organization’s classification system (ICD-11). Affected patients must meet the full criteria for PTSD, as well as exhibit (i) affect dysregulation, (ii) negative self-concept and (iii) disturbances in relationships.	2	2	3	0	0	0.495699	3	877
International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) – WHO Version for 2016 (“ICD-10 Version: 2016”), under Chapter V ‘Mental and behavioural disorders (F00-F99)’ and ‘Disorders of adult personality and behaviour (F60-F69)’ laid down a category called ‘Gender identity disorders’. Till early 2019, Transsexualism featured under this category (F64.0) as a disorder and was defined as “A desire to live and be accepted as a member of the opposite sex, usually accompanied by a sense of discomfort with, or inappropriateness of, one’s anatomic sex, and a wish to have surgery and hormonal treatment to make one’s body as congruent as possible with one’s preferred sex.” Similarly, Dual-role transvestism (F64.1) i.e. “The wearing of clothes of the opposite sex for part of the individual’s existence in order to enjoy the temporary experience of membership of the opposite sex, but without any desire for a more permanent sex change or associated surgical reassignment, and without sexual excitement accompanying the cross-dressing” and Gender identity disorder of childhood (F64.2) which was defined as “A disorder, usually first manifest during early childhood (and always well before puberty), characterized by a persistent and intense distress about assigned sex, together with a desire to be (or insistence that one is) of the other sex. There is a persistent preoccupation with the dress and activities of the opposite sex and repudiation of the individual’s own sex. The diagnosis requires a profound disturbance of the normal gender identity; mere tomboyishness in girls or girlish behaviour in boys is not sufficient” also featured in the list of disorders but were removed from this category in 2019 after feedback and deliberations (For example, as reported, Denmark no longer defined being transgender as a mental illness and the Government officials said classifying transgender people as mentally ill was “stigmatising” and they had “run out of patience” with the World Health Organisation’s (“WHO”) work on the definition). According to WHO’s website, the ICD is the foundation for the identification of health trends and statistics globally. It is the international standard for defining and reporting diseases and health conditions. It allows the world to compare and share health information using a common language. About 70% of the world’s health expenditures (USD $ 3.5 billion) are allocated using ICD for reimbursement and resource allocation. The first international classification edition, known as the International List of Causes of Death, was adopted by the International Statistical Institute in 1893. ICD-10 was endorsed in May 1990 by the Forty-third World Health Assembly. It is cited in more than 20,000 scientific articles and used by more than 100 countries around the world (117). ICD-11 (Version: 04 / 2019), removed the entire category of ‘Gender identity disorders’. Since the 2019 version, it is now considered as ‘Gender incongruence’ (also known as gender dysphoria) and a ‘Condition related to sexual health.’ Gender incongruence has been defined here as “characterized by a marked and persistent incongruence between an individual’s experienced gender and the assigned sex. Gender variant behaviour and preferences alone are not a basis for assigning the diagnoses in this group.” There is also a ‘Gender incongruence of adolescence or adulthood’ (HA60) which “is characterized by a marked and persistent incongruence between an individual´s experienced gender and the assigned sex, which often leads to a desire to ‘transition’, in order to live and be accepted as a person of the experienced gender, through hormonal treatment, surgery or other health care services to make the individual´s body align, as much as desired and to the extent possible, with the experienced gender. The diagnosis cannot be assigned prior the onset of puberty. Gender variant behaviour and preferences alone are not a basis for assigning the diagnosis” and ‘Gender incongruence of childhood’ (HA61) which “is characterized by a marked incongruence between an individual’s experienced/expressed gender and the assigned sex in pre-pubertal children. It includes a strong desire to be a different gender than the assigned sex; a strong dislike on the child’s part of his or her sexual anatomy or anticipated secondary sex characteristics and/or a strong desire for the primary and/or anticipated secondary sex characteristics that match the experienced gender; and make-believe or fantasy play, toys, games, or activities and playmates that are typical of the experienced gender rather than the assigned sex. The incongruence must have persisted for about 2 years. Gender variant behaviour and preferences alone are not a basis for assigning the diagnosis.” The Diagnostic and Statistical Manual of Mental Disorders (DSM-V) was also revised by the American Psychiatric Association in 2012 to remove the term “gender identity disorder” and add the term “gender dysphoria.” As far as India is concerned, when BuzzFeedNews conducted a survey in 2016, it found that majority of respondents said they think transgender people “have a form of mental illness”. They also found that majority believed transgender people “have a form of physical disability.” However, the Supreme Court of India, in the case of National Legal Services Authority vs. Union of India and others, Writ Petition (Civil) No. 400 of 2012 on 15th April, 2014 (“NALSA Judgment”) had held that “Self-determination of gender is an integral part of personal autonomy and self-expression and falls within the realm of personal liberty guaranteed under Article 21 of the Constitution of India” and therefore, “Self-identified gender can be either male or female or a third gender.” They did not consider it as a mental disorder. Further the recently passed Transgender Persons (Protection of Rights) Act, 2019, also under Section 4 states that a person recognised as transgender “shall have a right to self-perceived gender identity”. In Navtej Singh Johar and Ors. vs. Union of India (UOI) and Ors., W. P. (Crl.) No. 76 of 2016, decided by the Supreme Court of India on 6th September 2018, the Supreme Court held that “gay persons and transgenders are not persons suffering from mental disorder…” It also referred to the Mental Healthcare Act, 2017 and stated that this law “throws a great deal of light on recent parliamentary legislative understanding and acceptance of constitutional values…” It referred to Section 2(s) of the Act which defines mental illness as “a substantial disorder of thinking, mood, perception, orientation or memory that grossly impairs judgment, behaviour, capacity to recognise reality or ability to meet the ordinary demands of life, mental conditions associated with the abuse of alcohol and drugs, but does not include mental retardation which is a condition of arrested or incomplete development of mind of a person, specially characterised by subnormality of intelligence;” and stated that “This definition throws to the winds all earlier misconceptions of mental illness including the fact that same-sex couples who indulge in anal sex are persons with mental illness.” – Shivangi Prasad (Advocate and Partner, POSH at Work)	2	9	0	0	5	0.916663	5	1,590
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
Type 2 Diabetes Type 2 diabetes is a chronic disease in which your body is unable to maintain a normal blood sugar (glucose) level. - Birth Control Facts about birth control to help decide which type is right for you. - Type 2 Diabetes Basic facts about type 2 diabetes & risk factors to be aware of. - COPD Get the facts about chronic obstructive pulmonary disease (COPD), including symptoms and complications. - Diabetic Macular Edema Facts about diabetic macular edema, including the different types. - Flu Facts about influenza (flu), including symptoms and vaccines. - GERD Get the facts about gastroesophageal reflux disease (GERD). - Lupus Get the facts about lupus, including symptoms, risk factors, and the different types. - Menopause Facts about menopause, including the stages, symptoms, and types. - Ulcerative Colitis Facts about ulcerative colitis, including causes, signs and symptoms. - View All Care Guides Prepare for your next visit with our extensive library of Care Guides Dr. Patsy C Lazarous has the following 1 specialty - Internal Medicine An internist is a physician who focuses on the diagnosis and treatment of conditions that affect the adult population—both acute and chronic. These doctors are often who adults see as their primary physicians because they treat a broad range of illnesses that do not require surgical or specialist interventions. They also work to help a patient maintain optimal health in order to prevent the onset of disease. In addition to treating the common cold and flu, internists also treat chronic diseases like diabetes and heart disease. Dr. Patsy C Lazarous has the following 8 expertise - Weight Loss - Weight Loss (non-surgical) Dr. Patsy C Lazarous is Board Certified in 1 specialty See the board certifications this doctor has received. Board certifications provide confidence that this doctor meets the nationally recognized standards for education, knowledge and experience. Showing 5 of 14 Wanted to come in within a week to have them look at a possible blood clot in my leg (which could be life threatening) . I was really hoping to get the kind of care you can expect fro ma doctor like this, however, the doctor seems to overbook her practice for a full two months down the road... How can this be a good doctor if they do not leave pockets in their scheduled for serious cases? I was literally told to go to one of Seattle's horrendous ER instead. Why did i even try? This has happened on more than one occasion and I do not intend to return. For example, I saw her for an allergic reaction to something. She insists I have a problem with my tooth or I need to see a neurologist rather than treating the allergy. I tell her I have osteoporosis and severe stomach issues. She does nothing to help with the stomach issues and prescribes me a mediation for osteoporosis that specifically says not to take it if you have stomach problems. The list goes on. I would not recommend this physician. I switched to Dr Lazarus because I heard she was very, smart, genuine and patient with her patients. I was not disappointed! Every time I have been to see Dr. Lazarus, she is interested in me, my family and whatever brought me in to see her. My husband switched to her also and has been very satisfied with her care. We have moved to Seattle from the Eastside, but continue to go to her for our care - she is worth the drive! Patients' Choice Award (2008, 2009, 2011, 2012, 2013, 2014) Patients' Choice recognition reflects the difference a particular physician has made in the lives of his/her patients. The honor is bestowed to physicians who have received near perfect scores, as voted by patients. Top 10 Doctor - City (2014) Top 10 Doctors are chosen by the millions of patients who visit Vitals each year to find a new doctor and share their experiences by providing ratings and reviews. In order to differentiate highly-regarded doctors from the rest for patients in search of quality care, Vitals awards Top 10 Doctor honors to those physicians within a certain specialty and geographic area who are consistently given top ratings by their patients. Dr. Patsy C Lazarous accepts the following insurance providers. - Aetna Choice POS II - Aetna Managed Choice POS Open Access - Aetna Whole Health Pacific Medical Centers WA - Aetna Whole Health Providence Swedish WA BCBS Blue Card - BCBS Blue Card PPO - CIGNA HMO - CIGNA Open Access Plus - CIGNA PPO - First Health PPO - Humana Choice POS - Multiplan PPO - Moda Health First Choice Network - Premera Heritage and Heritage Plus 1 Regence Health Plans - Regence WA Preferred Provider Network Locations & DirectionsSwedish Medical Group, 12917 SE 38th St Ste 100, Bellevue, WA Take a minute to learn about Dr. Patsy C Lazarous in this video. Dr. Patsy C Lazarous is similar to the following 3 Doctors near Bellevue, WA.	2	8	1	0	0	0.901471	1	1,092
Leiomyosarcoma (LMS) is a malignant cancer of the smooth muscle cells. This is a rare type of tumor that is most frequently found to arise in the abdomen or the uterus. Soft tissue carcinomas arise in one out of every 100 cases of cancer. LMS is categorized as a carcinoma of the soft tissue. Most individuals affected by LMS are above 50 years of age. Leiomyosarcoma ICD 10 Code The ICD 10 Code for this condition is 49. LMS may develop in almost any area of the body that contains smooth muscle. This includes regions such as: Picture 1 – Leiomyosarcoma - Blood vessels - Gastrointestinal tract - Genitourinary tract - Retroperitoneum or the space lying behind the abdominal cavity The uterus is the commonest spot for the development of this type of malignant tumor. The condition also commonly affects the liver. When the liver is involved, patients experience problems like jaundice and enlargement of the liver. The majority of LMS tumors of the gastrointestinal tract are now reclassified as GIST (Gastrointestinal Stromal Tumors). The various types of cancer, including LMS, can be classified on the basis of the following factors: - The type of cell that is involved - The clinical course of the disorder - The particular nature of the malignancy In the early stages of LMS, affected individuals are usually asymptomatic. In other words, they do not display any signs or symptoms. Most LMS tumors are detected once a patient starts exhibit symptoms associated to this condition. These may include: - Bloated sensation or abdominal discomfort - Pain or inflammation in any region of the body - Swelling or development of lumps - Obstruction of the hepatic vein - Aches and presence of fluid in the abdominal cavity - Inflammation of the legs - Vaginal bleeding in menopausal women or change in periods in non-menopausal females Those experiencing one or more of the above mentioned problems should get in touch with a general practitioner. However, it is important to remember that these problems may also arise due to many other disorders or underlying conditions. Knowledge of having this type of growths may also give rise to various psychological issues like: These are normal reactions and friends and family members of sufferers should try to help them cope with such issues. In difficult cases, professional psychological assistance may be required. Types of Leiomyosarcoma According to the location of their growth, LMS tumors are classified into: It is a rare type of malignant growth arising from the smooth muscular lining of the uterine lining (myometrium). These arise from the pilo-erector muscles present in the skin. These can arise from the smooth muscle in the gastrointestinal tract or from a blood vessel. It is not exactly known why this type of tumor arises. Research is still to determine the exact reason for the origin and development of this cancerous growth. Certain factors have, however, been considered to be the possible causes of this disorder. These include: In extremely rare cases, sarcomas of the soft tissue may occur in regions that have been treated with radiotherapy any time earlier for any other type of cancer. However, the sarcomas do not usually arise until approximately 10 years after this type of treatment. Exposure to some types of chemicals may elevate the susceptibility of an individual to certain types of sarcomas. Such groups of chemicals include dioxins, some forms of weed-destroyers or herbicides or vinyl chloride (used for manufacturing plastics). As it is often asymptomatic in the initial stages, LMS is often difficult to diagnose early on. With its progression, the disorder begins to exhibit problems like swelling and discomfort which leads to its detection. Patients of LMS usually turn to general practitioners for medical guidance, who in turn refer them to hospital specialists. In hospital, diagnosis begins by a thorough analysis of the medical history of sufferers. Physical examination and blood tests are also used for the purpose of detection and checking the general health condition of affected individuals. Depending on the part of the body that is being investigated, various diagnostic tests may be used. These include: It is used to detect clinical issues in the womb. In this exam, physicians use hysteroscope (a thin, small tube with a camera and a light fitted at the end) to take a view of the womb and extract tissue samples for microscopic analysis. The instrument is passed into the womb through the vagina. The test may be used as an outpatient procedure under the effects of a local anesthetic. Sometimes, however, use of a general anesthetic is needed. Although it might be uncomfortable, the process is not painful. However, some women may suffer from cramps during the process and even for a few days after the test. The cramps are mild in intensity. It is the most common tests used for the detection of clinical issues in the gullet (oesophagus) and the stomach. Patients need to be on an empty stomach before the process is conducted. They must nit drink or eat anything for at least 4 hours prior to the exam. Following a sedative administration into the vein of an arm of the affected person, a local anesthetic is injected onto the back of the throat. This is followed by the insertion of an endoscope (a flexible tubular structure with a lens and a light fitted at the end) down the oesophagus and into the stomach. MRI (Magnetic Resonance Imaging) Scan The process is similar to CT scan. However, it involves the use of magnetism instead of x-rays to render cross-sectional images of the body. During the process, patients are asked to lie absolutely still on a couch located within a large, open-ended metallic cylinder. The test may take around an hour to be conducted. The exam involves production of loud noise, which might be difficult for some patients to bear. Due to this reason, sufferers are provided with headphones or earplugs to wear during the test. They are able to interact with the person in charge of the scanner. It is noteworthy that people fitted with pacemakers, surgical clips or metal in the eyes will not be able to undergo this exam. CT (Computerized Tomography) Scan The exam involves taking a series of x-rays that create 3D images of the internal structures of the body. It includes use of small amounts of radiation which is least likely to harm individuals undergoing this process. As in Endoscopy, patients are advised not to consume any solid or liquid substance from at least 4 hours prior to the actual time of the scan. Individuals are typically injected with a dye that allows clearer view of specific areas of the body. The injection may make patients experience a hot sensation. Sufferers should consult doctors if they are asthmatic or allergic to iodine. Otherwise, they could suffer from serious reactions due to the dye injection. In this test, audio waves are used to render images of the abdomen and its adjoining regions. Patients are asked not to consume anything solid. They are, however, permitted to drink liquids (although only clear fluids and nothing viscous or fizzy) 4-6 hours prior to the scan. During the actual process, patients are asked to lie on their back comfortably. A gel is spread over their abdomen and a probe (a tiny device shaped like a microphone) is rubbed over this. The probe emits audio waves that are afterwards converted into images rendered into a computer screen. In some cases, the probe is inserted slowly into the vagina to let physicians have a closer view of the womb. The test is not painful. It takes around 15-20 minutes to perform this examination. The exam is typically conducted in the scanning department of hospitals. It includes taking tissue strips or some cells from the affected region for microscopic analysis. Once the area is made numb by injecting a local anesthetic, a fine needle is inserted through its overlying skin and into the tumor. The treatment for this disorder depends on a number of factors. These include: Picture 2 – Leiomyosarcoma Image - General health status of sufferers - Size of tumor within the body - Location of tumor inside the body The results of diagnostic tests conducted for this disorder help physicians decide on the best treatment option for sufferers. Doctors discuss with patients about the treatment measure that is most suitable for them. The curative options for this tumor include: It is the most common treatment option used for curing LMS by removing the malignant growths. Radiotherapy may be used as a follow-up measure to lower the risk of recurrence of this cancerous condition. It is used for treating some cases of LMS. The process may either be used for curing an LMS that has spread to other regions of the body or for lowering the risk of recurrence of the growth. Leiomyosarcoma Survival Rate The outcome of LMS is not a good one. The condition usually has an unfavorable prognosis with the survival rate being less than 3-5 years in duration. This is due to the high risk of recurrence and metastasis associated with these form of malignant growths. Leiomyosarcoma Support Groups and Organizations Individuals affected by LMS may seek general advice and information from the following organizations: Northwest Sarcoma Foundation P.O. Box 91460 Portland, OR 97291 Rare Cancer Alliance 1649 North Pacana Way Green Valley, AZ 85614 National Cancer Institute 6116 Executive Blvd Bethesda, MD 20892-8322 American Cancer Society, Inc. 1599 Clifton Road NE Atlanta, GA 30329 Those experiencing the symptoms of LMS should seek medical attention at the earliest. This being a malignant condition, it is important not to delay treatment and seek professional medical care at the earliest stage to prevent later complications.	2	8	1	0	0	0.763663	1	2,089
International Classification of Diseases (ICD), in medicine, diagnostic tool that is used to classify and monitor causes of injury and death and that maintains information for health analyses, such as the study of mortality (death) and morbidity (illness) trends. The ICD is designed to promote international compatibility in health data collecting and reporting. History of the ICD Some of the first attempts to systematically classify diseases were made in the 1600s and 1700s, though the resulting classifications were considered to be of little utility, largely as a result of inconsistencies in nomenclature and poor statistical data. During the 1800s the importance of creating a uniform system was realized, and several medical statisticians commissioned the completion of that task. The International Statistical Institute adopted the first international classification of diseases in 1893. The system was based on the Bertillon Classification of Causes of Death, developed by French statistician and demographer Jacques Bertillon. In 1898 the American Public Health Association recommended that Canada, Mexico, and the United States use that system and that it be revised every decade. In the following years Bertillon’s classification became known as the International List of Causes of Death and ultimately as the ICD. The ICD became increasingly detailed through repeated revision, particularly after 1948, when the World Health Organization (WHO) assumed responsibility for publishing the ICD and began collecting international data for all general epidemiological surveillance and health management purposes. WHO significantly revised the ICD in the 1980s and early ’90s. The resulting three-volume work, known as ICD-10 (International Statistical Classification of Diseases and Related Health Problems), was published in 1992; it eventually replaced the two-volume ICD-9 in countries worldwide that used the classification. The ICD became a core classification of the WHO Family of International Classifications (WHO-FIC). Design of the ICD The ICD contains a description of all known diseases and injuries. Each disease is detailed with diagnostic characteristics and given a unique identifier that is used to code mortality data on death certificates and morbidity data from patient and clinical records. The core of the ICD-10 uses one single list of four-alphanumeric-character codes from A00.0 to Z99.0 . The first letter of the code designates a different chapter; there are 22 chapters in total (several letters are included in a single chapter together). Within each chapter, the four-character codes are divided so that they specify different classification axes. The fourth character (the number after the decimal) is not required for reporting and is used in various ways. Use of the ICD Every country subscribing to the ICD system uses it in varying degrees. Most countries subscribe to the entirety of the ICD system, whereas some use the ICD in hospitals only and others for morbidity only. Some countries have chosen to implement partial code use. Differences in mortality classification coding between ICD-9 and ICD-10 prevented direct comparisons between the two, though a method to adjust for the change was introduced. The U.S. Department of Health and Human Services felt that the ICD needed to provide better clinical information and developed a system that is referred to as ICD 9th revision: Clinical Modification (ICD-9-CM). The CM codes are much more precise and allow for strong analyses. The ICD-9-CM was used by hospitals and other health care facilities, particularly for reporting morbidity (the ICD-10 frequently was used to report mortality data). The ICD-9-CM was scheduled for replacement by the ICD-10-CM in 2014.	3	2	0	0	2	0.444649	2	742
Antisocial personality disorder From Wikipedia, the free encyclopedia Jump to: navigation, search Not to be confused with Avoidant Personality Disorder. Dissocial Personality Disorder Classification and external resources Cluster A (odd) Paranoid · Schizoid Cluster B (dramatic) Antisocial · Borderline Histrionic · Narcissistic Cluster C (anxious) Avoidant · Dependent Depressive · Passive–aggressive Sadistic · Self-defeating v • d • e Antisocial Personality Disorder (ASPD or APD) is defined by the American Psychiatric Association's Diagnostic and Statistical Manual as "...a pervasive pattern of disregard for, and violation of, the rights of others that begins in childhood or early adolescence and continues into adulthood." The individual must be age 18 or older, as well as have a documented history of a conduct disorder before the age of 15. People having antisocial personality disorder are sometimes mistakenly referred to as "sociopaths" and "psychopaths". However, an abundance of research has shown that antisocial personality disorder, psychopathy, and sociopathy are distinctly different personality disorders. 3 Diagnostic criteria (DSM-IV-TR = 301.7) 4 Diagnostic criteria (ICD-10) - dissocial personality disorder 5 Millon's subtypes 6 Differential diagnosis: associated and overlapping conditions 7 Prevalence (epidemiology) 9 See also 11 External links The history of the origins of antisocial personality disorder are closely related to the history of psychopathy – see history of psychopathy. Characteristics of people with antisocial personality disorder may include: Persistent lying or stealing Apparent lack of remorse or empathy for others Inability to keep jobs or stay in school Impulsivity and/or recklessness Lack of realistic, long-term goals — an inability or persistent failure to develop and execute long-term plans and goals Poor behavioral controls — expressions of irritability, annoyance, impatience, threats, aggression, and verbal abuse; inadequate control of anger and temper A history of childhood conduct disorder Recurring difficulties with the law Tendency to violate the boundaries and rights of others Aggressive, often violent behavior; prone to getting involved in fights Inability to tolerate boredom Disregard for the safety of self or others Persistent attitude of irresponsibility Difficulties with authority figures Diagnostic criteria (DSM-IV-TR = 301.7) The Diagnostic and Statistical Manual of Mental Disorders fourth edition, DSM IV-TR, a widely used manual for diagnosing mental disorders, defines antisocial personality disorder (in Axis II Cluster B) as: A) There is a pervasive pattern of disregard for and the rights of others occurring since the age of 15, 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; deceitfulness, 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 18 years of age. C) There is evidence of Conduct disorder with onset before age 15. D) The occurrence of antisocial behavior is not exclusively during the course of schizophrenia or a manic episode. Deceit and manipulation are considered essential features of the disorder. Therefore, it is essential in making the diagnosis to collect material from sources other than the individual being diagnosed. It is a requirement of DSM-IV that a diagnosis of any specific personality disorder also satisfies a set of general personality disorder criteria. Researchers have heavily criticized the ASPD DSM-IV criteria because not enough emphasis was placed on traditional psychopathic traits such as a lack of empathy, superficial charm, and inflated self appraisal. These latter traits are harder to assess than behavioral problems (like impulsivity and acting out). Thus, the DSM-IV framers sacrificed validity for reliability. That is, the ASPD diagnosis focuses on behavioral traits, but only limited emphasis is placed on affective and unemotional interpersonal traits. Researchers debate about whether psychopathy/sociopathy are incorrectly put together under ASPD. These clinicians and researchers who believe that it was incorrect to label the two in the same category are upset that an important distinction has been lost between these two disorders. In other words, the DSM-IV-TR considers ASPD and psychopathy to be the same, or similar. However, they are not the same since antisocial personality disorder is diagnosed via behavior and social deviance, whereas psychopathy also includes affective and interpersonal personality factors. Also, ASPD, unlike psychopathy, does not have biological markers confirmed to underpin the disorder. Other criticisms of ASPD are that it is essentially synonymous with criminality. Nearly 80%–95% of felons will meet criteria for ASPD — thus ASPD predicts nothing in criminal justice populations. Whereas, psychopathy scores (using the Hare Psychopathy Checklist-Revised (PCL-R)) is found in only ~20% of inmates and PCL-R is considered one of the best predictors of violent recidivism. Also, the DSM-IV field trials never included incarcerated populations. The official stance of the American Psychiatric Association as presented in the DSM-IV-TR is that "psychopathy" and "sociopathy" are obsolete synonyms for antisocial personality disorder. The World Health Organization takes a similar stance in its ICD-10 by referring to psychopathy, sociopathy, antisocial personality, asocial personality, and amoral personality as synonyms for dissocial personality disorder. Diagnostic criteria (ICD-10) - dissocial personality disorder The World Health Organization's ICD-10 defines a conceptually similar disorder to antisocial personality disorder called (F60.2) Dissocial personality disorder. It is characterized by at least 3 of the following: Callous unconcern for the feelings of others and lack of the capacity for empathy. Gross and persistent attitude of irresponsibility and disregard for social norms, rules, and obligations. Incapacity to maintain enduring relationships. Very low tolerance to frustration and a low threshold for discharge of aggression, including violence. Incapacity to experience guilt and to profit from experience, particularly punishment. Markedly prone to blame others or to offer plausible rationalizations for the behavior bringing the subject into conflict. The criteria specifically rule out conduct disorders. Dissocial personality disorder criteria differ from those for antisocial and sociopathic personality disorders. It is a requirement of ICD-10 that a diagnosis of any specific personality disorder also satisfies a set of general personality disorder criteria. Millon's subtypes Theodore Millon identified five subtypes of antisocial . Any individual antisocial may exhibit none, one or more than one of the following: covetous antisocial - variant of the pure pattern where individuals feel that life has not given them their due. reputation-defending antisocial - including narcissistic features risk-taking antisocial - including histrionic features nomadic antisocial - including schizoid, avoidant features malevolent antisocial - including sadistic, paranoid features. Differential diagnosis: associated and overlapping conditions The following conditions commonly coexist with antisocial personality disorder: Borderline personality disorder Histrionic personality disorder Narcissistic personality disorder When combined with alcoholism, people may show frontal function deficits on neuropsychological tests greater than those associated with each condition. Prevalence (epidemiology) Antisocial personality disorder in the general population is about 3% in males and 1% in females. It is seen in 3% to 30% of psychiatric outpatients. The prevalence of the disorder is even higher in selected populations, such as people in prisons (who include many violent offenders). 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. This section requires expansion. To date there have been no controlled studies reported which found an effective treatment for ASPD, although contingency management programs, or a reward system, has been shown moderately effective for behavioral change. Some studies have found that the presence ASPD does not significantly interfere with treatment for other disorders, such as substance abuse, although others have reported contradictory findings. See also DSM-IV codes (personality disorders) The Mask of Sanity ^ a b c d e Antisocial personality disorder - Diagnostic and Statistical Manual of Mental Disorders Fourth edition Text Revision (DSM-IV-TR) American Psychiatric Association (2000) - pages 645–650 ^ "Antisocial Personality, Sociopathy, and Psychopathy" ^ a b c "Antisocial Personality Disorder". Psychology Today. 2005. http://psychologytoday.com/conditions/antisocial.html. Retrieved 2007-02-20. ^ "Antisocial Personality Disorder Treatment". Psych Central. 2006. http://psychcentral.com/disorders/sx7t.htm. Retrieved 2007-02-20. ^ "Antisocial Personality Disorder". http://www.behavenet.com/capsules/disorders/antisocialpd.htm. Retrieved 2007-12-15. ^ Hare, R.D., Hart, S.D., Harpur, T.J. Psychopathy and the DSM—IV Criteria for Antisocial Personality Disorder (pdf file) ^ Dissocial personality disorder - International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) ^ 602 "F60.2 Dissocial personality disorder". World Health Organization. http://www.who.int/classifications/apps/icd/icd10online/?gf60.htm+F602. Retrieved 2008-01-12. ^ Early Prevention of Adult Antisocial Behavior. Cambridge University Press. p. 82. http://books.google.com/books?id=KtXU8R8oZYwC&pg=PA82&lpg=PA82&dq=dissocial+personality+disorder&source=web&ots=lVx_gb_9mM&sig=U_bMqyc-KlzHKEvzXBdeZxplN2E. Retrieved 2008-01-12. ^ Millon, Theodore, Personality Disorders in Modern Life, 2004 ^ Millon, Theodore - Personality Subtypes ^ a b c Internet Mental Health - antisocial personality disorder ^ 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. PMID 19557141. http://www.dovepress.com/getfile.php?fileID=4829. ^ Hare 1983 ^ "Antisocial Personality Disorder, Alcohol, and Aggression". Alcohol Research & Health. National Institute on Alcohol Abuse and Alcoholism. 2006. http://pubs.niaaa.nih.gov/publications/arh25-1/5-11.pdf. Retrieved 2007-02-20. ^ J. E. Fisher & W. T. O'Donohue (eds). (2006). Practitioner's Guide to Evidence-Based Psychotherapy, p63 ^ S. Darke, R. Finlay-Jones, S. Kaye, & T. Blatt. Anti-social personality disorder and response to methadone maintenance treatment. Drug and Alcohol Review, vol. 15, 271-276 (1996) ^ A. I. Alterman, M. J. Rutherford, J. S. Cacciola, J. R. McKay, & C. R. Boardman. Prediction of 7 months methadone maintenance treatment response by four measures of antisociality. Drug & Alcohol Dependence, vol. 49, 217-223 (1998) External links 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 Antisocial personality, Sociopathy, and psychopathy North Carolina Wesleyan College, 2005 Recent Studies Implicate Slow Monoamine Oxidase Enzyme/High Circulating T3 in Antisocial Behavior/Aggression/Violence 2007 [show]v • d • eDSM personality disorders DSM-III-R only Sadistic · Self-defeating (masochistic) DSM-IV Cluster A (odd) Paranoid · Schizoid · Schizotypal Cluster B (dramatic) Antisocial · Borderline · Histrionic · Narcissistic Cluster C (anxious) Avoidant · Dependent · Obsessive-compulsive Personality disorder not otherwise specified Appendix B (proposed) Depressive · Negativistic (passive-aggressive) [show]v • d • eICD-10 personality disorders Specific Anankastic · Anxious (avoidant) · Dependent · Dissocial · Emotionally unstable · Histrionic · Paranoid · Schizoid · Other Eccentric · Haltlose type · Immature · Narcissistic · Passive-aggressive · Psychoneurotic Mixed and other Mixed and other Retrieved from "http://en.wikipedia.org/wiki/Antisocial_personality_disorder" Categories: Abnormal psychology \| Forensic psychology \| Personality disorders \| Psychopathy Hidden categories: All articles with unsourced statements \| Articles with unsourced statements from April 2010 \| Articles with unsourced statements from February 2009 \| Articles with unsourced statements from November 2009 \| Articles to be expanded from November 2009 \| All articles to be expandedViewsArticle Discussion Edit this page History Personal toolsTry Beta Log in / create account Navigation Donate to Wikipedia What links here Cite this page Српски / Srpski From Wikipedia, the free encyclopedia	2	14	0	0	4	0.550411	4	3,129
\|Usual onset\|\|Young adulthood\| \|Frequency\|\|1-2% (general population)\| Depersonalization disorder (DPD), also known as depersonalization/derealization disorder, is a mental disorder in which the person has persistent or recurrent feelings of depersonalization or derealization. Depersonalization is described as feeling disconnected or detached from one's self. Individuals experiencing depersonalization may report feeling as if they are an outside observer of their own thoughts or body, and often report feeling a loss of control over their thoughts or actions; in some cases, individuals may be unable to accept their reflection as their own, or they may have out-of-body experiences. Derealization is described as detachment from one's surroundings. Individuals experiencing derealization may report perceiving the world around them as foggy, dreamlike/surreal, or visually distorted; in addition to these depersonalization-derealization disorder symptoms, the inner turmoil created by the disorder can result in depression, self-harm, low self-esteem, panic attacks, phobias, etc. It can also cause a variety of physical symptoms, including chest pain, blurry vision, visual snow, nausea, and the sensation of pins and needles in one's arms or legs. Depersonalization-derealization disorder is thought to be caused largely interpersonal trauma such as childhood abuse. Triggers may include significant stress, cannabis or hallucinogen use, it is unclear whether genetics plays a role; however, there are many neurochemical and hormonal changes in individuals with depersonalization disorder. The disorder is typically associated with cognitive disruptions in early perceptual and attentional processes. Diagnostic criteria for depersonalization-derealization disorder include, among other symptoms, persistent or recurrent feelings of detachment from one's mental or bodily processes or from one's surroundings. A diagnosis is made when the dissociation is persistent and interferes with the social and/or occupational functions of daily life. However, accurate descriptions of the symptoms are hard to provide due to the subjective nature of depersonalization/derealization and persons' ambiguous use of language when describing these episodes; in the DSM-5, it was combined with Derealization Disorder and renamed Depersonalization/Derealization Disorder (DDPD). In the DSM-5, it remains classified as a dissociative disorder, while the ICD-10 calls it depersonalization-derealization syndrome and classifies it as a neurotic disorder, although the disorder is an alteration in the subjective experience of reality, it is not a form of psychosis, as the person is able to distinguish between their own internal experiences and the objective reality of the outside world. During episodic and continuous depersonalization, the person can distinguish between reality and fantasy; in other words, the grasp on reality remains stable at all times. While depersonalization-derealization disorder was once considered rare, lifetime experiences with it occur in about 1–2% of the general population, the chronic form of the disorder has a reported prevalence of 0.8 to 1.9%. While these numbers may seem small, depersonalization/derealization experiences have been reported by a majority of the general population, with varying degrees of intensity. While brief episodes of depersonalization or derealization can be common in the general population, the disorder is only diagnosed when these symptoms cause substantial distress or impair social, occupational, or other important areas of functioning. The core symptoms of depersonalization-derealization disorder is the subjective experience of "unreality in one's self", or detachment from one's surroundings. People who are diagnosed with depersonalization also experience an urge to question and think critically about the nature of reality and existence, it results in significant distress. Individuals who experience depersonalization can feel divorced from their own personal physicality by sensing their body sensations, feelings, emotions and behaviors as not belonging to themselves, as such, a recognition of one's self breaks down. Depersonalization can result in very high anxiety levels, which can intensify these perceptions even further. Individuals with depersonalization describe feeling disconnected from their physicality; feeling as if they are not completely occupying their own body; feeling as if their speech or physical movements are out of their control; feeling detached from their own thoughts or emotions; and experiencing themselves and their lives from a distance. While depersonalization involves detachment from one's self, individuals with derealization feel detached from their surroundings, as if the world around them is foggy, dreamlike, or visually distorted, some people with depersonalization disorder also have visual alterations such as rapid fluctuations in light. While the exact cause of these perceptual changes has not been determined, it is thought that they may be due to previous drug use, these perceptual changes differ from true hallucinatory phenomena, as they are closer to being optical distortions or illusions rather than psychotic breaks from reality. Individuals with the disorder commonly describe a feeling as though time is "passing" them by and they are not in the notion of the present, these experiences which strike at the core of a person's identity and consciousness may cause a person to feel uneasy or anxious. Factors that tend to diminish symptoms are comforting personal interactions, intense physical or emotional stimulation, and relaxation. Distracting oneself (by engaging in conversation or watching a movie, for example) may also provide temporary relief, some other factors that are identified as relieving symptom severity are diet and/or exercise, while alcohol and fatigue are listed by some as worsening their symptoms. First experiences with depersonalization may be frightening, with patients fearing loss of control, dissociation from the rest of society and functional impairment, the majority of people with depersonalization-derealization disorder misinterpret the symptoms, thinking that they are signs of serious psychosis or brain dysfunction. This commonly leads to an increase of anxiety and obsession, which contributes to the worsening of symptoms. Occasional, brief moments of mild depersonalization can be experienced by many members of the general population; however, depersonalization-derealization disorder occurs when these feelings are strong, severe, persistent, or recurrent and when these feelings interfere with daily functioning. The exact cause of depersonalization is unknown, although biopsychosocial correlations and triggers have been identified. Childhood interpersonal trauma – emotional abuse in particular – is a significant predictor of a diagnosis, the most common immediate precipitators of the disorder are severe stress; major depressive disorder and panic; and hallucinogen ingestion. People who live in highly individualistic cultures may be more vulnerable to depersonalization, due to threat hypersensitivity and an external locus of control. One cognitive behavioral conceptualization is that misinterpreting normally transient dissociative symptoms as an indication of severe mental illness or neurological impairment leads to the development of the chronic disorder, this leads to a vicious cycle of heightened anxiety and symptoms of depersonalization and derealization. Not much is known about the neurobiology of depersonalization disorder; however, there is converging evidence that the prefrontal cortex may inhibit neural circuits that normally form the substrate of emotional experience. A PET scan found functional abnormalities in the visual, auditory, and somatosensory cortex, as well as in areas responsible for an integrated body schema. In an fMRI study of DPD patients, emotionally aversive scenes activated the right ventral prefrontal cortex. Participants demonstrated a reduced neural response in emotion-sensitive regions, as well as an increased response in regions associated with emotional regulation; in a similar test of emotional memory, depersonalization disorder patients did not process emotionally salient material in the same way as did healthy controls. In a test of skin conductance responses to unpleasant stimuli, the subjects showed a selective inhibitory mechanism on emotional processing. Depersonalization disorder may be associated with dysregulation of the hypothalamic-pituitary-adrenal axis, the area of the brain involved in the "fight-or-flight" response. Patients demonstrate abnormal cortisol levels and basal activity. Studies found that patients with DPD could be distinguished from patients with clinical depression and posttraumatic stress disorder. The symptoms are sometimes described by those with neurological diseases, such as amyotrophic lateral sclerosis, Alzheimer's, multiple sclerosis (MS), neuroborreliosis (Lyme disease), etc., that directly affect brain tissue. It has been thought that depersonalization has been caused by a biological response to dangerous or life-threatening situations which causes heightened senses and emotional neutrality. If this response occurs in real-life, non-threatening situations, the result can be shocking to the individual. Depersonalization disorder is classified differently in the DSM-IV-TR and in the ICD-10: In the DSM-IV-TR this disorder it is seen as a dissociative disorder; in the ICD-10 as an independent neurotic disorder. Whether depersonalization disorder should be characterized as a dissociative disorder can be discussed. Diagnosis is based on the self-reported experiences of the person followed by a clinical assessment. Psychiatric assessment includes a psychiatric history and some form of mental status examination, since some medical and psychiatric conditions mimic the symptoms of DPD, clinicians must differentiate between and rule out the following to establish a precise diagnosis: temporal lobe epilepsy, panic disorder, acute stress disorder, schizophrenia, migraine, drug use, brain tumour or lesion. No laboratory test for depersonalization-derealization disorder currently exists. The diagnosis of depersonalization disorder can be made with the use of the following interviews and scales: The Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D) is widely used, especially in research settings. This interview takes about 30 minutes to 1.5 hours, depending on individual's experiences. The Dissociative Experiences Scale (DES) is a simple, quick, self-administered questionnaire that has been widely used to measure dissociative symptoms, it has been used in hundreds of dissociative studies, and can detect depersonalization and derealization experiences. The Dissociative Disorders Interview Schedule (DDIS) is a highly structured interview which makes DSM-IV diagnoses of somatization disorder, borderline personality disorder and major depressive disorder, as well as all the dissociative disorders, it inquires about positive symptoms of schizophrenia, secondary features of dissociative identity disorder, extrasensory experiences, substance abuse and other items relevant to the dissociative disorders. The DDIS can usually be administered in 30–45 minutes. The Cambridge Depersonalization Scale (CDS) is a method for determining the severity of depersonalization disorder, it has been proven and accepted as a valid tool for the diagnosis of depersonalization disorder in a clinical setting. It is also used in a clinical setting to differentiate minor episodes of depersonalization from actual symptoms of the disorder. Due to the success of the CDS, a group of Japanese researchers underwent the effort to translate the CDS into the J-CDS or the Japanese Cambridge Depersonalization Scale. Through clinical trials the Japanese research team successfully tested their scale and determined its accuracy. One limitation is that the scale does not allow for the differentiation between past and present episodes of depersonalization, it should also be noted that it may be difficult for the individual to describe the duration of a depersonalization episode, and thus the scale may lack accuracy. The project was conducted in the hope that it would stimulate further scientific investigations into depersonalization disorder. The diagnostic criteria defined in section 300.6 of the Diagnostic and Statistical Manual of Mental Disorders are as follows: - Longstanding or recurring feelings of being detached from one's mental processes or body, as if one is observing them from the outside or in a dream. - Reality testing is unimpaired during depersonalization - Depersonalization causes significant difficulties or distress at work, or social and other important areas of life functioning. - Depersonalization does not only occur while the individual is experiencing another mental disorder, and is not associated with substance use or a medical illness. The DSM-IV-TR specifically recognizes three possible additional features of depersonalization disorder: - Derealization, experiencing the external world as strange or unreal. - Macropsia or micropsia, an alteration in the perception of object size or shape. - A sense that other people seem unfamiliar or mechanical. Dissociation is defined as a "disruption in the usually integrated functions of consciousness, memory, identity and perception, leading to a fragmentation of the coherence, unity and continuity of the sense of self. Depersonalisation is a particular type of dissociation involving a disrupted integration of self-perceptions with the sense of self, so that individuals experiencing depersonalisation are in a subjective state of feeling estranged, detached or disconnected from their own being." In ICD-10, this disorder is called depersonalization-derealization syndrome F48.1. The diagnostic criteria are as follows: - 1. one of the following: - depersonalization symptoms, i.e. the individual feels that his or her feelings and/or experiences are detached, distant, etc. - derealization symptoms, i.e. objects, people, and/or surroundings seem unreal, distant, artificial, colourless, lifeless, etc. - 2. an acceptance that this is a subjective and spontaneous change, not imposed by outside forces or other people (i.e. insight) The diagnosis should not be given in certain specified conditions, for instance when intoxicated by alcohol or drugs, or together with schizophrenia, mood disorders and anxiety disorders. Primary depersonalization disorder is mostly refractory to current treatments, the disorder lacks effective treatment in part because it has been neglected within the field of psychiatry, which, in turn, is partly because funding has mainly been allocated to the search for cures of other illnesses, like alcoholism. However, recognizing and diagnosing the condition may in itself have therapeutic benefits, considering many patients express their problems as baffling and unique to them, but are in fact: one, recognized and described by psychiatry; and two, those affected by it are not the only individuals to be affected from the condition. A variety of psychotherapeutic techniques have been used to treat depersonalization disorder, such as cognitive behavioral therapy. Clinical pharmacotherapy research continues to explore a number of possible options, including selective serotonin reuptake inhibitors, tricyclic antidepressants, anticonvulsants, and opioid antagonists. Cognitive behavior therapy An open study of cognitive behavior therapy has aimed to help patients reinterpret their symptoms in a nonthreatening way, leading to an improvement on several standardized measures. A standardized treatment for DPD based on cognitive behavioral principles was published in The Netherlands in 2011. Neither antidepressants nor antipsychotics have been found to be useful, Additionally antipsychotics can worsen symptoms of depersonalisation. To date, no clinical trials have studied the effectiveness of benzodiazepines. Tentative evidence supports naloxone and naltrexone. A combination of an SSRI and a benzodiazepine has been proposed to be useful for DPD patients with anxiety. Modafinil used alone has been reported to be effective in a subgroup of individuals with depersonalization disorder (those who have attentional impairments, under-arousal and hypersomnia). However, clinical trials have not been conducted. Men and women are diagnosed in equal numbers with depersonalization disorder. A 1991 study on a sample from Winnipeg, Manitoba estimated the prevalence of depersonalization disorder at 2.4% of the population. A 2008 review of several studies estimated the prevalence between 0.8% and 1.9%. This disorder is episodic in about one-third of individuals, with each episode lasting from hours to months at a time. Depersonalization can begin episodically, and later become continuous at constant or varying intensity. Onset is typically during the teenage years or early 20s, although some report being depersonalized as long as they can remember, and others report a later onset, the onset can be acute or insidious. With acute onset, some individuals remember the exact time and place of their first experience of depersonalization, this may follow a prolonged period of severe stress, a traumatic event, an episode of another mental illness, or drug use. Insidious onset may reach back as far as can be remembered, or it may begin with smaller episodes of lesser severity that become gradually stronger. Patients with drug-induced depersonalization do not appear to be a clinically separate group from those with a non-drug precipitant. Relation to other psychiatric disorders Depersonalization exists as both a primary and secondary phenomenon, although making a clinical distinction appears easy but is not absolute, the most common comorbid disorders are depression and anxiety, although cases of depersonalization disorder without symptoms of either do exist. Comorbid obsessive and compulsive behaviours may exist as attempts to deal with depersonalization, such as checking whether symptoms have changed and avoiding behavioural and cognitive factors that exacerbate symptoms. Many people with personality disorders such as schizoid personality disorder, schizotypal personality disorder, and borderline personality disorder will have high chances of having depersonalization disorder. Researchers at the Institute of Psychiatry in London, England suggest depersonalization disorder be placed with anxiety and mood disorders, as in the ICD-10, instead of with dissociative disorders as in the DSM-IV-TR. The word depersonalization itself was first used by Henri Frédéric Amiel in The Journal Intime, the 8 July 1880 entry reads: I find myself regarding existence as though from beyond the tomb, from another world; all is strange to me; I am, as it were, outside my own body and individuality; I am depersonalized, detached, cut adrift. Is this madness? Depersonalization was first used as a clinical term by Ludovic Dugas in 1898 to refer to "a state in which there is the feeling or sensation that thoughts and acts elude the self and become strange; there is an alienation of personality – in other words a depersonalization". This description refers to personalization as a psychical synthesis of attribution of states to the self. Early theories of the cause of depersonalization focused on sensory impairment. Maurice Krishaber proposed depersonalization was the result of pathological changes to the body's sensory modalities which lead to experiences of "self-strangeness" and the description of one patient who "feels that he is no longer himself". One of Carl Wernicke's students suggested all sensations were composed of a sensory component and a related muscular sensation that came from the movement itself and served to guide the sensory apparatus to the stimulus; in depersonalized patients these two components were not synchronized, and the myogenic sensation failed to reach consciousness. The sensory hypothesis was challenged by others who suggested that patient complaints were being taken too literally and that some descriptions were metaphors – attempts to describe experiences that are difficult to articulate in words. Pierre Janet approached the theory by pointing out his patients with clear sensory pathology did not complain of symptoms of unreality, and that those who have depersonalization were normal from a sensory viewpoint. Psychodynamic theory formed the basis for the conceptualization of dissociation as a defense mechanism. Within this framework, depersonalization is understood as a defense against a variety of negative feelings, conflicts, or experiences. Sigmund Freud himself experienced fleeting derealization when visiting the Acropolis in person; having read about it for years and knowing it existed, seeing the real thing was overwhelming and proved difficult for him to perceive it as real. Freudian theory is the basis for the description of depersonalization as a dissociative reaction, placed within the category of psychoneurotic disorders, in the first two editions of the Diagnostic and Statistical Manual of Mental Disorders. Some argue that because depersonalization and derealization are both impairments to one’s ability to perceive reality, they are merely two facets of the same disorder. Depersonalization also differs from delusion in the sense that the patient is able to differentiate between reality and the symptoms they may experience, the ability to sense that something is unreal is maintained when experiencing symptoms of the disorder. The problem with properly defining depersonalization also lies within the understanding of what reality actually is; in order to comprehend the nature of reality we must incorporate all the subjective experiences throughout and thus the problem of obtaining an objective definition is brought about again. Society and culture Depersonalization disorder has appeared in a variety of media, the director of the autobiographical documentary Tarnation, Jonathan Caouette, had depersonalization disorder. The screenwriter for the 2007 film Numb had depersonalization disorder, as does the film's protagonist played by Matthew Perry. Norwegian painter Edvard Munch's famous masterpiece The Scream may have been inspired by depersonalization disorder; in Glen Hirshberg's novel The Snowman's Children, main female plot characters throughout the book had a condition that is revealed to be depersonalization disorder. Suzanne Segal had an episode in her 20s that was diagnosed by several psychologists as depersonalization disorder, though Segal herself interpreted it through the lens of Buddhism as a spiritual experience. The song "Is Happiness Just a Word?" by hip hop artist Vinnie Paz describes his struggle with depersonalization disorder. Adam Duritz, of the band Counting Crows, has often spoken about his diagnosis of depersonalization disorder. - Baker, Dawn; Hunter, Elaine; Lawrence, Emma; Medford, Nicholas; Patel, Maxine; Senior, Carl; Sierra, Mauricio; Lambert, Michelle V.; Phillips, Mary L. (2003-05-01). "Depersonalisation disorder: clinical features of 204 cases". The British Journal of Psychiatry. 182 (5): 428–433. doi:10.1192/bjp.182.5.428. ISSN 0007-1250. PMID 12724246. - Hunter, EC; Sierra, M; David, AS (January 2004). "The epidemiology of depersonalisation and derealisation. A systematic review". Social psychiatry and psychiatric epidemiology. 39 (1): 9–18. doi:10.1007/s00127-004-0701-4. PMID 15022041. - American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (DSM-5). American Psychiatric Publishing. p. 620. ISBN 978-0-89042-557-2. - "Depersonalization derealization disorder: Epidemiology, pathogenesis, clinical manifestations, course, and diagnosis". - Simeon D (2004). 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Conversion Disorder (CD), also known as Functional Neurological Symptom Disorder is a psychiatric disorder where “one or more symptoms emerge quickly and affects [one’s] awareness, perception, sensation, or movement without any apparent physical cause” (American Psychiatric Association, 2015) and is listed under Somatic Symptom Disorders in the DSM-V. The DSM-V states that Conversion Disorder is diagnosed when one or more symptoms presented affect the normal functioning of bodily movements or sensations. There must not be a physiological cause upon in-depth medical review. The presented symptoms must also not be attributed to other medical conditions or mental disorders. These symptoms also inhibit the normal functioning of an individual such as in social or occupational contexts. Contrary to the DSM-V, the ICD-10 categorises Conversion Disorder under Dissociative Disorders instead of Somatoform Disorders, but the ICD-10 share a similar diagnostic criterion as the DSM-V. The causes of Conversion Disorder are not clearly and understood in its entirety, but it is attributed to biological and psychological factors. Some common symptoms of Conversion Disorder include sudden unexplained paralysis, psychogenic non-epileptic seizures (PNES), difficulty swallowing, mutism and even blindness. In cases where patients were diagnosed with Conversion Disorder, no physiological factors could be attributed to the presenting symptoms. The presenting symptoms are real and distress-causing where individuals exercise no control over their symptoms; symptoms are not due to malingering but rather caused by psychological conflicts (Ali, Jabeen, Pate, Shahid, Chinala, Nathani, & Shah, 2015). One common consensus is that Conversion Disorder is the unconscious “conversion” or manifestation of emotional problems into physical complaints (Ali et al., 2015). Biological factors are thought to have played a significant role too, having a pre-existing medical condition or neurological illness such as epilepsy would make PNES a more prominent presenting symptom in individuals with Conversion Disorder (American Psychiatric Association, 2015). Conversion Disorder commonly presents itself during the course of other psychiatric disorders, particularly in depressive and anxiety disorders. Epidemiology and Prevalence A research found that almost a quarter of outpatients in neurological clinics presented symptoms of Conversion Disorder. In the context of general medicine, up to one-fourth of patients showed some symptoms of Conversion Disorder, but only 5% met the full diagnostic criteria to be diagnosed with Conversion Disorder (Feinstein, 2018). Conversion Symptoms affects both men and women but has been found to be more prevalent in females, during their young adulthood. Past research has shown that populations in rural areas and of lower socioeconomic status (SES) are more likely to be affected by Conversion Disorder. However, more research must be conducted to reaffirm these statistics (Feinstein, 2011). Conversion Disorder has been classified in the National Organisation of Rare Diseases (NORD) as a rare condition within the general population. Conversion symptoms are believed to be psychogenic, which is defined as symptoms that result from psychological factors. The APA states that psychogenic symptom(s) “refer[s] to a disorder that cannot be accounted for by any identifiable physical dysfunction and is believed to be due to psychological factors”. History of Conversion and Somatic Symptom Disorders The modern understanding of Conversion Disorder has been greatly influenced by the work of Sigmund Freud and Josef Breuer who coined the term ‘hysteria’. Freud proposed that such symptoms were an unconscious attempt of an individual to resolve internal conflicts. The failure to reconcile such conflicts led to the unconscious expressing them through physical means. These symptoms commonly have underlying messages that the unconscious is attempting to express. It is a symbolic representation of irreconcilable internal conflicts, unacknowledged memories, or repressed emotions. Freud also emphasised that the failure to confront traumatic experiences would cause a considerable amount of mental torment that it would be “converted” into physical symptoms, or what we would now know as psychogenic symptoms. Psychogenic symptoms are physical symptoms that are presented with no known physiological cause and, hence, are attributed to psychological and emotional components. The case that would become a hallmark of Freud’s career was his treatment of ‘Anna O’ in Studies on Hysteria, Anna was first seen by Freud’s mentor and friend, Josef Breuer, for unexplained paralysis of her right arm and leg and abnormal speech. Anna was diagnosed with ‘hysteria’ by Breuer after he found that no physiological causes were present, it is believed that Anna was subsequently referred to and co-treated by Freud. However, whether or not Freud was directly involved in the treatment of Anna is contestable where some proponents suggest that Freud’s notes and hypotheses on Anna’s case were merely based on his study of Breuer’s case notes and not through his direct treatment of Anna. What was mentioned in Studies on Hysteria was that Anna’s paralysis could have been possibly linked to her father’s illness and his eventual death due to Tuberculosis in 1880, where she took on the role as his caregiver when he was bed-bound. Breuer recalled a dream that Anna shared, where she witnessed a black snake approaching a bed-bound patient but was unable to protect the patient as she felt like she was completely paralysed. Anna noted feeling helpless and powerless. Freud then associated this with her unexplained paralysis and linked it to her father’s illness where she acted as his caregiver but was severely restricted in what she could do to aid her father’s recovery. Freud concluded that her state of paralysis was due to her unresolved internal conflict of dealing with great amounts of frustration and helplessness in caring for her dying father. Therefore, this suggested that her symptoms were caused by ‘hysteria’ where her failure to confront and express traumatic experiences manifested into physical symptoms. ‘Hysteria’ in Females today Freud theorised that ‘hysteria’ was an “exclusively female disease” (Tasca, 2012) because he saw women to be mentally weaker and easily affected by psyche and libidinal forces. This theory, however, was eventually abandoned by Freud himself in 1897 where he described his period of unhappiness as “my little hysteria” (Tasca, 2012) and carried on to elaborate that “The chief patient I am preoccupied with is myself” (Tasca, 2012). Despite this, ‘hysteria’ is still widely alluded to females today. In the past, some physicians and psychoanalysts believed that Conversion symptoms are cause by females having “hyposexuality” and “tendency to cause trouble for others” (Maines, 2001). In recent times, because of medical advances; psychologists, counsellors and psychiatrics are tremendously well equipped and sufficiently trained to perform their duty. Now ‘female hysteria’ has been shown to be wrong. Freud was not the first who theorised the causes of ‘hysteria’. Most prominently Hippocrates, an Ancient Greek physician and philosopher wrote in his collected works Hippocratic Corpus, that he thought ‘hysteria’ symptoms were caused by women’s “wandering womb” (Gilman & Al, 1993). Plato held similar believes and personified the phenomenon of the “wandering womb” as a living animal which roamed around the female body and obstructed the functioning of various organs, and hence resulting in the presenting symptoms (King, 2007). Common treatments at that time were often pseudo-scientific, from massaging a woman’s genital area, inducing sneezes to placing aromatic scents on the female genitals and placing foul smells to the lady’s nose. All of which were believed to help ‘shift’ the “wandering womb” back to its rightful position. According to The British Library, one of the earliest recorded medical documentation of ‘hysteria’ was by an English physician Edward Jorden in 1603. He was the first physician who came forward in courts to defend women accused of witchcraft as he attributed ‘hysteria’ symptoms (then associated with witchcraft) to be a medical condition rather than evidence of witchcraft. Influenced by the works of Freud, the American Psychiatric Association (APA) kept the term “hysteria” until the 1980s. Prior to then, Conversion Disorder was diagnosed as “Hysterical Neurosis- Conversion type”, and after the 1980s, the term “hysteria” was no longer used in the DSM. Most of the international psychiatric community agree that Conversion Disorder can emerge as a method of psychological defence, a defence mechanism invoked in the face of a perceived threat that the mind may deem too overwhelming for an individual to confront. With current advances in the medical field of radiology and brain imaging, researchers are studying how the human brain reacts when faced with a perceived threat. On the biological side, it is suggested that Conversion Disorder could be as a result of a “disorder in the circuits that govern the processing of sensory stimuli or voluntary actions” (Harvard Health Publishing, 2014). Research in this area remains in the primary phase and the exact causes of Conversion Disorder are not fully understood. DSM-V noted that other than biological and psychological causes, factors such as personality and environment may also play a role in increasing one’s risk of getting Conversion Disorder. Individuals who often do not confront issues healthily, and individuals who tend to avoid confronting problems due to fear, are exposed to an increased risk of Conversion Disorder. Individuals who grew up in an abusive, unsafe, and neglectful environment were found to be exposed to a higher risk of Conversion Disorder. Although not invariably, the presence of recent strong stressor(s) or significant life event(s) is often a good qualifier of an increased risk of Conversion Disorder. Psychologists today commonly associate Conversion Disorder to the Learning Theory. The Learning Theory proposes how children receive, process, and retain knowledge acquired during the learning process. It takes into account cognitive, environmental, affective, prior knowledge, behavioural factors, and how these make an impact on the process of learning in children. All of which would influence how children would come to understand and view the world, thereby affecting how they deal with situations in their lives (Ormrod, 2012). Therefore, whichever means of coping that is picked up during childhood would by far and large be brought into one’s adulthood. For example, a child who is often told to “suck it up” whenever a conflicting situation arises may use silence as a coping mechanism. Such a coping method may translate into conversion symptoms such as conversion mutism where an individual is unable to speak under all circumstances. (differentiated from Selective Mutism which states that an individual would have the ability to speak under certain circumstances but not being able to do so in other situations). Pharmacological Therapy and Psychiatric Interventions Treatment of patients with Conversion Disorder is dependent on the presenting symptom(s) as treatment can range from physiotherapy to speech therapy. Above all, medications may be prescribed if the patient reports any issues such as anxiety and low moods. Physical examinations will be conducted by a physician, and they may include scans to ensure that any physical causes are ruled out. In some cases, psychological assessments like the MMPI-2-RF will be used. SCID-5 (Structured Clinical Interview for DSM Disorders V) is a method of interview consisting of open and closed-ended questions posed by a trained physician to assess a patient for a psychiatric disorder based on the DSM-V. The SCID-5 encompasses cognitive, behavioural, and affective perspectives in its assessments (Xiong et al., 2017). The APA published the SCID-5-RV which included a “core” and “enhanced” configuration, within the modules; module J included Somatic Symptom Disorders, which Conversion Disorder is a part of. ECT (Electro-Convulsive Therapy) has been suggested as a form of treatment for Somatic Symptom and Related Disorders (Lambert & Bergin, 2015). However, recent studies seemed to favour a more non-invasive form of treatment through the use of rTMS (repetitive Transcranial magnetic stimulation) which has shown some promising results to help reducing conversion symptoms as it addresses the neurophysiologic aspect of Conversion Disorder (Schönfeldt-Lecuona, Connemann, Viviani, Spitzer, & Herwig, 2006) . rTMS has been found to be especially effective for patients with conversion symptoms of weakness and paralysis (Schönfeldt-Lecuona et al., 2016). Counselling and psychotherapy are also another prominent treatment method used for patients with Conversion Disorder as it seeks to address the emotional aspects of the conversion symptoms (Allin, Streeruwitz, & Curtis, 2005). The most prominent model being CBT (Ali et al., 2015 and Sharpe et al., 2018). Habiba-Jasmine (2017) successfully utilised CBT methods and interventions to treat cases of Conversion mutism. The study concluded that CBT was an effective model of therapy as it cured the mutism, with the patients reporting improved moods, reduced anxiety and depressive symptoms as well as the reduction of scores on their Social Interaction Anxiety Scale (SIAS) which was about 43 before treatment, which indicated high levels of social anxiety, down to 10 which marked slight social anxiety. Using CBT to treat Conversion Disorder has produced evidence to show an improvement in patients’ condition after being in 3 to 6 months of CBT sessions (Williams et al., 2017). Psychotherapy is used as it helps individuals to resolve the inner conflict, which is considered to be a significant factor in causing conversion symptoms. However, the model used for patients can be subjective to the patient’s context, other models such as Hypnosis, Family Therapy and even Psychodynamic therapy has also been found to be useful in reducing conversion symptoms (Stonnington, Barry, & Fisher, 2016). Regardless of which psychotherapy model is adopted, the aims will consist of altering how the brain processes information. The goal is to help patients express emotional distress through words and not through physical symptoms. Psychotherapy will strive to “break the established, unconscious pattern that leads to [conversion] symptoms” (O’Neal & Baslet, 2018). Psychotherapists can also reassure patients that their conversion symptoms are not permanent. Typically, conversion symptoms are brief and would fade away spontaneously (Harvard Health Publishing, 2014). As conversion symptoms are psychogenic, psychotherapy addresses the psychological factor in patients with Conversion Disorder. It helps the patient to explore any problems that are causing distress and can even address deep-rooted issues that could be affecting the patient unconsciously. Through psychotherapy, patients are guided to confront their issues and not suppress it. This leads to increased self-awareness and allows the patients to have a more holistic view of the world and of their ‘self’. It equips patients with skills to tackle problems instead of triggering a coping mechanism that is dysfunctional in the long run. As the causes of Conversion Disorder are attributed to emotional stress, anxiety, and trauma (Feinstein, 2011). Addressing the root cause would mean working on any issues that are causing distress (Owens & Dein, 2006). Therefore, such management of conversion symptom(s) will avoid symptomatic treatment where it focuses on eradicating only the physical symptoms but not the emotional distress which is believed to be a significant factor in causing conversion symptom(s). Hence, the most effective method would be combining both psychotherapy and symptomatic treatment. To illustrate, conversion paralysis can be prescribed physiotherapy as well as psychotherapy. This two-pronged approach encompasses both symptomatic treatment and psychological assessment and counselling. Conversion Disorder has come a long way from just being termed “hysteria” and assumed to only affect females because of how it was thought that the womb wanders around the body. Now, we understand that it affects both genders and has a lot to do with how an individual perceives life situations and how they were taught to overcome them. Although we may not be consciously perceiving our every action because it can get exhausting, it will be good to note our thought processes during challenging circumstances. Understanding how we face difficult times can help us to identify healthy and unhealthy thought patterns. - Ali, S., Jabeen, S., Pate, R. J., Shahid, M., Chinala, S., Nathani, M., & Shah, R. (2015). Conversion Disorder- Mind versus Body: A Review. Innovations in clinical neuroscience, 12(5-6), 27–33. - Allin, M., Streeruwitz, A., & Curtis, V. (2005). Progress in understanding conversion disorder. Neuropsychiatric Disease and Treatment, 1(3), 205–209. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2416752/ - American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC - American Psychiatric Association. (2015). Understanding Mental Disorders: Your Guide to DSM-5®. American Psychiatric Pub. - APA Dictionary of Psychology. (n.d.). Dictionary.Apa.Org; American Psychological Association. Retrieved July 18, 2020, from https://dictionary.apa.org/psychogenic - Changes to the Organization and Diagnostic Coverage of the Changes to the Organization and Diagnostic Coverage of the SCID-5-RV Core vs. Enhanced SCID configuration. (n.d.). Retrieved July 24, 2020, from https://www.appi.org/getattachment/49385326-0f15-40cf-b3e3-5759ea981766/APA_Publishing_Diagnostic-Coverage-Changes-SCID-5-RV.pdf?lang=en-US - Feinstein, A. (2011). Conversion disorder: advances in our Maines, R. P. (2001). The technology of orgasm : hysteria, the vibrator, and women’s sexual statisfaction. Johns Hopkins University Press.understanding. CMAJ, 183(8), 915-920. - Feinstein, A. (2011). Conversion disorder: advances in our understanding. CMAJ, 183(8), 915-920. doi: https://doi.org/10.1503/cmaj.110490 - Feinstein, A. (2018). Conversion Disorder. CONTINUUM: Lifelong Learning In Neurology, 24(3), 861-872. doi: 10.1212/con.0000000000000601. - First English book on hysteria, 1603. (n.d.). The British Library. Retrieved July 23, 2020, from https://www.bl.uk/collection-items/first-english-book-on-hysteria-1603 - Freud, S., & Breuer, J. (2004). Studies on hysteria. London: Penguin. - Gervais, R. O., Louw, D., & Gibson, K. (2017). Using the MMPI-2-RF in discriminating between malingering and somatoform disorder. In K. B. Boone (Ed.), American Academy of Clinical Neuropsychology/Routledge continuing education series. Neuropsychological evaluation of somatoform and other functional somatic conditions: Assessment primer (p. 323–353). Routledge/Taylor & Francis Group. https://doi.org/10.4324/9781315266992-12 - Gilman, S. L., & Al, E. (1993). Hysteria beyond Freud. University Of California Press. - Habiba-Jasmine, U. (2017). Cognitive Behaviour Therapy to Treat a Case of Conversion Disorder with Mutism in Bangladesh. Psychology and Behavioral Science International Journal, 7(4). https://doi.org/10.19080/pbsij.2017.07.555716 - Harvard University Press & Harvard Health Publishing. (2014). Harvard Medical School: Conversion Disorder. Retrieved 10 February 2020, from https://www.health.harvard.edu/newsletter_article/Conversion_disorder - King, H. (2007). Hippocrates’ woman reading the female body in ancient Greece. London Routledge. - Leong, K., Fidel Vila-Rodriguez, F., Tham, J., & Scamvougeras, A. (2015). Electroconvulsive therapy treatment in patients with somatic symptom and related disorders. Neuropsychiatric Disease and Treatment, 11, 2565. https://doi.org/10.2147/ndt.s90969 - Mace, C. J., & Trimble, M. R. (1991). ‘Hysteria’, ‘functional’ or ‘psychogenic’? A survey of British neurologists’ preferences. Journal of the Royal Society of Medicine, 84(8), 471–475. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293375/ - Maines, R. P. (2001). The technology of orgasm : hysteria, the vibrator, and women’s sexual statisfaction. Johns Hopkins University Press. - Malcolm, J. (2011). In the Freud archives. Granta Books. - O’Neal, M. A., & Baslet, G. (2018). Treatment for Patients With a Functional Neurological Disorder (Conversion Disorder): An Integrated Approach. American Journal of Psychiatry, 175(4), 307–314. https://doi.org/10.1176/appi.ajp.2017.17040450 - Ormrod, J. (2012). Human learning (6th ed.). Boston: Pearson. - Owens, C., & Dein, S. (2006). Conversion disorder: the modern hysteria. Advances in Psychiatric Treatment, 12(2), 152-157. - Schönfeldt-Lecuona, C., Connemann, B. J., Viviani, R., Spitzer, M., & Herwig, U. (2006). Transcranial Magnetic Stimulation in Motor Conversion Disorder: A Short Case Series. Journal of Clinical Neurophysiology, 23(5), 473–476. https://doi.org/10.1097/01.wnp.0000219004.69158.1e - Schönfeldt-Lecuona, C., Lefaucheur, J.-P., Lepping, P., Liepert, J., Connemann, B. J., Sartorius, A., Gahr, M. (2016). Non-Invasive Brain Stimulation in Conversion (Functional) Weakness and Paralysis: A Systematic Review and Future Perspectives. Frontiers in Neuroscience, 10. https://doi.org/10.3389/fnins.2016.00140 - Sharpe, M., Walker, J., Williams, C., Stone, J., Cavanagh, J., Murray, G., … & Carson, A. (2011). Guided self-help for functional (psychogenic) symptoms: a - Stonnington, C., Barry, J., & Fisher, R. (2016). Conversion Disorder. American Journal of Psychiatry Residents’ Journal, 11(7), 1510–1517. https://doi.org/10.1176/appi.ajp-rj.2016.110701 - Tasca, C. (2012). Women And Hysteria In The History Of Mental Health. Clinical Practice & Epidemiology in Mental Health, 8(1), 110–119. https://doi.org/10.2174/1745017901208010110 - Williams, C., Carson, A., Smith, S., Sharpe, M., Cavanagh, J., & Kent, C. (2017). Overcoming functional neurological symptoms: a five areas approach. CRC Press. - World Health Organization. (2003). The ICD-10 Classification of Mental and Behavioural Disorders. Geneva. - World Health Organization. (2016). The ICD-10 classification of mental and behavioural disorders: Clinical descriptions and diagnostic guidelines. Geneva: World Health Organization. - Xiong, N., Zhang, Y., Wei, J., Leonhart, R., Fritzsche, K., Mewes, R., Hong, X., Cao, J., Li, T., Jiang, J., Zhao, X., Zhang, L., & Schaefert, R. (2017). Operationalization of diagnostic criteria of DSM-5 somatic symptom disorders. BMC Psychiatry, 17(1), 361. https://doi.org/10.1186/s12888-017-1526-5 Contributor: Julian Anschel Lai Jang Ein Julian is currently pursuing the Bachelor of Arts (Honours) Guidance and Counselling with Northumbria University. He is also a student member of APACS, actively contributing psychological articles.	2	6	3	0	0	0.978322	3	5,313
Clinical applications for optical coherence tomography (OCT) have expanded exponentially since its commercial introduction approximately 15 years ago. OCT measurements are increasingly used as clinical endpoints and for monitoring various ocular disorders. Numerous clinical studies, including large, multi-centered, prospective clinical trials, are employing OCT findings as study endpoints.1-2 \|SD-OCT macular change analysis demonstrating the development of DME over a period of less than four months. Click image to enlarge.\| Clinicians are now using OCT in clinical practice for both anterior and posterior segment pathologies, as it provides valuable data that can aid in the detection of ocular pathologies, as well as track progression of the condition and the response to treatment. For example, OCT can help detect optic neuropathies with retinal nerve fiber layer (RNFL) loss, such as in glaucomatous damage. The instrument can also be used to identify disc edema and even buried disc drusen. Analysis of retinal thickness over the macula and posterior pole can help detect retinal edema or atrophy. The retinal pigment epithelium (RPE) and choroid can also be better visualized with new imaging modalities such as enhanced-depth imaging (EDI). Anterior segment OCT can provide further insight into anterior chamber depth, angle anatomy and corneal pathologies. OCT is an important diagnostic tool, yet is currently not considered the standard of care for evaluating the retina and is not required to diagnose glaucoma. There is also no publication in peer-reviewed literature that has definitively proven that OCT can serve as a surrogate for functional vision tests such as visual acuity and visual fields. However, large, multi-centered clinical studies have used OCT in the assessment of macular thickness, and there is extensive literature demonstrating that RNFL and ganglion cell analyses are valuable in the diagnosis and management of glaucoma. Without any specific guidelines, clinicians vary on the use of OCT within their practice. The underuse of the instrument can lead to misdiagnosis of visually threatening conditions, while overuse can result in a financial burden to the health care system. This article discusses the role of OCT in clinical practice and looks at the literature for evidence to support its value and limitations. Common ocular pathologies such as age-related macular degeneration (AMD), diabetic macular edema (DME) and glaucoma will be discussed as examples of OCT’s use in clinical practice. OCT in AMD Management Age-related Macular DegenerationAn estimated 80% of AMD patients have non-neovascular, or “dry,” AMD. The remaining 20% have neovascular, or “wet,” AMD, which accounts for nearly 90% of the severe central visual acuity loss associated with AMD.3-5 Early detection of neovascular AMD is crucial to prevent permanent vision loss secondary to subretinal fibrosis.6 Previous clinical studies emphasize the importance of fluorescein angiography (FA) patterns in neovascular AMD to guide appropriate treatment.7,8 Specifically, the ideal treatment choice was dictated by differentiating between choroidal neovascular (CNV) membranes that exhibited classic vs. occult appearance as the type of membrane.7,8 However, now that anti-vascular endothelial growth factor (VEGF) agents are preferred for treating patients with all types of neovascular AMD, the CNV lesion type is no longer important.9-10 The detection of subtle subretinal fluid in early stages of choroidal neovascularization from neovascular AMD can be difficult to identify on biomicroscopy; however, OCT has proven to be valuable in diagnosing and managing neovascular AMD, as choroidal neovascularization is visible on OCT.1,11-13 The instrument can identify areas of retinal thickening and track thickness changes. Automated change analysis allows clinicians to compare scans to detect subtle retinal thickening that may have been missed on clinical examination. In one study, fluid detected on OCT, along with the presence of leakage on FA, was used to define active CNV.1 Foveal thickness determined by the OCT was also a secondary outcome and was used to guide when retreatment was indicated.1 The widespread use of OCT has minimized the role FA plays in AMD diagnosis and treatment, as many retinal specialists are now using OCT, especially SD-OCT, instead of FA as a guide when considering further anti-VEGF treatment. The updated 2015 AMD Preferred Practice Pattern guidelines (PPP) from the American Academy of Ophthalmology (AAO) notes that OCT is important in the diagnosis and management of AMD.5 OCT is especially helpful in detecting early CNV in patients with new complaints of metamorphopsia or unexplained blurred vision.5 However, systematic review of studies from 1995 to March 2013 revealed that, although time-domain (TD) OCT is a relatively sensitive test for the initial diagnosis of neovascular AMD, it is of moderate specificity.14,15 The review suggested that TD-OCT should not replace FA in the diagnosis of neovascular AMD and that further research is required to evaluate the diagnostic performance of SD-OCT, since there were limited studies in the literature comparing the instrument with FA.14,15 \|SD-OCT macular change analysis \| demonstrating the development of DME over a period of less than four months. Click image to enlarge. In non-neovascular AMD, OCT has helped identify many features related to the degenerative process and expand our understanding of the condition. Reticular drusen, subretinal drusen deposits, pseudocysts, outer retinal tubulation and drusen-associated acquired vitelliform lesions are only a few of the non-neovascular AMD findings OCT can detect.16-18 Additionally, change analysis software available on various SD-OCT instruments can be helpful in identifying drusen enlargement or reabsorption. SD-OCT findings identified in association with non-neovascular AMD have also predicted drusen-associated chorioretinal atrophy. This can be important in patient management when predicting the risk and rate of vision loss.19 Diabetic Macular EdemaThe Early Treatment Diabetic Retinopathy Study (ETDRS) emphasized the importance of treating clinically significant macular edema (CSME) to prevent vision loss. This landmark study used stereo contact lens biomicroscopy and stereo photography to define CSME, and FA was used to guide the photocoagulation treatment.20 Now, OCT is routinely used to evaluate DME in clinical practice. Large clinical trials evaluating the efficacy of anti-VEGF treatment, such as the RIDE and RISE studies, have incorporated OCT findings, along with a corresponding decrease in vision, in their definition of DME.21 In these studies, researchers used OCT, rather than stereoscopic photographs or clinical examination, because it allowed for an objective assessment and quantified the amount and location of retinal thickening.21-24 OCT in DME Management In clinical practice, the decision to treat DME is usually based on OCT findings. Added to that, the instrument allows for tracking the response to treatment. The American Academy of Ophthalmology’s Preferred Practice Pattern for diabetic retinopathy recognizes the role of OCT in assessing DME, stating that OCT can be used to evaluate unexplained visual acuity loss, identify areas of vitreomacular traction and evaluate patients with difficult or questionable examinations for DME. The PPP does not recommend using OCT to screen a patient with no or minimal diabetic retinopathy.25 A baseline OCT could be obtained as a reference, but routine macular OCT scans are not recommended if there is no suspicion of DME on clinical examination.25,26 For patients with subclinical DME detected with OCT, close monitoring is recommended because of the increased risk for developing visually significant CSME. A four to six month follow up interval has been suggested based on the generally slow change in OCT values and delayed time to treatment.26-31 Optic nerve head (ONH) evaluation in the management of glaucoma has been traditionally assessed by ophthalmoscopy and color stereo disc photography. Color stereo disc photographs of the optic nerve are still considered the standard for documenting the ONH status for glaucomatous optic neuropathy.32-35 Red-free photographs can be used to enhance the RNFL defects; however, these are limited by the subjectivity of the quantitative analysis and the dependence on the clinician.35,36 Studies have demonstrated measurement of ONH parameters by OCT can aid in the diagnosis of glaucoma.37 OCT imaging can also aid in distinguishing glaucomatous damage from eyes without glaucoma to help facilitate earlier diagnosis and detection of optic nerve damage.38 \|SD-OCT high-definition 5-line raster scan inferior to the fovea over the CNV. Click image to enlarge.\| In addition to assessing the ONH, OCT imaging also allows for evaluation of the peripapillary RNFL (pRNFL). The instrument provides an objective measurement of the structural changes in RNFL thickness and ONH parameters occurring in glaucoma.38 ONH parameters provided by OCT can include optic disc area, optic disc rim area, average cup-to-disc ratio, vertical cup-to-disc ratio, and cup volume. Patients with early glaucomatous damage can demonstrate preperimetric glaucoma, leading to structural alterations in the ONH, pRNFL and macular areas before functional changes occur.37,38 \|SD-OCT ONH and RNFL analysis in a patient with early POAG. Right eye has movement with motion artifact superiorly. Both eyes have RNFL loss that is borderline or outside normal limits compared with the normative database. Click image to enlarge.\| Peripapillary RNFL thickness as measured by OCT has been extensively studied to distinguish glaucomatous damage and the severity of the disease. The instrument provides average RNFL thickness, which can further be divided into RNFL thickness measures in quadrants and sectors. This separation allows the analysis of RNFL loss into specific patterns that can help distinguish non-glaucomatous optic neuropathies.39,40 Recently, new software has allowed analysis of the macular region for detection of glaucomatous damage. Segmentation software specifically evaluating the ganglion cell layer, inner plexiform layer, RNFL over the macula or a combination of all three has emphasized that early glaucomatous damage can involve central vision. Studies on these specific layers in the macular region have identified that these parameters are as sensitive as pRNFL analysis in the detection of glaucoma.41-43 However, the analysis is limited to those patients without macular pathology, and only updated SD-OCT software versions have this capability. The AAO PPP for primary open-angle glaucoma (POAG) suggests that computer-based image analysis of the ONH and RNFL, such as OCT, are complementary tests.34 One of the major limitations of OCT is the narrow range of the normative databases for each OCT manufacturer. Each manufacturer has a proprietary normative database that can range from 201 to 480 subjects. The ethnicities of the subjects included in the databases are generally not diverse. The normative data is also limited regarding the included age range and magnitude of refractive error.44-46 When analyzing the printout, clinicians must be cautious if the patient falls outside the normative database, as they may misinterpret the findings based on the colors of green or red that suggest normal or abnormal.46 In addition, scans between different OCT instruments cannot be used for comparison. For example, the pRNFL is measured by a collection of data points in a circle placed around the optic disc, and the diameter of the circle varies with each instrument. \|Peripapillary retinal nerve fiber layer thickness of various SD-OCT instruments.\| Because glaucoma is a progressive optic neuropathy, reproducible data is important in longitudinal evaluation to track RNFL loss. To track progression, the OCT must have excellent repeatability. Detectable RNFL loss requires a change greater than that expected from usual testing variations.47,48 Most instruments have tracking software to recall the baseline scan location. Without active eye tracking technology, pRNFL thickness can vary significantly; thus, the OCT’s ability to track eye movement improves its reliability. However, clinicians are still faced with the challenge of interpreting true progressive RNFL loss from glaucoma, other optic neuropathies, or changes secondary to artifacts. OCT in Glaucoma Management Artifacts such as vitreous opacities obscuring the scan circle, media opacities reducing the signal strength, vitreopapillary traction and peripapillary atrophy (PPA) can alter the pRNFL thickness and possibly mimic glaucomatous thinning.46,49,50 Progression software is a good adjunct for eyes with diffuse RNFL defects or an unidentifiable RNFL status in which photographic assessment is not reliable.51 However, in patients with advanced glaucomatous optic neuropathy, OCT has limited benefit for identifying progressive optic nerve changes.34 A New ViewOCT has proven to be a valuable diagnostic tool, and there is strong evidence for its applications for both retinal pathologies and optic neuropathies. For AMD, OCT can aid in the decision on whether further treatment is necessary. TD-OCT can aid in the initial diagnosis of neovascular AMD, although it should not replace the reference standard of FA yet. Further studies are needed to determine the role of SD-OCT. In DME, OCT can confirm macular edema, and decisions to treat are often based on its findings. However, OCT should not be used to screen diabetic patients with no or minimal retinopathy. Although considered complementary by the AAO PPP, OCT measurements of the pRNFL, ONH parameters and ganglion cell analysis have been shown to assist in the detection and progression of glaucoma. As newer technology such as swept-source OCT becomes available, it will play an increasing role in the management of glaucoma and other ocular conditions within clinical practice. Reimbursement for OCTFor billing purposes, OCT is considered a scanning computerized ophthalmic diagnostic imaging (SCODI) test. Anterior segment SCODI is recognized for the evaluation and treatment of diseases affecting the cornea, iris and other anterior chamber structures. The imaging can also provide additional information during planning and follow-up of anterior segment and cataract surgeries. Posterior segment SCODI can assist in the diagnosis and management of retinal and neuro-ophthalmic diseases. It is also used to follow glaucoma suspects, diagnose glaucoma, monitor glaucoma treatment and detect glaucoma progression. Limitations of coverage include the absence of an indication or for screening only. The Medicare administrative contractor (MAC) found in each contractor’s local coverage determination has a comprehensive list of ICD-10 diagnosis codes that are used in conjunction with the CPT codes. The list of ICD-10 diagnoses is grouped into 92132 (anterior segment), 92133 (posterior segment-optic nerve), and 92134 (posterior segment-retina). The patient’s medical record must contain documentation that fully supports the medical necessity for the services. Insurance providers may have an annual frequency limitation for SCODI billing. In general, diagnostic tests are reimbursed when medically indicated, and clear documentation is necessary for justification. Policies commonly state that diagnosis codes can only be billed one or two times per year for 92133 (posterior segment-optic nerve) for glaucoma, but more often for retinal diseases (92134) such as AMD and DME. Dr. Vien practices at the Veterans Affairs Palo Alto Healthcare System and is an assistant clinical professor at University of California Berkeley School of Optometry and Southern California College of Optometry at Marshall B. Ketchum University. Dr. Yang practices at the Veterans Affairs Palo Alto Healthcare System and is an associate clinical professor at the University of California Berkeley School of Optometry. 1. Martin DF, Maguire MG, Fine SL, et al. Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology. 2012;119:1388-98. 2. Brown DM, Quan DN, Marcus DM, et al. RISE and RIDE Research Group. Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials. Ophthalmology. 2013;120(10):2013-22. 3. Kahn HA, Leibowitz HM, Ganley JP, et al. The Framingham Eye Study. Outline and major prevalence findings. Am J Epidemiol. 1977;106:17-32. 4. Ferris FL III, Fine SL, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol. 1984;102:1640-2. 5. American Academy of Ophthalmology Retina/Vitreous Panel. Preferred Practice Pattern Guidelines. Age-related macular degeneration. San Francisco, CA: American Academy of Ophthalmology; 2015. www.aao.org/ppp. 6. Ramussen A, Brandi S, Fuchs J, et al. Visual outcomes in relation to time to treatment in neovascular age-related macular degeneration. Acta Ophthalmol. 2015;93:616-20. 7. Treatment of Age-Related Macular Degeneration With Photodynamic Therapy Study. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials–TAP Report 1. Arch Ophthalmol. 1999;117:1329-45. 8. Azab M, Boyer DS, Bressler NM, et al. Visudyne in Minimally Classic Choroidal Neovascularization Study Group. Verteporfin therapy of subfoveal minimally classic choroidal neovascularization in age-related macular degeneration: 2-year results of a randomized clinical trial. Arch Ophthalmol. 2005;123:448-57. 9. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 206;335:1419-31. 10. Brown DM, Kaiser PK, Michels M, et al. ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1432-44. 11. Khurana RN, Dupas B, Bressler NM. Agreement of time-domain and spectral-domain optic coherence tomography with fluorescein leakage from choroidal neovascularization. Ophthalmology. 2010;117;1376-80. 12. Do DV, Gower EW, Cassard SD, et al. Detection of new-onset choroidal neovascularization using optical coherence tomography: the AMD DOC study. Ophthalmology. 2012;119:771-8. 13. Wilde C, Patel M, Lakshmanan A, et al. The diagnostic accuracy of spectral-domain optical coherence tomography for neovascular age-related macular degeneration: a comparison with fundus fluorescein angiography. Eye. 2015;29;602-9. 14. Castillo MM, Mowatt G, Lois N, et al. Optical coherence tomography for the diagnosis of neovascular age-related macular degeneration: a systemic review. Eye. 2014;28:1399-1406. 15. Castillo MM, Mowat G, Elders A, et al. Optical coherence tomography for the monitoring of neovascular age-related macular degeneration. Ophthalmology. 2015;122:399-406. 16. Hogg RE, Silva R, Staurenghi G, et al. Clinical characteristics of reticular pseudodrusen in the fellow eye of patients with unilateral neovascular age-related macular degeneration. Ophthalmology. 2014;121:1748-55. 17. Hariri A, Nittala MG, Sadd SR. Outer retinal tubulation as a predictor of the enlargement amount of geographic atrophy in age-related macular degeneration. Ophthalmology. 2015;122:407-13. 18. Lima LH, Laud K, Freund KB, et al. Acquired vitelliform lesion associated with large drusen. Retina. 2012;32:647-51. 19. Wu Z, Luu CD, Ayton LN, et al. Optical coherence tomography-defined changes preceding the development of drusen-associated atrophy in age-related macular degeneration. Ophthalmology. 2014;121:2415-22. 20. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema: Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol. 1985;103:1796–806. 21. Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for diabetic macular edema: results from 2 phase II randomized trials: RISE and RIDE. Ophthalmology. 2012;119:789-801. 22. Brown DM, Nguyen QD, Marcus DM, et al. Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. Ophthalmology. 2013;120:2013-22. 23. Elman MJ, Qin H, Aiello LP, et al. Diabetic Retinopathy Clinical Research Network. Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: three-year randomized trial results. Ophthalmology. 2012;119:2312-8. 24. Do DV, Nguyen QD, Khwaja AA, et al. READ-2 Study Group. Ranibizumab for edema of the macula in diabetes study: 3-year outcomes and the need for prolonged frequent treatment. JAMA Ophthalmol. 2013;131:139-45. 25. American Academy of Ophthalmology Retina/Vitreous Panel. Preferred Practice Pattern Guidelines. Diabetic retinopathy. San Francisco, CA: American Academy of Ophthalmology; 2014. www.aao.org/ppp. 26. Pires I, Santos AR, Nunes S, et al. Subclinical macular edema as a predictor of progression to clinically significant macular edema in type 2 diabetes. Ophthalmologica. 2013;230:201-6. 27. Davis MD, Bressler SB, Aiello LP, et al. Comparison of time-domain OCT and fundus photographic assessments of retinal thickening in eyes with diabetic macular edema. Invest Ophthalmol Vis Sci. 2008;49:1745-52. 28. Virgili G, Menchini F, Casazza G, et al. Optical coherence tomography (OCT) for detection of macular oedema in patients with diabetic retinopathy. Cochrane Database Syst Rev. 2015 Jan;1:CD008081. 29. Browning DJ, Fraser CM. The predictive value of patient and eye characteristics on the course of subclinical diabetic macular edema. Am J Ophthalmol. 2008;145:149-54. 30. Bressler NM, Miller KM, Beck RW, et al. Observational study of subclinical diabetic macular edema. Eye. 2012;26:833-40. 31. Browning DJ. Diabetic retinopathy: evidenced-based management. New York, NY: Springer; 2010. 32. Kass MA, Heuer DK, Higginbotham EJ, et al. The ocular hypertension treatment study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open angle glaucoma. Arch Ophthalmol. 2002;120:701-3. 33. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the early manifest glaucoma trial. Arch Ophthalmol. 2002;120:1268-79. 34. American Academy of Ophthalmology Glaucoma Panel. Preferred Practice Pattern Guidelines. Primary open-angle glaucoma. San Francisco, CA: American Academy of Ophthalmology; 2014. www.aao.org/ppp. 35. Jonas JB, Budde WM, Panda-Jonas S. Ophthalmoscopic evaluation of the optic nerve head. Surv Ophthalmol. 1999;43:293-320. 36. Mills RP. Glaucoma imaging: technology in progress. J Glaucoma. 1999;8:87–9. 37. Mwanza JC, Oakley JD, Budenz DL, et al. Ability of cirrus HD-OCT optic nerve head parameters to discriminate normal from glaucomatous eyes. Ophthalmology. 2011;118:241-8. 38. Michelessi M, Lucenteforte E, Oddone F, et al. Optic nerve head and fibre layer imaging for diagnosing glaucoma. Cochrane Database Syst Rev. 2015;11:CD008803. 39. Gupta PK, Asrani S, Freedman SF, et al. Differentiating glaucomatous from non-glaucomatous optic nerve cupping by optical coherence tomography. Open Neurol J. 2011;5:1-7. 40. Pasol J. Neuro-ophthalmic disease and optical coherence tomography: glaucoma look-alikes. Curr Opin Ophthalmol. 2011;22:124-32. 41. Hood DC, Raza AS, de Moraes CG, et al. Glaucomatous damage of the macula. Prog Retin Eye Res. 2013;32:1-21. 42. Hood DC, Slobodnick A, Raza AS, et al. Early glaucoma involves both deep local, and shallow widespread, retinal nerve fiber damage of the macular region. Invest Ophthalmol Vis Sci. 2014;55:632-49. 43. Padhy D, Rao A. Macular ganglion cell/inner plexiform layer measurements by spectral domain optical coherence tomography for detection of early glaucoma and comparison to retinal nerve fiber layer measurements. Am J Ophthalmol. 2014;158:211. 44. Spaeth GL, Reddy SC. Imaging of the optic disc in caring for patients with glaucoma: ophthalmoscopy and photography remains the gold standard. Surv Ophthalmol. 2014;59:454-8. 45. Akashi A, Kanamori A, Ueda K, et al. The ability of SD-OCT to differentiate early glaucoma with high myopia from high myopic controls and nonhighly myopic controls. Invest Ophthalmol Vis Sci. 2015;56:6573-80. 46. Chong GT, Lee RK. Glaucoma versus red disease: imaging and glaucoma diagnosis. Curr Opin Ophthalmol. 2012;23:79-88. 47. Leung CK, Cheung CY, Weinreb RN, et al. Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: a variability and diagnostic performance study. Ophthalmology. 2009;116:1257–63. 48. Wu W, Boer JF, Chen TC. Reproducibility of retinal nerve fiber layer thickness measurements using spectral domain optical coherence tomography. J Glaucoma. 2011;20:470-6. 49. Liu Y, Simavil H, Que CJ, et al. Patient characteristics associated with artifacts in Spectralis optical coherence tomography imaging of the retinal nerve fiber layer in glaucoma. Am J Ophthalmol. 2015;159:565-76. 50. Asrani S, Essaid L, Alder BD, et al. Artifacts in spectral-domain optical coherence tomography measurements in glaucoma. JAMA Ophthalmol. 2014;132:396-402. 51. Lee JR, Sung KR, Na JH, et al. Discrepancy between optic disc and nerve fiber layer assessment and optical coherence tomography in detecting glaucomatous progression. Jpn J Ophthalmol. 2013;57(6):546–52. 52. Centers for Medicare and Medicaid Services. Local Coverage Determination: Scanning Computerized Ophthalmic Diagnostic Imaging. Accessed January 3, 2016. www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=34380.	2	9	4	0	0	0.367959	4	6,279
What is an arrhythmia? An arrhythmia is an abnormal heart rhythm. Some arrhythmias can cause problems with contractions of the heart chambers by: Not allowing the ventricles (lower chambers) to fill with an adequate amount of blood because an abnormal electrical signal is causing the heart to pump too fast or too slow. Not allowing a sufficient amount of blood to be pumped out to the body because an abnormal electrical signal is causing the heart to pump too slowly or too irregularly. Not allowing the top chambers to work properly. In any of these situations, the body's vital organs may not receive enough blood to meet their needs. What are the symptoms of arrhythmias? The effects on the body are often the same, however, whether the heartbeat is too fast, too slow, or too irregular. Some symptoms of arrhythmias include, but are not limited to: Palpitations (a sensation of fluttering or irregularity of the heartbeat) Low blood pressure Collapse and cardiac arrest Difficulty feeding (in babies) The symptoms of arrhythmias may resemble other conditions. Consult your doctor for a diagnosis. To better understand arrhythmias, is it helpful to understand the heart's electrical conduction system. The heart's electrical system The heart is, in the simplest terms, a pump made up of muscle tissue. The heart's pumping action is regulated by an electrical conduction system that coordinates the contraction of the various chambers of the heart. How does the heart beat? An electrical stimulus is generated by the sinus node (also called the sinoatrial node, or SA node), consisting of a small mass of specialized tissue located in the right atrium (right upper chamber) of the heart. The sinus node generates a regular electrical stimulus, which for adults, is usually 60 to 100 times per minute under normal conditions. This electrical stimulus travels down through the conduction pathways (similar to the way electricity flows through power lines from the power plant to your house) and causes the heart's lower chambers to contract and pump out blood. The right and left atria (the two upper chambers of the heart) are stimulated first and contract a short period of time before the right and left ventricles (the two lower chambers of the heart). The electrical impulse travels from the sinus node to the atrioventricular node (also called AV node), where impulses are slowed down for a very short period, then allowed to continue down the conduction pathway via an electrical channel called the bundle of His into the ventricles. The bundle of His divides into right and left pathways to provide electrical stimulation to the right and left ventricles. Each contraction of the ventricles represents one heartbeat. Each day the heart beats about 100,000 times, on average. Any abnormality in the heart's electrical conduction system can make the heartbeat too fast, too slow, or at an uneven rate, thus, causing an arrhythmia. What is an electrocardiogram (ECG)? The electrical activity of the heart is measured by an electrocardiogram (ECG or EKG). By placing electrodes at specific locations on the body (chest, arms, and legs), a graphic representation, or tracing, of the electrical activity can be obtained. Changes in an ECG from the normal tracing can indicate arrhythmias, as well as other heart-related conditions. What does an ECG mean? Almost everyone knows what a basic ECG tracing looks like. But what does it mean? The first little upward notch of the ECG tracing is called the "P wave." The P wave indicates that the atria (the two upper chambers of the heart) are electrically stimulated. This causes them to contract and pump blood to the ventricles. The delay in the conduction of the electrical signal from the atria to the ventricles from the beginning of the P wave to the R (or Q) wave is known as the PR interval. The next part of the tracing is a short downward section connected to a tall upward section. This part is called the "QRS complex." This part indicates that the ventricles (the two lower chambers of the heart) are electrically stimulated (undergo depolarization) to pump out blood to the body via the aorta or to the lungs via the pulmonary artery. The next short flat segment is called the "ST segment." The ST segment is a time when the ventricles are activated and the electrical signal for ventricular contraction is completed. The next upward curve is called the "T wave." The T wave is the electrical recovery period of the ventricles (ventricular repolarization). After the ventricles repolarize, they can then depolarize again. When your doctor studies your ECG, he or she looks at the size, length, and appearance of each part of the ECG. Variations in size and length of the different parts of the tracing may be significant. The tracing for each lead of a 12-lead ECG will look different, but will have the same basic components as described above. Each lead of the 12-lead is "looking" at a specific part of the heart, so variations in a lead may indicate a problem with the part of the heart associated with the lead. What are the different types of arrhythmias? An arrhythmia can occur in the sinus node, the atria, or the atrioventricular node. These are supraventricular arrhythmias. A ventricular arrhythmia is caused by an abnormal electrical focus within the ventricles, resulting in abnormal conduction of electrical signals within the ventricles. Arrhythmias can also be classified as slow (bradyarrhythmia) or fast (tachyarrhythmia). "Brady-" means slow, while "tachy-" means fast. Listed below are some of the more common arrhythmias: Sinus arrhythmia. A common condition in which the heart rate varies with breathing. Sinus arrhythmia is commonly found in children; adults may often have it as well. This is a benign (not dangerous) condition. Premature ventricular contractions (PVCs). A condition in which an electrical signal originates in the ventricles and causes the ventricles to contract before receiving the electrical signal from the atria. PVCs are common and typically do not cause symptoms or problems. However, if the frequency of the PVCs increases significantly, symptoms such as weakness, fatigue, dizziness, fainting, or palpitations may be experienced. Heart failure may develop. Sinus tachycardia. A condition in which the heart rate is faster than normal because the sinus node is sending out electrical impulses at a rate faster than usual. Most commonly, sinus tachycardia occurs as a normal response of the heart to exercise when the heart rate increases to cope with increased energy requirements. Sinus tachycardia can be completely appropriate and normal, such as when a person is exercising vigorously. Sinus tachycardia is often temporary, also occurring when the body is under stress from strong emotions, infection, fever, hyperthyroidism, or dehydration, to name a few causes. It may cause symptoms, such as weakness, fatigue, dizziness, or palpitations, if the heart rate becomes too fast to pump an adequate supply of blood to the body. Once the stress is removed, the heart rate will return to its usual rate. Ventricular tachycardia (VT). A potentially life-threatening condition in which an electrical signal is sent from the ventricles at a very fast, but often regular rate. If the heart rate is sustained at a high rate for more than 30 seconds, symptoms, such as weakness, fatigue, dizziness, fainting, or palpitations, may be experienced. Cardiac arrest may occur. A person in VT may require an electric shock or medications to convert the rhythm back to normal sinus rhythm. Sick sinus syndrome. A condition in which the sinus node sends out electrical signals too slowly. There may be alternation between too-fast and too-slow rates (tachy brady syndrome). This condition may cause symptoms if the rate becomes too slow for the body to tolerate. Ventricular fibrillation (VF). A condition in which many electrical signals are sent from the ventricles at a very fast and erratic rate. As a result, the ventricles are unable to fill with blood and pump. This rhythm is life-threatening because there is no pulse and complete loss of consciousness. A person in VF requires prompt defibrillation to restore the normal rhythm and function of the heart. It will result in sudden cardiac death if not treated within seconds. Premature supraventricular contractions or premature atrial contractions (PAC). A condition in which an atrial pacemaker site above the ventricles sends out an electrical signal early. The ventricles are usually able to respond to this signal, but the result is an irregular heart rhythm, which is typically benign. PACs are common and may occur as the result of stimulants such as coffee, tea, alcohol, cigarettes, or medications. Supraventricular tachycardia (SVT). A condition in which the heart rate speeds up due to abnormal tissue above the ventricles. There are several different forms of SVT arrhythmias. A couple of the more common examples include arrhythmias caused by an abnormal electrical connection between the top and bottom chambers of the heart, such as atrioventricular node reentry tachycardia also referred to as paroxysmal SVT, or atrioventricular reentry tachycardia due to an extra conduction pathway between the atria and the ventricles. If that pathway conducts signals from the atria to the ventricles, it is known as Wolff-Parkinson-White Syndrome. Another common SVT form can be caused by a site in the atria that fires rapidly called atrial tachycardia. SVT usually begins and ends rapidly, occurring in repeated periods. These arrhythmias can cause symptoms, such as weakness, fatigue, dizziness, fainting, or palpitations if the heart rate becomes too fast. They can cause shortness of breath or chest discomfort. Atrial flutter. A condition in which the electrical signals come from the atria at a fast but regular rate, often causing the ventricles to contract faster and increase the heart rate. When the signals from the atria are coming at a faster rate than the ventricles can respond to, the ECG pattern typically (but not always) develops a signature "sawtooth" pattern, showing two or more flutter waves between each QRS complex. The number of waves between each QRS complex is expressed as a ratio, for example, a two-to-one atrial flutter means that two waves are occurring between each QRS. Atrial fibrillation. A condition in which the electrical signals come from the atria at a very fast and erratic rate. The ventricles contract in an irregular manner because of the erratic signals coming from the atria A condition in which the electrical signals come from the atria at a very fast and erratic rate. The ventricles contract in an irregular manner because of the erratic signals coming from the atria that activate the AV node. The symptoms of various arrhythmias may resemble other medical conditions. Consult your doctor for a diagnosis. How are arrhythmias diagnosed? There are several different types of procedures that may be used to diagnose arrhythmias. Some of these procedures include the following: Electrocardiogram (ECG or EKG). An electrocardiogram is a measurement of the electrical activity of the heart. By placing electrodes at specific locations on the body (chest, arms, and legs), a graphic representation, or tracing, of the electrical activity can be obtained as the electrical activity is received and interpreted by an ECG machine. An ECG can indicate the presence of arrhythmias, damage to the heart caused by ischemia (lack of oxygen to the heart muscle) or myocardial infarction (MI, or heart attack), a problem with one or more of the heart valves, or other types of heart conditions. There are several variations of the ECG test: Resting ECG. For this procedure, the clothing on the upper body is removed and small sticky patches called electrodes are attached to the chest, arms, and legs. These electrodes are connected to the ECG machine by wires. The ECG machine is then started and records the heart's electrical activity for a minute or so. The patient is lying down during this ECG. Exercise ECG, or stress test. The patient is attached to the ECG machine as described above. However, rather than lying down, the patient exercises by walking on a treadmill or pedaling a stationary bicycle while the ECG is recorded. This test is done to assess changes in the ECG during stress, such as exercise. Signal-averaged ECG. This procedure is done in the same manner as a resting ECG, except that the heart's electrical activity is recorded over a longer period of time, usually 15 to 20 minutes. Signal-averaged ECGs are done when arrhythmia is suspected but not seen on a resting ECG. The signal-averaged ECG has increased sensitivity to abnormal ventricular activity called "late potentials." Signal-averaged ECG is used in research and seldom used in clinical practice. Electrophysiologic studies (EPS). A test in which a small, thin tube (catheter) is inserted in a large blood vessel in the leg or arm and advanced to the heart. This gives the doctor the capability of finding the site of the arrhythmia's origin within the heart tissue, thus determining how to best treat it. Sometimes an attempt to treat the arrhythmia may be made by doing an ablation at the time of the study. Holter monitor. A continuous ECG recording done over a period of 24 or more hours. Electrodes are attached to the patient's chest and connected to a small portable ECG recorder by lead wires. The patient goes about his or her usual daily activities (except for activities such as taking a shower, swimming, or any activity causing an excessive amount of sweating that would cause the electrodes to become loose or fall off) during this procedure. Holter monitoring may be done when an arrhythmia is suspected but not seen on a resting ECG, since arrhythmias may be transient in nature and not seen during the shorter recording times of the resting ECG. Event monitor. This is similar to a Holter monitor, but the ECG is recorded only when the patient starts the recording when symptoms are felt. Event monitors are typically worn longer than Holter monitors. The monitor can be removed to allow for showering or bathing. Mobile cardiac monitoring. This is similar to both a Holter and event monitor. The ECG is monitored constantly to allow for detection of arrhythmias, which are recorded and sent to your doctor regardless of whether symptoms are experienced. Recordings can also be initiated by the patient when symptoms are felt. These monitors can be worn up to 30 days. How are arrhythmias treated? Some arrhythmias may be present but cause few, if any, problems. In this case, the doctor may elect not to treat the arrhythmia. However, when the arrhythmia causes symptoms, there are several different options for treatment. The doctor will choose an arrhythmia treatment based on the type of arrhythmia, the severity of symptoms being experienced, and the presence of other conditions (such as, diabetes, kidney failure, or heart failure) which can affect the course of the treatment. Some treatments for arrhythmias include: © 2000-2014 The StayWell Company, LLC. 780 Township Line Road, Yardley, PA 19067. All rights reserved. This information is not intended as a substitute for professional medical care. Always follow your healthcare professional's instructions. Lifestyle modification. Factors, such as stress, caffeine, or alcohol, can cause arrhythmias. The doctor may order the elimination of caffeine, alcohol, or any other substances believed to be causing the problem. If stress is suspected as a cause, the doctor may recommend stress-reduction measures, such as meditation, stress-management classes, an exercise program, or psychotherapy. Medication. There are various types of medications that may be used to treat arrhythmias. If the doctor chooses to use medication, the decision of which medication to use will be determined by the type of arrhythmia, other conditions which may be present, and other medications already being taken by the patient. Cardioversion. In this procedure, an electrical shock is delivered to the heart through the chest to stop certain very fast arrhythmias such as atrial fibrillation, supraventricular tachycardia, or atrial flutter. The patient is connected to an ECG monitor which is also connected to the defibrillator. The electrical shock is delivered at a precise point during the ECG cycle to convert the rhythm to a normal one. Ablation. This is an invasive procedure done in the electrophysiology laboratory, which means that a catheter (a very thin, flexible hollow tube) is inserted into the heart through a vessel in the groin or arm. The procedure is done in a manner similar to the electrophysiology studies (EPS) described above. Once the site of the arrhythmia has been determined by EPS, the catheter is moved to the site. By use of a technique, such as radiofrequency ablation (very high frequency radio waves are applied to the site, heating the tissue until the site is destroyed) or cryoablation (an ultra-cold substance is applied to the site, freezing the tissue and destroying the site), the site of the arrhythmia may be destroyed. Pacemaker. A permanent pacemaker is a small device that is implanted under the skin (most often in the shoulder area just under the collar bone), and sends electrical signals to start or regulate a slow heart beat. A permanent pacemaker may be used to make the heart beat if the heart's natural pacemaker (the SA node) is not functioning properly and has developed an abnormal heart rate or rhythm or if the electrical pathways are blocked. Pacemakers are typically used for slow arrhythmias such as sinus bradycardia, sick sinus syndrome, or heart block. Implantable cardioverter defibrillator. An implantable cardioverter defibrillator (ICD) is a small device, similar to a pacemaker, that is implanted under the skin, often in the shoulder area just under the collarbone. An ICD senses the rate of the heartbeat. When the heart rate exceeds a rate programmed into the device, it delivers an electrical shock to the heart in order to correct the rhythm to a slower more normal heart rhythm. ICDs are combined with a pacemaker to deliver an electrical signal to regulate a heart rate that is too slow. ICDs are used for life-threatening fast arrhythmias such as ventricular tachycardia or ventricular fibrillation. Surgery. Surgical treatment for arrhythmias is usually done only when all other appropriate options have failed. Surgical ablation is a major surgical procedure requiring general anesthesia. The chest is opened, exposing the heart. The site of the arrhythmia is located, the tissue is destroyed or removed in order to eliminate the source of the arrhythmia. Last Annual Review Date: 03/26/2013	2	6	1	0	0	0.812191	1	4,172
\|MP 2.04.80\|\|Genetic Testing for Hereditary Hemochromatosis\| \|Original Policy Date \|Last Review Status/Date Reviewed with literature search/4:2014 \|Return to Medical Policy Index\| Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract. Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage. Medical technology is constantly changing, and we reserve the right to review and update our policies periodically. Hereditary hemochromatosis (HH), a common genetic disorder of iron metabolism, can lead to inappropriate iron absorption, toxic accumulation of iron, and organ damage. Genetic testing is available to assess mutations in the HFE gene, which are responsible for most clinically significant cases of hereditary hemochromatosis. Iron overload syndromes may be hereditary, secondary to some other disease (eg iron-loading anemias, parenteral iron overload, chronic liver disease, or dysmetabolic iron overload syndrome), or due to other miscellaneous conditions (eg, neonatal iron overload, aceruloplasminemia, congenital atransferrinemia). Iron overload, if left untreated, can lead to secondary tissue damage in a wide range of organs resulting in chronic liver disease (hepatic fibrosis, cirrhosis, hepatocellular carcinoma), endocrine dysfunction (diabetes, hypogonadism), arthralgia or arthritis (typically involving the second and third metacarpophalangeal joints), and cardiomyopathy (with either symptomatic cardiac failure or arrhythmias). HH, an autosomal recessive disorder, is the most common identified, genetic disorder in Caucasians, with an estimated prevalence of 1 in 250 Caucasians. However, fully expressed disease with end-organ manifestations is seen in less than 10% of affected individuals. Factors that influence phenotypic expression of HFE (high iron-related HH (ie, the clinical appearance of iron overload) are not clearly defined. Low clinical penetrance may be due to a complex interplay of genetic status and other factors such as age, sex, environmental influences, and comorbid diseases. HH leads to inappropriate iron absorption from the intestine and progressive increase in intracellular iron concentrations. Untreated HH leads to premature death, usually by liver complications. Treatment by removing excess iron with serial phlebotomy is simple and effective, and if started before irreversible end-organ damage, restores normal life expectancy. Diagnosis of Hemochromatosis Patients with hemochromatosis may present with nonspecific systemic symptoms or specific organ-related symptoms, or they may be asymptomatic. Clinical diagnosis of hemochromatosis is based on documentation of increased iron stores as demonstrated by abnormal serum iron indices, specifically elevated transferrin saturation and elevated serum ferritin concentration. Liver biopsy has been used to confirm diagnosis but is now generally limited to determining the degree of hepatic fibrosis and cirrhosis during disease management. Genetic testing can confirm a hereditary nature of iron overload. Genetics of Hereditary Hemochromatosis Most patients with HH have mutations in the HFE gene, located on the short arm of chromosome 6. The HFE gene was identified and cloned in 1996. The most common mutation in the HFE gene is C282Y, a missense mutation that changes cysteine at position 282 in the HFE protein to tyrosine. Homozygosity for the C282Y mutation is associated with 60% to 90% of all cases of HH. Additionally, 3% to 8% of affected individuals are heterozygous for this mutation. Penetrance for elevated serum iron indices among C282Y homozygotes is relatively high, but not 100%. However, penetrance for characteristic clinical end points (ie, end-organ damage) is quite low. There is no test that can predict whether a C282Y homozygote will develop clinical symptoms. Another significant mutation is referred to as H63D, which changes histidine at position 63 to aspartic acid. Homozygosity for H63D is insufficient to cause clinically significant iron overload in the absence of modifying factors. However, compound heterozygosity for C282Y/H63D has been associated with increased hepatic iron concentrations; approximately 1% to 2% of patients with this genotype will develop clinical evidence of iron overload, usually in the presence of another liver disease.(1) The clinical significance of a third HFE mutation, S65C (serine at position 65 changed to cysteine), appears to be minimal. This rare variant displays very low penetrance. Compound heterozygosity for C282Y/S65C may confer a low risk for mild HH. Individuals who are heterozygous for S65C and either the wild-type (normal) or H63D alleles do not seem to be at an increased risk for HH. Other mutations in HFE and in non-HFE genes (eg, transferrin receptor 2, TFR2) resulting in iron overload syndromes are rare.(2-4) With the advent of genetic testing in the late 1990s, HFE-related HH is now frequently identified in asymptomatic probands and in presymptomatic relatives of patients who are known to have the disease. (5) Therefore, a genetic diagnosis can be made in subjects who have not yet developed phenotypic expression; these subjects have a genetic susceptibility to developing iron overload but may never do so. A 2000 consensus conference of the European Association for the Study of Liver Diseases led to a recognition of different stages and progression of hemochromatosis. These stages were defined as: - Stage 1: Patients with “genetic susceptibility” who have the genetic disorder but no increase in iron stores. - Stage 2: Patients who have the genetic disorder and phenotypic evidence of iron overload but no tissue or end-organ damage. - Stage 3: Patients who have the genetic disorder with iron overload and iron deposition to the degree that tissue and end-organ damage occurs. No U.S. Food and Drug Administration (FDA)‒cleared genotyping tests were found. Thus, genotyping is offered as a laboratory-developed test. Clinical laboratories may develop and validate tests in-house (“home-brew”) and market them as a laboratory service; such tests must meet the general regulatory standards of the Clinical Laboratory Improvement Act (CLIA). The laboratory offering the service must be licensed by CLIA for high-complexity testing. Genetic testing for HFE gene mutations may be considered medically necessary in a patient with abnormal serum iron indices indicating iron overload. (See Policy Guidelines) Genetic testing for HFE gene mutations may be considered medically necessary in individuals with a family history of hemochromatosis in a first-degree relative. (See Policy Guidelines) Genetic testing for hereditary hemochromatosis in screening of the general population is considered investigational. Serum Iron Indices in the Diagnosis of HH(6) - Elevated fasting transferrin saturation (the ratio of serum iron to total iron-binding capacity) is the most sensitive initial phenotypic screening test. A minimum cut-off value of 45% will detect almost all affected C282Y homozygotes. - Serum ferritin reflects body iron stores and generally rises later in the progression of iron overload. In the absence of other causes of hyperferritinemia (alcohol abuse, metabolic syndrome, inflammatory states [eg, infection, cancer, active rheumatoid arthritis], acute and chronic hepatitis), serum ferritin is a good marker of the degree of iron overload. The negative predictive value of a normal transferrin saturation and serum ferritin is 97%. In this situation, no further testing is recommended.(6) 2011 Practice Guidelines by the American Association for the Study of Liver Diseases recommend HFE gene mutation testing in patients with abnormal serum iron indices (ie, serum ferritin and transferrin saturation), even in the absence of symptoms (eg, abnormal serum iron indices on routine screening chemistry panel). Genetic Testing in an Individual With a Family History of HH 2011 Practice Guidelines by the American Association for the Study of Liver Diseases recommend screening (iron studies [serum ferritin and transferrin saturation] and HFE mutation analysis) of first-degree relatives of patients with HFE-related HH to detect early disease and prevent complications.(5) For children of an identified proband, HFE testing of the other parent is generally recommended because, if results are normal, the child is an obligate heterozygote and need not undergo further testing because there is no increased risk of iron loading. If C282Y homozygosity or compound heterozygosity is found in adult relatives of a proband, and if serum ferritin levels are increased, then therapeutic phlebotomy can be initiated. If ferritin level is normal in these patients, then yearly follow-up with iron studies is indicated. When identified, C282Y heterozygotes and H63D heterozygotes can be reassured that they are not at risk for developing progressive or symptomatic iron overload. Occasional H63D homozygotes can develop mild iron overload. Beginning in 2012, there is specific CPT coding for genetic testing for HFE common variants: 81256: HFE (hemochromatosis) (eg, hereditary hemochromatosis) gene analysis, common variants (eg, C282Y, H63D) BlueCard/National Account Issues No applicable information This policy was created in 2012 and is based on a search of the MEDLINE database through March 23, 2014. Recent reviews highlight the pathogenesis, diagnosis and management of hereditary hemochromatosis (HH).(6-9) A 2001 TEC Assessment on genetic testing for HFE gene mutations related to HH concluded the following: - Genetic testing and counseling for HFE mutations in the management of patients with symptoms of iron overload consistent with hereditary hemochromatosis, in the setting of 2 consecutive transferrin saturation values of 45% or more and a serum ferritin value of less than 200–300 mcg/L, met the TEC criteria. - Genetic testing and counseling for HFE mutations in asymptomatic relatives of subjects with hereditary hemochromatosis also met the TEC criteria. The Assessment did not address the use of genetic testing for HFE gene mutations in screening of the general population.(10) Validation of the Clinical Use of a Genetic Test Validation of the clinical use of any genetic test focuses on 3 main principles: (1) analytic validity (technical accuracy of the test in detecting a mutation that is present or in excluding a mutation that is absent; (2) clinical validity (diagnostic performance of the test [sensitivity, specificity, positive and negative predictive values] in detecting clinical disease; and (3) clinical utility (ie, how results of the diagnostic test will be used to change management of the patient and whether these changes in management lead to clinically important improvements in health outcomes). Stuhrmann et al (2005) initiated a pilot study on DNA-based screening of hereditary hemochromatosis in Germany.(11) A focus of the study was the analytic validity of different test methods. A total of 3961 subjects provided blood samples for testing of the C282Y HFE mutation; of these, 3930 samples were successfully tested by 2 independent test methods (either polymerase chain reaction and restriction digest, reverse allele-specific oligonucleotide hybridization, solid-phase oligonucleotide ligation assay, or microarray [DNA-chip]). In all, 67 of the tested subjects were homozygous for C282Y; 42.6% of the homozygotes already knew their clinical diagnosis of HH before sending the blood sample. Iron accumulation with further signs or symptoms of HH was present in 8 (24%) of 34 newly diagnosed C282Y homozygous subjects. Of 7860 tests performed, 7841 (99.6%) gave correct results. The overall error rate was 0.24% (95% confidence interval [CI], 0.15 to 0.38). Analytic specificity of the test methods for detecting homozygosity for C282Y was 100% (7726/7726 nonhomozygous test challenges; 95% CI, 99.95 to 100), and analytic sensitivity was 97% (130/134 homozygous test challenges; 95% CI, 92.5 to 99.2). This evidence indicates that test methods for C282Y are robust and highly sensitive and specific. Bryant et al (2008) evaluated the clinical validity and clinical utility of DNA testing in people suspected of having hereditary hemochromatosis and in family members of those diagnosed with the disorder by conducting a systematic review of 15 electronic databases (including MEDLINE and the Cochrane library) up to April 2007.(12) Clinical validity, defined as the ability of the test to detect or predict the phenotype (disorder) of interest, involved establishing the probability that the test would be positive in people with clinical HH (sensitivity) and the probability that the test would be negative in people without the disease (specificity). Studies were included if they reported the use of DNA tests in Caucasians of northern European origin with iron overload suggestive of HH compared with a control population, and reported or allowed the calculation of sensitivity and specificity. Clinical utility studies were included if they reported the use of DNA tests in Caucasians with iron overload suggestive of HH (or relatives of suspected cases) compared with any case-identification strategy not involving DNA, and reported patient-based outcomes (such as morbidity or mortality). Eleven observational studies that evaluated the clinical validity of genotyping for the C282Y mutation in the diagnostic workup for HH were identified. Criteria used to define hemochromatosis varied among studies. Clinical sensitivity of C282Y homozygosity ranged from 28.4% to 100%; when considering studies that used strict criteria to classify HH, clinical sensitivity ranged from 91.3% to 92.4%. No clinical utility studies were found. The authors concluded that DNA testing for HH in at-risk populations has clinical validity and may have clinical utility. The clinical utility of genetic testing for HH depends on how results can be used to improve patient management. Although there has never been a randomized controlled trial of phlebotomy versus no phlebotomy in the treatment of HH, there is evidence that initiation of phlebotomy before the development of cirrhosis and/or diabetes will significantly reduce HH-associated morbidity and mortality.(5,13,14) Data exists on the psychosocial aspect of genetic testing for HH. Picot et al (2009) conducted a systematic review of the psychosocial aspects of DNA testing for HH in at-risk subjects.(15) Databases were searched through 2007 for any quantitative or qualitative primary research that considered DNA testing of subjects considered at-risk for HH and that reported psychosocial outcomes. Three observational studies were included; each had methodologic limitations. After receiving test results, patient anxiety levels fell or were unchanged, and general health-related quality-of-life outcomes improved in some aspects from pretest assessments, or were unchanged. Outcomes were not reported separately for those referred for diagnosis and those with a family history of HH. The authors concluded that, although evidence is limited, results suggested that genetic testing for HH in at-risk subjects is accompanied by few negative psychosocial outcomes. Population Screening for HH General population screening for HH has been proposed because of the high prevalence of disease, absence of or nonspecific early clinical findings, specificity of findings once they appear, low cost of diagnosis and treatment, and high cost and low success rate of late diagnosis and treatment. However, because genotype penetrance is low, and the natural history of untreated individuals is unpredictable, support for population-based screening is lacking. The American Academy of Family Physicians, Centers for Disease Control and Prevention, and U.S. Preventive Services Task Force recommend against population-based general screening.(16-18) McLaren and Gordeuk conducted the Hemochromatosis and Iron Overload Screening (HEIRS) study to evaluate the prevalence, genetic and environmental determinants, and potential clinical, personal, and societal impact of hemochromatosis and iron overload in a multiethnic, primary care-based sample of 101,168 adults enrolled over a 2-year period at 4 centers in the U.S. and 1 in Canada.(19) Initial screening included genotyping for the HFE C282Y and H63D alleles, measurement of serum ferritin, and calculation of transferrin saturation. The yield of HFE genotyping for identifying persons with C282Y homozygosity was low in racial/ethnic groups other than non-Hispanic Caucasians. Overall frequency of homozygosity for the C282Y mutation in non-Hispanic Caucasians was 4.4 per 1000. There was marked heterogeneity of disease expression in C282Y homozygotes. The authors concluded that (1) future studies to discover modifier genes that affect phenotypic expression in C282Y hemochromatosis should help identify patients who are at greatest risk of developing iron overload who may benefit from continued monitoring of iron status, and (2) although genetic testing is well-accepted and associated with minimal risk of discrimination, generalized population screening in a primary care population as performed in the HEIRS study is not recommended. In a substudy of Caucasian participants in the HEIRS study, Adams et al (2013) assessed the prevalence of HFE mutations in patients who had elevated serum ferritin levels less than 1000 µg/L (300-1000 µg/L for men, 200-1000 µg/L for women).(20) Among 3359 men and 2416 women, prevalence of potential iron-loading HFE genotypes (defined as C282Y homozygote, C282Y/H63D compound heterozygote, or H63D homozygote) was 10% and 12% in men and women, respectively. Prevalence of C282Y homozygosity was 2% and 4% among men and women, respectively. Likelihood of C282Y homozygosity increased with increasing serum ferritin levels, from 0.3% to 16% in men, and from 0.3% to 30% in women. Posttest likelihood ratios (likelihood of C282Y homozygosity given a positive test result) exceeded 1 at serum ferritin levels of 500 µg/L or more for men and at levels greater than 300 µg/L for women. In Caucasian subjects with mild hyperferritinemia, causes of elevated serum ferritin level other than C282Y or H63D HFE mutations (eg, liver disease, diabetes) were more likely. Hereditary hemochromatosis is a common genetic disorder in the Caucasian population. Abnormal serum iron indices, clinical symptoms of iron overload or a family history of hereditary hemochromatosis may provoke testing for diagnosis. Testing for mutations in the HFE gene, which contributes to most cases of hereditary hemochromatosis, can confirm a genetic etiology; if clinically indicated, serial phlebotomy may be initiated, which can lead to a restored normal life expectancy. Therefore, genetic testing for HFE gene mutations may be considered medically necessary for patients with a clinical suspicion of hemochromatosis (signs and symptoms of iron overload) or in patients with fasting serum iron indices that are suggestive of iron overload, as well as in individuals with a family history of hemochromatosis. General population screening has been proposed because of the high prevalence of disease, absence of or nonspecific early clinical findings, simplicity and effectiveness of treatment, and low success rate of late diagnosis and treatment. However, because genotype penetrance is low, and the natural history of untreated individuals is unpredictable, support for population-based screening is lacking. Therefore, genetic testing for hereditary hemochromatosis screening in the general population is considered investigational. Practice Guidelines and Position Statements American Academy of Family Physicians AAFP recommends against routine genetic screening for hereditary hemochromatosis in the asymptomatic general population. (Grade D recommendation: at least fair evidence that [the service] is ineffective or that harms outweigh benefits).(16) American Association for the Study of Liver Diseases A 2011 practice guideline from AASLD recommends(5): - Patients with abnormal iron studies should be evaluated as patients with hemochromatosis, even in the absence of symptoms (based on high quality evidence [A]). - In a patient with suggestive symptoms, physical findings, or family history of HH, a combination of transferrin saturation and ferritin should be obtained rather than relying on a single test, and if either is abnormal (transferrin saturation ≥45% or ferritin above the upper limit of normal), then HFE mutation analysis should be performed (strength of recommendation 1 [strong] by the classification of the Grading of Recommendation Assessment, Development, and Evaluation [GRADE] workgroup; based on moderate quality evidence [B]). - Screening (iron studies and HFE mutation analysis) of first-degree relatives of patients with HFE-related HH is recommended to detect early disease and prevent complications. (1A) - Screening for non-HFE-related HH is not recommended. Average risk population screening for HH is not recommended. (1B) Centers for Disease Control and Prevention CDC does not currently recommend population screening for HFE mutations.(17) U.S. Preventive Services Task Force USPSTF recommends against routine genetic screening for hereditary hemochromatosis in the asymptomatic general population. (Grade D recommendation: at least fair evidence that [the service] is ineffective or that harms outweigh benefits).(21) Medicare National Coverage There is no national coverage determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of local Medicare carriers. - Kanwar P, Kowdley KV. Metal storage disorders: Wilson disease and hemochromatosis. Med Clin North Am 2014; 98(1):87-102. - Sood R, Bakashi R, Hegade VS et al. Diagnosis and management of hereditary haemochromatosis. British Journal of General Practice 2013; 63(611):331-32. - Vujic M. Molecular basis of HFE-hemochromatosis. Front Pharmacol 2014; 5:42. - Radio FC, Majore S, Binni F et al. TFR2-related hereditary hemochromatosis as a frequent cause of primary iron overload in patients from Central-Southern Italy. Blood Cells Mol Dis 2014; 52(2-3):83-7. - Bacon BR, Adams PC, Kowdley KV et al. Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology 2011; 54(1):328-43. - Clark P, Britton LJ, Powell LW. The diagnosis and management of hereditary haemochromatosis. Clin Biochem Rev 2010; 31(1):3-8. - Alexander J, Kowdley KV. HFE-associated hereditary hemochromatosis. Genet Med 2009; 11(5):307-13. - Gan EK, Powell LW, Olynyk JK. Natural history and management of HFE-hemochromatosis. Semin Liver Dis 2011; 31(3):293-301. - Crownover BK, Covey CJ. Hereditary hemochromatosis. Am Fam Physician 2013; 87(3):183-90. - Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Genetic Testing for HFE Gene Mutations Related to Hereditary Hemochromatosis. TEC Assessments 2001; Volume 16, Tab 22. - Stuhrmann M, Strassburg C, Schmidtke J. Genotype-based screening for hereditary haemochromatosis. I: Technical performance, costs and clinical relevance of a German pilot study. Eur J Hum Genet 2005; 13(1):69-78. - Bryant J, Cooper K, Picot J et al. A systematic review of the clinical validity and clinical utility of DNA testing for hereditary haemochromatosis type 1 in at-risk populations. J Med Genet 2008; 45(8):513-8. - Adams PC, Speechley M, Kertesz AE. Long-term survival analysis in hereditary hemochromatosis. Gastroenterology 1991; 101(2):368-72. - Niederau C, Fischer R, Purschel A et al. Long-term survival in patients with hereditary hemochromatosis. Gastroenterology 1996; 110(4):1107-19. - Picot J, Bryant J, Cooper K et al. Psychosocial aspects of DNA testing for hereditary hemochromatosis in at-risk individuals: a systematic review. Genet Test Mol Biomarkers 2009; 13(1):7-14. - American Academy of Family Physicians. Hemochromatosis, 2006. Available online at: http://www.aafp.org/patient-care/clinical-recommendations/all/hemochromatosis.html. Last accessed March 2014. - Centers for Disease Control and Prevention. Hemochromatosis (iron storage disease). Training & education - epidemiology prevalence. Available online at: http://www.cdc.gov/ncbddd/hemochromatosis/training/epidemiology/prevalence.html. Last accessed March 2014. - Whitlock EP, Garlitz BA, Harris EL et al. Screening for hereditary hemochromatosis: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2006; 145(3):209-23. - McLaren GD, Gordeuk VR. Hereditary hemochromatosis: insights from the Hemochromatosis and Iron Overload Screening (HEIRS) Study. Hematology Am Soc Hematol Educ Program 2009:195-206. - Adams PC, McLaren CE, Speechley M et al. HFE mutations in Caucasian participants of the Hemochromatosis and Iron Overload Screening study with serum ferritin level <1000 microg/L. Can J Gastroenterol 2013; 27(7):390-2. - U.S. Preventive Services Task Force (USPSTF). Screening for hemochromatosis, August 2006. Available online at: http://www.uspreventiveservicestaskforce.org/uspstf/uspshemoch.htm. Last accessed March 2014. \|CPT\|\|81256\|\|HFE (hemochromatosis)(e.g., hereditary hemochromatosis) gene analysis, common variants (e.g., C282Y, H63D)\| \|ICD-9-CM Diagnosis\|\|275.01-275.09\|\|Disorders of iron metabolism code range\| \|V18.19\|\|Family history of other endocrine and metabolic diseases\| \|ICD-10-CM (effective 10/1/15)\|\|E83.10\|\|Disorder of iron metabolism, unspecified\| \|E83.110-E83.119\|\|Hemochromatosis code range\| \|Z83.49\|\|Family history of other endocrine, nutritional and metabolic diseases\| \|ICD-10-PCS (effectve 10/1/15)\|\|Not applicable. ICD-10-PCS codes are only used for inpatient services. There are no ICD procedure codes for laboratory tests.\| Genetic testing, hereditary hemochromatosis Hemochromatosis, genetic testing \|4/12/12\|\|New Policy add to Medicine – Pathology/ Laboratory section\|\|Genetic testing for HFE gene mutations may be considered medically necessary in patients with abnormal serum iron indices indicating iron overload and in individuals with a family history of hemochromatosis in a first degree relative. Investigational in screening of the general population.\| \|04/11/13\|\|Replace Policy\|\|Policy updated with literature search through February 2013. Reference 5 and 12-14 added. No change in policy statements.\| \|05/09/13\|\|Replace policy - correction only\|\|Reference 15 added\| \|4/10/14\|\|Replace policy\|\|Policy updated with literature review through March 23, 2014; references 1-4 and 20-21 added; references 16-17 updated. No change in policy statements.\|	2	20	4	0	2	0.943524	6	6,089
Email : [email protected] The central nervous system consists of the brain and the spinal cord immersed in the cerebrospinal fluid. Weighing about 3 pounds (1.4 kilograms) the brain lies within the cranial cavity. The brain and the spinal cord are completely surrounded by three membranes, the Meninges,lying between the skull and the brain and between the vertebrae and the spinal cord. Named from outside inwards they are - Dura mater - Arachnoid mater - Pia mater. (Piamater and arachnoid mater together forms the leptomeninges) Brain is composed of Cerebrum – includes cerebral hemispheres,separated by the cerebral falx within the longitudinal cerebral fissure.Each hemisphere is divided into four lobes for descriptive purposes. Frontal lobe,Parietal lobe,Occipital lobe,Temporal lobe. Diencephalon – is the central core of the brain. Brainstem is comprised of - Midbrain – rostral part of brain - Pons – Part between the midbrain rostrally and the medulla caudally. - Medulla – most caudal part of brainstem that is continouos with the spinal cord. Cerebellum – consists of two lateral hemispheres. Ventricular System of Brain. - The structures of the ventricular system are embryologically derived from the centre of the neural tube (the neural canal). - The ventricular system of the brain consists of four irregular-shaped cavities or ventricles - Two lateral ventricles (right and left). - The midline third and fourth ventricles connected by the cerebral aqueduct. - CSF,largely secreted by the choroid plexus of ventricles,fills these brain cavities and the subarachinoid space of the brain and spinal cord. Ventricles of the Brain The lateral ventricles, the 1st and 2nd ventricles,are the largest cavities of the ventricular system and occupy large areas of the cerebral hemispheres.Each lateral ventricle opens through an interventricular foramen into the 3rd ventricle. The 3rd ventricle is a slit like cavity between the right and left halves of the diencephalons is continuous posteroinferiorly with the cerebral aqueduct,a narrow channel in the midbrain connecting the 3rd and 4th ventricles. The pyramid-shaped 4th ventricle in the posterior part of the pons and medulla extends inferoposteriorly..Inferiorly,it tapers to a narrow channel that continues into the cervical region of the spinal cord as the central canal. CSF pressure remains almost constant at about 10cm H20 when the individual is lying on his side and about 30cm H20 when sitting up.If the brain is enlarged by,eg:haemorhage or tumour,some compensation is made by a reduction in the amount of CSF.When the volume of brain tissue is reduced,such as degeneration or atrophy,the volume of CSF is increased. CSF is a clear,slightly alkaline fluid with a specific gravity of 1.005,consisting of - mineral salts - plasma proteins - few leucocytes. Secretion of Cerebrospinal fluid Is secreted continuously at the rate of 400-500ml/day,by the choroid epithelial cells of the choroid plexus in the lateral,third and fourth ventricles.The amount around the brain and spinal cord remains fairly constant at about 120 ml,which means that absorption keeps pace with secretion. - consists of vascular fringes of piameter covered by cuboid epithelium. - are invaginated into the roof of third and fourth ventricles and on the - floors of the bodies and inferior horns of lateral ventricles. Circulation of Cerebrospinal fluid CSF leaves the lateral ventricles through the interventricular foramen or foramina of Monro and enters third ventricle.From here,CSF passes through the cerebral aqueduct into the fourth ventricle.From there it can pass into the central canal of the spinal cord or into the cisterns of the subarachnoid space via three small foramina: the central foramen of Magendie and the two lateral foramina of Luschka.CSF also passes into the extensions of the subarachnoid space around the cranial nerves,the most important of which are those surrounding optic nerve. The fluid then flows around the superior sagittal sinus to be reabsorbed via the arachnoid villi into the venous system. CSF within the spinal cord can flow all the way down to the lumbar cistern at the end of the cord around the cauda equina where lumbar punctures are performed. Absorption of Cerebrospinal fluid Is at the same rate as of production. The main site of absorption into the venous system is through the arachnoid granulations. CSF enters the venous system through two routes -Through the cells of the arachnoid granulations into the dural venous sinuses. -Some CSF moves between the cells. Functions of Cerebrospinal fluid - Supports and protects, brain and spinal chord by providing a cushion and shock absorber between brain and cranial bones. - Provides buoyancy – CSF in the subarachnoid space provides buoyancy that prevents the weight of the brain from compressing the cranial nerve roots and blood vessels against the internal surface of cranium. - Maintains a uniform pressure around the delicate structures. - Keeps the brain and spinal cord moist and there may be interchange of substances between CSF and nerve cells,such as nutrients and waste products. Subarachnoid Cisterns – At certain areas on the base of the brain the arachnoid and pia are widely separated by subarachnoid cisterns which contain CSF and soft tissue structures that anchor the brain. Eg: Cerebellomedullary cistern - Monro – Kellie Doctrine - States that the cranial cavity is a closed rigid box and that a change in the quantity of intracranial blood can occur only through the displacement or replacement of CSF. - Methods of obtaining CSF - To obtain CSF for examination it is necessary to puncture either the cerebral ventricles or the subarachnoid space,either in the cisterna magna or in the lumbar theca beyond the termination of the spinal cord. Is the simplest method.The spinal cord terminates at the lower border of the first lumbar vertebra in the adult and at a slightly lower level in the child.The arachnoid continues downwards below the termination of the spinal cord as far as the second sacral vertebra and forms a lumbar cul-de-sac of the subarachnoid space nomally containing CSF.A needle can be introduced into this space without injuring the cord. LP or spinal tap is done to extract samples of CSF from lumbar cistern.Lumbar spinal puncture is performed with the patient leaning forward or lying on the side with the back flexed.Under aseptic conditions ,the skin coverig the lower lumbar vertebra is anaesthetized and a lumbar puncture needle fitted with a stylet is inserted in the midline between the L3 and L4 or L4 and L5 spinous processes.At these levels there is no danger of damaging the spinal cord.After passing 4-6 cms in adults the needle punctures the duramater and arachnoid mater and enters the lumbar cistern.When stylet is removed,CSF escapes at the rate of one drop per second.If subarachnoid pressure is high,CSF flows out or escapes as a jet.Lumbar puncture is not done in cases with increased ICT. - 1) Obtain CSF for cytological,chemical and other investigations and to estimate its pressure. - 2) Introduce into the subarachnoid space therapeutic substances or local anaesthetics. - 3) Introduce air into the sub arachnoid space for encephalography or myelography. - 4) Introduce opaque media for myelography. - 5) In benign intracranial hypertension,lumbar puncture is safe and may even be beneficial as it temporarily reduces the pressure. - 1) Raised intracranial pressure especially due to a tumour in the posterior fossa of the skull,sudden withdrawal of fluid from the spinal canal may cause herniation of the medulla and cerebellar tonsils into the foramen magnum-the cerebellar pressure cone – with fatal results. - 2) When ICSOL is present or suspected in one cerebral hemisphere,herniation of the medial part of the temporal lobe through the tentorial hiatus results in compression and distortion of the upper brainstem which is disastrous. - 3) Skin sepsis or extradural suppuration in the lumbar region owing to the risk of infecting spinal canal. - 4) Marked spinal deformity in dorsal or lumbar region may render it difficult or impossible. Is the failure to obtain CSF due to faulty procedure.The point of needle may not have entered the subarachnoid space.A genuine dry tap may occur when the spinal subarachnooid space is blocked at a higher level or when the lumbar sac itself is filled by a neoplasm or lipoma. A throbbing headache which comes on after a few hours is the commonest sequelae.May be associated with nausea,vomiting,giddiness and pain in the neck and back.Headache which lasts for few days to weeks is due to leakage of CSF through the punctured wound. Occasionally LP intensifies the already existing symptoms especially when a lesion is compressing the spinal cord as symptoms may be exacerabated by alterations of pressure induced by the withdrawal of fluid. Prolapsed intervertebral disc following puncture of the annulus fibrosis. Ventricular puncture - Puncture via a burr hole or via the lateral angle of the anterior fontanelle is now rarely used. Cisternal puncture - Is done by penetrating the cisterna magna (cerebellomedullary cistern) which is a dilatation of the subarachnoid space. - 1) when lumbar puncture is not possible,eg – lumbar sepsis,deformity of spine. - 2) To compare the composition of or pressure of cisternal and lumbar fluids - 3) To inject opaque media,therapeutic substance,air for encephalography - 1) tumour or abscess in posterior fossa - 2) Raised ICP - 3) Inflammatory adhesions in cistern - Lumbar puncture needle is inserted at a point 1 cm above the spinous process of the cervical vertebra. - Lateral Ventricuar puncture - Technique introduced in the recent years and is used especially as a method of myelography in cervical spinal lesions.Here needle is inserted 1 cm caudal and 1 cm posterior to the tip of mastoid process. Measurement of CSF pressure Method of determination The CSF pressure can be measured with a simple manometer.A graduated glass tube is attached to the lumbar puncture needle and the height in mm to which the fluid ascends in the tube is measured.The normal CSF pressure in adults is 60 to 150 mm of fluid and 45 to 90 mm in children. Pathological variations of pressure Abnormally high pressure is found in ICSOL,haemorrhage,hypertensive encephalopathy,hypervitainosisA,hydrocephalus, intracranial sinus thrombosis,meningism,some forms of meningitis,encephalitis,uremia,corpulmonale. Subnormal pressure is seen in : Head injury,dehydration,spinal subarachnoid block, Abnormally Low : Second LP is performed shortly after previous one. Normally if one compresses the jugular veins during lumbar puncture,there is an immediate and rapid rise in CSF pressure and rapidly falls to normal when compression ceases.Venous compression causes raised pressure in the intracranial venous sinuses and hence in the cranium.This test is used to check the patency of the subarachnoid space between the cranial cavity and the lumbar sac. CSF may be obtained by lumbar,cisternal or lateral cervical puncture or through ventricular cannulas or shunts.A manometer is attached before any fluid is removed to record the opening pressure.A dramatic pressure droop of 1 to 2 ml suggests herniation or spinal block above the puncture site. No further fluid should be withdrawn in this situation. Upto 20ml of spinal fluid may be removed normally. Indications for lumbar puncture can be divided into four major disease catogories.ie - 1) meningeal infection - 2) subarachnoid hemorrhage - 3) CNS malignancy - 4) Demyelinating diseases Identification of infectious meningitis,esp bacterial is the most important indication of CSF examination.The potential yield of CSF examination in diseases should be weighed against the small risk of potentially serious complications of LP. - Diseases detected by CSF Examination - High sensitivity,high specificity - Bacterial,tuberculous,fungal meningitis - High sensitivity and moderate specificity - Viral meningitis,Subarachnoid hemorrhage,Multiple sclerosis,CNS syphilis,Infectious polyneuritis,Paraspinal abscess - Moderate sensitivity,high specifity Moderate sensitivity moderate specificity- Intracranial,Viral encephalitis,Sub dural haematoma. (Sensitivity = Ability of a test to detect disease when it is present, Specificity = Ability of a test to exclude disease when it is not present) - Normal CSF is clear and colorless,with a viscosity similar to water. - Cloudiness or turbidity is seen in leucocytosis,presence of microorganisms,aspirated epidural fat,protein - Clot formation in traumatic taps,spinal block,suppurative and tuberculous meningitis - Viscous CSF is seen in metastatic mucin producing adenocacinomas,cryptococcal meningitis,needle injury to the annulus fibrosis. - Pink red CSF indicates presence of blood. - Xanthochromic CSF is pink,orange,or yellow due to RBC lysis and hemoglobin breakdown. Total Cell Count: Normal leucocyte count 0 to 5 cells/micro litre in adults and 0 to 30 cells in neonates.Red Cells have limited diagnostic value but may allow a useful approximation of the true CSF WBC count or total protein in the presence of traumatic puncture by correcting for WBCs or protein introduced by bleed. Lymphocytes normal range – 62 to 92 Lymphocytosis is seen in Meningitis ie viral,tuberculous,fungal,bacterial Degenerative diseases like subacute Sclerosing panencephalitis,Multiple sclerosis,GB syndrome Neutrophils normal range – 2 to 7 Increased neutrophils are seen in Meningitis ie Bacterial,Early tuberculous,Early Mycotic,Early viral meningoencephalitis. Infections like Cerebral abscess,Subdural empyema, Following seizures,CNS hemorrhage,CNS infarct Metastatic tumours in contact with CSF. Plasma cells are not normally found in CSF Plasmacytosis in CSF is seen in Tuberculous meningitis,MS,SSP,GB syndrome,A/c viral infections Eosinophils may be rarely seen in normal CSF Eosinophilia in CSF is commonly associated with Parasitic and fungal infections,A/c polyneuritis,Idiopathic hypereosinophilic syndrome. Normal protein range is 15 to 45 mg/dl. Increased CSF protein is seen in Traumatic spinal tap Increased blood- CSF permeability Increased IgG synthesis Oligoclonal bands are seen in MS,SSPE,viral CNS infections. Increased levels of this acute phase reactant is used to differentiate bacterial from viral meningitis. Normal CSF glucose levels is 50 to 80 mg/dl. Decreased levels are characteristic of Meningitis – bacterial,tuberculous,fungal Increased CSF glucose is of no clinical significance May be seen in traumatic tap. Normal range is 9.0 to 26.0 mg/dl Elevated levels eflect anaerobic metabolism within CNS due to tissue hypoxia. Used to differentiate viral from bacterial,mycoplasmal,fungal,and tuberculous meningitis. Persistent elevation of Ventricular CSF lactate levels are associated with a poor prognosis in patients with severe head injury. CSF Glutamic-oxaloacetic transaminase activity is raised in some cases of cerebral infarction and MS CSF creatnine kinase activity is raised in muscular dystrophy CSF cholesterol is raised in MS Presence of keratin in CSF may indicate the presence of an intracranial epidermoid cyst. To differentiate Bacterial,Viral,Fungal and tuberculous meningitis Also useful in Neurosyphilis,HIV,Primary An anaesthetic agent can be injected into the CSF.Anaesthesia usually occurs within 1 minute.A headache may follow a spinal block,which likely results from the leakage of CSF through lumbar puncture. An anaesthetic can be injected into the extradural space. Eg:- lumbar epidural block,caudal epidural block. Regional anaesthesia for childbirth can be done by spinal or caudal epidural block. Diseases of the ventricular system include -abnormal enlargement (hydrocephalus) -inflammation of the CSF spaces (meningitis) caused by infection or introduction of blood following trauma or hemorrhage. - Overproduction of CSF. - Obstruction to flow of CSF. - Interference with absorption of CSF. - Excess fluid in Cerebral ventricles. - Brain is squeezed between ventricular fluid and calvarial bone. - In infants raised internal pressure results in expansion of brain and calvaria because sutures and fontanelles are open. Obstruction to flow of CSF can occur at any place,the blockage usually occurs in cerebral aqueduct or at interventricular foramen.Aqueductal stenosis may be caused by a nearby tumour or cellular debris following infection or haemorrhage.It is possible to bypass the blockage and allow CSF to escape there by lessening the damage. In Communicating Hydrocephalus,flow of CSF is not impaired.But movement of CSF into venous system is partly or completely blocked.Blockage may be caused by the congenital absence of arachnoid granulations or the granulation may be blocked by RBC after haemorrhage. Hydrocephalus ex-vacuo occurs when there is damage to the brain caused by stroke or injury, in which there may be actual shrinkage of brain tissue.Hydrocephalus ex-vacuo is essentially only hydrocephalus by default,the csf pressure itself is normal.In old age or persons with Alzheimer’ disease,the entire brain itself may shrink and the CSF itself may occupy the space created by shrinkage. Acquired hydrocephalus As a result of something blocking the drainage of CSF after birth.Culprits can include a brain tumour,arachinoid cyst,inflammation of brain,haemorrhage or trauma.Bacterial meningitis is also an imp cause. Congenital hydrocephalus due to birth defect or brain malformation.Causes include viral infection,inheritance as an X-linked genetic trait. Normal pressure hydrocephalus (NPH) – Due to gradual blockage of CSF drainage pathways in brain.Although ventricles enlarge the intracranial pressure remains within normal range.Occurs as a complication of infection or bleeding.Clinically presents as memory loss,gait disorder,urinary incontinence and a general slowing of activity Ventriculoatrial or ventriculoperitoneal shunting may be necessary wen hydrocephalus is progressive or causes symptoms.Neurosurgical removal of tumours should be carried out in appropriate cases. Hedra helix Chronic hydrocephalus,Rhinorrhoea,cerebro-spinalis.Cataract.Acts on blood vessels,menorrhagia. Helleborus A remedy in low states of vitality and serious disease. Characteristic aggravation from 4 to 8 p.m.SINKING SENSATION. State of effusion in hydrocephalus. Mania of a melancholy type.Hydrocephalus; in stage of effusion; with signs of depression; stupor and unconsciousness pupils sluggish; forehead corrugated, automatic action of one arm or one leg; the face flushes and pale; drinks greedily from nervousness; child suddenly screams out and bores its head into the pillow; the head is hot and the eyeballs are distorted;motion of jaws as if chewing. Laburnum or Cystisus Laburnum – Hydrocephalus. Constant vertigo; intense sleepiness. Zincum Met – Hydrocephalus. Rolls head from side to side. Bores head into pillow. Argentum nitricum – Hydrocephalus-where the child begins to roll its head, throw it back and cry out in sleep or awake Calcarea carbonica – Calcarea carbonica finds its place in the early stage of acute hydrocephalus when Belladonna does not act; the abdomen is distended, the limbs wasted; there is sweating of the head during sleep; weak memory. Apis mellifica - Its favorable action is shown by an increase of urine. The child is very drowsy and the accumulation of fluid in the brain is very rapid.Child bores its head backwards into the pillow, rolls it from side to side, rouses from sleep with a shrill, piercing cry; on side of the body may be convulsed or paralyzed; thee is strabismus and the urine is scanty. Apocynum - Acute hydrocephalus.Bradycardia is a prime indication. The dropsy is characterized by great thirst and gastric irritability. It is suitable to more advanced cases where the head is large, the fontanelles are wide open; it lacks the cephalic cry of Apis. Silicea - Head large sweat on whole head rather than on scalp alone, sudden startings in sleep, sour eructations, and redness of face, cold hands and feet will well indicate. Digitalis - When the urine is scanty and aluminous, and when the pulse is also; perhaps cold sweat on surface of body. Sulphur – When Apis fails and when general Sulphur symptoms are present; the child is in a stupor; cold wet; jerking of the limbs, suppressed urine; child wants to lie with its head low; cries out in sleep as if frightened; face red and pupils dilated. - [Complete ] [Head]Hydrocephalus: - [Complete ] [Vision]Loss of vision, blindness:Hydrocephalus, in: - [Complete ] [Face]Coldness:Hydrocephalus, in: - [Complete ] [Rectum]Diarrhea:Hydrocephalus, during acute: - [Complete ] [Generalities]Convulsions:Hydrocephalus, with: - [Kent ] [Head]Hydrocephalus: - [Kent ] [Face]Coldness:Hydrocephalus,in: - [Kent ] [Rectum]Diarrhoea:Hydrocephalus acutus,during: - [Kent ] [Urine]Milky:Hydrocephalus in,little but frequent milky urine with unconsciousness and delirium: - [Boenning ] [Sensation and complaints in general]Infants:Head, hypertrophy, hydrocephalus, etc.: - [Boger ] [Supplimentary references]Hydrocephalus: - [Knerr ] [Inner Head]Brain:Hydrocephalus: - [Knerr ] [Outer Head]Large:Hydrocephalic: - [Knerr ] [Inner Head]Brain:Hydrocephaloid: May be caused by bacteria,viruses,fungi,other organisms,malignant cells,drugs and contrast media,blood(following SAH).Microorganisms reach the meninges either by direct extension from the ears,nasopharynx,a cranial injury,or by spread via the blood stream.Immunocomprimised patients are at an increased risk. C/f : Meningitic syndrome means the triad of headache,neck stiffnes and fever.Photophobia and vomiting are often present. Specific varieties of meningitis Acute bacterial meningitis Sudden onset with rigors and high fever. Benign,self limiting,lasting for 4-10 days Headache may follow for some weeks Gradual onset of signs Drowsiness,focal signs and seizures are common Due to malignant cells Subacute or chronic noninfective CSF cell count is raised with high protein and low glucose. \|Protein\|\|0.2 – 0.4g/l\|\|0.4 – 0.8g/l\|\|0.5-2.0g/l\|\|0.5-3gm/l\| \|Glucose\|\|>1/2 RBS\|\|>1/2 RBS\|\|<1/2 RBS\|\|<1/3 RBS\| Aconite-When caused be exposure to the sun. Apis-fidgetiness, there are shrill outcries in sleep. the eruption is either suppressed or undeveloped; stage of effusion. Squinting, grinding of teeth, violent fever. Belladonna-The symptoms are severe and violent. There is intense congestion, throbbing, grinding of teeth and crying out in sleep; it picture acute meningitis before exudation. Sharp pains, red face and acuteness of symptoms are marked. Bryonia – In the stage of effusion. Face flushes and pales alternately; child screams if move the least. Has a hastiness in manner. White tongue and is thirsty. Cuprum- When it arises from a suppressed eruption. There is violent delirium, blue face, convulsions, with clenched hands, rolling of eyeballs, grinding of teeth, followed by deep sleep. Hellebores – Stage of exudation. Shooting pains in head; bores head into pillow; automatic motion of an arm and foot;eyeballs turned upwards; is hasty in manner. Zincum-Sharp pains through head; especially in meningitis arising from non-development of an eruption; constant fidgety motions of feet. Little or no fever and hyperaesthes of all the senses and skin. Artemisia vulgaris, Baryta carb. and Calcarea carb. - [Kent ] [Back]Inflammation:Membranes,spinal meningitis: - [Kent ] [Extremities]Paralysis:Upper limbs:Meningitis,during: - [Complete ] [Generalities]Convulsions:Meningitis, in cerebro-spinal: - [Complete ] [Back]Inflammation:Membranes, spinal meningitis: - [Complete ] [Head]Inflammation, of:Meninges, meningitis: - [Complete ] [Mind]Unconsciousness, coma:Meningitis, in: - [Complete ] [Mind]Stupor:Meningitis, in: - [Complete ] [Mind]Shrieking, screaming, shouting:Meningitis, in: - [Complete ] [Mind]Delirium:Meningitis cerebrospinalis, encephalitis, in: Is the extravasation of blood into the subarachoid space particularly of the basal cisterns and into the cerebrospinal fluid pathways. C/f Worst of all headaches Abrupt onset of headache associated with photophobia and stiff neck Focal neurological defecits such as hemiparesis or dilated pupil Typically occurs at 50 to 60 yrs of age with a high mortality rate of 35%. Warning leak – minor leaks hours or days prior to the major haemorrhage often misdiagnosed as simple headaches or migraine. Commonly caused by ruptured aneurysm,atreriovenous malformation,hypertension or trauma to the circle of Willis (often at MCA).Trauma is the most common cause.Rarely tumors and blood dyscrasias also become the cause. D/d : Intracerbral haematoma,Meningitis,benign cephalagia. Imaging – CT Scan is used to establish the diagnosis in 95% cases.This scan demonstrates blood in the cisterns and may help to localize the source of haemorrage.It can used for ruling out mass effect so that LP can be done safely.Blood appears white in non contrast CT. An immediate LP is done if CT is negative to look for RBCs,Xanthochromasia and elevated ICP. Angiography is performed to localize the source of bleeding once SAH is confirmed. - Cerebral ischemia - Acute hydrocephalus [Complete ] [Head]Cerebral hemorrhage:Subarachnoid: Leakage of CSF Fistulous communications may develop between the subarachnoid space and paranasal sinuses or middle ear following head injury,raised ICP due to pituiutary tumour resulting in CSF leakage. CSF ottorrhea – Fractures in the floor of the middle cranial fossae may result in CSF leakage from external acoustic meatus. CSF rhinorrhoea – Fractures in the floor of the anterior cranial fossae may involve the cribriform plate of ethmoid resulting in CSF leakage through nose. CSF can be distinguished from mucus by testing its Glucose levels.But Protein electrophoresis with immunofixation for transferring is a non invasive and highly specific test.CSF will show two isoform bands while other body fluids and secretions lack the second form. Recent research indicates that there may be a pathogenic relationship between the degenerative changes of the cerebral cortex and those of the choroid plexus. Moreover, some research indicates that degenerative fibrillary changes in the plexus are one of the earliest manifestations of Alzheimer’s disease.Furthermore, in alzheimers disease, molecular modifications suggest that the transport and secretion of major molecules are altered in the brain. This may consequently be the result of alterations of the basement membrane of epithelial cells in the choroid plexus.Cells of the choroid plexus can also become cancerous. Although tumours of the choroid plexus are rare and constitute less than 1% of all brain tumours, it is one of the most frequent brain tumours in infants (up to 15%). Interestingly, scientific study of CAT scans of the ventricles in the late 1970s revolutionized the study of mental illness. Researchers found that patients with schizophrenia had enlarged ventricles compared to healthy subjects. This became the first “evidence” that mental illness was biological in origin and led to a reinvigoration of the study of such conditions via modern scientific techniques	2	17	0	0	1	0.684678	1	7,018
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 groupedor classifiedaccording 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	5,634
\|Classification and external resources\| Template:Personality disorders sidebar Personality disorders, formerly referred to as character disorders, are a class of personality types and behaviors that the American Psychiatric Association (APA) defines as "an enduring pattern of inner experience and behavior that deviates markedly from the expectations of the culture of the individual who exhibits it". Personality disorders are noted on Axis II of the Diagnostic and Statistical Manual of Mental Disorders or DSM-IV-TR (fourth edition, text revision) of the American Psychiatric Association. Personality disorders are also defined by the International Statistical Classification of Diseases and Related Health Problems (ICD-10), which is published by the World Health Organization. Personality disorders are categorized in ICD-10 Chapter V: Mental and behavioural disorders, specifically under Mental and behavioral disorders: 28F60-F69.29 Disorders of adult personality and behavior. These behavioral patterns in personality disorders are typically associated with severe disturbances in the behavioral tendencies of an individual, usually involving several areas of the personality, and are nearly always associated with considerable personal and social disruption. Additionally, personality disorders are inflexible and pervasive across many situations, due in large part to the fact that such behavior is ego-syntonic (i.e. the patterns are consistent with the ego integrity of the individual) and are, therefore, perceived to be appropriate by that individual. This behavior can result in the client adopting maladaptive coping skills, which may lead to personal problems that induce extreme anxiety, distress and depression in clients. The onset of these patterns of behavior can typically be traced back to late adolescence and the beginning of adulthood and, in rarer instances, childhood. It is therefore unlikely that a diagnosis of personality disorder will be appropriate before the age of 16 or 17 years. General diagnostic guidelines applying to all personality disorders are presented below; supplementary descriptions are provided with each of the subtypes. Diagnosis of personality disorders can be very subjective; however, inflexible and pervasive behavioral patterns often cause serious personal and social difficulties, as well as a general functional impairment. Rigid and ongoing patterns of feeling, thinking and behavior are said to be caused by underlying belief systems and these systems are referred to as fixed fantasies or "dysfunctional schemata" (Cognitive modules). World Health OrganizationEdit - (F60.) Specific personality disorders - (F60.0) Paranoid personality disorder - (F60.1) Schizoid personality disorder - (F60.2) Antisocial personality disorder - (F60.3) Borderline personality disorder - (F60.4) Histrionic personality disorder - (F60.5) Obsessive–compulsive personality disorder - (F60.6) Anxious (avoidant) personality disorder - (F60.7) Dependent personality disorder - (F60.8) Other specific personality disorders - (F60.9) Personality disorder, unspecified - (F61.) Mixed and other personality disorders The DSM-IV lists ten personality disorders, grouped into three clusters in Axis II. The DSM also contains a category for behavioral patterns that do not match these ten disorders, but nevertheless exhibit characteristics of a personality disorder. This category is labeled Personality disorder not otherwise specified. Cluster A (odd or eccentric disorders) Edit - Paranoid personality disorder (DSM-IV code 301.0): characterized by irrational suspicions and mistrust of others. - Schizoid personality disorder (DSM-IV code 301.20): lack of interest in social relationships, seeing no point in sharing time with others, anhedonia, introspection. - Schizotypal personality disorder (DSM-IV code 301.22): characterized by odd behavior or thinking. Cluster B (dramatic, emotional or erratic disorders) Edit - Antisocial personality disorder (DSM-IV code 301.7): a pervasive disregard for the law and the rights of others. - Borderline personality disorder (DSM-IV code 301.83): extreme "black and white" thinking, instability in relationships, self-image, identity and behavior often leading to self-harm and impulsivity. Borderline personality disorder occurs in 3 times as many females as males - Histrionic personality disorder (DSM-IV code 301.50): pervasive attention-seeking behavior including inappropriate sexual seductiveness and shallow or exaggerated emotions. - Narcissistic personality disorder (DSM-IV code 301.81): a pervasive pattern of grandiosity, need for admiration, and a lack of empathy. Cluster C (anxious or fearful disorders)Edit - Avoidant personality disorder (DSM-IV code 301.82): social inhibition, feelings of inadequacy, extreme sensitivity to negative evaluation and avoidance of social interaction. - Dependent personality disorder (DSM-IV code 301.6): pervasive psychological dependence on other people. - Obsessive-compulsive personality disorder (not the same as obsessive-compulsive disorder) (DSM-IV code 301.4): characterized by rigid conformity to rules, moral codes and excessive orderliness. Appendix B: Criteria Sets and Axes Provided for Further StudyEdit - Depressive personality disorder - is a pervasive pattern of depressive cognitions and behaviors beginning by early adulthood. - Passive-aggressive personality disorder (negativististic personality disorder) - is a pattern of negative attitudes and passive resistance in interpersonal situations. The following disorders are still considered to be valid disorders by Millon. They were in DSM-III-R but were deleted from DSM-IV. Both appeared in an appendix entitled “Proposed diagnostic categories needing further study”, and so did not have any concrete diagnostic criteria. - Sadistic personality disorder - is a pervasive pattern of cruel, demeaning and aggressive behavior. - Self-defeating personality disorder (masochistic personality disorder) - is characterised by behaviour consequently undermining the person's pleasure and goals. A study of almost 600 male college students, averaging almost 30 years of age and who were not drawn from a clinical sample, examined the relationship between childhood experiences of sexual and physical abuse and currently reported personality disorder symptoms. Childhood abuse histories were found to be definitively associated with greater levels of symptomatology. Severity of abuse was found to be statistically significant, but clinically negligible, in symptomatology variance spread over Cluster A, B and C scales Child abuse and neglect consistently evidence themselves as antecedent risks to the development of personality disorders in adulthood. In the following study, efforts were taken to match retrospective reports of abuse with a clinical population that had demonstrated psychopathology from childhood to adulthood who were later found to have experienced abuse and neglect. The sexually abused group demonstrated the most consistently elevated patterns of psychopathology. Officially verified physical abuse showed an extremely strong role in the development of antisocial and impulsive behavior. On the other hand, cases of abuse of the neglectful type that created childhood pathology were found to be subject to partial remission in adulthood. According to ICD-10, the diagnosis of a personality disorder must satisfy the following general criteria, in addition to the specific criteria listed under the specific personality disorder under consideration: - There is evidence that the individual's characteristic and enduring patterns of inner experience and behaviour as a whole deviate markedly from the culturally expected and accepted range (or "norm"). Such deviation must be manifest in more than one of the following areas: - cognition (i.e., ways of perceiving and interpreting things, people, and events; forming attitudes and images of self and others); - affectivity (range, intensity, and appropriateness of emotional arousal and response); - control over impulses and gratification of needs; - manner of relating to others and of handling interpersonal situations. - The deviation must manifest itself pervasively as behaviour that is inflexible, maladaptive, or otherwise dysfunctional across a broad range of personal and social situations (i.e., not being limited to one specific "triggering" stimulus or situation). - There is personal distress, or adverse impact on the social environment, or both, clearly attributable to the behaviour referred to in criterion 2. - There must be evidence that the deviation is stable and of long duration, having its onset in late childhood or adolescence. - The deviation cannot be explained as a manifestation or consequence of other adult mental disorders, although episodic or chronic conditions from sections F00-F59 or F70-F79 of this classification may coexist with, or be superimposed upon, the deviation. - Organic brain disease, injury, or dysfunction must be excluded as the possible cause of the deviation. (If an organic causation is demonstrable, category F07.- should be used.) In children and adolescentsEdit Early stages and preliminary forms of personality disorders need a multi-dimensional and early treatment approach. Personality development disorder is considered to be a childhood risk factor or early stage of a later personality disorder in adulthood. In executives Edit In 2005, psychologists Belinda Board and Katarina Fritzon at the University of Surrey, UK, interviewed and gave personality tests to high-level British executives and compared their profiles with those of criminal psychiatric patients at Broadmoor Hospital in the UK. They found that three out of eleven personality disorders were actually more common in executives than in the disturbed criminals: - Histrionic personality disorder: including superficial charm, insincerity, egocentricity and manipulation - Narcissistic personality disorder: including grandiosity, self-focused lack of empathy for others, exploitativeness and independence. - Obsessive-compulsive personality disorder: including perfectionism, excessive devotion to work, rigidity, stubbornness and dictatorial tendencies. - ↑ 1.0 1.1 Diagnostic and Statistical Manual of Mental Disorders - ↑ Other authorities echo the importance of deviation from social expectations in personality disorder diagnosis, e.g. Berrios, G E (1993) European views on personality disorders: a conceptual history. Comprehensive Psychiatry 34: 14-30 - ↑ 3.0 3.1 Millon, Theodore; Roger D. Davis (1996). Disorders of Personality: DSM-IV and Beyond. New York: John Wiley & Sons, Inc.. pp. 226. ISBN 0-471-01186-x. - ↑ Kernberg, O. 1984. Severe Personality Disorders. New Haven, CT: Yale University Press - ↑ Hartig C, Widger T gender differences in the diagnosis of mental disorders: conclusions and controversies of the DSM-IV. Psychological bullentin 1998;123 PP260-278 - ↑ "Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision". psychiatryonline.com. doi:10.1176/appi.books.9780890423349.5088. http://www.psychiatryonline.com/content.aspx?aID=5088. Retrieved 25 November 2010. - ↑ 7.0 7.1 Millon, Theodore, Personality Disorders in Modern Life, 2004 - ↑ Fuller, AK, Blashfield, RK, Miller, M, Hester, T Sadistic and self-defeating personality disorder criteria in a rural clinic sample Journal of Clinical Psychology, 48(6), 827-831 (2006) - ↑ Miller, P. M. & Lisak, D. (1999). "Associations Between Childhood Abuse and Personality Disorder Symptoms in College Males". Journal of Interpersonal Violence 14: 642. doi:10.1177/088626099014006005. http://jiv.sagepub.com/cgi/content/abstract/14/6/642. Retrieved May 25, 2010. - ↑ 10.0 10.1 Cohen, Patricia, Brown, Jocelyn, Smailes, Elizabeth. "Child Abuse and Neglect and the Development of Mental Disorders in the General Population" Development and Psychopathology. 2001. Vol 13, No 4, pp981-999. ISSN 0954-5794 - ↑ Board, Belinda Jane; Fritzon, Katarina (2005). "Disordered personalities at work". Psychology Crime and Law 11: 17. doi:10.1080/10683160310001634304. - American Psychiatric Association. (2000). Diagnostic and Statistical Manual of Mental Disorders. 4th ed. (text revision). (DSM-IV-TR). Arlington, VA. - Häcker, H. O. Stapf (2004). Dorsch Psychologisches Wörterbuch, Verlag Hans Huber, Bern - Marshall, W. & Serin, R. (1997) Personality Disorders. In Sm.M. Turner & R. Hersen (Eds.) Adult Psychopathology and Diagnosis. New York: Wiley. 508-541 - Murphy, N. & McVey, D. (2010) Treating Severe Personality Disorder: Creating Robust Services for Clients with Complex Mental Health Needs. London: Routledge - Millon, Theodore (and Roger D. Davis, contributor) - Disorders of Personality: DSM IV and Beyond - 2nd ed. - New York, John Wiley and Sons, 1995 ISBN 0-471-01186-X - Yudofsky, Stuart C. M.D. (2005) Fatal Flaws: Navigating Destructive Relationships With People With Disorders of Personality and Character, by ISBN 1-58562-214-1 - Interview with Dr. Martha Stout, author of The Sociopath Next Door on the Living Hero podcast, November 2010. - The Institute for Advanced Studies in Personology and Psychopathology the official website for Theodore Millon, Ph.D., D.Sc. - Personality Disorders Foundation - National Personality Disorder website for England - Dangerous severe personality disorder - National Mental Health Association Personality Disorder Fact Sheet - Personality Diagnostic Questionnaire (PDQ) web site - Personality Disorders information leaflet from mental health charity The Royal College of Psychiatrists bar:Persönlichkeitsstörung ca:Trastorn de la personalitat cs:Porucha osobnosti da:Personlighedsforstyrrelse de:Persönlichkeitsstörung es:Trastorno de personalidad fa:اختلال شخصیت fr:Trouble de la personnalité ga:Neamhord pearsantachta gl:Trastorno de personalidade ko:인격장애 it:Disturbo di personalità he:הפרעת אישיות lt:Asmenybės sutrikimas nl:Persoonlijkheidsstoornis ja:人格障害 no:Personlighetsforstyrrelse pl:Zaburzenie osobowości pt:Transtorno de personalidade ru:Расстройство личности simple:Personality disorder sk:Porucha osobnosti ta:ஆளுமைச் சிதைவு fi:Persoonallisuushäiriöt sv:Personlighetsstörning tr:Kişilik bozukluğu vi:Rối loạn nhân cách zh:人格障礙	3	8	2	0	6	0.496658	8	3,286
This week Dr. Doreen Granpeesheh breaks down the autism diagnosis criteria in the new DSM-V (Diagnostic and Statistical Manual of Mental Disorders), to be put into affect May 22nd, 2013. Language delays no longer part of diagnostic criteria for autism nac17.Filed Under: Special Needs Memoir, Disability Support and Science Tagged With: DSM 5 and autism, DSM 5 criteria, DSM-V criteria for ASD. Revised DSM-5 Diagnostic Criteria for Autism Spectrum Disorder. Autism Diagnosis Criteria in the DSM-V. Autism Spectrum Disorder and DSM-5 - Presented by Martin Lubetsky, MD. Tools: DSM-IV Criteria for ASDs. 299.00 Autistic Disorder.For example, this category includes "atypical autism" --presentations that do not meet the criteria for autistic disorder because of late age of onset, atypical symptomatology, or subthreshold symptomatology, or all of these. The Medical/Psychiatric Diagnosis of Autism: The DSM-V Criteria. The American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders is the main diagnostic reference used by mental health professionals and insurance providers in the United States. Between the DSM-III and the DSM-III-R criteria for autism, there were some tremendous differences.In the DSM-V, in order to be diagnosed as autistic, an individual must meet all markers of impairment of social interaction and communication, as well as at least 2 signs of repetitive behavior. The American Psychiatric Associations Diagnostic and Statistical Manual, Fifth Edition ( DSM-5) provides standardized criteria to help diagnose ASD. Diagnostic Criteria for 299.00 Autism Spectrum Disorder. Changes to the DSM Autism Diagnostic Criteria. By Leanne Tull, BCBA. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) debuted at the American Psychiatric Association (APA) annual meeting in May 2013. Starting in May of 2013, the American Psychiatric Association (APA) released the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). One of the major changes made in the DSM-V was the diagnostic criterion for Autism Spectrum Disorders (ASDs). South West Autism Network DSM-5 Diagnostic Criteria. Page 1. D. Symptoms cause clinically significant impairment in social, occupational, or other important areas of current functioning. Will the new Diagnostic Criteria for Autism Deprive Children of Services They Need?With the new DSM V criteria, 91 of the children qualified for a diagnosis, exhibiting six or more of twelve specified behaviors. The criteria for diagnosis of autism are outlined in the Diagnostic and Statistical Manual-V (DSM-V), a publication of the American Psychiatric Association that describes and classifies all developmental and behavioral health disorders. The latest edition of the Diagnostic and Statistical Manual of Mental Disorders , called the DSM-V, includes some significant changes to diagnostic criteria for autism, grouping several previously separate disorders under one umbrella. SoI Was Reading About the Proposed Changes to the Autism Diagnostic Criteria in the DSM-V. I thought that I would be steadfastly opposed to the propose changes for autism diagnostic criteria. DSM IV DSM V Autistic Disorder, Aspergers Disorder, and PDD-NOS replaced with Autism. Spectrum Disorder (ASD). Individuals who have marked deficits in social communication, but whose symptoms do not otherwise meet criteria for autism spectrum disorder, should be evaluated Those findings were preliminary and controversial, but further worrisome conference reports trickled in, all suggesting that the new autism diagnostic criteria proposed for the DSM-5 would exclude a good-sized percentage of people currently diagnosed on the autism spectrum. What is the DSM-V Criteria? For some diagnoses, the DSM-V has merged all of the formerly individual diagnoses, such as Childhood Disintegrative Disorder, Aspergers, Autistic Disorder, and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS), into two separate diagnoses: Autism There is so much pathologized language that presents all behavior as negative as well as being difficult to understand. Thus, I have taken the DSM-V criteria for autism and broken them down into examples of how each criteria can be met. Autism Spectrum Disorder in DSM-5. Brian Reichow reichowuchc.edu. Comments regarding classification Diagnostic history of autism Objectives of the DSM-5 revision DSM-5 Criteria and differences from DSM-IV Evaluating diagnostic changes associated with DSM-5 Potential Impact Dsm V Criteria For Autism , Here at www.galleryhip.com you will find The Hippest Pics that will delight inspire you.DSM 5 And Autism Autism Sp 63 Best DSM IV Images On P Comparing Diagnostic Outco DSM 5 Criteria And ASD Pre A proposed revision to the DSM-IV criteria for a diagnosis of autism had critics charging that many patients with autism spectrum disorders would no longer qualify for their diagnoses and would lose access to government services. Editor-In-Chief: C. Michael Gibson, M.S M.D. Note: Individuals with a well-established DSM-IV diagnosis of autistic disorder, Aspergers disorder, or pervasive developmental disorder not otherwise specified should be given the diagnosis of autism spectrum disorder. Diagnostic Criteria for Aspergers Disorder. Retts Disorder Childhood Disintegrative Disorder.PDD-NOS. DSM-V .2013. Category change. Neurodevelopmental Disorders. Autism Spectrum Disorder. Diagnostic Criteria for 299.00 Autistic Disorder. [The following is from Diagnostic and Statistical Manual of Mental Disorders: DSM IV ].(III) The disturbance is not better accounted for by Retts Disorder or Childhood Disintegrative Disorder. Sensitivity and specificity of proposed DSM-5 diagnostic criteria for autism spectrum disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 51(4), 368-383. 7Taheri, A Perry, A. (2012). In our class we have talked and researched a lot on how the Aspergers community has responded to the changing criteria in the DSM-V (both positive and negative).2. Are you aware of the changes being made to the diagnostic criteria for Autism in the new DSM-5? This week Dr. Doreen Granpeesheh breaks down the autism diagnosis criteria in the new DSM-V (Diagnostic and Statistical Manual of Mental Disorders), to be put into affect May 22nd, 2013. I finally had a name for my difficulties. This will not change under the new DSM-V because I am clearly within the new diagnostic guidelines for Autism Spectrum Disorder. In fact, I actually fit those criteria more accurately than the previous. DSM-5 Criteria for Autism Spectrum Disorders. An individual must meet criteria A, B, C and D: A. Persistent deficits in social communication and social interaction across contexts, not accounted for by general developmental delays, and manifest by all 3 of theDSM-V Criteria. New to the Center? New Diagnostic Criteria for Autism Spectrum Disorder.DSM-V Changes for Autism Spectrum Disorders. The latest revision of the DSM will be released in May of 2013, but many practitioners are already working off of the proposed revisions. 3. The DSM V criteria for Autism Spectrum Disorder (ASD). The full diagnostic criteria for the pervasive developmental disorders are outlined below.3. The DSMV V criteria for ASD 4. What is PDD and Aspergers disorder? This week Dr. Doreen Granpeesheh breaks down the autism diagnosis criteria in the new DSM-V (Diagnostic and Statistical Manual of Mental Disorders), to be UCLA CART "Autism 2014" Symposium, Jan 31, 2014 Revised DSM-5 Diagnostic Criteria for Autism Spectrum DisorderThis week Dr. Doreen Granpeesheh breaks down the autism diagnosis criteria in the new DSM-V (Diagnostic and Statistical Manual of Mental Disorders), to be DSM-5 (DSM-V) Diagnostic Criteria. young dsm-5: the new diagnostic criteria introducing the dsm-5 diagnostic criteria for autism spectrum disorder what is the dsm-5?autism name) clinical diagnosis: dsm-5 checklist dsm-5 criteria autism spectrumdsm-5 asd moves forward. Autism Spectrum Disorder 299.00 (F84.0) (DSM-V, American Psychiatric Association, 2013 Retrieved from Autism Speaks: httpSensitivity and Specificity of Proposed DSM-5 Diagnostic Criteria for Autism Spectrum Disorder. The criteria for meeting an autism diagnosis will become considerably stricter. Under the current criteria, a person can qualify for the diagnosis by exhibiting 6 or more of 12 behaviors under the proposed criteria in the DSM-V Diagnostic criteria for autism spectrum disorders Screening/referral Associated medical problems Treatments/therapies. Do not meet criteria for either Autistic Disorder or Aspergers Disorder. Proposed DSM-V Criteria for Autism Spectrum Disorder. The English dsm v autism criteria pdf in this article or section may not be easy for everybody to understand.Diagnostic criteria: The requirements that need to be met before the condition is diagnosed. 3d, A new diagnostic html doh pregnancy Safeminds-impact-of-the-dsm-- criteria-for-asd-community-update-may- cached similarbecause autism similar dec asd classification Autism speaks is dsm-v-new-diagnostic-criteria-for-autism-spectrum-disorder-asd cachedin DSM-5 Diagnostic Criteria for ASD, 2013. Autism Spectrum Disorder Must meet criteria A, B, C, and D: A. Persistent deficits in social communication and social interaction across multiple contexts, as manifested by the following, currently or by history (examples are illustrative, not exhaustive): 1 The current diagnostic criteria for Autism (299.0 in the DSM IV) is pretty complicated (read it here). One must have several symptoms off of one checklist, and several off of a different list, and one off of a third list etc. About Autism Spectrum Disorder.DSM IV Criteria for Autistic Disorder. ICD-10 Criteria for Autism. PDD-NOS. Childhood Disintegrative Disorder.Acknowledgements: Dr. Catherine Rice and others associated with the CDC ADDM (Centers for Disease Control and Prevention Autism and.Dr. Rice, Dr. Catherine Cheely, and Dr. Catherine Lord collaborated with Dr. Carpenter in the categorization of behaviors relative to DSM 5 criteria. Autism Speaks is pleased to provide the full-text of the diagnostic criteria for autism spectrum disorder (ASD) and the related diagnosis of social communication disorder (SCD), as they appear in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). 1) DSM-5 criteria for autism do not disqualify significant numbers of individuals who now meet DSM-IV criteria for Aspergers or related disorders from receiving or retaining a diagnosis of Autism Spectrum Disorder, and that. The term Autism Spectrum Disorder, which is commonly used by parents and autism professionals, will also be used as a synonym for Autistic Disorder. The following is the proposed revision diagnostic criteria for Autistic Disorder in the DSM-V DSM-V Criteria for ASD. (The following is from the Diagnostic and Statistical Manual of Mental Disorders: DSM V). Autism Spectrum Disorder (ASD) 299.00 (F84.0). Asperger syndrome is now part of the Autism Spectrum criteria officially.One of their comments is that there are no diagnostic tools by which to measure the new DSM V criteria for Autism Spectrum Conditions. Keywords: Autism spectrum disorder DSM-IV Diagnostic criteria. ABSTRACT. The DSM-V-committee has recently published proposed diagnostic criteria for autism spectrum disorders. Dsm 4 pervasive developmental disorders. Why make Changes in the ASD criteria for DSM 5?Why are people upset about these changes? What about children under 3? Dsm V and autism spectrum disorder criteria	2	11	0	0	2	0.474872	2	2,475
The flashcards below were created by user on FreezingBlue Flashcards. What is the most important factor resulting in thrombosis? Reduction in speed of blood flow. Cardiac failure is a result of stenosis of which valve in the heart? - Mitral valve stenosis: narrowing of the left AV valve. - = more blood accumulates in the left aorta = decreased speed of blood leaving the heart = thrombulous. - Ball-valve thrombus: a thrombi in circulation (thromboembolite) gets stuck in the atria, blocking the AV valve. True or false: polycythemia results in decreased blood viscosity. - False: polycythemia results in increased blood viscosity. - A/k/a: erythremia = overproduction of RBC's. - 7-8 million in 1 square mm of blood (vs the normal 5 million). Is blood flow slower in veins or arteries? - Veins: lower blood pressure = slower rate. - Veins are dependent upon muscular contractions to get the blood back to the heart. What are the 3 risk factors for thrombosis? - 1. Physical inactivity. - 2. Varicose veins. - 3. Blood hypercoagulation. Sequelae of thrombosis: - 1. Resolution: dissolving of a thrombus = most benign. - 2. Organization: elimination of blood clot & tissue debris via pahgocytosis = replaced by CT. - 3. Recanalization: formation of canals through a thrombus (angiogenesis). - 4. Propagation: enlargement of thrombus in the veins, occurring near the branching of veins, (most commonly in the legs). - 5. Infarction: an area of necrosis due to hypoxia. What type of necrosis occurs in the heart? Strokes = liquefactive necrosis: replaced with neural glia = area of gliosis. - Coagulative necrosis: preserves the size & shape of the necrotic tissue, allowing for healing to occur. - The necrotic tissue is replaces with CT. Which step in the sequelae of thombosis is responsible for returning functioning back to normal? - Dissolving of a thrombus activates the fibrinolytic anticoagulation system (plasminogen -> plasmin) to take care of the thrmobus. What is the most common cause of infarction? - Myocardial infarction - coagulative necrosis. - Ischemic stroke (brain infarct) = liquefactive necrosis. - Stroke + myocardial infarct = most common cause of death in the U.S. Name 2 examples of vasculitis. - 1. Temporal arteritis ("giant cell arteritis," "horton's disease"). - 2. Polymyalgia rheumatica: dramatic pain in the upper & lower extremities, commonly associated with Horton's Disease. Horton's Disease generally involves which 6 arteries? - 1. Superficial temporal artery. - 2. Cerebral artery. - 3. Opthalmic artery. - 4. Vertebral artery. - 5. Arch of aorta. - 6. Thoracic aorta. - The most common type of vasculitis. - Chronic granulomatous inflammation of the vascular wall. - =headaches & blindness in the elderly. Where do fat emboli usually wind up? - In the lungs, causing minor respiratory problems. - Fat embolus: fat gets into the venous system via fractured bones releasing yellow marrow. Define air lock. Air lock: following an air embolus, compressible air does not leave the heart upon contraction, also reducing the flow of blood leaving the heart. Rest patient on their RIGHT side Which type of hernia protrudes through the esophageal hiatus of the diaphragm? - Paraesophageal hernia. - = diaphragm may pinch veins to the stomach thus preventing blood flow = gangrenous necrosis. What is another name for sheeham syndrome? Post-partum syndrome: after delivery leads to anterior pituitary infarct. True or false: the liver is most vulnerable to hypoxia. False: the brain & myocaridum are most vulnerable... the liver is not vulnerable. Why are the lungs well protected from infarction? - 1. Clot retraction: reduction in size of the thrombus. - 2. Double blood supply to the lungs: supplied from the pulmonary system & the independent bronchial arteries. - 3. Fibrinolytic activity. Which vitamin maintains membrane conduction of neuron cells & axons? - Thiamin (Vitamin B1). - Think (th1am1n). What are the 3 diseases associated with B1 deficiency? - 1. Dry beriberi, peripheral polyneuropathy: symmetrical loss of peripheral NS myelenation = wrist drop, foot frop, & first toe drop. - 2. Wet beriberi, cardiovascular syndrome: peripheral vasodialation (loss of sympathetic vasoconstriction). - 3. Wernicke Korsakoff syndrome: Opthalmoplegia, apathy, listlessness, disorientation... Korasakoff’s psychosis, retrograde amnesia, confabulation. What is the term used to describe retrograde amnesia, the inability to accept new information, & non-stop talking (confabulation)? Beriberi is associated with a deficiency of which vitamin? Dry Beriberi is associated with which pathological condition? Wernicke-Koraskoff Syndrome is associated with deficiency of which vitamin? Which vitamin is also known as riboflavin? Ariboflavinosis is characterized by what 4 symptoms? - Ariboflavinosis: lack of B2. - 1. Cheilosis (chelitis): cracks in corner of mouth which get infected. - 2. Glossitis: inflammation of tongue. - 3. Superficial interstitial keratitis: scar tissue in the corneas. - 4. Dermatitis: rash on cheeks, behind the ears, around the naso-labial folds, scrotum, & vulva. True or false: vitamin B2 is associated with diseases of the nervous system. False: B2 & B6 are not associated with diseases of the nervous system. Name 3 a/k/a's for Vitamin B3. - 1. Niacin. - 2. Nicotinic acid. - 3. Nicotinamide. B3 is synthesized in small amounts by the human body. True or false? Name 3 functions of Niacin. - 1. Vasodialation. - 2. Prevention of LDL production in the liver (sometimes used to atherosclerosis). - 3. Antioxidant. Which disease is also known as the "4 D's?" May show symptoms as VB2 deficiency. - Pellegra: lack of B3 (niacin) = rough/dry skin. - 1. Dermatitis: rough red skin... Cassal’s necklace. - 2. Diarrhea: resulting in atrophy of columnar epithelial cells, submucosal inflammation, ulcerations. - 3. Dementia: affects grey matter cerebral cells resulting in weakness, dizziness, headache, & depression. - 4. Death. Which vitamin is associated with Pellagra? What is the major function of Pyrodoxine? - Pyrodoxine (B6): metabolism of epithelial cells. - Made of pyrodoxine, pyridoxal, & pyridoxamine. - If you heat the food, B6 undergoes destruction. Which patients are at risk for developing a B6 deficiency? - 1. Alcoholics. - 2. Pregnant women. - 3. Medicated patients... TB, birth control pills, Wilson's Disease, Systemic Sclerosis. Which drug interferes with the functions of both B3 & B6? Izoniazid: medication used to treat TB. Name the 8 pathologies associated with B6 deficiencies. - 1. Cheilosis: corners of mouth turn white (also seen with B2). - 2. Glossitis: (also seen with B2&3). - 3. Brain growth impairment. - 4. Seborrheic dermatitis: wet scales in hair. - 5. Peripheral polyneuropathy: (also seen w/ B1&12). - 6. Convulsive seizures in infants. - 7. Promotion of oxalate kidney stones: decreased epithelial cell metabolism results in a nidus (network of organic material). - 8. Hypochromic anemia: less hemoglobin in RBC's. Cheilosis & glossitis result from deficiency of which 2 vitamins? - 1. B2 (riboflavin). - 2. B6 (pyrodoxine). Name 2 a/k/a's for Vitamin B12. - Vitamin B12: Cyan, Cobalamin. - B12 is bound to proteins. Is B12 absorbed into the body via an intrinsic or extrinsic factor? - Intrinsic factor (of Cassel): B12 is picked up in the duodenum via the intrinsic factor. - Intrinsic factor is produced by parietal cells in the stomach wall, flows into duodenum, SI, then the ileum… the ileum has receptors for the intrinsic factor, allowing release into the blood flow. What are 6 predisposing factors for a B12 deficiency? - 1. Malabsorption. - 2. Vegetarians. - 3. Chronic gastritis. - 4. Following gastrectomy. - 5. Regional enteriris. - 6. Tropical sprue. Name 3 ways a B12 deficiency can occur. - 1. Blocking antibodies: prohibits intrinsic factor from binding to B12 or blocks the intrinsic factor from binding to receptors in the ileum... Type II hypersensitivity reaction... Autoimmune. - 2. Different antibodies: blocks binding of intrinsic factor & B12... Type II hypersensitivity reaction. - 3. Chronic autoimmune gastritis: inflammation of the stomach wall, selectively killing PARIETAL cells of the stomach... no intrinsic factor can produce this. Name 2 a/k/a's for Pernicious Anemia. - Pernicious anemia: one of the two megaloblastic anemias, interfering with hematopoiesis. - 1. Malignant Anemia. - 2. B12 Deficient Anemia. How does B12 play into pathology of the CNS? - Lack of B12 = demylenation of the posterior & lateral tracts of the spinal cord. - B12 maintinas the membranes of the nervous system. - Deficiency = demyelenation of the posterior & lateral tracts. - Results in ataxia in lower extremities initially. Cobalamin deficiency leads to pathology of which 2 systems of the body? - 1. Nervous system. - 2. Hematpoietic system.: macrocytosis, rigid cell membranes, hypersegmented neutrophils. B12 promotes the reduction of folic acid (folate, B9) into tetrahydropholate. THP promotes hematopoiesis. Note that B9 (folic acid) plays a role in the development of the neural tube in the embryo. - monofolate → reductase → tetrahydropholate (THF) → DNA. - *Vitamin B12: can restore THF so it’s active again. - (Methotrexate: inhibits reductase for treatment of cancer, Hodgkin’s disease, etc). - (folate → dihydrofolate→ tetrahydrofolate ↔ methylene-THF → methyl-THF). Deficiency of which 2 vitamins can lead to megaloblastic anemia? - 1. B12 deficiency. - 2. B9 (folic acid) deficiency. : production of RBC’s with very ridged membranes... RBC’s are much larger & they are unable to bend to fit through capillaries. - Boudeinyi WTF moment: …WBC’s are also involved… - …hypersegmented neutrophils: too many lobes.-cells are immature & undergo death earlier. - -pancitopenia: ……..glossitis, chelossis (cheilitis)… Name 4 functions of Vitamin C (ascorbic acid). - 1. Hydroxylation of procollagen (proline into hydroxyproline). - 2. Stimulation of protein formation. - 3. Provides strength for collagen fibers (via hydroxyproline). - 4. Antioxidant (free radical scavenger along with selenium & vitamin E). Name 3 results from ascorbic acid deficiency. - 1. Scurvy. - 2. Skeletal changes. - 3. Decreased wound healing: delayed wound healing because it takes a longer time to build the necessary connective tissue. Impairment of wound healing is associated with the deficiency of which vitamin? Which pathology is characterized by bone abnormalities in children, leg bowing (genu varus), hemorrhages, improper healing, loss of teeth/gingivitis, death of pupils, & an inward depression of the sternum of babies, subperiostal hematoma, & hemarthrosis? Development of subperiosteal hematomas are a manifestation of which vitamin deficiency? Vitamin C (ascorbic acid): scurvy. Vitamin C deficiency results in impaired function of which substance? - Retinol (Vit A) = rhodopsin. - Thiamine (B1) = myelin. - Vit K = prothrombin. Which vitamin actively participates in collagen synthesis (through the synthesis of its precursor, procollagen)? Ascorbic acid (vitamin C). Skeletal changes in scurvy are associated with disturbance of which process? Formation of osteoid matrix. Vitamin A consists of retinol, retinal, & reinoic acid, thus making it fat insoluble. True or false? False: vitamin A is fat soluble. 90% of Vitamin A is stored in the liver. This gives humans enough storage for how long? - 6 months. - Vitamin A is stored in the liver is Retinol. Which food is Provitamin A abundantly found in? Carrots via beta-carotene (a carotenoid). The synthetic substance 'Retenoid' has a close chemical formula to Vitamin A & is used to treat which pathology? - Psoriasis: the proretenoid activity serves as an anti-inflammatory medication. - However, Retenoids are actually very dangerous medications. What are the 3 main functions of Vitamin A? - 1. Maintaining normal vision in reduced light. - 2. Differentiation of specialized epithelial cells: via retinoic acid. - 3. Enhances immunity to infections. Which component of Vitamin A is responsible for maintaining normal vision in reduced light? - Retinal: used as a material for rhodopsin synthesis in the rods of the eye. - Rhodopsin: most light sensitive light pigment. Which component of Vitamin A is responsible for potentiating the differentiation of specialized epithelial cells in the human body? Retenoic acid: potentiates the differentiation of specialized epithelial cells (mainly mucus-secreting cells). Name 3 manifestations of Vitamin A deficiencies. - 1. Poor night vision. - 2. Squamous cell metaplasia: the replacement of normal epithelial cells with kereatinizing epithelia which cannot preform normally. - 3. Measles, pneumonia, or infectious diarrhea: 30% more likely to kill a patient with a Vitamin A deficiency. What are the 4 organs typically affected by squamous cell metaplasia? - 1. Eye: resulting in xeropthalmia (dry eyes) resulting in bitot's spots, corneal erosion, keratomalacia, & blindness. - 2. Urinary Tract: normal cells are sloughed off being replaced by keratinizing cells, thus forming a nidus (stone). - 3. Repsiratory tract: resulting in an increased susceptibility for secondary pulmonary infections. - 4. Adnexal glands: sebaceous glands resulting in follicular or papular dermatosis. Why does squamous cell metaplasia increase vulnerability to secondary pulmonary infections? Because normal epithelial cells have an immune function of brushing away foreigners with their villi, but keratinized epithelia have lost this function. Which is worse, hypervitaminoses A or hypovitaminoses A? Hypervitaminoses A: Vitamin A is not supposed to be in the body in high amounts, especially if it is synthetic. Name 7 manifestations of hypervitaminoses A. - 1. Increased ICP = headache, nausea/vomiting, papilledema. - 2. Weight loss. - 3. Bone pain & muscle pain. 4. Skin rash/dermatosis. - 5. Nausea/vomiting. - 6. Hyperostosis: too much bone growth (DISH: calcification/ALL). - 7. Hepatomegaly (enlarged liver) = liver fibrosis. Overdose of which vitamin results in hyperostosis? - Vitamin A. - Hyperostosis = DISH. Which vitamin is responsible for lowering mortality rate due to infectious diseases in children? Bitot's spots are characteristic with deficiency of which vitamin? The deficiency of which 2 vitamins results in kidney & bladder stones? What are the 2 a/k/a's for Vitamin E? - 1. Tocopherol. - 2. Alfa-tocopherol. What 2 things does Vitamin E specialize in protecting as a free radical scavenger? - 1. Nervous system: deficiency results in demyelenation of peripheral sensory nerves & the posterior columns. - 2. RBC's: deficiency results in anemia in children & babies. - May also result in impaired eye movements. Which 2 vitamins are considered antioxidants & free radical scavengers? - 1. Vitamin E. - 2. Vitamin C. - Sometimes B3 also. Vitamin E can be regenerated by which vitamin? Which vitamin is characterized by damage to the posterior column of the spinal cord, atrophy of DRG, demyelenation of peripheral sensory fibers, damage to the spinocerebellar tract leading to ataxia, abscence of DTR's, & loss of pain sensation? - Vitamin E. - DRG atrophy. - Periphreal sensory fiber demyelenation. - Abscence of DTR's. - Loss of pain sensation. Vitamin E prevents the formation of HDL's along with B3, C, A, & D. True or flase? False: prevents the formation of LDL's. Vitamin K plays a role in Koagulation by promoting the formation of which clotting factors in the liver? II (prothrombin), VII, IX (Christmas), & X. Which 2 vitamins are produced by the gut flora? Body = K, B2/3. - 1. Vitamin K. - 2. B2. - B3 is also synthesized in small amounts by the human body, via tryptophan. How does Vitamin K play a role in calcification of bone proteins? - Vitamin K promotes the formation of osteocalcin. - Vitamins involved with bone formation: C, K. Deficiency of Vitamin K may result from which 3 things? - 1. Fat malabsorption: vitamin K is fat soluble. - 2. Diffused liver disease. - 3. Long term intake of antibiotics. Vitamin K deficiencies are result in which 6 manifestations? - 1. Hemorrhagic disease of newborns: in first week of life since the gut flora is still producing vitamin K. - 2. Bleeding diathesis. - 3. Hemorrhages. - 4. Brusies (ecchymoses)/ hematomas. - 5. Melena: black poo. - 6. Gum bleeding. Hemorrhagic disease of newborns is associated with deficiency of which vitamin? Which vitamin accounts for the production of ostecalcin? Vitamin K: osteocalcin promotes calcification of bones. Deficiency of which vitamin results in a reduction of clotting factors synthesized in the liver? Look @ diagram of vitamins! - NS: B1, B12, E. - Body: B2, B3, K. - Epithelia: B6, A. - Anemia: B9, B12. - Free Rad's: B3, C, E. - C&G: B2, B6. - Kidneys: B6, A. - LDL: A, B3, C, D. - Bone: C, K. What does PEM stand for? - PEM: protein-energy malnutrition. - Range of clinical syndromes characterized by inadequate dietary intake of proteins & calories to meet the body’s needs. If a person is down to 80% of their normal body weight they have which condition? - Marasmus: a person is down to 60% or less of their body weight. - It is caused by lack of energy intake & protein containing foods. - The body begins to steal protein from the somatic protein compartment (skeletal muscles). - Results in emaciation (too thin) & growth retardation. - The head will appear to be too large for the body. - Serum albumin (protein carriers in blood) levels are normal, or slightly lower. Kwashiorkor patients have higher or lower protein deprivation in relation to calories? There is enough energy intake, but not enough protein intake. - Higher protein deficiency. - More common in Africa & SE Asia due to diets high in carbs & low in protein. Which protein compartment is affected in Kwashiorkor patients? - The visceral protein compartment. - Results in a decreased amount of albumins in the blood, thus reducing oncotic pressure resulting in generalized edema. Which comes first in Kwashiorkor patients, hypoalbumenia or fatty liver? - Steps of Kwashiorkor: - 1. Hypoalbuminemia. - 2. Generalized edema. - 3. Skin lesions: zones of hyperpigmentation, desqumation, hypopigmentation... flaky paint appearance. - 4. Hair changes: loss of color, straightening, fine texture. - 5. Fatty liver (steatosis): without proteins the liver cannot produce LDL's so FFA's build up causing fibrosis. - 6. Apathy, listlessness, anorexia. - 7. Defects in immunity, secondary infections. The prognosis is worse than with marasmus. Which disorder is caused predominately by insufficient dietary intake of calories? Which disease is characterized by ammenorrhea, thyroid pathology, arrthmias, hypokalmeia, osteoporosis, hypoalbuminemia, constipation, & sudden death? - Anorexia nervosa. - Note there are significant decreases in secretion of GRH, LH, & FSH. - Hypothyroidism = cold, listlessness, weakness, dry hair, etc. Which disease is characterized by amenorrhea 50% of the time, normal weight & GRH levels, esophageal cancer, espohageal rupture, hypokalemia, & pulmonary aspirations? Which type of hypersensitivty reaction is characterized by the relase of histamine & other vasoactive substances that are derived from mast cells? - Type I Hypersensitivity Reaction: affects vascular permeability & smooth muscles in various organs. - Associated with mast cells & basophils. - Mast cells: basophils fixed in the tissue, subepithelial areas. Which hypersensitivity reaction is associated with anaphalactic shock? - Type 1 hypersensitivity reaction: anaphalactic (allergic) reaction… anaphalactic shock. - Release of vasoactive amines & other mediators derived from the mast cells or basophils. - Affects vascular permeability & smooth muscles in various organs. Will the first exposure to an allergen result in a physiological reaction? No: the first reaction results in the degranulation of the cytosome within mast cells , thus allowing for allergic reactions in the future. - Type I Hypersensitivity Reaction Mechanism - Allergen goes into body --> activates CD4 & T Helper cells (TH2) --> secretion of IL-4 & 5 cytokines --> IgE antibody production & recruitment of eosinophils (& mast cells). What are the 4 functions of histamine? - 1. Vasodialation. - 2. Increased vessel permeability = swelling. - 3. Bronchospasm. - 4. Increased mucous production. Systemic anaphylaxis is characterized by a long onset. True or false? False: systemic anaphylaxis has a rapid onset of 1-2 minutes. A patient is getting a cavity filled. Unbeknownst to the doctor, they are allergic to novocaine. Name the 6 clinical manifestations which would occur rapidly. Is this reaction systemic or local? - 1. Itching. - 2. Hives (urticaria). - 3. Bronchospasm. - 4. Laryngeal edema. - 5. Nausea/vomiting/diarrhea. - 6. Vascular shock. A patient comes in to your office in the spring, complaining of seasonal allergies. Which type of reaction is this? And what are the possible 5 symptoms? - 1. Itching of the skin. - 2. Hives (urticaria). - 3. Hay fever. - 4. Atopic bronchial asthma. - 5. Rhinitis (runny nose). Which of the following disorders is an example of Type I Hypersensivity Reactions? A. Hemotransfusion reactions. B. Laryngeal edema. D. Graft rejection. - Which of the following disorders is an example of Type I Hypersensivity Reactions? - A. Hemotransfusion reactions: type II, complement dependent. - B. Laryngeal edema. - C. TB: type IV, delayed type hypersensitivity. - D. Graft rejection: type IV, cell-mediated cytotoxicity. Type I Hypersensitivity Reactions are associated with which class of immunoglobulins? Type II Hypersensitivity Reactions are mediated by which 2 types of immunoglobulins? - 1. IgG. - 2. IgM. - They are both directed at antigens on the body's own cells. How many types of reactions are associated with Type II Hypersensitivity Reactions? - 1. Complement dependent: hemotransfusion reactions, erythroblastosis fatalis, auto-immune diseases, & certain drug reactions. - 2. Antibody-dependent cell-mediated cytotoxicity: parasites, tumors. - 3. Antibody-mediated cellular dysfunction: Myasthenia Gravis, Hoshimoto's, Grave's Disease. Which 4 cells are associated with antibody-dependent cell-mediated cytotoxicity? - 1. Monocytes. - 2. Eosinophils. - 3. Neutrophils. - 4. Natural killers. Name 3 pathologies associated with Type II Antibody-Dependent Hypersensitivy Reactions. - 1. Myasthenia Gravis. - 2. Hoshimoto's. - 3. Grave's Disease. - Antibody dependent = antibody-mediated cellular dysfunction. What is the most common subtype for Type II Hypersensitivity Reactions? - Complement dependent: antibody attaches to the antigen & fragments into an Ab & Fc fragment. - Opsonization stops @ C3b, & is more favorable for phagocytosis. Name 2 pathologies associated with Type II Hypersensitivity Reactions. - 1. Erythroblastosis fetalis. - 2. Pernicious anemia. What is the name of the injection given to a Mom after delivery of her first Rh+ child to prevent erythroblastosis fetalis? - Rhogam: needs to be given after abortions as well. - 1st pregnancy: Mom Rh-, Baby Rh+... blood mixes @ birth... Mom develops Rh+ antibodies within the first 72 hours, & her body kills the cells. - 2nd pregnancy: Mom Rh-, Baby Rh+... blood mixes @ birth, antibodies get into baby = baby need blood transfusion. True or false: erythroblastosis fetalis could result from a scenario when mother is Rh-, & fetus is Rh+. Type II & Type III Hypersensitivity Reactions are very similar. How can you tell the difference? - Type II: fixed in tissue. - Type III: circulating in blood. What is the a/k/a for Type III Hypersensitivity Reactions? Immune Complex Mediated Type. Name 2 examples of Immune Complex Mediated Type Reactions: (Type III Hypersensitivity Reaction) - 1. Serum sickness. - 2. Arthus reaction: local Type III... Farmer's Lung. Vasculitis is usually associated with which type of hypersensitivity reactions? Type III. (Immune complex mediated type). Sidenote on trace elements: yay! - Iron: hypochromic, microcytic anemia. - Iodine: hypothyroidism, goiter. - Selenium: Keshan disease, myopathy, congestive cardiomyopathy, (also a free radical scavenger along with vitamins C & E). - Zinc: distinctive rash, acrodermatitis enteroptahica, anorexia/diarrhea, growth retardation, hypogonadism/infertility, impaired wound healing, impaired night vision, impaired immune function, depressed mental function. - Copper: muscle weakness, hypopigmentation, nueorological defects. What is an a/k/a for Type IV Hypersensitivity Reaction? - Cell Mediated = antibody independent mechanism. - Involves CD4 & CD8 lymphocytes. What are the 2 subdivision of Cell Mediated Hypersensitivity Reactions (Type IV)? - 1. Delayed Type Hypersensitivity: TB, contact dermatitis. - 2. Cell-Mediated Cytotoxicity: anti-viral, graft rejection, tumors. Which pathology is characteristic of Delayed Type (Type IV) Hypersensitivity Reactions? - TB (mycobacterium tuberculosis). - CD4 (T4) T-helper cells are activated by antigens. - T4 cells release cytokines which recruit macrophages. - The macrophages result in a granulomatous reaction. Describe the mechanism associated with Delayed Type (IV) Hypersensitivity Reactions. - CD4+ T Cells of the TH1 type - Recruitment of macrophages What are the 3 main functions of cell-mediated cytotoxicity reactions? - 1. Anti-tumor activity. - 2. Anti-viral activity. - 3. Graft rejection. - also immune suppression. Delayed-type hypersensitivity reactions are induced by sensitization of which of the following cells? - Delayed-type hypersensitivity reactions are induced by sensitization of which of the following cells? - A. Neutrophils. - B. B-cells. - C. T-helpers: type IV, delayed type hypersensitivity. - D. T-cytotoxic: type IV, cell-mediated cytotoxicity. Anaphalactyic: Type I. - 1.1) Systemic: bee sting... rapid developing. - 1.2) Local: asthma attack. Cytotoxic: "Antibody Dependent": Type II. Fixed in tissue. Triggered when anti-bodies attach to the surface of individual cells. - 2.1) Complement Dependent: most common of type II. - i) Blood transfusion. - ii) Erythroblastosis fetalis. - iii) Auto-immune hemolytic reactions. - iv) Certain drug reactions. - 2.2) ADCM (Anti-body Dependent Cell Mediated): involves NK & MAC. - i) Parasites. - ii) Tumors. - iii) Cells. - 2.3) AMCD (Antibody-Mediated Cellular Dysfunction): - i) MG. - ii) Grave's Disease. - iii) Hoshimoto's. Immune Complex Mediated: Type III. In blood circulation. Glomerulonephritis, RA, Lupus, Autoimmune Diseases. - 3.1) Local reaction: - i) Arthus reaction: Farmer's lung. - ii) Vasculitis. - 3.2) Systemic reaction: - i) Serum sickness. Delayed Hypersensitivity "Cell Mediated": Type IV. - 4.1) Delayed type: CD4/T4, marcrophages, granulomatous reaction. - i) TB. - ii) Contact dermatitis. - 4.2) Cell-mediated cytotoxicitiy: CD8/T8, Gamma IFN. - i) Anti-tumor. - ii) Anti-viral. - iii) Graft rejection. - iv) Immune supression. Which cell growth process occurs in response to increased demands? - Hypertrophy: process of cell & organ enlargement that occurs in response to increased demands. - Ex) Left ventricular hypertrophy resulting from systemic hypertension. Which term means shrinking of the cell (or organ) due to a lack of neuronal or endocrinological stimulation? - May also result from disease. True or false; the term "trophy" refers to the number of cells present. - False: trophy refers to the cell size. - Ex) Hypertrophy: the amount of cells are the same but they are bigger than they were before which makes the whole organ larger. Which term reefers to mitosis? - Plasia: referring to mitosis (new cells forming). - The formation of new cells makes the organ bigger. Does hyperplasia involve the enlargement of cell size? - No... Hyperplasia: the process of mitosis producing new cells, but only in quantities needed to meet a particular demand. - Hyperplasia is still considered normal or ok. Name 2 examples of hyperplasia. - 1. Increased amounts of glandular tissue in the female breast during pregnancy. - 2. Restoration of liver cells following liver resection. Which form of cell growth is characterized by a change in the type of cell? Metaplasia: a reversible condition in which there is replacement of normal cells by cells that aren't supposed to be there. Name 2 examples of metaplasia. - 1. Chronic gastritis: replacement of stomach columnar epithelial cells by intestinal type cells. - 2. Heavy smokers: replacement of columnar bronchial epithelial cells by stratified squamous cells. - Squamous epithelial cells: most important predisposing factor for lung cancer. Which form of cell growth is a precursor for neoplasm? Which type of cell growth is characterized by a loss in uniformity of the individual cells, as well as a loss of their architectural orientation? - Dysplasia: very close to neoplasia. Which type of cell growth do you see both normal & abnormal cells? What is the term used to describe the variability of cell size & shape, in contrast to regularity of the cell structure seen in normal tissue? - Larger more darkly stained nuclei. - Increased mitosis rates. Which 2 forms of cell growth display signs of pleomorphism? - 1. Neoplasia. - 2. Dysplasia. Name 3 characteristics of neoplsitic dysplasia. - 1. Larger more darkly stained nuclei. - 2. Increased mitosis rates = higher risk for cancer. - 3. Irreversible alteration of cell growth patterns. What is the term used to describe the uncontrolled mitosis of cells beyond normal anatomical boundaries due to the irreversible alteration of cell growth pattern? What is an a/k/a for neoplasm? - Neoplasia: tissue formation, involving the overgrowth of a tissue to form a neoplastic mass, of neoplasm, which is called tumor. - Cells are abnormal. - Polymorphic cells. What does aplasia mean? - Aplasia: the complete lack of organ development. - All cells are abnormal. Which type of cell growth results in structures that are immature & functionally deficient? ?????? : development that is inadequate, so that the resulting structure is immature & functionally deficient. Hypoplasia: inadequate development = immature & functionally deficient. ????? : the process of cell & organ enlargement that occurs in response to increased demands. Hypertrophy: cellular & organ enlargement due to increased demands. ????? : a loss in uniformity of the individual cells as well as a loss in their architectural orientation. Dysplasia: loss in uniformity & architectural orientation. ????? : lack of organ development. ????? : production of new cells, but only in quantities needed to meet a particular demand. Hyperplasia: new cells to meet a demand. ????? : change of the cell type. ????? : lack or reverse of cell differentiation. Anaplasia: the less mature (lack of cell differentiation) the tissue organ, the more malignant the cells are. Which of the following is NOT a characteristic of pleomorphism? A. Increased mitosis rates. B. Larger, more darkly stained nuclei. C. Uniformity of cell size & shape. D. Variability of cell size & shape. - Which of the following is NOT a characteristic of pleomorphism? - A. Increased mitosis rates. - B. Larger, more darkly stained nuclei. - C. Uniformity of cell size & shape. - D. Variability of cell size & shape. Pleomorphism is typical for which of the following? A. Benign tumor. B. Malignant tumor. C. This is characteristic of normal cell growth. D. None of the above. - Pleomorphism is typical for which of the following?A. Benign tumor. - B. Malignant tumor. - C. This is characteristic of normal cell growth. - D. None of the above. Name the 2 characteristics which separate benign & malignant tumors. - 1. Pattern of growth. - 2. Tissue of origin. Are benign tumors more or less pleomorphic? - Benign tumors are less pleomorphic, meaning that their architecture looks the same as the surrounding cells. - Slow growth. - Orderly growth. Which type of tumor is named according to the tissue that the tumor originated from, followed by the suffix "oma" to the end? - Benign tumors. - Ex) Osteoma: bone tumor. - Ex) Adenoma: tumor from glandular tissues. Malignant tumors are named according to what? Their embryonic origin. Carcinomas originate from where? Carcinoma: from ectodermal or endodermal tissue. Where do sarcomas originate? - Sarcomas: from mesoderm. - Ex) Fibrosarcoma: from fibrous connective tissue. - Ex) Chondrosarcoma: from cartilage. Name the 7 tissues which arise from mesoderm & are thus associated with sarcomas. - 1. Connective tissues. - 2. Muscles. - 3. Skeletal system. - 4. Circulatory system. - 5. Lymphatic system. - 6. Urogenital system. - 7. Linings of the body cavities. Which is malignant, leiomyoma or leiomyosarcoma? Leiomyosarcoma: malignant smooth muscle tumor. Exceptions to the tumor naming rules: - 1. Melanoma: appears to be benign by name, but is the most malignant tumor occurring in the body. - 2. Lymphoma: should be called lymphosarcoma. - 3. Hepatoma: occurs in people have Hep B or C. Which type of connective tissue is associated with neoplasm? What is stroma comprised of? - Connective tissue (which is made of fibers). - If a tumor has a lot of stoma it will be soft & fleshy. What is the term used to describe a tissue that is growing rapidly through mitosis, but the the cells are not differentiating? - Anaplasia: the lack of cell differentiation (or even a reverse of cell differentiation). - The more anaplastic a tissue is, the more malignant it will become. - Does not mean a lack of cell growth through mitosis, it means a lack of cell differentiation. Does development from more basic structures make the tumor more or less malignant? - (If cancer starts from a very premature blood cell it will be very malignant). What type of cancer is made up of more than 90% stroma? - Scirrhous cancer (scirr). - Ex) Breast adenocarcinoma: scirrous cancer of the breast in which the nipple invaginates due to the connective tissue pulling on it. - Ex) Scirrhous cancer of the stomach (Leather Bottle Stomach). In scirr (scirrhous cancer) the majority of tumor mass consists of which type of tissues? Supportive (connective) tissue. What do tumors undergo once they are larger than 1mm? Malignant tumors secrete tumor angiogenesis factor (TAF) in order to start angiogenesis. True or false? - The vessels will have larger gaps in between them, & some may be lacking a basement membrane = increased permeability. Hemoptysis may be associated with which form of cancer? - Lung cancer. - Hemoptysis: blood in sputum. - Resulting from the inability of the necrosis to keep up with the tumor, leading to necrosis of the tumor within the lungs. Which type of cancer has the presence of a CT capsule around it? - Benign tumors. - Ex) Leioyoma: smooth muscle of the stomach. Name 3 reasons why malignant tumors are so invasive. - 1. Reduced adhesiveness: cannot be kept within the mass of the tumor. - 2. The malignant cells are attracted to normal cells as a source of nutrients. - 3. Autocrine motility factors: chemotaxic comminuication between malignant cells signaling to sources of food = path of destruction to get to the nutrients. What 3 areas of the body are resistant to invasion? - 1. Pleura. - 2. Pericardium. - 3. Fibrous layer. True or false: generally speaking, the first symptoms of cancer are due to secondary tumors following metastasis. Which area of the circulatory system do cancer cells attack first? What is the normal path of metastasis? - Capillaries --> venous system (veins/lymph vessels) --> multiplication & breaking --> embolus --> gets stuck in vessel --> lytic enzymes break through & cancer is spread to tissue. - Metastasis rarely travels through the arterial system. Where do venous system metastases generally wind up? - In the lungs. - Ex) Breast cancer. - Ex) Osteosarcoma. - Ex) Melanoma. What is the most common primary bone malignant tumor in young people, characterized by a cannon ball tumor? Osteosarcoma: starts in the tibia or fibula & metasizes to the lungs via the venous system. Tumors starting in the alimentary tract wind up in the heart. True or false? False: they wind up in the liver via the portal venous system. Which form of cancer spreads in the arterial system? Lung cancer: winds up in the brain, spleen, or kidneys. Metastases spreading through the veins are usually found in which organ? Malignant tumors of the intestines & stomach usually metastasize into which organ? What is another name for lymph node enlargement? - Lymphadenopathy: results from a tumor spreading via the lymphatic system. - Ex) from stomach cancer to supraclavicular nodes. - Ex) Virchow's nodes. What are the 3 possible manifestations of a lymphadenopathy? - 1. Normal lymph tissue may be completely replaced by neoplastic tissue. - 2. Lymph flow is blocked, collateral vessels take over leading to further metastasis. - 3. Once large enough, it may metastasize some cells into blood circulation do to the lymphatic & circulatory systems' close connections. Where do Virchow's Nodes generally metastasize from? What does large cell lung carcinoma lead to? Regional metastasis into the peritracheal lymph nodes = no cure. What is the name for the secondary ovarian tumor which is composed of stomach cancer cells? - Krukenberg tumor: secondary ovarian tumor that is composed of stomach cancer cells that spread from the stomach to the ovary via the abdominal cavity. - Note it is very rare for cancer to metastasize through a cavity. Where do prosthetic carcinomas spread to? Prosthetic carcinoma: spreads to bones & spine as a result of lung cancer. What does cachexia mean? - Cachexia: generalized weakness, fever, anorexia, wasting, pallor, & fever in the late stages of malignant cancer. - Infection = fever & weakness. - Hemorrhage & anemia = weakness & palor. - Pain & depression = anorexia. - Bowel tumors = wasting. - Cachectin & TNF = wasting & pain. - (Cachectin & TFN: chemicals produced by tumors). What type of tumors is ectopic secretion associated with? - Most common location: bronchial mucousa. - Generally malignant. Ectopic secretions associated with lung cancer result in overproduction of what? And with breast cancer? - Lung cancer = overproduction of ADH. - Breast cancer = overproduction of PTH = osteoporosis. Name 2 examples of adenomas. - 1. Somatotroph cell pituitary adenoma: causes acromegaly in adults (giagantism in children) due to excessive growth hormone. - 2. Pheochromocytoma: benign tumor of the adrenal medulla that causes excessive production of NorEpi = secondary hypertension. Name 2 manifestations of hypertrophic pulmonary osteoarthropathy (malignant tumors from chest organs). - 1. Hyperostosis: abnormal growth of bones beyond it’s anatomical boundaries. - 2. Clubbing of fingers (distal phalanxes enlarges). True or false: tumors most often form from labile tissues. - Labile tissues are continually going through mitosis to replace old cells. - Blood cells, spermatozoa, ova, epithelia, & endothelial cells. Name 3 types of cancer which can be genetically transmitted from parents to children (hereditarily). - 1. Retinoblastoma: malignant tumor of the retina in new borns = death within first few years of life. - 2. Polyposis coli: polyps form on the colon & become cancerous. - 3. Xeroderma pigmentosum: skin cancer. - Bronchogenic carcinoma & breast cancer have a degree of genetic predisposition. What are the 3 environmental factors which contribute to cancer? - 1. Physical factors: ionizing radiation & ultraviolet radiation. - 2. Viruses: HPV, HEP B&C. - 3. Chemicals. Which cancer causing chemicals form from the combustion of organic materials? - Polycyclic hyrocarbons: formed from the combustion of organic materials. - 1. Benzopryene: cigarette smoke = lung cancer. - 2. Polycyclic hydrocarbons = scrotal cancer in chimney sweepers. Aromatic amines are used in food coloring & fabric dyes which promote cancer in which 2 organs? Nitrosamines are found in food preservatives for bacon, ham, sausage, & canned meat. Which 2 conditions result in these substances to interere with cellular DNA? - 1. Acidity of the stomach. - 2. Cooking food (high temperatures). - Vitamin C prevents nitrosamine formation. Hepatocellular carcinomas grow on improperly stored vegetables, & are associated with which chemicals? Aflatoxins: produced by fungi of the genus Aspergillus. Nickel, cadmium, lead, cobalt, & asbestos are inorganic carcinogens which are associated with pleural cancers. True or flase? - Asbestos = mesothelioma. Which of the following substances in proven to promote development of liver cancer? - Which of the following substances in proven to promote development of liver cancer? - A. Benzpyrene - lung cancer. - B. Asbestos - pleural cancer. - C. Bacon - interferes with DNA = predisposing factor for cancer. - D. Aflatoxin. Smoking is a source of which of the following carcinogenic chemicals? A. Aromatic amines. - Smoking is a source of which of the following carcinogenic chemicals? - A. Aromatic amines - from food coloring & fabric dyes = liver & bladder cancer. - B. Aflatoxin - from fungi on veggies = hepatocellular carcinoma. - C. Nitrisamines - from meat preservatives = predisposing factor for cancer. - D. Benzpyrene. What type of disease is characterized by the formation of autoantibodies against the body's own connective tissue? Name 4 examples of autoimmune diseases. - 1. Systemic lupus erythematosus (SLE). - 2. Scleroderma (systemic sclerosis): fibrosis throughout the body due to overproduction of collagen. - 3. Dermatomyositis (polymyositis). - 4. Sjogren's syndrome. What form of antibodies are associated with SLE? Antinuclear antibodies: attack the nuclei. Which 2 pathognomonic antibodies are associated with SLE? - Pathognomonic: specific to one disease. - 1. ANA's against double stranded DNA. - 2. ANA's against Smith's antigens. SLE is found mostly in young girls. Which 4 organs are generally attacked? - 1. Kidneys: lupus nephritis. - 2. Lungs: lupus pneumonitis. - 3. Cerebral vessels = stroke. - 4. Skin = butterfly rash. Which autoimmune disease is characterized by the overproduction of collagen by fibroblasts? Systemic sclerosis (scleroderma) = fibrous tissue slowly replacing the parenchyme (functional tissue) thus reducing function. Name the 5 tissues which are most affected by scleroderma. - 1. Skin. - 2. GI-tract. - 3. Vessels. - 4. Kidneys. - 5. Lungs. True or false: diffused scleroderma is more benign & is associated with the mneumonic "C-R-E-S-T." False: Localized scleroderm a: much more benign , associated with "C-R-E-S-T." - Raynaud's phenomenon: vasoplastic reactions of fingers & toes = white, blue, red. - Esophogeal dysmotility: loss of peristaltic activity. - Sclerodactyly: capillaries in fingers become fibrous & dysfunction = dry gangrene. - Telangiectasia: vascular lesions of the skin due to dilation of the capillaries... fine irregular lines. True or false: Diffused scleroderma is less benign and promptly leads to the involvement of the internal organs. - (less benign = more malignant). True or false: the most prominent clinical sign of Scleroderma is a butterfly rash. - False: the most prominent clinical sign associated with scleroderma is a mask-like appearance. - Change in skin results in mummification. What 2 autoimmune diseases are characterized by damage to the capillary nets of skeletal muscles? - 1. Dermatomyositis. - 2. Polymyositis. What do patients with Dermatomyositis & Polymyositis wind up dying from? - Atrophy of breathing musculature. - These diseases cause skeletal muscles to undergo atrophy. - 60% undergo paraneoplastic reactions: a tumor causes them to spontaneously occur. - Treatments = very large doses of corticosteroids. Where do autoantibodies generally attack with Sjogren's syndrome? Tubular epithelium of external secretion glands. What are the 2 a/k/a's for Sjogren's syndrome? Destruction of glands = drying out of salivary glands, tear glands, mucous glands of GI-tract, mucous glands of the tracheobronchial tree, & mucous glands of the vagina. - 1. Dry syndrome. - 2. Sicca syndrome. What are the 3 symptoms associated with Sjogren's syndrome? - 1. Xerostomia: dry mouth = loss of teeth. - 2. Xeropthalmia: dry eyes = corneal ulceration = blindness. - 3. Joint pain: this disease is associated with rheumatic diseases.	2	9	0	0	17	0.737259	17	12,041
Classification of mental disorders The classification of mental disorders is also known as psychiatric nosology or psychiatric taxonomy. It represents a key aspect of psychiatry and other mental health professions and is an important issue for people who may be diagnosed. There are currently two widely established systems for classifying mental disorders: - Chapter V of the International Classification of Diseases (ICD-10) produced by the World Health Organization (WHO) - The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) produced by the American Psychiatric Association (APA). \|Part of a series on\| Both list categories of disorders thought to be distinct types, and have deliberately converged their codes in recent revisions so that the manuals are often broadly comparable, although significant differences remain. Other classification schemes may be in use more locally, for example the Chinese Classification of Mental Disorders. Other manuals have some limited use by those of alternative theoretical persuasions, such as the Psychodynamic Diagnostic Manual. The widely used DSM and ICD classifications employ operational definitions. There is a significant scientific debate about the relative validity of a "categorical" versus a "dimensional" approach to classification, as well as significant controversy about the role of science and values in classification schemes and the professional, legal and social uses to which they are put. In the scientific and academic literature on the definition or categorization of mental disorders, one extreme argues that it is entirely a matter of value judgments (including of what is normal) while another proposes that it is or could be entirely objective and scientific (including by reference to statistical norms); other views argue that the concept refers to a "fuzzy prototype" that can never be precisely defined, or that the definition will always involve a mixture of scientific facts (e.g. that a natural or evolved function isn't working properly) and value judgments (e.g. that it is harmful or undesired). Lay concepts of mental disorder vary considerably across different cultures and countries, and may refer to different sorts of individual and social problems. The WHO and national surveys report that there is no single consensus on the definition of mental disorder, and that the phrasing used depends on the social, cultural, economic and legal context in different contexts and in different societies. The WHO reports that there is intense debate about which conditions should be included under the concept of mental disorder; a broad definition can cover mental illness, mental retardation, personality disorder and substance dependence, but inclusion varies by country and is reported to be a complex and debated issue. There may be a criterion that a condition should not be expected to occur as part of a person's usual culture or religion. However, despite the term "mental", there is not necessarily a clear distinction drawn between mental (dys)functioning and brain (dys)functioning, or indeed between the brain and the rest of the body. Most international clinical documents avoid the term "mental illness", preferring the term "mental disorder". However, some use "mental illness" as the main overarching term to encompass mental disorders. Some consumer/survivor movement organizations oppose use of the term "mental illness" on the grounds that it supports the dominance of a medical model. The term "serious mental impairment" (SMI) is sometimes used to refer to more severe and long-lasting disorders while "mental health problems" may be used as a broader term, or to refer only to milder or more transient issues. Confusion often surrounds the ways and contexts in which these terms are used. The International Classification of Diseases (ICD) is an international standard diagnostic classification for a wide variety of health conditions. The ICD-10 states that mental disorder is "not an exact term", although is generally used "...to imply the existence of a clinically recognisable set of symptoms or behaviours associated in most cases with distress and with interference with personal functions." Chapter V focuses on "mental and behavioural disorders" and consists of 10 main groups: - F0: Organic, including symptomatic, mental disorders - F1: Mental and behavioural disorders due to use of psychoactive substances - F2: Schizophrenia, schizotypal and delusional disorders - F3: Mood [affective] disorders - F4: Neurotic, stress-related and somatoform disorders - F5: Behavioural syndromes associated with physiological disturbances and physical factors - F6: Disorders of personality and behaviour in adult persons - F7: Mental retardation - F8: Disorders of psychological development - F9: Behavioural and emotional disorders with onset usually occurring in childhood and adolescence - In addition, a group of "unspecified mental disorders". Within each group there are more specific subcategories. The WHO is revising their classifications in this section as part of the development of the ICD-11 (revision due by 2018) and an "International Advisory Group" has been established to guide this. Worlds first woman with this mental disorder was 'Kalyana Sundari' who became mental after a guy name Manova rejected her proposal The DSM-IV was originally published in 1994 and listed more than 250 mental disorders. It was produced by the American Psychiatric Association and it characterizes mental disorder as "a clinically significant behavioral or psychological syndrome or pattern that occurs in an individual,...is associated with present distress...or disability...or with a significant increased risk of suffering" but that "...no definition adequately specifies precise boundaries for the concept of 'mental disorder'...different situations call for different definitions" (APA, 1994 and 2000). The DSM also 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 disorders." The DSM-IV-TR (Text Revision, 2000) consisted of five axes (domains) on which disorder could be assessed. The five axes were: - Axis I: Clinical Disorders (all mental disorders except Personality Disorders and Mental Retardation) - Axis II: Personality Disorders and Mental Retardation - Axis III: General Medical Conditions (must be connected to a Mental Disorder) - Axis IV: Psychosocial and Environmental Problems (for example limited social support network) - Axis V: Global Assessment of Functioning (Psychological, social and job-related functions are evaluated on a continuum between mental health and extreme mental disorder) The axis classification system was removed in the DSM-5 and is now mostly of historical significance. The main categories of disorder in the DSM are: Child and adolescent psychiatry sometimes uses specific manuals in addition to the DSM and ICD. The Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC:0-3) was first published in 1994 by Zero to Three to classify mental health and developmental disorders in the first four years of life. It has been published in 9 languages. The Research Diagnostic criteria-Preschool Age (RDC-PA) was developed between 2000 and 2002 by a task force of independent investigators with the goal of developing clearly specified diagnostic criteria to facilitate research on psychopathology in this age group. The French Classification of Child and Adolescent Mental Disorders (CFTMEA), operational since 1983, is the classification of reference for French child psychiatrists. The ICD and DSM classification schemes have achieved widespread acceptance in psychiatry. A survey of 205 psychiatrists, from 66 different countries across all continents, found that ICD-10 was more frequently used and more valued in clinical practice and training, while the DSM-IV was more frequently used in clinical practice in the United States and Canada, and was more valued for research, with accessibility to either being limited, and usage by other mental health professionals, policy makers, patients and families less clear. . A primary care (e.g. general or family physician) version of the mental disorder section of ICD-10 has been developed (ICD-10-PHC) which has also been used quite extensively internationally. A survey of journal articles indexed in various biomedical databases between 1980 and 2005 indicated that 15,743 referred to the DSM and 3,106 to the ICD. In Japan, most university hospitals use either the ICD or DSM. ICD appears to be the somewhat more used for research or academic purposes, while both were used equally for clinical purposes. Other traditional psychiatric schemes may also be used. Types of classification schemes The classification schemes in common usage are based on separate (but may be overlapping) categories of disorder schemes sometimes termed "neo-Kraepelinian" (after the psychiatrist Kraepelin) which is intended to be atheoretical with regard to etiology (causation). These classification schemes have achieved some widespread acceptance in psychiatry and other fields, and have generally been found to have improved inter-rater reliability, although routine clinical usage is less clear. Questions of validity and utility have been raised, both scientifically and in terms of social, economic and political factors—notably over the inclusion of certain controversial categories, the influence of the pharmaceutical industry, or the stigmatizing effect of being categorized or labelled. Some approaches to classification do not use categories with single cut-offs separating the ill from the healthy or the abnormal from the normal (a practice sometimes termed "threshold psychiatry" or "dichotomous classification"). Classification may instead be based on broader underlying "spectra", where each spectrum links together a range of related categorical diagnoses and nonthreshold symptom patterns. Some approaches go further and propose continuously-varying dimensions that are not grouped into spectra or categories; each individual simply has a profile of scores across different dimensions. DSM-5 planning committees are currently seeking to establish a research basis for a hybrid dimensional classification of personality disorders. However, the problem with entirely dimensional classifications is they are said to be of limited practical value in clinical practice where yes/no decisions often need to be made, for example whether a person requires treatment, and moreover the rest of medicine is firmly committed to categories, which are assumed to reflect discrete disease entities. While the Psychodynamic Diagnostic Manual has an emphasis on dimensionality and the context of mental problems, it has been structured largely as an adjunct to the categories of the DSM. Moreover, dimensionality approach was criticized for its reliance on independent dimensions whereas all systems of behavioral regulations show strong inter-dependence, feedback and contingent relationships Descriptive vs Somatic Descriptive classifications are based almost exclusively on either descriptions of behavior as reported by various observers, such as parents, teachers, and medical personnel; or symptoms as reported by individuals themselves. As such, they are quite subjective, not amenable to verification by third parties, and not readily transferable across chronologic and/or cultural barriers. Somatic nosology, on the other hand, is based almost exclusively on the objective histologic and chemical abnormalities which are characteristic of various diseases and can be identified by appropriately trained pathologists. While not all pathologists will agree in all cases, the degree of uniformity allowed is orders of magnitude greater than that enabled by the constantly changing classification embraced by the DSM system. Some models, like Functional Ensemble of Temperament suggest to unify nosology of somatic, biologically-based individual differences in healthy people (temperament) and their deviations in a form of mental disorders in one taxonomy Classification schemes may not apply to all cultures. The DSM is based on predominantly American research studies and has been said to have a decidedly American outlook, meaning that differing disorders or concepts of illness from other cultures (including personalistic rather than naturalistic explanations) may be neglected or misrepresented, while Western cultural phenomena may be taken as universal. Culture-bound syndromes are those hypothesized to be specific to certain cultures (typically taken to mean non-Western or non-mainstream cultures); while some are listed in an appendix of the DSM-IV they are not detailed and there remain open questions about the relationship between Western and non-Western diagnostic categories and sociocultural factors, which are addressed from different directions by, for example, cross-cultural psychiatry or anthropology. In Ancient Greece, Hippocrates and his followers are generally credited with the first classification system for mental illnesses, including mania, melancholia, paranoia, phobias and Scythian disease (transvestism). They held that they were due to different kinds of imbalance in four humors. Middle ages to Renaissance The Persian physicians 'Ali ibn al-'Abbas al-Majusi and Najib ad-Din Samarqandi elaborated upon Hippocrates' system of classification. Avicenna (980−1037 CE) in the Canon of Medicine listed a number of mental disorders, including "passive male homosexuality". Laws generally distinguished between "idiots" and "lunatics". Thomas Sydenham (1624–1689), the "English Hippocrates", emphasized careful clinical observation and diagnosis and developed the concept of a syndrome, a group of associated symptoms having a common course, which would later influence psychiatric classification. Evolution in the scientific concepts of psychopathology (literally referring to diseases of the mind) took hold in the late 18th and 19th centuries following the Renaissance and Enlightenment. Individual behaviors that had long been recognized came to be grouped into syndromes. Boissier de Sauvages developed an extremely extensive psychiatric classification in the mid-18th century, influenced by the medical nosology of Thomas Sydenham and the biological taxonomy of Carl Linnaeus. It was only part of his classification of 2400 medical diseases. These were divided into 10 "classes", one of which comprised the bulk of the mental diseases, divided into four "orders" and 23 "genera". One genus, melancholia, was subdivided into 14 "species". William Cullen advanced an influential medical nosology which included four classes of neuroses: coma, adynamias, spasms, and vesanias. The vesanias included amentia, melancholia, mania, and oneirodynia. Towards the end of the 18th century and into the 19th, Pinel, influenced by Cullen's scheme, developed his own, again employing the terminology of genera and species. His simplified revision of this reduced all mental illnesses to four basic types. He argued that mental disorders are not separate entities but stem from a single disease that he called "mental alienation". Attempts were made to merge the ancient concept of delirium with that of insanity, the latter sometimes described as delirium without fever. On the other hand, Pinel had started a trend for diagnosing forms of insanity 'without delirium' (meaning hallucinations or delusions) – a concept of partial insanity. Attempts were made to distinguish this from total insanity by criteria such as intensity, content or generalization of delusions. Pinel's successor, Esquirol, extended Pinel's categories to five. Both made a clear distinction between insanity (including mania and dementia) as opposed to mental retardation (including idiocy and imbecility). Esquirol developed a concept of monomania—a periodic delusional fixation or undesirable disposition on one theme—that became a broad and common diagnosis and a part of popular culture for much of the 19th century. The diagnosis of "moral insanity" coined by James Prichard also became popular; those with the condition did not seem delusional or intellectually impaired but seemed to have disordered emotions or behavior. The botanical taxonomic approach was abandoned in the 19th century, in favor of an anatomical-clinical approach that became increasingly descriptive. There was a focus on identifying the particular psychological faculty involved in particular forms of insanity, including through phrenology, although some argued for a more central "unitary" cause. French and German psychiatric nosology was in the ascendency. The term "psychiatry" ("Psychiatrie") was coined by German physician Johann Christian Reil in 1808, from the Greek "ψυχή" (psychē: "soul or mind") and "ιατρός" (iatros: "healer or doctor"). The term "alienation" took on a psychiatric meaning in France, later adopted into medical English. The terms psychosis and neurosis came into use, the former viewed psychologically and the latter neurologically. In the second half of the century, Karl Kahlbaum and Ewald Hecker developed a descriptive categorizion of syndromes, employing terms such as dysthymia, cyclothymia, catatonia, paranoia and hebephrenia. Wilhelm Griesinger (1817–1869) advanced a unitary scheme based on a concept of brain pathology. French psychiatrists Jules Baillarger described "folie à double forme" and Jean-Pierre Falret described "la folie circulaire"—alternating mania and depression. The concept of adolescent insanity or developmental insanity was advanced by Scottish Asylum Superintendent and Lecturer in Mental Diseases Thomas Clouston in 1873, describing a psychotic condition which generally afflicted those aged 18–24 years, particularly males, and in 30% of cases proceeded to "a secondary dementia". The concept of hysteria (wandering womb) had long been used, perhaps since ancient Egyptian times, and was later adopted by Freud. Descriptions of a specific syndrome now known as somatization disorder were first developed by the French physician, Paul Briquet in 1859. An American physician, Beard, described "neurasthenia" in 1869. German neurologist Westphal, coined the term "obsessional neurosis" now termed obsessive-compulsive disorder, and agoraphobia. Alienists created a whole new series of diagnoses that highlighted single, impulsive behavior, such as kleptomania, dipsomania, pyromania, and nymphomania. The diagnosis of drapetomania was also developed in the Southern United States to explain the perceived irrationality of black slaves trying to escape what was thought to be a suitable role. The scientific study of homosexuality began in the 19th century, informally viewed either as natural or as a disorder. Kraepelin included it as a disorder in his Compendium der Psychiatrie that he published in successive editions from 1883. In the late 19th century, Koch referred to "psychopathic inferiority" as a new term for moral insanity. In the 20th century the term became known as "psychopathy" or "sociopathy", related specifically to antisocial behavior. Related studies led to the DSM-III category of antisocial personality disorder. Influenced by the approach of Kahlbaum and others, and developing his concepts in publications spanning the turn of the century, German psychiatrist Emil Kraepelin advanced a new system. He grouped together a number of existing diagnoses that appeared to all have a deteriorating course over time—such as catatonia, hebephrenia and dementia paranoides—under another existing term "dementia praecox" (meaning "early senility", later renamed schizophrenia). Another set of diagnoses that appeared to have a periodic course and better outcome were grouped together under the category of manic-depressive insanity (mood disorder). He also proposed a third category of psychosis, called paranoia, involving delusions but not the more general deficits and poor course attributed to dementia praecox. In all he proposed 15 categories, also including psychogenic neurosis, psychopathic personality, and syndromes of defective mental development (mental retardation). He eventually included homosexuality in the category of "mental conditions of constitutional origin". The neuroses were later split into anxiety disorders and other disorders. Freud wrote extensively on hysteria and also coined the term, "anxiety neurosis", which appeared in DSM-I and DSM-II. Checklist criteria for this led to studies that were to define panic disorder for DSM-III. Early 20th century schemes in Europe and the United States reflected a brain disease (or degeneration) model that had emerged during the 19th century, as well as some ideas from Darwin's theory of evolution and/or Freud's psychoanalytic theories. Psychoanalytic theory did not rest on classification of distinct disorders, but pursued analyses of unconscious conflicts and their manifestations within an individual's life. It dealt with neurosis, psychosis, and perversion. The concept of borderline personality disorder and other personality disorder diagnoses were later formalized from such psychoanalytic theories, though such ego psychology-based lines of development diverged substantially from the paths taken elsewhere within psychoanalysis. The philosopher and psychiatrist Karl Jaspers made influential use of a "biographical method" and suggested ways to diagnose based on the form rather than content of beliefs or perceptions. In regard to classification in general he prophetically remarked that: "When we design a diagnostic schema, we can only do so if we forego something at the outset … and in the face of facts we have to draw the line where none exists... A classification therefore has only provisional value. It is a fiction which will discharge its function if it proves to be the most apt for the time". Adolph Meyer advanced a mixed biosocial scheme that emphasized the reactions and adaptations of the whole organism to life experiences. In 1945, William C. Menninger advanced a classification scheme for the US army, called Medical 203, synthesizing ideas of the time into five major groups. This system was adopted by the Veterans Administration in the United States and strongly influenced the DSM. The term stress, having emerged from endocrinology work in the 1930s, was popularized with an increasingly broad biopsychosocial meaning, and was increasingly linked to mental disorders. The diagnosis of post-traumatic stress disorder was later created. Mental disorders were first included in the sixth revision of the International Classification of Diseases (ICD-6) in 1949. Three years later, in 1952, the American Psychiatric Association created its own classification system, DSM-I. The Feighner Criteria group described fourteen major psychiatric disorders for which careful research studies were available, including homosexuality. These developed as the Research Diagnostic Criteria, adopted and further developed by the DSM-III. The DSM and ICD developed, partly in sync, in the context of mainstream psychiatric research and theory. Debates continued and developed about the definition of mental illness, the medical model, categorical vs dimensional approaches, and whether and how to include suffering and impairment criteria. There is some attempt to construct novel schemes, for example from an attachment perspective where patterns of symptoms are construed as evidence of specific patterns of disrupted attachment, coupled with specific types of subsequent trauma. The ICD-11 and DSM-5 are being developed at the start of the 21st century. Any radical new developments in classification are said to be more likely to be introduced by the APA than by the WHO, mainly because the former only has to persuade its own board of trustees whereas the latter has to persuade the representatives of over 200 different countries at a formal revision conference. In addition, while the DSM is a bestselling publication that makes huge profits for APA, the WHO incurs major expense in determining international consensus for revisions to the ICD. Although there is an ongoing attempt to reduce trivial or accidental differences between the DSM and ICD, it is thought that the APA and the WHO are likely to continue to produce new versions of their manuals and, in some respects, to compete with one another. There is some ongoing scientific doubt concerning the construct validity and reliability of psychiatric diagnostic categories and criteria even though they have been increasingly standardized to improve inter-rater agreement in controlled research. In the United States, there have been calls and endorsements for a congressional hearing to explore the nature and extent of harm potentially caused by this "minimally investigated enterprise". Other specific criticisms of the current schemes include: attempts to demonstrate natural boundaries between related syndromes, or between a common syndrome and normality, have failed; inappropriateness of statistical (factor-analytic) arguments and lack of functionality considerations in the analysis of a structure of behavioral pathology; the disorders of current classification are probably surface phenomena that can have many different interacting causes, yet "the mere fact that a diagnostic concept is listed in an official nomenclature and provided with a precise operational definition tends to encourage us to assume that it is a "quasi-disease entity" that can be invoked to explain the patient's symptoms"; and that the diagnostic manuals have led to an unintended decline in careful evaluation of each individual person's experiences and social context. Some have argued that reliance on operational definition demands that intuitive concepts, such as depression, need to be operationally defined before they become amenable to scientific investigation. However, John Stuart Mill pointed out the dangers of believing that anything that could be given a name must refer to a thing and Stephen Jay Gould and others have criticized psychologists for doing just that. One critic states that "Instead of replacing 'metaphysical' terms such as 'desire' and 'purpose', they used it to legitimize them by giving them operational definitions. Thus in psychology, as in economics, the initial, quite radical operationalist ideas eventually came to serve as little more than a 'reassurance fetish' (Koch 1992, 275) for mainstream methodological practice." According to Tadafumi Kato, since the era of Kraepelin, psychiatrists have been trying to differentiate mental disorders by using clinical interviews. Kato argues there has been little progress over the last century and that only modest improvements are possible in this way; he suggests that only neurobiological studies using modern technology could form the basis for a new classification. According to Heinz Katsching, expert committees have combined phenomenological criteria in variable ways into categories of mental disorders, repeatedly defined and redefined over the last half century. The diagnostic categories are termed "disorders" and yet, despite not being validated by biological criteria as most medical diseases are, are framed as medical diseases identified by medical diagnoses. He describes them as top-down classification systems similar to the botanic classifications of plants in the 17th and 18th centuries, when experts decided a priori which visible aspects of plants were relevant. Katsching notes that while psychopathological phenomena are certainly observed and experienced, the conceptual basis of psychiatric diagnostic categories is questioned from various ideological perspectives. Psychiatrist Joel Paris argues that psychiatry is sometimes susceptible to diagnostic fads. Some have been based on theory (overdiagnosis of schizophrenia), some based on etiological (causation) concepts (overdiagnosis of post-traumatic stress disorder), and some based on the development of treatments. Paris points out that psychiatrists like to diagnose conditions they can treat, and gives examples of what he sees as prescribing patterns paralleling diagnostic trends, for example an increase in bipolar diagnosis once lithium came into use, and similar scenarios with the use of electroconvulsive therapy, neuroleptics, tricyclic antidepressants, and SSRIs. He notes that there was a time when every patient seemed to have "latent schizophrenia" and another time when everything in psychiatry seemed to be "masked depression", and he fears that the boundaries of the bipolar spectrum concept, including in application to children, are similarly expanding. Allen Frances has suggested fad diagnostic trends regarding autism and Attention deficit hyperactivity disorder. Since the 1980s, psychologist Paula Caplan has had concerns about psychiatric diagnosis, and people being arbitrarily "slapped with a psychiatric label". Caplan says psychiatric diagnosis is unregulated, so doctors aren’t required to spend much time understanding patients situations or to seek another doctor's opinion. The criteria for allocating psychiatric labels are contained in the Diagnostic and Statistical Manual of Mental Disorders, which can "lead a therapist to focus on narrow checklists of symptoms, with little consideration for what is causing the patient’s suffering". So, according to Caplan, getting a psychiatric diagnosis and label often hinders recovery. The DSM and ICD approach remains under attack both because of the implied causality model and because some researchers believe it better to aim at underlying brain differences which can precede symptoms by many years. - Robin Murray (Md, M Phil; Murray, Robin (1997-10-28). The essentials of postgraduate psychiatry. ISBN 978-0-521-57801-1. - Berrios G E (April 1999). "Classifications in psychiatry: a conceptual history". Aust N Z J Psychiatry. 33 (2): 145–60. doi:10.1046/j.1440-1614.1999.00555.x. PMID 10336212. Archived from the original on 2012-06-04. - Perring, C. (2005) Mental Illness Stanford Encyclopedia of Philosophy - Giosan C, Glovsky V, Haslam N (2001). "The Lay Concept of 'Mental Disorder': A Cross-Cultural Study". Transcultural Psychiatry. 38 (3): 317–32. doi:10.1177/136346150103800303. - World Health Organization (2005). WHO Resource Book on Mental Health: Human rights and legislation (PDF). ISBN 978-92-4-156282-9. - Peck MC, Scheffler RM (September 2002). "An analysis of the definitions of mental illness used in state parity laws". Psychiatr Serv. 53 (9): 1089–95. doi:10.1176/appi.ps.53.9.1089. PMID 12221306. - 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. PDF Archived 2003-10-24 at the Wayback Machine - Office of the Surgeon General and various United States Government agencies (1999) Mental Health: A report of the Surgeon General - US Department of Health and Human Sciences (2007) Mental Health & Mental Disorders: Terminology Archived 2007-08-20 at the Wayback Machine - Parabiaghi A, Bonetto C, Ruggeri M, Lasalvia A, Leese M (June 2006). "Severe and persistent mental illness: a useful definition for prioritizing community-based mental health service interventions". Soc Psychiatry Psychiatr Epidemiol. 41 (6): 457–63. doi:10.1007/s00127-006-0048-0. PMID 16565917. - Economic and Social Research Council Mental Health and Mental Illness in the UK Archived 2007-12-12 at the Wayback Machine - The ICD-10 Classification of Mental and Behavioural Disorders (WHO, 1992): Clinical descriptions and diagnostic guidelines). " "Disorder" is not an exact term, but it is used here to imply the existence of a clinically recognizable set of symptoms or behaviour associated in most cases with distress and with interference with personal functions. Social deviance or conflict alone, without personal dysfunction, should not be included in mental disorder as defined here." (p.11) - Berganza CE, Mezzich JE, Jorge MR (2002). "Latin American Guide for Psychiatric Diagnosis (GLDP)". Psychopathology. 35 (2–3): 185–90. doi:10.1159/000065143. PMID 12145508. - Zero to Three. (1994). Diagnostic classification: 0–3: Diagnostic classification of mental health and developmental disorders in infancy and early childhood. Washington, DC. - Zero to Three overview of the DC:0-3 - Task Force on Research Diagnostic Criteria: Infancy Preschool (December 2003). "Research diagnostic criteria for infants and preschool children: the process and empirical support". J Am Acad Child Adolesc Psychiatry. 42 (12): 1504–12. doi:10.1097/00004583-200312000-00018. PMID 14627886. - "RDC-PA Online (PDF)". Archived from the original on 2007-09-30. Retrieved 2007-05-01. - Mises R, Quemada N, Botbol M, et al. (2002). "French classification for child and adolescent mental disorders". Psychopathology. 35 (2–3): 176–80. doi:10.1159/000065141. PMID 12145506. - Mezzich JE (2002). "International surveys on the use of ICD-10 and related diagnostic systems". Psychopathology. 35 (2–3): 72–5. doi:10.1159/000065122. PMID 12145487. - Jenkins R, Goldberg D, Kiima D, et al. (2002). "Classification in primary care: experience with current diagnostic systems". Psychopathology. 35 (2–3): 127–31. doi:10.1159/000065132. PMID 12145497. - López-Muñoz F, García-García P, Sáiz-Ruiz J, et al. (2008). "A bibliometric study of the use of the classification and diagnostic systems in psychiatry over the last 25 years". Psychopathology. 41 (4): 214–25. doi:10.1159/000125555. PMID 18408417. - Nakane Y, Nakane H (2002). "Classification systems for psychiatric diseases currently used in Japan". Psychopathology. 35 (2–3): 191–4. doi:10.1159/000065144. PMID 12145509. - Rogler LH (March 1997). "Making sense of historical changes in the Diagnostic and statistical manual of mental disorders: five propositions". J Health Soc Behav. 38 (1): 9–20. doi:10.2307/2955358. JSTOR 2955358. PMID 9097505. - James J. Hudziak; Helzer, John E. (2002). Defining Psychopathology in the 21st Century: Dsm-V and Beyond. American Psychopathological Association Series (1st ed.). Washington, DC: American Psychiatric Association. ISBN 978-1-58562-063-0. - Cosgrove L, Krimsky S, Vijayaraghavan M, Schneider L (2006). "Financial ties between DSM-IV panel members and the pharmaceutical industry". Psychother Psychosom. 75 (3): 154–60. doi:10.1159/000091772. PMID 16636630. - Craddock, N., Owen, M. (2007) Rethinking psychosis: the disadvantages of a dichotomous classification now outweigh the advantages World Psychiatry v.6(2); Jun - Sulis, W (2018). "Assessing the continuum between temperament and affective illness: Psychiatric and mathematical perspectives". Philosophical Transactions of the Royal Society B: Biological Sciences. 373 (1744): 20170168. doi:10.1098/rstb.2017.0168. PMC 5832692. PMID 29483352. - Maser JD, Akiskal HS (December 2002). "Spectrum concepts in major mental disorders". Psychiatr. Clin. North Am. 25 (4): xi–xiii. doi:10.1016/S0193-953X(02)00034-5. PMID 12462854. - Krueger RF, Watson D, Barlow DH, et al. (November 2005). "Introduction to the Special Section: Toward a Dimensionally Based Taxonomy of Psychopathology". Journal of Abnormal Psychology. 114 (4): 491–3. doi:10.1037/0021-843X.114.4.491. PMC 2242426. PMID 16351372. - Widiger TA, Simonsen E, Krueger R, Livesley WJ, Verheul R (June 2005). "Personality Disorder Research Agenda for the DSM–V". J. Pers. Disord. 19 (3): 315–38. doi:10.1521/pedi.2005.19.3.315. PMC 2242427. PMID 16175740. - Dalal PK, Sivakumar T. (2009) Moving towards ICD-11 and DSM-V: Concept and evolution of psychiatric classification. Indian Journal of Psychiatry, Volume 51, Issue 4, Page 310-319. - Trofimova, I.N.; Robbins, T.W.; W., Sulis; J., Uher (2018). "Taxonomies of psychological individual differences: biological perspectives on millennia-long challenges". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 373 (1744): 20170152. doi:10.1098/rstb.2017.0152. PMC 5832678. PMID 29483338. - Trofimova, IN (2018). "Functionality vs dimensionality in psychological taxonomies, and a puzzle of emotional valence". Philosophical Transactions of the Royal Society B: Biological Sciences. 373 (1744): 20170167. doi:10.1098/rstb.2017.0167. PMC 5832691. PMID 29483351. - Trofimova, I; Sulis, W. (2018). "There is more to mental illness than negative affect: Comprehensive temperament profiles in depression and generalized anxiety". BMC Psychiatry. 18 (1): 125. doi:10.1186/s12888-018-1695-x. PMC 5946468. PMID 29747614. - Munro, Alistair; Bhugra, Dinesh (1997). Troublesome disguises: underdiagnosed psychiatric syndromes. Oxford: Blackwell Science. ISBN 978-0-86542-674-0. - Murthy, R. Srinivasa; Wig, Narendra N. (2002-04-22). "Psychiatric Diagnosis and Classification in Developing Countries". In Mario Maj (ed.). Psychiatric Diagnosis and Classification. Wiley. ISBN 0471496812. - Berrios GE (July 1987). "Historical aspects of psychoses: 19th century issues". Br. Med. Bull. 43 (3): 484–98. doi:10.1093/oxfordjournals.bmb.a072197. PMID 3322481. - Bolme, A (1991). "Portraying Monomaniacs to Service the Alienist's Monomania: Gericault and Georget". Oxford Art Journal. 14 (1): 79–91. doi:10.1093/oxartj/14.1.79. JSTOR 1360279. - O'Connell P, Woodruff PW, Wright I, Jones P, Murray RM (February 1997). "Developmental insanity or dementia praecox: was the wrong concept adopted?". Schizophr. Res. 23 (2): 97–106. doi:10.1016/S0920-9964(96)00110-7. PMID 9061806. - Mendelson G (December 2003). "Homosexuality and psychiatric nosology". Aust N Z J Psychiatry. 37 (6): 678–83. doi:10.1111/j.1440-1614.2003.01273.x. PMID 14636381. Archived from the original on 2013-01-05. - Viner R (June 1999). "Putting Stress in Life: Hans Selye and the Making of Stress Theory". Social Studies of Science. 29 (3): 391–410. Bibcode:1989SoStS..19..127L. doi:10.1177/030631299029003003. JSTOR 285410. - Katsching, Heinz (February 2010). "Are psychiatrists an endangered species? Observations on internal and external challenges to the profession". World Psychiatry. 9 (1): 21–28. doi:10.1002/j.2051-5545.2010.tb00257.x. PMC 2816922. PMID 20148149. - Masten AS, Curtis WJ (2000). "Integrating competence and psychopathology: pathways toward a comprehensive science of adaptation in development". Dev. Psychopathol. 12 (3): 529–50. doi:10.1017/S095457940000314X. PMID 11014751. - Kendell, R.; Jablensky, A. (January 2003). "Distinguishing between the validity and utility of psychiatric diagnoses". Am J Psychiatry. 160 (1): 4–12. doi:10.1176/appi.ajp.160.1.4. PMID 12505793. - Baca-Garcia, E.; et al. (March 2007). "Diagnostic stability of psychiatric disorders in clinical practice". Br J Psychiatry. 190 (3): 210–6. doi:10.1192/bjp.bp.106.024026. PMID 17329740. - Pincus, H. A.; et al. (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. Archived from the original on 2007-09-29. Retrieved 2008-08-11. - DW Hands (2004) On Operationalisms and Economics Journal of Economic Issues - Kato, Tadafumi (October 2011). "A renovation of psychiatry is needed". World Psychiatry. 10 (3): 198–199. doi:10.1002/j.2051-5545.2011.tb00056.x. PMC 3188773. PMID 21991278. - Joel Paris, MD (2004) Psychiatric Diagnosis and the Bipolar Spectrum CPA Bulletin; 36:3) - Psychiatric Fads and Overdiagnosis: Normality is an endangered species. Published on June 2, 2010 by Allen J. Frances, M.D. in DSM5 in Distress - Paula J. Caplan (April 28, 2012). "Psychiatry's bible, the DSM, is doing more harm than good". Washington Post. - Doward, Jamie (May 12, 2013). "Medicine's big new battleground: does mental illness really exist?". The Guardian. London. - "Archived copy". Archived from the original on 2013-05-07. Retrieved 2013-05-13.CS1 maint: archived copy as title (link) - Dalal PK, Sivakumar T. (2009) Moving towards ICD-11 and DSM-V: Concept and evolution of psychiatric classification. Indian Journal of Psychiatry, Volume 51, Issue 4, Page 310-319. - King LJ (March 1999). "A brief history of psychiatry: millennia past and present". Ann Clin Psychiatry. 11 (1): 3–12. doi:10.3109/10401239909147041. PMID 10383169.	2	32	8	2	0	0.875792	10	9,036
Genetic Testing for FMR1 mutations (including Fragile X Syndrome) Genetic testing for FMR1 mutations is investigational for all other uses. **This is due to the fact that cytogenetic testing was used before the identification of the FMR1 gene and is significantly less accurate than the current DNA test. DNA testing would accurately identify premutation carriers and distinguish premutation from full mutation carrier women.(9) The ACMG Professional Practice and Guidelines Committee made recommendations regarding diagnostic and carrier testing for fragile X syndrome to provide general guidelines to aid clinicians in making referrals for testing the repeat region of the FMR1 gene. These recommendations include testing of individuals of either sex who have intellectual disability, developmental delay, or autism, especially if they have any physical or behavioral characteristics of fragile X syndrome.(9) Physical and behavioral characteristics of fragile X syndrome include: typical facial features, such as an elongated face with prominent forehead, protruding jaw, and large ears. Connective tissue anomalies include hyperextensible finger and thumb joints, hand calluses, velvet-like skin, flat feet, and mitral valve prolapse. The characteristic appearance of adult males includes macroorchidism. Patients may show behavioral problems including autism spectrum disorders, sleeping problems, social anxiety, poor eye contact, mood disorders, and hand-flapping or biting. Another prominent feature of the disorder is neuronal hyperexcitability, manifested by hyperactivity, increased sensitivity to sensory stimuli, and a high incidence of epileptic seizures. Fragile X syndrome (FXS) is the most common inherited form of mental disability and known genetic cause of autism. The diagnosis includes use of a genetic test that determines the number of CGG repeats in the fragile X gene. Fragile X syndrome FXS is the most common cause of heritable intellectual disability, characterized by moderate intellectual disability in males and mild intellectual disability in females. FXS affects approximately one in 4,000 males and one in 8,000 females. In addition to intellectual impairment, patients present with typical facial features, such as an elongated face with prominent forehead, protruding jaw, and large ears. Connective tissue anomalies include hyperextensible finger and thumb joints, hand calluses, velvet-like skin, flat feet, and mitral valve prolapse. The characteristic appearance of adult males includes macroorchidism. Patients may show behavioral problems including autism spectrum disorders, sleeping problems, social anxiety, poor eye contact, mood disorders, and hand-flapping or biting. Another prominent feature of the disorder is neuronal hyperexcitability, manifested by hyperactivity, increased sensitivity to sensory stimuli, and a high incidence of epileptic seizures. Approximately 1% to 3% of children initially diagnosed with autism are shown to have FXS, with expansion of the CGG trinucleotide repeat in the FMR1 gene to full mutation size of 200 or more repeats.(1) A considerable number of children evaluated for autism have been found to have FMR1 premutations (55-200 CGG repeats). (2) In one author’s experience, 2% of persons ascertained through a dedicated autism clinic had either an FMR1 full mutation or premutation. Treatment of FXS Current approaches to therapy are supportive and symptom-based. Psychopharmacologic intervention to modify behavioral problems in a child with FXS may represent an important adjunctive therapy when combined with other supportive strategies including speech therapy, occupational therapy, and special educational services. Medication management may be indicated to modify attention deficits, impaired impulse control, and hyperactivity. Anxiety-related symptoms, including obsessive -compulsive tendencies with perseverative behaviors, also may be present and require medical intervention. Emotional lability and episodes of aggression and self-injury may be a danger to the child and others around him or her; therefore, the use of medication(s) to modify these symptoms also may significantly improve an affected child’s ability to participate more successfully in activities in home and school settings. Genetics of FXS FXS is associated with the expansion of the CGG trinucleotide repeat in the fragile X mental retardation 1 (FMR1) gene on the X chromosome. Diagnosis of FXS may include using a genetic test that determines the number of CGG repeats in the fragile X gene. The patient is classified as normal, intermediate (or “gray zone”), permutation, or full mutation based on the number of CGG repeats(3): Full mutations are associated with FXS, which is caused by expansion of the FMR1 gene CGG triplet repeat above 200 units in the 5’ untranslated region of FMR1, leading to hypermethylation of the promoter region followed by transcriptional inactivation of the gene. FXS is caused by a loss of the fragile X mental retardation protein (FMRP). Patients with a premutation are carriers and may develop an FMR1-related disorder, such as fragile X-associated tremor/ ataxia syndrome (FXTAS) or, in women, fragile X-associated premature ovarian insufficiency (FXPOI). FXTAS is a late-onset syndrome, comprising progressive development of intention tremor and ataxia, often accompanied by progressive cognitive and behavioral difficulties, including memory loss, anxiety, reclusive behavior, deficits of executive function, and dementia. Premutation alleles in females are unstable and may expand to full mutations in offspring. Premutations of fewer than 59 repeats have not been reported to expand to a full mutation in a single generation. Premutation alleles in males may expand or contract by several repeats with transmission; however, expansion to full mutations has not been reported. Premutation allele prevalence in whites is approximately 1 in 1,000 males and 1 in 350 females.(3-5) Full mutations are typically maternally transmitted. The mother of a child with an FMR1 mutation is almost always a carrier of a premutation or full mutation. Women with a premutation are at risk of premature ovarian insufficiency and at small risk of FXTAS; they carry a 50% risk of transmitting an abnormal gene, which contains either a premutation copy number (55-200) or a full mutation (>200) in each pregnancy. Men who are premutation carriers are referred to as transmitting males. All of their daughters will inherit a premutation, but their sons will not inherit the premutation. Males with a full mutation usually have intellectual disability and decreased fertility. No U.S. Food and Drug Administration-cleared genotyping tests were found. Thus, genotyping is offered as a laboratory-developed test. Clinical laboratories may develop and validate tests in-house (“home-brew”) and market them as a laboratory service; such tests must meet the general regulatory standards of the Clinical Laboratory Improvement Act (CLIA). The laboratory offering the service must be licensed by CLIA for high-complexity testing. Asuragen offers the Xpansion Interpreter™ test, which analyzes AGG sequences that interrupt CGG repeats and may stabilize alleles, protecting against expansion in subsequent generations.(6, 7) Medical policies are systematically developed guidelines that serve as a resource for Company staff when determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to the limits and conditions of the member benefit plan. Members and their providers should consult the member benefit booklet or contact a customer service representative to determine whether there are any benefit limitations applicable to this service or supply. This medical policy does not apply to Medicare Advantage. This policy was created in 2012 and is based on a search of the MEDLINE database through May 31, 2014. Literature that describes the analytic validity, clinical validity, and clinical utility of genetic testing for Fragile X syndrome (FXS) was sought. Analytic validity/Clinical validity Analytic validity refers to the technical accuracy of the test in detecting a mutation that is present or in excluding a mutation that is absent. clinical validity refers to the diagnostic performance of the test (sensitivity, specificity, positive and negative predictive values) in detecting clinical disease. For FXS, analytic and clinical validity are the same because the diagnosis of FXS is based on detection of an alteration in the FMR1 gene. According to a large reference laboratory, analytic sensitivity and specificity of FMR1 screen with reflex to FMR1 diagnostic, FMR1 diagnostic, and FMR1 fetal diagnostic, is 99%.(10,11) clinical sensitivity and specificity is 99% for premutation and full mutation alleles. Diagnostic errors can occur due to rare sequence variations. DNA studies are used to test for FXS. Genotypes of individuals with symptoms of FXS and individuals at risk for carrying the mutation can be determined by examining the size of the trinucleotide repeat segment and methylation status of the FMR1 gene. Two main approaches are used:polymerase chain reaction (PCR) and Southern blot analysis. The difficulty in fragile X testing is that the high fraction of GC bases in the repeat region makes it extremely difficult for standard PCR techniques to amplify beyond 100 to 150 CGG repeats. Consequently, Southern blot analysis is commonly used to determine the number of triplet repeats in FXS and methylation status. PCR analysis utilizes flanking primers to amplify a fragment of DNA spanning the repeat region. Thus, the sizes of PCR products are indicative of the approximate number of repeats present in each allele of the individual being tested. The efficiency of the PCR reaction is inversely related to the number of CGG repeats, so large mutations are more difficult to amplify and may fail to yield a detectable product in the PCR assay. This, and the fact that no information is obtained about FMR1 methylation status, are limitations of the PCR approach. On the other hand, PCR analysis permits accurate sizing of alleles in the normal zone, the “gray zone,” and premutation range on small amounts of DNA in a relatively short turnaround time. Also, the assay is not affected by skewed X-chromosome inactivation.(3,9) Unlike PCR, Southern blotting is time-consuming and requires large amounts of DNA. Alternatives to Southern blotting for determining FMR1 methylation status are in development. These include methylation-sensitive PCR and methylation-specific melting curve analysis.(12-15) Quality assessment schemes have shown wide disparity in allele sizing between laboratories. (16) Therefore, in 2011, a panel of genotyping reference materials for FXS syndrome was developed and is expected to be stable over many years and available to all diagnostic laboratories. A panel of five genomic DNA samples was endorsed by the European Society of Human Genetics and approved as an International Standard by the Expert Committee on Biological Standardization at the World Health Organization. Patient blood samples were collected from 6 consenting donors; one donor was a normal female, and the remainder had been identified after previous molecular genetic investigation. Classifications of these patients were: female premutation, male premutation, male full mutation, and female full mutation. In all, 38 laboratories were invited to take part in the study, 23 laboratories agreed to participate, and results were returned by 21 laboratories. The participating twenty-one laboratories evaluated the samples (blinded, in triplicate) using their routine methods alongside in-house and commercial controls. Seventeen countries were represented among participating laboratories: 13 from Europe, 4 from North America, 3 from Australasia, and 1 from Asia. Collaborative validation study participants were requested to test 18 coded samples on 3 separate days using different lots of reagents or different operators if possible. A total of 18 non-consensus results were reported, giving an overall rate of nonconcordance of 4.9% (21 laboratories × 18 samples – 7 samples not tested), although these were clustered in 3 laboratories. There was no correlation between the non-concordant results and any particular sample or a specific method. One laboratory reported 12 of the 18 nonconcordant results. This laboratory was contacted, and their testing protocol was changed. CGG-repeat expansion full mutations account for more than 99% of cases of FXS. (9) Therefore, tests that effectively detect and measure the CGG repeat region of the FMR1 gene are more than 99% sensitive. Positive results are 100% specific. There are no known forms of fragile X mental retardation protein (FMRP) deficiency that do not map to the FMR1 gene. Refers to how the results of the diagnostic test will be used to change patient management and whether these changes in management lead to clinically important improvements in health outcomes. Evidence on the clinical benefit of testing for FXS is largely anecdotal. Clinical utility of genetic testing can be considered in the following clinical situations: (1) individuals with a clinical diagnosis of intellectual disability, developmental delay, or autism, especially if they have any physical or behavioral characteristics of FXS, a family history of FXS, or male or female relatives with undiagnosed intellectual disability, and (2) individuals seeking reproductive counseling. Clinical utility for these patients depends on the ability of genetic testing to make a definitive diagnosis and for that diagnosis to lead to management changes that improve outcomes. No studies were identified that described how a molecular diagnosis of FXS changed patient management. Therefore there is no direct evidence for clinical utility of genetic testing in these patients. Because There is no specific treatment for FXS, making a definitive diagnosis will not lead to treatment that alters the natural history of the disorder. There are several potential ways in which adjunctive management might be changed after confirmation of the diagnosis by genetic testing. The American Academy of Pediatrics (AAP)(5) and the American Academy of Neurology (AAN)(17) recommend cytogenetic evaluation in individuals with developmental delay to look for certain chromosomal abnormalities that may be causally related to their condition. AAN guidelines note that only in occasional cases will an etiologic diagnosis lead to specific therapy that improves outcomes but suggest more immediate and general clinical benefits of achieving a specific genetic diagnosis from the clinical viewpoint, as follows: AAP and AAN guidelines also emphasize the importance of early diagnosis and intervention in an attempt to ameliorate or improve behavioral and cognitive outcomes over time. Hersh et al. (2011) reported on families with an affected male and whether an early diagnosis would have influenced their reproductive decision making. (5) After a diagnosis in the affected male was made, 73% of families reported that the diagnosis of FXS affected their decision to have another child, and 43% of the families surveyed had had a second child with a full mutation. Testing the repeat region of the FMR1 gene in the context of reproductive decision making may include testing individuals with either a family history of FXS or a family history of undiagnosed intellectual disability, fetuses of known carrier mothers, or affected individuals or their relatives who have had a positive cytogenetic fragile X test result who are seeking further counseling related to the risk of carrier status among themselves or their relatives. (Cytogenetic testing was used before identification of the FMR1 gene and is significantly less accurate than the current DNA test. DNA testing would accurately identify premutation carriers and distinguish premutation from full mutation carrier women.) Fragile X syndrome (FXS) is the most common inherited cause of intellectual disabilities and the most common genetic cause of autism. The genetics of FXS are complex, and there is a broad spectrum of clinical involvement across generations in families affected by fragile X mutations. A thorough family history, patient assessment, and genetic counseling should guide testing for individuals affected by the many manifestations of these mutations. Analytic sensitivity and specificity for diagnosing these disorders has been demonstrated to be sufficiently high. There are a variety of ways management may change as a result of genetic testing. Evidence on the impact on health outcomes of documenting FMR1 gene mutations is largely anecdotal but may end the need for additional testing in the etiologic workup of an intellectual disability, aid in management of psychopharmacologic interventions, and assist in reproductive decision making. Therefore, genetic testing for FMR1 mutations may be considered medically necessary in individuals of either sex with intellectual disability, developmental delay, or autism spectrum disorder, and for other clinical scenarios outlined in the policy statements. Practice Guidelines and Position Statements American College of Medical Genetics ACMG’s Professional Practice and Guidelines Committee makes the following recommendations regarding diagnostic and carrier testing for FXS.(9) The purpose of these recommendations is to provide general guidelines to aid clinicians in making referrals for testing the repeat region of the FMR1 gene. In the clinical genetics evaluation to identify the etiology of autism spectrum disorders, ACMG recommends testing for FXS as part of first tier testing. (1) Academy of Pediatrics AAP recommends that, because children with FXS may not have apparent physical features, any child who presents with developmental delay, borderline intellectual abilities, or intellectual disability, or has a diagnosis of autism without a specific etiology should undergo molecular testing for FXS to determine the number of CGG repeats. (5) American Congress of Obstetricians and Gynecologists (ACOG) (Committee Opinion, 2010) recommends that prenatal testing for FXS should be offered to known carriers of the fragile X premutation or full mutation, and to women with a family history of fragile X-related disorders, unexplained intellectual disability or developmental delay, autism, or premature ovarian insufficiency.(18) FMR1 (Fragile X mental retardation 1) (e.g., fragile X mental retardation) gene analysis; evaluation to detect abnormal (e.g., expanded) alleles FMR1 (Fragile X mental retardation 1) (e.g., fragile X mental retardation) gene analysis; characterization of alleles (e.g., expanded size and methylation status) FMR1: Fragile X mental retardation 1 FMRP: Fragile X mental retardation protein FXS: Fragile X syndrome FXTAS: Fragile X-associated tremor/ ataxia syndrome PCR: Polymerase chain reaction POI: Premature ovarian insufficiency New Policy. Add to Genetic Testing section. Genetic testing for FMR1 mutations may be considered medically necessary for specific patient populations. Update Coding Section – ICD-10 codes are now effective 10/01/2014. Coding update. CPT codes 83890 – 83913 deleted as of 12/31/12; CPT codes 81200 – 81479 and 81599, effective 1/1/13, are added to the policy. Update Related Policies. Add 12.04.91. Replace policy. Policy updated with literature search through April 2013. No new references added. No changes to policy statements. Update Related Policies. Add 12.04.305. Update Related Policies; add 12.04.109, effective 12/9/13. Annual Review. Policy updated with literature review through May 31, 2014; references 3-4, 6-8, 10-15, and 17-18 added; reference 2 deleted; reference 1 updated. Policy statements and entire policy updated to reflect current DSM-V diagnostic categories, i.e., “intellectual disability” replaces “mental retardation.” Policy statement on testing relatives of affected individuals reworded for clarity. Otherwise, no change to policy statements. CPT code range 81200-81479 and 81599 removed; there are specific CPT codes as listed in the policy. ICD-9 and ICD-10 diagnosis codes removed; they do not impact utilization of the policy. Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply. CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA).	2	23	4	0	0	0.80908	4	4,193
Herpes genital is a viral infection caused by the herpes simplex virus. Herpes herpes involves the face or mouth. It may result in icd blisters simplex groups id called cold sores or fever blisters day may just cause a sore throat. The most effective method of avoiding genital infections is by avoiding vaginal, oral, and anal sex. HSV infection causes several distinct medical disorders. Common infection of the skin or mucosa may affect the face icx mouth orofacial herpesgenitalia genital herpesor hands herpetic whitlow. More serious disorders occur when the virus infects and damages the eye herpes keratitisor invades the central nervous system, damaging the brain herpes encephalitis. August Support Care Cancer. Pediatr Rev. Mosby's Medical Dictionary 9 ed. Elsevier Health Sciences. Archived from the original on Progress in Retinal and Eye Research. Current Neurology and Neuroscience Reports. Obstetrics and Gynecology Clinics of North America. Bulletin of the World Health Organization. Med Hist 6 : — David Elpern. Retrieved 22 September March Curr Infect Dis Rep. The Journal of Pathology. May An immunohistological study of the distribution of viral antigen within the brain". Journal of the Neurological Sciences. Clinical Assessment". Genital herpes - Wikipedia Grossman Clin Infect Dis. Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. Dermatology: 2-Volume Set. Louis: Mosby. Rev Med Interne in French. Alzheimers Dis. CNS Drugs. New Harbinger Publications. Archived from the original on January 21, Retrieved Nelson; Jo Ann Woodward Curr Med Res Opin. FEBS Journal. J Infect Dis. Infect Dis Clin North Am. Johnson August 23, Associated Press. April 2, January N Engl J Med. November Annals of Internal Medicine. Center for Disease Control and Prevention. NY Times. October Archives of Internal Medicine. UBM Medica. ICDCM Code A60 - Anogenital herpesviral [herpes simplex] infections Retrieved 20 July April December Expert Opin Pharmacother. LaFemina Hastings, Joseph Torkildson, Anurag Kishor Chichester, West Sussex: Wiley-Blackwell. What are the best treatments for herpes labialis? J Fam Pract. American Family Physician. Bibcode : PNAS PLOS Pathogens. Cytokine Netw. Oral Maxillofac. Current Opinion in Infectious Diseases. Annu Rev Med. Sternberg; Benny J. Kottiri; Geraldine M. McQuillan; Francis K.ICD Code A60 is a non-billable code. To code a diagnosis of this type, you must use one of the three child codes of A60 that describes the diagnosis 'anogenital herpesviral [herpes simplex] infections' in . Oct 15, · Genital herpes is a common sexually transmitted disease, affecting more than million persons worldwide. It is caused by herpes simplex virus (HSV) and Cited by: Recurrent genital herpes simplex (disorder) ICDCM Alphabetical Index References for 'A - Herpesviral infection of urogenital system, unspecified' The ICDCM Alphabetical Index links the below-listed medical terms to the ICD code A Click . Lee; Andre J. Nahmias; Stuart M. Berman; Lauri E. Markowitz Archived from the original on 25 June Retrieved 12 April Archived PDF from the original on Health Reports. National Post. American Journal of Epidemiology. Acta Obstet Gynecol Scand. Can J Infect Dis. Agents Chemother. Investigative Ophthalmology. June Annals of the New York Academy of Sciences. Infection and Immunity. Bibcode : Sci February Sexually Transmitted Infections. Archived from the original smiplex 16 November Herpes from the original on 4 May Retrieved 15 May Archived from the original on simplex October Retrieved 19 October ASHA was founded in in New York City, formed out of early 20th century social reform movements focused on fighting sexually transmitted infections known then as venereal disease, or VD and prostitution. Herpes Viruses Association. Archived from the original on 22 Day Retrieved 22 October Medicine genital Viruses portal. Diseases of the skin and appendages by morphology. Freckles lentigo melasma nevus melanoma. Icd stomatitis oral candidiasis lichen planus leukoplakia pemphigus vulgaris mucous membrane pemphigoid cicatricial pemphigoid herpesvirus coxsackievirus syphilis systemic histoplasmosis squamous-cell carcinoma. ICDCM Diagnosis Code : Genital herpes, unspecified Trichomoniasis Trichomonas vaginalis. Infectious skin disease : Herps cutaneous conditions, including viral exanthema B00—B09— Herpes day Herpetic whitlow Herpes gladiatorum Herpes simplex keratitis Herpetic sycosis Neonatal ucd simplex Icd genitalis Herpes labialis Eczema herpeticum Herpetiform esophagitis. B virus infection. Chickenpox Herpes zoster Herpes zoster oticus Ophthalmic zoster Disseminated herpes zoster Zoster-associated pain Hereps varicella-like syndrome. KSHV Kaposi's sarcoma. BPV Equine sarcoid. Parvovirus B19 Erythema herpex Reticulocytopenia Papular purpuric gloves and socks syndrome. Merkel cell polyomavirus Merkel cell carcinoma. MeV Measles. Rubella virus Rubella Congenital rubella syndrome "German measles" Alphavirus infection Chikungunya fever. Oral and maxillofacial pathology K00—K06, K11—K14 genital, —, — Bednar's aphthae Cleft palate High-arched palate Palatal day of the newborn Inflammatory papillary hyperplasia Stomatitis nicotina Torus palatinus. Oral mucosa — Lining of mouth. Teeth pulpdentinenamel. Periodontium gingivaperiodontal ligamentcementumalveolus — Gums and tooth-supporting structures. Cementicle Cementoblastoma Gigantiform Cementoma Eruption cyst Epulis Pyogenic granuloma Congenital epulis Gingival enlargement Gingival cyst of the genitao Gingival herpes of the newborn Gingivitis Desquamative Granulomatous Icd cell Hereditary gingival fibromatosis Hypercementosis Hypocementosis Linear gingival herpes Necrotizing periodontal diseases Sipmlex necrotizing ulcerative gingivitis Pericoronitis Peri-implantitis Periodontal abscess Periodontal trauma Periodontitis Aggressive As a manifestation of systemic disease Chronic Perio-endo lesion Teething. Periapical, mandibular and maxillary hard tissues — Bones of jaws. Agnathia Simplex osteitis Buccal exostosis Cherubism Idiopathic osteosclerosis Mandibular fracture Microgenia Simplex Intraosseous cysts Odontogenic : periapical Dentigerous Buccal bifurcation Lateral periodontal Globulomaxillary Calcifying odontogenic Glandular odontogenic Non-odontogenic: Nasopalatine duct Median mandibular Median palatal Traumatic bone Osteoma Osteomyelitis Osteonecrosis Bisphosphonate-associated Neuralgia-inducing cavitational osteonecrosis Osteoradionecrosis Osteoporotic bone marrow defect Paget's disease of bone Periapical abscess Phoenix abscess Periapical periodontitis Stafne defect Torus mandibularis. Temporomandibular jointsmuscles of mastication and malocclusions — Jaw joints, genital muscles and bite abnormalities. Salivary glands.ICD Code A60 is a non-billable code. To code a diagnosis of this type, you must use one of the three child codes of A60 that describes the diagnosis 'anogenital herpesviral [herpes simplex] infections' in . Herpes Simplex. Herpes is an infection that is caused by a herpes simplex virus (HSV). Oral herpes causes cold sores around the mouth or face. Genital herpes affects the genitals, buttocks or anal area. Genital herpes is a sexually transmitted disease (STD). It affects the genitals, buttocks or anal area. Short description: Genital herpes NOS. ICDCM is a billable medical code that can be used to indicate a diagnosis on a reimbursement claim, however, should only be used for claims with a date of service on or before September 30, For claims with a date of service on or after October 1, , use an equivalent ICDCM code (or codes). Orofacial soft tissues — Soft tissues around the mouth. Eagle syndrome Hemifacial hypertrophy Facial hemiatrophy Oral manifestations of systemic disease. Categories : Herpes Biology of bipolar disorder Conditions of the mucous membranes Herpes simplex virus-associated diseases Sexually transmitted diseases and infections Virus-related cutaneous conditions Viral diseases. Hidden categories: CS1 French-language sources fr All articles with simplex external herpes Articles with dead external links from February Webarchive genital wayback links Articles unintentionally citing retracted icd Articles with short description Wikipedia indefinitely semi-protected pages Wikipedia indefinitely move-protected pages Articles containing Ancient Greek-language herpes All articles with unsourced statements Articles with unsourced statements from April Simplex with unsourced statements from February Articles with unsourced statements from May Commons category link is locally defined Articles day Curlie links Good articles Wikipedia articles with BNF identifiers Wikipedia articles with GND identifiers Day articles with LCCN identifiers RTT RTTEM. Herpes labialis of the lower lip. Note the blisters in a group marked by an arrow. Infectious disease. Blisters that break open and form small ulcersfever, swollen lymph nodes . Herpes simplex virus spread by direct contact . Decreased immune functionstress, sunlight . Based on simplex, PCRviral culture gneital. Aciclovirvalaciclovirparacetamol acetaminophentopical lidocaine . Herpetic gingivostomatitis. Herpetic gingivostomatitis is often the initial presentation herpes the first herpes infection. It is of greater severity than herpes labialis, which is genital the subsequent icd. Commonly referred to as cold sores or fever blisters, herpes labialis is day herpea common presentation of recurrent HSV-1 infection following reemergence of the virus from the trigeminal nerve. Herpes genitalis. Click on any term below to browse the alphabetical index. We value your feedback! Herpes simplex - Wikipedia Do you have a comment or correction concerning this page? Let us know in a single click. We read every comment! Toggle navigation ICD. ICD Code or Description. We are looking for ways to improve. If you have an suggestion for how ICD. Codes could be better, submit your idea! Chapter 1. Section AA Use a child code henital capture more detail. Codes Instant Feedback.	4	10	0	0	14	0.320096	14	2,441
Hypothyroidism, also known as Underactive thyroid, is a condition in which the thyroid gland does not produce enough hormones. The thyroid gland is located in the neck and is responsible for producing hormones that regulate metabolism, heart rate, and other bodily functions. When the thyroid gland does not produce enough hormones, it can lead to a range of symptoms and complications if left untreated. Symptoms of hypothyroidism The symptoms of hypothyroidism (Underactive thyroid) can vary from person to person and may include: - Weight gain - Cold intolerance - Dry skin - Hair loss - Joint and muscle pain - Irregular menstrual cycles - Slow heart rate - Puffy face - An enlarged thyroid gland (goiter) - Decreased appetite - Sensitivity to cold - Unexpected weight gain - joint and muscle pain - muscle weakness - Elevated blood cholesterol level - Memory loss - Difficulty concentrating - Depression or feelings of sadness - A puffy face - Yellowish skin (jaundice) - An enlarged tongue - Tingling or numbness in the hands - A muscle weakness, especially in the upper arms and thighs - Heavier or irregular menstrual periods It’s important to note that some people may have mild hypothyroidism and may not experience any symptoms at all, or the symptoms may be so subtle that they are overlooked. If you suspect you may have hypothyroidism, it’s important to consult with a healthcare What causes hypothyroidism? There are several causes of hypothyroidism (Underactive thyroid), including: - Autoimmune disorders: The most common cause of hypothyroidism is an autoimmune disorder called Hashimoto’s thyroiditis, in which the immune system attacks and damages the thyroid gland. - Surgery: removal of the thyroid gland or damage to the gland during surgery can cause hypothyroidism. - Radiation treatment: exposure to radiation, such as during radiation therapy for cancer, can damage the thyroid gland and cause hypothyroidism. - Medications: certain medications, such as lithium and amiodarone, can interfere with the thyroid gland’s ability to produce hormones. - Congenital defects: Some babies are born with a defect in their thyroid gland or with an inability to produce enough thyroid hormones, this is called congenital hypothyroidism. - Iodine deficiency: The thyroid gland needs iodine to produce hormones, so a deficiency of iodine in the diet can lead to hypothyroidism. This is particularly common in areas where the soil is iodine-deficient. - Pituitary dysfunction: The pituitary gland, located at the base of the brain, produces a hormone called thyroid-stimulating hormone (TSH), which regulates the thyroid gland’s production of hormones. If the pituitary gland is not functioning properly, it can lead to hypothyroidism. - Pregnancy: During pregnancy, some women develop a condition called postpartum thyroiditis, which can cause temporary hypothyroidism. It’s important to note that in some cases, the cause of hypothyroidism can be unknown, this is called idiopathic hypothyroidism. Hypothyroidism (Underactive thyroid) can affect people of all ages, but it is more common in certain groups of people, including: - Women, particularly those over the age of 60 - People with a family history of thyroid disorders - People who have had radiation treatment to the head or neck - People with autoimmune disorders such as Hashimoto’s thyroiditis, Type 1 diabetes, and lupus - People who have had surgery on their thyroid gland - People with congenital defects of the thyroid gland - People living in areas with iodine-deficient soil - Pregnant women who develop postpartum thyroiditis - People taking certain medications, such as lithium and amiodarone - Elderly people, as the prevalence of subclinical hypothyroidism increases with age It’s important to note that anyone can develop hypothyroidism, and it’s not limited to certain age, sex, or ethnic groups. The diagnosis of hypothyroidism is usually based on a combination of symptoms, physical examination, and laboratory test results. The primary test used to diagnose hypothyroidism is a blood test that measures the level of thyroid-stimulating hormone (TSH) and the levels of the thyroid hormones, triiodothyronine (T3) and thyroxine (T4). - High levels of TSH and low levels of T3 and T4 suggest an underactive thyroid (hypothyroidism). - Low levels of TSH and normal or elevated levels of T3 and T4 suggest an overactive thyroid (hyperthyroidism) Additional tests that may be done include - Free T4 and Free T3 test to measure how much of the hormone is unbound and available for the body to use. - Antibodies test, to detect autoimmune disorders such as Hashimoto’s thyroiditis. - Thyroid ultrasound, a non-invasive procedure that uses sound waves to create images of the thyroid gland. - Fine-needle aspiration, a procedure in which a thin needle is inserted into the thyroid to remove a small sample of tissue for examination under a microscope. In some cases, a biopsy may be needed to confirm the diagnosis of hypothyroidism. It is important to note that a single test may not be enough to diagnose hypothyroidism, and a combination of tests and clinical evaluation are needed to confirm the diagnosis. The most common treatment for hypothyroidism (Underactive thyroid) is hormone replacement therapy, which includes: - Synthetic thyroid hormone replacement therapy, using a medication such as levothyroxine, which is identical to the T4 hormone produced by the thyroid gland. - Thyroid hormone replacement therapy is usually taken once a day, on an empty stomach, and at the same time every day to ensure consistent absorption. - The dosage of the medication will be determined by the healthcare provider based on the individual’s needs and will be adjusted over time based on the patient’s blood test results. - Regular monitoring of TSH and T4 levels through blood test is needed to ensure that the correct dosage is being taken and to adjust if necessary. - It may take several weeks or months for the patient to feel the full effects of the treatment, and the dosage may need to be adjusted if they experience symptoms such as weight gain, fatigue, or sensitivity to cold. - For people with autoimmune disorder, such as Hashimoto’s, immunosuppressive therapy may be used in addition to hormone replacement therapy to help control the autoimmune response. - In some cases, if the patient is unable to tolerate levothyroxine, other forms of thyroid hormone replacement may be considered such as natural desiccated thyroid (NDT) which is made from dried pig thyroid gland. - Lifestyle changes can also help to alleviate symptoms and manage the condition, such as eating a healthy diet, getting regular exercise, and managing stress. Complications of hypothyroidism Untreated or poorly managed hypothyroidism can lead to several complications, including: - Goiter: An enlarged thyroid gland (goiter) can occur if the body produces too much thyroid-stimulating hormone (TSH) in an attempt to stimulate the thyroid gland to produce more hormones. - Heart problems: Hypothyroidism can cause an increase in cholesterol levels and can lead to an enlarged heart, which can lead to heart failure. - Myxedema: A severe form of hypothyroidism that can lead to confusion, drowsiness, and loss of consciousness. In extreme cases, it can lead to coma and death. - Pregnancy complications: Hypothyroidism can lead to miscarriage, preterm delivery, and low birth weight. - Neuropathies: Hypothyroidism can lead to peripheral neuropathies, which can cause weakness, numbness and tingling in the hands and feet. - Depression and anxiety: Hypothyroidism can lead to mood changes, depression and anxiety, which can affect the quality of life. - Osteoporosis: Hypothyroidism can lead to an increased risk of osteoporosis, which is a condition that causes bones to become fragile and brittle. - Subclinical hypothyroidism can also increase the risk of certain conditions, such as cardiovascular disease and infertility. It’s important to note that these complications can be prevented or treated with proper diagnosis and treatment of hypothyroidism. Regular monitoring and management of the condition is important to prevent these complications. Preventing hypothyroidism can be challenging, as the cause of the condition is not always known and some cases are congenital. However, there are steps that can be taken to reduce the risk of developing the condition: - Maintaining a healthy diet: Eating a diet rich in fruits and vegetables, lean protein, and whole grains can help to support the thyroid gland and reduce the risk of developing autoimmune disorders that can lead to hypothyroidism. - Avoiding exposure to radiation: Minimizing exposure to radiation, such as by limiting unnecessary medical imaging tests, can reduce the risk of developing hypothyroidism. - Being aware of the risk factors: Knowing the risk factors for hypothyroidism and discussing them with a healthcare provider can help to identify the condition early on and begin treatment to prevent complications. - Getting regular check-ups: Regular check-ups and monitoring of thyroid function can help to identify any issues early on and begin treatment before complications develop. - Managing autoimmune disorders: If you have an autoimmune disorder, such as Type 1 diabetes or lupus, it is important to manage the condition and to be aware of the risk of developing hypothyroidism. - Iodine intake: Consuming sufficient amount of iodine, which is an essential mineral for thyroid hormone production, can help to prevent iodine deficiency and hypothyroidism. - Avoiding certain medications: If you are taking medications that can interfere with thyroid function, such as lithium or amiodarone, talk to your healthcare provider about alternative options. It’s important to note that while some steps can be taken to reduce the risk of developing hypothyroidism, the condition is not always preventable. Early diagnosis and treatment is the key to prevent any serious complications. What is hypothyroidism icd 10? In the International Classification of Diseases, 10th Revision (ICD-10), hypothyroidism is coded as E03. The ICD-10 codes are a standardized way of identifying medical conditions and are used for billing and statistical purposes. The specific code for hypothyroidism is E03.9, which stands for “unspecified hypothyroidism.” This code is used when the specific type of hypothyroidism (such as Hashimoto’s thyroiditis or postpartum thyroiditis) is not known or not specified. If the specific type of hypothyroidism is known, a more specific code can be used. For example: - E03.0 for Hashimoto’s thyroiditis - E03.1 for postpartum thyroiditis - E03.2 for atrophic hypothyroidism - E03.8 for other specified hypothyroidism Is hypothyroidism an autoimmune disease? Hypothyroidism is not considered an autoimmune disease, but it can be caused by an autoimmune disorder called Hashimoto’s thyroiditis. In Hashimoto’s thyroiditis, the immune system attacks the thyroid gland, leading to inflammation and damage to the gland, which can result in hypothyroidism. Can hypothyroidism cause anxiety? Hypothyroidism can cause anxiety. Hypothyroidism is a condition in which the thyroid gland does not produce enough thyroid hormone, which can lead to a variety of symptoms, including anxiety. People with hypothyroidism may experience feelings of nervousness, worry, and fear, as well as physical symptoms such as a rapid heartbeat, sweating, and trembling. It is important to consult with a medical professional if you suspect you have hypothyroidism or if you are experiencing symptoms of anxiety. They can help to diagnose the condition and provide appropriate treatment.	2	2	0	0	5	0.967183	5	2,604
Medical coding terminology can be intimidating, but it doesn’t have to be. Medical billers and coders must be familiar with medical coding terminology, including names of conditions and illnesses, treatments and medications, and medical code vocabulary. Our team remains updated with changing coding standards as an experienced medical billing and coding company in the United States. They understand billing and coding terminologies and vocabulary, diseases with their diagnosis and treatment options. As you learn more about coding, there are a few key terms you should become acquainted with. Let’s take a look at some of them now. CPT is an abbreviation for Current Procedural Terminology. The American Medical Association maintains the Current Procedural Terminology (CPT) code set through the CPT Editorial Panel, a set of medical codes used to report medical, surgical, and diagnostic procedures and services. These codes are also used in administrative management, such as claim processing and developing guidelines for medical care review. The CPT code set is divided into three components: Category I: The most commonly used codes describes medical procedures, technologies, and services. Category II: This category is used for performance management and additional data. Category III: Houses the codes for emerging, experimental medical procedures and services. International Classification of Disease codes(ICD) helps in classifying diseases, injuries, and causes of death. These codes ensure proper treatment and charging for all medical services rendered. The World Health Organization (WHO) maintains the ICD code set, which is distributed in countries worldwide. The National Centre for Health Statistics created this designation, which is added to the ICD code sets when they are implemented in the United States. Many countries expand and clarify ICD code sets for national use; for example, the United States expanded ICD-10 from 14,000 to over 68,000 individual codes. Evaluation and Management (E/M) Codes: E/M coding is the use of CPT® codes from 99202 to 99499 to represent services provided by a physician or other qualified healthcare professional. As the name implies, these medical codes apply to visits and services that involve analyzing and maintaining patient health. Private health insurance companies have adopted it as the standard guidelines for determining the type and severity of patient conditions. That enables medical service providers to document and bill for services rendered. Codes for services such as surgeries and radiologic imaging are found outside of the CPT® code set’s E/M section. A modifier is a two-character code that is appended to a procedure code to show an important variation that does not change the definition of the procedure on its own. HCPCS codes have alphanumeric modifiers, whereas CPT codes have numeric modifiers. These are placed at the end of a code with a hyphen and may contain information about the procedure itself, its Medicare eligibility, and various other important details. EOB stands for an explanation of benefits. It is a detailed statement from your health insurance company based on payment for a medical billing service you received. It explains which services were covered by your insurance plan and which you are responsible for paying. When you consult a health care provider, you will be asked if you want the treatment billed to your insurance. The medical office should file a health insurance claim with your insurance company if you do. That is a claim to your insurance company for payment to meet the visit, treatment, or equipment expense. When your health care provider submits a claim on your behalf, your insurance company sends it to you. Make sure you understand every line of your EOB when you read it. Use it to keep track of your expenses and ensure no billing mistakes. When the insurance company receives the claim, they will assess it, prepare an Explanation of Benefits, and mail it to you. They may also make a digital version available on their website. Whether you have private insurance, employer-provided insurance, or Medicare, you should receive an EOB. You should receive an EOB for each service you received, regardless of whether you owe anything for the service. You will receive an EOB for each service you got or for the same service performed on different days. AR stands for accounts receivables. Accounts receivable is a corporate asset that represents the amount of money due to you by unpaid customers. Even if the company has not yet received the money, AR symbolizes its value. Accrual-basis accounting acknowledges income just as cash-basis accounting does when it is earned rather than paid. In general, when both parties honor the deal’s conditions, the AR is converted into bankable cash. If a receivable account is not converted into payment on the client-side of the transaction, the value of the AR may decrease. A provider should send you a notice before receiving service if your provider has reason that Medicare will not pay for the service based on Medicare coverage criteria is known as Advance Beneficiary Notice (ABN). You may receive an ABN if you have Original Medicare, otherwise you have a Medicare Advantage Plan. The ABN may differ based on the source which provides it to you. The ABN enables you to choose whether or not to receive the care in question and bear financial responsibility for the service on your own If Medicare denies reimbursement. The note must state why the provider believes Medicare will refuse payment. Billing Executive – a Medical Billing and Coding Knowledge Base for Physicians, Office staff, Medical Billers and Coders, including resources pertaining to HCPCS Codes, CPT Codes, ICD-10 billing codes, Modifiers, POS Codes, Revenue Codes, Billing Errors, Denials and Rejections. We have more than 10 years experience in US Medical Billing and hand-on experience in Web Management, SEO, Content Marketing & Business Development with Research as a special forte.	4	3	2	0	0	0.325016	2	1,203
Single Payer 101 Source: American Medical Student Association (AMSA) Single payer refers to a way of financing health care, which includes both the collection of money for health care and reimbursement of providers for health care costs. In a single payer system, both the collection of funds and the reimbursement are the responsibility of one entity: the government. The government collects funds from individuals and businesses, mainly in the form of taxes, and the government reimburses providers for health care services delivered to individuals enrolled in the public health insurance program. In the United States, there are multiple payers, not a single payer. The collection of money for health care is a joint responsibility of the private insurance industry, which collects premiums and other payments from individuals and businesses, and the government, which collects taxes from individuals and businesses. Similarly, reimbursement responsibilities fall on both the private insurance industry, which reimburses providers for health care services delivered to privately insured individuals, and the government, which reimburses providers for health care services delivered to publicly insured individuals (e.g. people enrolled in Medicare, Medicaid, S-CHIP, or the VA). Denmark, Sweden, and Canada are example of countries with single payer financing of health care. There is also a single payer system in America: the Medicare program, which is the health insurance program for almost every American aged 65 and over. A provider taking care of a Medicare patient has only one entity to bill: the government. In contrast, a provider has multiple entities to bill when dealing with privately insured individuals due to the large number of private insurance companies in America. Importantly, the term “single payer” is different from “socialized medicine” and “universal health care.” Socialized medicine refers to a system like the National Health Service of the U.K., in which the mechanisms of delivery of health care are owned by the government. That is, the government owns the health care facilities and physicians work for the government. In contrast, the mechanisms of delivery of health care in a single payer system are not necessarily owned by the government. Physicians can be either in private practice or public practice, and hospitals can be both publicly or privately owned. In Canada, for example, physicians are predominantly in private practice, while hospitals are both public and private. As another example, American physicians and hospitals that take care of Medicare patients are usually private. Single payer does not specify a health care delivery mechanism; it specifies a health care financing mechanism. The term “universal health care”, in a general sense, refers to providing every citizen of a country with health insurance. Although universal health care connotes a national public insurance program to some people, there are in reality a variety of ways of achieving universal health care, some of which are predominantly public, and others of which use a mixture of public and private elements. Single payer is one way of achieving universal health care, but other ways include the multi-payer systems of Germany and Japan. FEATURES OF SINGLE PAYER SYSTEMS Single payer systems are heterogeneous; Canada’s system is different from Sweden’s system, which is different from U.S. Medicare, and so on. The well-known Proposal of the Physicians’ Working Group for Single Payer National Health Insurance illustrates one way single payer might look in the United States. The following discussion is based on the details of this proposal.1 Eligibility and Benefits: Every resident of the United States would be enrolled in a public insurance system (the National Health Insurance or “NHI” program). Coverage would include all necessary medical care, including mental health, long-term illness, dental services, and prescription drugs. Coverage decisions would be determined by a national board of experts and community representatives; unnecessary or ineffective interventions would not be covered. Patients would not be billed for medical care covered under the NHI program; rather, all costs for covered services would be paid by the NHI program. Private insurance that covers services covered by the NHI program would be forbidden, although private insurance would be available to insure patients for services not covered under the NHI program. The program would be funded by combining current sources of government health spending (Medicare, Medicaid, etc.) into a single fund with modest new taxes, such as a small payroll tax or earmarked income taxes. While taxes will increase for individual citizens, the increase will be offset by reductions in premiums and out-of-pocket spending. Employees may also receive higher wages from employers, who will no longer have to pay as much for health benefits as part of employee compensation (i.e. instead of paying employees in health benefits, employers will pay higher wages). Hospitals would receive a global budget from the NHI program, which means that they would receive a lump sum to cover all operating expenses every month. Hospitals would need to find a way to stay within their global budget while still providing all necessary medical care. The global budget for the hospital would not cover “capital expenditures” (e.g. facility expansions, purchasing new equipment). Such expenditures would be funded by the NHI program separately from the global budget. Approval for capital expenditures would be based on community needs to prevent over-concentration of technology and facilities in one area. Physicians would remain in private practice or continue to work for private hospitals. In terms of reimbursement, physicians could choose one of three ways of being reimbursed: - Fee-for-service: A national fee schedule will be negotiated each year between the NHI program and provider organizations (e.g. medical associations). - Salary at health care facility: Physicians who work for hospitals and other health care facilities would receive an annual salary. - Salary within a capitated group: A group practice or nonprofit HMO that employs physicians would receive payments from the NHI to pay their physicians. These payments would be capitated – that is, a payment would be made every month for each patient enrolled with a physician to cover the cost of taking care of patients. Medications and supplies: An expert panel would create and maintain a national formulary of prescription drugs covered under the NHI program. Prices for drugs and supplies would be negotiated with the NHI program, which would get a good price from manufacturers due to its bulk purchasing power. THE ARGUMENT FOR SINGLE PAYER The argument for universal health care is both similar to and different from the argument for single payer as the specific mechanism for achieving universal health care. Both arguments include the moral travesty of allowing millions to suffer because they lack health insurance, the economic losses associated with lower productivity due to uninsurance, and the cultural dissonance created when there is not health care for all in a country that purports to believe in equality and equal opportunity.2 In this primer, the argument for single payer will focus on its advantages over methods of achieving universal health care that retain the current system of employer-based insurance and for-profit health insurance companies (employer mandates, individual mandates, expansions of Medicaid, tax credits, etc.). Note that a discussion of single payer vs. multi-payer systems like Germany and Japan, while extremely important, is far beyond the scope of this text. Suffice it to say that many of the advantages ofsingle payer systems are retained by these other systems, and that both single payer and non-single payer universal health care systems have distinct advantages over the other. The argument for single payer can be broken down into two parts: philosophical and economic. The philosophical argument for single payer The U.S. health care system is driven largely by market forces, which are predicated on the profit motive. The theory behind the U.S. system is that private health insurance companies seeking to maximize profit will compete with each other, thus driving down costs. How well does this theory work in practice? From 2000-2004, profits for the top 17 U.S. health insurance companies rose 114%; in contrast, the profits of companies in the S&P 500 (an index of 500 commonly owned stocks) rose 5% during the same period.3 Simultaneously, the number of uninsured individuals grew by six million people, and health insurance premiums rose 60%.3,4 Contrary to popular belief, the newly uninsured were overwhelmingly native citizens, not immigrants.5 This situation – private insurance companies making record profits while health insurance premiums and the number of uninsured skyrocket – suggests that insurance companies have an incentive to price people out of health care to maximize profit. The methods by which private health insurance companies achieve this include denial of insurance to people with pre-existing conditions, heavy utilization review, and “cherry- picking” (selectively insuring the healthy and charging higher premiums for the less healthy).2 Whether this is an acceptable situation depends foremost on how valuable society believes it is to have equitable, universal health care access. The free market in health care may deliver a good health insurance product to those who can afford it, but it is not designed to distribute health insurance equally or universally. Private health insurance companies seeking to maximize profit have no incentive to insure everyone, as this would require them to insure patients with high health care costs. If society believes that equality and universality are important features of a health care system, then the current system is necessarily unacceptable. A single payer system would be a far better alternative. The economic argument for single payer The economic argument for single payer is twofold. First, single payer will save money by reducing administrative costs. Second, and more importantly, single payer greatly facilitates cost control because of its centralized administration. The complexity of the American health care system has been the subject of much criticism. As the prominent Brookings Institute economist Henry Aaron wrote, “Like many other observers, I look at the U.S. health care system and see an administrative monstrosity, a truly bizarre mélange of thousands of payers with payment systems that differ for no socially beneficial reason, as well as staggeringly complex public systems with mind-boggling administered prices and other rules expressing distinctions that can only be regarded as weird.”6 Although administrative costs are commonly discussed, there is much confusion as to exactly what they are. The following figure illustrates the nature of some of the functions that induce administrative costs in the U.S. health care system.7 A 2003 New England Journal of Medicine study calculated the administrative costs involved with insurance overhead, employers’ costs to manage health care benefits, hospital administration (e.g. billing), administrative costs of practitioners (e.g. billing), and administrative costs of long-term care facilities. The study estimated that in 1999, as much as $294.3 billion was used for administrative costs, representing 31.0% of health care expenditures in America. In contrast, in Canada’s single payer system, administrative costs represented 16.7% of health care expenditures.8 A few caveats must be applied here: - The authors themselves acknowledge the imprecision of their estimate and the methodological problems involved with studying administrative costs.8 In addition, one study argued that the $294.3 billion amount is an overestimate of at least $50 billion based on methodological issues.6 The actual number of $294.3 billion should not be taken too literally; the more important point is that the administrative costs in America are very high. - Administrative costs are not bad in and of themselves. Some administrative costs, such as quality improvement or utilization review, may improve quality. Others, such as marketing, advertising, or complex billing due to the plethora of private payers in America, are much more questionable in their usefulness.8 The goal is to reduce administrative costs that are wasteful, not to reduce administrative costs in general. - Comparisons of administrative costs are somewhat difficult to interpret, because different health care systems perform different functions. For instance, Canada’s health care system does not cover outpatient prescription drugs for the most part, while the opposite is true for most American private insurers, Medicaid, the VA, and, as of 2006, Medicare. Such differences are the basis for the common argument from single payer opponents that comparing the administrative costs of the U.S. and Canada is like “comparing apples and oranges.” Although no one claims that the cost of administering a drug plan accounts for more than a small percentage of the difference in administrative costs between American and Canada, it is worth remembering that a simple comparison of administrative costs in two countries is most useful when the specific functions each country’s system performs are identical. - Finally, it should be kept in mind that if the United States adopts a single payer system, the administrative functions the system performs will clearly be different from those of Canada’s.6 No two health care systems are identical. Even with all these caveats in mind, there is little doubt that the administrative costs in America are higher than that in Canada. More importantly, much evidence also suggests that a large portion of administrative costs in the U.S. go to functions that likely do not improve patient care. In support of this notion, a 2005 study showed that in California, private insurers devote 20-22% of their spending to “billing and insurance-related functions” (BIR). While the definition and measurement of BIR is potentially controversial, one conclusion that can be comfortably drawn from the study is that physicians, hospitals, and insurers devote a large amount of money to handling claims and hiring administrative staff to deal with billing.9 These costs, along with costs like marketing and advertising, are among the administrative costs that would be saved by switching to a single-payer system. The specific amount saved would vary according to the design and functions of the new system. Cost control mechanisms To slow the rate of health care expenditure growth, a health care system needs to be able to address the major drivers of health care inflation. In general, administrative costs are not thought to be a major cause of health care inflation.10-12 While these costs represent a large expenditure, reducing administrative costs in a single payer system without instituting other cost control mechanisms would do little to slow the growth of health care costs overall. The strongest economic argument for single payer is that it can control costs in a coordinated fashion because of the centralized nature of its administration. In contrast, because of the non-centralized administration of the U.S. health care system, effective cost controls are difficult to institute. For example, Medicare has been more successful at controlling costs than private insurers in recent years, but these cost controls have had little effect on overall health care costs because private insurers have not instituted the same cost controls as Medicare10-12. In essence, when a health care system has multiple payers who all play by different rules, it is extraordinarily difficult to institute systemic cost controls. When a health care system has a single payer and only one set of rules, cost controls can apply to the entire system. To illustrate this point, consider one of the major drivers of health care inflation: the diffusion of new medical technology.11 Overall, technological innovation has improved health care outcomes for patients, but it has done so at the cost of rapidly increasing health expenditures. Furthermore, not every technological innovation is cost-effective, nor is every technological innovation necessarily an improvement over previous technologies.11 In many other industrialized countries, including countries with single payer systems, there are nationally coordinated attempts to assess the cost-effectiveness of health technologies; the results of these evidence-based assessments are made into national policy. The same cannot be said of the United States. While there are various attempts at evidence-based assessment of health technology in America, the results of these assessments often do not substantially affect the practice of medicine. One reason is that specialists and manufacturers of technology have a disproportionate impact on whether a health insurance company covers new technologies, potentially blunting the effects of any evidence-based reports.11 A more important reason is that in the non-centralized U.S. health care system, the effect of any report will necessarily be limited by how much a given payer decides to use the findings to make decisions about what services to cover.11 For example, even if Medicare decides not to cover a technology deemed ineffective by its internal health technology assessment studies, the government has little power to influence whether private insurance companies cover that particular technology. In a single payer system, the government could theoretically use evidence-based assessment of technology to determine what is covered throughout the system, thus minimizing the use of ineffective technologies. As another example of the power of single payer systems to control costs because of its centralized administration, consider cost controls such as global budgeting for hospitals and supply limitations (e.g. preventing the purchase of too many MRIs in an area that is already oversaturated with MRIs). These measures are known to be some of the strongest cost controls available to policy makers. Indeed, other countries have been able to successfully institute such controls, slow down the rate of health care expenditure inflation, and still provide high-quality coverage to its citizens.12 However, the U.S. experience with such controls is limited. This can partly be attributed to politics, but it can also be partly attributed to the impracticality of attempting to institute such controls when there is not one centralized entity overseeing the system. Other cost controls There are a variety of other economic advantages of single payer systems in terms of cost control. First, single payer systems can get better prices for goods and services because of their bulk purchasing power. One study compared the price of a defined group of medications in different countries. The price of these medications in Canada, which uses its purchasing power to negotiate with drug companies, was 60% of the cost of the medications in America.12 Second, because billing is done by one entity, single payer systems facilitate the collection of massive databases that can be used to study and potentially improve practice patterns. The databases can also be used to screen for fraudulent billing by providers, as has been done in Taiwan’s new single-payer system.14 A caveat about cost controls in single payer systems It is important to note that all cost control mechanisms have potential disadvantages and that none of these cost controls discussed above are intrinsic to single payer systems. That is, any given single payer system would not necessarily have global budgeting for hospitals, limitations on technology, etc. The important point is that a single payer system enables the option of instituting these cost controls, whereas that option is not available to policymakers in the current fragmented U.S. health care system. Another important point is that decisions about cost controls in a single payer system will involve a good deal of public debate, as they do in Canada. For example, the public will have influence over what is and what is not covered in the single payer system; if there is a public outcry for technology even though it means paying more for health care, then the system will adapt to these demands. In the current system, as discussed above, coverage decisions by private insurance companies are dominated by special interests, and consumers play a very minor role.11 A system in which decision makers are directly accountable to the public is more likely to be more responsive to public opinion than the current system, in which decision makers (i.e. private insurance company executives) are not directly accountable to the public. In summary, perhaps the strongest economic argument for single payer is that it gives policymakers the option of controlling costs. Whether they elect to use this option will be influenced by a democratic process that incorporates the needs of the American public. ADVANTAGES OF SINGLE PAYER TO VARIOUS GROUPS OF PEOPLE The benefits of single payer are numerous, but they do not accrue to all sectors of society. Clearly, private health insurance companies do not stand to gain from a single payer system, as their role would be dramatically minimized. Furthermore, the pharmaceutical industry does not stand to gain from a single payer system because of the potential for price controls and bulk purchasing. For most Americans, though, single payer would represent a clear improvement over the current system: Advantages to patients - Improved health. The most prominent benefit of single payer is that patients will be able to access health care with minimal financial barriers. This improved access will increase health by increasing preventive/primary care and allowing patients to afford their treatment regimens. - Free choice of provider. Patients will have free choice to choose their doctor. In the current system, not every provider accepts every form of health insurance, and the existence of managed care preferred provider networks is an impediment to free choice of providers. - Portability of coverage. In the current system, insurance status is linked to employment. In a single payer system, a person can go from job to job without experiencing interruptions in health insurance coverage. - De-linking insurance status with employment will also increase the number of small businesses, as there are many people who refrain from starting their own businesses because they are afraid to lose their health insurance (the “job lock” phenomenon).15 Advantages to physicians - Restoration of clinical autonomy: The United States arguably has some of the most intrusive regulation of physician behavior of any industrialized country.16 This regulation comes mainly through private insurance companies, particularly managed care companies that require pre-approval for interventions and institute heavy utilization reviews. In a single payer system, physicians will be relieved from the burden of these regulations, increasing their clinical autonomy. - Lower malpractice premiums: Currently, a significant portion of malpractice jury awards are devoted to future medical costs for the patient. Under a single payer system, this percentage would decrease, as the government would pay for these future medical costs.8 In addition, a single payer system may be able to decrease medical errors and therefore the number of malpractice suits by increasing continuity of care. That is, patients would not shuttle from doctor to doctor because they change insurance companies or their insurance company alters its preferred provider network. - Improved patient care. Physicians will be able to make clinical decisions based on best practices, as the influence of a patient’s financial circumstances will be decreased. Physicians will also enjoy increased compliance by patients, who will be able to afford the medications and interventions prescribed to them. - Simplified billing. Since physicians will have only one entity to bill, billing will be greatly simplified. Physicians will save money on overhead because they will not have to hire to hire as many administrative staff to deal with billing. Advantages to businesses - Decreased health care costs. In 2005, the average employer-based health insurance premium for a family of four was $10,880, while the premium was $4,024 for an individual.17 Under a single payer system, businesses will no longer be required to cover the vast majority of health insurance premiums for their employees. Depending on the specific proposal, businesses might be required to fund the new health care system through a payroll tax, but for most businesses, such a payroll tax is likely to cost less than providing health insurance for employees. - Equal playing field. The businesses that stand to lose money in a single payer system are those that do not currently provide health insurance. Workers in such businesses either enroll in Medicaid, which is taxpayer-funded, or they become uninsured and receive uncompensated care, which is predominantly financed by taxpayer money. Moreover, businesses that do not provide health insurance gain an advantage over businesses that do provide health insurance. Single payer would eliminate this advantage, thus leveling the playing field for businesses. - Improved global competitiveness. The relief of the health care burden on businesses will help stimulate the economy and improve the global competitiveness of U.S. businesses. Currently, U.S. businesses are a competitive disadvantage to foreign companies, which have lower health care costs and therefore lower prices on their products.18 THE POTENTIAL DISADVANTAGES OF SINGLE PAYER The vitality of any public program lies in its funding levels, and the biggest potential disadvantage to a single payer system is the threat of underfunding. There are several ways in which this might occur: - Underfunding by a hostile government: a government that favors privatization might take measures to undermine the public system. In America, the strength of private special interests makes this possibility especially worrisome. - Mismanagement: an inept or corrupt government could misallocate funds in a single payer system, taking away money from vital services and decreasing quality. - Recession: public systems rely on tax dollars, which decrease during recessions. Another potential disadvantage of single payer relates to one of its strengths: the ability to control costs. As noted above, all cost control mechanisms have downsides, and overly aggressive cost control could result in decreases in quality. For instance, inappropriately strict limits on the diffusion of technology might stifle positive innovation in technology. Along with underfunding, this can be avoided through prudent management of the health care system, but it remains a potential concern. The transition from the current system to a single payer would undoubtedly be very difficult. Thousands of people who work for private insurance companies would need to be shifted to other sectors of the economy. Even though these individuals could be trained to work in the new public system, they would still experience a significant change in their lives. Because of these considerations, most single payer advocates and policy analysts believe that any transition to a single payer system would necessarily be gradual, taking place over the course of many years. Finally, there are some important tradeoffs that Americans will have to make in a single payer system. The first is that technology-hungry Americans will have to accept limits on ineffective, questionable, or medically unnecessary interventions that would not be covered by the single payer system. Such interventions could be likely be covered by supplemental private insurance, as is the case in other countries with single payer. The second major tradeoff is that Americans will have to accept less choice in insurance plans. Some Americans want to choose the health insurance plan that is tailored to their individual needs, but a single payer system would give everyone the same insurance plan. The last major tradeoff is that Americans will have to accept more government control and less private control of the health care system. Neither the government nor the private insurance industry can currently claim great popularity with Americans, and the question is which entity Americans will trust more to manage the health care system. This primer has endeavored to articulate the nature and advantages of a single payer system. Solutions that achieve universal health care through mechanisms that build on the current system of for-profit employer-based insurance, while potentially beneficial, do not achieve the philosophical purity, administrative simplification, or cost control potential that a single payer system achieves. Single payer, however, has significant potential disadvantages that must be addressed. Although many of the disadvantages can be avoided through proper management of the system (e.g. funding the system at a very high level and insuring adequate capacity), others represent true tradeoffs that the American public must debate in its mind. The time for such debates is now. In the current system, insurance companies have a financial incentive to avoid insuring the people who need it the most, which means that more and more Americans suffer every year. It is only a matter of time before some type of reform takes place, and single payer should be a reform option that should be seriously considered. Contact: Written by Kao-Ping Chua Flávio Casoy AMSA Jack Rutledge Fellow 2005-2006 AMSA Jack Rutledge Fellow Updated by Flávio Casoy 1902 Association Drive AMSA Jack Rutledge Fellow 2007-2008 Reston, VA 20191 (703) 620-6600 x256 1. Physicians’ Working Group. “Proposal of the Physicians’ Working Group for Single Payer Health Insurance”. JAMA 290(6):798-805, 2003. 2. American Medical Student Association. “The Case for Universal Health Care”, 2006. 3. Britt, R. “Health Insurers Getting Bigger Cut of Medical Dollars.” Investors’ Business Daily, Oct. 15, 2004. Available at 4. Kaiser Family Foundation. “The Uninsured and Their Access to Health Care.” Fact Sheet #1402-07, November 2005. 5. Holahan, J. and Cook, A. “Are Immigrants Responsible for Most of the Growth in the Uninsured?” Kaiser Commission on Medicaid and the Uninsured, October 2005. 6. Aaron, H. "The Costs of Health Care Administration in the United States and Canada—Questionable Answers to a Questionable Question," New England Journal of Medicine 349(9):801–803, 2003. 7. Thorpe, K. “Inside the Black Box of Administrative Costs.” Health Affairs 11(2):41- 55, 1992. 8. Woolhandler, S., Campbell, T., and Himmelstein, D. “Costs of Health Care Administration in the United States and Canada.” New England Journal of Medicine 349:768-775, 2003. 9. Kahn, J., Kronick R., Kreger, M., and Gans, D. “The Cost of Health Insurance Administration in California: Estimates for Insurers, Physicians, and Hospitals.” Health Affairs 24(6):1629-1639, 2005. 10. Bodenheimer, T. “High and Rising Health Care Costs. Part 1.” Annuals of Internal Medicine, 142: 847-854, 2005. 11. Bodenheimer, T. “High and Rising Health Care Costs. Part 2.” Annuals of Internal Medicine, 142: 932-937, 2005. 12. Bodenheimer, T. “High and Rising Health Care Costs. Part 3.” Annuals of Internal Medicine, 142: 996-1002, 2005. 13. Bodenheimer, T. “High and Rising Health Care Costs. Part 4.” Annuals of Internal Medicine, 143: 26-31, 2005. 14. Lu, R. and Hsiao, B. “Does Universal Health Insurance Make Health Care Unaffordable? Lessons from Taiwan.” Health Affairs 22(3):77-88, 2003. 15. Hopkins, J. “Health Insurance Costs Dog Would-Be Entrepreneurs.” USA Today, August 8, 2005. 16. Oberlander J. and Marmor, T. “The path to universal health care.” In: Borosage R., Hickey, R., editors. The next agenda. Boulder (CO): Westview Press; 2001. p. 93- 125. 17. Kaiser Family Foundation. “Employer Health Benefits 2005 Annual Survey”, 2005. 18. Associated Press. “GM to slash jobs, close more plants.” Available at	2	6	1	0	0	0.646588	1	6,435
Hereditary or idiopathic pancreatitis is a condition characterized by recurrent episodes of inflammation of the pancreas. The pancreas produces enzymes that help digest food, and it also produces insulin, a hormone that controls blood sugar levels in the body. Episodes of pancreatitis can lead to permanent tissue damage and loss of pancreatic function. A sudden attack can cause abdominal pain, fever, nausea, or vomiting. Recurrent acute pancreatitis leads to chronic pancreatitis, which occurs when the pancreas is persistently inflamed. Years of inflammation damage the pancreas, causing the formation of scar tissue in place of functioning pancreatic tissue. Pancreatic fibrosis leads to the loss of pancreatic function in many affected individuals. This loss of function can impair the production of digestive enzymes and disrupt normal digestion, leading to fatty stool, weight loss, and protein and vitamin deficiencies. Because of a decrease in insulin production due to a loss of pancreatic function, about a quarter of individuals with hereditary pancreatitis will develop type 1 diabetes mellitus; the risk of developing diabetes increases with age. Chronic pancreatic inflammation and damage to the pancreas increase the risk of developing pancreatic cancer. The risk is particularly high in people with hereditary pancreatitis who also smoke, use alcohol, have type 1 diabetes mellitus, or have a family history of cancer. We provide sequencing analysis for the genes that are associated with pancreatitis. \|Hereditary pancreatitis (HPC) \|\| Mutations in this gene are the cause for 65-80% of cases of HPC. The PRSS1 gene provides instructions for making an enzyme called cationic trypsinogen. This enzyme is produced in the pancreas and helps with the digestion of food. When cationic trypsinogen is needed, it is released from the pancreas and transported to the small intestine, where it is cut into its working form called trypsin. Mutations of PRSS1 can prevent this process from occurring. \|Idopathic pancreatitis (ICP) \|\|An association has been found between CFTR gene mutations and idopathic chronic pancreatitis (ICP). CFTR specifies a widespread chloride channel and severe mutations cause classic CF. Different types of mutation causing different types of channel malfunction probably result in different diseases. CFTR is so large that only complete sequencing can tell which mutations may cause ICP. Mutations account for approxiately 20% of patients with ICP. \|Hereditary pancreatitis (HPC) \|\|Pancreatic secretory trypsin inhibitor (PSTI) is a protein that in humans is encoded by the SPINK1 gene. SPINK1 acts as the first line of defense against prematurely activated trypsinogen in the acinar cells. Mutations causing loss of function have been linked to chronic pancreatitis. Mutations account for less than 10% of patients with HPC. Chronic susceptibility to pancreatitis \|\|Mutations in the CTRC gene encoding the digestive enzyme chymotrypsin C have been shown to increase the risk of chronic pancreatitis. The CTRC gene encodes a protease that functions to prevent premature trypsinogen activation in the pancreas as well as promote trypsin, M. Loss-of-function mutations in CTRC predispose to pancreatitis. Mutations account for less than 5% of patients with ICP. Purpose: Confirmation of Clinical Diagnosis Methodology: Next-Generation Sequencing Test Requisition: Sequencing Requisition Specimen Requirements: 2-5 mL Blood-Lavender Top Tube Panel CPT Codes: 81404x2, 81223, 81479 Cost: $3500.00 Oklahoma Medicaid requires preauthorization for this test) Provider can also select specific genes to be analyzed, this will affect pricing and CPT codes used for insurance filing. Turn-around-time: 5-6 weeks 1. Greer JB, Whitcomb DC. Inflammation and pancreatic cancer: an evidence-based review. Curr Opin Pharmacol. 2009 Aug;9(4):411-8. 2. Keiles S, Kammesheidt A. Identification of CFTR, PRSS1, and SPINK1 mutations in 381 patients with pancreatitis. Pancreas. 2006 Oct;33(3):221-7. 3. Solomon S, Whitcomb DC. Genetics of pancreatitis: an update for clinicians and genetic counselors. Curr Gastroenterol Rep. 2012 Apr;14(2):112-7. 4. Ooi CY, Dorfman R, Cipolli M, Gonska T, Castellani C, Keenan K, Freedman SD, Zielenski J, Berthiaume Y, Corey M, Schibli S, Tullis E, Durie PR. Type of CFTR mutation determines risk of pancreatitis in patients with cystic fibrosis. Gastroenterology. 2011 Jan;140(1):153-61 5. Szmola R, Sahin- Tóth M. Chymotrypsin C (caldecrin) promotes degradation of human cationic trypsin: Identity with Rinderknecht's enzyme Y. PNS. 2007 May; 104(27): 11227–11232. 6. Rosendahl J, Witt H, Szmola R, Bhatia E, Ozsvári B, Landt O, et al. Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated with chronic pancreatitis. Nat Genet 2008; 40:78-82 7. Entrez Gene: SPINK1 serine peptidase inhibitor, Kazal type 1 Gene ID: 6690, updated on 22-Sep-2013. 8. Masson, E, Chen, J, Audrezet, M, Cooper, D, Ferec, C (2013). “A Conservative Assessment of the Major Genetic Causes of Idiopathic Chronic Pancreatitis: Data from a Comprehensive Analysis of PRSS1, SPINK1, CTRC and CFTR Genes in 253 Young French Patients”. PloS ONE 8(8): e73522.	2	7	3	0	0	0.554198	3	1,313
Documentation of chronic kidney disease (CKD) and its stage are crucial for correct coding, which affects hospital revenue and severity of illness classification. Precise diagnosis and reporting of CKD stage improve the accuracy of our national health care database used for research and for projections of national health care needs. The 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease published by the National Kidney Foundation (NKF) is the authoritative, consensus standard for the diagnosis, classification and management of CKD. The guideline identifies five stages of CKD (listed in Table 1), which are defined by either glomerular filtration rate (GFR) decreased to less than 60 mL/min/1.73 m2 or by presence of certain kidney damage markers (listed in Table 2) for more than three months. The diagnosis of CKD stage 1 or 2 requires the presence of one or more of the markers of kidney damage. Therefore, a patient with a GFR greater than or equal to 60 mL/min/1.73 m2 does not have CKD if there are no markers of kidney damage. Stages 3, 4, and 5 are based on GFR cutoffs alone, although such patients may also have markers of kidney damage. Lab reports of creatinine values typically include the calculated GFR for both African-American and non-African-American patients. The calculated GFR is proportional to serum creatinine but also depends on age, race, and gender. The NKF recommends using the CKD-EPI Creatinine Equation, published in 2009, to estimate GFR (available on the NKF website). It is not necessary to perform a 24-hour urine collection to measure creatinine clearance, even though this may be a more precise measure of GFR if done correctly. The stage of CKD can only be correctly assigned when GFR and therefore creatinine levels are at a stable baseline. Staging cannot be performed when the creatinine is in flux, such as during an inpatient admission. Renal function must be stabilized before staging. The currently preferred clinical terminology of “chronic kidney disease” or CKD should be used in diagnostic documentation. Clinicians should avoid nonspecific, imprecise terminology such as “renal insufficiency” or “chronic renal insufficiency (CRI)” as the correct codes for CKD will not be assigned. End-stage renal disease (ESRD) represents the culmination of progressive stage 5 CKD. It has been a long-standing clinical practice to classify patients with CKD who require either dialysis or transplantation as ESRD. However, ICD-10-CM defines ESRD (code N18.6) as “dialysis-dependent stage 5 CKD.” Dialysis dependence means that the requirement for dialysis is expected to last three months or more. A significant conflict exists between the clinical documentation standards and ICD-10-CM coding practices for a patient who has had a kidney transplant. Clinically, transplant patients are considered to have ESRD even though the transplanted kidney may be functioning well. On the other hand, ICD-10-CM requires the transplant status code Z94.0 plus a code for the current CKD stage of the transplanted kidney. All transplant patients are considered to have CKD so any of the five stages will apply, based on the GFR. As an example, the code for a patient with a GFR of 50 mL/min/1.73 m2 after transplant would be N18.3 (CKD-3) and Z94.0. The code for ESRD (N18.6) cannot be assigned because it requires chronic dialysis dependence If the transplant patient eventually became dependent on dialysis again, code N18.6 could then be assigned together with Z94.0. In summary, correct documentation of CKD stage is crucial for accurate coding, hospital reimbursement, and severity of illness classification. Clinicians should always review the calculated GFR associated with the creatinine level on clinical lab reports and remember that CKD stage can only be determined when renal function (GFR and creatinine levels) are stable, unless a recent baseline measurement is available. CKD stages are defined by either a GFR below 60 mL/min/1.73 m2 or by the presence of certain kidney damage markers for more than three months. ESRD is defined clinically as either dialysis dependence or kidney transplant status, but the ICD-10-CM definition requires dialysis dependence. Transplant patients are identified with the transplant status code (Z94.0) plus a code for the current CKD stage of the transplanted kidney. Ask Dr. Pinson Q: A patient with alcohol dependency was admitted for alcohol intoxication with confusion and disorientation. Blood alcohol level was 412 mg/dL. Subsequently he began experiencing signs and symptoms of delirium tremens (DTs) and was transferred to the ICU. In your opinion, is it appropriate to query for toxic encephalopathy due to alcohol intoxication? A: Clinicians should be aware of the coding implications of toxic encephalopathy due to alcohol. Yes, a clarification query may be submitted. Without a query, the code assignment would be: 1. Principal diagnosis code: F10.229, alcohol dependence with intoxication (present on admission [POA] indicator = yes) 2. Secondary diagnosis code: F10.231, alcohol dependence with withdrawal delirium (DTs) (POA = no, since it occurred after admission) The diagnosis-related group (DRG) is 897. If the patient's condition is clarified as toxic encephalopathy due to alcohol, then the code assignment would change to: 1. Principal diagnosis code: T51.0X4A, toxic effect of ethanol, initial encounter (POA = yes) 2. Secondary diagnosis codes: G92, toxic encephalopathy (POA = yes), followed by F10.229 (POA = yes), then F10.231 (POA = no) The resulting DRG is 917. Clinicians should also be aware that documentation of “alcoholic encephalopathy” results in assignment of code G31.2 for a chronic degenerative brain condition (Wernicke-Korsakoff) rather than acute encephalopathy due to alcohol. Q: I was disappointed by your column “Linking Severe Sepsis and Hyperlactatemia” in the June 2018 ACP Hospitalist. You seem comfortable with preserving the Sepsis-2 definition, instead of adopting the 2016 Sepsis-3 criteria that I believe should be embraced by the medical community. Hyperlactatemia is not one of the Sequential Organ Failure Assessment (SOFA) organ dysfunction parameters in the Sepsis-3 definition. A: Thank you for your concern about the Sepsis-2/Sepsis-3 controversy. The June edition of Coding Corner was written in response to a specific question from a reader working at a facility where, whether we agree with it or not, the Sepsis-2 definition is still used—a not uncommon situation at this time. The article was devoted to the diagnostic, documentation, and coding nuances of hyperlactatemia pursuant to the ICD-10-CM Official Guidelines for Coding and Reporting, the Surviving Sepsis Campaign (SSC), CMS's Hospital Inpatient Quality Reporting (IQR) system, and Sepsis-2. I believe we agree on the authoritativeness of Sepsis-3. As I wrote in the June article: “Another issue is that Sepsis-2 definitions and criteria (systemic inflammatory response syndrome [SIRS] due to infection) are no longer the authoritative clinical diagnostic standard for sepsis recognized by SSC, having been replaced by Sepsis-3, which was published in February 2016 and adopted by SSC in March 2017. Appeals of auditor denials based on Sepsis-2 criteria are unlikely to be successful, but all such cases should be reviewed for the possibility of using Sepsis-3 diagnostic criteria as the basis for appeal.” It is widely recognized that the SIRS criteria are overly sensitive, leading to overdiagnosis of sepsis in patients who are not truly “septic.” We should also acknowledge that many of our colleagues do not yet trust the sensitivity of Sepsis-3 and qSOFA without prospective outcomes research and are concerned about underrecognition of truly septic patients. Lastly, the CMS IQR measure for management of severe sepsis still follows selected SIRS diagnostic and severe sepsis criteria (not Sepsis-3/SOFA), so clinicians must utilize these Sepsis-2 criteria for initiating a severe sepsis management bundle to demonstrate quality care. This is certainly an unsettled period in the evolution of our definitions, diagnostic tools, and effective management of sepsis. I hope this discussion offers some clarity for all our readers.	4	8	0	0	18	0.855515	18	1,899
Glioblastoma multiforme GBM also called glioblastoma is a fast-growing glioma that develops from star-shaped glial cells astrocytes and oligodendrocytes that support the health of the nerve cells within the brain. GBM is often referred to as a grade IV astrocytoma.These are the most invasive type of glial tumors, rapidly growing and commonly spreading into nearby brain tissue. Doctor answers on Symptoms, Diagnosis, Treatment, and More: Dr. Stansby on glioblastoma death symptoms: Headaches and seizures it is very unlikely to have brain tumor at your age. See neurologist if you want more assurance. for topic: Glioblastoma Death Symptoms. Glioblastoma causes symptoms when it presses on parts of your brain. If the tumor isn’t very large, you might not have any symptoms. Glioblastoma is a specific type of astrocytoma or cancer of the brain. It is the most common brain tumor in adults. Glioblastoma grows very aggressively because it creates its own blood supply and it destroys normal brain tissue rapidly. There are treatment options available that can ease the symptoms. Glioblastoma can cause death. Glioblastoma is a kind of brain cancer and it is the most common kind of malignant brain tumor for adults. It can develop and spread in fast pace. Its possible signs include headaches, nausea, and some symptoms like those of strokes. Glioblastoma, also known as glioblastoma multiforme, can be very difficult to treat and a cure is often not possible. Treatments may slow progression of the cancer and reduce signs and symptoms. Diagnosis. Tests and procedures used to diagnose glioblastoma include: Neurological exam. Glioblastoma Multiforme - an easy to understand guide covering causes, diagnosis, symptoms, treatment and prevention plus additional in depth medical information. Glioblastoma multiforme is the most agressive cerebral tumor that afflicts humans. It is primarily found in the hemisperes of the brain and is almost always associated with considerable edema swelling of the surrounding tissue. It’s also not unc. Glioblastoma, also known as glioblastoma multiforme GBM, is the most aggressive cancer that begins within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality changes, nausea, and symptoms similar to those of a stroke. Worsening of symptoms often is rapid, and may progress to unconsciousness. 12.03.2017 · I have replaced the last video with this one. I had uploaded the unedited version. Apologies and thank you for the previous comments. Brittany Maynard's Death: Why Is Brain Cancer So Lethal? Brittany Maynard Takes Medicine to End Her Life at 29 Nov. 3,. 56, diagnosed in July 2013 with level 4 glioblastoma. 12.01.2017 · Coping with brain cancer Glioblastoma GBM G1GB GBM army. Loading. Inside Indiana State Prison S1 • E1 Meeting America's Death Row Inmates: Part 1 Prison Documentary Real. Glioblastoma multiforme malignant brain tumor cells. Make an appointment with your doctor if you have any signs and symptoms common to glioma. Request an Appointment at Mayo Clinic. Causes. Like most primary brain tumors, the exact cause of gliomas is not known. Glioblastoma multiforme from diagnosis to death: a prospective, hospital-based, cohort, pilot feasibility study of patient reported symptoms and needs Heidrun Golla & Maryam Ale Ahmad & Maren Galushko & Jürgen Hampl & Mohammad Maarouf & Michael Schroeter & Ulrich Herrlinger &. Glioblastoma multiforme GBM is a type of brain tumour. If you're suffering from glioblastoma multiforme, or know someone who is,. Looking at him now, it seems he’s displaying all the end of life symptoms that present in patients with brain tumours and I can’t help but see his current state and wish it would all end soon. What Are the Signs and Symptoms of Glioblastoma? How do doctors recognize glioblastoma? There is no simple test. Doctors suspect that a brain tumor, possibly a glioblastoma, is a potential. What is Glioblastoma Multiforme?In This Article1 What is Glioblastoma Multiforme?2 Symptoms of Glioblastoma Multiforme3 Causes of Glioblastoma Multiforme4 Treatment for glioblastoma multiforme5 Stage 4 glioblastoma multiforme Life expectancy6 Prognosis and Survival Rate Glioblastoma Multiforme is referred as Grade IV Astrocytoma. Glioblastoma MultiformeRead more ›. Den mest ondartede typen hjernesvulst glioblastom, gir gjerne symptomer som gjør at den som rammes søker hjelp etter bare noen uker, mens personer med langsomtvoksende svulster for eksempel meningeom, kan gå i flere år før de søker hjelp for sine symptomer. Av og til oppstår blødning i svulsten. 24.05.2013 · She underwent 6 weeks of chemo and radiation. The last few months she has been on temador. The other day she had difficulty walking but it only lasted a few minutes. As her mom Iam interesting in what symptoms Ishould be watching for. Your timeline very interesting.thank u! Deaths from Glioblastoma including outcomes, complications, fatality, life expectancy and survival rate information. Glioblastoma can be difficult to treat since some cells may respond well to certain therapies, while others may not be affected at all. Because of this, the treatment plan for glioblastoma may combine several approaches. The first step in treating glioblastoma is a surgical procedure to make a diagnosis, to relieve pressure on the brain, and to safely remove as much tumor as possible. FORMER Labour MP Tessa Jowell spoke out about her cancer battle before her death in May 2018. But what is glioblastoma and what are the symptoms? What is glioblastoma? Glioblastoma. Learn about Glioblastoma, also known as glioblastoma multiforme or a grade 4 astrocytoma, one of the most common and aggressive types of brain tumors. The average time from first symptoms to death is approximately 14 to 16 months, though this varies somewhat between individuals. When it comes to health, Deborah Britting has one message for others: Don't ignore potential symptoms. As a glioblastoma survivor, she's speaking from experience. A painful headache turned out to be a brain tumor symptom that led to her brain tumor diagnosis: glioblastoma. Deborah came to MD Anderson for her glioblastoma clinical trial treatment, which used intensity modulated proton therapy. Glioblastoma can develop and spread in fast pace. Its possible signs in the early stage include headaches, nausea, and some symptoms like those of strokes. Worsening of symptoms often is rapid, during the final days patient may be unconscious. 20.09.2014 · I am very inspired by your story and wish you all the luck in the world. My dad had Glioblastoma and unfortunately died when i was very young. i am 12 now and have come to age where i want to know more about what caused my dads death and your blog has helped me very much. keep going strong! Georgia Australia. Some symptoms of glioblastoma are headaches, vision problems, speech issues and possible seizures. Treating glioblastoma is difficult, but doctors can recommend surgery for tumor removal. If the entire tumor is not easily accessible, then a partial tumor removal is possible. Hi- My 77 year old mother just passed away 3 months ago from Glioblastoma. Now that time has passed I am more and more confused about her death because she had no real symptoms. Famous Deaths Caused by Glioblastoma and Other Brain Tumors. by kick node. After Ted Kennedy’s brain tumor diagnosis and recently seeing a complete list of famous names who died of or survived brain tumors over the last twenty years,. you’ll find out some of the horrible symptoms he had to experience as the tumor progressed. “When the patient‘s condition declines due to tumor progression, and further tumor-directed treatment is not an option, the end-of-life phase begins. During this phase, symptom burden becomes high and patients are often troubled by seizures and de. Tykt Hår Hodebunn Corgi And Dotson Mix Butler Community College Lerret Pakistan New Zealand 2. T20 Høydepunkter Flower Moon Movie Cpr Instruktorsertifisering Online Vannparker I Hotell I Nærheten Av Meg Irctc E Ticket Booking Ny Nettside Forskjellen Mellom Canadian Club Og Canadian Mist Bruins Radio Online 3m Ultrathon Insektmiddel Finnes Det En Vedtektsbegrensning I Sivile Saker Fot Og Ankel Rehab Seventh Avenue Promo Heklet Blomsterteppe Mønster Gratis Beste App For Å Lære Koreansk Alfabet Min 4 Måneder Gamle Sover Hele Tiden Starter Et Forhold Om Igjen Sitater Eksempelbrev For Innsamlingsanmodning Om Sponsing Hi Tech Gulvrensing Sør-Afrika Mot Pakistan 5. 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I'm a provider You will be redirected to myBlue. Would you like to continue? Please wait while you are redirected. DESCRIPTIONHyperhidrosis may be defined as excessive sweating, beyond a level required to maintain normal body temperature in response to heat exposure or exercise. Hyperhidrosis can be classified as either primary or secondary. Primary hyperhidrosis is idiopathic in nature, typically involving the hands (palmar), feet (plantar), or axillae. Secondary hyperhidrosis can result from a variety of drugs, such as tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), or underlying diseases/conditions, such as febrile diseases, diabetes mellitus, or menopause. Gustatory hyperhidrosis is an unusual iatrogenic cause of facial hyperhidrosis in response to hot or spicy foods, resulting from surgery to the parotid gland and subsequent aberrant regenerating parasympathetic fibers. Frey’s syndrome is an uncommon type of secondary gustatory hyperhydrosis that arises from injury to or surgery near the parotid gland resulting in damage to the secretory parasympathetic fibers of the facial nerve. After injury, these fibers regenerate and miscommunication occurs between them and the severed postganglionic sympathetic fibers that supply the cutaneous sweat glands and blood vessels. The aberrant connection results in gustatory sweating and facial flushing with mastication. Aberrant secondary gustatory sweating follows up to 73 percent of surgical sympathectomies and is particularly common after bilateral procedures. The consequences of hyperhidrosis are primarily psychosocial in nature. Excessive sweating may be socially embarrassing (i.e., limiting the ability to shake hands) or interfere with certain professions. For example, palmar hyperhidrosis may preclude artwork, working with electrical components, or playing certain musical instruments. In addition, hyperhidrosis may require several changes of clothing a day; excessive sweating may also result in staining of clothing or shoes. Symptoms such as fever, night sweats, or weight loss require further investigation to rule out secondary causes. Sweat production can be assessed with the minor starch iodine test, which is a simple qualitative measure to identify specific sites of involvement. A variety of therapies have been investigated for primary hyperhidrosis, including topical therapy with aluminum chloride or tanning agents, iontophoresis, botulinum toxin, and endoscopic transthoracic sympathectomy and surgical excision of axillary sweat glands. Treatment of secondary hyperhydrosis focuses on treatment of the underlying cause, such as discontinuing certain drugs or hormone replacement therapy as a treatment of menopausal symptoms. The outcome of different surgical and medical treatment modalities is best assessed by using a combination of tools. Quantitative tools include gravimetry, evaporimetry, and Minor's starch and iodine test. Qualitative assessment tools include general health surveys and hyperhydrosis -specific surveys. Of these, the Hyperhidrosis Disease Severity Scale (HDSS) has been found to have a good correlation to other assessment tools and to be practical in the clinical setting. Drysol™ (aluminum chloride [hexahydrate] 20% topical solution, Person and Covey, Inc.) is FDA approved as an astringent to be used as an aid in the management of hyperhidrosis (axillae, palmar, plantar, and craniofacial) available by prescription. In 2004, the U.S. Food and Drug Administration (FDA) approved OnabotulinumtoxinA (marketed as Botox) [formerly botulinum toxin type A] to treat primary axillary hyperhydrosis (severe underarm sweating) that cannot be managed by topical agents such as prescription (Drysol™) and over-the-counter (OTC) (i.e., Certain Dri® 12%) topical agents with aluminum chloride. A typical dosage would be intradermal injections of 50 units per axilla. Efficacy begins in about 7 to 10 days and lasts approximately 4 to 12 months. Contraindications to OnabotulinumtoxinA (Botox) toxin include infection at the proposed injection site(s), pregnancy, and lactation. OnabotulinumtoxinA (Botox) should be used with caution in patients with neuromuscular disorders (i.e., myasthenia gravis) and patients taking medications such as aminoglycosides, pencillamine, quinine, and calcium channel blockers. The safety and effectiveness has been established for patients 18 years and older. Botulinum toxin has also been investigated as a treatment of hyperhydrosis in body areas other than the axilla and for secondary gustatory hyperhydrosis. The FDA completed a safety review of botulinum toxin products, which included OnabotulinumtoxinA (marketed as Botox) [formerly botulinum toxin type A] and RimabotulinumtoxinB (marketed as Myobloc) [formerly botulinum type B]. On July 31, 2009, the FDA approved the following revisions to the prescribing information: In January 2011, the miraDry System (Miramar Labs, Inc.; Sunnydale, CA) was cleared by the FDA through the 510(k) process for treating primary axillary hyperhidrosis. This is a microwave device designed to heat tissue at the dermal-hypodermal interface, the location of the sweat glands. Treatment consists of 2 sessions of approximately one hour in duration. Sessions occur in a physician’s office and local anesthetic is used. Prior Authorization is required for Botox®. Refer to the Botulinum Toxin medical policy for other indications. Primary Focal Hyperhidrosis Primary focal hyperhidrosis is defined as excessive sweating induced by sympathetic hyperactivity in selected areas that is not associated with an underlying disease process. The most common locations are underarms (axillary hyperhidrosis), palms (palmar hyperhidrosis), soles (plantar hyperhidrosis) or face (craniofacial hyperhidrosis). In the majority of patients, treatment of hyperhidrosis would be considered not medically necessary based on the lack of functional impairment or medical complications. In a small subset of patients, treatment of primary hyperhidrosis may be considered medically necessary with the following medical complications: * FDA approved indications Secondary hyperhidrosis is excessive sweating that can be generalized or craniofacial sweating and may occur as a result of olfactory or gustatory stimuli, neurologic lesions, intrathoracic neoplasms, Raynaud’s disease and Frey’s syndrome. Secondary Gustatory Hyperhidrosis The following treatments would be considered medically necessary for the treatment of severe gustatory hyperhidrosis: The following treatments are considered investigational as a treatment for severe gustatory hyperhidrosis including, but not limited to: * FDA approved indication Treatment of severe primary axillary hyperhidrosis with OnabotulinumtoxinA (Botox) is considered medically necessary after a consultation with a dermatologist, and prior authorization. Botox Administration by a Nurse Practitioner in Mississippi In accordance with the Mississippi State Board of Medical Licensure and the Mississippi State Board of Nursing, the appropriately prepared Nurse Practitioner can administer Botox injections provided that all of the following criteria are met: Federal Employee Program 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. State Health Plan (State and School Employees): OnabotulinumtoxinA (Botox®) does not require prior authorization. However, it will be reviewed for medical necessity based on medical policy guidelines. Out of State Providers: The criteria for Botox® administration by a Nurse Practitioner do not apply to out of state providers; however, the prior authorization and medical necessity criteria outlined in the Policy section must be met. POLICY GUIDELINESA multispecialty working group defines primary focal hyperhidrosis as a condition that is characterized by visible, excessive sweating of at least 6 months’ duration without apparent cause and with at least 2 of the following features: bilateral and relatively symmetric sweating, impairment of daily activities, frequency of at least once per week, age at onset younger than 25 years, positive family history, and cessation of focal sweating during sleep. In the hyperhidrosis disease severity scale, patients rate the severity of symptoms on a scale of 1-4: Investigative 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 HISTORY3/25/2004: Approved by Medical Policy Advisory Committee (MPAC) 4/29/2004: Code Reference section completed 9/9/2004: Policy statement "Treatment of hyperhidrosis with botulinum toxin is considered investigational and not medically necessary since it is not FDA approved for this indication." changed from investigational to medically necessary as follows: "Treatment of severe primary axillary hyperhidrosis with botulinum toxin is considered medically necessary after failed treatment using topical agents."; "The treatment of axillary hyperhidrosis is considered cosmetic and therefore not eligible for coverage." deleted, Code Reference section updated, ICD-9 diagnosis code 780.8 description revised and "Note" added covered table, HCPCS J0585 added covered table, non-covered table added, CPT code 15878, 17999, 97033 added non-covered table, ICD-9 procedure code 86.3, 86.83, 99.27 added non-covered table 11/18/2004: Reviewed by MPAC, Treatment of severe primary axillary hyperhidrosis with botulinum toxin is considered medically necessary after failed treatment using topical agents, consultation with a dermatologist, and prior authorization. Sources updated 5/5/2005: Code Reference section updated, ICD-9 diagnosis code 705.21 added with Note: "Use code 780.8 to report all forms of hyperhidrosis for dates of service prior to 10/1/2004. See POLICY statement for coverage information regarding the various forms of hyperhidrosis." ICD-9 diagnosis code 780.8 description "Hyperhidrosis (includes palmar hyperhidrosis, axillary hyperhidrosis, and primary hyperhidrosis)" revised to read "Generalized Hyperhidrosis" with a Note change from "See POLICY statement regarding the coverage of palmar, axillary, and primary hyperhidrosis added 9/9/2004" to "See POLICY statement regarding the coverage of the various types of hyperhidrosis" 3/14/2006: Coding updated. CPT4 2006 revisions added to policy 8/7/2006: Policy reviewed and policy statement re-written for clarification. 01/01/2009: Accredo preferred provider information removed. BCBSMS information added. 07/27/2009: Policy Description section updated for a clearer understanding of primary and secondary hyperhidrosis symptoms and treatments, Policy Statement section revised to add table with treatments considered medically necessary per region and treatments considered investigational per region for a clearer understanding of the intent of the policy, Policy Guidelines section updated to add features of hyperhidrosis, note added to HCPCS code J0585 under covered table, HCPCS code J0587 added to non covered table. 08/03/2010: Policy description updated to add new FDA information about the safety evaluation of botulinum toxin products and the new drug names established to reinforce individual potencies and prevent medication errors. Botulinum type A and botulinum B were changed to OnabotulinumtoxinA and RimabotulinumtoxinB, respectively, throughout the policy. Added links to related medical policy. FEP verbiage added to the Policy Exceptions section. Code Reference Section updated to add ICD-9 code 705.22 and J3490 to the Covered Codes table. Moved CPT code 17999 from non-covered to covered. Added 64818 and J0856 to the Non-covered Codes table. Revised the descriptions of J0585 and J0587. Added the FDA Web site to the Sources section. 08/03/2011: Policy reviewed; no changes. 05/07/2012: For clarity purposes, added "if a medically necessary medical complication listed above is present" to the table regarding treatments considered medically necessary for primary hyperhidrosis. Intent of policy statement unchanged. 07/12/2012: Microwave treatment added as investigational for primary focal hyperhidrosis. 11/06/2013: Radiofrequency ablation added as investigational for palmar hyperhidrosis. Clarified that OnabotulinumtoxinA (Botox) is considered investigational for palmar hyperhidrosis. 09/15/2014: Policy reviewed; no changes. 12/15/2014: Added criteria for coverage of Botox administration by a Mississippi Nurse Practitioner. Policy Exceptions section updated to add the State Health Plan member exception to be consistent with the Botulinum Toxin medical policy. Policy Exceptions section also updated to state that the criteria for Botox® administration by a Nurse Practitioner do not apply to out of state providers; however, the prior authorization and medical necessity criteria outlined in the Policy section must be met. Added Mississippi State Board of Medical Licensure and Mississippi Board of Nursing to the Sources section. SOURCE(S)Blue Cross Blue Shield Association policy # 8.01.19 Hayes Medical Technology Directory Patrick J. Lillis, MD, and William P. Coleman III, MD, Liposuction for Treatment of Axillary Hyperhidrosis, Dermatologic Clinics July 1990; Vol 8, No 3.; 479-482. Strutton et al. US Prevalence of hyperhidrosis and impact on individuals with axillary hyperhidrosis: Results from a national survey. Journal of The American Academy of Dermatology. August 2004; Vol 51, Number 2; 241-248. (added 11-18-2004) Hornberger et al. Recognition, diagnosis, and treatment of primary focal hyperhidrosis. Journal of The American Academy of Dermatology. August 2004; Vol 51, Number 2; 275-286. Hayes Alert, Vol VII, Number 8 – August 2004 www.fda.gov: Information for Healthcare Professionals: OnabotulinumtoxinA (marketed as Botox/Botox Cosmetic), AbobotulinumtoxinA (marketed as Dysport) and RimabotulinumtoxinB (marketed as Myobloc) Mississippi State Board of Medical Licensure Mississippi Board of Nursing CODE REFERENCEThis may not be a comprehensive list of procedure codes applicable to this policy. The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document. Not Medically Necessary Codes	4	18	6	9	0	0.812797	15	3,232
Somerset and Wessex Eating Disorders Association "Supporting those affected by eating disorders" As you will see from our Definitions section, technically speaking there exist only a small number of 'official' eating disorders (plus their atypical variants), Anorexia Nervosa, Bulimia Nervosa and Eating Disorders Not Otherwise Specified (EDNOS) as defined in the two diagnostic manuals DSM-IV and ICD-10. The latter category - EDNOS - provides a convenient, generic place to stow away a variety of eating disordered behaviour that does not conform to the diagnostic criteria for Anorexia and Bulimia Nervosa. Currently Binge Eating Disorder, although recognised as possibly being a distinct eating disorder in its own right, would constitute an Eating Disorder Not Otherwise Specified. There are a number of other conditions in which disordered eating or body image/weight play a significant part. A number of them may be considered by some to be eating disorders in their own right but which, by lacking a formal diagnosis and definition, are to be consigned to the Eating Disorders Not Otherwise Specified (EDNOS - DSM-IV) category, or Eating Disorders Unspecified (ICD-10). Others may be distinct disorders in themselves and have diagnostic criteria and classification in the diagnostic manuals but not being considered eating disorders (DSM-IV ~ 307, ICD ~ F50) despite having a disordered eating or distorted body image component. We have given some examples below along with a brief description. Please note that the groups that these conditions have been ordered in are for illustrative purposes only and may vary between different organisations. This information is by no means complete or authoritative and provided only to give an illustration of other conditions with food, eating or body image distortion elements. Unofficial Eating Disorders is a 'homemade' catagory we have created in order to include 'disorders' created by third parties such as authors, the media etc. to describe certain patterns of eating or body image related behaviour. They are not 'official' in the sense that they do not appear in the diagnostic systems either as recognised disorders or, as in the case of Binge Eating Disorder, as research criteria. It should be noted that experts in the field of eating disorders may themselves label eating disordered behaviour which may then be adopted by some quarters of the medical profession. • Anorexia Athletica The term has since come to be used, rather loosely, in some quarters to simply refer to compulsive exercising. There is much information and research available on the internet for anyone wishing to look into anorexia athletica further, for example the 1994 paper by Sundgot-Borgen - "Risk and trigger factors for the development of eating disorders in female elite athletes" . • Bigorexia (Muscle Dysmporphia) Although unrecognised some members of the scientific community do consider it to be link to eating disorders (in particular anorexia nervosa) in that similar body image distortions and extreme preoccupations to remedy the situation occur (albeit in a reverse direction). The use of steriods and anabolic agents and the associated health risks to achieve the desired goal may be seen to be strikingly similar to the use of laxative, diueretics and slimming pill with anorexia nervosa and bulimia nervosa. They are also likely to have self-esteem and 'coping' issues in common. Bigorexia is considered to affect more men than women and there may be connections between Bigorexia and anorexia nervosa in terms of percieved gender ideals. • Ortharexia Nervosa Ortharexia Nervosa is not a recognised condition and lacks the 'clarity' of diagnostic criteria when it comes to defining whether an individual has Ortharexia Nervosa. Individuals with obsessive and/or dangerous behaviour around 'proper' food might be considered to fit Dr. Bratman's label but equally may not. Lacking diagnostic criteria and therefore differential diagnosis it is unclear whether individuals following extreme dietary practices for religous or moral reasons would be considered. Any connections with Obsessive Compulsive Disorder are also unclear. Most people would not consider Ortharexia Nervosa an eating disorder on the grounds that the emphasis and concern relates to the quality or purity of food rather than on a desire to be thin and/or any body distortion issues. However if one considers 'eating disorders' to be mechanisms of coping with underlying distress the definition 'may' fit. • Multi-Impulsive Bulimia Multi-impulsive bulimia is not a formal diagnosis and has been challenged but is recognised by some agencies and clinics. It should be noted that both DSM-IV and ICD-10 consider eating disorders to be a catagory in their own right and not impulse control disorders. It may also be worth noting that it is not unkown for additional self-harming behaviours to be used by individuals suffering from bulimia nervosa as a way of copy with the distress of their bulimic condition. Multi-impulsive bulimia is a complex area and much information (for and against) can be found on the internet. Eating Problems in Children There are a number of eating problems found in children which are not generally considered to be eating disorders and lack formal diagnostic criteria and classification. It is argued that these childhood eating problems are not eating disorders because it is felt that they have different causes and symptoms and require different treatment. This view is, however, not universally accepted and some do considered certain of them to be eating disorders in themselves. Things can be further complicated as, due to the lack of formal diagnostic criteria, different professionals may choose to apply different names to the same problem. In some instances some professionals may consider a pattern of disordered eating in a child to be simply an extreme manifestation of 'picky eating' behaviour which often occurs normally in children; it is not unheard of for childhood eating problems to be dismissed as faddy eating which the child will "grow out of". Which ever view is subscribed to these childhood disordered eating problems can be very distressing and, in some cases, have serious consequences. Below are some examples of childhood eating problems, this list is by no means complete nor does the inclusion of a condition necessarily mean that that condition is restricted on to children. • Food Avoidance Emotional Disorder This can be mistaken for child onset anorexia nervosa but there are a number of differences. Notably it is considered that the avoidance of food results from symptoms of emotional difficulties (such as depression or worry) which affect appetite and is not an attempt to use food to suppress these difficulties. The sufferer will often be aware of their eating difficulties and thinness (unlike the distorted body image that can occur in anorexia) and express a desire to eat more. Food Avoidance Emotional Disorder sufferers are also not considered to have preoccupations with weight or aspirations to be thin. • Food Refusal Despite appearing to be manipulative it is often felt that some form of stress, sadness or upset may underlie the behaviour. • Restrictive Eating A child with Restrictive Eating may be below normal height/weight norms for their age but, due to their generally balanced diet, are often considered to be healthy. As with Selective Eating there appears to be no preoccupation with weight or aspirations to be thin. • Selective Eating [Disorder] There does not seem to be a group of foods common to selective eating and consequently the the consequences of the problem can be dependant on the type and range of foods taken but malnutrition must be considered. Body weight may be high, low or normal and as such is not a good indication of the condition. Dental problems may occur is the child's acceptable range of food contains sugary foods. Selective Eating does not seem to have the preoccupation with weight and desire to be thin components of anorexia nervosa. Other [related?] Disorders There are a number of other disorders which are sometimes considered to be related in some way to 'eating disorders' in that they posses a symptomatic component which can be seen to be similar to symptoms existing with 'eating disorders'. These disorders are often conditions in their own right with their own diagnostic criteria. Some examples are shown below. • Body Dysmorphic Disorder Body Dysmorphic Disorder is sometime considered to have associations with Social Phobia and Obsessive Compulsive Disorder. It is sometimes associated with eating disorders in that the 'body dysmorphia' can be seen to have similarities with the dissatisfaction with, and distorted view of, body shape and size seen in anorexia nervosa. Interestingly Body Dysmorphic Disorder cannot be diagnosed in the presence of a dissatisfaction with, or distorted image of, body size/shape cause by anorexia nervosa (differential diagnosis). • Food Phobia Where the phobia is related to food (Sitophobia) or the process of eating, the fear and avoidance of eating can show 'eating disorder' like symptoms. There are a number of Specific Phobias that can fall into this category. • Night Eating It is unclear exactly what Night Eating Syndrome is, it is variously considered to be a form of eating disorder, a dysfunction in the body clock, that it may be stress induced, physiological rather than psychological (possibly hormonal) and others. Obsessional behaviour around food/dieting may present 'eating disorder' like symptoms. It is also thought by some the OCD and eating disorders 'may' be related in some way. It is not uncommon for someone to suffer both an eating disorder and OCD. Pica is not generally considered a serious condition, however depending on the substances consumed intestinal blockages can occur and the ingestion of toxic non-food substances is possible as is contracting parasitic or bacterial infections. There is an obvious 'food' connection between Pica and eating disorders and one of the reasons often cited for Pica, the eating of non-calorie non-food items to ease hunger (when dieting), is often mirrored in eating disorders. Pica in adults is included is ICD-10's 'Other Eating Disorders' (F50.8) catagory and as such is an eating disorder under this diagnostic system. • Pervasive Refusal Pervasive Refusal Syndrome is a very serious, non-organic, condition in which a child may present an overwhelming refusal to eat, drink, engage in activities (e.g. walking) or generally care for themselves in any way (including washing, toileting etc.). This is obviously a life threatening condition and since the refusal to eat and drink is likely to elicit concern first, it may be that the condition is seen to an eating disorder. In some quarters Pervasive Refusal Syndrome is considered to be a child form of 'catatonia'. The condition is often linked to a previous, severe trauma. One symptom of Prader-Willi Syndrome, thought to be caused by hypothalamic dysfunction, is appetite and satiation dysfunction in which there is an overwhelming physiological urge to eat and an obsession with food. This is compounded by the fact that individuals with Prader-Willi Syndrome have lower than normal calorie requirements. Whilst this is clearly not an 'eating disorder', Prader-Willi Syndrome does have a food/weight component. The Prader-Willi Syndrome Association UK can provide information and support. • Sleep Eating © 2004 ~ 2013 Somerset and Wessex Eating Disorders Association	2	4	0	0	4	0.610802	4	2,383
You are right. Here are the questions for exam 1: 1. In the Tabular List, where would you find alternative terms and explanatory phrases? A. In parentheses B. After a colon C. In square brackets D. In double braces 2. Codes that have mandatory fifth digits are codes that A. require the use of the digit "5" as the fifth character. B. use the numbers 1 or 2 as the fifth digit. C. require four supporting codes. D. always require a fifth digit to fully describe them. 3. A patient presents in the office with diarrhea. Physician documents gastroenteritis. What is the first listed diagnosis? C. Both have equal precedence. Code either one first. D. E&M code for office visit Which of the following is not one of the most common forms of Medicare fraud? Billing for services provided Misrepresenting a diagnosis to justify a payment Routine waiver of copayment Billing for services not furnished What convention in the Alphabetic Index tells you to look elsewhere before assigning a code? An established patient is seen for amenorrhea and galactorrhea, to rule out pituitary tumor. Identify the Amenorrhea and galactorrhea What are the correct code(s) for acute and chronic laryngitis? What category can not be assigned with any other delivery code in the 630–676 range? What volume of the ICD-9-CM is used by hospitals to report inpatient procedures? Volume 1, Supplement An established patient is seen for redness, blurriness and sensitivity to light in her right eye. The documentation states the diagnosis is iritis. Using the ICD-10 guidelines, which would be the diagnosis for this patient encounter? Iritis of the right eye Sensitivity to light The abbreviation NOS is used to indicate that another code may describe the condition more completely or specifically. to provide assurance that the code is correct by listing various terms that are covered by the code. when the medical record doesn't provide enough information to permit assignment of a more specific code. when a separate code for a specific condition isn't provided in the classification system. The correct ICD-10 reporting block that would contain acute cholecystitis with cholelithiasis with A patient is diagnosed with controlled Type 2 Diabetes on insulin without complication. Assign the Identify the correct code for status asthmaticus. What are the correct codes for dehydration due to pneumonia? Identify the correct code for family history of breast cancer, female. What is the main term for "fractured clavicle"? E codes are used to report external causes of injury and poisoning. extra descriptors for coding. extenuating circumstances surrounding an injury. exercise method after injury. When a correct substance is properly administered but has an adverse effect, this is called Patient is admitted for radiation therapy for metastatic bone cancer, primary unknown. Patient develops severe vomiting secondary to the course of radiation and is kept an extra day for stabilization. Assign the V58.0, 787.03, 198.05, 199.1 V58.0, 787.03, 198.05, 199.1, E879.2 170.9, V58, 787.03, 198.05, 199.1, E879.2 787.03, 198.05, 199.1, E879.2 Which chapter in the ICD-10 contains codes for the perinatal period? Which of the following is true about the ICD-10-CM? There's additional information relevant to inpatient encounters. There are limited injury codes. An eighth character was added. There are combination diagnosis/symptom codes. When coding late effects, the code for the _______ is usually sequenced first. Single braces are used in the Tabular List to connect terms on both sides of the braces. connect a series of terms on the left with one term on the right. indicate fifth digits required with a code. include nonessential modifiers and alternative codes. What does the acronym ICD-9-CM mean? International Classification of Diseases, 9th Edition, Coding Manual International Coding Definitions, 9th Version, Coding Manual International Classification of Diseases, 9th Revision, Clinical Modification International Classification of Diagnoses, 9th Edition, Coding Modification If a QIO provider renders a covered service that costs $100 and bills Medicare for the services and Medicare allows $58, the provider would bill _______ to the patient. Identify the correct diagnosis code for benign essential hypertension. A physician has certified that a patient is terminally ill and is expected to live six months or less. The patient is receiving hospice care. Which part of Medicare will cover this service? What is the main term in the diagnosis "pituitary gland hypofunction"? What is the correct code for impending shock? No code is assigned. _______ are used to indicate factors influencing health status and contact with health services. Which of the following is the correct code for a threatened spontaneous abortion, unspecified episode End of exam An established patient presents with chest pain. He has a history of previous myocardial infarction and coronary artery bypass surgery. Using the ICD-10 guidelines, which would be the first-listed diagnosis for this patient encounter? Previous myocardial infarction Possible myocardial infarction Status-post coronary artery bypass surgery For which of the following does Medicare Part A pay? Physician services and durable medical equipment Hospital/facility care and durable medical equipment Professional services and durable medical equipment In which edition of the Federal Register would hospital facilities be especially interested? Its Exam # XXXXX Tomorrow by 3:00 PM. Hi Cher. Sorry about that. That would be Eastern standard. Also if this exam is satisfactory (95-100%), I would like to employ your services on the other 6 exams at the agreed upon price. How are you? I have been sick for a few days and still recovering...but feeling better. I am satisfied with the last exam and thank you for the quick help. I received an 80% which is good but I think I will bump the next help against my answers prior to submitting. Basically like you suggested. Attachments are only available to registered users. I have another exam I need help with if you are willing... 381755RR - CPT AND HCPCS BASICS; EVALUATION AND MANAGEMENT. I'll look for those answers that I missed but in the mean time here are the exam questions I am now referring to: Where is specific coding information about each section located in the CPT? Code assignments in the Evaluation and Management section vary according to three factors. Which factor below is not one of these factors? Place of service Type of service To qualify for a given level of multi-specialty examination, how many content and documentation requirements should be met? At times, the five-digit CPT code may not reflect completely the services or procedures provided. In this situation, you would add a/an Level II code. When a neonate or infant is not considered critically ill but still needs intensive observation and other intensive care services, the initial and continuing intensive care services codes are 99499, unlisted evaluation and management services. What CPT code is assigned to an ED service that has a detailed history and exam with a moderate level What type of code includes all the words that describe the procedure the code represents? The _______ is the universal health insurance form for submission of outpatient services. J codes in the HCPCS Level II system are used to indicate medications and dosages. durable medical equipment. When a range of CPT codes are given in the index, this range is indicated by which symbol? Mr. Smith presents to the Emergency Department at the local hospital for chest pain and is seen by the ED physician on duty. The physician obtains an extended HPI, an extended ROS, and a pertinent PFSH. What is the level of history? How often are Category III codes released? As often as necessary Every three years Twice a year An attending physician asks a specialist to see a patient about a specific problem and to advise him regarding treatment. This situation is called a transfer of care. The words that follow a code number in the CPT manual are called the Critical care codes are reported based on the three key components—history, exam, MDM. amount of documentation. In the index of the CPT manual, which punctuation mark between codes indicates a range of codes is A list of all CPT modifiers used to alter or modify codes may be found in which CPT Appendix? The physician must consider multiple diagnoses and management options. There is a moderate amount of data to be reviewed and the risk of complications or death is moderate. What is the level of MDM? Modifier -59, distinct procedure service, is used to indicate that a subsequent surgery was planned or staged at the time of the first surgery. a patient was taken back to the operating room for surgical treatment of a complication resulting from a previous surgery. services that are usually bundled into one payment were provided as separate services. a service was repeated. A surgical assistant provides service (an extra set of hands) to the primary surgeon during a surgical procedure. The assistant surgeon's services are reported using the same codes as the primary surgeon's, but What year was CPT first developed and published? When a physician performs a preventive care service, the extent of the exam is determined by the patient's gender and age. length of time elapsed since last exam. A procedure or service not found in the CPT manual can be coded as an unlisted procedure if no category I or II exists to describe the procedure/service provided. Unlisted Service or Procedure codes end Which category number or level codes represent services and procedures that have been approved by the FDA and have been proven to have clinical effectiveness? Which of the following types of examination is limited to an affected body area or organ system and other related organ systems? Expanded problem focused After the first eligible procedure is reimbursed at 100% of Medicare allowance, the remaining (up to four) procedures are reimbursed at _______ percent. Modifier -58, staged or related procedure or service by the same physician during the postoperative period, is used to indicate that a subsequent surgery was planned at the time of the first surgery. Modifier -51, Multiple Procedure, is used on what type of services? The physician performs an extended exam of the affected body areas and related organ systems. What is the level of the examination? In which CPT appendix would additions, deletions, and revisions be found? Which one of the following items must be included in a general multisystem examination of a Palpation of lymph nodes Inspection of teeth and gums Auscultation of the lungs Who publishes CPT? How many main sections are in the CPT manual? Which modifier is used by an anesthesiologist to indicate a service for which general anesthesia was used when normally the anesthesia would have been local or regional? Which of the following range of codes is located in the Evaluation and Management section of the CPT	4	3	2	0	2	0.273011	4	2,468
- 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 What is Behcet’s Disease (Behcet’s syndrome) 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	0.818605	3	2,201
Malabsorption Classification and external resources Whipple's disease: Alcian blue with apparently eosin counterstain enlarged villus with many macrophages ICD-10 (K90) ICD-9 579 DiseasesDB 7698 MedlinePlus 000299 eMedicine med/1384 MeSH D008286 Some prefer to classify malabsorption clinically into three basic categories: - (1) selective, as seen in lactose malabsorption; - (2) partial, as observed in a-Beta-lipoproteinaemia, and - (3) total as in coeliac disease. The main purpose of the gastrointestinal tract is to digest and absorb nutrients (fat, carbohydrate, and protein), micronutrients (vitamins and trace minerals), water, and electrolytes. Digestion involves both mechanical and enzymatic breakdown of food. Mechanical processes include chewing, gastric churning, and the to-and-fro mixing in the small intestine. Enzymatic hydrolysis is initiated by intraluminal processes requiring gastric, pancreatic, and biliary secretions. The final products of digestion are absorbed through the intestinal epithelial cells. Malabsorption constitutes the pathological interference with the normal physiological sequence of digestion (intraluminal process), absorption (mucosal process) and transport (postmucosal events) of nutrients. - Mucosal damage (enteropathy) - Congenital or acquired reduction in absorptive surface - Defects of specific hydrolysis - Defects of ion transport - Pancreatic insufficiency - Impaired enterohepatic circulation Due to infective agents Due to structural defects - Blind loops - Inflammatory bowel diseases commonly in Crohn's Disease - Intestinal hurry from Post-gastrectomy; post-vagotomy, gastro-jejunostomy - Fistulae, diverticulae and strictures, - Infiltrative conditions such as amyloidosis, lymphoma, Eosinophilic gastroenteropathy - Radiation enteritis - Systemic sclerosis and collagen vascular diseases - Short bowel syndrome Due to mucosal abnormality Due to enzyme deficiencies Due to digestive failure Due to other systemic diseases affecting GI tract They can occur in a variety of ways and features might give a clue to the underlying condition. Symptoms can be intestinal or extra-intestinal - the former predominates in severe malabsorption. - Diarrhoea, often steatorrhoea is the most common feature. Watery, diurnal and nocturnal, bulky, frequent stools are the clinical hallmark of overt malabsorption. It is due to impaired water, carbohydrate and electrolyte absorption or irritation from unabsorbed fatty acid. Latter also results in bloating, flatulence and abdominal discomfort. Cramping pain usually suggests obstructive intestinal segment e.g. in Crohn's disease, especially if it persists after defecation. - Weight loss can be significant despite increased oral intake of nutrients. - Growth retardation, failure to thrive, delayed puberty in children - Swelling or oedema from loss of protein - Anaemias, commonly from vitamin B12, folic acid and iron deficiency presenting as fatigue and weakness. - Muscle cramp from decreased vitamin D, calcium absorption. Also lead to osteomalacia and osteoporosis - Bleeding tendencies from vitamin K and other coagulation factor deficiencies. There is no specific test for malabsorption. As for most medical conditions, investigation is guided by symptoms and signs. A range of different conditions can produce malabsorption and it is necessary to look for each of these specifically. Many tests have been advocated, and some, such as tests for pancreatic function are complex, vary between centres and have not been widely adopted. However, better tests have become available with greater ease of use, better sensitivity and specificity for the causative conditions. Test are also needed to detect the systemic effects of deficiency of the malabsorbed nutrients (such as anaemia with vitamin B12 malabsorption). - Routine blood tests may reveal anaemia, high ESR and CRP or low albumin; which shows a high correlation for the presence of an organic disease. In this setting, microcytic anaemia usually implies iron deficiency and macrocytosis can be caused by impaired folic acid or B12 absorption or both. Low cholesterol or triglyceride may give a clue toward fat malabsorption as low calcium and phosphate toward osteomalacia from low vitamin D. - Specific vitamins like vitamin D or micro nutrient like zinc levels can be checked. Fat soluble vitamins (A, D, E & K) are affected in fat malabsorption. Prolonged prothrombin time can be caused by vitamin K deficiency. - Serological studies - Specific tests are carried out to determine the underlying cause. - IgA Anti-transglutaminase antibodies or IgA Anti-endomysial antibodies for Coeliac disease(gluten sensitive enteropathy). - Microscopy is particularly useful in diarrhoea, may show protozoa like Giardia, ova, cyst and other infective agents. - Fecal fat study to diagnose steatorrhoea is rarely performed nowadays. - Low fecal pancreatic elastase is indicative of pancreatic insufficiency. Chymotrypsin and pancreolauryl can be assessed as well - Barium follow through is useful in delineating small intestinal anatomy. Barium enema may be undertaken to see colonic or ileal lesions. - CT abdomen is useful in ruling out structural abnormality, done in pancreatic protocol when visualising pancreas. - Magnetic resonance cholangiopancreatography (MRCP) to complement or as an alternative to ERCP - OGD to detect duodenal pathology and obtain D2 biopsy (for coeliac disease, tropical sprue, Whipple's disease, abetalipoproteinaemia etc.) - Enteroscopy for enteropathy and jejunal aspirate and culture for bacterial overgrowth - Capsule Endoscopy is able to visualise the whole small intestine and is occasionally useful. - Colonoscopy is necessary in colonic and ileal disease. - ERCP will show pancreatic and biliary structural abnormalities. - 75SeHCAT test to diagnose bile acid malabsorption in ileal disease or primary bile acid diarrhea. - Glucose hydrogen breath test for bacterial overgrowth - Lactose hydrogen breath test for lactose intolerance - Sugar probes or 51Cr-EDTA to determine intestinal permeability. Obsolete tests no longer used clinically - D-xylose absorption test for mucosal disease or bacterial overgrowth. Normal in pancreatic insufficiency. - Bile salt breath test (14C-glycocholate) to determine bile salt malabsorption. - Schilling test to establish cause of B12 deficiency. Treatment is directed largely towards management of underlying cause: - Replacement of nutrients, electrolytes and fluid may be necessary. In severe deficiency, hospital admission may be required for parenteral administration, often advice from dietitian is sought. People whose absorptive surface are severely limited from disease or surgery may need long term total parenteral nutrition. - Pancreatic enzymes are supplemented orally in insufficiencies. - Dietary modification is important in some conditions: - Antibiotic therapy will treat Small Bowel Bacterial overgrowth. - Cholestyramine or other bile acid sequestrants will help reducing diarrhoea in bile acid malabsorption. - Practice guideline from World Gastroenterology Organisation - Tests for malabsorption; from British Society for Gastroenterology (2003) - ^ Jensen, Jonathan E. "Malabsorption Syndromes - Page 1". Colorado center for digestive disorders. Archived from the original on 2007-04-11. http://web.archive.org/web/20070411100726/http://www.gastromd.com/education/malabsorptionsyndromes.html. Retrieved 2007-05-10. - ^ Gasbarrini G, Frisono M: Critical evaluation of malabsorption tests; in G. Dobrilla, G. Bertaccini, G. Langman (Editor) (1986). Problems and Controversies in Gastroenterology. New York: Raven Pr. pp. 123–130. ISBN 88-85037-75-5. - ^ a b c Bai J (1998). "Malabsorption syndromes". Digestion 59 (5): 530–46. doi:10.1159/000007529. PMID 9705537. - ^ Walker-Smith J, Barnard J, Bhutta Z, Heubi J, Reeves Z, Schmitz J (2002). "Chronic diarrhea and malabsorption (including short gut syndrome): Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition". J. Pediatr. Gastroenterol. Nutr. 35 Suppl 2: S98–105. doi:10.1097/00005176-200208002-00006. PMID 12192177. - ^ M. S Losowsky, (1974). Malabsorption in clinical practice. Edinburgh: Churchill Livingstone. ISBN 0-443-01007-2. - ^ health a to z"Malabsorption syndrome". http://www.healthatoz.com/healthatoz/Atoz/common/standard/transform.jsp?requestURI=/healthatoz/Atoz/ency/malabsorption_syndrome.jsp. Retrieved 2007-05-10. - ^ Bertomeu A, Ros E, Barragán V, Sachje L, Navarro S (1991). "Chronic diarrhea with normal stool and colonic examinations: organic or functional?". J. Clin. Gastroenterol. 13 (5): 531–6. doi:10.1097/00004836-199110000-00011. PMID 1744388. - ^ Read N, Krejs G, Read M, Santa Ana C, Morawski S, Fordtran J (1980). "Chronic diarrhea of unknown origin". Gastroenterology 78 (2): 264–71. PMID 7350049. - ^ Thomas P, Forbes A, Green J, Howdle P, Long R, Playford R, Sheridan M, Stevens R, Valori R, Walters J, Addison G, Hill P, Brydon G (2003). "Guidelines for the investigation of chronic diarrhoea, 2nd edition". Gut 52 Suppl 5 (90005): v1–15. doi:10.1136/gut.52.suppl_5.v1. PMC 1867765. PMID 12801941. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1867765. . - ^ http://www.worldgastroenterology.org/malabsorption.html - ^ http://www.bsg.org.uk/pdf_word_docs/cd_body.pdf Wikimedia Foundation. 2010. Look at other dictionaries: malabsorption — [ malapsɔrpsjɔ̃ ] n. f. • av. 1969; de 2. mal et absorption ♦ Méd. Trouble du processus d absorption des aliments à travers la muqueuse intestinale. ● malabsorption nom féminin Trouble du processus d absorption des aliments à travers la muqueuse… … Encyclopédie Universelle malabsorption — 1879, from MAL (Cf. mal ) + ABSORPTION (Cf. absorption) … Etymology dictionary malabsorption — [mal΄əb sôrp′shən, mäl΄əzôrp′shən] n. the poor absorption of nutrients by the alimentary canal … English World dictionary Malabsorption — Unter Malassimilation von lateinisch malus (schlecht, schädlich, böse) und assimilare (angleichen, ähnlich machen) wird eine beeinträchtigte, das heißt verminderte Nährstoffausnutzung aufgrund unterschiedlichster Störungen im Verdauungstrakt… … Deutsch Wikipedia Malabsorption — Syndrome de malabsorption La malabsorption de nutriments du fait d une maladie de l intestin grêle est rare, mais de diagnostic aisé. La malabsorption est définie par l incapacité du tube digestif à absorber l ensemble des substances alimentaires … Wikipédia en Français malabsorption — Imperfect, inadequate, or otherwise disordered gastrointestinal absorption. congenital selective glucose and galactose m. an inherited disorder in which d glucose and d galactose accumulate in the intestinal lumen and exert an osmotic … Medical dictionary Malabsorption — Mal\|ab\|sorptio̱n [aus gleichbed. engl. malabsorption (eigtl. = schlechte Absorption)] w; , en: Störung der Resorption von Nahrungsstoffen im Darm, vor allem bei Vitaminmangelzuständen … Das Wörterbuch medizinischer Fachausdrücke Malabsorption — Mal\|ab\|sorp\|ti\|on die; <aus gleichbed. engl. malabsorption zu male »schlecht , bös(e) «, dies aus lat. malus (vgl. ↑Malus) u. ↑Absorption> Störung der Resorption von Nahrungsstoffen im Darm, vor allem bei Vitaminmangelzuständen (Med.) … Das große Fremdwörterbuch malabsorption — noun Date: circa 1929 faulty absorption especially of nutrient materials from the gastrointestinal tract … New Collegiate Dictionary malabsorption — /mal euhb sawrp sheuhn, zawrp /, n. Pathol. faulty absorption of nutritive material from the intestine. [1930 35; MAL + ABSORPTION] * * * … Universalium	2	8	5	0	7	0.743294	12	3,139
Millions of people have diabetes and don’t know it. Left undiagnosed, diabetes can lead to severe complications such as heart disease, stroke, blindness, kidney failure, leg and foot amputations, pregnancy complications, and death related to pneumonia and flu. Diabetes is the leading cause of blindness among adults, and the leading cause of end-stage renal disease. The good news is that scientific evidence now shows that early detection and treatment of diabetes with diet, physical activity, and new medicines can prevent or delay many of the illnesses and complications associated with diabetes. Section 613 of the Medicare Prescription Drug, Improvement, and Modernization Act (MMA) of 2003 expanded preventive services covered by Medicare to include preventive screening for beneficiaries at risk for diabetes or those diagnosed with pre-diabetes. This benefit will help to improve the quality of life for Medicare beneficiaries by preventing more severe conditions that can occur without proper treatment from undiagnosed or untreated diabetes. Diabetes (diabetes mellitus) is defined as a condition of abnormal glucose metabolism using the following criteria: A fasting blood glucose greater than or equal to 126 mg/dL on two different occasions. A 2-hour post-glucose challenge greater than or equal to 200 mg/dL on two different occasions. *A random glucose test over 200 mg/dL for a person with symptoms of uncontrolled diabetes ` CPT Codes for Diabetes Screening Tests 82947 – Glucose; quantitative, blood (except reagent strip) 82950 – Glucose; post glucose dose (includes glucose) 82951 – Glucose; tolerance test (GTT), three specimens (includes glucose) Medicare providers must report the screening (“V”) diagnosis code V77.1 (Special Screening for Diabetes Mellitus). Effective April 1, 2005, when a Medicare provider submits a claim for diabetes screening where the beneficiary meets the definition of pre-diabetes, they should report the appropriate diagnosis code with modifier TS. The appropriate CPT code(s) are also required on the claim	4	7	2	0	2	0.948119	4	432
I'm a member You will be redirected to myBlue. Would you like to continue? Please wait while you are redirected. Printer Friendly Version DESCRIPTIONLyme disease (LD) is a multisystem inflammatory disease caused by the spirochete Borrelia burgdorferi transmitted by the bite of an infected ixodid tick endemic to Northeastern, North Central, and Pacific coastal regions of the United States. The disease is characterized by stages, beginning with localized infection of the skin (erythema migrans) followed by dissemination to many sites. Manifestations of early disseminated disease may include lymphocytic meningitis, facial palsy, painful radiculoneuritis, atrioventricular nodal block, or migratory musculoskeletal pain. Months to years later, the disease may be manifested by intermittent oligoarthritis, particularly involving the knee joint, chronic encephalopathy, spinal pain, or distal paresthesias. While most manifestations of LD can be adequately treated with oral antibiotics, intravenous (IV) antibiotics are indicated in some patients with neurologic involvement or atrioventricular heart block. However, overdiagnosis and overtreatment of LD is common due to its nonspecific symptoms, lack of standardization of serologic tests, and difficulties in interpreting serologic tests. In particular, patients with chronic fatigue syndrome or fibromyalgia are commonly misdiagnosed as possibly having LD and undergo inappropriate IV antibiotic therapy. The purpose of this policy is to provide diagnostic criteria for the appropriate use of IV antibiotic therapy. The following paragraphs describe the various manifestations of LD that may prompt therapy with IV antibiotics and the various laboratory tests that are used to support the diagnosis of LD. Neurologic Manifestations of Lyme Disease (Neuroborreliosis) Lymphocytic meningitis, characterized by head and neck pain, may occur during the acute disseminated stage of the disease. Analysis of the cerebrospinal fluid (CSF) is indispensable for the diagnosis of Lyme meningitis. If the patient has LD, the CSF will show a lymphocytic pleocytosis (lymphocyte count greater than normal) with increased levels of protein. Intrathecal production of antibodies directed at spirochetal antigens is typically present. A normal CSF analysis is strong evidence against Lyme meningitis. Treatment with a 2- to 4-week course of IV antibiotics, typically ceftriaxone or cefotaxime, is recommended. Cranial neuritis, most frequently Bell’s palsy, may present early in the course of disseminated LD, occasionally prior to the development of antibodies, such that a LD etiology may be difficult to rule in or out. While Bell’s palsy typically resolves spontaneously with or without treatment with oral antibiotics, some physicians have recommended a lumbar puncture and a course of IV antibiotics if pleocytosis in the CSF is identified, primarily as a prophylactic measure to prevent further neurologic symptoms. A subacute encephalopathy may occur months to years after disease onset, characterized by subtle disturbances in memory, mood, sleep, or cognition accompanied by fatigue. These symptoms may occur in the absence of abnormalities in the electroencephalogram (EEG), magnetic resonance imaging (MRI), or CSF. In addition, the symptoms are nonspecific and overlap with fibromyalgia and chronic fatigue syndrome. Thus diagnosis of Lyme encephalopathy may be difficult and may be best diagnosed with a mental status exam or neuropsychological testing. However, treatment with IV antibiotics is generally not indicated unless CSF abnormalities are identified. Much rarer, but of greater concern, is the development of encephalomyelitis, characterized by spastic paraparesis, ataxias, cognitive impairment, bladder dysfunction, and cranial neuropathy. CSF examination reveals a pleocytosis and an elevation in protein. Selective synthesis of antispirochetal antigens can also be identified. A course of IV antibiotics with 3 to 4 weeks of ceftriaxone is suggested when CSF abnormalities are identified. A variety of peripheral nervous system manifestations of LD have also been identified. Symptoms of peripheral neuropathy include paresthesias, or radicular pain with only minimal sensory signs. Patients typically exhibit electromyographic (EMG) or nerve conduction velocity abnormalities. CSF abnormalities are usually seen only in those patients with a coexistent encephalopathy. Cardiac Manifestations of Lyme Disease Lyme carditis may appear during the early dissemination stage of the disease; symptoms include atrioventricular heart block, tachyarrhythmias, and myopericarditis. Antibiotics are typically given, although no evidence proves that this therapy hastens the resolution of symptoms. Both oral and IV regimens have been advocated. Intravenous regimens are typically used in patients with a high degree atrioventricular block or a PR interval on the electrocardiogram (EKG) of greater than 0.3 second. Patients with milder forms of carditis may be treated with oral antibiotics. Lyme arthritis is a late manifestation of infection and is characterized by an elevated IgG response to B. burgdorferi and intermittent attacks of oligoarticular arthritis, primarily in the large joints such as the knee. Patients with Lyme arthritis may be successfully treated with a 30-day course of oral doxycycline or amoxicillin, but care must be taken to exclude simultaneous central nervous system (CNS) involvement requiring IV antibiotic treatment. In the small subset of patients that do not respond to oral antibiotics, an additional 30-day course of oral or IV antibiotics may be recommended. Fibromyalgia and Chronic Fatigue Syndrome Fibromyalgia and chronic fatigue syndrome are the diseases most commonly confused with LD. Fibromyalgia is characterized by musculoskeletal complaints, multiple trigger points, difficulty in sleeping, generalized fatigue, headache, or neck pain. The joint pain associated with fibromyalgia is typically diffuse, in contrast to Lyme arthritis, which is characterized by marked joint swelling in one or a few joints at a time, with few systemic symptoms. Chronic fatigue syndrome is characterized by multiple subjective complaints, such as overwhelming fatigue, difficulty in concentration, and diffuse muscle and joint pain. In contrast to LD, both of the above conditions lack joint inflammation, have normal neurological test results, or have test results suggesting anxiety or depression. Neither fibromyalgia nor chronic fatigue syndrome has been shown to respond to antibiotic therapy. The antibody response to infection with B. burgdorferi follows a typical pattern. During the first few weeks after the initial onset of infection, there is no antibody production. The specific IgM response characteristic of acute infection peaks between the third and sixth week. The specific IgG response develops only after months and includes antibodies to a variety of spirochetal antigens. IgG antibodies produced in response to LD may persist for months or years. Thus detection of IgG antibodies only indicates exposure, either past or present. In LD endemic areas, underlying asymptomatic seropositivity may range up to 5%–10%. Thus, as with any laboratory test, interpretation of serologic tests requires close correlation with the patients’ signs and symptoms. For example, patients with vague symptoms of LD, chronic fatigue syndrome, or fibromyalgia may undergo multiple serologic tests over many weeks to months in an effort to establish the diagnosis of LD. Inevitably, in this setting of repeat testing, one enzyme-linked immunosorbent assay (ELISA) or test, whether IgG or IgM, may be reported as weakly positive or indeterminate. These results most likely represent false positive test results in the uninfected patient who has had long-standing symptoms from a different condition and previously negative test results. Currently, the Centers for Disease Control and Prevention (CDC) recommends a two-step method for the serologic diagnosis of LD: Other tests include: Polymerase Chain Reaction (PCR) In contrast to the above 2 serologic tests, which only indirectly assess prior or present exposure to B. burgdorferi, PCR directly tests for the presence of the spirochete. Because PCR technology involves amplification of DNA from a portion of B. burgdorferi, there is a high risk of exogenous contamination, resulting in false positive results. Positive results in the absence of clear clinical indicators or positive serology are not definitive for diagnosis. In addition, the test cannot distinguish between live spirochetes or fragments of dead ones. The PCR technique has been studied using a variety of specimens. PCR has the best detection rates for skin biopsies from patients with erythema migrans and for synovial tissue (and synovial fluid, to a lesser extent) from patients with lyme arthritis. CSF may be positive by PCR during the first two weeks of infection, but thereafter the detection rate is low. PCR is not recommended for urine or blood specimens. Borrelia PCR also provides information on which of the three major species pathogenic for humans has been found in the specimen tested (genotyping). T-Cell Proliferative Assay T-lymphocyte proliferation assays are not recommended as diagnostic tests; they are difficult to perform and standardize, and their sensitivity is not well characterized. Evaluation of the Cerebrospinal Fluid (CSF) Aside from the standard evaluation of CSF for pleocytosis, protein levels, and glucose levels, various tests are available to determine whether anti-B. burgdorferi antibodies are being selectively produced within the central nervous system. Techniques include a variety of immunoassays. For example, intrathecal antibody production can be detected by the CSF/serum index of B. burgdorferi antibodies. CSF and serum samples diluted to match the total IgG concentration in CSF are run in parallel in an IgG ELISA. Excess Borrelia-specific antibody in CSF indicates a positive result. As noted, PCR can also be used to detect the spirochete in the CSF, most successfully within the first 2 weeks of infection. Treatment of Lyme Disease As noted above, treatment with IV antibiotics is generally indicated only in those patients with symptoms and laboratory findings consistent with CNS or peripheral neurologic involvement, and in a small subset of patients with heart block or documented Lyme arthritis who have not responded to oral antibiotics. Typical IV therapy consists of a 2- to 4-week course of ceftriaxone or cefotaxime, both third-generation cephalosporins, or penicillin or chloramphenicol. No data suggest that prolonged or repeated courses of IV antibiotics are effective. Lack of effect should suggest an incorrect diagnosis or slow resolution of symptoms, which is commonly seen in LD. In addition, some symptoms may persist after treatment, such as Lyme arthritis; this phenomenon may be related to various self-sustaining inflammatory mechanisms rather than persistent infection. POLICYTreatment of LD consists of oral antibiotics, except for the following indications: Objective neurologic findings include: Lyme disease may be documented either on the basis of serologic testing or by clinical findings of erythema migrans in early infection. Documentation of CSF abnormalities is required for suspected CNS infection, as indicated above. Serologic documentation of infection requires: Documented CSF abnormalities include ALL of the following: PCR-based direct detection of B. burgdorferi in CSF samples may be considered medically necessary in patients with a short duration of neurologic symptoms (<14 days) during the window between exposure and production of detectable antibodies. PCR-based direct detection of B. burgdorferi in the blood when results of serologic studies are equivocal. Intravenous antibiotic therapy is considered not medically necessary in the following situations: Investigative 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 HISTORY1/1994: Approved by Medical Policy Advisory Committee (MPAC) 5/1/2002: Type of Service and Place of Service deleted 3/25/2004: Reviewed by MPAC, Policy title “Lyme Disease Treatment” renamed “Intravenous Antiobiotic Therapy for Lyme Disease”, Description and Policy sections revised to be consistent with BCBSA policy # 5.01.08, intravenous antibiotic therapy changed from investigational to medically necessary for certain indications, investigation definition added, Sources updated, tables added to Code Reference section 5/5/2004: Code Reference section completed 3/13/2006: Policy reviewed, no changes 9/12/2006: Coding reviewed. ICD9 2006 revisions added to policy 11/13/2006: Code Reference section updated: CPT codes 87475, 87476, and 87477 deleted from policy 4/24/2007: Policy reviewed, policy statement rewritten for clarification 6/21/2007: Policy reviewed, description updated. Policy statement revised; IV antibiotic therapy is not medically necessary for uncomplicated cranial nerve palsy associated with Lyme disease and antibiotic-refractory Lyme arthritis 7/19/2007: Reviewed and approved by MPAC 7/10/2009: Policy reviewed, no changes 12/15/2009: Coding Section revised with 2010 CPT4 and HCPCS revisions 02/23/2011: Added the following to the policy statement: Determination of levels of the B lymphocyte chemoattractant CXCL13 for diagnosis or monitoring treatment is considered investigational. No changes to other policy statements. Removed deleted HCPCS codes J0530, J0540, and J0550 from the Code Reference section. 02/24/2012: Add the following policy statement: A single 2- to 4-week course of IV antibiotics may be considered medically necessary in patients with Lyme carditis, as evidenced by positive serologic findings (defined above) and associated with a high degree of atrioventricular block or a PR interval of greater than 0.3 second. Documentation of Lyme carditis may include PCR-based direct detection of B burgdorferi in the blood when results of serologic studies are equivocal. The last policy statement was revised to state that other diagnostic testing is considered investigational including but not limited to C6 peptide ELISA or determination of levels of the B lymphocyte chemoattractant CXCL13 for diagnosis or monitoring treatment. It previously stated that determination of levels of the B lymphocyte chemoattractant CXCL13 for diagnosis or monitoring treatment is considered investigational. Deleted outdated references from the Sources section. 11/28/2012: Policy reviewed; no changes. 03/10/2014: Policy reviewed; no changes to policy statement. Removed deleted HCPCS codes J0560, J0570, and J0580 from the Code Reference section. Added HCPCS code J0561. SOURCE(S)Blue Cross Blue Shield Association policy # 5.01.08 CODE REFERENCEThis may not be a comprehensive list of procedure codes applicable to this policy. The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.	2	7	2	6	0	0.594252	8	3,279
Deep vein thrombosis \|Deep vein thrombosis\| DVT in the right leg with swelling and redness \|Classification and external resources\| \|Patient UK\|\|Deep vein thrombosis\| Deep vein thrombosis, or deep venous thrombosis, (DVT) is the formation of a blood clot (thrombus) within a deep vein,[a] predominantly in the legs. Non-specific signs may include pain, swelling, redness, warmness, and engorged superficial veins. Pulmonary embolism, a potentially life-threatening complication, is caused by the detachment (embolization) of a clot that travels to the lungs. Together, DVT and pulmonary embolism constitute a single disease process known as venous thromboembolism. Post-thrombotic syndrome, another complication, significantly contributes to the health-care cost of DVT. Prevention options for at-risk individuals include early and frequent walking, calf exercises, anticoagulants, aspirin, graduated compression stockings, and intermittent pneumatic compression. In 1856, German pathologist Rudolf Virchow postulated the interplay of three processes resulting in venous thrombosis, now known as Virchow's triad: a decreased blood flow rate (venous stasis), increased tendency to clot (hypercoagulability), and changes to the blood vessel wall. DVT formation typically begins inside the valves of the calf veins, where the blood is relatively oxygen deprived, which activates certain biochemical pathways. Several medical conditions increase the risk for DVT, including cancer, trauma, and antiphospholipid syndrome. Other risk factors include older age, surgery, immobilization (as with bed rest, orthopedic casts, and sitting on long flights), combined oral contraceptives, pregnancy, the postnatal period, and genetic factors such as a non-O blood type. The frequency of occurrence (incidence) increases dramatically from childhood to old age; in adulthood, about 1 in 1000 adults develops DVT annually. Individuals suspected of having DVT may be assessed using a clinical prediction rule such as the Wells score. A D-dimer test may also be used to assist with excluding the diagnosis (because of its high sensitivity) or to signal a need for further testing. Diagnosis is most commonly done with ultrasound of the suspected veins. Anticoagulation is the standard treatment; typical medications include a low-molecular-weight heparin and a vitamin K antagonist. Wearing graduated compression stockings appears to reduce the risk of post-thrombotic syndrome. - 1 Signs and symptoms - 2 Causes - 3 Pathophysiology - 4 Diagnosis - 5 Prevention - 6 Treatment - 7 Prognosis - 8 Epidemiology - 9 Economics - 10 History - 11 Research directions - 12 Notes - 13 References - 14 External links Signs and symptoms Common signs and symptoms of DVT include pain or tenderness, swelling, warmth, redness or discoloration, and distention of surface veins, although about half of those with the condition have no symptoms. Signs and symptoms alone are not sufficiently sensitive or specific to make a diagnosis, but when considered in conjunction with known risk factors can help determine the likelihood of DVT. In most suspected cases, DVT is ruled out after evaluation, and symptoms are more often due to other causes, such as cellulitis, Baker's cyst, musculoskeletal injury, or lymphedema. Other differential diagnoses include hematoma, tumors, venous or arterial aneurysms, and connective tissue disorders. A severe and uncommon form of DVT, phlegmasia cerulea dolens, may develop in association with a life-threatening illness. It is characterized by an acute and almost total venous occlusion of the entire extremity outflow, including the iliac and femoral veins. The leg is usually painful, cyanosed (blue from lack of oxygen), and edematous (filled with fluid), which may result in venous gangrene. The three factors of Virchow's triad—venous stasis, hypercoagulability, and changes in the endothelial blood vessel lining (such as physical damage or endothelial activation)—contribute to DVT and are used to explain its formation. Other related causes include activation of immune system components, the state of microparticles in the blood, the concentration of oxygen, and possible platelet activation. Various risk factors contribute to DVT, though many at high risk never develop it. Acquired risk factors include the strong risk factor of older age, which alters blood composition to favor clotting. Other important acquired risk factors include major surgery and trauma, both of which may increase the risk because of tissue factor from outside the vascular system entering the blood. In orthopedic surgery, venous stasis may be temporarily provoked by a cessation of blood flow as part of the procedure. Cancer can grow in and around veins, causing venous stasis, and can also stimulate increased levels of tissue factor. Pregnancy causes blood to favor clotting, and in the postpartum, placental tearing releases substances that favor clotting. Oral contraceptives[b] and hormonal replacement therapy increase the risk through a variety of mechanisms, including altered blood coagulation protein levels and reduced fibrinolysis. The disease term venous thromboembolism (VTE) includes the development of either DVT or pulmonary embolism (PE). Genetic factors that increase the risk of VTE include deficiencies of three proteins that normally prevent blood from clotting—protein C, protein S, and antithrombin—in addition to non-O blood type and mutations in the factor V and prothrombin genes. Deficiencies in antithrombin, protein C, and protein S are rare but strong, or moderately strong, risk factors. These three thrombophilia[c] increase the risk of VTE by about 10 times. Factor V Leiden, which makes factor V resistant to inactivation by activated protein C, and the genetic variant prothrombin G20210A, which causes increased prothrombin levels, are predominantly expressed in Caucasians.[d] They moderately increase risk for VTE, by three to eight times for factor V Leiden and two to three times for prothrombin G20210A. Having a non-O blood type approximately doubles VTE risk. Non-O blood type is common in all races, making it an important risk factor. Individuals without O blood type have higher blood levels of von Willebrand factor and factor VIII than those with O blood type, increasing the likelihood of clotting. Some risk factors influence the location of DVT within the body. In isolated distal DVT, the profile of risk factors appears distinct from proximal DVT. Transient factors, such as surgery and immobilization, appear to dominate whereas thrombophilias and age do not seem to increase risk. In upper-extremity DVT, the most important risk factor is having a central venous catheter, and thoracic outlet syndrome also increases risk. DVT often develops in the calf veins and "grows" in the direction of venous flow, towards the heart. When DVT does not grow, it can be cleared naturally and dissolved into the blood (fibrinolysis). Veins in the calf or thigh are most commonly affected, including the femoral vein, the popliteal vein, and the iliofemoral vein (as with May–Thurner syndrome). Extensive lower-extremity DVT can reach into the iliac vein of the pelvis or the inferior vena cava. Occasionally the veins of the arm are affected, as after central venous catheter placement and with the rare Paget–Schrötter disease. The mechanism behind arterial thrombosis, such as with heart attacks, is more established than the steps that cause venous thrombosis. With arterial thrombosis, blood vessel wall damage is required, as it initiates coagulation, but clotting in the veins mostly occurs without any such damage. The beginning of venous thrombosis is thought to be caused by tissue factor, which leads to conversion of prothrombin to thrombin, followed by fibrin deposition. Red blood cells and fibrin are the main components of venous thrombi, and the fibrin appears to attach to the blood vessel wall lining (endothelium), a surface that normally acts to prevent clotting. Platelets and white blood cells are also components. Platelets are not as prominent in venous clots as they are in arterial ones, but they may play a role. Inflammation is associated with VTE,[f] and white blood cells play a role in the formation and resolution of venous clots. Often, DVT begins in the valves of veins. The blood flow pattern in the valves can cause low oxygen concentrations in the blood (hypoxemia) of a valve sinus. Hypoxemia, which is worsened by venous stasis, activates pathways—ones that include hypoxia-inducible factor-1 and early-growth-response protein 1. Hypoxemia also results in the production of reactive oxygen species, which can activate these pathways, as well as nuclear factor-κB, which regulates hypoxia-inducible factor-1 transcription. Hypoxia-inducible factor-1 and early-growth-response protein 1 contribute to monocyte association with endothelial proteins, such as P-selectin, prompting monocytes to release tissue factor-filled microvesicles, which presumably begin clotting after binding to the endothelial surface. DVT diagnosis requires the use of imaging devices such as ultrasound. Clinical assessments, which predict DVT likelihood, can help determine if a D-dimer test is useful. In those not highly likely to have DVT, a normal D-dimer result[g] can rule out a diagnosis. Provoked DVTs occur in association with acquired risk factors, such as surgery, oral contraceptives, trauma, immobility, obesity, or cancer; cases without acquired states are called unprovoked or idiopathic. Acute DVT is characterized by pain and swelling and is usually occlusive, which means that it obstructs blood flow, whereas non-occlusive DVT is less symptomatic. The label of chronic has been applied to symptomatic DVT that persists longer than 10 or 14 days. DVT that has no symptoms, but is found only by screening, is labeled asymptomatic or incidental. DVT in the legs is proximal (or iliofemoral) when above the knee and distal (or calf) when below the knee. DVT below the popliteal vein, a proximal vein behind the knee, is classified as distal and has limited clinical significance compared to proximal DVT. An initial episode of DVT is called incident and any subsequent DVT is termed recurrent. Bilateral DVT refers to clots in both legs while unilateral means that only a single leg is affected. Wells score or criteria: (possible score −2 to 9) - Active cancer (treatment within last 6 months or palliative): +1 point - Calf swelling ≥ 3 cm compared to asymptomatic calf (measured 10 cm below tibial tuberosity): +1 point - Swollen unilateral superficial veins (non-varicose, in symptomatic leg): +1 point - Unilateral pitting edema (in symptomatic leg): +1 point - Previous documented DVT: +1 point - Swelling of entire leg: +1 point - Localized tenderness along the deep venous system: +1 point - Paralysis, paresis, or recent cast immobilization of lower extremities: +1 point - Recently bedridden ≥ 3 days, or major surgery requiring regional or general anesthetic in the past 12 weeks: +1 point - Alternative diagnosis at least as likely: −2 points Those with Wells scores of two or more have a 28% chance of having DVT, those with a lower score have 6% odds. Alternatively, Wells scores can be categorized as high if greater than two, moderate if one or two, and low if less than one, with likelihoods of 53%, 17%, and 5% respectively. D-dimers are a fibrin degradation product, and an elevated level can result from plasmin dissolving a clot—or other conditions. Hospitalized patients often have elevated levels for multiple reasons. When individuals are at a high-probability of having DVT, diagnostic imaging is preferred to a D-dimer test. For those with a low or moderate probability of DVT, a D-dimer level might be obtained, which excludes a diagnosis if results are normal. An elevated level requires further investigation with diagnostic imaging to confirm or exclude the diagnosis. For a suspected first leg DVT in a low-probability situation, the American College of Chest Physicians (ACCP) recommends testing either D-dimer levels with moderate or high sensitivity or compression ultrasound of the proximal veins. These options are suggested over whole-leg ultrasound, and D-dimer testing is the suggested preference overall. The UK National Institute for Health and Care Excellence (NICE) recommends D-dimer testing prior to proximal vein ultrasound. For a suspected first leg DVT in a moderate-probability scenario, a high-sensitivity D-dimer is suggested as a recommended option over ultrasound imaging, with both whole-leg and compression ultrasound possible. The NICE guideline uses a two-point Wells score, and does not refer to a moderate probability group. Imaging tests of the veins are used in the diagnosis of DVT, most commonly either proximal compression ultrasound or whole-leg ultrasound. Each technique has drawbacks: a single proximal scan may miss a distal DVT, while whole-leg scanning can lead to distal DVT overtreatment. Doppler ultrasound, CT scan venography, MRI venography, or MRI of the thrombus are also possibilities. The gold standard for judging imaging methods is contrast venography, which involves injecting a peripheral vein of the affected limb with a contrast agent and taking X-rays, to reveal whether the venous supply has been obstructed. Because of its cost, invasiveness, availability, and other limitations this test is rarely performed. Depending upon the risk for DVT, different preventative measures are used. Walking and calf exercises reduce venous stasis because leg muscle contractions compress the veins and pump blood up towards the heart. In immobile individuals, physical compression methods improve blood flow. Anticoagulation, which increases the risk of bleeding, might be used in high-risk scenarios. The risk of major bleeding with long-term anticoagulation is about 3% per year, and the point where annual VTE risk is thought to warrant long-term anticoagulation is estimated to be between 3 and 9%. Usually, only when individuals exceed a 9% annual VTE risk is long-term anticoagulation a common consideration. Antithrombin deficiency, a strong or moderately strong risk factor, carries an annual risk of VTE of only 0.8–1.5%; as such, asymptomatic individuals with thrombophilia do not warrant long-term anticoagulation. Aside from anticoagulation, the anti-platelet drug aspirin might be used in some people following orthopedic surgery and in those with a previous VTE. Statins might decrease the risk for people who are otherwise healthy, but the evidence is not clear. In 2011, the American College of Physicians (ACP) issued a clinical practice guideline making three strong recommendations based on moderate-quality evidence: that hospitalized patients be assessed for their risk of thromboembolism and bleeding before prophylaxis is started; that heparin or a related drug be used if potential benefits are thought to outweigh potential harms; and that graduated compression stockings not be used. The ACP also drew attention to a lack of support for any performance measures encouraging physicians to apply universal prophylaxis without regard to the risks. A 2014 Cochrane review found that using heparin in medical patients did not change the risk of death or pulmonary embolism. While its use decreased peoples risks of DVTs it also increased peoples risks of major bleeding. The review thus recommended the need to balance risks and benefits. The 2012 ACCP guidelines for non-surgical patients[h] recommend anticoagulation for the acutely ill in cases of elevated risk when there is no bleeding nor a high risk of bleeding. Mechanical prophylaxis is suggested when risks for bleeding and thrombosis are elevated. For the critically ill, either pharmacological or mechanical prophylaxis is suggested depending upon the risk. Heparin is suggested in outpatients with cancer who have solid tumors and additional risk factors for VTE—listed as "previous venous thrombosis, immobilization, hormonal therapy, angiogenesis inhibitors, thalidomide, and lenalidomide"—and a low risk of bleeding. Major orthopedic surgery—total hip replacement, total knee replacement, or hip fracture surgery—has a high risk of causing VTE. If prophylaxis is not used after these surgeries, symptomatic VTE has about a 4% chance of developing within 35 days. Options for VTE prevention in people follow non-orthopedic surgery include early walking, mechanical prophylaxis (intermittent pneumatic compression or graduated compression stockings), and drugs (low-molecular-weight heparin [LMWH] and low-dose-unfractionated heparin [LDUH]) depending upon the risk of VTE, risk of major bleeding, and person's preferences. Following major orthopedic surgery, the ACCP recommends treatment with drugs that reduce the risk of clots (such as fondaparinux and aspirin) with LMWH suggested as a preference. Intermittent pneumatic compression is also an option. Graduated compression stockings are effective after both general and orthopedic surgery. The risk of VTE is increased in pregnancy by about five times because of a more hypercoaguable state, a likely adaptation against fatal postpartum hemorrhage. Additionally, pregnant women with genetic risk factors are subject to an approximate three to thirty times increased risk for VTE. Preventative treatments for pregnancy-related VTE in hypercoaguable women were suggested by the ACCP. Homozygous carriers of factor V Leiden or prothrombin G20210A with a family history of VTE were suggested for antepartum LMWH and either LMWH or a vitamin K antagonist (VKA) for the six weeks following childbirth. Those with another thrombophilia and a family history but no previous VTE were suggested for watchful waiting during pregnancy and LMWH or—for those without protein C or S deficiency—a VKA. Homozygous carriers of factor V Leiden or prothrombin G20210A with no personal or family history of VTE were suggested for watchful waiting during pregnancy and LMWH or a VKA for six weeks after childbirth. Those with another thrombophilia but no family or personal history of VTE were suggested for watchful waiting only. Warfarin, a common VKA, can cause harm to the fetus and is not used for VTE prevention during pregnancy. The 2012 ACCP guidelines offered weak recommendations. For at-risk long-haul travelers—those with "previous VTE, recent surgery or trauma, active malignancy, pregnancy, estrogen use, advanced age, limited mobility, severe obesity, or known thrombophilic disorder"—suggestions included calf exercises, frequent walking, and aisle seating in airplanes to ease walking. The use of graduated compression stockings that fit below the knee and give 15–30 mm Hg of pressure to the ankle was suggested, while aspirin or anticoagulants were not. Compression stockings have sharply reduced the levels of asymptomatic DVT in airline passengers, but the effect on symptomatic VTE is unknown, as none of the individuals studied developed symptomatic VTE. Anticoagulation, which prevents further coagulation but does not act directly on existing clots, is the standard treatment for DVT.[i] Balancing risk vs. benefit is important in determining the duration of anticoagulation, and three months is generally the standard length of treatment. In those with an annual risk of VTE in excess of 9%, as after an unprovoked episode, extended anticoagulation is a possibility. Those who finish VKA treatment after idiopathic VTE with an elevated D-dimer level show an increased risk of recurrent VTE (about 9% vs. about 4% for normal results), and this result might be used in clinical decision-making. Thrombophilia test results rarely play a role in the length of treatment. For acute cases in the leg, the ACCP recommended a parenteral anticoagulant (such as LMWH, fondaparinux, or unfractionated heparin) for at least five days[j] and a VKA, the oral anticoagulant, the same day. LMWH and fondaparinux are suggested over unfractionated heparin, but both are retained in those with compromised kidney function, unlike unfractionated heparin. The VKA is generally taken for a minimum of three months to maintain an international normalized ratio of 2.0–3.0, with 2.5 as the target. The benefit of taking a VKA declines as the duration of treatment extends, and the risk of bleeding increases with age. The ACCP recommended treatment for three months in those with proximal DVT provoked by surgery. A three-month course is also recommended for those with proximal DVT provoked by a transient risk factor, and three months is suggested over lengthened treatment when bleeding risk is low to moderate. Unprovoked DVT patients should have at least three months of anticoagulation and be considered for extended treatment. Those whose first VTE is an unprovoked proximal DVT are suggested for anticoagulation longer than three months unless there is a high risk of bleeding. In that case, three months is sufficient. Those with a second unprovoked VTE are recommended for extended treatment when bleeding risk is low, suggested for extended treatment when bleeding risk is moderate, and suggested for three months of anticoagulation in high risk scenarios. Home treatment, stockings, walking, and repeat imaging The ACCP recommended initial home treatment instead of hospital treatment for those with acute leg DVT. This applies as long as individuals feel ready for it, and those with severe leg symptoms or comorbidities would not qualify. An appropriate home environment is expected: one that can provide a quick return to the hospital if necessary, support from family or friends, and phone access. In addition to anticoagulation, the ACCP suggested graduated compression stockings—which apply higher pressure (30–40 mm Hg) at the ankles and a lower pressure around the knees—for those with symptomatic DVT. Use should begin as soon as possible after anticoagulation. Existing randomized controlled trials give moderate-quality evidence that these stockings reduce the risk of post-thrombotic syndrome. An estimate on the number needed to treat suggests about four people need stockings to prevent one post-thrombotic syndrome case. Trials do not indicate a reduction in recurrent VTE. Use is suggested for two years, though inconvenience and discomfort can reduce compliance. Walking is also suggested for those without severe pain or edema. Unless a person has medical problems preventing movement, after a person starts anti-coagulation therapy bed rest should not be used to treat acute deep vein thrombosis. There are clinical benefits associated with walking and no evidence that walking is harmful, but people with DVT are harmed by bed rest except when it is medically necessary. Instead of anticoagulation, a follow-up imaging test (typically ultrasound) about one week post-diagnosis is an option for those with an acute isolated distal DVT without a high risk for extension; if the clot does not grow, the ACCP does not recommend anticoagulation. This technique can benefit those at a high risk for bleeding. Patients may choose anticoagulation over serial imaging however, to avoid the inconvenience of another scan if concerns about the risk of bleeding are insignificant. When applied to symptomatic patients with a negative initial ultrasound result, serial testing is inefficient and not cost effective. IVC filters, thrombolysis, and thrombectomy Inferior vena cava filters (IVC filters) are used on the presumption that they reduce PE, although their effectiveness and safety profile are not well established. In general, they are only recommended in some high risk scenarios. The ACCP recommended them for those with a contraindication to anticoagulant treatment but not in addition to anticoagulation, unless an individual with an IVC filter but without a risk for bleeding develops acute proximal DVT. In this case, both anticoagulation and an IVC filter is suggested. NICE recommends caval filters in settings where someone with an acute proximal DVT or PE cannot receive anticoagulation, and that the filter is removed when anticoagulation can be safely started. While IVC filters themselves are associated with a long-term risk of DVT, they are not reason enough to maintain extended anticoagulation. Thrombolysis is the administration of an enzyme (intravenous or directly into the affected vein through a catheter), which acts to enzymatically break up clots. This may reduce the risk of post-thrombotic syndrome by a third, and possibly reduce the risk of leg ulcers, but is associated with an increased risk of bleeding. The ACCP currently suggests anticoagulation rather than thrombolysis, but patients may choose thrombolysis if prevention of post-thrombotic syndrome outweighs concerns over the complexity, bleeding risk, and cost of the procedure. NICE recommends that thrombolysis in considered in those who have had symptoms for less than two weeks, are normally well, have a good life expectancy and a low risk of bleeding. A mechanical thrombectomy device can remove venous clots, although the ACCP considers it an option only when the following conditions apply: "iliofemoral DVT, symptoms for < 7 days (criterion used in the single randomized trial), good functional status, life expectancy of ≥ 1 year, and both resources and expertise are available." Anticoagulation alone is suggested over thrombectomy. The most frequent complication of proximal DVT is post-thrombotic syndrome, which is caused by a reduction in the return of venous blood to the heart. Some symptoms of post-thrombotic syndrome are pain, edema, paresthesia, and in severe cases, leg ulcers. An estimated 20–50% of those with DVT will develop it, and 5–10% will develop the severe form. PE is the most serious complication of proximal DVT, and the risk of PE is higher when clots are present in the thigh and pelvis. Distal DVT itself is hardly if ever associated with post-thrombotic syndrome or PE. Untreated lower extremity DVT has a 3% PE-related mortality rate, while deaths associated with upper extremity DVT are extremely rare. The presence of a remaining thrombus after a DVT frequently occurs in a minority of people, and it increases the risk of recurrence, though to a lesser extent than an elevated D-dimer. In the 10 years following a VTE, approximately a third of individuals will have a recurrent episode. About 1 in 1000 adults per year has DVT, but as of 2011, available data is dominated by North American and European populations. VTE is rare in children, with an incidence of about 1 in 100,000 a year. From childhood to old age, incidence increases by a factor of about 1000, with almost 1% of the elderly experiencing VTE yearly. During pregnancy and after childbirth, acute VTE occurs about once per 1000 deliveries. After surgery with preventative treatment, VTE develops in about 10 of 1000 people after total or partial knee replacement, and in about 5 of 1000 after total or partial hip replacement. About 300,000–600,000 Americans develop VTE each year, with about 60,000–100,000 deaths attributable to PE. In England, an estimated 25,000 a year die from hospital-related VTE. For unclear reasons, people of Asian descent have a lower VTE risk than whites. In North American and European populations, around 4–8% of people have a thrombophilia, most commonly factor V leiden and prothrombin G20210A. For populations in China, Japan, and Thailand, deficiences in protein S, protein C, and antithrombin predominate. Non-O blood type is present in around 50% of the general population and varies with ethnicity, and it is present in about 70% of those with VTE. Altogether, global data is incomplete. Initial DVT costs for an average hospitalized patient in the U.S. are around $7,700–$10,800. VTE follow-up costs at three months, six months, and a year are about $5,000, $10,000, and $33,000 respectively; in Europe, the three and six-month figures are about €1,800 and €3,200. Post-thrombotic syndrome is a significant contributor to DVT follow-up costs. Annual DVT costs in the U.S. are an estimated $5 billion or in excess of $8 billion, and the average annual cost per treated individual is thought to be about $20,000. As an example, if 300,000 symptomatic DVT patients were treated at costs averaging $20,000 annually, that would cost $6 billion a year. The earliest case of DVT was described by Sushruta in his book Sushruta Samhita around 600–900 BC. Another documented case is thought to have occurred in the 13th century, in the leg of a 20-year-old male. At some point, the increased incidence of DVT in women after childbirth was noticed, and in the late 1700s, a public health recommendation was issued to encourage women to breast feed as a means to prevent this phenomenon; the DVT was called "milk leg", as it was thought to result from milk building up in the leg. In 1856, German physician and pathologist Rudolf Virchow published what is referred to as Virchow's triad, the three major causes of thrombosis. The triad provides the theoretical framework for the current explanation of venous thrombosis, although it was focused on the effect of a foreign body in the venous system and the conditions required for clot propagation. Multiple pharmacological therapies for DVT were introduced in the 20th century: oral anticoagulants in the 1940s, subcutaneous LDUH in 1962, and subcutaneous LMWH in 1982. Diagnoses were commonly performed by impedance plethysmography in the 1970s and 1980s, but the use of Doppler ultrasound techniques, with their increased sensitivity and specificity, largely superseded this method. As of 2011, three large randomized controlled trials—the Norwegian CaVent trial, the North American ATTRACT trial, and the Dutch CAVA trial—are studying the effectiveness and safety of catheter-directed thrombolysis. In 2012, two studies found a clinical benefit in taking aspirin to prevent recurrent VTE. - Thrombosis associated with the abdominal organs (viscera)—such as portal vein thrombosis, renal vein thrombosis, and Budd–Chiari syndrome—are separate diseases excluded from the scope of this definition. - Third-generation combined oral contraceptives (COCs) have an approximate two to three times higher risk than second-generation COCs. 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"Vena caval filters for the prevention of pulmonary embolism". Cochrane Database Syst Rev (2): CD006212. doi:10.1002/14651858.CD006212.pub4. PMID 20166079. - Guyatt et al. 2012, p. 21S: 2.13.1.–3. - Guyatt et al. 2012, p. 21S: 2.13. - Watson L, Broderick C, Armon MP (23 Jan 2014). "Thrombolysis for acute deep vein thrombosis". Cochrane Database Syst Rev 1: CD002783. doi:10.1002/14651858.CD002783.pub3. PMID 24452314. - Guyatt et al. 2012, p. 21S: 2.9 & 2.10. - Guyatt et al. 2012, p. 21S: 2.11. - Kahn SR (2009). "How I treat postthrombotic syndrome". Blood 114 (21): 4624–31. doi:10.1182/blood-2009-07-199174. PMID 19741190. - "Deep vein thrombosis/pulmonary embolism (DVT/PE)". Centers for Disease Control and Prevention. 8 June 2012. Retrieved 5 July 2012. - Severinsen MT, Johnsen SP, Tjønneland A, et al. (2010). "Body height and sex-related differences in incidence of venous thromboembolism: A Danish follow-up study". Eur J Intern Med 21 (4): 268–72. doi:10.1016/j.ejim.2010.03.013. PMID 20603033. - Zakai NA, McClure LA (2011). "Racial differences in venous thromboembolism". J Thromb Haemost 9 (10): 1877–82. doi:10.1111/j.1538-7836.2011.04443.x. PMID 21797965. - Rosendaal 2009, p. 5. - Januel JM, Chen G, Ruffieux C, et al. (2012). "Symptomatic in-hospital deep vein thrombosis and pulmonary embolism following hip and knee arthroplasty among patients receiving recommended prophylaxis: A systematic review". JAMA 307 (3): 294–303. doi:10.1001/jama.2011.2029. PMID 22253396. - Young A, Chapman O, Connor C, et al. (2012). "Thrombosis and cancer". Nature Reviews Clinical Oncology 9 (8): 437–49. doi:10.1038/nrclinonc.2012.106. PMID 22777060. - Margaglione M, Grandone E (2011). "Population genetics of venous thromboembolism: A narrative review". Thromb Haemost 105 (2): 221–31. doi:10.1160/TH10-08-0510. PMID 20941456. - "Blood types". American Red Cross. Retrieved 15 August 2012. - Hamasaki N (2012). "Unmasking Asian thrombophilia: is APC dysfunction the real culprit?". J Thromb Haemost 10 (10): 2016–8. doi:10.1111/j.1538-7836.2012.04893.x. PMID 22905992. - Dobesh PP (2009). "Economic burden of venous thromboembolism in hospitalized patients". Pharmacotherapy 29 (8): 943–53. doi:10.1592/phco.29.8.943. PMID 19637948. - Ruppert A, Steinle T, Lees M (2011). "Economic burden of venous thromboembolism: A systematic review". J Med Econ 14 (1): 65–74. doi:10.3111/13696998.2010.546465. PMID 21222564. - Grosse SD (2012). "Incidence-based cost estimates require population-based incidence data. A critique of Mahan et al.". Thromb Haemost 107 (1): 192–3. doi:10.1160/TH11-09-0666. PMID 22159589. - Mahan CE, Holdsworth MT, Welch SM, et al. (2011). "Deep-vein thrombosis: A United States cost model for a preventable and costly adverse event". Thromb Haemost 106 (3): 405–15. doi:10.1160/TH11-02-0132. PMID 21833446. - Mahan CE, Holdsworth MT, Welch SM, et al. (2012). "Long-term attack rates, as compared with incidence rates, may provide improved cost-estimates in venous thromboembolism. A reply to S. D. Grosse". Thromb Haemost 107 (1): 194–5. doi:10.1160/TH11-11-0802. - Goodman, LR (Oct 2013). "In search of venous thromboembolism: the first 2913 years.". AJR. American journal of roentgenology 201 (4): W576–81. doi:10.2214/AJR.13.10604. PMID 24059395. - Rosendaal 2009, p. 3. - Bagot CN, Arya R (2008). "Virchow and his triad: A question of attribution". Br J Haematol 143 (2): 180–9. doi:10.1111/j.1365-2141.2008.07323.x. PMID 18783400. - Dalen 2003, p. 2. - Dalen 2003, p. 3. - Becattini C, Agnelli G, Schenone A, et al. (2012). "Aspirin for preventing the recurrence of venous thromboembolism". N Engl J Med 366 (21): 1959–67. doi:10.1056/NEJMoa1114238. PMID 22621626. - Brighton TA, Eikelboom JW, Mann K, et al. (2012). "Low-dose aspirin for preventing recurrent venous thromboembolism". N Engl J Med 367 (21): 1979–87. doi:10.1056/NEJMoa1210384. PMID 23121403. - Dalen, James E. (2003). Venous thromboembolism. CRC Press. ISBN 978-0-8247-5645-1. - Guyatt, GH; Akl EA; Crowther M; et al. (2012). "Executive Summary: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines". Chest 141 (suppl 2): 7S–47S. doi:10.1378/chest.1412S3. PMC 3278060. PMID 22315257. - Hecht, M. E. (2010). A practical guide to hip surgery: From pre-op to recovery. Sunrise River Press. ISBN 978-1-934716-12-0. - Rosendaal, Frits R. (2009). van Beek, Edwin J. R.; Büller, Harry R.; Oudkerk, Mathijs, eds. Deep vein thrombosis and pulmonary embolism. John Wiley & Sons. ISBN 978-0-470-74499-4. - Welch, Ellen (2010). Venous thromboembolism: A nurse's guide to prevention and management. John Wiley & Sons. ISBN 978-0-470-51189-3. - International Society on Thrombosis and Haemostasis - North American Thrombosis Forum - Clot Connect - National Blood Clot Alliance	2	76	23	3	1	0.945306	27	15,393
Asthma and COPD are two chronic conditions common enough in the general population that most physicians will want to know the documentation needs for coding in ICD-10. I’ll compare them to documentation for ICD-9. Asthma coding has changed. Two axes of classification that physicians rarely documented in ICD-9 have been eliminated, and two axes of classification (that hopefully physicians will find useful) have been added in ICD-10. As a result, the total number of asthma and COPD codes is roughly the same in ICD-9 and ICD-10 -- 17 ICD-9 codes and 20 ICD-10 codes. Here are the two hair-splitting ICD-9 axes of classification that have been eliminated in ICD-10: - ICD-10 does not force physicians to categorize asthma as intrinsic or extrinsic. Asthma is just asthma. - ICD-10 does not have separate codes for chronic obstructive asthma, as opposed to chronic obstructive bronchitis or plain old chronic obstructive pulmonary disease. COPD is just COPD in ICD-10. More about COPD when we finish with asthma. Here are the two (hopefully more useful) axes of classification for asthma that have been added to ICD-10: - Asthma is categorized by degree of severity — mild, moderate and severe are the terms used in the codes to distinguish the level of severity. - Asthma is further categorized as either intermittent or persistent. (Intermittent often means the asthma has an external trigger; therefore, extrinsic/allergic in its cause. But it doesn’t rule out non-allergic asthma that is also intermittent. Let’s face it, asthma causes are not that easy to pin down, and having the classification hinge on the physician’s ability to use mutually exclusive terminology to declare the cause of the asthma doesn’t make sense. It is probably in your interest to use the ICD-10 terminology in documenting a patient encounter. Unlike the discontinued detail in ICD-9, the ICD-10 codes clearly distinguish the behavior of an illness rather than its cause. They tell how sick a patient is, and therefore how much effort is involved in monitoring and treatment. A patient with severe persistent asthma is clearly distinguishable from a patient with mild persistent asthma. And eventually, if not immediately, those distinctions are going to be used by the (evil) people who use diagnosis codes to calculate what to pay you and to comment on how well you do your job. You of course have the right to vote against the entire ICD system by not documenting to comply with measures of clinical significance cooked up by a global committee, but at some point it may, literally, cost you. These clinical distinctions will no doubt be used wherever possible to fine-tune payment systems and quality report cards and all the rest of it. It is no secret that the healthcare system is not optimized for the physician’s convenience or preferences on how to best deliver care, but by being a practicing physician in the United States you are playing this game, which includes using ICD codes to eke out all the justifiable credit you can for the work you do. As an example, here are the ICD-10 asthma codes for a patient with severe persistent asthma, with the ICD-9 codes they replace. J45.50 Severe persistent asthma, uncomplicated 493.00 Extrinsic asthma, unspecified 493.10 Intrinsic asthma, unspecified J45.51 Severe persistent asthma with (acute) exacerbation 493.02 Extrinsic asthma with (acute) exacerbation 493.12 Intrinsic asthma with (acute) exacerbation J45.52 Severe persistent asthma with status asthmaticus 493.01 Extrinsic asthma with status asthmaticus 493.11 Intrinsic asthma with status asthmaticus Notice you still have the ability to capture acute exacerbation and status asthmaticus. The same is true of all the flavors of asthma mentioned earlier -- severe intermittent, moderate persistent, moderate intermittent, etc. The whole category is perfectly regular. There is also an unspecified subcategory if you choose not to play the documentation game. If you document only “patient is on prescribed inhalers for asthma” the default code is J45.909 Unspecified asthma, uncomplicated Not a lot to say about COPD beyond what I mentioned earlier. As with asthma coding, an axis of classification that wasn’t seen as useful was eliminated. ICD-10 added a code for a common acute exacerbation that brings a patient with COPD back to seek care — COPD with acute lower respiratory infection such as acute bronchitis or pneumonia. The specific pneumonia or bronchitis code can be coded in addition. J44.0 Chronic obstructive pulmonary disease with acute lower respiratory infection As with ICD-9, there is an ICD-10 code for COPD with exacerbation, which captures “decompensated” COPD, without any additional documentation. J44.1 Chronic obstructive pulmonary disease with (acute) exacerbation 491.21 Obstructive chronic bronchitis with (acute) exacerbation 493.22 Chronic obstructive asthma with (acute) exacerbation And of course there is an unspecified option, which no longer splits hairs about whether the COPD is predominantly asthma or predominantly bronchitis — it’s just COPD. J44.9 Chronic obstructive pulmonary disease, unspecified 491.20 Obstructive chronic bronchitis without exacerbation 493.20 Chronic obstructive asthma, unspecified 496 Chronic airway obstruction, not elsewhere classified Getting rid of dead wood in the classification is one of the benefits of these periodic revisions of the ICD. In the case of asthma and COPD, distinctions of dubious relevance have been abandoned. Even if you could say with absolute certainty that the cause of the patient’s asthma is extrinsic, the fact remains that regardless of the cause there is constriction of airways and inflammation in the lungs that must be treated. Instead of forcing you to declare the underlying cause, the ICD-10 asthma codes give a clearer indication how sick the patient is and therefore supports what you did to treat that patient. Rhonda Butler is a senior clinical research analyst with 3M Health Information Systems. She is responsible for the development and maintenance of the ICD-10 Procedure Coding System since 2003 under contract to CMS, and for the development and maintenance of the ICD-10 General Equivalence Mappings (GEMs) and Reimbursement Mappings under contract to CMS and the CDC. She leads the 3M test project to convert the MS-DRGs to ICD-10 for CMS, and is on the team to convert 3M APR-DRGs to ICD-10. Rhonda also writes for the 3M Health Information Systems blog.	4	4	0	0	9	0.556749	9	1,470
Use of Defribillators After Acute Myocardial Infarction: Who Is It Right for? Implantable cardioverter-defibrillators (ICDs) have been used to prolong life in patients with certain types of serious heart disease. An ICD is an electronic device that works by monitoring a patient’s heart rhythm. If the surgically implanted device detects a dangerous rhythm change, it delivers an electric pulse through a lead that rests against the heart tissue. If a patient experiences tachycardia, or a heartbeat that is too fast, for example, the ICD can send an electric signal to stabilize the rhythm before it has an opportunity to harm the patient. Clinical studies have shown that ICDs are very useful in preventing ]]>sudden cardiac death]]> in certain patient populations, such as those with a history of sustained tachycardia or heart failure. Since ICD therapy seems to be so effective in these patients, researchers have been studying their effect in other patient populations, to determine who else might benefit from an ICD device. One such population of interest is recent heart attack victims. After a ]]>heart attack]]> , or myocharidal infarction (MI), patients are at greater risk of developing ]]>arrhythmia]]> —an abnormal, sometimes fatal, heart rhythm—for the next 6-12 months. Other than a type of medication called a beta-blocker, no drug therapy that has been consistently shown to reduce this risk. A study published in the December 9th edition of The New England Journal of Medicine evaluated whether the preventive use of an ICD device had an impact on the risk of mortality in patients who had had a recent MI. About the Study This was a randomized study that compared 332 patients that received an ICD device with 342 patients who did not (control group). The study included patients aged 18-80 who had all experienced a recent MI. Patients were also required to have some degree of heart failure and evidence of diminished neurologic control over their heart. None, however, showed signs of a dangerous heart rhythm at the time they were enrolled in the study. The patients in the ICD group underwent surgery for implantation of the ICD, and the control group received personalized conventional medical care. The primary endpoint for the study was mortality from any cause, cardiac or other. The secondary endpoint was death from an arrhythmia. The researchers followed the study participants for an average of 30 months, and during that time, there was no statistical difference between the two groups in terms of mortality. In the ICD treatment group, 62 patients died and in the control group, a total of 58 patients died. The authors concluded that ICD devices used preventively do not reduce overall mortality in high risk patients who have recently had a heart attack. Interestingly, the ICD treatment group did in fact experience a reduced risk of death due to arrhythmia. The deaths in the ICD group due to arrhythmia were significantly lower (12 deaths) than the arrhythmia deaths in the control group (29 deaths). However, the ICD group experienced more deaths due to non-cardiac causes, which offset this finding. How Does This Affect You? The findings of this study revealed that overall survival in heart attack patients was not improved by the prophylactic use of an ICD device. Previous studies of ICD devices have shown that for other patient types, it is effective at preventing death. Unfortunately, while the ICD devices in this study appear to have prevented death from arrhythmia, there were enough deaths due to other causes in the ICD group to negate this apparent benefit. The reason for the increased deaths is a bit of mystery since there was no evidence that the increased deaths were in any way associated with the surgical procedure or complications due to the device. A number of studies have shown ICDs to be effective at preventing death in certain patient populations. Patients with sustained heart failure appear to have the most benefit from ICD devices. However, the positive findings of studies in these patients have led to an increased use of ICDs worldwide, often for patients with many different cardiac problems. What can be learned from this study is that the benefits of ICDs may not necessarily be generalized to all cardiac patients. Another recent study of patients recovering from coronary-artery-bypass-graft surgery (CABG) showed no benefit from ICD implantation either. Implantation of an ICD device is a complicated procedure that is not appropriate for all patients suffering from a cardiac condition. If you feel you may benefit from an ICD device, or have more questions about its risks and benefits, do not hesitate to discuss it with your cardiologist. ACC/AHA/NASPE 2002 guideline update for the implantation of cardiac pacemakers and antiarrhythmia devices Amerian Heart Association American Academy of Family Physicians General information about ICD devices Implantable Cardioverter Defibrillator American Heart Association Gillis AM. Prophylactic implantable cardioverter-defibrillators after myocardial infarction-not for everyone. New England Journal of Medicine ; 351 (24): 2481-8. Hohnloser SH, Heniz Kuck K, Dorian P, Roberts RS, Hampton JR, Hatala R, Fain E, Gent M, and Connolly SJ. Prophylactic use of an implantable cardioverter- defibrillator after acute myocardial infarction. New England Journal of Medicine ; 351 (24): 2540-2. Implantable cardioverter defibrillation. Available at: http://www.americanheart.org/presenter.jhtml?identifier=11227 . Accessed December 6, 2004. Jauhar S and Slotwiner DJ. The economics of ICDs. New England Journal of Medicine ; 351 (24): 2542-4. Last reviewed Dec 9, 2004 by ]]>Richard Glickman-Simon]]> Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition. Copyright © 2007 EBSCO Publishing All rights reserved.	2	10	1	0	0	0.931026	1	1,373
2 edition of On primary and secondary syphilis of the uterus. found in the catalog. On primary and secondary syphilis of the uterus. Reprinted from the British Medical Journal. Secondary syphilis is the stage of the sexually transmitted disease syphilis in which the patient is most contagious. The main clinical feature is a maculopapular rash that appears on the whole body that extends to the palms and soles, while generalized lymphadenopathy and constitutional symptoms may be present as well. The diagnosis can be made clinically and confirmed by serology. Congenital syphilis is still a cause of perinatal morbidity and mortality. Untreated maternal infection leads to adverse pregnancy outcomes, including early fetal loss, stillbirth, prematurity, low birth weight, neonatal and infant death, and congenital disease among newborns. Clinical manifestations of congenital syphilis are influenced by gestational age, stage of maternal syphilis, maternal. Most of the time, syphilis is passed from mom to baby during pregnancy, but it can happen during vaginal birth if a baby has direct contact with a syphilis sore. Vaginal birth is when contractions in your uterus (womb) help push your baby out through the vagina. When your baby is born with syphilis, it’s called congenital syphilis. Primary syphilis typically presents as a solitary, painless chancre, whereas secondary syphilis can have a wide variety of symptoms, especially fever, lymph- adenopathy, rash, and genital or. Syphilis in pregnancy remains an important medical condition due to its consequences. We present two cases of young pregnant women who were diagnosed syphilis during their antenatal visit. The first case was a year-old Malay lady diagnosed with syphilis during the first trimester of pregnancy, while the second case was a year-old Chinese. Primary, Secondary and Terciary Syphilis // Symptoms, Causes and Treatment classification of sexually transmitted diseases Secondary syphilis Nihil views. Signs of . Picture of slavery in the United States of America Changing political leadership in an Indian province Financing U.S. airports in the 1980s United States policy toward Iraq The rise and fall of apartheid The end of race? Police training in addictions Hearing on (H.R. 10259) for the Relief of Charles W. Eaton legend of Delaware Valley Botswana handbook of seed certification standards and rules, May 1994. International Brand Packaging Awards 2 (International Brand Packaging Awards) Report on the operation of the Student Assistance Act 1992 King of Rome. A pill for the doctor Prehistoric communities of the British Isles. Running costs of motor vehicles as affected by road design and traffic. Syphilis is a common sexually transmitted disease ().It’s easily cured but can be serious if it’s not treated. This STD develops in four stages. Symptoms in the first two can be so mild that. Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum subspecies pallidum. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, and tertiary). The primary stage classically presents with a single chancre (a firm, painless, non-itchy skin ulceration usually between 1 cm and 2 cm in diameter Diagnostic method: Blood tests, dark field microscopy of. The symptoms of secondary syphilis develop two to eight weeks after a person first becomes infected with primary syphilis. The secondary stage is usually marked by a non-itchy : Rose Kivi. There are four stages of syphilis: the primary, secondary, latent, and tertiary stages. In each stage, the signs and symptoms of syphilis are different. In the primary stage, a person usually just has a wound on their skin, called a "chancre."In the secondary stage, a person usually gets a the "latent" stage, syphilis has few or no symptoms. Primary syphilis. Primary syphilis causes painless sores (chancres) on your genitals, rectum, tongue or lips. The disease can be present with the appearance of a. Male-to-female ratios of primary and secondary syphilis increased from in to nearly in After, the ratio decreased, reaching a nadir in The past decade has seen a sharp rise in syphilis cases among men, driven mostly by the MSM community. Males with primary and secondary syphilis outnumber females 10 to 1. The incubation period for primary syphilis is 14 to 21 days. Symptoms of primary syphilis are: Small, painless open sore or ulcer (called a chancre) on the genitals, mouth, skin, or rectum that heals by itself in 3 to 6 weeks; Enlarged lymph nodes in the area of the sore ; The bacteria continue to grow in the body, but there are few symptoms until the second stage. Secondary syphilis. Secondary syphilis becomes ary syphilis is characterised by rash and systemic symptoms, during which the patient is very infectious. If the patient is untreated, these symptoms will eventually resolve over a number of weeks, but they can recur. Untreated, 25% of patients develop secondary syphilis within three months (average six weeks) after. Primary and Secondary Syphilis United States, After declining every year duringthe rate of primary and secondary (P&S) syphilis in the United States increased in To characterize the epidemiology of syphilis in the United States, CDC analyzed national surveillance data for *. is a rapid access, point-of-care medical reference for primary care and emergency clinicians. Started inthis collection now contains interlinked topic pages divided into a tree of 31 specialty books and chapters. Current and Historical Conditions Indexed list of current and historical nationally notifiable conditions. Primary genital syphilis () Concepts: Disease or Syndrome (T) ICD9: ICD A SnomedCT:English: Genital syphilis (primary. Primary and Secondary Syphilis -- United States, Rates of primary and secondary (P&S) syphilis have been declining in the United States since the last national epidemic in (1).Syphilis causes substantial morbidity and mortality in the form of cardiac and neurologic disease, stillbirth and developmental disability from congenital syphilis, and by facilitating transmission of human. There are four stages of syphilis called Primary, secondary, latent and Tertiary syphilis. Primary stage: It occurs weeks after contact with the bacteria. The disease starts as a small, round sore called chancre which is painless but highly infectious. This sore/s may appear in the genitals, mouth and or rectum. The sore remains for about 6. Syphilis – Primary (stage) can be completely treated and cured, if an early diagnosis and proper management is rendered. A full recovery is possible and the outcome is excellent in such cases The condition of infected individuals without treatment will progressively worsen over many years. chancres located in the rectum, vagina, or the uterus are still highly contagious despite their ability to go unnoticed. Secondary Syphilis the stage of syphilis that occurs three months to four months after the appearance of primary syphilis in which the disease has become systemic. Syphilis has three distinct stages of progression; each stage more aggressive than the previous one: Primary, Secondary, and Tertiary After the Secondary stage, there is a latent stage, known as Asymptomatic Syphilis which may last for many years (even decades). Reproductive system disease - Reproductive system disease - Syphilis: Syphilis is caused by the bacterial spirochete Treponema pallidum. Although known in Europe since the 15th century, syphilis was not recognized as a sexually transmitted disease until some years ago. It first appears as a painless sore, called a chancre, on the skin or mucous membranes of the genitals two to four weeks. primary syphilis: n. The first stage of syphilis, characterized by formation of a painless chancre at the point of infection and hardening and swelling of adjacent lymph nodes. The management of syphilis is based upon its classification into stages of disease: early syphilis (includes primary, secondary, and early latent syphilis); late (includes late latent, cardiovascular, and gummatous syphilis); and neurosyphilis (includes central nervous system disease and ocular syphilis at any time). Primary, Secondary, & Early Latent Syphilis -Benzathine Penicillin G mu IM x1 - Doxycycline mg BID x 14 days (PCN allergy) • Late Latent Syphilis - Benzathine Penicillin G mu IM q weekly x 3 - Doxycycline mg BID x 28 days (PCN allergy) • Tertiary Syphilis, Neurosyphilis & Congenital Syphilis.Communicable during primary & secondary syphilis Secondary syphilis followed by a period of clinical quiescence called early latent phase and after one year, latent phase Latent syphilis may be followed many years or decades later by tertiary syphilis. Primary syphilis.Initially, Syphilis appears as a painless sore (ulcer) where the infection entered — either the mouth or more frequently the genitals, and may go unnoticed. The sore is known as a chancre, and this phase of the infection is known as primary syphilis. The sore typically heals within weeks.	2	11	1	0	0	0.321876	1	1,975
NORD gratefully acknowledges Rabi Tawil, MD, Professor of Neurology, University of Rochester Medical Center, for assistance in the preparation of this report. Andersen-Tawil syndrome is a rare genetic disorder characterized by episodes of muscle weakness and paralysis (periodic paralysis); abnormalities affecting the electrical system of the heart that can cause abnormal heart rhythms (arrhythmias); and a variety of distinctive facial and skeletal features. The specific symptoms and severity can vary greatly from one person to another, even among members of the same family. Some individuals will not develop all of the characteristic findings. Distinctive facial features may be so mild as to go unnoticed. In some cases, Andersen-Tawil syndrome is caused by mutations in the KCNJ2 gene; in other cases, the associated gene is unknown. The KCNJ2 gene mutation can occur randomly for unknown reasons (sporadically) or be inherited in an autosomal dominant manner. Andersen-Tawil syndrome is sometimes referred to as long QT syndrome 7 because some individuals in early reports of the disorder had a prolonged QT interval, which is measured on an electrocardiogram and indicates that the heart muscle is taking longer than usual to recharge between beats. However, subsequent clinical reports have shown the QT interval is not prolonged or only mildly prolonged in most cases. Instead, the Q-U interval is markedly prolonged. In addition, unlike most forms of long QT syndrome, Andersen-Tawil syndrome is associated with symptoms in addition to disturbances of the electrical system of the heart. Although still sub-classified as a form of long QT syndrome, the disorder is recognized as separate from traditional long QT syndromes. Andersen-Tawil syndrome can also be classified as a form of periodic paralysis, a group of rare neuromuscular disorders characterized by episodes of weakness or paralysis. The terms Andersen-Tawil syndrome type 1 or type 2 are also used in the medical literature. Type 1 refers to cases caused by a known KCNJ2 gene mutation; type 2 refers to cases without an identified KCNJ2 mutation. Andersen-Tawil syndrome is defined by three main features (i.e. a clinical triad), specifically periodic paralysis, arrhythmias and heart abnormalities, and distinctive physical features. However, the disorder is highly variable and not all affected individuals will develop all three of these characteristic symptoms. Andersen-Tawil syndrome can vary greatly in expression and severity from one person to another, even among members of the same family. Although researchers have established a clear syndrome with characteristic or “core” symptoms, much about the disorder is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of other genes influencing the disorder prevent physicians from developing a complete picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis. Affected individuals may experience temporary episodes of flaccid, muscle weakness or paralysis, known as periodic paralysis. The legs are most often affected and the severity of muscle weakness can range from mild weakness to an inability to walk unassisted. The arms, hands, legs and feet are also commonly affected. The frequency and duration of episodes varies from one person to another and from one episode to the next for the same person. Some episodes may last only minutes to hours; others can go on for days. Episodes can occur without warning (spontaneously), but can also occur following prolonged exercise, prolonged rest (e.g. upon awaking in the morning), rest after exercise, going too long without eating, eating a large meal, or emotional stress. Episodes can range in frequency from once per day to once per year. In some cases, a mild, but permanent weakness, present even between episodes, can develop with age and progress slowly over time. In most cases, periodic paralysis may be associated with low levels of potassium in the blood (hypokalemia), a common finding with other forms of periodic paralysis. However, some individuals who experience periodic paralysis have had normal potassium levels or even elevated levels (hyperkalemia). Low potassium levels can also impact the function of heart muscle cells. Affected individuals may experience disturbances of the normal rhythm of the heartbeat (arrhythmias), which can include abnormally fast heartbeats that originate in the lower chamber of the heart (ventricular tachycardia). Generally, this may not cause any symptoms (asymptomatic) or may cause shortness of breath or palpitations. In some cases, these arrhythmias may cause episodes of fainting or loss of consciousness (syncope). In severe cases, the possibility of cardiac arrest and sudden death exists. Although sudden death due to the cardiac abnormalities has occurred in Andersen-Tawil syndrome, it is extremely rare. Some affected individuals also have characteristic physical features including distinctive facial features, which are often mild in expression. Such features include a broad forehead, low-set ears, eyes that are spaced apart wider than usual (hypertelorism), and a small jaw (micrognathia). Additional facial features include a round (bulbous) nose, a thin upper lip, a triangular-shaped face, highly-arched roof of the mouth (palate), a cleft palate, and underdevelopment of the cheek bones (malar hypoplasia). Common physical features include webbing (syndactyly) of the second and/or third toes, pinkies that are fixed in a bent or crooked position (clinodactyly), and disproportionately small fingers and toes (brachydactyly). Additional findings include small hands and feet, loose joints, and abnormal sideways curvature of the spine (scoliosis). Dental anomalies have also been reported including delayed loss of primary or ‘baby’ teeth (persistent primary dentition), multiple missing teeth (oligodontia), and teeth that are abnormally crowded together. As affected children grow into adulthood, short stature may become evident. Short stature refers to an individual whose height is much shorter than would otherwise be expected based upon age and gender. Some individuals with Andersen-Tawil syndrome have experienced neuropsychiatric abnormalities including mild learning disabilities, depression, and deficits in executive functioning and abstract reasoning. Some infants experience seizures without fever (afebrile seizures). In approximately 60% of cases, Andersen-Tawil syndrome is caused by a mutation in the KCNJ2 gene. In the other 40% of cases, the underlying genetic mutation is unknown, suggesting that additional as-yet-unidentified genes also cause the disorder. 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. In approximately 50% of cases, the KCNJ2 gene mutation occurs sporadically, which means that in those specific cases the gene mutation has occurred at the time of the formation of the egg or sperm for that child only and no other family member will be affected. The disorder is usually not inherited from or “carried” by a healthy parent. When the disorder runs in families, the mutations are inherited in an autosomal dominant manner. 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 mutated (changed) gene 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. The KCNJ2 gene produces (encodes) a protein essential for the proper development and function of certain ion channels. These channels are pores in cell membranes that regulate the movement of electrically-charged particles called ions (e.g. potassium and sodium ions) into muscle cells, including heart muscle and limb muscle cells and tissue. These ions carry electrical impulses necessary for the normal function of the cells involved. Mutations in the KCNJ2 gene results in abnormal functioning of the ion channels and, in turn, affect the proper function and development of skeletal muscle and the heart’s electrical system. The exact manner this mutation affects bone development and cause the distinctive facial and other skeletal features associated with Andersen-Tawil syndrome is not known. Andersen-Tawil syndrome affects males and females in equal numbers. The exact incidence or prevalence of the disorder is unknown. More than 100 cases have been reported in the medical literature. Because many cases go undiagnosed or misdiagnosed, determining the true frequency of Andersen-Tawil syndrome in the general population is difficult. A diagnosis of Andersen-Tawil syndrome is based upon identification of characteristic symptoms (e.g. periodic paralysis, symptomatic arrhythmias, and/or distinctive facial and skeletal features), a detailed family and patient history, a thorough clinical evaluation and a variety of specialized tests. Clinical Testing and Workup Because potassium levels may be reduced during an episode of periodic paralysis, a blood test to determine the serum potassium levels during an episode can be helpful in diagnosing the disorder in some cases. Long exercise nerve conduction studies have been used to help diagnose individuals with Andersen-Tawil syndrome. During this test, an affected individual will perform voluntary muscle contractions of a small muscle on the ulnar side of the palm of the hand for approximately 2-5 minutes. This test allows physician to evaluate muscle function and specific results can be indicative of periodic paralysis. An electrocardiogram or EKG records the heart’s electrical impulses and may reveal abnormal electrical patterns or activity commonly associated with Andersen-Tawil syndrome including prominent U waves, prolonged QU intervals, prolonged QT intervals, premature ventricular contractions, or polymorphic ventricular tachycardia. Some individuals may undergo 24-Holter monitoring, during which an affected individual wears a small device for 24 hours. Through electrodes attached to the chest, this device continuously records the rhythm of the heart in order to detect the presence, frequency and duration of ventricular tachycardia and other symptoms. Molecular genetic testing can confirm a diagnosis of Andersen-Tawil syndrome in some cases. Molecular genetic testing can detect mutations in the KCNJ2 gene known to cause the disorder, but is available only as a diagnostic service at specialized laboratories. The treatment of Andersen-Tawil syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, neurologists experienced in the treatment of periodic paralysis, cardiologists experienced in the treatment of long QT syndrome, and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment. There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disorder, 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 Andersen-Tawil syndrome. Affected individuals are encouraged to avoid potential triggers of periodic paralysis (e.g. rest following exercise or prolonged exercise). Avoidance of drugs that can prolong the QT interval is also recommended. When periodic paralysis is associated with low potassium levels, treatment with oral supplemental potassium can be beneficial. In individuals prone to low potassium levels, daily potassium supplementation can be considered. Potassium supplementation may also shorten the QT interval, which can be of benefit for individuals who also experience a long QT interval. A periodic paralysis episode that occurs when potassium levels are high usually resolve on their own within 60 minutes. However, eating carbohydrates or continuing mild exercise can shorten the duration of the episode. Specific drugs known as carbonic anhydrase inhibitors, such as acetazolamide and dichlorpenamide, are used to treat periodic paralysis in individuals with Andersen-Tawil syndrome. Clinical trials in other forms of periodic paralysis showed that dichlorphenamide reduces the frequency and severity of attacks of periodic paralysis and is now an FDA approved for the treatment of periodic paralysis. Despite a high frequency of ventricular arrhythmias in some individuals with Andersen-Tawil syndrome, they rarely degenerate into life-threatening arrhythmias. Many arrhythmias do not cause symptoms and go away on their own without problems (self-terminate). Various different drugs have been used, but no standard, effective therapy has been established. Beta-adrenergic blocking drugs (beta blockers), drugs that suppress abnormal heart rhythms (anti-arrhythmics) such as flecainide or amiodarone, or calcium-channel blocking drugs such as verapamil have all shown some effect. Beta blockers are commonly used to treat abnormal heart rhythms. These drugs, which include propranolol, atenolol, metroprolol, and nadolol, reduce the workload of the heart by decreasing the electrical stimulation of the heart, thereby slowing the heartbeat and preventing symptoms. Beta blockers have been used in conjunction with flecainide. Some anti-arrhythmic drugs can worsen neuromuscular symptoms and should be used with caution in individuals with Andersen-Tawil syndrome. Treatment with an implantable automatic cardioverter-defibrillator or ICD is necessary in rare cases. ICDs are considered for individuals in whom cardiac arrhythmias are severe and symptomatic. These small devices are implanted under the skin of the chest. The device detects the abnormal heartbeat automatically and selectively delivers an electrical impulse to restore the proper heartbeat. Opting for an ICD is a lifelong therapy that carries significant implications including the potential for complications, especially in younger individuals, and should be undertaken only after consultation with appropriate medical personnel and a careful risk vs. benefit evaluation. Genetic counseling is recommended for affected individuals and their families. 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: Tollfree: (800) 411-1222 TTY: (866) 411-1010 Email: [email protected] Some current clinical trials also are posted on the following page on the NORD website: For information about clinical trials sponsored by private sources, contact: For information about clinical trials conducted in Europe, contact: Tristani-Firouzi M, Tawil R. Andersen-Tawil Syndrome. In: Cardiac Electrophysiology: From Cell to Bedside, 6th ed. Zipes DP, Jalife J, editors. 2014 Elsevier Saunders, Philadelphia, PA. pp. 947-952. Kostera-Pruszczyk A, Potulska-Chromik A, Pruszczyk P, et al. Andersen-Tawil syndrome: report of 3 novel mutations and high risk of symptomatic cardiac involvement. Muscle Nerve. 2015;51:192-196. http://www.ncbi.nlm.nih.gov/pubmed/24861851 Almuqbil M, Srour M. Child neurology: Andersen-Tawil syndrome. Neurology. 2015;84:e78-80. http://www.ncbi.nlm.nih.gov/pubmed/25780024 Miyamoto K, Aiba T, Kimura H, et al. Efficacy and safety of flecainide for ventricular arrhythmias in patients with Andersen-Tawil syndrome and KCNJ2 mutations. Heart Rhythm. 2015;12:596-603. http://www.ncbi.nlm.nih.gov/pubmed/25496985 Wilde AA. Andersen-Tawil syndrome, scarier for the doctor than for the patient? Who, when, and how to treat. Europace. 2013;15:1690-1692. http://www.ncbi.nlm.nih.gov/pubmed/24128811 Delannoy E, Sacher F, Maury P, et al. Cardiac characteristics and long-term outcome in Andersen-Tawil syndrome patients related to KCNJ2 mutation. Europace. 2013;15:1805-1811. http://www.ncbi.nlm.nih.gov/pubmed/23867365 Nguyen HL, Pieper GH, Wilders R. Andersen-Tawil syndrome: clinical and molecular aspects. Int J Cardiol. 2013;170:1-16. http://www.ncbi.nlm.nih.gov/pubmed/24383070 Kimura H, Zhou J, Kawamura M, et al. Phenotypic variability in patients carrying KCNJ2 mutations. Circ Cardiovasc Genet. 2012;5:344-353. http://www.ncbi.nlm.nih.gov/pubmed/22589293 Tan SV, Matthews E, Barber M, et al. Refined exercise testing can aid DNA-based diagnosis in muscle channelopathies. Ann Neurol. 2011;69:328-340. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3051421/ Barajas-Martinez H, Hu D, Ontiveros G, et al. Biophysical and molecular characterization of a novel de novo KCNJ2 mutation associated with Andersen-Tawil syndrome and CPVT mimicry. Circ Cardiovasc Genet. 2011;4:51-57. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3041844/ Airey KJ, Ehteridge SP, Tawil R, Tristani-Firouzi M. Resuscitated sudden cardiac death in Andersen-Tawil syndrome. Heart Rhythm. 2009;6:1814-1817. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789273/ Pellizzon OA, Kalaizich L, Ptacek LJ, Tristani-Firouzi M, Gonzalez MD. Flecainaide suppresses bidirectional ventricular tachycardia and reverses tachycardia-induced cardiomyopathy in Andersen-Tawil syndrome. J Cardiovasc Electrophysiol. 2008;19:95-97. http://www.ncbi.nlm.nih.gov/pubmed/17655675 Peters S, Schulze-Bahr E, Etheridge SP, Tristani-Firouzi M. Sudden cardiac death in Andersen-Tawil syndrome. Europace. 2007;9:162-166. http://www.ncbi.nlm.nih.gov/pubmed/17272325 Sansone V, Tawil R. Management and treatment of Andersen-Tawil syndrome (ATS). Neurotherapeutics. 2007;4:233-237. http://www.ncbi.nlm.nih.gov/pubmed/17395133 Yoon G, Oberoi S, Tristani-Firouzi M, et al. Andersen-Tawil syndrome: prospective cohort analysis and expansion of the phenotype. Am J Med Genet A. 2006;140:312-321. http://www.ncbi.nlm.nih.gov/pubmed/16419128 Tristani-Firouzi M, Jensen JL, Donaldson MR, et al. Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). J Clin Invest. 2002;110:381-388. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC151085/ Veerapandiyan A, Statland JM, Tawil R. Andersen-Tawil Syndrome. 2004 Nov 22 [Updated 2018 Jun 7]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1264/ Accessed June 19, 2018. Sripathi N. Periodic Paralyses.Medscape Updated: Apr 30, 2018. Available at: http://emedicine.medscape.com/article/1171678-overview Accessed June 19, 2018. McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:170390; Last Update:04/23/2014. Available at: http://omim.org/entry/170390 Accessed June 19, 2018. The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional. The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright. National Organization for Rare Disorders (NORD) 55 Kenosia Ave., Danbury CT 06810 • (203)744-0100	2	11	1	0	0	0.755449	1	4,645
- Atrial septal defect Atrial septal defect Classification and external resources Heart of human embryo of about thirty-five days ICD-10 Q21.1 ICD-9 745.5-745.6 OMIM 108800 DiseasesDB 1089 eMedicine med/3519 MeSH C14.240.400.560.375 Atrial septal defect (ASD) is a form of congenital heart defect that enables blood flow between the left and right atria via the interatrial septum. The interatrial septum is the tissue that divides the right and left atria. Without this septum, or if there is a defect in this septum, it is possible for blood to travel from the left side of the heart to the right side of the heart, or vice versa. This results in the mixing of arterial and venous blood, which may or may not be clinically significant. This mixture of blood may or may not result in what is known as a "shunt". The amount of shunting present, if any, dictates hemodynamic significance (see Pathophysiology below). A "right-to-left-shunt" typically poses the more dangerous scenario (see Pathophysiology below). The right side of the heart contains venous blood with a low oxygen content, and the left side of the heart contains arterial blood with a high oxygen content. A normal heart has an interatrial septum that prevents oxygen-rich blood and oxygen-deficient blood from mixing together. During development of the fetus, the interatrial septum develops to separate the left and right atrium. However, the foramen ovale ( / /) allows blood from the right atrium to the left atrium during fetal development. This opening allows blood to bypass the nonfunctional fetal lungs when the fetus obtains its oxygen from the placenta. A layer of tissue called the septum primum acts as a valve over the foramen ovale during fetal development. After birth, the pressure in the pulmonary circulatory system drops, thus causing the foramen ovale to close entirely. In approximately 25% of adults, the foramen ovale does not entirely seal. In this case, elevation of pressure in the pulmonary circulatory system (i.e.: pulmonary hypertension due to various causes, or transiently during a cough) can cause the foramen ovale to remain open. This is known as a patent foramen ovale (PFO). - 1 Pathophysiology - 2 Epidemiology - 3 Types of atrial septal defects - 4 Diagnosis - 5 Treatment - 6 Associated conditions - 7 See also - 8 External links - 9 References In unaffected individuals, the chambers of the left side of the heart are under higher pressure than the chambers of the right side of the heart. This is because the left ventricle has to produce enough pressure to pump blood throughout the entire body, while the right ventricle only has to produce enough pressure to pump blood to the lungs. In the case of a large ASD (>9mm), which may result in a clinically remarkable left-to-right shunt, blood will shunt from the left atrium to the right atrium. This extra blood from the left atrium may cause a volume overload of both the right atrium and the right ventricle. If untreated, this condition can result in enlargement of the right side of the heart and ultimately heart failure. Any process that increases the pressure in the left ventricle can cause worsening of the left-to-right shunt. This includes hypertension, which increases the pressure that the left ventricle has to generate in order to open the aortic valve during ventricular systole, and coronary artery disease which increases the stiffness of the left ventricle, thereby increasing the filling pressure of the left ventricle during ventricular diastole. The right ventricle will have to push out more blood than the left ventricle due to the left-to-right shunt. This constant overload of the right side of the heart will cause an overload of the entire pulmonary vasculature. Eventually pulmonary hypertension may develop. The pulmonary hypertension will cause the right ventricle to face increased afterload in addition to the increased preload that the shunted blood from the left atrium to the right atrium caused. The right ventricle will be forced to generate higher pressures to try to overcome the pulmonary hypertension. This may lead to right ventricular failure (dilatation and decreased systolic function of the right ventricle) or elevations of the right sided pressures relative to left sided pressures. When the pressure in the right atrium rises to the level in the left atrium, there will no longer be a pressure gradient between these heart chambers, and the left-to-right shunt will diminish or cease. If left uncorrected, the pressure in the right side of the heart will be greater than the left side of the heart. This will cause the pressure in the right atrium to be higher than the pressure in the left atrium. This will reverse the pressure gradient across the ASD, and the shunt will reverse; a right-to-left shunt will exist. This phenomenon is known as Eisenmenger's syndrome. Once right-to-left shunting occurs, a portion of the oxygen-poor blood will get shunted to the left side of the heart and ejected to the peripheral vascular system. This will cause signs of cyanosis. As a group, atrial septal defects are detected in 1 child per 1500 live births. PFO are quite common (appearing in 10 - 20% of adults) but asymptomatic and therefore undiagnosed. ASDs make up 30 to 40% of all congenital heart disease that is seen in adults. The ostium secundum atrial septal defect accounts for 7% of all congenital heart lesions. This lesion shows a female preponderance, with a male : female ratio of 1:2. Types of atrial septal defects There are many types of atrial septal defects. They are differentiated from each other by whether they involve other structures of the heart and how they are formed during the developmental process during early fetal development. Ostium secundum atrial septal defect The ostium secundum atrial septal defect is the most common type of atrial septal defect, and comprises 6-10% of all congenital heart diseases. The secundum atrial septal defect usually arises from an enlarged foramen ovale, inadequate growth of the septum secundum, or excessive absorption of the septum primum. Ten to twenty percent of individuals with ostium secundum ASDs also have mitral valve prolapse. Most individuals with an uncorrected secundum ASD do not have significant symptoms through early adulthood. About 70% develop symptoms by the time they are in their 40s. Symptoms are typically decreased exercise tolerance, easy fatigueability, palpitations, and syncope. While pulmonary hypertension is unusual before 20 years of age, it is seen in 50% of individuals above the age of 40. Progression to Eisenmenger's syndrome occurs in 5 to 10% of individuals late in the disease process. Patent foramen ovale A patent foramen ovale (PFO) is a small channel that has little hemodynamic consequence; it is a remnant of the fetal foramen ovale. Clinically it is linked to decompression sickness, paradoxical embolism and migraine. On echocardiography, there may not be any shunting of blood noted except when the patient coughs. There is debate within the neurology and cardiology communities about the role of a PFO in cryptogenic (i.e. of unknown cause) neurologic events such as strokes and transient ischemia attacks (TIAs) without any other potential cause. Some data suggested that PFOs may be involved in the pathogenesis of some migraine headaches. Several clinical trials are currently underway to investigate the role of PFO in these clinical situations. Ostium primum atrial septal defect Sinus venosus atrial septal defect A sinus venosus ASD that involves the superior vena cava makes up 2 to 3% of all interatrial communication. It is located at the junction of the superior vena cava and the right atrium. It is frequently associated with anomalous drainage of the right-sided pulmonary veins into the right atrium (instead of the normal drainage of the pulmonary veins into the left atrium). Common or single atrium Common (or single) atrium is a failure of development of the embryologic components that contribute to the atrial septal complex. It is frequently associated with heterotaxy syndrome. Mixed Atrial septal defect The inter atrial septum can be divided in to 5 septal zones. If the defect involves 2 or more of the 5 septal zones, then the defect is termed a mixed atrial septal defect. Diagnosis in children Diagnosis in adults Some individuals with an ASD will have undergone surgical correction of their ASD during childhood. The development of signs and symptoms due to an ASD are related to the size of the intracardiac shunt. Individuals with a larger shunt tend to present with symptoms at a younger age. Adults with an uncorrected ASD will present with symptoms of dyspnea on exertion (shortness of breath with minimal exercise), congestive heart failure, or cerebrovascular accident (stroke). They may be noted on routine testing to have an abnormal chest x-ray or an abnormal ECG and may have atrial fibrillation. Physical exam auscultation of the heart The physical findings in an adult with an ASD include those related directly to the intracardiac shunt, and those that are secondary to the right heart failure that may be present in these individuals. Upon auscultation of the heart sounds, there may be an ejection systolic murmur that is attributed to the pulmonic valve. This is due to the increased flow of blood through the pulmonic valve rather than any structural abnormality of the valve leaflets. In unaffected individuals, there are respiratory variations in the splitting of the second heart sound (S2). During respiratory inspiration, the negative intrathoracic pressure causes increased blood return into the right side of the heart. The increased blood volume in the right ventricle causes the pulmonic valve to stay open longer during ventricular systole. This causes a normal delay in the P2 component of S2. During expiration, the positive intrathoracic pressure causes decreased blood return to the right side of the heart. The reduced volume in the right ventricle allows the pulmonic valve to close earlier at the end of ventricular systole, causing P2 to occur earlier. In individuals with an ASD, there is a fixed splitting of S2. The reason that there is a fixed splitting of the second heart sound is that the extra blood return during inspiration gets equalized between the left and right atrium due to the communication that exists between the atria in individuals with ASD. The right ventricle can be thought of as continuously overloaded because of the left to right shunt, producing a widely split S2. Because the atria are linked via the atrial septal defect, inspiration produces no net pressure change between them, and has no effect on the splitting of S2. Thus, S2 is split to the same degree during inspiration as expiration, and is said to be “fixed.” In transthoracic echocardiography, an atrial septal defect may be seen on color flow imaging as a jet of blood from the left atrium to the right atrium. If agitated saline is injected into a peripheral vein during echocardiography, small air bubbles can be seen on echocardiographic imaging. It may be possible to see bubbles travel across an ASD either at rest or during a cough. (Bubbles will only flow from right atrium to left atrium if the RA pressure is greater than LA). Because better visualization of the atria is achieved with transesophageal echocardiography, this test may be performed in individuals with a suspected ASD which is not visualized on transthoracic imaging. Newer techniques to visualize these defects involve intracardiac imaging with special catheters that are typically placed in the venous system and advanced to the level of the heart. This type of imaging is becoming more common and involves only mild sedation for the patient typically. If the individual has adequate echocardiographic windows, it is possible to use the echocardiogram to measure the cardiac output of the left ventricle and the right ventricle independently. In this way, it is possible to estimate the shunt fraction using echocardiograpy. Transcranial Doppler (TCD) Bubble study A less invasive method for detecting a PFO or other ASDs than transesophagal ultrasound is Transcranial Doppler with bubble contrast. This method reveals the cerebral impact of the ASD or PFO. The ECG findings in atrial septal defect vary with the type of defect the individual has. Individuals with atrial septal defects may have a prolonged PR interval (a first degree heart block). The prolongation of the PR interval is probably due to the enlargement of the atria that is common in ASDs and the increased distance due to the defect itself. Both of these can cause an increased distance of internodal conduction from the SA node to the AV node. In addition to the PR prolongation, individuals with a primum ASD have a left axis deviation of the QRS complex while those with a secundum ASD have a right axis deviation of the QRS complex. Individuals with a sinus venosus ASD exhibit a left axis deviation of the P wave (not the QRS complex). A common finding in the ECG is the presence of incomplete RBBB (Right Bundle Branch Block). In fact this finding is so characteristic that if it is absent, the diagnosis of ASD should be revised. Once someone is found to have an atrial septal defect, a determination of whether it should be corrected has to be made. Surgical mortality due to closure of an ASD is lowest when the procedure is performed prior to the development of significant pulmonary hypertension. The lowest mortality rates are achieved in individuals with a pulmonary artery systolic pressure of less than 40 mmHg. If Eisenmenger's syndrome has occurred, there is significant risk of mortality regardless of the method of closure of the ASD. In individuals who have developed Eisenmenger's syndrome, the pressure in the right ventricle has raised high enough to reverse the shunt in the atria. If the ASD is then closed, the afterload that the right ventricle has to act against has suddenly increased. This may cause immediate right ventricular failure, since it may not be able to pump the blood against the pulmonary hypertension. Closure of an ASD in individuals under age 25 has been shown to have a low risk of complications, and individuals have a normal lifespan (comparable to a healthy age-matched population). Closure of an ASD in individuals between the ages of 25 and 40 who are asymptomatic but have a clinically significant shunt is controversial. Those that perform the procedure believe that they are preventing long-term deterioration in cardiac function and preventing the progression of pulmonary hypertension. Methods of closure of an ASD include surgical closure and percutaneous closure. Evaluation prior to correction Prior to correction of an ASD, an evaluation is made of the severity of the individual's pulmonary hypertension (If present at all) and whether it is reversible (Closure of an ASD may be recommended for prevention purposes, to avoid such a complication in the first place. Pulmomary hypertension is not always present in adults that are diagnosed with an ASD in adulthood). If pulmonary hypertension is present, the evaluation may include a right heart catheterization. This involves placing a catheter in the venous system of the heart and measuring pressures and oxygen saturations in the SVC, IVC, right atrium, right ventricle, pulmonary artery, and in the wedge position. Individuals with a pulmonary vascular resistance (PVR) of less than 7 wood units show regression of symptoms (including NYHA functional class). On the other hand, individuals with a PVR of greater than 15 wood units have increased mortality associated with closure of the ASD. If the pulmonary arterial pressure is more than 2/3 the systemic systolic pressure, there should be a net left-to-right shunt of at least 1.5:1 or evidence of reversibility of the shunt when given pulmonary artery vasodilators prior to surgery. (If eisenmenger's physiology has set in, it must be proven that the right-to-left shunt is reversible with pulmonary artery vasodilators prior to surgery.) Until the early 1990s, surgery was the usual method for closing all ASDs. Now, thanks to medical advances, doctors can use catheter procedures to close secundum ASDs, the most common type of ASD. For this procedure, the patient is given medicine so he or she will sleep through it and not feel any pain. During the procedure, the doctor inserts a catheter (a thin, flexible tube) into a vein in the groin (upper thigh) and threads it to the heart's septum. The catheter has a tiny umbrella-like device folded up inside it.When the catheter reaches the septum, the device is pushed out of the catheter and positioned so that it plugs the hole between the atria. The device is secured in place and the catheter is withdrawn from the body.Within 6 months, normal tissue grows in and over the device. There is no need to replace the closure device as the child grows.Doctors often use echocardiography (echo) or transesophageal (tranz-ih-sof-uh-JEE-ul) echo (TEE) as well as angiography (an-jee-OG-ra-fee) to guide them in threading the catheter to the heart and closing the defect. TEE is a special type of echo that takes pictures of the heart through the esophagus (the passage leading from the mouth to the stomach).Catheter procedures are much easier on patients than surgery because they involve only a needle puncture in the skin where the catheter is inserted. This means that recovery is faster and easier.The outlook for children having this procedure is excellent. Closures are successful in more than 9 out of 10 patients, with no significant leakage. Rarely, a defect is too large for catheter closure and surgery is needed. Surgical ASD closure Surgical closure of an ASD involves opening up at least one atrium and closing the defect with a patch under direct visualization. Percutaneous ASD closure Percutaneous closure of an ASD is currently only indicated for the closure of secundum ASDs with a sufficient rim of tissue around the septal defect so that the closure device does not impinge upon the SVC, IVC, or the tricuspid or mitral valves. The Amplatzer Septal Occluder (ASO) is commonly used to close ASDs. The ASO consists of two self-expandable round discs connected to each other with a 4 mm waist, made up of 0.004–0.005´´ Nitinol wire mesh filled with Dacron fabric. Implantation of the device is relatively easy. The prevalence of residual defect is low. The disadvantages are a thick profile of the device and concern related to a large amount of nitinol (a nickel-titanium compound) in the device and consequent potential for nickel toxicity. Percutaneous closure is the method of choice in most centres. Due to the communication between the atria that occurs in ASDs, disease entities or complications from the condition, are possible. ASDs, and particularly PFOs, are a predisposing risk factor for decompression sickness in divers because a proportion of venous blood carrying inert gases, such as helium or nitrogen does not pass through the lungs. The only way to release the excess inert gases from the body is to pass the blood carrying the inert gases through the lungs to be exhaled. If some of the inert gas-laden blood passes through the PFO, it avoids the lungs and the inert gas is more likely to form large bubbles in the arterial blood stream causing decompression sickness. Venous thrombi (clots in the veins) are quite common. Embolization (dislodgement of thrombi) normally go to the lung and cause pulmonary emboli. In an individual with ASD, these emboli can potentially enter the arterial system. This can cause any phenomenon that is attributed to acute loss of blood to a portion of the body, including cerebrovascular accident (stroke), infarction of the spleen or intestines, or even a distal extremity .......(i.e.: finger or toe). This is known as a paradoxical embolus because the clot material paradoxially enters the arterial system instead of going to the lungs. Some recent research has suggested that a proportion of cases of migraine may be caused by patent foramen ovale. While the exact mechanism remains unclear, closure of a PFO can reduce symptoms in certain cases. This remains controversial. 20% of the general population have a PFO, which for the most part, is asymptomatic. 20% of the female population have migraines. And, the placebo effect in migraine typically averages around 40%. The high frequency of these facts makes statistically significant relationships between PFO and migraine difficult (i.e., the relationship may just be chance or coincidence). In a large randomized controlled trial the higher prevalence of patent foramen ovale in migraine patients was confirmed, but migraine headache cessation was not more prevalent in the group of migraine patients that underwent closure of their patent foramen ovale. It's likely that a virus can pass through PFO, therefore not being filtered by the lungs, and sent directly to the brain. This can cause a type of sinusitis which can lead to viral meningitis. (This claims requires supporting evidence) - Atrioventricular septal defect - Cardiac output - Congenital heart disease - Heart sounds - Pulmonary hypertension - Vascular resistance - Pulmonary vascular resistance - Ventricular septal defect - Illnesses of Ariel Sharon - Minimally Invasive Heart Surgery - Pediatric Heart Surgery - The Congenital Heart Surgery Video Project - Pediatric Cardiac Surgery: Atrial Septal Defect Repair - ^ Atrial septal defect at Mount Sinai Hospital - ^ Robbins Basic Pathology, 8th Edition, p. 384 - ^ Atrial Septal Defect in PediatriceMedicine - ^ a b , Mixed Atrial Septal Defect: Coexisting Ostium Secundum and Sinus Venosus Atrial Septal Defect . - ^ Kaplan S (1993). "Congenital heart disease in adolescents and adults. Natural and postoperative history across age groups". Cardiol Clin 11 (4): 543–56. PMID 8252558. - ^ Feldt R, Avasthey P, Yoshimasu F, Kurland L, Titus J (1971). "Incidence of congenital heart disease in children born to residents of Olmsted County, Minnesota, 1950-1969". Mayo Clin Proc 46 (12): 794–9. PMID 5128021. - ^ Leachman R, Cokkinos D, Cooley D (1976). "Association of ostium secundum atrial septal defects with mitral valve prolapse". Am J Cardiol 38 (2): 167–9. doi:10.1016/0002-9149(76)90144-2. PMID 952260. - ^ "Atrial Septal Defect Types - Mayo Clinic". http://www.mayoclinic.org/atrial-septal-defect/types.html. Retrieved 2007-10-14. - ^ Fix, James D.; Dudek, Ronald W. (1998). Embryology. Baltimore: Williams & Wilkins. pp. 52. ISBN 0-683-30272-8. - ^ Q21.2 - ^ Davia J, Cheitlin M, Bedynek J (1973). "Sinus venosus atrial septal defect: analysis of fifty cases". Am Heart J 85 (2): 177–85. doi:10.1016/0002-8703(73)90458-4. PMID 4569755. - ^ Valdes-Cruz LM, Cayre RO (1998). Echocardiographic diagnosis of congenital heart disease. Philadelphia. - ^ Glen, S.; J. Douglas. (1995). "Transcranial doppler monitoring. (letter to editor)". South Pacific Underwater Medicine Society Journal 25 (2). ISSN 0813-1988. OCLC 16986801. http://archive.rubicon-foundation.org/6409. Retrieved 2008-04-06. - ^ Clark E, Kugler J (1982). "Preoperative secundum atrial septal defect with coexisting sinus node and atrioventricular node dysfunction". Circulation 65 (5): 976–80. doi:10.1161/01.CIR.65.5.976. PMID 7074763. - ^ Bjørnstad P (2006). "Is interventional closure the current treatment of choice for selected patients with deficient atrial septation?". Cardiol Young 16 (1): 3–10. doi:10.1017/S1047951105002027. PMID 16454871. - ^ Lier H, Schroeder S, Hering R (2004). "[Patent foramen ovale: an underrated risk for divers?]". Dtsch Med Wochenschr 129 (1–2): 27–30. doi:10.1055/s-2004-812652. PMID 14703578. - ^ Saary M, Gray G (2001). "A review of the relationship between patent foramen ovale and type II decompression sickness". Aviat Space Environ Med 72 (12): 1113–20. PMID 11763113. - ^ Adams H (2004). "Patent foramen ovale: paradoxical embolism and paradoxical data". Mayo Clin Proc 79 (1): 15–20. doi:10.4065/79.1.15. PMID 14708944. - ^ Azarbal B, Tobis J, Suh W, Chan V, Dao C, Gaster R (2005). "Association of interatrial shunts and migraine headaches: impact of transcatheter closure". J Am Coll Cardiol 45 (4): 489–92. doi:10.1016/j.jacc.2004.09.075. PMID 15708691. - ^ "Migraine Intervention With STARFlex Technology (MIST) trial: a prospective, multicenter, double-blind, sham-controlled trial to evaluate the effectiveness of patent foramen ovale closure with STARFlex septal repair implant to resolve refractory migraine headache. - Dowson A et al. 117 (11): 1397-1404 - Circulation". http://circ.ahajournals.org/cgi/content/full/117/11/1397. Retrieved 2008-10-26. This article incorporates public domain material from the United States Department of Health and Human Services document "National Heart, Lung, and Blood Institute". Congenital heart defects (Q20–Q24, 745–746) Cardiac shunt/ heart septal defectAortopulmonary septal defectAtrial septal defectL→R: Sinus venosus atrial septal defect · Lutembacher's syndromeL→R: Ostium primum Valvular heart disease/ Wikimedia Foundation. 2010. См. также в других словарях: atrial septal defect — ▪ pathology congenital opening in the partition between the two upper chambers (atria) of the heart. The most common atrial septal defect is persistence of the foramen ovale, an opening in this partition that is normal before birth and that … Universalium atrial septal defect — (ASD) a congenital defect of the heart in which there is a hole in the partition (septum) separating the two atria (see septal defect). There are two kinds of ASD ostium primum and ostium secundum. Ostium primum defects are rarer but more serious … Medical dictionary atrial septal defect — ASD a congenital defect of the heart in which there is a hole in the partition (septum) separating the two atria (see septal defect). There are two kinds of ASD – ostium primum and ostium secundum. Ostium primum defects are rarer but more serious … The new mediacal dictionary atrial septal defect — noun an abnormal opening between the left and right atria of the heart • Hypernyms: ↑septal defect … Useful english dictionary Atrial septal defect (ASD) — A hole in the septum, the wall, between the atria, the upper chambers of the heart. Commonly called an ASD. ASDs constitute a major class of heart formation abnormalities present at birth (congenital cardiac malformations). Normally, when clots… … Medical dictionary Ostium primum atrial septal defect — Classification and external resources Schemating drawing showing the location of different types of ASD, the view is into an opened right atrium. HV: right ventricle; VCS: superior caval vein; VCI: inferior caval vein; 1: upper sinus venosus… … Wikipedia Дефект Межпредсердной Перегородки (Atrial Septal Defect, Asd) — см. Дефект перегородки. Источник: Медицинский словарь … Медицинские термины septal defect — a hole in the partition (septum) between the left and right halves of the heart. This abnormal communication is congenital due to an abnormality of heart development in the fetus. It may be found between the two atria (see atrial septal defect)… … Medical dictionary septal defect — a hole in the partition (septum) between the left and right halves of the heart. This abnormal communication is congenital due to an abnormality of heart development in the fetus. It may be found between the two atria (see atrial septal defect)… … The new mediacal dictionary septal defect — noun a congenital abnormality in the septum between the left and right sides of the heart • Hypernyms: ↑congenital heart defect • Hyponyms: ↑atrial septal defect, ↑ventricular septal defect … Useful english dictionary	2	27	3	0	4	0.936239	7	6,798
Chronic fatigue syndrome Chronic fatigue syndrome (CFS) is a condition of excessive fatigue, cognitive impairment and other varied symptoms. Classified by the World Health Organisation (WHO) as a disease of the nervous system, it is of unknown etiology and may last months or years, causing severe disability. In strict medical terms, the name chronic fatigue syndrome refers only to a pattern of symptoms (see below), and may in fact reflect several different disorders causing similar symptoms. While it can certainly be classified as a disease, there are no investigations that can confirm or rule out the diagnosis. Certain scoring systems have been designed to classify symptoms. There are a number of different syndromes which have been at various times identified with CFS. * Chronic Fatigue Syndrome (CFS); this name was introduced in 1988 by a group of researchers, given that most other names were inaccurate. * Chronic Fatigue Immune Dysfunction Syndrome (CFIDS); many people, especially patients in the United States, use the term CFIDS (pronouced [See-Fids]), which was originally an acronym for " or "Chronic Fatigue & Immune Dysregulation Syndrome". These terms were based on the belief that the illness is caused by problems with the immune system. Although this view is less prevalent, the acronym CFIDS is still used. * Myalgic Encephalomyelitis Myalgic Encephalitis (ME); outside the United States, "ME" is in common use, meaning "infection and swelling of the brain with muscle pain" or "infection of the brain with muscle pain" respectively. Like CFIDS, the term ME is often used although its original meaning is inaccurate. * Post-viral (fatigue) syndrome (PVS or PVFS); this is a slightly more general and therefore more accurate equivalent of ME. * Chronic Epstein-Barr Virus (CEBV) or Chronic Mononucleosis; this name was in common use before CFS became more prevalent. The Epstein-Barr virus, a virus that commonly causes mononucleosis, was thought to be the cause of CFS. This has proven not to be true (see etiology below), although the symptoms develop in some people after contracting mononucleosis. * Low Natural Killer Cell Disease; This name is used widely in Japan; it reflects the belief that CFS is related to the number of natural killer cells the patient has. * Yuppie Flu; this was a nickname for CFS, especially in the 1980s. It reflects the belief that CFS mainly affects the affluent ("yuppies"), and implies that it is a form of malingering or burnout. CFS, however, affects people of all races, genders, and social standings, and this name is inaccurate. * Akureyri Disease * Iceland Disease: A name given in Iceland. * Raphe Nucleus Encephalopathy * Tapanui Flu; this is after the New Zealand town Tapanui where a doctor who investigated the disease lived. * Da Costa syndrome (The Netherlands) Symptoms and course There are six main categories of symptoms in CFS: * Fatigue: People with CFS experience profound, overwhelming exhaustion, which gets worse after exertion and can never be fully relieved by sleep. * Pain: Pain in CFS includes muscle pain, joint pain, headaches, abdominal pain, lymph node pain, and sore throats. * Cognitive and neurological problems: o Cognitive problems: people with CFS may have trouble remembering words, names, and places, find it hard to concentrate, and have trouble thinking straight. o Neurological problems include dizziness and light-headedness, especially when standing up quickly. * Hypersensitivity: people with CFS are often sensitive to light, sound, and some chemicals and foods. * Poor temperature control: people with CFS often report either running too hot or too cold, possible due to involvement of the hypothalamus, which regulates body temperature. * Sleep problems: many sufferers find going to sleep at night at the normal time very difficult and have to resort to medication in order to sleep properly. Also vivid dreams are a symptom in many people with CFS leading to disturbed sleep patterns and the ability to recall dream moments many months later, because of their intensity. Some cases of CFS start gradually, but the majority start suddenly, often triggered by the flu or some other illness. People with CFS may get better after a few years or many years or may not get better at all. No one is sure whether anybody is truly cured or whether their illness has just subsided enough for them to live a more normal life. Most people with CFS report a sudden, drastic start to their illness. Sometimes people can remember a specific day or even hour when they first got sick. Often, the illness starts with, or is triggered by, another illness. Many people report getting a case of the flu which slowly evolves into CFS. Other people have had a case of Lyme disease which has been treated adequately, but the symptoms change from those of Lyme to those of CFS. Other triggers include car accidents, moving house, and stressful life situations. Some patients say they felt unusual or uneasy for a short period (days or weeks) before the onset. The other cases have a very slow, gradual onset, sometimes spread over years. People with gradual onsets often don't realize there is anything wrong for years because it happens so slowly. There is no standard course for CFS. Everyone diagnosed with CFS has had it for at least six months; they would not be diagnosed otherwise. It is possible that not all cases of CFS are chronic: some people may have CFS for four months and never get diagnosed. It's also possible that there are people who have CFS whose level of disability is so low they never get diagnosed. People with CFS may get better after a few years or after many years, or never at all. They may reach a plateau at some constant level of health or may progressively decline. Often, the most prominent symptoms change over time or cycle through time. No one is sure whether anybody is truly cured or whether their illness has just subsided enough for them to live a more normal life. Relapses are common, especially after stressful life events. Some people are more limited than others. The sickest are bedbound, while some people are self-reliant, and some are able to work or attend school. Some people with CFS can push themselves to do extraordinary things but feel much worse afterward. One notable CFS sufferer is soccer legend Michelle Akers, who reported struggling with the illness for much of the later years of her career. However, extreme sufferers like those confined to bed felt that an active professional athlete "poster child" like Akers only helped to trivialize the syndrome in the eyes of the public (the infamous "Michelle Akers has it and she plays soccer, so why are you complaining?" reaction), and thereby made it much more difficult for those who are highly incapacitated to be taken seriously. One of the most common and recognizable aspects of CFS is what is called "post-exertional malaise," or, more colloquially, the "Payback Effect." When people with CFS exert themselves, their symptoms get worse afterward. Exertion could be physical or mental exercise, doing routine tasks, such as driving, cleaning, or eating, or handling a stressful situation. The harder the exertion and the longer it lasts, the worse the symptoms will be afterward. The payback effect leads to a few typical patterns, sometimes called "The Yo-Yo Pattern" and "The Downward Spiral." The Yo-Yo pattern: The Yo-Yo Pattern happens when people work very hard at some activity, but only on good days. This leads to worse symptoms which prevents them from working for the next few days. When they feel better, they work extra hard to make up for the bad days or just because they're so excited to feel good but this leads to them feeling bad again... The downward spiral: The Downward Spiral happens whenever feeling bad puts a patient in a situation that makes them feel worse. This is similar to the yo-yo, but in the downward spriral, people don't have time to recover on bad days. Here are some examples: * A person works very hard one day at work. This makes them feel worse, which leads to them not working as effectively. In order to catch up, they work harder, which leads to them feeling worse... * A person loses their appetite when they don't sleep well because they're so tired, they don't realize they're hungry. Then, they don't sleep well at night because they wake up very hungry... * A person does not feel well, and therefore cancels a date with a friend. This leads to them feeling depressed and sleeping poorly, which leads to them cancelling more dates... These patterns can happen over days, weeks, or longer periods. They can happen together (over different periods of time) or alone. Diagnosing CFS is very difficult. There is no conclusive test for CFS, so doctors must rely on their experience and intuition. Once a doctor suspects CFS in a patient who meets the general diagnostic criteria, the doctor must successively eliminate all other potential testable causes of their set of symptoms. CFS, therefore, is what is called an exclusionary diagnosis. According to the 1994 CDC case definition, a diagnosis of CFS requires incapacitating fatigue that is unexplained, lasts at least 6 months, and is not improved by rest. The fatigue must be accompanied by a minimum of 4 of the following: * Impairment of short-term memory and concentration * Muscle pain * Multi-joint pain * Unrefreshing sleep * Headaches of a new type, pattern, or severity * Sore throat * Tender lymph nodes * Post-exertional malaise (fatigue lasting more than 24 hours after exertion) Historically, many doctors have been unfamiliar with CFS, and some have refused to diagnose it. This situation is rapidly changing, with more doctors willing to diagnose it and more diagnoses each year. In the UK, the Chief Medical Officer's report stated that all doctors should consider CFS as a serious chronic illness and treat patients accordingly. Unfortunately there appears to be considerable skepticism amongst doctors about the existence of CFS, which has led to frustration in some patients, who feel strongly that their disability is not psychological in origin but has a biochemical substrate. Some more vocal patients' groups maintain that research into CFS (ME) in the UK has been mostly hijacked by the psychologists/psychiatric lobby, who they claim hold significant power within the medical fraternity, with a resultant "abuse of patients' rights". Some scoring systems, while being considered imperfect, have been proposed to quantify CFS symptoms for research purposes. These include the Holmes et al (1988) and the Fukuda et al (1994) scoring systems. Due to problems with the definition of CFS, estimates of its prevalence vary widely. Studies in the United States have found between 75 and 420 cases of CFS for every 100,000 adults. Far more women than men get CFS between 60 and 85% of cases are women. Minorities and low income people are slightly more likely to have CFS. Though people of all ages can get CFS, and precise statistics are not available, the prevalence among children and adolescents appears to be lower than for adults. Among minors with CFS, about half are boys and half girls. CFS occurs both in isolated cases and large-scale outbreaks. Blood relatives of people who have CFS appear to be more predisposed. Some diseases show a considerable overlap with CFS, and it may be hard to distinguish between them. People with fibromyalgia have muscle pain and sleep disturbances. Those with multiple chemical sensitivities (MCS) are sensitive to chemicals and have sleep disturbances. Many veterans with Gulf War syndrome (GWI) have symptoms almost identical to CFS. Post-polio syndrome also bears remarkable resemblance to CFS. Some researchers maintain these disorders are all expressions of a general, yet undefined, syndrome with protean symptoms. Other disorders with known causes and treatments that may produce CFS-like symptoms are Lyme disease, gluten intolerance (Celiac disease and related disorders), and vitamin B12 deficiency. The cause of CFS is unknown, although a large number of causes have been proposed, and several proposed causes have very vocal and partisan advocates. Among proposed causes: * Infectious agents: This includes several viruses (see below), Lyme and related bacteria, mycoplasma, and yeast and other fungi. * Toxic agents: Mercury, particularly from dental amalgams and vaccines, various organic solvents, herbicides, and several other chemical compounds are often named. The artificial sweetener aspartame is also often blamed. * Immune dysfunction: Both autoimmune disorders (representing a hyperactive immune system) and immunodeficiency (representing an underactive one) have been suggested. * Hormonal dysfunction: Thyroid disorders can cause CFS-like symptoms, as can several other known endocrine disorders. It's possible that disruption of the hormonal "master control" in the hypothalamus somehow causes CFS by upsetting the body's hormone balance. * Dysautonomia: Dysautonomia is the disruption of the function of the autonomic nervous system (ANS). The ANS is tightly tied to the body's endocrine system and also directly controls some aspects of blood pressure control and metabolism. The dysautonomia that evidences itself in CFS shows up mostly in problems of orthostatic intolerance - the inability to stand up without feeling dizzy, faint, nauseous etc. Research into the orthostatic intolerance found in CFS indicates it is very similar to that found in postural tachycardia syndrome (POTS). POTS and CFS patient exhibit reduced blood flows to the heart upon standing that result in reduced blood flow to the brain. The reduced blood flows to the heart are believed to originate in blood pooling in the lower body upon standing. * Chiari malformation and other spinal problems: Arnold-Chiari malformation is constriction where the cerebellum meets the spinal cord. This area can become constricted due to a portion of the cerebellum sagging too low or problems with the bone structure of the lower skull or upper spinal column. The constriction can impede the flow of cerebrospinal fluid between brain and spinal column, and can also compress some nerves in the area. This may cause paralysis or hydrocephalus in extreme cases, but this or other spinal problems may cause autonomic nervous system problems in less severe cases. * Metabolic disorders: Metabolic disorders such as McArdle's disease, CPT II deficiency, myoadenylate deaminase deficiency, and mitochondrial disorder can cause symptoms that strongly resemble CFS. * Nutritional deficiency or imbalance: Certain dietary practices, particularly the consumption of large amounts of carbohydrates, are sometimes blamed for CFS. Celiac disease or gluten intolerance is known to cause CFS-like symptoms in some individuals, as is vitamin B12 deficiency. Other forms of food allergies are also often blamed, especially in cases of Leaky Gut Syndrome. * Malnutrition: In some cases, simple malnutrition may be responsible for CFS (or CFS-like symptoms). Particularly highly restrictive vegetarian diets could cause problems, even though they appear sufficient from the standpoint of calories and essential vitamins and amino acids. Most people cannot manufacture the entire amounts of ribose, carnitine, CoQ10, fatty acids, and several other "semi-essential" nutrients that are critical for cellular metabolism and for nervous system health. A diet deficient in these can lead to a form of malnutrition that results in the classical CFS symptoms. * Depression: Many cases of CFS are attributed to depression, and there is no doubt that severe depression can cause most of the symptoms of CFS. While depression is not uncommon among CFS patients, there are many CFS patients without depressive signs, suggesting that depression is not a direct cause of the symptoms. In contrast to depressed patients, CFS patients may have low rather than high cortisol levels. The depression in CFS patients could also be of the type that is not uncommon in people suffering from chronic and untreatable diseases. * Dental infections: Some have implicated focal infections from root canals and cavitations in tooth sockets where the periodontal ligament was not removed when a tooth was extracted. The theory is that anaerobic bacteria can exist inside a tooth with a root canal or a cavitation because of the lack of blood supply. The bacteria produce toxins that cause system wide problems. Some individuals with CFS like symptoms have seen great improvement after the removal of all root canals and/or cavitation surgery to clean out the sockets from tooth extraction sites. Many members of the Herpesvirus family have been implicated as causative agents in CFS. For many years the ubiquitous Epstein-Barr virus, present in 90% of the population, was the principal suspect. Other viruses implicated include cytomegalovirus, and human herpesvirus type-6 (HHV-6). The evidence has not been consistent with these hypotheses, however, and they are generally no longer believed to explain the etiology of CFS. (Soto & Straus, 2000) More recently, however, similarities to post-polio syndrome have led to a reexamination of the viral link. A number of viruses of the enterovirus family, notably the Coxsackie virus, can produce an infection of the nervous system similar to that caused by the poliovirus, and an even wider range of viruses have been shown capable of triggering an autoimmune reaction that attacks the nervous system. It is believed by some that one of these mechanisms causes damage to areas of the brain responsible for alertness and metabolism, resulting in many of the symptoms of CFS. The role of the ascending reticular activating system The ascending reticular activating system (ARAS) that extends upward from the reticular formation has been known since the early part of the 20th century to be associated with sleep function, and research since roughly 1950 has greatly extended this knowledge. Postmortem examination of the brains of polio patients and imaging studies of the brains of people with post-polio syndrome have shown lesions in the area of the ARAS and reticular formation. Other imaging studies of the brains of CFS patients have shown metabolic abnormalities in this area, though the results have often been equivocal. It seems likely, however, that damage to the ARAS may be reponsible for at least some cases of CFS. Such damage could arise from direct viral damage to the area (most likely from an enterovirus similar to those that cause polio), or from an autoimmune attack on the region. Studies with animal models (primarily cats) have shown that a malfunction of the ARAS is capable of causing behaviors similar to those of CFS patients. The treatments that are proposed and often attempted for CFS are as varied as the suggested causes, and can generally be classified according to the specific cause that they presume. Unfortunately, since CFS symptoms tend to vary over time and will usually get gradually better once the initial crisis is past, it is very easy for someone to become convinced that a particular treatment has helped them (or not), regardless of its true effectiveness. Alternative medicine is often used for CFS, especially when conventional treatments are too toxic, ineffective or otherwise poorly tolerated. * Antibiotics: Antibiotics are commonly used to treat Lyme disease and mycoplasma infections. Both of these infections can be hard to eradicate, so often when an antibiotic cure fails it is claimed that the duration of treatment was insufficient or the wrong antibiotic was used. Another view is that some antibiotics have specific immuno-modulating side effects, quite separately from their antibiotic action. In the MedLine database, ciprofloxacine, doxycycline and the penicillines are reported to be of significant (albeit temporary) effect in some patients. It's worth noting that an even larger group of patients may have adverse effects, and a third group no effect at all. * Antifungals: Antifungal drugs are used to treat yeast and fungus infections. Proponents of the yeast hypothesis for CFS claim, however, that the drugs are largely useless unless combined with a low-carbohydrate diet that effectively "starves" the fungus at the same time. * Immune enhancers: These are generally "food supplements" of various types that are claimed to enhance the immune system, although they can include various antiviral drugs. They are often proposed either to treat some presumed viral infection or to treat a presumed general immune deficiency. * Detoxifiers': Various detoxification agents are often advocated, from simple intestinal purgatives to "liver cleanses" to various types of chelating agents for the removal of mercury and other heavy metals. * Hormones: Various hormones have been tried from time to time, including specifically steroids(cortisol) and thyroid hormones. Though steroids may produce some short-term pain relief, they have not been shown to be of any general benefit. Thyroid hormones occasionally are effective for certain people who may either have a thyroid hormone deficiency or lack an enzyme that allows them to effectively use thyroid hormones. * Antidepressants: Antidepressants are often given to CFS patients, for a number of reasons: o On the asumption that the illness is caused by depression o Because the illness often causes depression, and the patient may experience some overall improvement if this symptom is treated o Because tricyclic antidepressants often give pain relief without resorting to stronger pain killers such as codeine. o Because tricyclic antidepressants can help correct a drifting sleeping pattern. o Because sometimes certain antidepressants appear to help CFS symptoms, even when depression isn't present o To be doing "something" (out of therapeutic embarassment) * Sleep aids: Sleep aids are often given to CFS patients, either on the assumption that lack of restful sleep is causing the CFS symptoms, or because CFS disrupts restful sleep. * Pain relievers: Many CFS patients experience significant amounts of pain, and various narcotic and non-narcotic pain relievers are often given for symptomatic relief. * Mito cocktail: Given that the symptoms of CFS generally resemble those of metabolic disorders, a combination of supplements often known as a mito cocktail is sometimes used to treat the disorder. This "cocktail" consists of relatively large amounts of l-carnitine and CoQ10, and possibly d-ribose, vitamin B12, biotin, and several other nutrients. As with mitochondrial disorder, it is believed that large amounts (eg, 2-10g/day l-carnitine) are necessary to have a significant effect, and smaller amounts of these nutrients will not generally be helpful. * ANS stimulants: Drugs such as atomoxetine (Strattera®), which stimulate the autonomic nervous system, appear to have significant positive effects in some people with CFS symptoms. * Surgery: For Chiari malformation and some other disorders (eg, thoracic outlet syndrome) that are occasionally blamed for CFS symptoms, surgery to release trapped nerves or otherwise correct neurological problems may be helpful. * Location: Many CFS patients find relief in moving to warmer climes. * Dental cleanup: Some individuals suffering from CFS have reported a major reduction of symptoms and improvement in health after the removal of teeth with root canals. Cavitation surgery to clean up the sockets of sites where the periodontal ligament was not removed after a tooth extraction has also been helpful to some. * Graded exercise: A monitored 'self-developed' gradual exercise program to increase strength and cardiovascular health has proven helpful to some patients. However, the risks of post-exertional malaise, which can cause significant, if usually temporary, worsening of symptoms, make this a difficult regimen to implement successfully. Some studies which have suggested that graded exercise can improve the condition of sufferers have been criticized for ignoring individuals who fall out of the trials because they can't cope with the exercise program required. Indeed, in the UK, rigid enforcement of GE by medical professionals on people seriously ill with CFS may have led to many becoming much more ill than before. * Self-controlled exercise, "pacing": although accepting the above conclusions about 'graded exercise,' some exercise, however, is absolutely necessary in order to make any progress at all. "Pacing" is being advocated by a large number of patients as one of the few really effective means of improvement. The principles are: 1. Accept your limitations. 2. "Listen" to the first body signals of fatigue, and stop any exercise before becoming noticeably tired. Rule of thumb: dont exert more than 70% of your capacity. 3. rest. Shift between limited exercise/ rest, etc. "Body signals of fatigue" are individual. An understanding nurse, doctor or therapist may be of help. * Cognitive behavioural therapy: Cognitive therapy may benefit up to 25% of sufferers. This does not imply that CFS is a primary psychiatric condition, but rather that the protracted course of the illness may cause depression, anxiety and misinterpretations. In addition, CBT may teach patients various "coping strategies" to help them deal with cognitive impairments such as a deterioration of short-term memory or abbreviated attention span. * Legal advice, economic counselling: Many CFS patients face the stress of economic and legal problems, which can cause a serious deterioration and paralysis of the patient. As there is no one identifiable cause or falsifiable diagnosis for CFS, there is also no one treatment protocol or "magic bullet". Due to the multi-systemic nature of the illness, and others like it, an emerging branch of medical science called psychoneuroimmunology is looking into how all the various theories fit together. Chronic fatigue syndrome suffers a considerable stigma and has been lumped together with various factitious diseases by some, both healthcare professionals and laypeople. As there is no objective measure of the condition, many argue that it is easy to "invent" CFS-like symptoms for financial, social or emotional benefits, adding to the stigma. This has contributed to a distorted picture of the average CFS patient as a resentful, claiming and depressed person. Cross-sectional studies disprove this picture. The information above is not intended for and should not be used as a substitute for the diagnosis and/or treatment by a licensed, qualified, health-care professional. This article is licensed under the GNU Free Documentation License. It incorporates material originating from the Wikipedia article 2012 Anxiety Zone - Anxiety Disorders Forum. All Rights Reserved.	2	8	0	0	3	0.937663	3	5,613
\|Author\|\|American Psychiatric Association\| \|Series\|\|Diagnostic and Statistical Manual of Mental Disorders\| \|Subject\|\|Classification and diagnosis of mental disorders\| \|Published\|\|May 18, 2013\| \|Media type\|\|Print (hardcover, softcover); e-book\| The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) is the 2013 update to the American Psychiatric Association's (APA) classification and diagnostic tool. In the United States the DSM serves as a universal authority for psychiatric diagnosis. Treatment recommendations, as well as payment by health care providers, are often determined by DSM classifications, so the appearance of a new version has significant practical importance. The DSM-5 was published on May 18, 2013, superseding the DSM-IV-TR, which was published in 2000. The development of the new edition began with a conference in 1999, and proceeded with the formation of a Task Force in 2007, which developed and field-tested a variety of new classifications. In most respects DSM-5 is not greatly changed from DSM-IV-TR. Notable changes include dropping Asperger syndrome as a distinct classification; loss of subtype classifications for variant forms of schizophrenia; dropping the "bereavement exclusion" for depressive disorders; a revised treatment and naming of gender identity disorder to gender dysphoria, and removing the A2 criterion for posttraumatic stress disorder (PTSD) because its requirement for specific emotional reactions to trauma did not apply to combat veterans and first responders with PTSD. Various authorities criticized the fifth edition both before and after it was formally published. Critics assert, for example, that many DSM-5 revisions or additions lack empirical support; inter-rater reliability is low for many disorders; several sections contain poorly written, confusing, or contradictory information; and the psychiatric drug industry unduly influenced the manual's content. Various scientists have argued that the DSM-5 forces clinicians to make distinctions that are not supported by solid evidence, distinctions that have major treatment implications, including drug prescriptions and the availability of health insurance coverage. General criticism of the DSM-5 ultimately resulted in a petition, signed by many mental health organizations, which called for outside review of DSM-5. - 1 Changes - 1.1 Section I - 1.2 Section II: diagnostic criteria and codes - 1.2.1 Neurodevelopmental disorders - 1.2.2 Schizophrenia spectrum and other psychotic disorders - 1.2.3 Bipolar and related disorders - 1.2.4 Depressive disorders - 1.2.5 Anxiety disorders - 1.2.6 Obsessive-compulsive and related disorders - 1.2.7 Trauma- and stressor-related disorders - 1.2.8 Dissociative disorders - 1.2.9 Somatic symptom and related disorders - 1.2.10 Feeding and eating disorders - 1.2.11 Sleep–wake disorders - 1.2.12 Sexual dysfunctions - 1.2.13 Gender dysphoria - 1.2.14 Disruptive, impulse-control, and conduct disorders - 1.2.15 Substance-related and addictive disorders - 1.2.16 Neurocognitive disorders - 1.2.17 Paraphilic disorders - 1.2.18 Personality disorders - 1.3 Section III: emerging measures and models - 2 Conditions for further study - 3 Development - 4 Revisions and updates to DSM-5 - 5 Criticism - 6 References - 7 External links This part of the article summarizes changes from DSM-IV to DSM-5. DSM-5 is divided into three Sections, using Roman numerals to designate each Section. The same organizational structure is used in this overview, e.g., Section I (immediately below) summarizes relevant changes discussed in DSM-5, Section I. Note that if a specific disorder (or set of disorders) cannot be seen, e.g., enuresis and other elimination disorders, mentioned in Section II: diagnostic criteria and codes (below), it means that the diagnostic criteria for those disorders did not change significantly from DSM-IV to DSM-5. Section I describes DSM-5 chapter organization, its change from the multiaxial system, and Section III's dimensional assessments. The DSM-5 deleted the chapter that includes "disorders usually first diagnosed in infancy, childhood, or adolescence" opting to list them in other chapters. A note under Anxiety Disorders says that the "sequential order" of at least some DSM-5 chapters has significance that reflects the relationships between diagnoses. This introductory section describes the process of DSM revision, including field trials, public and professional review, and expert review. It states its goal is to harmonize with the ICD systems and share organizational structures as much as is feasible. Concern about the categorical system of diagnosis is expressed, but the conclusion is the reality that alternative definitions for most disorders is scientifically premature. The new version replaces the NOS categories with two options: other specified disorder and unspecified disorder to increase the utility to the clinician. The first allows the clinician to specify the reason that the criteria for a specific disorder are not met; the second allows the clinician the option to forgo specification. DSM-5 has discarded the multiaxial system of diagnosis (formerly Axis I, Axis II, Axis III), listing all disorders in Section II. It has replaced Axis IV with significant psychosocial and contextual features and dropped Axis V (Global Assessment of Functioning, known as GAF). The World Health Organization's (WHO) Disability Assessment Schedule is added to Section III (Emerging measures and models) under Assessment Measures, as a suggested, but not required, method to assess functioning. Section II: diagnostic criteria and codes - "Mental retardation" has a new name: "intellectual disability (intellectual developmental disorder)." - Phonological disorder and stuttering are now called communication disorders—which include language disorder, speech sound disorder, childhood-onset fluency disorder, and a new condition characterized by impaired social verbal and nonverbal communication called social (pragmatic) communication disorder. - Autism spectrum disorder incorporates Asperger disorder, childhood disintegrative disorder, and pervasive developmental disorder not otherwise specified (PDD-NOS) - see Diagnosis of Asperger syndrome#DSM-5 changes. - A new sub-category, motor disorders, encompasses developmental coordination disorder, stereotypic movement disorder, and the tic disorders including Tourette syndrome. Schizophrenia spectrum and other psychotic disorders - All subtypes of schizophrenia were removed from the DSM-5 (paranoid, disorganized, catatonic, undifferentiated, and residual). - A major mood episode is required for schizoaffective disorder (for a majority of the disorder's duration after criterion A [related to delusions, hallucinations, disorganized speech or behavior, and negative symptoms such as avolition] is met). - Criteria for delusional disorder changed, and it is no longer separate from shared delusional disorder. - Catatonia in all contexts requires 3 of a total of 12 symptoms. Catatonia may be a specifier for depressive, bipolar, and psychotic disorders; part of another medical condition; or of another specified diagnosis. - New specifier "with mixed features" can be applied to bipolar I disorder, bipolar II disorder, bipolar disorder NED (not elsewhere defined, previously called "NOS", not otherwise specified) and MDD. - Allows other specified bipolar and related disorder for particular conditions. - Anxiety symptoms are a specifier ( called "anxious distress") added to bipolar disorder and to depressive disorders (but are not part of the bipolar diagnostic criteria). - The bereavement exclusion in DSM-IV was removed from depressive disorders in DSM-5. - New disruptive mood dysregulation disorder (DMDD) for children up to age 18 years. - Premenstrual dysphoric disorder moved from an appendix for further study, and became a disorder. - Specifiers were added for mixed symptoms and for anxiety, along with guidance to physicians for suicidality. - The term dysthymia now also would be called persistent depressive disorder. - For the various forms of phobias and anxiety disorders, DSM-5 removes the requirement that the subject (formerly, over 18 years old) "must recognize that their fear and anxiety are excessive or unreasonable". Also, the duration of at least 6 months now applies to everyone (not only to children). - Panic attack became a specifier for all DSM-5 disorders. - Panic disorder and agoraphobia became two separate disorders. - Specific types of phobias became specifiers but are otherwise unchanged. - The generalized specifier for social anxiety disorder (formerly, social phobia) changed in favor of a performance only (i.e., public speaking or performance) specifier. - Separation anxiety disorder and selective mutism are now classified as anxiety disorders (rather than disorders of early onset). - A new chapter on obsessive-compulsive and related disorders includes four new disorders: excoriation (skin-picking) disorder, hoarding disorder, substance-/medication-induced obsessive-compulsive and related disorder, and obsessive-compulsive and related disorder due to another medical condition. - Trichotillomania (hair-pulling disorder) moved from "impulse-control disorders not elsewhere classified" in DSM-IV, to an obsessive-compulsive disorder in DSM-5. - A specifier was expanded (and added to body dysmorphic disorder and hoarding disorder) to allow for good or fair insight, poor insight, and "absent insight/delusional" (i.e., complete conviction that obsessive-compulsive disorder beliefs are true). - Criteria were added to body dysmorphic disorder to describe repetitive behaviors or mental acts that may arise with perceived defects or flaws in physical appearance. - The DSM-IV specifier “with obsessive-compulsive symptoms” moved from anxiety disorders to this new category for obsessive-compulsive and related disorders. - There are two new diagnoses: other specified obsessive-compulsive and related disorder, which can include body-focused repetitive behavior disorder (behaviors like nail biting, lip biting, and cheek chewing, other than hair pulling and skin picking) or obsessional jealousy; and unspecified obsessive-compulsive and related disorder. - Posttraumatic stress disorder (PTSD) is now included in a new section titled "Trauma- and Stressor-Related Disorders." - The PTSD diagnostic clusters were reorganized and expanded from a total of three clusters to four based on the results of confirmatory factor analytic research conducted since the publication of DSM-IV. - Separate criteria were added for children six years old or younger. - For the diagnosis of acute stress disorder and PTSD, the stressor criteria (Criterion A1 in DSM-IV) was modified to some extent. The requirement for specific subjective emotional reactions (Criterion A2 in DSM-IV) was eliminated because it lacked empirical support for its utility and predictive validity. Previously certain groups, such as military personnel involved in combat, law enforcement officers and other first responders, did not meet criterion A2 in DSM-IV because their training prepared them to not react emotionally to traumatic events. - Two new disorders that were formerly subtypes were named: reactive attachment disorder and disinhibited social engagement disorder. - Adjustment disorders were moved to this new section and reconceptualized as stress-response syndromes. DSM-IV subtypes for depressed mood, anxious symptoms, and disturbed conduct are unchanged. - Depersonalization disorder is now called depersonalization/derealization disorder. - Dissociative fugue became a specifier for dissociative amnesia. - The criteria for dissociative identity disorder were expanded to include "possession-form phenomena and functional neurological symptoms". It is made clear that "transitions in identity may be observable by others or self-reported". Criterion B was also modified for people who experience gaps in recall of everyday events (not only trauma). - Somatoform disorders are now called somatic symptom and related disorders. - Patients that present with chronic pain can now be diagnosed with the mental illness somatic symptom disorder with predominant pain; or psychological factors that affect other medical conditions; or with an adjustment disorder. - Somatization disorder and undifferentiated somatoform disorder were combined to become somatic symptom disorder, a diagnosis which no longer requires a specific number of somatic symptoms. - Somatic symptom and related disorders are defined by positive symptoms, and the use of medically unexplained symptoms is minimized, except in the cases of conversion disorder and pseudocyesis (false pregnancy). - A new diagnosis is psychological factors affecting other medical conditions. This was formerly found in the DSM-IV chapter "Other Conditions That May Be a Focus of Clinical Attention". - Criteria for conversion disorder (functional neurological symptom disorder) were changed. Feeding and eating disorders - Criteria for pica and rumination disorder were changed and can now refer to people of any age. - Binge eating disorder graduated from DSM-IV's "Appendix B -- Criteria Sets and Axes Provided for Further Study" into a proper diagnosis. - Requirements for bulimia nervosa and binge eating disorder were changed from "at least twice weekly for 6 months to at least once weekly over the last 3 months". - The criteria for anorexia nervosa were changed; there is no longer a requirement of amenorrhea. - "Feeding disorder of infancy or early childhood", a rarely used diagnosis in DSM-IV, was renamed to avoidant/restrictive food intake disorder, and criteria were expanded. - "Sleep disorders related to another mental disorder, and sleep disorders related to a general medical condition" were deleted. - Primary insomnia became insomnia disorder, and narcolepsy is separate from other hypersomnolence. - There are now three breathing-related sleep disorders: obstructive sleep apnea hypopnea, central sleep apnea, and sleep-related hypoventilation. - Circadian rhythm sleep–wake disorders were expanded to include advanced sleep phase syndrome, irregular sleep–wake type, and non-24-hour sleep–wake type. Jet lag was removed. - Rapid eye movement sleep behavior disorder and restless legs syndrome are each a disorder, instead of both being listed under "dyssomnia not otherwise specified" in DSM-IV. - DSM-5 has sex-specific sexual dysfunctions. - For females, sexual desire and arousal disorders are combined into female sexual interest/arousal disorder. - Sexual dysfunctions (except substance-/medication-induced sexual dysfunction) now require a duration of approximately 6 months and more exact severity criteria. - A new diagnosis is genito-pelvic pain/penetration disorder which combines vaginismus and dyspareunia from DSM-IV. - Sexual aversion disorder was deleted. - Subtypes for all disorders include only "lifelong versus acquired" and "generalized versus situational" (one subtype was deleted from DSM-IV). - Two subtypes were deleted: "sexual dysfunction due to a general medical condition" and "due to psychological versus combined factors". - DSM-IV gender identity disorder is similar to, but not the same as, gender dysphoria in DSM-5. Separate criteria for children, adolescents and adults that are appropriate for varying developmental states are added. - Subtypes of gender identity disorder based on sexual orientation were deleted. - Among other wording changes, criterion A and criterion B (cross-gender identification, and aversion toward one’s gender) were combined. Along with these changes comes the creation of a separate gender dysphoria in children as well as one for adults and adolescents. The grouping has been moved out of the sexual disorders category and into its own. The name change was made in part due to stigmatization of the term "disorder" and the relatively common use of "gender dysphoria" in the GID literature and among specialists in the area. The creation of a specific diagnosis for children reflects the lesser ability of children to have insight into what they are experiencing and ability to express it in the event that they have insight. Disruptive, impulse-control, and conduct disorders Some of these disorders were formerly part of the chapter on early diagnosis, oppositional defiant disorder; conduct disorder; and disruptive behavior disorder not otherwise specified became other specified and unspecified disruptive disorder, impulse-control disorder, and conduct disorders. Intermittent explosive disorder, pyromania, and kleptomania moved to this chapter from the DSM-IV chapter "Impulse-Control Disorders Not Otherwise Specified". - Antisocial personality disorder is listed here and in the chapter on personality disorders (but ADHD is listed under neurodevelopmental disorders). - Symptoms for oppositional defiant disorder are of three types: angry/irritable mood, argumentative/defiant behavior, and vindictiveness. The conduct disorder exclusion is deleted. The criteria were also changed with a note on frequency requirements and a measure of severity. - Criteria for conduct disorder are unchanged for the most part from DSM-IV. A specifier was added for people with limited "prosocial emotion", showing callous and unemotional traits. - People over the disorder's minimum age of 6 may be diagnosed with intermittent explosive disorder without outbursts of physical aggression. Criteria were added for frequency and to specify "impulsive and/or anger based in nature, and must cause marked distress, cause impairment in occupational or interpersonal functioning, or be associated with negative financial or legal consequences". - Gambling disorder and tobacco use disorder are new. - Substance abuse and substance dependence from DSM-IV-TR have been combined into single substance use disorders specific to each substance of abuse within a new "addictions and related disorders" category. "Recurrent legal problems" was deleted and "craving or a strong desire or urge to use a substance" was added to the criteria. The threshold of the number of criteria that must be met was changed and severity from mild to severe is based on the number of criteria endorsed. Criteria for cannabis and caffeine withdrawal were added. New specifiers were added for early and sustained remission along with new specifiers for "in a controlled environment" and "on maintenance therapy". DSM-5 substance dependencies include: - 303.90 Alcohol dependence - 304.00 Opioid dependence - 304.10 Sedative, hypnotic, or anxiolytic dependence (including benzodiazepine dependence and barbiturate dependence) - 304.20 Cocaine dependence - 304.30 Cannabis dependence - 304.40 Amphetamine dependence (or amphetamine-like) - 304.50 Hallucinogen dependence - 304.60 Inhalant dependence - 304.80 Polysubstance dependence - 304.90 Phencyclidine (or phencyclidine-like) dependence - 304.90 Other (or unknown) substance dependence - 305.10 Nicotine dependence There are no more polysubstance diagnoses in DSM-5; the substance(s) must be specified. - Dementia and amnestic disorder became major or mild neurocognitive disorder (major NCD, or mild NCD). DSM-5 has a new list of neurocognitive domains. "New separate criteria are now presented" for major or mild NCD due to various conditions. Substance/medication-induced NCD and unspecified NCD are new diagnoses. - New specifiers "in a controlled environment" and "in remission" were added to criteria for all paraphilic disorders. - A distinction is made between paraphilic behaviors, or paraphilias, and paraphilic disorders. All criteria sets were changed to add the word disorder to all of the paraphilias, for example, pedophilic disorder is listed instead of pedophilia. There is no change in the basic diagnostic structure since DSM-III-R; however, people now must meet both qualitative (criterion A) and negative consequences (criterion B) criteria to be diagnosed with a paraphilic disorder. Otherwise they have a paraphilia (and no diagnosis). - Personality disorder previously belonged to a different axis than almost all other disorders, but is now in one axis with all mental and other medical diagnoses. However, the same ten types of personality disorder are retained. Section III: emerging measures and models Alternative DSM-5 model for personality disorders An alternative hybrid dimensional-categorical model for personality disorders is included to stimulate further research on this modified classification system. Conditions for further study These conditions and criteria are set forth to encourage future research and are not meant for clinical use. - Attenuated psychosis syndrome - Depressive episodes with short-duration hypomania - Persistent complex bereavement disorder - Caffeine use disorder - Internet gaming disorder - Neurobehavioral disorder associated with prenatal alcohol exposure - Suicidal behavior disorder - Non-suicidal self-injury In 1999, a DSM–5 Research Planning Conference; sponsored jointly by APA and the National Institute of Mental Health (NIMH), was held to set the research priorities. Research Planning Work Groups produced "white papers" on the research needed to inform and shape the DSM-5 and the resulting work and recommendations were reported in an APA monograph and peer-reviewed literature. There were six workgroups, each focusing on a broad topic: Nomenclature, Neuroscience and Genetics, Developmental Issues and Diagnosis, Personality and Relational Disorders, Mental Disorders and Disability, and Cross-Cultural Issues. Three additional white papers were also due by 2004 concerning gender issues, diagnostic issues in the geriatric population, and mental disorders in infants and young children. The white papers have been followed by a series of conferences to produce recommendations relating to specific disorders and issues, with attendance limited to 25 invited researchers. On July 23, 2007, the APA announced the task force that would oversee the development of DSM-5. The DSM-5 Task Force consisted of 27 members, including a chair and vice chair, who collectively represent research scientists from psychiatry and other disciplines, clinical care providers, and consumer and family advocates. Scientists working on the revision of the DSM had a broad range of experience and interests. The APA Board of Trustees required that all task force nominees disclose any competing interests or potentially conflicting relationships with entities that have an interest in psychiatric diagnoses and treatments as a precondition to appointment to the task force. The APA made all task force members' disclosures available during the announcement of the task force. Several individuals were ruled ineligible for task force appointments due to their competing interests. The DSM-5 field trials included test-retest reliability which involved different clinicians doing independent evaluations of the same patient—a common approach to the study of diagnostic reliability. Revisions and updates to DSM-5 Beginning with the fifth edition, it is intended that diagnostic guidelines revisions will be added incrementally. The DSM-5 is identified with Arabic rather than Roman numerals, marking a change in how future updates will be created. Incremental updates will be identified with decimals (DSM-5.1,DSM-5.2, etc.), until a new edition is written. The change reflects the intent of the APA to respond more quickly when a preponderance of research supports a specific change in the manual. The research base of mental disorders is evolving at different rates for different disorders. Robert Spitzer, the head of the DSM-III task force, has publicly criticized the APA for mandating that DSM-5 task force members sign a nondisclosure agreement, effectively conducting the whole process in secret: "When I first heard about this agreement, I just went bonkers. Transparency is necessary if the document is to have credibility, and, in time, you're going to have people complaining all over the place that they didn't have the opportunity to challenge anything." Allen Frances, chair of the DSM-IV task force, expressed a similar concern. Although the APA has since instituted a disclosure policy for DSM-5 task force members, many still believe the Association has not gone far enough in its efforts to be transparent and to protect against industry influence. In a 2009 Point/Counterpoint article, Lisa Cosgrove, PhD and Harold J. Bursztajn, MD noted that "the fact that 70% of the task force members have reported direct industry ties---an increase of almost 14% over the percentage of DSM-IV task force members who had industry ties---shows that disclosure policies alone, especially those that rely on an honor system, are not enough and that more specific safeguards are needed." David Kupfer, chair of the DSM-5 task force, and Darrel A. Regier, MD, MPH, vice chair of the task force, whose industry ties are disclosed with those of the task force, countered that "collaborative relationships among government, academia, and industry are vital to the current and future development of pharmacological treatments for mental disorders." They asserted that the development of DSM-5 is the "most inclusive and transparent developmental process in the 60-year history of DSM." The developments to this new version can be viewed on the APA website. Public input was requested for the first time in the history of the manual. During periods of public comment, members of the public could sign up at the DSM-5 website and provide feedback on the various proposed changes. In June 2009, Allen Frances issued strongly worded criticisms of the processes leading to DSM-5 and the risk of "serious, subtle, (...) ubiquitous" and "dangerous" unintended consequences such as new "false 'epidemics'". He writes that "the work on DSM-V has displayed the most unhappy combination of soaring ambition and weak methodology" and is concerned about the task force's "inexplicably closed and secretive process". His and Spitzer's concerns about the contract that the APA drew up for consultants to sign, agreeing not to discuss drafts of the fifth edition beyond the task force and committees, have also been aired and debated. The appointment, in May 2008, of two of the taskforce members, Kenneth Zucker and Ray Blanchard, led to an internet petition to remove them. According to MSNBC, "The petition accuses Zucker of having engaged in 'junk science' and promoting 'hurtful theories' during his career, especially advocating the idea that children who are unambiguously male or female anatomically, but seem confused about their gender identity, can be treated by encouraging gender expression in line with their anatomy." According to The Gay City News, "Dr. Ray Blanchard, a psychiatry professor at the University of Toronto, is deemed offensive for his theories that some types of transsexuality are paraphilias, or sexual urges. In this model, transsexuality is not an essential aspect of the individual, but a misdirected sexual impulse." Blanchard responded, "Naturally, it's very disappointing to me there seems to be so much misinformation about me on the Internet. [They didn't distort] my views, they completely reversed my views." Zucker "rejects the junk-science charge, saying there 'has to be an empirical basis to modify anything' in the DSM. As for hurting people, 'in my own career, my primary motivation in working with children, adolescents and families is to help them with the distress and suffering they are experiencing, whatever the reasons they are having these struggles. I want to help people feel better about themselves, not hurt them.'" In 2011, psychologist Brent Robbins co-authored a national letter for the Society for Humanistic Psychology that brought thousands into the public debate about the DSM. Approximately 13,000 individuals and mental health professionals signed a petition in support of the letter. Thirteen other American Psychological Association divisions endorsed the petition. In a November 2011 article about the debate in the San Francisco Chronicle, Robbins notes that under the new guidelines, certain responses to grief could be labeled as pathological disorders, instead of being recognized as being normal human experiences. In 2012, a footnote was added to the draft text which explains the distinction between grief and depression. The DSM-5 has been criticized for purportedly saying nothing about the biological underpinnings of mental disorders. A book-long appraisal of the DSM-5, with contributions from philosophers, historians and anthropologists, was published in 2015. The financial association of DSM-5 panel members with industry continues to be a concern for financial conflict of interest. Of the DSM-5 task force members, 69% report having ties to the pharmaceutical industry, an increase from the 57% of DSM-IV task force members. Borderline personality disorder controversy In 2003, the Treatment and Research Advancements National Association for Personality Disorders (TARA-APD) campaigned to change the name and designation of borderline personality disorder in DSM-5. The paper How Advocacy is Bringing BPD into the Light reported that "the name BPD is confusing, imparts no relevant or descriptive information, and reinforces existing stigma." Instead, it proposed the name "emotional regulation disorder" or "emotional dysregulation disorder." There was also discussion about changing borderline personality disorder, an Axis II diagnosis (personality disorders and mental retardation), to an Axis I diagnosis (clinical disorders). The TARA-APD recommendations do not appear to have had an impact on the American Psychiatric Association, the publisher of the DSM. As noted above, the DSM-5 does not employ a multi-axial diagnostic scheme, therefore the distinction between Axis I and II disorders no longer exists in the DSM nosology. The name, the diagnostic criteria for, and description of, borderline personality disorder remain largely unchanged from DSM-IV-TR. British Psychological Society response The British Psychological Society stated in its June 2011 response to DSM-5 draft versions, that it had "more concerns than plaudits". It criticized proposed diagnoses as "clearly based largely on social norms, with 'symptoms' that all rely on subjective judgements... not value-free, but rather reflect[ing] current normative social expectations", noting doubts over the reliability, validity, and value of existing criteria, that personality disorders were not normed on the general population, and that "not otherwise specified" categories covered a "huge" 30% of all personality disorders. It also expressed a major concern that "clients and the general public are negatively affected by the continued and continuous medicalisation of their natural and normal responses to their experiences... which demand helping responses, but which do not reflect illnesses so much as normal individual variation". The Society suggested as its primary specific recommendation, a change from using "diagnostic frameworks" to a description based on an individual's specific experienced problems, and that mental disorders are better explored as part of a spectrum shared with normality: \|“\|\|[We recommend] a revision of the way mental distress is thought about, starting with recognition of the overwhelming evidence that it is on a spectrum with 'normal' experience, and that psychosocial factors such as poverty, unemployment and trauma are the most strongly-evidenced causal factors. Rather than applying preordained diagnostic categories to clinical populations, we believe that any classification system should begin from the bottom up – starting with specific experiences, problems or 'symptoms' or 'complaints'... We would like to see the base unit of measurement as specific problems (e.g. hearing voices, feelings of anxiety etc.)? These would be more helpful too in terms of epidemiology. While some people find a name or a diagnostic label helpful, our contention is that this helpfulness results from a knowledge that their problems are recognised (in both senses of the word) understood, validated, explained (and explicable) and have some relief. Clients often, unfortunately, find that diagnosis offers only a spurious promise of such benefits. Since – for example – two people with a diagnosis of 'schizophrenia' or 'personality disorder' may possess no two symptoms in common, it is difficult to see what communicative benefit is served by using these diagnoses. We believe that a description of a person's real problems would suffice. Moncrieff and others have shown that diagnostic labels are less useful than a description of a person's problems for predicting treatment response, so again diagnoses seem positively unhelpful compared to the alternatives. - British Psychological Society June 2011 response National Institute of Mental Health \|“\|\|The goal of this new manual, as with all previous editions, is to provide a common language for describing psychopathology. While DSM has been described as a “Bible” for the field, it is, at best, a dictionary, creating a set of labels and defining each. The strength of each of the editions of DSM has been “reliability” – each edition has ensured that clinicians use the same terms in the same ways. The weakness is its lack of validity ... Patients with mental disorders deserve better.\|\|”\| Insel also discussed an NIMH effort to develop a new classification system, Research Domain Criteria (RDoC), currently for research purposes only. Insel's post sparked a flurry of reaction, some of which might be termed sensationalistic, with headlines such as "Goodbye to the DSM-V", "Federal institute for mental health abandons controversial 'bible' of psychiatry", "National Institute of Mental Health abandoning the DSM", and "Psychiatry divided as mental health 'bible' denounced." Other responses provided a more nuanced analysis of the NIMH Director's post. In May 2013, Insel, on behalf of NIMH, issued a joint statement with Jeffrey A. Lieberman, MD, president of the American Psychiatric Association, that emphasized that DSM-5 "... represents the best information currently available for clinical diagnosis of mental disorders. Patients, families, and insurers can be confident that effective treatments are available and that the DSM is the key resource for delivering the best available care. The National Institute of Mental Health (NIMH) has not changed its position on DSM-5." Insel and Lieberman say that DSM-5 and RDoC "represent complementary, not competing, frameworks" for characterizing diseases and disorders. However, epistemologists of psychiatry tend to see the RDoC project as a putative revolutionary system that in the long run will try to replace the DSM, its expected early effect being a liberalization of the research criteria, with an increasing number of research centers adopting the RDoC definitions. - "Coalition for DSM-5 Reform". Coalition for DSM-5 Reform. Retrieved October 31, 2013. - "Highlights of Changes from DSM-IV-TR to DSM-5" (PDF). American Psychiatric Association. May 17, 2013. Archived from the original (PDF) on February 26, 2015. - American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (Fifth ed.). Arlington, VA: American Psychiatric Publishing. pp. 5–25. ISBN 978-0-89042-555-8. - "A Guide to DSM-5: Neurodevelopmental Disorders". Medscape.com. 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\|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
Master Muscle Anatomy to Properly Report Multiple Strabismus Surgery- Published on Fri, Feb 01, 2002 Coding strabismus surgery requires understanding the muscle anatomy. In each eye, there are two horizontal muscles (one on the nasal side, and one on the temporal side), two vertical muscles (one on the top, and one on the bottom), and two oblique muscles (called superior and inferior). Because of muscle placement, strabismus coding is particularly confusing when multiple procedures are performed. Bilateral means the same muscle in each eye, not two muscles on opposite sides of the same eye. The nasal and temporal horizontal muscles in one eye do not constitute a bilateral procedure. However, a horizontal muscle in the left eye and a horizontal muscle in the right eye do. Horizontal Muscles For surgery on one horizontal muscle in one eye, report CPT 67311 (strabismus surgery, recession or resection procedure; one horizontal muscle ). For surgery on both horizontal muscles in the same eye, use 67312 ( two horizontal muscles When surgery is performed on one horizontal muscle in the left eye the lateral (temporal side) rectus muscle or the medial (nasal side) rectus muscle and the lateral rectus or medial rectus muscle in the right eye, code the single horizontal muscle on each eye on two lines: 67311 and 67311-50 (bilateral procedure ) or 67311-RT (right side ) and 67311-LT (left side ). Do not use 67312 for this procedure. Code 67312 is appropriately valued lower than 67311 billed bilaterally. Reporting 67312 for 67311 bilaterally is improper coding that will cost reimbursement, says Lise Roberts, vice president of Health Care Compliance Strategies, a CD-ROM-based compliance training firm in Jericho, N.Y. Vertical Muscles If one vertical muscle the superior rectus or inferior rectus is operated on, report 67314 ( one vertical muscle [excluding superior oblique] ). If two vertical muscles are operated on in the same eye, use 67316 ( two or more vertical muscles [excluding superior oblique] "Two or more vertical muscles" might lead one to believe that this is a bilateral code. There are technically only two vertical muscles in one eye, but CPT considers the inferior oblique muscle a vertical muscle for coding purposes. The superior oblique muscle has its own code, 67318 (strabismus surgery, any procedure, superior oblique muscle Medicare views 67316 as unilateral, and therefore expects 67316 to be billed twice when operating on two or more vertical muscles on each eye. For example, use 67316 when both vertical muscles in one eye are treated, but when a single vertical muscle is treated in each eye code on two lines: Line 1: 67314 (or 67314-RT) Line 2: 67314-50 (or 67314-LT). If a single vertical muscle is operated on in one eye and two or more vertical muscles are operated on the other, report 67316 -RT or -LT for the first eye and [...]	4	6	13	0	0	0.398273	13	669
There are a number of important terms you’ll want to familiarize yourself with as you learn more about coding. Let’s look at some of these now. The CPT code set is divided into three Categories. Category I, which is the largest and most commonly used, describes medical procedures, technologies and services. Category II is used for performance management and additional data. Category III houses the codes for emerging and experimental medical procedures and services. In ICD, the category is the first three characters of the code, which describes the basic manifestation of the injury or sickness. In some cases, the category is all that is needed to accurately describe the condition of the patient, but more often than not the coder must list a more detailed description of the injury or illness (see “Subcategory,” and “Subclassification”). In ICD-10-CM, categories are three numbers. This designation, created by the National Center for Health Statistics, is added to the ICD codes sets when they are implemented in the United States. Many countries expand and clarify ICD code sets for their national use; the US, for example, expanded ICD-10 from 14,000 codes to over 68,000 individual codes. This term is abbreviated “-CM” and is added to the end of the ICD code title. For instance, ICD-10-CM can be read “International Classification of Diseases, Tenth Revision, Clinical Modification. The Center for Medicare and Medicaid Services. This federal agency updates and maintains the HCPCS code set and is one of the most important organizations in healthcare today. Current Procedural Terminology. Published, copyrighted, and maintained by the American Medical Association, CPT is a large set of codes that describe what procedure or service was performed on a patient. This code is divided into three Categories, with the first Category being the most important and widely used. CPT codes are an integral part of the reimbursement process. These codes are five characters long and may be numeric or alphanumeric. Healthcare Common Procedure Coding System, pronounced hick-picks. This is main procedural code set for reporting procedures to Medicare, Medicaid, and a large number of other third-party payers. Maintained by CMS (See “CMS”), HCPCS is divided into two levels. Level I is identical to CPT, and is used in the same way. Level II describes the equipment, medication, and out-patient services not included in CPT. E-codes are a set of ICD-10-CM codes that includes codes for external causes of injury, such as auto accidents, poisoning, and homicide. Evaluation and Management (CPT) Evaluation and Management, or E&M, is a section of CPT codes used to describe the assessment of a patient’s health and the management of their care. The codes for visits to doctor’s office and trips to the emergency room, for instance, are included in E&M. E&M is found at the front of the CPT manual, despite being out of numerical order. The codes for E&M are 99201 – 99499. The International Classification of Diseases is a set of medical diagnostic codes established over a hundred years ago. Maintained today by the WHO (See “WHO”), ICD codes create a universal language for reporting diseases and injury. Currently, we use ICD-10-CM (See “Clinical Modification”). ICD codes are numeric or alphanumeric. They have a three-character category (See “category (ICD)”), which describes the injury or disease, which is typically followed by a decimal point and two-to-four more characters, depending on the code set, which give more information about the manifestation and/or location of the disease. A modifier is a two-character code that is added to a procedure code to demonstrate an important variation that does not, by itself, change the definition of the procedure. CPT codes have numeric modifiers, while HCPCS codes have alphanumeric modifiers. These are added at the end of a code with a hyphen, and may provide information about the procedure itself, that’s procedure’s Medicare eligibility, and a host of other important facets. The CPT modifier -51, for example, notifies the payer that this procedure was one of multiple procedures. The HCPCS modifier –LT, on the other hand, describes a bilateral procedure that was performed only on the left side of the body. Modifier Exempt (CPT) Certain codes in CPT cannot have modifiers added to them. This is a fairly short list that can be found in the appendices of the CPT manual. The National Center for Health Statistics. The NCHS is a government agency that tracks health information, and is responsible for creating and publishing both the clinical modifications to ICD codes (See “Clinical Modification”) and their annual updates. The science of the causes and effects of disease. In ICD codes, the subcategory describes the digit that comes after the decimal point. This digit further describes the nature of the illness or injury, and gives additional information as to its location or manifestation. The subclassification follows the subcategory (See “Subcategory”) in ICD codes. The subclassification further expands on the subcategory, and gives additional information about the manifestation, severity, or location of the injury or disease. In ICD-10-CM there is also a subclassification that describes which encounter this is for the doctor—whether this is a first treatment for the ailment, a follow-up, or the assessment of a condition that is the result of a previous injury or disease (See “Sequela”). There may be as many as three subclassification characters in ICD-10-CM. The portion of a medical procedure that concerns only the technical aspect of the procedure, but not the interpretative, or professional aspect (See “Professional component”). A technical component might include the administration of a chest X-ray, but would not include the assessment of that X-ray for disease or abnormality. The World Health Organization. This international body, which is an agency of the United Nations, oversees the creation of ICD codes and is one of the most important organizations in international health. These codes describe circumstances outside of injury or disease that cause a patient to visit a health professional. This may include a patient visiting a doctor because of family medical history.	4	1	2	0	0	0.439352	2	1,378
Understanding Insurance and Medical Billing Terminology Part 2: Cracking the Medical Billing Code This is part two of “Understanding Insurance And Medical Billing Terminology.” You can read part one here. In order to get reimbursed for providing care, medical professionals need to puzzle together a set of codes – diagnosis codes along with separate procedure codes – to comprehensively describe a condition and its treatment. These codes were created to simplify the process of billing and reimbursement, and reduce errors in medical records. But coding errors are easy to make, a single decimal mistake can result in higher bills, incorrect medical records, and insurance reimbursement claim denial. A good understanding of how these codes work is essential in order to review a complex medical bill properly. There are three sets of codes used in medical billing: CPT, ICD, and/or HCPCS. Dentists use CDC (also known as “ADA”) coding. CPT Codes (Current Procedural Terminology): This is a five-digit number that identifies the service or procedure received. Insurance companies use these codes to determine the portion of the bill that is covered by insurance – and how much a patient must pay out of pocket. CPT codes are listed next to the items in a bill’s description of services. Compare CPT codes on a bill to the codes noted on the Explanation of Benefits to see if they match. You can look up the meaning of CDC codes, to see if the code matches the treatment/service received. ICD Codes (The International Classification of Diseases) these codes are used to describe patient symptoms and the medical procedures used to address the problem. ICD-10, the version currently in use, contains about 70,000 codes representing every conceivable issue that a healthcare professional might encounter. ICD codes tend to have decimal points (A00.111), and can be verified online. HCPC Codes (Healthcare Common Procedure Coding System is used by Medicare to determine provider reimbursements. There are two levels of HCPC codes in wide usage: Level I are identical to the CPT codes. Level II is used by healthcare service or equipment suppliers. ADA/CDC: Dentists use a similar set of codes for insurance claims and billing. Known as “CDC” (Current Dental Terminology) codes, the list was developed and is annually updated by the American Dental Association (ADA), which is why this code set is also referred to as “ADA codes.” Check a dental insurance plan or dental saving’s plan fee schedule for a list of these codes. Other Terms to Know Balance billing: hospitals, clinics, doctors’ offices and other medical facilities may attempt to bill patients for the difference between what an insurance company will pay, and the cost (see above) of a treatment or service. Balance billing is illegal for all Medicare patients and individuals older than 65 years of age. It’s also illegal in 47 states for in-network providers. There is an exception if a healthcare provider tells the patient ahead of time that a service will probably not be covered by the insurance company. Duplicate Billing: Multiple entries for a single service or treatment is a very common error on medical bills. These are often innocent errors that occur when a medical team doesn’t know that another team member already recorded the procedure – both a doctor and a nurse might make a note that medication was given to a patient, or both the admitting department and a private doctor could record a hospital admittance. Check for duplicate entries; if found call the healthcare provider. Upcoding: this describes a mistake in CPT coding that result in a higher cost for treatment. The mistake could be an error, or a deliberate attempt to boost the total of a medical bill. If you spot a coding error on a bill, check with the provider. If Upcoding occurs more than once, report the problem to your insurance provider. Code Bundling/Bundled Costs: medical coding “bundles” describe a set of related services (such as an injection, the medication that was injected, and the illness being treated). These are usually (but not always) marked with a “b” on the bill. Watch for duplications in codes: a bundled set as well as a single charge that replicates a procedure included in the bundle. Unbundling: if a provider lists services separately, rather than bundling them, the bill can be much higher than it should be. This can be difficult to spot, as most people don’t know whether procedures should be listed as a bundle or separate entries. Check also to ensure that a bundle charge along with charges for each separate procedure don’t appear on the bill. Finding Help: Medical Advocacy Services An entire industry has been created around medical coding – there are expert coders who translate health records into codes, and equally expert insurance company analysts who carefully review these codes to spot errors, inconsistencies, and outright fraud. If an insurance company refuses to make a reimbursement due to a coding error, the patient may be faced with an unexpected, huge bill. To manage this issue, many businesses now offer medical advocacy services as part of their compensation package. :DP HealthNow includes a benefit that provides unlimited, free access to medical advocacy services. Along with untangling billing issues, medical advocates also provide help with coordinating care, getting second opinions, explaining diagnoses and treatments, and finding the most suitable healthcare services and programs within the community or across the nation. To find out more about this offering, and all the advantages of the DP HealthNow telehealth package, visit DPHealthNow.com.	4	2	0	0	2	0.477796	2	1,173
ICD-10 is the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD), a medical classification list by the World Health Organization (WHO). It contains codes for diseases, signs and symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or diseases. Work on ICD-10 began in 1983, became endorsed by the Forty-third World Health Assembly in 1990, and was first used by member states in 1994. It will be replaced by ICD-11 on January 1, 2022. While WHO manages and publishes the base version of the ICD, several member states have modified it to better suit their needs. In the base classification, the code set allows for more than 14,000 different codes and permits the tracking of many new diagnoses compared to the preceding ICD-9. Through the use of optional sub-classifications, ICD-10 allows for specificity regarding the cause, manifestation, location, severity, and type of injury or disease. The adapted versions may differ in a number of ways, and some national editions have expanded the code set even further; with some going so far as to add procedure codes. ICD-10-CM, for example, has over 70,000 codes. The WHO provides detailed information regarding the ICD via its website - including an ICD-10 online browser and ICD training materials. The online training includes a support forum, a self-learning tool and user guide. \|I\|\|Certain infectious and parasitic diseases\| \|III\|\|Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism\| \|IV\|\|Endocrine, nutritional and metabolic diseases\| \|V\|\|Mental and behavioural disorders\| \|VI\|\|Diseases of the nervous system\| \|VII\|\|Diseases of the eye and adnexa\| \|VIII\|\|Diseases of the ear and mastoid process\| \|IX\|\|Diseases of the circulatory system\| \|X\|\|Diseases of the respiratory system\| \|XI\|\|Diseases of the digestive system\| \|XII\|\|Diseases of the skin and subcutaneous tissue\| \|XIII\|\|Diseases of the musculoskeletal system and connective tissue\| \|XIV\|\|Diseases of the genitourinary system\| \|XV\|\|Pregnancy, childbirth and the puerperium\| \|XVI\|\|Certain conditions originating in the perinatal period\| \|XVII\|\|Congenital malformations, deformations and chromosomal abnormalities\| \|XVIII\|\|Symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified\| \|XIX\|\|Injury, poisoning and certain other consequences of external causes\| \|XX\|\|External causes of morbidity and mortality\| \|XXI\|\|Factors influencing health status and contact with health services\| \|XXII\|\|Codes for special purposes\| Approximately 27 countries use ICD-10 for reimbursement and resource allocation in their health system, and some have made modifications to ICD to better accommodate its utility. The unchanged international version of ICD-10 is used in 117 countries for performing cause of death reporting and statistics. Introduced in 1998, ICD-10 Australian Modification (ICD-10-AM) was developed by the National Centre for Classification in Health at the University of Sydney. It is currently maintained by the Australian Consortium for Classification Development. Canada began using ICD-10 for mortality reporting in 2000. A six-year, phased implementation of ICD-10-CA for morbidity reporting began in 2001. It was staggered across Canada's ten provinces, with Quebec the last to make the switch. ICD-10-CA is available in both English- and French-language versions. The Czech Republic adopted ICD-10 in 1994, one year after its official release by WHO. Revisions to the international edition are adopted continuously. The official Czech translation of ICD-10 2016 10th Revision was published in 2018. Germany's ICD-10 German Modification (ICD-10-GM) is based on ICD-10-AM. ICD-10-GM was developed between 2003 and 2004, by the German Institute for Medical Documentation and Information. A Korean modification has existed since 2008. The Ministry of Healthcare of the Russian Federation ordered in 1997 to transfer all health organizations to ICD-10. ICD-10 was implemented in July 2005 under the auspice of the National ICD-10 Implementation Task Team which is a joint task team between the National Department of Health and the Council for Medical Schemes. The current Swedish translation of ICD-10 was created in 1997. The ICD-10-TM (Thai Modification) is a Thai language version based on the 2016 ICD-10. An unusual feature of the index of ICD-10-TM is that it is bilingual, containing both Thai and English trails. ICD-10 was first mandated for use in the UK in 1995. In 2010 the UK Government made a commitment to update the UK version of ICD-10 every three years. On 1 April 2016, following a year's delay, ICD-10 5th Edition[note 1] replaced the 4th Edition as the mandated diagnostic classification within the UK. For disease reporting, the US utilizes its own national variant of ICD-10 called the ICD-10 Clinical Modification (ICD-10-CM). A procedural classification called ICD-10 Procedure Coding System (ICD-10-PCS)[note 2] has also been developed for capturing inpatient procedures. The ICD-10-CM and ICD-10-PCS were developed by the Centers for Medicare and Medicaid Services (CMS) and the National Center for Health Statistics (NCHS). 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. There was much controversy when the transition from the ICD-9-CM to the ICD-10-CM was first announced in the US. Many providers were concerned about the vast number of codes being added, the complexity of the new coding system, and the costs associated with the transition. The Centers for Medicare and Medicaid Services (CMS) weighed these concerns against the benefits of having more accurate data collection, clearer documentation of diagnoses and procedures, and more accurate claims processing. CMS decided the financial and public health cost associated with continuing to use the ICD-9-CM was too high and mandated the switch to ICD-10-CM. The deadline for the United States to begin using ICD-10-CM for diagnosis coding and Procedure Coding System ICD-10-PCS for inpatient hospital procedure coding was set at October 1, 2015, a year later than the previous 2014 deadline. Before the 2014 deadline, the previous deadline had been a year before that on October 1, 2013. All HIPAA "covered entities" were required to make the change; a pre-requisite to ICD-10-CM is the adoption of EDI Version 5010 by January 1, 2012. Enforcement of 5010 transition by the Centers for Medicare & Medicaid Services (CMS), however, was postponed by CMS until March 31, 2012, with the federal agency citing numerous factors, including slow software upgrades. The implementation of ICD-10-CM has been subject to previous delays. In January 2009, the date was pushed back to October 1, 2013, rather than an earlier proposal of October 1, 2011. The examples and perspective in this section may not represent a worldwide view of the subject. (August 2018) (Learn how and when to remove this template message) The expansion of healthcare delivery systems and changes in global health trends prompted a need for codes with improved clinical accuracy and specificity. The alphanumeric coding in ICD-10 is an improvement from ICD-9 which had a limited number of codes and a restrictive structure. Early concerns in the implementation of ICD-10 included the cost and the availability of resources for training healthcare workers and professional coders. Two common complaints in the United States about the ICD-10-CM are 1) the long list of potentially relevant codes for a given condition (such as rheumatoid arthritis) which can be confusing and reduce efficiency and 2) the assigned codes for seldom seen conditions (e.g. W55.22XA: Struck by cow, initial encounter and V91.07XA: Burn due to water-skis on fire, initial encounter). \|journal=(help). 77 FR 54664 of 5 September 2012. 77 FR 60629 of 4 October 2012.	4	10	2	0	2	0.850418	4	1,845
- Open Access Dissemination of definitions and concepts of allergic and hypersensitivity conditions World Allergy Organization Journal volume 9, Article number: 24 (2016) Allergy and hypersensitivity can affect people of any age and manifest with problems in a range of organ systems. Moreover, they can have a significant impact on the quality of life of patients and their families. Although once rare, there is presently an epidemic of allergic disorders with associated considerable societal consequences. Our understanding of the pathophysiology of these disorders has changed substantially over the last 20 years. In the light of these developments, the Joint Allergy Academies have made concerted efforts to ensure that these are reflected in the current definitions and concepts used in clinical allergy and to ensure these are reflected in the forthcoming International Classification of Diseases-11 (ICD-11). In this review, we seek to provide an update on the current definitions and concepts in relation to allergic disorders. Once the new section has been built in the ICD-11 to address allergic and hypersensitivity conditions, we have been moving actions to try to support awareness by disseminating updated concepts in the field. Aligned with the ICD and the WAO philosophy of being global, this document presents fundamental and broad allergy concepts to strengthen the understanding by different health professionals worldwide, besides to support the formation of in training students. This current review intends to be accepted and used universally by all health professionals involved in diseases’ classification and coding and, therefore, contribute to improve care and outcomes in this increasing sub-section of the world’s population. Allergy and hypersensitivity: stating the problems The importance of disease classification Many patients have chronic conditions or episodes of illness in which allergy triggers may be implicated. These conditions and episodes can be assigned different classifications and terminologies by different healthcare professionals. Some of these labels are misrepresentative labels leading to misconceptions. These varied working definitions have hampered our real understanding of these conditions. Inaccurate disease classification can lead to suboptimal patient care and moreover this misclassification can influence the understanding and development of allergy (Fig. 1). In the diagnosis and management of patients, diagnostic labels are important since they drive investigation and treatment strategies. The misunderstanding of diseases’ concepts is likely to hamper the indication of diagnostic method procedures as well as can induce inappropriate management. For example, using the term wheezy bronchitis to describe asthma steers people towards prescribing antibiotics for exacerbations. Some physicians and health care professionals consider wheezy bronchitis to be attributable to bacteria without appreciation that often viruses such are responsible for symptoms. In epidemiology, terminologies and concepts are currently translated into codes and these data provide morbidity and mortality statistics. These data build a global picture and are used as the basis of health policy. If the records are unable to provide reliable data, decreasing the visibility of some conditions in detriment to others, there is a possibility of negative outcomes in health decision-making and management actions, affecting the supply and demand of goods and services at both national and global levels. As an example, research showed an under-notification of anaphylaxis deaths due to difficult coding under the ICD-10 using the Brazilian national mortality database, given that there are no anaphylaxis-specific ICD-10, which are considered valid for coding underlying causes-of-death . In an economic context, these data are also able to provide aggregated indicators to understand how the whole health economy functions and, therefore, influence directly the allocation of resources for both management and research. Indeed, the weak identity of the allergy specialty in the international health classification and coding systems contributes to the lack of ascertainment and recognition of their importance for healthcare planning and resource allocation, and prevents clinical research from being performed, especially in countries in which allergy is not an academic discipline. For example, the lack of realistic anaphylaxis mortality epidemiological data to support public and private decision-making to offer appropriate treatment, such as auto-injectable adrenaline, still missing in some countries [1, 2]. In an educational context, although we now have a culture of evidence-based medicine, the dissemination of misconceptions of medical terms and definitions, even informally, can impact negatively in the formation of the new generations of health professionals. Furthermore, in today’s world, medical information is widely available through both print and online media and the source of information that patients rely on are frequently written by non-medical professionals or are based on lack of evidence data, what can perpetuate the misconceptions . Evidence for the need of reviewing the allergy and hypersensitivity definitions and the associated semantic framework Allergy and hypersensitivity, previously perceived as simple and rare disorders, are now common and increasingly a major global public health problem. Numerous reports over the last 20 years have been indicating that the world is dealing with an allergy epidemic [4, 5]. They are complex conditions able to be expressed in many different organs and in any age, having a significant impact on the quality of life of patients and their families [6–9]. All health care professionals, in whatever role may thus encounter patients with allergic conditions. Concepts in medicine and the new knowledge generated in the last years [4–50] have substantially changed our view of the immune system and its interaction with the environment and external agents (Fig. 2). Such developments in pathophysiology, pharmacology and clinical practice necessitate reviewing current definitions and terminologies. The World Health Organization (WHO) decided for starting the 11th revision process with the aim of adapting the ICD frame to the new knowledge generated since the last revision. However, allergic and hypersensitivity conditions have not been adequately tracked in the ICD framework as previously demonstrated [1, 10]. Since 2013, an international collaboration of Allergy Academies, composed first by the American Academy of Allergy Asthma and Immunology (AAAAI), the European Academy of Allergy and Clinical Immunology (EAACI), the World Allergy Organization (WAO), and then by the American College of Allergy Asthma and Immunology (ACAAI), the Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI) and the Latin American Society of Allergy, Asthma and Immunology (SLAAI), has worked to improve and update the classification of allergies in the forthcoming ICD-11 version, by providing scientific evidence for the need for changes [1, 10–17]. A major achievement of this process is the construction of an “Allergic and hypersensitivity conditions” parented subchapter (under the “Disorders of the immune system” chapter) guided by the World Health Organization (WHO) ICD representatives . However, during the detailed technical/scientific labor-intensive building process in which we had to reach a consensus with all the “sister-specialties” with whom we have overlapping conditions, it became clear that definitions and concepts currently used in routine allergy clinical practice are not broadly known outside our community. For all the reasons mentioned above, we have compiled this review which addresses the concepts and semantic frameworks of key allergic and hypersensitivity conditions with the idea that this should be accessible to all health care professionals in clinical practice, education and research. It is hoped that this revision will be globally accepted as a tool of improving the communication between health professionals and also support the tremendous efforts of the Joint Allergy Academies to update and standardize the allergy and hypersensitivity definitions throughout the new ICD-11. The strategy for a better classification of allergic and hypersensitivity diseases in the ICD-11 The 2004 European Academy of Allergy and Clinical Immunology (EAACI) - World Allergy Organization (WAO) revised nomenclature was the basis of the proposed document, updated by new knowledge generated since its publication [19–50]. We also took the advances in the ICD-11 revision process to support this review manuscript since all the “allergic and hypersensitivity conditions” chapter was originally constructed by crowdsourcing the allergy community leadership . Briefly, after a large survey of the allergy community , the identification of the gaps and trade-offs in both ICD-10 and ICD-11 beta phase codes a classification model for allergic and hypersensitivity conditions has been constructed following the ICD/WHO rules and validated by crowdsourcing allergist leaderships’ community [17, 51]. The classification proposal has been presented and endorsed by the WHO revising steering group. The simplified constructed framework was the basis for the construction of the “Allergic and hypersensitivity conditions” parented subchapter into the ICD-11 beta draft . Once the new section has been built, we have been moving actions to try to support awareness by disseminating updated concepts in the field. Aligned with the ICD philosophy of being of global use, this document intends to be basic, fundamental and broad to make the allergy concepts fully understood by different health professionals worldwide, besides supports the formation of in training students. Although some countries use national modifications of ICD-10, such as United States of America (ICD-10-CM), Australia (ICD-10-AM) and Canada (ICD-CA), they may be advised by the WHO to move to the ICD-11 once it is available and proven stable. There is a substantial improvement of allergic and hypersensitivity conditions codes into the ICD-10 CM when compared with the ICD-10, even the most recent version of it . However, we observe that the ICD-10 CM, as well as most of the other national adaptations, keeps the same framework, inheriting many trade-offs. The simple search of the term “Allergy” into both ICD-10 (2016 version) and ICD-10 CM platforms addresses to the T78 section, entitled “Adverse effects, not elsewhere classified”. The allergy and hypersensitivity definitions and semantic framework The allergy and hypersensitivity definitions Outside the allergy community, the terms “hypersensitivity” and “allergy” have often been considered to be synonymous. However, currently in the field of allergy they receive different hierarchical positions since (Fig. 3) “hypersensitivity” is defined as “conditions clinically resembling allergy that cause objectively reproducible symptoms or signs, initiated by exposure to a defined stimulus at a dose tolerated by normal subjects” and “allergy” as “a hypersensitivity reaction initiated by proven or strongly suspected immunologic mechanisms” . Therefore, the heading “hypersensitivity” includes allergic hypersensitivity conditions, such as milk-induced anaphylaxis (IgE-mediated) or antiepileptic-induced Stevens-Johnson syndrome (non-IgE mediated), as well as non-allergic hypersensitivity conditions, such as angiotensin-converting enzyme inhibitor induced angioedema or cold-induced urticaria (non-immune mediated hypersensitivity). An allergic reaction occurs when triggered by allergens to which the affected individual is sensitized (i.e., has immune antigen receptors directed against them). Although the term “intolerance” has been wrongly used to describe allergic clinical presentations by other specialties and laypersons, it has been mentioned as a non-allergic (non-immunological) hypersensitivity condition , out of the area of allergy practice. Therefore, this term has been added as exclusion of allergy in the new ICD-11 framework. Table 1 shows some misunderstandings related to the concepts of “allergy”, “sensitization”, “atopy” and “atopic diseases”. The concept of “allergy” is an umbrella that covers both IgE- and non-IgE mediated conditions with different degrees of severity and is not synonymous with “atopy” or in cases of increased isolated total or specific IgE serum level. The diagnosis of allergy is based on a compatible clinical history and in vivo and/or in vitro tests to prove underlying (allergy) mechanism and etiology (cause). Therefore the tests cannot be used in isolation, for example to screen the general population for allergic conditions, because many people are sensitized, but have no allergic condition. The term atopy is used when individuals have an IgE sensitization as documented by IgE antibodies in serum or by a positive skin prick test. Since the concept of “hypersensitivity” covers many different conditions such as asthma, rhinitis, anaphylaxis, drug, food, and insect hypersensitivity, eczema, urticaria and angioedema, we have focused on the current definitions of conditions covered by the allergy specialty (Table 2) and to update them to the new ICD-11 “Allergic and hypersensitivity conditions” chapter. As shown in Table 2, the semantic framework on using the nomenclature “allergic” and “non-allergic” has been extended to most of the conditions. We would like to highlight the terminology used for “anaphylaxis” now used throughout the world to cover both allergic and non-allergic anaphylaxis. The term “anaphylactoid”, that was used to connote non-allergic anaphylaxis, has fallen into disuse. Another example is the term “intrinsic” or “extrinsic” used for asthma. These terms are still listed in the ICD-10 (and adaptations) and used to be in use to evoke underlying mechanism. However, following the new concepts, the terms have been tuned to “allergic asthma” and “non-allergic asthma” and now implemented into the new ICD-11. The development of medicine and new technological knowledge has dramatically changed the landscape in which we practice medicine. Within the specialty of clinical allergy, many diagnostic procedures have emerged to support the correct diagnosis of allergic and hypersensitivity conditions (Table 3). However, apart from minor modifications, the in vivo tests, such as skin prick and patch tests, still resemble the original methods described. In this regard, we would like to further underline that skin tests and in vitro procedures (Table 3) are not usually indicated as a screening of the general population (without symptoms and a working or suspected diagnosis). The tests are used to support diagnosis in patients with a suspicious history and have to be carefully interpreted. The management of allergy and hypersensitivity has also been affected with the implementation of novel therapeutic agents, drug classes and new devices to optimize the best treatment of these patients. For this reason, the concepts used for desensitization/tolerance induction and immunotherapy have been recently reviewed. From the allergy specialty perspective, all allergen immunotherapies (AIT) are desensitization procedures. However, the desensitization/tolerance induction procedures can be used with allergens (procedure named AIT) or other products not made of allergens (e.g., AIT for allergic rhinitis), procedure named allergy immunotherapy (e.g., the anti-IgE monoclonal antibody omalizumab for asthma). It can address both allergic hypersensitivity conditions, such as IgE-mediated food-induced anaphylaxis (e.g., milk-induced anaphylaxis), as well as non-immune-mediated hypersensitivity conditions (e.g., NSAIDs-exacerbated respiratory disease) . The allergic and hypersensitivity in process The allergic and hypersensitivity concepts have been evolving substantially and efforts have been addressed to allow harmonization of work definitions and terminology. The classification systems are used to categorize ideas and concepts to support the real-life management decision-making and are, in general, translated automatically into codes. In clinical practice, clinicians select diagnostic labels based on classification knowledge. This current review intends to be accepted and used universally by all health professionals involved in diseases’ classification and coding and, therefore, contribute to improve care and outcomes in this increasing sub-section of the world’s population (Fig. 4). AAAAI, American Academy of Allergy Asthma and Immunology; ACAAI, American College of Allergy, Asthma and Immunology; AIT, allergen immunotherapies; APAAACI, Asia Pacific Association of Allergy, Asthma and Clinical Immunology; BAT, basophil activation test; CAST, Cellular Antigen Stimulation Test; EAACI, European Academy of Allergy and Clinical Immunology; ELISPOT, Enzyme-Linked ImmunoSpot; ICD, International Classification of Diseases; IgE, immunoglobulin E; SLAAI, Latin American Society of Allergy, Asthma and Immunology; WAO, World Allergy Organization; WHO, World Health Organization Tanno LK, Ganem F, Demoly P, Toscano CM, Bierrenbach AL. Undernotification of anaphylaxis deaths in Brazil due to difficult coding under the ICD-10. Allergy. 2012;67:783–9. Simons FE, Ardusso LR, Bilò MB, Cardona V, Ebisawa M, El-Gamal YM, Lieberman P, Lockey RF, Muraro A, Roberts G, Sanchez-Borges M, Sheikh A, Shek LP, Wallace DV, Worm M. International consensus on (ICON) anaphylaxis. 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Accepted, JACI in practice Dreborg S. Debates in allergy medicine: food intolerance does not exist. World Allergy Organ J. 2015;8:37. World Health Organization, ICD-10 version 2016 website. (cited, available: http://apps.who.int/classifications/icd10/browse/2016/en#/T78 accessed Jan 2016) Centers for Disease Control and Prevention website. (cited, available: http://www.cdc.gov/nchs/icd/icd10cm.htm accessed Jan 2016) We are extremely grateful to all the representatives of the ICD-11 revision with whom we have been carrying on fruitful discussions, helping us to tune the here presented classification: Robert Jakob, Linda Best, 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), Asia Pacific Association of Pediatric Allergy, Respirology & Immunology (APAPARI) Role of funding source Luciana Kase Tanno received a grant from the Brazilian National Council for Scientific and Technological Development (CNPq). Availability of data and materials No data will be shared since there is no additional material to be shared besides the manuscript. LKT and PD contributed to the construction of the document (designed the study, analyzed and interpreted the data, and wrote the manuscript). MAC, HES, MS-B and AS contributed in tuning the document and with the revision of the manuscript. All authors read and approved the final manuscript. The authors declare that they have no competing interests. Consent for publication Not applicable. The current manuscript does not contain any persons’ data. All the co-authors participated in the construction of the current document are acknowledged the submission to the WAO Journal. Ethics approval and consent to participate No ethical approval and consent to participate has been required since it is a review document, not involving intervention, human or animals models. About this article Cite this article Tanno, L.K., Calderon, M.A., Smith, H.E. et al. Dissemination of definitions and concepts of allergic and hypersensitivity conditions. World Allergy Organ J 9, 24 (2016). https://doi.org/10.1186/s40413-016-0115-2 - Allergic conditions - Hypersensitivity conditions	2	6	3	0	4	0.543436	7	8,344
I'm a member You will be redirected to myBlue. Would you like to continue? Please wait while you are redirected. Please enter a username and password. Printer Friendly Version Portable devices have been developed to provide point-of-care nerve conductions studies (NCSs). These devices have computational algorithms that are able to drive stimulus delivery, measure and analyze the response, and provide a report of study results. Automated nerve conduction could be used in various settings, including primary care, without the need for specialized training or equipment. Nerve conductions studies (NCS) and needle electromyography (EMG), when properly performed by a trained practitioner, are considered the criterion standard of electrodiagnostic testing. However, the need for specialized equipment and personnel may limit the availability of electrodiagnostic testing for some patients. One proposed use of automated nerve conduction devices is to assist in the diagnosis of carpal tunnel syndrome (CTS). CTS is a pressure-induced entrapment neuropathy of the median nerve as it passes through the carpal tunnel, resulting in sensorimotor disturbances. This syndrome is defined by its characteristic clinical symptoms, which may include pain, subjective feelings of swelling, and nocturnal paresthesia. A variety of simple diagnostic tools are available, and a positive response to conservative management (steroid injection, splints, modification of activity) can confirm the clinical diagnosis. Electrodiagnostic studies may also be used to confirm the presence or absence of a median neuropathy at the wrist, assess the severity of the neuropathy, and assess alternate associated diagnoses. Nerve conduction is typically assessed before surgical release of the carpal tunnel, but the use of EMG in the diagnosis of CTS is controversial. Point-of-care nerve conduction testing has also been proposed for the diagnosis of peripheral neuropathy and, in particular, for detecting neuropathy in patients with diabetes. Peripheral neuropathy is relatively common in patients with diabetes mellitus, and the diagnosis is often made clinically through the physical examination. Diabetic peripheral neuropathy can lead to important morbidity including pain, foot deformity, and foot ulceration. Clinical practice guidelines recommend using simple sensory tools such as the 10-g Semmes-Weinstein monofilament or the 128-Hz vibration tuning fork for diagnosis. These simple tests predict the presence of neuropathy defined by electrophysiologic criteria with a high level of accuracy. Electrophysiologic testing may be used in research studies and may be required in cases with an atypical presentation. NC-stat® by NeuroMetrix is a portable nerve conduction test device designed to be used at the point-of-care. The system comprises a biosensor array, an electronic monitor, and a remote report generation system. The biosensor is a single use, preconfigured array consisting of a stimulation anode and cathode, skin surface digital thermometer, and response sensor. Biosensor arrays are available for assessment of sensory and motor nerves of the wrist (median and ulnar), and for the foot (peroneal, posterior tibial, and sural). A chip imbedded in the biosensor panel measures skin surface temperature, the analysis algorithm adjusts for differences in temperature from 30º C, or if skin surface temperature is less than 23º C, the monitor will indicate that limb warming is necessary. Data are sent to a remote computer via a modem in the docking station, and the remote computer generates a report based on the average of 6 responses that is sent back by fax or email. In addition to the automated stimulus delivery and reporting, NC-stat® analysis adjusts the calculation for body temperature, height, and weight, and uses the average of 6 responses. Sensitivity of the device for sensory nerve amplitude potentials is 2.1 µV, values lower than this are analyzed as zero, and responses with artifact are automatically eliminated from the analysis. The Axon-II™ (PainDx) is an automated system that is being marketed for the detection of various sensory neurologic impairments caused by various pathologic conditions or toxic substance exposures, including signs of sympathetic dysfunction and detection of down-regulated A-delta function to locate injured nerve(s) The Axon-II software works with the Neural-Scan™ system (Neuro Diagnostics) and lists 7 automated studies (Cervical, Thoracic, Lumbar, Upper Extremities, Lower Extremities, Neuroma, Trigeminal), as well as a custom study. The Neural-Scan™ is a voltage-actuated sensory nerve conduction test device, which measures the voltage amplitude necessary to cause a discernible nerve impulse. Results are adjusted and compared with population means; the most severe hypoesthesia is considered the primary lesion. Several devices are now being marketed for point-of-care neural conduction testing. NeuroMetrix received specific clearance to market NC-stat® via the U.S. Food and Drug Administration's (FDA) 510(k) process in 1998, listing as predicate devices the TECA model-10 electromyograph and the Neurometer® by Neurotron, which measures vibration threshold. The FDA-listed intended use was "to measure neromuscular signals that are useful in diagnosing and evaluating systemic and entrapment neuropathies." In addition, the approved application stated that "The NC-stat is intended to be used as an adjunct to and not a replacement for conventional electrodiagnostic measurements." NeuroMetrix subsequently received FDA clearance to market newer models with biosensors and engineering changes that enable the NC-stat to be used for motor and sensory nerves of the wrist (median and ulnar) and foot (peroneal, tibial, and sural). The intended use as listed on the 510(k) approval from 2006 (K060584) is "to stimulate and measure neuromuscular signals that are useful in diagnosing and evaluating systemic and entrapment neuropathies." The NeuroMetrix ADVANCE™ system received marketing clearance in 2008 (K070109). It is intended to perform nerve conduction studies using disposable surface electrodes (similar to NC-stat) with an additional module for invasive needle EMG. The ADVANCE™ system includes a real-time display of nerve conduction waveforms with a stylus for assignment of waveforms. The Brevio® from Neurotron Medical received marketing clearance from FDA in 2001. The Brevio® is intended “for use for the measurement of nerve response latency and amplitude in the diagnosis and monitoring of peripheral neuropathies.” The XLTek Neuropath (Excel- Tech) received clearance for marketing through the FDA’s 510(k) process in 2006; the indications are the same as those for NC-stat®. The Neural-Scan™ NCS (Neuro Diagnostics) is a Class I diagnostic device (FDA clearance not usually required) that is being marketed “as part of the [sic] neurological examination or for screening to detect peripheral neuropathies.” POLICYAutomated nerve conduction tests are considered investigational. 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 GUIDELINESNerve conduction studies performed without needle electromyography studies, unless contraindicated (i.e., an individual receiving anticoagulant therapy) are considered investigational. Investigative 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 HISTORY3/2/2007: Policy added 3/22/2007: Reviewed and approved by Medical Policy Advisory Committee (MPAC) 6/14/2007: Code Reference section updated per quarterly HCPCS and Category III revisions 10/11/2007: Code Reference section reviewed. CPT 95900, 95903, and 95904 removed from policy as non-covered for an automated point of care nerve conduction test (Note: Standard nerve conduction tests may be covered with these Copts); a specific HCPCS code for an automated point of care nerve conduction test became effective 7-1-2007 7/6/2009: Policy reviewed, description updated, policy statement unchanged 11/03/2010: Policy description section revised to provide a list of devices and research findings regarding portable automated nerve conduction tests compared to standard testing. Policy statement unchanged. FEP verbiage added to the Policy Exceptions section. Added the following statement to the Policy Guidelines: Nerve conduction studies performed without needle electromyography studies, unless contraindicated (i.e., an individual receiving anticoagulant therapy) are considered investigational. Code Reference section revised to add 95905, 95999, and G0255 to the Non-Covered Codes Table. A note was also added to state that CPT Codes 95900, 95903 and 95904 should not be used to bill for automated nerve conduction testing. 08/02/2011: Policy reviewed; no changes. 07/17/2012: Policy reviewed; no changes. 09/03/2013: Policy reviewed; no changes. 08/01/2014: Policy reviewed; description updated regarding devices. Policy statement unchanged. SOURCE(S)Blue Cross Blue Shield Association Policy # 2.01.77 CODE REFERENCEThis is may not be a comprehensive list of procedure codes applicable to this policy.	4	6	6	2	0	0.511528	8	2,080
New Perspectives on Adenomyosis Adenomyosis, defined as the presence of endometrial tissue within the uterine myometrium, may be associated with substantial dysmenorrhea, chronic pelvic pain, menorrhagia, bowel and bladder pressure, infertility, and pregnancy complications. Of note, similar to endometriosis, there is a wide variation in morbidity across patients and may be poor correlation with extent of disease. Current prevalence estimates range from approximately 1% when based on ICD codes to 20% by ultrasound in symptomatic women to as high as 60% in hysterectomy specimens. With improved awareness and increased utilization of pelvic ultrasound, it is becoming clear that adenomyosis presents earlier and may be a more common cause of gynecologic and obstetric complications than previously appreciated. As disorders of ectopic endometrium, adenomyosis and endometriosis have previously been designated “endometriosis interna” and “endometriosis externa,” respectively. Although they share common features and frequently coexist, some experts believe they should be considered distinct entities due to differences in pathogenesis, risk factors, and clinical presentations. Others highlight similarities between adenomyosis and deep infiltrating endometriosis and emphasize the many ways in which adenomyosis can be viewed as “myometrial endometriosis.” The etiology of adenomyosis is poorly defined and may differ between focal adenomyosis and diffuse forms of the disease. Current thinking focuses on two primary models, either breakdown of the endometrial–myometrial border allowing endometrial cell migration or metaplasia of embryonic Mullerian remnants. Similarly, little is known about the contribution of genomic or epigenomic variants or of stem cell dysfunction to the pathogenesis of this disorder. Treatment is primarily hysterectomy, although medical management and less aggressive surgical and interventional radiologic approaches are emerging. The “benign” nature of adenomyosis is frequently emphasized in the literature and in discussions with patients. This terminology minimizes the substantial morbidity experienced by patients and, as for other noncancerous gynecologic conditions, may have diminished the intensity of the search for adequate diagnosis and treatment. Recognizing the significant need to better understand this disorder, the Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD) sponsored a meeting entitled “Adenomyosis: Diagnosis, Pathogenesis, and Treatment” on April 24, 2019. This issue is the extension of this workshop which was attended by many of the authors who have contributed here. The following articles are designed to review the current state-of-the science in adenomyosis research and clinical care, including the epidemiology, diagnosis, pathogenesis, pathophysiology, and treatment of this disorder. The overlap of adenomyosis and its clinical presentation with other gynecologic disorders, particularly endometriosis, is presented to emphasize the high potential for misdiagnosis and, as a result, suboptimal treatment. The currently available in vitro and in vivo models are analyzed for their ability to address ongoing research questions. Throughout, authors highlight gaps in our knowledge and suggest research tools, models, and investigative approaches which are poised to advance research in this field. We hope that this issue will be a useful resource for clinicians and investigators, and spur enthusiasm for the increased study of this highly prevalent and morbid disorder. While many questions remain, the emerging interest in this field promises great hope for the future care of these patients. 24 November 2020 (online) © 2020. Thieme. All rights reserved. Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA - 1 Yu O, Schulze-Rath R, Grafton J, Hansen K, Scholes D, Reed SD. Adenomyosis incidence, prevalence and treatment: United States population-based study 2006-2015. Am J Obstet Gynecol 2020; 223 (01) 94.e1-94.e10 - 2 Munro MG. Classification and reporting systems for adenomyosis. J Minim Invasive Gynecol 2020; 27 (02) 296-308 - 3 García-Solares J, Donnez J, Donnez O, Dolmans MM. Pathogenesis of uterine adenomyosis: invagination or metaplasia?. Fertil Steril 2018; 109 (03) 371-379 - 4 Vannuccini S, Tosti C, Carmona F. et al. Pathogenesis of adenomyosis: an update on molecular mechanisms. Reprod Biomed Online 2017; 35 (05) 592-601 - 5 Rabinovici J, Stewart EA. New interventional techniques for adenomyosis. Best Pract Res Clin Obstet Gynaecol 2006; 20 (04) 617-636	2	13	1	0	0	0.877018	1	1,046
Prevention and Patient Safety Online Continuing Education Course 6-contact-hour comprehensive overview on the prevention of medical errors. Course defines the scope of the problem and includes ways to avoid medication errors and medical mistakes. Explore why medical errors are underreported and learn new strategies for how to decrease medical errors, optimize communication, and increase patient safety and quality of care. This course is applicable for nursing, occupational therapy, and physical therapy for CEU credit. Course Price: $39.00 Contact Hours: 6 Prevention and Patient Safety Copyright © 2018 Wild Iris Medical Education, Inc. All Rights Reserved. LEARNING OUTCOME AND OBJECTIVES: Upon completion of this course, you will understand current, evidence-based interventions to prevent medical errors in the practice setting. Specific learning objectives include: - Discuss the scope of medical errors in the U.S. healthcare environment. - Define the terminology associated with medical errors. - Describe the causes of medical errors. - Review the most common medical errors and strategies to prevent them. - Summarize the elements of effective communication and documentation. - Identify error risks among populations of special vulnerability. - Describe various initiatives of the patient safety movement. - Discuss accrediting agency standards and goals. - Outline institutional strategies to prevent medical errors. TABLE OF CONTENTS - Scope of the Medical Error Problem - Terminology Associated with Medical Errors - Why Do Medical Errors Happen? - Common Medical Errors and How to Prevent Them - Developing Effective Documentation and Communication - Error Risks among Populations of Special Vulnerability - Patient Safety Initiatives - Joint Commission and AAAHC Standards and Goals - Institutional Strategies for Addressing Errors It would seem essential that every healthcare encounter a person has should be safe and free from harm. Unfortunately, this is not always the case. Although the vast majority of Americans are having positive experiences with the healthcare system, nearly a quarter of adults report having personally experienced a medical error. Errors occur in hospitals, clinics, surgery centers, doctors’ offices, nursing homes, pharmacies, and even in patients’ homes. These facts make medical errors a serious public health issue, with every patient involved in the healthcare system a potential recipient of harm. Injuries and death can occur, for example, when patients develop healthcare-associated infections, receive a wrong medication or dose of medication, experience mistakes in surgery, receive treatments meant for another patient, experience a fall in the hospital, develop a pressure ulcer/injury, are misdiagnosed, orders are misinterpreted, or equipment fails. Those in leadership roles claim that the main reason for preventable medical mistakes is a healthcare system that is inadequate for the complexities of 21st-century medicine. It is acknowledged that the U.S. healthcare system is resistant to change because it is a fragmented, nonuniform system that lacks any centralized control and that many healthcare systems do not adequately invest in patient safety by putting well-known safety improvement strategies in place (Kavanagh et al., 2017). Errors can occur at any point in the healthcare system. Analyzing why medical errors happen has traditionally been focused on the human factor, concentrating on individual responsibility for making an error, and the solutions have involved training or retraining, additional supervision, or even disciplinary action. The alternative to this is a system-centered approach, which assumes that humans are fallible and that systems must be designed so that humans are prevented from making errors. Acknowledging that errors happen, learning from them, and working to prevent errors in the future are important goals and represent a major change in the culture of healthcare—a shift from blame and punishment to analysis of the root causes of errors and the creation of strategies to improve. In other words, healthcare organizations need to create a culture of safety that views medical errors as opportunities to improve the system. Every person on the healthcare team has a role in making healthcare safer for patients and workers. SCOPE OF THE MEDICAL ERROR PROBLEM Current studies estimate that medical errors are the third leading cause of death in the United States, trailing heart disease and cancer. In 2016, the Leapfrog Group estimated there were 206,201 avoidable deaths in hospitals, and a Johns Hopkins University team estimated deaths at greater than 250,000. However, there is an ongoing debate regarding these estimates, as there are no well-established means as yet for calculating mortality caused by medical harm. Such numbers are hard to determine because, although there are ICD codes to report mistakes, death certificates lack a place to indicate whether a medical mistake caused or contributed to a patient’s death, and there remains the question as to whether physicians will want to report them on death certificates, which are usually considered public records (Kavanagh et al., 2017). The great majority of healthcare takes place in the outpatient setting. It is estimated that 5% of adults in the United States experience a missed or delayed diagnosis each year, and 4.5 million outpatient visits occur every year due to adverse drug events. These are two of the most common problems encountered in ambulatory care. Over the past few years, efforts have been focused in improving patient safety in this area. The Joint Commission has developed National Patient Safety Goals to improve patient safety and has issued Ambulatory Health Care National Patient Safety Goals effective January 2017 to provide further guidance in the enhancement of safety in all ambulatory facilities (AHRQ, 2017a). A national survey released in September 2017 found that 21% of adults report having personally experienced a medical error, often with a lasting impact on their physical and emotional health, financial well-being, or family relationships. The survey also found that 31% of Americans report that an individual they are closely involved with experienced an error. Ambulatory settings were found to be a frequent site of errors, and errors related to diagnosis and patient-provider communications were the most common. The survey also found that 8 in 10 Americans believe that patient safety is the responsibility of healthcare providers, hospital leaders, and administrators, as well as family members and patients (NPSF, 2017; IHI, 2017a). Looking at malpractice payout statistics in all settings provides a broad view of medical errors overall; however, these show only a fraction of the actual number of medical errors, as most patients who are harmed by error do not seek damages, and many who do are denied compensation. An analysis of malpractice payout statistics for 2016 based on the U.S. Department of Health and Human Services’ National Practitioner Data Bank Public Use Data File are reported in the table below. \|Source: Diederick Healthcare, 2017.\| \|Due to errors in:\|\| \|Severity of outcome\|\| Progress in Patient Safety In 1999 the Institute of Medicine published To Err Is Human: Building a Safer Health System. Since that time, efforts have been ongoing to improve patient safety. IN INPATIENT SETTINGS The U.S. Department of Health and Human Services’ Agency for Health Research and Quality (AHRQ) estimates the incidence of medical errors that occur each year in U.S. hospitals. AHRQ reports that 2015 data indicated a 21% decline in hospital-acquired conditions compared to data from 2010. The following percentages reflect these reductions: - Adverse drug events: 29% decrease - Catheter-associated urinary tract infections: 33% decrease - Central line–associated bloodstream infections: 91% decrease - Falls: 15% decrease - Obstetrical events: 10% decrease - Pressure ulcers: 10% decrease - Surgical-site infections: 16% decrease - Post-op venous thromboembolism: 76% decrease AHRQ estimates that nearly 125,000 fewer patients died in the hospital as a result of hospital-acquired conditions and that approximately $28 billion in healthcare costs were saved from 2010 to 2015. The exact cause of the decline in patient harm is not fully understood; however, increased attention to safety to reduce adverse events by hospitals throughout the country has occurred. Likely reasons for this progress may be Medicare and Medicaid payment incentives, the U.S. Department of Health and Human Services Partnership for Patient Initiative, public reporting of hospital-level results, and technical assistance offered to hospitals by the Quality Improvement Organization program (AHRQ, 2016b). IN AMBULATORY CARE Although there has been a great deal of research done on adverse events in hospital settings, AHRQ estimates that only 10% of patient-safety studies have been performed in outpatient settings, even though outpatient settings may pose the greater challenge (AHRQ, 2017c). As a result, far less is known about the nature, causes, or consequences of incidents in primary care, and no studies thus far have been able to confidently state the rate of patient safety incidents in such settings. It is generally agreed, however, that the focus on outpatient patient safety is just beginning to be addressed, and efforts are underway to make improvements in this practice setting. An example of such an effort is the Health Partners Ambulatory Patient Safety Toolkit for 2017, which provides practical tools and suggestions to incorporate into clinical operation. The goal is to promote well-designed systems and processes that allow an organization to deliver care with reliability, consistency, and the ability to detect and quickly recover from an error before harm occurs (Health Partners, 2017). The AHRQ also provides guidance in the improvement of patient safety in primary care settings by offering tools and resources that enhance the reliability of laboratory testing; establish a culture of patient safety; improve the safety of care transitions; and identify techniques, tools, and strategies for clinicians to improve teamwork and performance (AHRQ, 2017c). TERMINOLOGY ASSOCIATED WITH MEDICAL ERRORS Medical error, also referred to as adverse event, is a broad term ascribed to an act of commission (doing something wrong) or omission (failing to do something right) in medical management that leads to an undesirable outcome or serious potential for such an outcome that is unrelated to the patient’s underlying condition. Such adverse events are unintended and may require additional monitoring, treatment, hospitalization, or result in disability or death. Important subcategories of adverse events include: - Unpreventable adverse events result from a complication that cannot be prevented. Example: A patient has an allergic reaction to a drug appropriately prescribed, dispensed, and administered. - Preventable adverse events occur due to error or failure to apply an accepted standard for prevention. Example: A patient with diabetes has the wrong foot amputated. - Ameliorable adverse events are those that could have been less harmful if different actions or procedures had been performed or followed. Example: A clinician fails to respond to medication-related symptoms. - Negligence is the result of care that falls below the standards expected of clinicians in the community. Example: A clinician fails to check the patient’s record, which indicates an allergy to the antibiotic being prescribed. Near misses are events that could have had an adverse consequence but did not. In a near miss, an error was committed but the patient did not experience clinical harm because of early detection or sheer luck. They are indistinguishable from adverse events in all but outcome. Example: A nurse recognizes a potential drug overdose in a physician’s prescription and does not administer the drug but instead calls the error to the physician’s attention (AHRQ, 2017b). The Joint Commission defines sentinel event as a patient safety event, incident, or condition that could have resulted or did result in any of the following: - Permanent harm - Severe temporary harm and intervention required to sustain life Sentinel events are so named because they signal the need for immediate investigation and response. Sentinel events and medical errors are not identical. Not all sentinel events occur because of an error, and not all medical errors result in sentinel events. For example, a patient has a severe allergic reaction to a medication taken successfully in the past (TJC, 2017a). The National Quality Forum (NQF, 2017) has developed and endorsed a list of 29 events that are termed serious reportable events (SREs) and considered to be extremely rare medical errors. These errors are also referred to as never events—events that should never happen—and are grouped into seven categories, as follows: - Surgery/invasive procedure performed on wrong body parts - Surgery/invasive procedure performed on the wrong patient - Wrong surgical/invasive procedure performed on a patient - Unintended retention of a foreign object in a patient post surgery/procedure - Intraoperative or immediately postoperative/postprocedure death in an American Society of Anesthesiologists Class I patient (an otherwise healthy person with no medical problems beyond those which the proposed surgery is intended to address) - Patient death/serious injury associated with use of contaminated drugs, devices, or biologics provided by the healthcare setting - Patient death/serious injury associated with use or function of a device in patient care where the device is used for functions other than as intended - Patient death/serious injury associated with intravascular air embolism occurring while being cared for in a healthcare setting - Discharge or release of a patient/resident of any age who is unable to make decisions to other than an authorized person - Patient death/serious disability associated with patient elopement - Patient suicide, attempted suicide, or self-harm resulting in serious disability while being cared for in a healthcare facility Care Management SREs - Patient death/serious injury associated with a medication error involving: - Wrong drug - Wrong dose - Wrong patient - Wrong time - Wrong rate - Wrong preparation - Wrong route - Patient death/serious injury associated with unsafe administration of blood products - Maternal death/serious injury associated with labor or delivery in a low-risk pregnancy while in a healthcare setting - Death/serious injury of a neonate associated with labor/delivery in a low-risk pregnancy - Artificial insemination with the wrong donor sperm/wrong egg - Patient death/serious injury associated with a fall while cared for in healthcare settings - Any stage 3, stage 4, or unstageable pressure ulcer/injury acquired after admission/presentation to a healthcare facility - Patient death/serious disability resulting from the irretrievable loss of an irreplaceable biological specimen - Patient death/serious injury resulting from failure to follow up or communicate laboratory, pathology, or radiology test results - Patient/staff death/serious disability associated with electric shock in the course of a patient care process in a healthcare setting - Any incident in which a line designated for oxygen or other gas to be delivered to a patient contains no gas, the wrong gas, or is contaminated by toxic substances - Patient/staff death/serious injury associated with burns incurred from any source in the course of patient care in a healthcare setting - Patient death/serious injury associated with the use of restraints/bedrails while cared for in a healthcare setting - Patient/staff death/serious injury associated with the introduction of a metallic object into an MRI area - Any instance of care ordered or provided by someone impersonating a physician, nurse, pharmacist, or other licensed healthcare provider - Abduction of a patient/resident of any age - Sexual abuse/assault on a patient within or on the grounds of a healthcare setting - Patient/staff death/significant injury resulting from a physical assault that occurs within or on the grounds of a healthcare setting Active and Latent Errors Active errors (human errors) are those that involve individuals who are actively doing a task, and the effects are felt almost immediately. Example: A surgeon amputates the wrong foot. Latent errors are errors in system or process design, faulty installation or maintenance of equipment, or ineffective organizational structure. They are accidents waiting to happen. Example: A hospital does not follow a consistent system for stocking central supply carts. When a latent error combines with an active human error, an event occurs. Example: The hospital’s lack of a consistent system for stocking central supply carts (latent error) may cause a nurse to select the wrong intravenous drip size tubing (active error), resulting in a drug overdose in a patient (AHRQ, 2017d). St. Vincent Hospital At St. Vincent Hospital all cylinders containing medical gases used in the operating room are stored in metal tubes in a tank room. All cylinders containing any concentration of carbon dioxide are color-coded grey and labeled “carbon dioxide.” Beneath that, a continuation of the label identifies any other gas with which it is combined, such as oxygen. When the cylinders are in their metal tubes, the capped connecting neck and top several inches of each cylinder, as well as several inches of the top of the label, are visible above the top of the tube. (Since the full label is not visible, this is an example of a latent error.) On Tuesday a delivery of medical gas cylinders containing CO2 was accepted by a logistics technician from the cardiac catheterization lab. The delivery included at least one cylinder containing a CO2/O2 blend. As there was inadequate storage space for the entire delivery in the cath lab’s tank room, the technician asked his counterpart in the OR to store an extra tank of the gas blend. The OR logistics technician agreed but did not inform anyone in his or the OR’s chain of command. On Thursday, during a routine laparoscopic cholecystectomy, the alarm for the pressure indicator in the gas delivery system sounded. The circulating nurse went to the tank room to obtain a cylinder replacement. She unknowingly selected the tank with the CO2/O2 blend and used it to replace the empty pure CO2 tank in the OR. (Selecting an incorrect medical gas cylinder is an example of an active error). The surgeon activated the electrosurgical cautery unit to stop oozing from the area of the liver from which the gallbladder had been bluntly dissected. There was a millisecond flash of flame (not an electrical arc, which can occur with the use of cautery) followed by a puff of smoke. The incident was confined to the contact area of the electrosurgical instrument, and careful examination indicated that there was no evidence of injury to the patient. (This is an example of a near miss; by chance, no adverse event occurred). Investigation of the incident used the “fire triangle” concept and revealed that the patient’s tissue was the fuel; the medical-grade CO2/O2 blend gas used to expand the patient’s abdomen was the oxidizing agent; and the instrument, the cord connecting it to the electrical generator, and the generator were the ignition source. All elements of the system were eliminated as possible causes for the flash of flame except for one. The medical gas cylinder was found to contain not just CO2 but a CO2/O2 blend. The erroneous presence of this gas mixture was determined to be the single deviation from normal practice and the cause of the accident. (continued under “Root Cause Analysis” later in this course) WHY DO MEDICAL ERRORS HAPPEN? In the past, medicine has viewed errors as failures on the part of individual healthcare providers that are the result of inadequate knowledge or skill. The current understanding is that most errors occur due to predictable human failures in the context of poorly designed systems, and according to the AHRQ (2003), there are eight common causes of medical errors. Breakdowns in communication are the most common causes of medical errors. These breakdowns can be either verbal or written and can occur between healthcare workers and the organization, between individual healthcare team members, or between team members and patients. Communication breakdowns occur when there is a failure to provide timely, accurate information or when information is not understood by the recipient. Problems in communication can result from issues such as educational differences, skill level, ethnicity, language, personality, or past and present personal or professional experiences. Poor communication of patient information is the most frequent root cause of sentinel events. Research into why errors happen has studied different types of human information processing involved in the performance of tasks and has classified them using a knowledge-, rule-, or skill-based approach. These terms refer to the degree of conscious control exercised by an individual over his or her activities. - Knowledge-based: New situations in which learning must take place and knowledge stored. The task is carried out in an almost completely conscious manner. Example: A student nurse learning to perform urinary catheterization following step-by-step instructions in the lab. - Rule-based: Application of stored rules to familiar problems, and conscious control is intermediate between knowledge and skill. Example: A new RN performing urinary catheterization who has memorized all the materials and steps required. - Skill-based: Patterns of preprogrammed instructions have been stored, and virtually no conscious monitoring is required. Example: An experienced nurse who performs urinary catheterization steps smoothly in the right order. Types of errors based upon these levels of performance include: - Knowledge-based mistakes: Errors that occur in novel situations due to deficits in knowledge; intended actions do not achieve the intended outcome. Example: A clinician prescribing the wrong (inappropriate) medication due to lack of knowledge about the drug of choice (the interactions with medications the patient is already taking). - Rule-based mistakes: Errors that occur in familiar situations due to incorrect application of a rule or an inadequate plan; actions do not achieve the intended outcome. Example: Making an incorrect diagnosis by failing to review all of the ordered diagnostic test results and proceeding with an inappropriate treatment plan based on incomplete information. - Skill-based mistakes: Errors that occur in experienced situations due to an attention slip or lapse of memory. Example: A nurse intending to give one medication but giving a different medication instead due to not reading the complete information on the unit-dose label. (Gregory & Kaprielian, 2016) Issues related to patients arise from: - Inappropriate patient identification - Incomplete assessments of the patient - Failure to obtain consent - Complexity of care in intensive care, which involves multiple disciplines and sources of information - Inadequate education of the patient - Patient characteristics that are beyond the control of staff Organizational Transfer of Knowledge Issues Errors can occur during the transfer of organizational, situational, or domain-specific knowledge and skills from one entity to another within or between organizations. Examples may include deficiencies in orientation of new or inexperienced staff or failure in quality or availability of protocols. Staffing and Workflow Factors Studies show that unmanageable patient workloads, worker fatigue, and high provider-to-patient ratios increase the risk for medical errors by putting workers into situations where they are more apt to make a mistake. Increased workload can lead to tasks being left undone. Interruptions occurring while providing care affect patient outcomes by interfering with a healthcare worker’s ability to complete essential tasks. Technical issues involve failures of medical devices, equipment, implants, or grafts due to poor design, defects in material, or incorrect construction or set-up of equipment. Information Flow Factors Errors occur when there is inadequate flow of information vital to a patient’s care on transfer to another facility or discharge from one area to another, resulting in errors in making decisions about treatment or during communication of test results. Policy and Procedure Factors Failures in the process of providing care can be the result of poorly documented, nonexistent, or clinically inadequate policies and procedures. COMMON MEDICAL ERRORS AND HOW TO PREVENT THEM Errors can be placed into five general categories: surgical, diagnostic, medication, devices and equipment, and systems failures (including healthcare-associated infections, falls, and healthcare technology). Common areas in each of these categories are described below. Wrong-site, wrong-procedure, and wrong-patient surgical errors are relatively rare. It is estimated that in the United States such errors occur in approximately 1 of 112,000 surgical procedures and are infrequent enough that an individual hospital would only experience one such incident every 5 to 10 years (AHRQ, 2017e). The number of cases in which a foreign body is left behind during a procedure is estimated at 1,500 per year. Sponges are the most common foreign body retained after surgery. Surgical instruments also can be left behind, especially in the abdominal cavity. Approximately 88% of retained foreign body cases occur in a situation where the sponge and instrument counts were declared to be “correct” at the end of the procedure (Zejnullahu et al., 2017). Perioperative peripheral nerve injury following anesthesia and surgery is a rare event and in many instances is related to the positioning of the patient during the surgical procedure (Welch, 2017). Anesthesia-related harm during surgery can include damage to teeth, nerve damage, organ damage, cardiopulmonary arrest, and death. Errors can lead to death or coma, but in recent decades improvements in operating room technology and education have led to fewer such events. Specialties with the highest risk of errors are neuro-, thoracic, and cardiovascular surgery followed by general surgery (Novak, 2016). PREVENTING SURGICAL ERRORS Surgical errors are not the sole responsibility of the operating surgeon. All operating room personnel have a role in ensuring patient safety by verifying the surgical site and pointing out a possible error. To reduce the risk of wrong-site, wrong-procedure, or wrong-person surgeries, the Joint Commission has developed a Universal Protocol checklist that includes the concept of a surgical “timeout,” a planned pause before beginning a procedure in order to review important aspects with all involved personnel. It was initially designed for operating room procedures but is now required before any invasive procedure (AHRQ, 2017e). The WHO Surgical Safety Checklist was likewise developed by an international team of researchers to decrease errors and adverse events and to increase teamwork and communication in surgery. Since its inception, it has shown significant reductions in both morbidity and mortality and is now used by a majority of surgical providers around the world to increase patient safety and reduce intraoperative complications. An electronic version of this checklist has shown an increased compliance rate and a reduction in the number of risk events. In addition, OR personnel have stated a belief in its ability to have a positive impact on patient safety (Gitelis et al., 2017). ELEMENTS OF THE SURGICAL SAFETY CHECKLIST A surgical checklist is an algorithmic listing of actions to be taken in any given clinical situation intended to make everyone aware that others expect these things to be done. “SIGN IN” checklist must be completed before induction of anesthesia (with at least a circulating nurse and anesthesia provider) - Has the patient confirmed his/her identify, site, procedure, and consent? - Is the site marked? - Is the history and physical present? - Is the anesthesia machine and medication check complete? - Are diagnostic and radiologic test results present? - Are blood products available? - Is the pulse oximeter on the patient and functioning? - Are all special equipment, devices, and implants present? - Does the patient have a: - Known allergy? - Difficult airway or aspiration risk? - Risk of >500 ml blood loss (7ml/kg in children)? “TIME OUT” checklist must be completed before skin incision (with circulating nurse, anesthetist, and surgeon) - Have all team members introduced themselves by name and role? - Has the patient’s name, procedure, and where the incision will be made been confirmed? - Has antibiotic prophylaxis been given within the last 60 minutes? - For the anticipated critical event: - What are the critical or nonroutine steps? - How long will the case take? - What is the anticipated blood loss? - Are there any patient-specific concerns? - Nursing team - Has sterility (including indicator results) been confirmed? - Are there equipment issues or any concerns? - Is essential imaging displayed? “SIGN OUT” checklist must be completed before the patient leaves the operating room (with circulating nurse, anesthesia provider, and surgeon) - Have the scrub and circulating personnel verbally confirmed: - The name of the procedure? - Completion of instrument, sponge, and needle counts? - Specimen labeling (read aloud specimen labels, including patient name)? - Whether there are any equipment problems to be addressed? - Have the surgeon, anesthetist, and nursing personnel discussed: - What are the key concerns for recovery and management of this patient? Source: WHO, 2017a. Cheryl, a left-hand-dominant author, was scheduled for a left carpal tunnel release to alleviate her left-hand pain. Immediately prior to her being transferred to the operating room, her surgeon verified the procedure and side with her and marked the surgical site with a purpose-made surgical site marker in accordance with facility policy. After the “time out” and induction of general anesthesia, the site was prepped and draped, the surgeon made a Z-shaped incision from the proximal phalanx of Cheryl’s left middle finger to the middle of her left palm and began to carefully dissect down through the soft tissue. The scrub, an experienced perioperative nurse, was perplexed by the placement of the incision, since the usual incision for a carpal tunnel release goes from the palm (in line with the ring finger) toward the wrist. The scrub did not say anything, since the surgeon was new to the facility, had just completed a fellowship in hand surgery, and had already performed several newly developed procedures with which the nursing personnel were not familiar. After examining the tissue in Cheryl’s palm, the surgeon commented on the lack of thickening of the ligament in the palm and the inconsistency between his findings and her reported symptoms of ring finger pain and difficulty in doing keyboard work. At this point, both the circulating nurse and anesthesia provider stated that the proposed procedure was a carpal tunnel release. This was confirmed by the surgeon, anesthesia provider, circulating nurse, and scrub visualizing the surgical schedule and Cheryl’s chart (history and physical, surgical consent, and surgical safety checklist). The surgeon closed the incision and made an appropriate incision for a carpal tunnel release, and the procedure was completed without further issue. After Cheryl was transported to the postanesthesia care unit (PACU), the surgeon spoke with her husband. He informed him of the incident and told him that a complete review of all that had transpired would be done that day. The surgeon later spoke to Cheryl and told her that he would give her a complete explanation the following day once all of the medications she had received were no longer affecting her understanding or memory. The surgeon met with Cheryl and her husband and adult daughter the following day. He described the nature of the error (that a trigger finger release incision was made instead of the carpal tunnel release incision intended), how it had occurred, and what steps would be taken to improve that aspect of OR safety. The night of surgery, the family had briefly considered filing a lawsuit, but after meeting with the surgeon, they were satisfied with the full and honest disclosure of the incident and decided not to sue. Diagnostic errors are common, accounting for 17% of preventable errors in hospitalized patients. A systematic review of autopsy results done over four decades found that almost 9% of the deceased patients experienced a major diagnostic error that was not detected prior to death (AHRQ, 2017f). Diagnoses can be unintentionally delayed (when sufficient information was available earlier), wrong (another diagnosis was made before the correct one), or missed (no diagnosis was made). Diagnostic errors can be broken down into three subcategories: - No-fault errors arise from factors that are outside the control of the clinician or the healthcare system. They can be attributed to masked or unusual presentation of a disease and to patient-related factors such as lack of cooperation or provision of misleading information. - System-related errors include technical or organizational barriers, such as communication and care coordination problems, inefficient processes, and equipment or technical failures. - Cognitive errors include inadequate knowledge, poor critical-thinking skills, lack of competency, problems in data collection, failure to synthesize data, and cognitive bias. A clinician’s cognitive biases (shortcuts or “rules of thumb”) can occur when making a provisional diagnosis, especially for a patient with common symptoms. Cognitive biases may include: - Diagnosis of current patient biased by experience with past cases (e.g., chest pain assumed to be cardiac in origin) - Relying on the initial diagnostic impression despite subsequent contradictory information (e.g., dismissing test results as being in error) - Diagnostic decision-making biased by subtle cues and collateral information (e.g., assumption of heroin withdrawal rather than a perforated bowel) - Placing undue reliance on test results or “expert” opinion (e.g., assuming the absence of a clinically obvious condition based on false-negative test results) Underlying problems in the healthcare delivery system increase the risk for missed or delayed diagnoses. These may include poor teamwork and communication, a situation found to be common in emergency medicine and surgery. A lack of reliable systems for common outpatient situations and lack of structured protocols for telephone triage, teamwork, and communication training also increase the risk (AHRQ, 2017d; NAS, 2015). Whatever causes an error in making a correct and timely diagnosis, the outcome can result in inappropriate treatment being given and failure or delay in appropriate treatment, which may reduce the number of treatment options a patient will be able to pursue (e.g., cancer treatments) (Singh, 2017). A serious outbreak of the Ebola virus was underway in Liberia in western Africa. A man traveled from Liberia back to his home in Texas, where he began to experience fever, nausea, and abdominal pains, prompting him to go to the emergency room. There he reported to the nurse his recent travel to Liberia but denied contact with sick people. He was misdiagnosed and sent home. Days later he returned to the emergency room, tested positive for Ebola, began receiving care but died soon after. Investigation of this misdiagnosis discovered that the patient’s travel history was obtained by the nurse and entered into his electronic medical record (EMR). The patient, however, had not mentioned the fact that he had had contact with an Ebola patient prior to leaving Liberia. Additionally, the examining doctor did not see the travel portion of the patient’s history because it was in the nursing section of the EMR, which doctors can, but often don’t, routinely check. Nurses are not required to inform doctors about everything they do and document. However, important information is generally personally communicated to the physician. Although the importance of this patient’s travel history should have been recognized because of the amount of publicity surrounding the Ebola outbreak, the nurse did not inform the doctor personally. Not all the information that nursing collects has to be reviewed by the doctor. Every facility makes choices about what information shows up routinely in what part of the EMR, and this hospital chose not to include the travel history in the physician section of the EMR. The nurse asked the right questions about travel, but the patient failed to disclose important information for an unknown reason. The nurse correctly entered the travel history into the medical record but failed to verbally inform the physician, and the physician chose not to read the nurse’s notes. All of these actions illustrate the importance of communication in the prevention of medical errors such as this misdiagnosis and delayed treatment. Medication errors are one of the most common types of error and are of primary concern to clinicians who administer medications, practitioners who prescribe medications, and pharmacists who dispense them. Medication errors cause at least one death every day and injure approximately 1.3 million people annually in the United States (WHO, 2017b). Medication errors are considered preventable adverse drug events. The National Coordinating Council for Medication Error Reporting and Prevention (2018) defines a medication error as: Any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the healthcare professional, patient, or consumer. Such events may be related to professional practice, healthcare products, procedures, and systems, including prescribing; order communication; product labeling, packaging, and nomenclature; compounding; dispensing; distribution; administration; education; monitoring; and use. At least a quarter of all medication-related adverse events are preventable. Preventable adverse events include errors made by the clinician and systematic errors. Potential adverse drug events are medication errors that pose a significant risk but do not cause harm to the patient. It is estimated that 28% of adverse drug events requiring hospital admission are preventable. In the hospital setting, more than a quarter of adverse drug events are preventable, and 27% of adverse drug events following discharge from the hospital were found to be preventable (Zhu & Weingart, 2017). The U.S. Food and Drug Administration (FDA) (2017a) notes that a medication error refers to an error of commission or omission at any step along the pathway that begins with prescribing a medication and ends when the patient receives the medication and is safely monitored following it. For each step along the pathways, there are also strategies recommended to prevent adverse drug reactions. Steps include: - Transcribing (order communication) - Packaging, repackaging and nomenclature - Use and monitoring ERRORS IN PRESCRIBING AND TRANSCRIBING The FDA (2017a) reports that the majority of errors occur at the prescribing and transcribing stages. Prescribing and transcribing errors include: - Incorrect drug selection for a patient - Errors in quantity and indication - Prescribing a contraindicated drug - Inaccurate or incomplete medication history taking - Illegible handwriting - Confusion with the dosing or drug names - Inappropriate use of decimal points - Use of abbreviations Illegible prescription: Avandia (a diabetic medication) confused with Coumadin (an anticoagulant), both available as 4 mg oral tablets. (Source: PNNet, 2003.) When prescribing, strategies recommended to prevent adverse drug reactions include: - Review the patient’s medication list at each encounter and consider the dosages, directions, drug interactions, and side effects. - Consider making notations on the prescription to indicate the reason for the medication. - Be vigilant about high-risk drugs and avoid prescribing them whenever possible. - Replace high-risk drugs with drugs that are less likely to cause adverse events. - Discontinue unnecessary medications. - Consider drugs as a cause of any new symptom. - Avoid treating side effects with another drug. - Educate patients on indications for each medication, possible side effects, and alternative options. - Use computerized prescriber order entry (CPOE) to improve the medication ordering process. CPOE improves safety by: - Providing a means for standardization of practice - Improving completeness and legibility of orders - Being alerted to drug allergies, drug-drug interactions, and cumulative dose limits - Updating clinicians with current medication information - Providing dosage adjustment calculations based on patient characteristics - Offering timely communication of critical changes in a patient’s condition There are many facilities that have instituted the practice of medication reconciliation at all transitions in care to prevent adverse drug events. Medication reconciliation is the process of identifying any discrepancies between the medication ordered and those on the patient’s medication list, making appropriate changes to the orders, documenting any changes, and communicating the updated list to the next provider within or outside the facility. Patients should also be provided with written information on the medications when discharged. Strategies to prevent medical errors when transcribing include: - Carefully check handwritten medication orders, clarify they are legible, and ensure they are interpreted correctly. - Double check all math calculations before entering the dosage into the nursing documentation form. - Utilize computerized medication records to eliminate the problem of misinterpretation. (Zhu & Weingart, 2017) Verbal orders are especially susceptible to errors. Steps to follow to ensure safety include: - Minimize the use of verbal orders whenever possible. - Have the prescriber repeat and verify the verbal order. - When possible, have another RN listen to the order. - Record the verbal order in the patient’s medical record, making sure to include: - Name of prescriber - Name of recipient of order - Name of person who implemented the order - Read back the order to the prescriber as written down to confirm correct documentation. ERRORS IN DISPENSING Dispensing errors can occur at any point along the dispensing pathway from when the prescription arrives in the pharmacy through the supplying of the dispensed medication to the patient or the healthcare worker who will administer it. Errors include: - Selecting the wrong medication or strength - Dispensing the wrong dose - Dispensing to the wrong patient - Failure to see dangerous complications such as harmful interaction of drugs - Failure to warn of dangerous side effects of drugs Errors happen due to: - Heavy workload and long hours - Insufficient pharmacist training - Negligence in supervising pharmacy technicians - Poor communication between pharmacists and prescribers - Over-reliance on automated systems Strategies to prevent medical errors when dispensing include: - Check that the prescription entry is correct. Errors in transcription account for many errors in dispensing. - Clarify any ambiguous information. Prescriptions that are illegible or ones that use nonstandard abbreviations and other symbols need verification. - Check prescriptions thoroughly and consider verification by another person. - Provide patient counseling. - Check for drug-to-drug interactions and allergies. - Supervise dispensing medications by pharmacist assistants. - Open containers and show them to the patient. Patients can raise an alert if the medication looks different from what they usually take. - Use different lettering and other strategies in order to reduce confusion between medications that look alike or sound alike. (“Tall man” lettering is the practice of writing part of a drug’s name in uppercase, e.g. chlorproMAZINE and chlorproPAMIDE.) MEDICATION MANAGEMENT IN NONHEALTHCARE SETTINGS Many health professionals work or consult in nonhealthcare settings such as adult daycare, summer camps, schools, group homes, board-and-care facilities, and jails. These facilities are usually licensed by the state but often use unlicensed staff members to dispense medications to patients. According to the National Coordinating Council for Medication Error Reporting and Prevention, medication errors are a significant problem in these settings. The council recommends that nonhealthcare settings: - Have written policies and procedures on medication management - Provide training to all personnel with responsibilities for medication management - Provide safeguards to prevent and detect theft and diversion of controlled substances - Encourage the reporting of medication errors to appropriate state and national medication error reporting programs to identify significant trends that can lead to improved quality and safety Source: NCCMERP, 2015. ERRORS IN ADMINISTRATION Medication administration errors are very common in both inpatient and outpatient settings. In hospitals, most medication errors occur in medical-surgical units, followed by intensive care and then intermediate care units. Ten percent of errors cause harm to patients, and 11% of errors require increased monitoring. More than half of errors do not cause harm to patients, and approximately one fifth of errors are identified before reaching patients (Volpe et al., 2016). A study that examined medication error (ME) incident reports made by RNs in hospital settings found that the most common drug class associated with MEs was cardiovascular drugs and that the most errors occurred with anticoagulants. Antimicrobial medications were the second most common drug class involved in errors, with vancomycin the most common in this category. Medication administration errors occurred more often in medical-surgical and intensive care units (Muroi et al., 2017). Errors in administration include: - Administration of the wrong drug - Failure to administer a prescribed drug - Administering via the wrong route - Failure to check the patient’s identity prior to administration - Wrong dosage calculation - Patient misuse due to poor understanding of directions - Deliberate violation of medication administration guidelines, policies, and procedures Factors that increase the risk for administration errors include: - Poor communication - Workload and time pressures - RN staffing - Distractions or interruptions by both healthcare staff and patients - Ambiguous product names, directions for use, medical abbreviations, or writing - Poor procedures or technique - Lack of standardized protocols and procedures - Lack of practitioner knowledge or training - Similar labeling or packaging of products - Illegible handwriting - Patient characteristics, including personality, literacy, language barriers, complexity of clinical case (Parry et al., 2015) At any point along the pathway from prescribing to administration, drugs with similar names or packing can lead to medication errors. Safe medication administration requires the nurse to have sound knowledge about a drug, including: - Mode of action - Side effects - Appropriate dosage - Rate and route of excretion - Interaction with other drugs Nurses should perform a three-way check prior to administering a medication, which includes the physician order compared with medication administration record compared with the pharmacy label. Each should be checked three times to ensure agreement. Serious administration errors can be avoided by following these rules: - Avoid interruptions and distractions. - Prepare medications for one patient at a time. - Administer the medication to the patient as soon as it has been prepared. - Never leave medications at the bedside. - Utilize barcode medication administration to guarantee accuracy. In the past, nurses were instructed to follow the “5 rights” of medication administration. Currently, the list has expanded to include “10 rights” (see box below). “10 RIGHTS” OF MEDICATION ADMINISTRATION 1. Right Patient - Check the patient’s identification bracelet. - Ask the patient to state his or her name and date of birth. - Compare the medication order to the identification bracelet and the patients’ stated name and date of birth. - Verify patient’s allergies with the chart and with the patient. 2. Right Medication - Perform a triple check of the medication’s label: - When retrieving the medication - When preparing the medication - Before administering the medication to the patient - Always check the medication label with the prescriber’s order. - Never administer a medication prepared by another person. - Never administer a medication that is not labeled. 3. Right Dose - Check the label for the concentration of the medication. - Compare the dispensed dose with the medication order. - Perform all medication calculations three times. - Check all medication calculations with another nurse. - Verify that the dosage is within the appropriate range for the medication and the patient. 4. Right Time - Verify the schedule of medication with the order for: - Date to be administered - Time to be administered - Specific length of time to be administered - Check when the last dose of the medication was given. - Administer the medication within 30 minutes of the scheduled time (30 minutes before or 30 minutes after). This does not refer to PRN medications that must be given within an exact time limit, e.g. every 4 hours. 5. Right Route - Verify the medication route with the medication order. - Confirm that the patient can take or receive the medication by the ordered route. 6. Right Assessment - Prior to medication being administered: - Assess patient and laboratory tests to determine if medication is safe and appropriate. - Confirm the rationale for the ordered medication. 7. Right Evaluation - After the medication has been administered: - Assess the patient for any adverse side effects. - Assess the patient for effectiveness of the medication. - Compare the patient’s prior clinical status with postmedication status. - Document the patient’s response to the medication. 8. Right Education - Inform the patient of the medication being administered. - Inform the patient of the desired effects of a medication. - Inform the patient of the side effects that may be expected from the medication. 9. Right to Refuse - Know that the patient or legally responsible person has the right to refuse any medication. - Inform the responsible person of the consequences of refusing the medication. - Verify that the responsible person understands the consequences. - Notify the ordering clinician of the refusal and document that notification. 10. Right Documentation - Time given - Site of injection, if applicable - Laboratory value or vital signs needed prior to administration, if indicated - Document the refusal of a medication and that the responsible party understands the consequences. - Never document before a medication has been administered. - Document the patient’s response to the medication. Source: Nwagwu, 2016. ERRORS IN MONITORING Monitoring and assessment are essential to the process of administration of medications. Errors can occur regarding the assessment of vital signs, lab values, ability to swallow, and patient’s self-report. Monitoring involves observing the patient to determine if the medication is working, being used appropriately, and not harming the patient. Types of errors in monitoring that can occur include: - Inadequate monitoring for side effects - Drug levels not measured, or measured but not checked or acted upon - Failure to educate patients about potential side effects - Failure to monitor patient’s subjective response - Drug not discontinued if not effective or prescribed course completed - Drug ceased before the course was completed - Communication failures during handoff procedures to accepting nurse In a large Midwestern city, a nurse working on the obstetrics unit of a local hospital was halfway through the second of two eight-hour shifts and asked to go home because she was tired. The hospital denied her request, stating staffing would be inadequate (fatigue and RN staffing). The nurse was assigned a young female in active labor. The patient stated that she had spoken to her doctor beforehand and had agreed to an epidural for delivery. In order to save time (workload and time pressures), the nurse took a bag of epidural anesthesia from a storage locker without a doctor’s order, brought it to the patient’s room, and laid it on the work counter (deliberate violation of medication administration guidelines, policies, and procedures). The IV bag had a bright red label that read “for epidural use only.” In the meantime, an IV antibiotic was ordered and delivered to the patient’s room. The nurse picked up what she believed was the IV antibiotic (similar packaging or product) and hung it (deliberate violation of medication administration guidelines, policies, and procedures). Shortly thereafter, the patient had a seizure and died. Her infant was delivered live by Caesarean section. The investigation of the incident revealed that the nurse: - Was fatigued and under time pressure - Failed to follow hospital procedures requiring a doctor’s order before removing drugs from the storage locker - Failed to recognize the bright red intrathecal warning label on the IV bag - Failed to follow the hospital’s policy and procedure to scan medication labels before drugs were administered - Failed to follow the “rights” of medication administration as described in the hospital’s policy and procedure manual Investigation further revealed that shortcuts were common practice on the unit. Initially the nurse was charged with a felony, which was later reduced to civil charges, and her license was suspended. ERRORS AND HIGH-ALERT MEDICATIONS The Institute for Safe Medication Practices (ISMP) defines a high-alert medication as a drug that has a heightened risk of causing significant patient harm when used in error. Although errors may or may not be more common with such medications, the consequences of errors are much more devastating. High-alert medications are at the top of the list of drugs involved in moderate-to-severe patient outcomes when an error occurs. The ISMP lists high-risk medications according to what is commonly used in acute care settings, community settings, and long-term settings. The Joint Commission standards require a hospital to develop its own list of high-alert medications, to have a process for managing them, and to implement that process. Many hospitals select medications from the ISMP’s list, which is updated every few years based on error reports submitted to ISPM, reports of harmful errors in the literature, and input from practitioners and safety experts. It is agreed that it is essential for every hospital’s list to include (when used): - Concentrated electrolytes - Neuromuscular blocking agents - All opioids - All anticoagulants - Epidural or intrathecal medications - Chemotherapeutic drugs Other drugs should be added if use is prevalent or misuse is a concern. A hospital should update its high-alert medication list as needed and review the list at least every two years (Grissinger, 2017). Safe System Design for High-Alert Medications The Institute for Healthcare Improvement provides a how-to guide for the prevention of harm from high-alert medications, recommending three principles of safe system design: 1) design processes to prevent errors and harm, 2) design methods to identify errors and harm when they do occur, and 3) design methods to lessen the harm that may result from the error. Processes to prevent errors and harm: - Standardize the approach to treatment by developing order sets, preprinted orders, clinical pathways, or protocols. - Standardize concentrations and dose strength to the minimum needed for safe care. - Centralize pharmacist- or nurse-run anticoagulation, insulin management, and pain management services. - Implement protocols for vulnerable populations (elderly, pediatric, obese patients). - Use “tall man” lettering for pharmacy-produced labels for differentiation of drug names that look alike or sound alike. Methods to identify errors and harm when they do occur: - Include in order sets, protocols, and flow sheets reminders and other information about monitoring parameters. - Ensure availability of critical lab information. - Use independent double-checks. - Educate patients to monitor for symptoms and when to contact their provider. Methods to lessen the harm that may result from the error: - Utilize protocols allowing for administration of reversal agents without having to contact the physician. - Ensure rescue protocols are available. FDA Warnings for High-Risk Medications The FDA requires high-risk medications with serious or life-threatening risks be given a label referred to as a black box warning, the FDA’s strongest labeling requirement. Before adding a box warning, however, the FDA must have evidence that the drug poses a significant risk. This comes from observations and studies conducted after the drug has been on the market. Unfortunately, this means that new drugs that have just been put on the market rarely will have these warnings. Despite these warnings, however, it has been shown there has been no associated reduction in prescribing such medications. This may be attributed to: - Unawareness by prescribers that the FDA has issued the warnings - Prescribers thinking that even though there is a high risk, the drugs have a superior benefit-risk ratio to alternative medications - Prescribers thinking that the safety concern is not as severe as the warning suggests - Prescribers choosing to continue prescribing them while using strategies to reduce risk, such as close monitoring of patients Recommendations for Administering High-Alert Medications When administering high-alert medications, the following is recommended: - Identify high-alert medications based on the facility’s approved list. - Monitor medication dosing carefully, especially if dosing adjustments are required due to narrow therapeutic windows. - Obtain and review any laboratory values required for dosing adjustments; collaborate with the prescriber if values are out of the therapeutic range. - Before administering a high-alert medication, ask another nurse to perform an independent double-check to verify: - The patient’s identity - The medication is correct - Medication’s indication corresponds with the patient’s diagnosis - Dosage calculations are correct - Route of administration is safe and appropriate for the patient - If giving an infusion, that pump settings are correct and the infusion line is attached to the correct port - Watch for adverse effects. (Lippincott Solutions, 2015) PREVENTING ADVERSE EVENTS DUE TO PATIENT-CONTROLLED ANALGESIA The Physician-Patient Alliance for Health and Safety (PPAHS) reports a cause for concern in patients using patient controlled analgesia (PCA), and there is a great lack of consistency in safety procedures followed by hospitals across the country. This is believed to account for a large proportion of adverse events and deaths related to its use. There is evidence that hospitals that continuously monitor their patients with pulse oximetry and/or capnography are better able to avert adverse events. Checklists for safe use of PCA pumps are available. The PPAHS checklist recommends certain steps be taken when initiating, refilling, or reprogramming PCA pumps, and PCA checks to be taken at shift change and hourly. PCA pump initiation, refilling, or programming a change require: - Assessment of the patient for increased risk of respiratory distress: - Low body weight - Current medication that can potentiate sedative effects - Preexisting conditions such as asthma, COPD, and sleep apnea - Advanced age - Pre-procedural cognitive assessment to determine the capability of patient to participate in pain management (may not be suitable for pediatric patients) - Provision of information to the patient on proper use of the PCA and purpose of monitoring - Two healthcare providers independently double check: - Patient’s identification - Drug selection and concentration confirmed as prescribed - Any dose adjustment completed - PCA pump settings - Line is attached to the patient and tubing is inserted into pump - Electronic monitoring: - Pulse oximetry Change of shift and every hour require: - Assessing patient for level of pain, alertness, and adequacy of ventilation - Verifying PCA pump settings - Verifying electronic monitoring of pulse oximetry and capnography - Documenting patient assessment and condition, PCA dosing, and monitoring Source: PPAHS, 2016. The FDA reports that medical device misconnections can occur when one type of medical device is attached in error to another type of medical device that performs a different function. Tubing misconnections can occur for several reasons, including: - Similar design of many connectors and the widespread use of connectors with similar shapes and in similar sizes - Human error arising from conditions such as: - Multiple connections for one patient - Poor lighting - Lack of training - Time pressure - High-stress environment EXAMPLES OF TUBING MISCONNECTIONS - Enteral feeding tube connected to an IV - Enteral feeding tube connected to ventilator-inline suction catheter - Blood pressure cuff connected to an IV - IV tubing connected to trach cuff - IV tubing connected to nebulizer - Oxygen tubing connected to a needleless IV port - IV tubing connected to nasal cannula - Syringe connected to trach cuff - Epidural solution connected to a peripheral or central IV catheter - Epidural line connected to an IV infusion - Bladder irrigation solution utilizing primary IV tubing connected to a peripheral or central IV catheter - Foley catheter connected to NG tube - IV infusion connected to an indwelling urinary catheter - IV infusion connected to a nasogastric tube - Primary IV tube connected to a blood product meant for transfusion Patient’s feeding tube is incorrectly connected to the instillation port on the ventilator in-line suction catheter, delivering tube feeding into the patient’s lungs, causing death. (Source: FDA, 2017b.) PREVENTING TUBING MISCONNECTIONS Because tubing misconnections continue to cause patient injury and death, new International Organization for Standardization (ISO) tubing connector standards went into development in 2014. These new standards for manufacturing connectors are meant to make it physically impossible for misconnections to occur. It is predicted that as they become more available, the likelihood of risk for misconnection errors is expected to decrease (FDA, 2017b). Bringing new, safer connectors to the healthcare market requires coordination between manufacturers, medical-device companies that incorporate connectors into their equipment, and healthcare facilities. As a result, the transition to new and safer connectors has been slow. Some facilities have not yet started the process of evaluating how long their current inventory of tubing and connectors will last in order to determine when to make the changeover. Internationally, the shift to new connectors is inconsistent, with just a few countries now introducing mandates or campaigns to encourage use of new connectors. California is the only state requiring facilities to switch to new enteral feeding and epidural connectors in 2016 and 2017 (MD+DI, 2016; California Legislature, 2015). In those instances where the old connectors remain in use, the Joint Commission and the ECRI Institute (formerly the Emergency Care Research Institute) recommend the following safety measures for nurses and other healthcare providers: - Clearly label each device, especially certain high-risk catheters such as epidural, intrathecal, and arterial. - Do not use catheters that have injection ports. - Trace all lines back to their origin before connecting any new devices or replacing old ones. - Check and recheck Luers to ensure proper connections prior to each use. - Develop a policy of positioning different lines on different sides of the patient, or route tubes and catheters with different purposes in unique and standardized directions (e.g., IV lines routed toward the head, enteric lines toward the feet). - Ensure good communication between healthcare staff during patient transfers. - Recheck connections and trace all patient tubes and catheters to their sources upon the patient’s arrival in a new setting or service as part of the handoff process. Standardize this line reconciliation process. - Inform nonclinical staff, patients, families, and caregivers they must get help from clinical staff whenever there is a real or perceived need to connect or disconnect devices or tubing. - Do not force connections; if it is difficult or not secure, it may not be the right pairing. - Do not use adaptors unless they are very clearly intended for the application. - Identify and minimize conditions and practices that may contribute to healthcare worker fatigue and take appropriate action. Problems Related to Medical Devices and Equipment Design flaws, misuse, and malfunction of medical devices and equipment are all common causes of medical errors. Subtle differences in a familiar pattern using a device can affect the speed and accuracy of data entry, and the lack of standardization invites user mistakes. Poor medical device design and lack of usability testing have also been repeatedly discussed as being key factors in many device-related incidents. An increasing number of medical devices are also implanted in patients. These include complex programmable cardiac pacemakers, defibrillators, deep brain stimulation neurotransmitters, and laser surgical devices. Any malfunction of such devices can be serious and even life threatening. The FDA regulates devices that support or sustain human life, are of substantial importance in preventing impairment of human health, or present a potential unreasonable risk of illness or injury by using a process of scientific and regulatory review to evaluate safety and effectiveness. The FDA has three levels of classification for medical devices and equipment: - Class I devices include those with “low risk,” such as bedpans, bandages, and examination gloves. - Class II devices are a higher risk and include such things as infusion pumps, powered wheelchairs, and surgical drapes. - Class III devices are seen as “life sustaining.” These have the highest risk and are therefore subject to the most stringent regulatory controls. Such devices include pacemakers and artificial heart valves, among many others. Medical devices have become more and more complex and are increasingly used in a life-sustaining way. New, innovative devices have increased rapidly in every area of medical practice, bringing with them the risk for complications and failures. Along with a rise in Class III devices, there has been an increase in the number of adverse events reported to the FDA. Each year, the FDA receives several hundred thousand medical device reports of suspected device-associated deaths, serious injuries and malfunctions, with nearly 700,000 reports of medical device adverse events being reported in 2017. Mandatory reporting of such events must be done by manufacturers, importers, and device user facilities. Healthcare professionals, patients, caregivers, and consumers are also encouraged to voluntarily report adverse events. The FDA uses the reported information to monitor device performance, detect potential device-related safety issues, and contribute to benefit-risk assessments of these products (FDA, 2016; FDA 2017c). Health professionals should familiarize themselves with their institution’s procedures for reporting adverse events to the FDA. Under the Safe Medical Devices Act of 1990, facilities (hospitals, ambulatory surgical centers, nursing homes, or outpatient centers) are required to: - Report to the FDA and to the manufacturers any suspected medical device–related deaths - Report medical device–related serious injury only to the manufacturer, if known; if the manufacturer is unknown, report serious injury to the FDA - Submit an annual report to the Secretary of Health and Human Services summarizing adverse events attributed to medical devices Jory, a 17 year-old boy, fractured his arm in several places following a tackle and fall while playing football. He was taken to the nearby hospital, where he underwent surgical repair. Postoperatively he was placed on morphine delivered via a pump. His heart rate, respirations, and blood oxygen levels were being monitored. Through the evening hours, Jory was alert, oriented, and had stable vital signs. When the night shift took over, it was ordered that the morphine should be shut off and that he should be placed on routine vital sign checks and oral pain medication. During the night, the nurse entered his room to assess his vital signs and found that he was nonresponsive and barely breathing. It was discovered that the morphine pump, a newly acquired piece of equipment, had not been shut off but had accidently been turned to the “high” setting. Jory was lucky; he survived the overdose. The following investigation found that the new device was designed differently than the old one, with an additional step required in the shut-off process, and the nurse had not received training in the use of the new pump. Healthcare-Associated Infections (HAIs) HAIs are infections that a patient gets while receiving medical treatment in a healthcare facility. HAIs are considered system failures and are often preventable. The CDC reports that on any given day approximately 1 in 25 hospital patients has at least one healthcare-associated infection. Common types of HAIs include: - Catheter-associated urinary tract infections (CAUTIs). Among UTIs acquired in the hospital, about 75% are associated with a urinary catheter, and the most important risk factor is prolonged use. - Surgical site infections (SSIs). These can be superficial incisional, deep incisional or organ or space SSIs. - Central line–associated bloodstream infections (CLABSIs). Central lines pose the greatest risk of device-related infections compared to other types of medical devices. They are the main source of bacteremia and septicemia in hospitalized patients and a major cause of morbidity and mortality. - IV catheter–related bloodstream infections (CRBSIs). - Clostridium difficile (C. diff) infections (CDIs). Those most at risk are patients—especially older adults—who take antibiotics and also receive medical care. CDIs are related to poor antibiotic prescribing practices. Many studies have shown that 30% to 50% of antibiotics prescribed in hospitals are unnecessary or incorrect. - Pneumonias. Healthcare-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) both may be caused by a wide variety of pathogens, can be polymicrobial, and can be due to multidrug-resistant organisms (MDROs). Among all hospital-acquired infections, HAP is the leading cause of death. (CDC, 2015; File, 2017) Efforts have been made to reduce these infections, and research shows that when healthcare facilities and teams, individual doctors, and nurses become aware of the issue and take steps to prevent them, rates of some HAIs can decrease by more than 70%. In 2017, the CDC reported a national decrease of 50% in central line–associated bloodstream infections since 2008 as a result of those efforts. The financial benefit of this decrease is estimated to be $25 billion to $31 billion in medical cost savings (CDC, 2017a). Failure of physicians, nurses, and other caregivers to practice basic hand hygiene helps spread bacteria, some of which are antibiotic-resistant and can prove life threatening. Studies show that on average healthcare providers clean their hands less than half of the times they should, contributing to the spread of HAIs (CDC, 2017b). PREVENTING CATHETER-ASSOCIATED URINARY TRACT INFECTIONS The CDC (2016a) recommends the following actions supported by evidence-based research for preventing urinary tract infections: - Insert catheters only for appropriate indications. - Leave catheters in place only as long as needed. - Avoid use of urinary catheters in patients and nursing home residents for management of incontinence. - Avoid routinely using urinary catheters in operative patients unless necessary. - For operative patients requiring an indwelling catheter, remove as soon as possible, preferably within 24 hours. - Perform hand hygiene immediately before and after insertion or any manipulation of catheter device or site. - Ensure that only properly trained persons insert and maintain catheters. - In acute-care hospital settings, insert catheters using aseptic technique and sterile equipment - In nonacute-care settings, use clean technique for intermittent catheterization. - If ultrasound bladder scanners are used, ensure that equipment is adequately cleaned and disinfected between patients. - Follow aseptic insertion; maintain a closed drainage system. - If breaks in aseptic technique, disconnection, or leakage occur, replace the catheter and collection system. - Maintain unobstructed urine flow. - Keep collecting bag below level of bladder at all times. - Do not rest collecting bag on the floor. - Empty collecting bag regularly using separate, clean container for each patient; avoid contact of spigot with the container. - Obtain urine samples aseptically. If small amount needed, aspirate from needleless sampling port with sterile syringe/cannula adapter after cleaning the port with a disinfectant. - If obstruction occurs and catheter material is contributing to obstruction, change the catheter. - Comply with CDC hand hygiene recommendations and Standard Precautions. - Alternatives to indwelling urinary catheterization in selected patients - Urinary catheter systems with preconnected, sealed catheter-tubing junctions - Use of portable ultrasound devices for assessing urine volume to reduce unnecessary catheterizations - Use of antimicrobial/antiseptic-impregnated catheters Brenda is a nursing assistant instructor at the local technical college. Today she has taken a group of students to their clinical site, the Marshall Green Nursing Home, which has had a higher than usual number of urinary tract infections over the last several months. One of her students, Annie, is assigned to an elderly gentleman who has an indwelling urinary catheter in place. The care plan indicates he should use a bedside drainage bag during the night and a leg bag during the day. The nursing assistant assigned to the patient tells Brenda his leg bag is in the bedside stand wrapped in a towel. When Annie locates the bag, it is in a washbasin wrapped in a towel. She finds there is no cap on the end of the tubing that is to be inserted into the catheter, and she shows this to Brenda. Annie has been taught that the end of the tubing must be protected by capping it with a sterile cap in order to maintain a closed system and to prevent bacteria from contaminating the system. Brenda approaches the nursing assistant and tells her about the lack of the cap and the risk for infection. The nursing assistant replies, “We never put a cap on the end of it.” Brenda tells Annie to obtain a new leg drainage bag, instructing her to ensure that she cleans the end of the bedside drainage bag connection and caps it with the cap removed from the new leg-bag tubing before storing it in the bedside cabinet. She then brings the contaminated leg bag to the supervising nurse, who says she will report it and speak to the nursing assistant about it. With the help of Brenda, Annie completes an incident report. PREVENTING SURGICAL SITE INFECTIONS CDC (2017c) recommendations for preventing surgical site infections include: - Administer antimicrobial prophylaxis in accordance with evidence-based standards and guidelines. - Avoid inappropriate use of broad-spectrum antibiotics or prolonged courses of prophylactic antibiotics. - Instruct patients to shower or bathe with soap or an antiseptic agent prior to operation. - Avoid hair removal at the operative site unless it will interfere with the operation; use clippers, not razors. - Use the appropriate antiseptic agent and technique for skin preparation in the period prior to surgery and immediately before the placement of surgical drapes. - Keep OR doors closed during surgery except as needed for passage of equipment, personnel, and the patient. - Use at least a 50% fraction of inspired oxygen intraoperatively and immediately postoperatively in select procedure(s). - Exclude surgeons or other care providers with infections. - Use closed suction drains. - Do not apply topical antimicrobial agents to the surgical incision. - Delay primary closure for heavily contaminated wounds. - Consider the use of triclosan-coated sutures. - Perform hand hygiene with each patient contact. - Maintain immediate postoperative normothermia. - Protect primary closure incisions with sterile dressing. - Control blood glucose level during the immediate postoperative period - Discontinue antibiotics according to evidence-based standards and guidelines. PREVENTING CENTRAL LINE–ASSOCIATED BLOODSTREAM INFECTIONS CDC (2016d) guidelines for prevention of CLABSIs include a checklist that covers the following: - Promptly remove unnecessary central lines. - Perform daily audits to assess if each central line is still needed. - Follow proper insertion practices. - Perform hand hygiene before insertion. - Adhere to aseptic technique. - Use maximal sterile barrier precautions (mask, cap, gown, sterile gloves, and sterile full body drape). - Perform skin antisepsis with >0.5% chlorhexidine with alcohol. - Choose the best site to minimize infections and noninfectious complications. - Avoid femoral site in obese adult patients. - Cover the site with sterile gauze or sterile, transparent, semipermeable dressings. - Handle and maintain central lines appropriately. - Comply with hand hygiene requirements. - Bathe ICU patients over 2 months of age with chlorhexidine preparation on a daily basis. - Scrub the access port or hub immediately prior to each use with an appropriate antiseptic (chlorhexidine, povidone iodine, an iodophor, or 70% alcohol). - Access catheters only with sterile devices. - Replace dressings that are wet, soiled, or dislodged. - Perform dressing changes under aseptic technique using clean or sterile gloves. - Ensure healthcare personnel are educated about indications for central lines, proper procedures for insertion and maintenance, and appropriate infection prevention measures. - Empower staff to stop nonemergent insertion if proper procedures are not followed. - “Bundle” supplies (e.g., in a kit) to ensure items are readily available for use. - Provide the checklist above to clinicians to ensure all insertion practices are followed. - Ensure efficient access to hand hygiene. - Monitor and provide prompt feedback for adherence to hand hygiene. - Provide recurring education sessions on central line insertion, handling, and maintenance. - Use 2% chlorhexidine for bathing ICU patients over 2 months of age. - Use antimicrobial/antiseptic-impregnated catheters. - Use chlorhexidine-impregnated dressings. PREVENTING IV CATHETER–RELATED BLOODSTREAM INFECTIONS - For peripheral catheters, an upper extremity site is preferred in adults. In pediatric patients, the upper or lower extremities or the scalp (in neonates or young infants) can be used. - Avoid steel needles when administering fluids and medications that might cause tissue necrosis if extravasation occurs. - Wear clean gloves, rather than sterile, for insertion. Use sterile gloves when touching the catheter site after prepping the skin. - Prep skin at insertion site with an alcohol/chlorhexidine solution, scrubbing back and forth for 30 seconds, and then air dry. If chlorhexidine is contraindicated, use tincture of iodine or 70% alcohol. - Use sterile transparent dressing. If patient is diaphoretic or site is bleeding or oozing, use sterile gauze dressing until resolved. - Do not use topical antibiotic ointment or creams on catheter insertion sites. - Use closed IV catheter systems with integrated extension sets and stabilization platforms. - Minimize contamination risk by scrubbing the access port with an appropriate antiseptic. - Replace peripheral catheters no more frequently than every 72 to 96 hours. Replace peripheral catheters in children only when clinically indicated. - Change needleless components at least as frequently as the administration set. - Evaluate site by palpation and inspection at least every 2 hours with continuous infusions, or at least twice in a 24-hour period when IV site is locked for intermittent infusions. - Remove peripheral venous catheters if patient develops signs of phlebitis, infection, or a malfunctioning catheter. - Encourage patients to report any changes in their catheter site or any new discomfort. - Assess the necessity of peripheral IV lines on a daily basis or per facility policy. - Do not submerge catheter or catheter site in water when bathing or showering. - Do not hang IV fluids mixed by pharmacy or nursing longer than 24 hours, unless otherwise indicated. - Do not hang premixed fluids for adults longer than 96 hours. - Change tubing for adults every 96 hours for continuous infusions or every 24 hours for intermittent infusions. (CDC, 2017d; CHCS, 2015) PREVENTING CLOSTRIDIUM DIFFICILE INFECTIONS - Use antimicrobials only as necessary. - Perform hand hygiene per CDC/WHO recommendations. (Note that not all hand hygiene products are effective against C. diff.) - Since spores may be difficult to remove from hands even with handwashing or hand sanitizer, adhere strictly to glove use. - Presumptively isolate symptomatic patients pending confirmation of CDI. - Isolate patients with CDI and initiate Contact Precautions immediately. - Private rooms are preferred for patients with fecal incontinence. - Maintain Contact Precautions until discharge, as patients continue to shed spores following treatment. - Use disposable or dedicated patient care equipment (e.g., stethoscopes, BP cuffs, and thermometers). - Clean room surfaces thoroughly on a daily basis and upon discharge or transfer. - Clean and disinfect equipment and environment using EPA-approved sporicidal disinfectant. - Communicate Contact Precautions at shift handoff and notify new facility on transfer. - Implement an antimicrobial stewardship program. PREVENTING MULTIDRUG-RESISTANT ORGANISM INFECTIONS - Comply with hand hygiene as recommended by the CDC. - Implement Contact Precautions when working with patients with MDRO infection and for those who have been previously identified as being colonized. - Use antibiotics only when needed and for the shortest time possible. - Place patients with an MDRO infection in a private room or share a room with others who have the same infection. When this is not possible, place in rooms with patients who are at low risk for acquiring an MDRO and who are likely to have short lengths of stay. - Dedicate noncritical medical items (e.g., BP cuffs, stethoscopes, thermometers) for patients known to be infected or colonized with MDROs. - Clean and disinfect all patient care items, equipment, and room surfaces every day; utilize a checklist to ensure compliance. - Wear masks when performing splash-generating procedures, when caring for patients with open tracheostomies or potential projectile secretions, and in circumstances where there is evidence of transmission from heavily colonized sources such as burn wounds. PREVENTING VENTILATOR-ACQUIRED LUNG INFECTIONS - Follow routine infection control practices and hand hygiene. - Keep head of bed elevated 30 to 45 degrees. - Assess daily readiness for extubation. - Change ventilator circuit if visibly soiled or mechanically malfunctioning. - Use sterile suctioning techniques and handling of respiratory equipment. - Perform oral care at least every 2 to 4 hours with an antiseptic swab to clean the oral cavity and teeth. Brush the teeth twice a day. - Combine respiratory therapy with nursing in performance of oral care. Falls are common, especially for older adults, both in the community and in healthcare settings. The CDC estimates that 1 in 3 U.S. adults age 65 or older and 50% to 75% of nursing home residents fall every year. AHRQ states that between 70,000 and 1 million people fall in hospitals each year (ECRI Institute, 2016). According to the Joint Commission (2015a), hundreds of thousands of patients fall in hospitals each year, 30% to 50% of which result in injury. Between 2009 and 2015, TJC received 465 reports of falls with injuries, the majority occurring in hospitals, with 63% resulting in death. Hip fractures are one of the most common types of serious injury resulting from a fall. Fall-related injuries result in significant healthcare costs, and according to the CDC (2017g), costs for fall injuries for individuals 65 or older are $34 billion annually. The Joint Commission reports the average cost for a fall resulting in injury is $14,000. In 2008 the Centers for Medicare and Medicaid Services stopped reimbursing for care resulting from injuries occurred from in-hospital falls if the fall could have been prevented. The Joint Commission identifies the most common contributing factors to falls with injury as follows: - Inadequate assessment - Communication failures - Lack of adherence to protocols and safety practices - Inadequate staff orientation, supervision - Inadequate staffing levels or skill mix - Deficiencies in the physical environment - Lack of leadership The CDC and ECRI Institute consider both intrinsic and extrinsic risk factors. Intrinsic factors include issues that generally cannot be changed and concern the patient’s medical, psychological, and physical issues. Extrinsic factors that generally can be changed address environmental risks that patients encounter. Examples include: Intrinsic Risk Factors - Advanced age - Previous falls - Muscle weakness - Gait and balance problems - Poor vision - Postural hypotension - Chronic conditions such as arthritis, stroke, incontinence, diabetes, Parkinson’s disease, dementia - Fear of falling Extrinsic Risk Factors - Lack of stair handrails - Poor stair design - Lack of bathroom grab bars - Dim lighting or glare - Obstacles and tripping hazards - Slippery or uneven surfaces - Psychoactive medications - Improper use of assistive devices - Ill-fitting or inappropriate footwear - Prolonged length of stay - Use of restraints - Attachment to equipment such as heart monitor or intravenous lines (ECRI Institute, 2016; TJC, 2015a; CDC, 2017c) Older patients are not the only population at risk. Any patient who has had excessive blood loss may experience postural hypotension, increasing the risk of falling. Maternity patients or other patients who have epidural anesthesia are at risk for falls due to decreased lower-body sensation. PRACTICE ERRORS IN REHABILITATION THERAPY Practice errors occur throughout the healthcare industry, including the fields of physical and occupational therapy. However, compared to other healthcare professions, few studies have been conducted to examine the nature of those practice errors, and there are few articles in the allied health literature that address the topic of error or the analysis of error using a system approach. Of those studies that have been done, most errors in both occupational and physical therapy practice realms have been shown to occur in the intervention phase of the therapy, which includes: Errors have been attributed to: - Lack of preparation - Lack of experience - Overload or time constraints - Insufficient or miscommunication - Lack of knowledge - Issues related to the patient - Inadequate preparation It has been noted that physical therapists may be less involved than other medical providers in error reduction efforts because physical therapy is often perceived as a lower-risk profession in that the errors made by therapists may be less likely to be life-threatening (Van Zytveld et al., 2016). Preventing falls involves assessing patients for risk for falls, developing a personalized plan of care, and utilizing consistent preventive interventions. A fall risk assessment should be done on admission, and reassessment should be done whenever there is a change in a patient’s condition or when a patient is being transferred to another unit. A reliable, standardized, and validated assessment scale should be used that includes a history of falls, mobility problems, use of assistive devices, medications, and mental status. While some institutions have created their own assessment tools, tools that have been studied the most are recommended. These include: - Morse Fall Scale - STRATIFY Scale - Henrich II scale - Medication Fall Risk Scale and Evaluation Tools - Delirium Evaluation Bundle Additional tools found to be valid for use in outpatient settings include: - Timed Up & Go (TUG) - 4-Stage Balance Test - Berg Balance Test (CDC, 2017h; CDC, 2017i; Physical Therapy Haven, 2017) Although there are several pediatric falls assessment tools, none have been found to be reliable and valid across institutions and diverse populations (DiGerolamo & Davis, 2017). MORSE FALL SCALE (MFS) The MFS is used widely in both hospital and long-term care inpatient settings. The MFS requires systematic, reliable assessment of a patient’s fall risk factors upon admission, after a fall, upon change in status, and at discharge or transfer to a new setting. MFS subscales include assessment of: \|History of falling, immediate or within 3 months \|No = 0\| \|Yes = 25\| \|Secondary diagnosis\|\|No = 0\| \|Yes = 15\| \|Ambulatory aid\|\|None, bed rest, wheelchair, nurse = 0\| \|Crutches, cane, walker = 15\| \|Furniture = 30\| \|IV/heparin lock\|\|No = 0\| \|Yes = 20\| \|Gait/transferring\|\|Normal, bed rest, immobile = 0\| \|Weak = 10\| \|Impaired = 20\| \|Mental status\|\|Oriented to own ability = 0\| \|Forgets limitations = 15\| \|MFS Score\|\|Risk Level\|\|Action\| \|0–24\|\|None\|\|Basic nursing care\| \|25–50\|\|Low\|\|Standard fall prevention interventions\| \|51+\|\|High\|\|High-risk fall prevention interventions\| Source: AHRQ, 2017g. Fall Prevention Plan AHRQ (2017g) states that the cornerstone of any hospital’s fall prevention program is the use of universal fall precautions because they apply to all patients at all times, regardless of fall risk. These precautions include: - Familiarize the patient with the environment. - Have the patient demonstrate call light use. - Maintain call light within reach. - Keep the patient’s personal possessions within patient safe reach. - Have sturdy handrails in patient bathrooms, room, and hallway. - Place the hospital bed in low position when a patient is resting in bed; raise bed to a comfortable height when the patient is transferring out of bed. - Keep hospital bed brakes locked. - Keep wheelchair wheel locks in locked position when stationary. - Keep nonslip, comfortable, well-fitting footwear on the patient. - Use night lights or supplemental lighting. - Keep floor surfaces clean and dry; clean up all spills promptly. - Keep patient care areas uncluttered. - Follow safe patient handling practices. Once risk assessment is completed and universal fall precautions are in place, additional interventions are tailored to individual patient’s needs. Examples may include: - More intense supervision such as sitters or 15-minute checks for a cognitively impaired patient who is agitated or tries to wander - Participation in a mobility program through physical or occupational therapy for a patient with impaired gait or mobility at risk for deconditioning - An hourly (scheduled) rounding protocol for all patients, during which toileting needs are assessed PHYSICAL AND OCCUPATIONAL THERAPY FALL INTERVENTIONS Both physical and occupational therapists have a significant impact in preventing falls. Physical therapists help prevent falls by: - Assessing individual patients for risk factors - Making a patient’s home as safe as possible - Measuring strength and assessing balance and mobility - Designing individualized exercises and balance training - Providing patient education about medical risk factors linked to falls - Working with other healthcare professionals and community services to create programs for people who want to reduce the risk of falling Occupational therapists consider how the person functions in their day-to-day environment. They assess for hazards and patient limitations that contribute to falls and offer education in safety to patients and/or caregivers during activities of daily living. Occupational therapists can also earn specialty certification in fall prevention. Fall risk factors addressed by occupational therapy include: Intrinsic Risk Factors - Lower-extremity weakness - Impaired balance - Cognitive impairment - Urinary incontinence - Sensory impairment - Fear of falling - Side effects of medication Extrinsic Risk Factors - Throw rugs and loose carpeting - Lighting and glare - Uneven sidewalks and thresholds - Unstable or nonexistent handrails Sources: APT, 2017; AOTA, 2017. Julie is a 78-year-old woman admitted to the surgical unit following repair of a fracture of the left ankle. The nurse completes her initial assessment, including an assessment for risk for falls using the Morse Fall Scale. She notes that: - Julie has a history of falling twice in the past three months, the first on the ice in her driveway, the last one this morning tripping over her cat (25 points). - Julie has a diagnosis of adult-onset diabetes with lower extremity neuropathy (15 points). - She does not use an ambulatory aid (0 points). - She arrives at the unit with one heparin lock and one IV infusing (20 points). - She will require assistance with transfers and gait (20 points). - Julie has dementia requiring assistance with ADLs (15 points). The nurse totals Julie’s risk for falls and records a score of 95. She then adjusts Julie’s care plan to include the evidence-based interventions required for her high-risk fall status, including close supervision with 15-minute checks and referrals to both OT and PT for prevention of deconditioning as well as for gait training. Health Information Technology Problems Healthcare facilities across the United States have made great efforts in moving from paper to electronic systems and processes since the Health Information Technology for Economic and Clinical Health (HITECH) Act was passed in 2009. In 2008, only 17% of physicians and 9% of hospitals had at least a basic electronic health record (EHR). In 2015, 96% of hospitals and 78% of physician offices used certified EHR technology. Hospitals across the country have also achieved increases in electronic health information exchanges. However, there remain a number of significant problems that need to be addressed and overcome (U.S. DHSS, 2016). Compared to paper records, EHRs improve healthcare quality and safety. There are numerous studies that support health information technology’s important role in patient safety. CPOE (computerized physician order entry) systems can improve patient safety by eliminating transcription errors due to illegible handwriting, providing clinical decision support, and alerting clinicians to a potentially dangerous order (U.S. DHSS, 2016). Other studies point out unintended consequences of health information technology (IT), noting that if technology is designed and applied inappropriately, it can add additional complexity to an already complex delivery of healthcare, leading to unintended adverse consequences. Errors can occur at the interface between a computer user and the health IT system, and glitches can occur in how the equipment software functions (U.S. DHSS, 2016). If an individual uses the health IT system incorrectly, there are several problems that can lead to errors. These include: - Failure to identify the patient properly, causing clinical information to be entered into the wrong record - Multiple open records, leading to data being entered into the wrong record - Data not entered into the system - Incomplete and missing data from the entry - User ignoring or overriding an alert - Delay in data entry due to inadequate number of devices or equipment for providers - Lab test results not reviewed in a timely manner - Scanning an item from an outside source into the wrong patient record - Lack of evidence in the patient record of a written order or care provided - Data from an archived paper record not being available at the time of a patient’s visit - Test results sent to the wrong provider, causing delay in taking appropriate action - Processes being missed or done incorrectly due to inadequate training of staff - Text entries not shared due to poorly designed interfaces between systems - Failure to document reasons for not using clinical decision support Health IT system glitches in how the software functions can also lead to errors. Such problems include: - Improperly displayed data in the system - Down or slowed network - Interface issues with a laboratory system, causing delays in retrieving data - Outdated software - Software that does not meet the needs of the provider - Improperly functioning software - Lost data - Internet or server connectivity issues that prevent real-time data entry - Breach in the security of the system (virus or malware) - Use of unapproved data-entry devices DEVELOPING EFFECTIVE DOCUMENTATION AND COMMUNICATION It is clear that good communication lies at the heart of good practice and thus promotes patient safety. Many errors have been demonstrated to arise from the lack of adequate or accurate communication. There is a great deal of support for the development of effective documentation and communication in the provision of safe patient care. Documenting to Prevent Errors Documentation must be credible and timely and must accurately reflect the patient’s condition as well as the care given. Illegible writing and poor transfer of information (both within a department and when a patient transfers to another department or facility) can cause medical errors. Healthcare professionals must learn and follow their facility’s policies and procedures about charting. To help prevent medical errors, the following charting measures should be taken: - Record all pertinent health or drug information (e.g., drug allergy, post-radical mastectomy/lymph node dissection status) in order to prevent adverse events. - Record nursing observations or changes in a patient’s condition and interventions, actions taken, and further monitoring or intervention that may be required in order to prevent other providers from being unaware. - Record that a medication was given in order to prevent a patient from being over-medicated, possibly leading to an adverse response or death. - Follow up on an ordered medication that was not charted as given (by asking the patient if the medication was given, calling the pharmacy to determine if the dose had been dispensed, or calling the handoff nurse at home). - Record in the correct chart. (Adverse events can occur when there are two patients with the same last name, two patients in the same room, two patients with the same condition, or two patients with the same doctor. Always read the name on the chart and compare it to the patient’s ID band. When there are two patients with the same name, it is best practice to avoid assigning the same nurse to both.) - Document a medication that has been discontinued for any reason in order to prevent a patient continuing to receive an unnecessary medication or to experience an adverse event related to a medication’s effects or side effects. - Record drug reactions. (When a patient complains of new symptoms after receiving a first dose of a medication, consider the possibility of an adverse reaction, take appropriate action, and document the patient’s condition and intervention.) - Transcribe orders accurately in the correct patient’s chart in order to prevent a patient from missing a needed medication or treatment, receiving an unnecessary medication or treatment, or receiving the wrong dosage of medication. - Obtain clarification from the prescribing clinician when there is a suspect order. - Follow charting guidelines on paper or electronic medical record (see box below). - If handwriting is difficult to read, print. - Sign full name and title on each page used. - Do not leave blank spaces, lines, or boxes. If space is not used, draw a line through it or write “N/A” (not applicable). - Record all entries in ink. - Use only facility-approved abbreviations. - Chart in chronological order. - Record nursing actions as soon as possible following their completion. - Never alter a record. If an error is made, mark through with one line, indicate correction made, and initial or sign the correction. - Record only the facts. Charting should contain only what is seen, heard, felt, smelled, measured, and counted, not assumptions or opinions (e.g., do not chart “the patient fell out of bed” unless it was witnessed or the patient reports it. Instead chart “patient found lying on the floor”). - Do not document what someone else said, heard, felt, or smelled unless it is pertinent, and if so, place it in quotation marks, and identify the other individual. - Document in a timely manner throughout the shift. - Never document before completing an action. - Avoid documenting for another person. However, if it is necessary to document care, tasks, or procedures performed by another provider, indicate clearly the individual who rendered the care. - Never document the existence of an incident report; it is an internal document meant to facilitate improvement of systems and processes within the healthcare facility. Communication Tools to Prevent Errors Research indicates that poor communication is a root cause of the great majority of all sentinel events. Whether it is nurse-to-nurse, nurse-to-physician, or physician-to-physician communication, having a standard framework and proven tools for reporting and sharing information can enable more effective communication. One increasingly popular communication tool is the SBAR format: Situation (S), Background (B), Assessment (A), and Recommendation (R). It was originally developed by the U.S. Navy and since the 1990s has been used in healthcare settings. This tool can be used for hand-offs between shifts and between caregivers, as well as for debriefings on internal issues, information on new procedures, and email communication. \|S\|\|Situation\|\|What’s happening right now?\| \|B\|\|Background\|\|What are the circumstances that led up to this situation?\| \|A\|\|Assessment\|\|What do I think the problem is with this patient?\| \|R\|\|Recommendation\|\|What should be done to correct the situation?\| Source: IHI, 2017c. ERROR RISKS AMONG POPULATIONS OF SPECIAL VULNERABILITY The safety of all patients is of paramount concern for all care providers. However, some patients—for example, the very young, the very old, and the very sick—are particularly vulnerable to the effects of medical errors, often due to their inability to participate actively as a member of the healthcare team due to communication issues. In addition, their physical status (including but not limited to body weight and body mass composition, nutritional status, and metabolism) may also cause them react differently to interventions, putting them at special risk. Healthcare providers need to recognize the special needs of these patients and act accordingly. There are multiple issues of concern when providing healthcare to an aging individual. Failure to recognize the unique problems of this age group can result in adverse events. Polypharmacy, the use of more than five medications, some of which may be clinically inappropriate and/or incompatible, creates a significant risk for adverse drug events. Up to 30% of hospital admissions of older adults are the result of adverse drug events (Cantlay et al., 2016). With age there are significant changes in drug pharmacokinetics (how the body responds to a drug) and pharmacodynamics (how the drug affects the body). Factors that can affect these actions include reductions in body weight, renal excretion, and liver enzyme function. The older adult is more sensitive to the effects of certain drugs, particularly those that affect the central nervous system, and aging is associated with decreased regulatory functions. Therefore, an antihypertensive medication, for example, can more easily result in postural hypotension, increasing the risk for falls. Opiates can increase the risk of respiratory depression. Older patients often have multiple comorbidities, putting them at risk for polypharmacy. When a patient enters a hospital, clinicians may not have access to the patient’s current or previous medication list and/or may fail to realize that a new symptom is an adverse drug reaction or a side effect, and so another drug may be prescribed to treat that symptom. Patients who see several different physicians at several different locations also increase the risk of duplicated medications or drug interactions. Other problems may arise due to repeat prescribing without proper review, failing to do regular medication reviews with patients, and poor knowledge of drug interactions on the part of the clinician. Polypharmacy can also negatively affect medication adherence in the older adult due to a number of factors, such as visual or hearing impairment, cognitive or functional impairment, social isolation, and complexity of the therapeutic regimen. Confusion and/or delirium in the older adult, especially someone with preexisting cognitive impairment, can be due to certain aspects of hospitalization, such as changes in environment and sensory deprivation. Delirium can also be the result of polypharmacy. The most common medications to cause delirium are opiates, benzodiazepines, and anticholinergics. Anticholinergic effect can also worsen a developing dementia. Confusion can also worsen when sensory input is affected, such as when the patient does not have access to eyeglasses or hearing aids. Functional decline may be the result of lack of mobility resulting in physical deconditioning and muscle weakness. The older adult experiences functional decline when unable to engage in activities of daily living. When an older adult is hospitalized, functional decline can occur as early as the second day of hospitalization. In 30% of hospitalized older people, functional decline is unrelated to their primary diagnosis, and only 50% recover postdischarge (SA Health, 2016). Risk for falls is increased in the older adult and may be due to the effects of acute illness compounded by an unfamiliar environment and side effects of treatments. Tethering medical devices such as urinary catheters, IV lines, cardiac monitor leads, and restraints make it more difficult to mobilize patients safely and are associated with increased rates of delirium, infection, and falls. Immobility in the older adult can result in skin integrity issues such as pressure ulcers/injuries and venous thromboembolic disease. The older adult often has fragile skin, poor mobility, and decreased blood circulation. Incontinence of urine and stool may also be related to reduced mobility, increasing the risk for skin breakdown. Malnutrition and dehydration in older patients may result due to impairment in cognition, restriction of movement, no access to dentures, difficulty with self-feeding, missed meals or interrupted meals, reduced appetite due to illness or lack of activity, lack of assistance with meals and drinks, and severely restricted diet orders, such as nothing by mouth (Mattison, 2017; Cantlay et al., 2016; SA Health, 2016). Infants and Children The potential for adverse drug events is higher in the pediatric population than in hospitalized adult patients. Children and infants often do not look as sick as they are, and they can get sick very quickly. The factors that place them at higher risk include: - Different and changing pharmacokinetic parameters between patients at various ages and stages in development - Fewer internal reserves to buffer any medication errors that may occur - Need for calculation of individualized doses based on the patient’s age, weight, body surface area, and clinical condition (weight changes requiring recalculation can occur quickly, particularly in neonates) - Inadequate availability of appropriate dosage forms and concentrations needed - Need for precise dosage measurement and appropriate delivery systems A recent study identified an 11% rate of adverse drug events in pediatric patients and has shown the most common types of harmful pediatric medication errors to be: - Improper dose or quantity (37%) - Omission error (20%) - Unauthorized or wrong drug (14%) - Prescribing error (9%) These errors were followed in frequency by: - Issues related to administration technique - Drug given at the wrong time - Drug prepared incorrectly - Drug given in the wrong dosage form - Drug given by the wrong route (Patient Safety Movement, 2017a) Such errors demonstrate the need to check the label, compare the dispensed dose with the medication order, perform all medication calculations three times, check all medication calculations with another nurse, and verify that the dosage is within the appropriate range for the medication and the patient. Infants and young children do not have the communication abilities needed to alert clinicians to effects they experience. Parents of infants and children need to be fully informed and involved in their child’s care during any encounter with the healthcare system and must be educated to question caregivers about medications and procedures. Pediatric Patients with Special Needs Children and adolescents with medical complexity and special needs are a fast-growing population in pediatrics. Because of the complexity of their care, these children and their families depend on a variety of services from multiple disciplines. It is not uncommon for such a child to have as many as 25 ongoing healthcare needs that are being met by 10 or more different providers. As a result, their health services are rarely integrated or reliable, and because of these systemic shortcomings, they experience the highest rates of adverse events, including medical errors, of all children. The development of a shared plan of care can minimize such errors and adverse outcomes (Berry, 2015). There is moderate support for the hypothesis that medical homes provide improved outcomes for children with special health care needs, however, further research is recommended (Homer et al., 2017). A medical home extends beyond facility walls to provide comprehensive primary care through partnerships between patients, clinicians, medical staff, and families by offering specialty care, educational services, family support, as well as other services as needed (Calvin, 2017). Intensive Care Patients Intensive care patients are severely ill and receive a great number of medical interventions, making them prone to injury from medical errors. These patients often have more comorbidities and are less resilient to errors. They may receive more medications, and pharmacokinetics can be altered in critically ill patients. Additionally, they are often unable to help facilitate their own care. The ICU is a complex setting where healthcare personnel interact with complicated equipment while under conditions of high stress. Errors most commonly occurring in an ICU are due to medications, ventilation, central line insertions, and nosocomial infections. Medication errors may occur because of the use of multiple medications and high-risk potent drugs. Drugs used in the ICU often require dose calculations and are administered as boluses or continuous infusions (Chiche et al., 2015; Kruer et al., 2014). Patients in Isolation Patients who are placed in isolation have been found to be at higher risk of harm, including delays in treatment and increased incidence of adverse events. They risk physical harm as well as psychological harm with increased levels of anxiety and depression. Hospitalized older patients may be especially vulnerable to such harm. Patients in isolation have less time in contact with providers despite the fact their acuity may be higher. Vital signs are more likely to be inaccurate, incomplete, or not completed as ordered. In hospital teaching settings, patients in isolation are less likely to be examined by an attending physician. There are a higher number of reported incidents related to IVs, medication, and treatments. Patients in isolation are eight times more likely to experience a failure in supportive care, which may be attributed to the limits personal protective equipment place on effective patient assessment and disincentive to enter the isolation room (James, 2015). Patients with Low English Proficiency Persons with low English proficiency (LEP) have a limited ability to read, speak, write, or understand English. There are more than 300 languages spoken or signed in the United States. About 20% of the U.S. population speaks a language other than English at home, and approximately 9% are defined as having LEP. Individuals with LEP have problems with language competence that negatively affect communication and can greatly define the ease with which they navigate all areas of the healthcare system. Because of this, they experience adverse events resulting in physical harm at rates over 50% higher than English-proficient persons (TJC, 2015b). LEP patients can experience: - Longer hospital stays when professional interpreters are not used on admission and/or discharge - Greater risk of line infections, surgical infections, falls, and pressure ulcers/injuries - Greater risk of surgical delays due to difficulty understanding instructions, including how to prepare for a procedure - Greater chance for readmission for certain chronic conditions because of difficulty understanding how to manage their condition and take their medications, which symptoms should require a return to care, or when to follow up Factors that contribute to failure in communication errors include: - Use of family members, friends, or nonqualified staff as interpreters (the most commonly reported cause of errors) - Provider reliance on basic language skills that allow one “to get by” - Cultural beliefs and traditions that affect care, such as expression of pain, respecting authority, gender roles, and class biases Other people who may have identical issues include: - Patients who have limited proficiency or literacy in any language - Patients who have visual or hearing impairments - Patients on ventilators - Patients with cognitive impairments (TJC, 2015b; Halado & Lundy, 2017) Patients with Low Health Literacy Health literacy is defined as the degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions. Health literacy requires numerical literacy, ability to communicate, ability to fill out forms, and ability to understand concepts such as risk and probability. Health literacy is not necessarily tied to years of education or to general reading ability. Someone who has no difficulties at home or work may have minimal or inadequate literacy in a healthcare setting. Low health literacy contributes to longer length of hospital stays, delays in seeking care, suboptimal adherence to plans of care, and errors due to: - Failure to follow instructions - Inability to recognize and/or articulate signs and symptoms - Difficulty understanding prescription medication warning labels - Misuse of prescription medications - Lack of understanding of treatment options The populations most impacted by low health literacy are: - Patients over 65 years of age - Members of racial and ethnic minority groups - Patients with low socioeconomic status - Patients with chronic physical or mental illness PATIENT SAFETY INITIATIVES When the book To Err Is Human made headlines across the country in 1999, it captured the attention of the public and launched the modern patient safety movement. Federal funding for patient safety initiatives increased, accreditation and reporting standards tightened, and research on effectiveness of patient safety measures expanded. Over the ensuing years, the patient safety movement has grown to involve many agencies and organizations in both the public and private sectors, and many important milestones have been achieved along the way. Annually, the Patient Safety Movement Foundation meets to nominate and elect new patient safety challenges to be addressed for the following year in attempt to reach their primary goal of zero preventable deaths by 2020 (PTSF, 2017b). AGENCIES AND ORGANIZATIONS IN THE PATIENT SAFETY MOVEMENT AAAHC - Accreditation Association for Ambulatory Health Care. Develops standards to advance and promote patient safety, quality care, and value for ambulatory healthcare settings, including ambulatory surgery centers, community health centers, medical and dental group practices, medical home practices, and managed care organizations, as well as Indian and student health centers. ABMS - American Board of Medical Specialties. Recognizes medical specialists and establishes standards for physician certification. ACGME - Accreditation Council for Graduate Medical Education. Responsible for accrediting the majority of medical residency and internship programs. AHRQ - Agency for Healthcare Research and Quality. Produces evidence to make healthcare safer, of higher quality, more accessible, more equitable, and more affordable, working with the U.S. Department of Health and Human Services. ANA - American Nurses Association. Represents the interests of registered nurses to advance the profession to improve healthcare. CDC - Centers for Disease Control and Prevention. Promotes health and disease prevention and preparedness. HCUP - Health Care Utilization Project. Maintains hospital care data enabling research on a range of health policy issues. HRET - Health Research and Education Trust. A research and education affiliate of the American Hospital Association that promotes research and education efforts. IHI - Institute for Healthcare Improvement. Redesigns healthcare into a system without errors, waste, delay, or unsustainable costs. IOM - Institute of Medicine. Asks and answers the nation’s most pressing questions about health and healthcare. ISMP - Institute for Safe Medication Practices. Watchdog organization devoted to medication error prevention and safe medication use. NGC - National Guideline Clearinghouse. A public resource for evidence-based clinical practice guidelines. NIH - National Institutes of Health. Conducts medical research. NPSF - National Patient Safety Foundation. Advances patient and healthcare workforce safety; disseminates strategies to prevent harm. NQF - National Quality Forum. Leads national collaboration to improve health and healthcare quality through measurement. TJC - The Joint Commission. Accredits and certifies healthcare organizations and programs in the United States. WHO - World Health Organization. WHO World Alliance for Patient Safety serves as the directing and coordinating authority for health within the United Nations system. Federal and State Efforts In 2006, Congress passed the Deficit Reduction Act of 2005, authorizing Medicare and Medicaid to tie healthcare facilities’ Medicare eligibility to the occurrence of preventable never events. At the onset, the Center for Medicare and Medicaid Services (CMS) listed only eight types of hospital-acquired conditions, but as of August 2013, CMS revised the list to include additional conditions raising the total to fourteen, closely mirroring the NQF’s list of serious reportable events (Zung, 2014). In 2007, CMS issued a new rule giving hospitals a powerful incentive to reduce medical errors. This rule denied reimbursement to hospitals for treatment of preventable errors, injuries, and infections. This rule also stipulated that these charges may not be passed along to the beneficiary. This new rule was mandated by the Patient Safety and Quality Improvement Act to take effect in October 2008 (CMS, 2015). Follow up of this initiative in 2015 showed improvements, with a reduction of 11% in the rate of central line–acquired bloodstream infections and a 10% reduction in the rate of change in catheter-associated urinary tract infections, conditions for which there is strong evidence that better hospital processes produce better outcomes. However, the initiative has not shown improvements in injuries from falls or hospital-acquired pressure ulcers/injuries, conditions for which there is less evidence that changing hospital processes leads to significantly better outcomes (Waters et al., 2015). More than 25 states and the District of Columbia have mandatory reporting of never events, but only a few states report publicly. Minnesota has had a mandatory reporting program in place since 2005 and has averaged approximately 100 to 150 reported never events each year (Leapfrog Group, 2016). PREVENTABLE COMPLICATIONS (NEVER EVENTS) NOT COVERED BY MEDICARE AND MEDICAID The following preventable complications are not reimbursed by Medicare and Medicaid if acquired during an inpatient stay: - Foreign object retained after surgery - Air embolism - Blood incompatibility - Stage III and IV pressure ulcers - Falls and trauma: - Fractures and dislocation - Intracranial injuries - Crushing injuries - Other injuries - Manifestations of poor glycemic control: - Diabetic ketoacidosis - Nonketotic hyperosmolar coma - Secondary diabetes with ketoacidosis - Secondary diabetes with hyperosmolarity - Catheter-associated urinary tract infection - Vascular catheter-associated infection - Surgical site infection following: - Mediastinitis following coronary artery bypass graft - Bariatric surgery for obesity - Laparoscopic gastric bypass - Laparoscopic gastric restrictive surgery - Surgical site infection following certain orthopedic procedures: - Surgical site infection following cardiac implantable electronic device - Deep vein thrombosis/pulmonary embolism following total knee or hip replacement - Iatrogenic pneumothorax with venous catheterization Medicare and Medicaid also will not reimburse for wrong-site, wrong-procedure, and wrong-patient surgery. Source: CMS, 2015. Since Medicare initiated its nonpayment policy for preventable errors, many private insurers have followed suit, further benefiting patient safety. In addition, some have implemented incentives for hospitals that adhere to standards designed to improve patient safety. Evidence-based practice (EBP) is vital for the improvement in the quality of treatment and for assuring patient safety. EBP attempts to standardize practices in order to make outcomes more predictable. EBP involves collecting, evaluating, and implementing practices that can improve patient care safety and outcomes. EBP is beneficial in decreasing healthcare costs and reducing medical complications. It is the integration of clinical expertise, patients’ values and preferences, and best research evidence into the decision-making process for providing patient care (Duke University Medical Center, 2017). Components of evidence-based practice. (Source: J. Swan.) FIVE STEPS TO IMPLEMENT EVIDENCE-BASED PRACTICE - Ask: Assess the patient and formulate a well-written clinical question. - Acquire: Identify appropriate resources, including background and quantitative and qualitative research findings, and search the literature. - Appraise: Critically appraise the evidence to determine its validity and potential usefulness. - Apply: Integrate the evidence with clinical expertise and patient preferences and apply to practice. - Assess: Evaluate performance through a process of self-reflection, audit, or peer assessment to determine whether the action taken has achieved the desired results. Source: Duke University Medical Center, 2017. Jai, a pharmacist working in skilled nursing facilities, was involved in reviewing and updating a facility’s manual of medication policies and procedures. While reviewing the section on digoxin monitoring, he found that an apical pulse should be taken daily before administering digoxin, and the drug should not be given if the pulse is below 60 beats per minute. While looking over medication administration records, he found that residents with hypertension receiving antihypertensives had their blood pressure taken once a week and other residents had vital signs done once a month. Apical pulses for residents receiving digoxin were obtained daily. As he thought about this, he realized that in all the time he has been working as a pharmacist in healthcare facilities, he could only recall digoxin being withheld once or twice because of a pulse below 60. He began to question the necessity for performing apical pulses and asked, “Why are medication nurses in skilled nursing facilities checking apical pulses daily?” With that question in mind, Jai began to acquire relevant resources by talking with medication nurses, directors of nursing, and other pharmacists about their experiences with digoxin monitoring. All of the nurses he questioned had been in nursing for 10 or more years in skilled nursing facilities, and none could remember holding digoxin more than once or twice for a pulse below 60 on a single day which returned to normal on the next day. This number was compared to the hundreds of doses they had administered over their careers. Jai then began to search databases for the best evidence for digoxin monitoring. He found that the initiation of digoxin occurred in hospital settings, and that it was critical to take apical pulses to determine the correct dosage. Once the patient was properly dosed and discharged, this monitoring was no longer required. Indeed, the research showed that patients discharged to “home” are not instructed to monitor their apical pulse every day and there were no negative outcomes reported. Following his critical appraisal of the resources, Jai determined that persons who reside in nursing homes have been discharged to their “home” and that medication nurses were performing a time-consuming unnecessary procedure. Jai brought his findings to the director of nursing and the medical director, and together they enacted (applied) a new policy that stated the apical pulse rate of residents receiving digoxin is to be obtained once a week. If the apical pulse is less than 60, digoxin should be given as ordered, and the apical pulse is to be monitored daily for three days while continuing to give the medication. If it continues to be below 60 after three days, the medication should be withheld and the attending physician notified. The change in policy was explained to patients and their families so there would be no perception of the staff “cutting corners” once the new practice started. Aside from a few joking comments by patients about missing the “hand holding,” there was no push back. The policy was assessed after it was in place for nine months. During that time there was not a single dose of digoxin held. It was determined that this change resulted in one less procedure to be performed by the medication nurse, leaving more time to provide other care for the patients. Source: Vogenberg, 2004. Attitudes towards EBP are mostly positive within the nursing, occupational therapy, and physical therapy fields. There does remain, however, resistance to acceptance of EBP despite scientifically supported knowledge. Many practices that are not evidence-based continue, including: - Taking vital signs every 4 hours during the night on stable patients, disrupting sleep needed for recovery - Treating children with asthma in the ER using nebulizers instead of a bronchodilator with a metered-dose inhaler and spacer, which has been shown to be more effective - Removing urinary catheters only upon a physician’s order, even though nurse-driven protocol is more efficient and may prevent urinary tract infections - Continuing the practice of 12-hour nursing shifts when research evidence demonstrates adverse outcomes for both nurses and patients SAFE HARBOR LEGISLATION Traditionally, healthcare has operated on a “culture of blame.” One of the common tools for redress in a culture of blame is the lawsuit. The fear of being sued presumably leads to more careful and safer behavior by health professionals. But neither studies nor anecdotal evidence bear this out. On the contrary, fear of being sued leads to the practice of defensive medicine. Defensive medicine involves ordering diagnostic tests or procedures, making referrals, or taking other treatment steps that are not based on best practice and are not of benefit to the patient’s care primarily to protect the clinician against litigation. The Agency for Healthcare Research and Quality has offered funding grants to investigate the effects of “safe harbor” legislation as a way to reform the malpractice system and improve patient safety by inducing greater clinician adherence to evidence-based care guidelines. Safe harbors grant liability protection to clinicians if they can demonstrate adherence to state-endorsed, evidence-based medical guidelines. A legal safe harbor gives clinical practice guidelines a special status in the medical liability system and is intended to provide greater clarity about the standard of care expected of a medical professional. Such a grant was provided to the state of Oregon to conduct a survey of more than 2,000 providers, with the goal of obtaining input about the feasibility of implementing a legal safe harbor. Respondents to the survey agreed that a safe harbor rule would likely reduce the impact of medical liability, would increase their adherence to guidelines, and would result in improved patient safety. Source: AHRQ, 2016a. Quality Assurance and Performance Improvement (QAPI) Quality Assurance is the process of meeting quality standards and assuring that care reaches an acceptable level, and Performance Improvement is the continuous analysis of performance and the development of systematic efforts to improve it. Beginning in 2011, the Centers for Medicare and Medicaid Services began mobilizing some of the best practices in nursing homes. QA and PI were combined and a prototype QAPI program was begun in a small number of facilities, which provided the agency with best practices for helping nursing homes upgrade their current quality programs. QAPI is made up of five elements: - Design and Scope - Must be comprehensive and ongoing - Should address all systems of care and management practices - Aims for safety and high quality with all clinical interventions - Emphasizes autonomy and choice in daily life for residents - Utilizes the best available evidence to define and measure goals - Governance and Leadership - Develops a culture that seeks input from facility staff, residents, and families - Assures adequate resources exist - Designates person(s) to be accountable - Ensures staff time, equipment, and technical training as needed - Ensures that policies are developed to sustain QAPI - Ensures a culture of safety - Feedback, Data Systems, and Monitoring - Uses performance indicators to monitor a wide range of care processes and outcomes - Reviews findings against established benchmarks or targets - Includes tracking, investigating, and monitoring of adverse events - Develops action plan to prevent adverse event recurrences - Performance Improvement Projects - Gathers information systematically to clarify issues or problems - Intervenes to make improvements - Systematic Analysis and Systemic Action - Uses a systematic approach to determine when in-depth analysis is needed - Uses a thorough and highly organized structured approach to examine the way care and services are organized or delivered - Develops policies and procedures and demonstrates proficiency in the use of Root Cause Analysis - Takes systemwide actions to prevent future events - Focuses on continual learning and continuous improvement JOINT COMMISSION AND AAAHC STANDARDS AND GOALS The Joint Commission The Joint Commission is an independent, not-for-profit agency whose mission is to continuously improve the safety and quality of care provided to the public. The Joint Commission accredits and certifies more than 21,000 healthcare organizations and programs in the United States, including hospitals and healthcare organizations that provide ambulatory and office-based surgery, behavioral health, home health care, laboratory, and nursing care center services. Accreditation by the Joint Commission is not mandatory. Healthcare organizations, programs, and services voluntarily pursue accreditation and certification. Joint Commission surveyors visit accredited healthcare organizations a minimum of once every 39 months (two years for laboratories) to evaluate standards compliance. This visit is referred to as a survey. All regular Joint Commission surveys are unannounced, and accreditation and certification decisions are rendered two weeks to two months following the survey. During a survey, the surveyors randomly select patients, and using their medical records, the surveyors evaluate standards compliance. As they review each patient’s experience, they talk to doctors, nurses, and other staff who interacted with the patients. They also observe doctors, nurses, and other caregivers providing care and often speak to the patients themselves. The standards of the Joint Commission focus on patient safety and quality of care. They are updated regularly, number more than 250, and address patient rights and education, infection control, medication management, preventing medical errors, improving practices and procedures, and how the organization verifies that its doctors, nurses, and other staff are qualified and competent (TJC, 2017b). SENTINEL EVENT POLICY The Joint Commission encourages, but does not require, reporting of any sentinel event. However, in the interest of continuous improvement in safety and quality of care, the Joint Commission requires that healthcare organizations: - Have a process in place to recognize sentinel events - Conduct thorough and credible root cause analyses (see below) that focus on process and system factors, not on individual blame - Document a risk-reduction strategy and internal corrective action plan within 45 days of the organization becoming aware of the sentinel event The sentinel event policy has four goals: - To have a positive impact in improving patient care, treatment, and services and preventing sentinel events - To focus the attention of an organization that has experienced a sentinel event on understanding the factors that contributed to the event (such as underlying causes, latent conditions and active failures in defense systems, or organizational culture) and on changing the organization’s culture, systems, and processes to reduce the probability of such an event in the future - To increase the general knowledge about sentinel events, their contributing factors, and strategies for prevention - To maintain the confidence of the public and accredited organizations that patient safety is a priority in accreditation practices Although accredited facilities are expected to identify and respond appropriately to all sentinel events, but not to report them, if the Joint Commission becomes aware of an event, facilities are required to submit the findings of their root cause analyses and corrective action plans. This information can be included in the Joint Commission’s review of sentinel events, helping to track national trends and develop strategies for improving patient safety. NATIONAL SAFETY GOALS The Joint Commission’s National Patient Safety Goals program assists accredited organizations to address areas of concern regarding patient safety. Such assistance involves the advice provided by a panel of patient safety experts referred to as the Patient Safety Advisory Group. This group assists in the identification of emerging patient safety issues and advises on how best to address them, such as through sentinel event alerts, standards and survey processes, performance measures, educational material, and the Center for Transforming Healthcare projects. Such projects that have been addressed include: - Hand hygiene - Hand-off communications - Preventing avoidable heart failure hospitalizations - Preventing falls - Preventing surgical site infection - Reducing sepsis mortality - Safety culture - Safe and effective use of insulin - Safe surgery (TJC, 2017c; 2017d) “DO NOT USE” ABBREVIATION LIST Misreading medical abbreviations can be a cause of serious medication errors, and the Joint Commission has created a “do not use” list of abbreviations that endanger patients’ safety and that it requires its members to follow. \|Do Not Use\|\|Potential Problem\|\|Instead Use\| \|Source: TJC, 2017e.\| \|U, u\|\|Mistaken for “0” (zero), the number “4” (four), or “cc”\|\|Unit\| \|IU\|\|Mistaken for IV (intravenous) or the number 10 (ten)\|\|International unit\| \|Q.D., QD, q.d., qd\|\|Period after the Q mistaken for “I” “O”\|\|Daily\| \|Q.O.D., QOD, q.o.d, qod\|\|“O” mistaken for “I”\|\|Every other day\| \|Lack of leading zero\|\|Decimal point is missed\|\|0.X mg\| \|MS\|\|Can mean morphine sulfate or magnesium sulfate\|\|Morphine sulfate or Magnesium sulfate\| \|MSO4 and MgSO4\|\|Confused for one another\|\|Magnesium sulfate\| \|Trailing zero \|\|Decimal point is missed\|\|X mg\| \| Exception: A “trailing zero” may be used only where required to demonstrate the level of precision of the value being reported, such as for laboratory results, imaging studies that report size of lesions, or catheter/tube sizes. It may not be used in medication orders or other medication-related documentation.\| The Institute for Safe Medication Practices has also compiled an extensive list of abbreviations, symbols, and dose designations that are frequently misinterpreted and involved in harmful medication errors, which can be accessed online (see also “Resources” at the end of this course). ROOT CAUSE ANALYSIS The Joint Commission has mandated the use of root cause analysis (RCA) to analyze sentinel events since 1997. It requires that a thorough, credible root cause analysis and corrective action plan be performed for each reported sentinel event within 45 days of the event’s occurrence or of the organization’s becoming aware of the event (TJC, 2017f). Root cause analysis is a widely used method in healthcare and other industries to analyze adverse events and near misses. The central principle of a root cause analysis is to identify: - What happened (the course of events) - Why an incident happened (the root cause or causes) - How to prevent it from occurring again in the future (corrective actions) Root cause analysis does not seek to lay blame on individuals for errors but rather to work toward preventing them. Strategies for an effective root cause analysis include: - Finding and resolving latent conditions as well as root causes - Treating the cause rather than trying to change people - Following through to ensure change A thorough and credible root cause analysis should: - Be precise - Be accurate - Be relevant - Be complete - Be systematic - Possess depth - Possess breadth of scope RCAs follow a specific protocol that collects data and reconstructs the event through record review and participant interviews. A multidisciplinary team analyzes the sequence of events leading to the error, attempting to identify how the event occurred, why it occurred, and how to eliminate the latent errors that underlie the event (AHRQ, 2017h). Since 2016, however, experts have reported ongoing problems with root cause analysis in healthcare, most importantly emphasizing the difficulty of measuring the impact of the process on reducing future risk. The National Patient Safety Foundation and others have made recommendations for improvement and also recommend renaming RCA to demonstrate reinvention of this process (Gupta & Lyndon, 2017; Peerally et al., 2016). ROOT CAUSE ANALYSIS AND ACTION PLAN TEMPLATE The Joint Commission has developed a template to be used while conducting a root cause analysis that recommends the following questions be asked and answered and an action plan developed for any finding that can be considered a risk-reduction strategy. - What was the planned flow of the procedure? - What steps in the procedure did not occur as planned? - What human factors were pertinent to the outcome? - How did performance of equipment affect outcome? - What controllable environmental factors directly affected the outcome? - What external controllable factors affected the outcome? - Were there any other factors that directly affected the outcome? - In what other areas of the organization could this happen? - Was the staff properly qualified and currently competent at the time of the event? - How did real staffing compare with ideal levels? - What is the plan for dealing with unforeseen staffing problems? - Were such problems a factor in this event? - Did staff perform to expectations during the event? - Was all the necessary information available when needed? Was it accurate, complete, and explicit? - Was communication among participants sufficient for this situation? - Was this the appropriate physical environment for the situation? - What systems are in place to recognize environmental risks? - What planned and tested emergency and failure-mode responses are in place? - How does the culture support risk reduction? - What barriers exist to the communication of potential risk factors? - What methods are utilized to communicate the high priority of prevention of adverse outcomes? - What orientation and in-service training revisions are necessary to reduce risk of events in the future? - Was available technology used as intended? - What technology or redesign of technology might reduce risk in the future? Source: TJC, 2017f. St. Vincent Hospital (continued from above under “Active and Latent Errors”) Following identification of the cause of the accident in St. Vincent Hospital’s operating room, a root cause analysis was begun that day. The root cause was determined to be the use of an inappropriate gas mixture to expand the abdomen during laparoscopic surgery. Contributing factors included: - All extra cylinders containing medical gases used in the OR are stored in metal tubes in a tank room, but only the top several inches of each cylinder and a portion of each tank’s label is visible above the top of the storage tubes. The tube height is to provide adequate support for the cylinders, so shortening the tubes to allow visualization of the entire label is not an appropriate option. - All tanks containing any percentage of CO2 are color-coded the same (grey). This is an industry standard over which individual facilities have no control. - When an OR logistics technician allowed a logistics technician from the cath lab to store an extra CO2/O2 tank in the OR tank room, no one in the OR, anesthesia, or logistics chain of command was informed. This is an example of well-intentioned interunit cooperation gone awry due to lack of appropriate communication. - The circulating nurse mistakenly replaced an empty CO2 tank with a blended CO2/O2 tank, not noticing the difference because they were both grey, with similar labeling, and because there was no history of anything but pure CO2 being stored in the OR tank room or used in the OR. - There was no pin indexing at the connection point between the cylinder and the gas delivery system that differentiates between pure CO2 and CO2 blends. Any cylinder containing any percentage of CO2 fits to any yoke designed to accept CO2 in any concentration. Corrective actions included policy changes and an intensive education initiative for all involved personnel: - Only medical gases intended for use in the OR are to be stored in the OR tank room. - Should a deviation from this policy be indicated for safety reasons and no other alternatives exist: - Tanks containing gases not used in the OR are to be stored in the OR tank room only until safe storage elsewhere is available. - If no alternative storage is available, storage in the OR tank room may be approved only by the senior professional and technical personnel in the OR and the anesthesia service. If the decision is made during “off” hours by a shift charge person, that person is responsible for notifying the appropriate senior personnel by the next shift or delegating and documenting that this notification is to be made by a specific, named person. - Any such tanks are to be indicated by orange fluorescent tags reading “Not for use in the OR” and placed in the most remote storage tubes in the tank room. - Information about the temporary storage is to be conveyed at each OR and anesthesia shift report and in the OR shift change log until the tank is removed. - Medical gases are elevated to the status of medications and the triple-check policy used for medications has been implemented for medical gases. - The OR manager will personally brief each shift for the next two days to minimize rumors. - All members of the involved surgical and logistics teams will be debriefed by their supervisors. - A description of the incident and follow-up will be published in the quality assurance journal for the healthcare system. Céline is an 82-year-old patient who has suffered a stroke and been transferred to a local nursing home where inadequate staffing has been a recurrent problem. Céline has right-sided paralysis and requires total care. Her care plan includes repositioning every two hours. Today the nurse does the required biweekly skin assessment and finds a small open crater with visible subcutaneous tissue on the heel of her right foot, a stage 3 pressure injury. The nurse documents and reports this long-term care sentinel event and a root cause analysis is begun. By asking questions as outlined in the facility’s root cause analysis template, the first step is to identify and define the problem: - Stage 3 pressure injury (damage to tissue leading to death of tissue) has developed on the heel of the patient’s right foot. - Tissue damage has negatively impacted the goal of patient safety. The second step is to identify the cause: - Death of tissue caused by mechanical damage - Mechanical damage caused by pressure - Pressure injury due to patient remaining in same position - Patient remaining in same position due to failure to reposition every 2 hours - Failure to reposition every 2 hours due to inadequate level of staffing The third step in the process is to select the best solution to reduce the risk of pressure injuries in the future. - Reposition patients at risk every 2 hours and document the action. - Utilize pressure-relieving devices such as beds, mattresses, or overlays. - Review and revise staffing formulas; improve staffing to meet the U.S. Department of Health and Human Services recommendations of 1 hour per resident per day for total licensed staff, 27 minutes per day for RNs, and 2 hours per day for nursing assistants. Following completion of the root cause analysis, the facility determines to institute the action plan: - Alternating pressure pads are applied to the beds of all residents at high risk for pressure injuries. - The use of heel/elbow protectors becomes standard for all patients with immobility issues. - Documentation on a turning schedule is instituted for each resident with immobility. - Staffing issues remained unresolved due to budget restraints, but ongoing exploration of means to improve the staffing level is being carried out. Accreditation Association for Ambulatory Health Care The Accreditation Association for Ambulatory Health Care (AAAHC) was founded in 1999 by the AAAHC Institute for Quality Improvement, which offers ambulatory healthcare organizations opportunities to learn about and become involved in performance measurement, benchmarking, and quality improvement. Since its beginning, the AAAHC has promoted a voluntary, peer-based, consultative, and education survey process to advance patient care. Ambulatory care organizations are offered accreditation by AAAHC to demonstrate that the organization takes part in ongoing self-evaluation, peer review, and education to continuously improve its care and services. The organization performs on-site surveys by healthcare professionals at least every three years. Areas surveyed by AAAHC include: - Adherence to patient rights - Governance processes - Administration policies and procedures - Quality of care - Quality management and improvement policies and procedures - Clinical records and health information - Infection prevention and control - Facility environment - Anesthesia services - Surgical and related services - Personnel professional improvement INSTITUTIONAL STRATEGIES FOR ADDRESSING ERRORS Changes in organizational culture, involvement of leadership, education of providers, development of patient safety committees, adoption of safe protocols and procedures, and use of technology are all essential strategies healthcare facilities must consider in their efforts to reduce medical errors. Creating a Culture of Safety The mistaken attitude in healthcare that errors are solely the fault of individual practitioners has proven a major barrier to reporting. Instead of analyzing the multiple factors that contribute to errors, past efforts have often focused on making clinicians more careful and afraid of punishment when they fail. When the reporting of medical errors focuses on the identification and punishment of individual health professionals, there is a huge disincentive for reporting errors, and this punitive attitude severely limits the reporting of errors. This “culture of blame” bypasses the opportunity for analysis and corrective measures to prevent recurrence. One of the main goals of organizations working to improve patient safety should be to encourage the creation of a “culture of safety” in which medical errors are discussed openly and addressed thoroughly. When an organization values safety, this commitment is evident throughout the organization from top management to the bedside. Creating a culture of safety requires: - Recognition that errors occur and are a part of the healthcare industry, requiring a nonpunitive approach unless specific behavior warrants disciplinary action - Effective teamwork, communications, and shared learning - Recognition that it is everyone’s role to watch for errors or system failures - Openness or transparency, which indicates an acceptance of the human elements in error, and a conscious means of reporting any error, near miss, or identified potential for an error - A “just culture” where retribution is confined to reckless or malicious behavior (see below) - Accountability to ensure everyone is aware of their responsibility to maintain safety JUST CULTURE MODEL A culture of safety promotes open reporting of adverse events and risky situations, and even stop-work in certain situations, in a blame-free context. However, leaders must include the necessary component—a just culture. Such a culture does not default to punishment but rather makes an effort to determine if discipline is necessary when an incident occurs. An important aspect of a just culture is the systematic, fair, and nonarbitrary method of determining system versus individual accountability. A just culture seeks to determine whether an incident was due to human error, at-risk behavior, or reckless behavior. Reckless behavior may be grounds for disciplinary action and civil and/or criminal charges. Punishment may be the appropriate consequence, including termination. A just culture acknowledges that competent professionals make mistakes and recognizes that competent professionals may develop unhealthy norms such as shortcuts and routine rule violations, but has zero tolerance for reckless behavior (Moriates & Wachter, 2015). As the field of safety has grown, so has the recognition that organizational leadership plays a significant role in prioritizing patient safety. In the past, hospital board members have been leaders in the community who may have little or no healthcare experience. Despite being accountable for the quality and safety of the care being provided in their organization, the boards, executives, and medical staff leadership at most U.S. hospitals placed little importance on identifying and addressing issues of safety. They often lacked the knowledge to understand the complex information and data about quality and safety of care. Today, however, there is a shift toward more direct oversight of safety and quality of care at the organizational level. Hospital boards now use strategic initiatives to influence quality and safety, however data shows that executives and management can further improve safety by having more direct interactions with frontline workers. Visits by management (walkarounds) to clinical areas to engage in open and frank discussions with the staff about safety concerns have been shown to have a positive impact on safety culture. To be credible among frontline staff during these walkarounds, however, it is important that issues raised by the staff be addressed promptly and that leaders follow up sufficiently after an error has been reported. Leadership can also directly address safety concerns by recognizing that disruptive and unprofessional behavior by clinicians poses a definite threat to patient safety, increasing the potential for medical errors and preventable deaths. For instance, disruptive and disrespectful behavior by physicians has been shown to be connected to adverse events in operating rooms. In an environment where caregivers at the frontline are demeaned or harassed, there is an imbalance in decision-making power, contributing to a breakdown in teamwork and poor communication, the leading cause for medical errors. Although there is limited evidence at this time about strategies leadership can use to address this issue, some organizations are emphasizing early intervention using a structured approach for clinicians who exhibit recurrent unprofessional behavior or are the focus of multiple patient complaints (AHRQ, 2017i). Health information technology (IT) encompasses a technical system of computers and software that operates in the context of a larger socio-technical system. Health IT has great potential for improvement in the quality and safety of health care. Electronic health records (EHRs) should help reduce medication errors, avoid the need to repeat laboratory tests, and improve continuity of care across the healthcare system. Expectations for health IT include the enhancement of workflow and making it easy to transfer information to and from other organizations and providers. All healthcare providers within a system are expected to have access to accurate and complete information when they need it. Facilities should carefully select the best system available, adopt best practices for EHR implementation and management, monitor how the health IT system is used, and report any adverse events. For nearly two decades, patient safety has been a topic of both national and international concern. Everyone has a stake in the safety of the healthcare system—healthcare workers as well as the general public. In the past, patient safety was not a traditional part of the education of most healthcare workers, but today this is no longer true. All healthcare workers are being actively educated about their roles in the prevention of avoidable negative outcomes for those we care for. It is essential that all clinicians understand the journey every patient makes through the system, recognizing how the system can fail, and take action to prevent those failures. To counter errors and safeguard patients, changes must continue to be made in how the workforce is deployed; in how work processes are designed; and in the leadership, management, and the culture of healthcare organizations. Because communication issues are so commonly involved in medical errors, it is crucial that physicians, nurses, therapists, and other healthcare personnel work together as a team, respecting each other’s contributions to the well-being of the patients in their care. Collaborative teamwork is essential for optimizing quality and safety in healthcare. 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Vascular dementia is a condition arising secondarily to cerebrovascular disease. It is characterized by executive dysfunction and difficulty in performing activities of daily living. It must be differentiated from other causes of dementia, primarily Alzheimer's disease. Vascular dementia (VaD) is the second most common cause of dementia and its prevalence increases after the sixth decade of life . It is defined as a condition characterized by features of stroke or subclinical vascular brain injury which involves malfunction of at least two cognitive domains leading to a decrease in the ability to perform activities of daily living . The cognitive features of VaD depend on the anatomical location of the vascular injury and this has led to the classification of VaD into different subtypes: small, large, or mixed vessel disease . Patients with small vessel disease present with a higher incidence of executive dysfunction whereas dysfunctional language and visuospatial perception are noticed more often in patients with large vessel VaD . Clinical presentation of VaD in cortical injury includes speech abnormalities and neglect while a subcortical injury is associated with cognitive, emotional and behavioral difficulties, psychomotor retardation, pseudobulbar palsy, and gait dysfunction . Other features of VaD are restlessness, agitation, aggressive behavior, hallucinations, delusions, paranoia, circadian mood disturbances (sundowning), disorientation, and depression. As the brain injury is variable in VaD, memory disturbances may also be variable or may be completely absent . The intellectual decline in VaD is classically described as "step-wise" (multi-infarct dementia) but can be continuous (lacunar infarcts) too. Clinical presentation of VaD may resemble that of Alzheimer's disease (AD) although the following features help to differentiate between the two conditions: impairment and other deficits to meet operationalized criteria for dementia, and (3) the use of limited test batteries whose psychometric properties are incompletely understood. [ncbi.nlm.nih.gov] The development of multiple cognitive deficits manifested by both: Memory impairment (impaired ability to learn new information or to recall previously learned information) One or more of the following cognitive disturbances: (a) aphasia (language disturbance [strokecenter.org] Symptoms of vascular dementia include the following: Memory impairment Impairment in at least 1 other cognitive domain (eg, orientation, language, praxis, executive functions, visuospatial abilities) Worsening of cognitive abnormalities Impact on activities [emedicine.medscape.com] Transcortical sensory and motor aphasia was observed in four patients with thalamic hemorrhages and infarcts. In these patients SPECT detected hypoperfusion in adjacent cortical areas. [ncbi.nlm.nih.gov] Exclusion criteria : cases with disturbance of consciousness, delirium, psychosis, severe aphasia, or major sensorimotor impairment precluding neuropsychological testing. [strokecenter.org] […] neurologic deficits often develop: Exaggeration of deep tendon reflexes Extensor plantar response Gait abnormalities Weakness of an extremity Hemiplegias Pseudobulbar palsy with pathologic laughing and crying Other signs of extrapyramidal dysfunction Aphasias [merckmanuals.com] Those symptoms include confusion; memory loss; struggles with word recall, or aphasia; difficulty paying attention, or following a conversation; impaired motor skills, and vision loss. [lcbseniorliving.com] Visual constructive apraxia is very common in dementia and impairment in these abilities can provide clinical information for differential diagnosis. [ncbi.nlm.nih.gov] […] of multiple cognitive deficits manifested by both: Memory impairment (impaired ability to learn new information or to recall previously learned information) One or more of the following cognitive disturbances: (a) aphasia (language disturbance) (b) apraxia [strokecenter.org] In addition, the person must have one or more of the following symptoms: Aphasia - A deterioration of language abilities Apraxia - Difficulty executing motor activities Agnosia - An impaired ability to recognize or identify objects Problems with executive [mentalhelp.net] Apraxia: It is an inability to carry out simple or complex movements. Attention Deficit: Moderate or severe distraction. Fluctuating course: The person with vascular dementia does not remain stable throughout. [blog.cognifit.com] Clinical presentation of VaD in cortical injury includes speech abnormalities and neglect while a subcortical injury is associated with cognitive, emotional and behavioral difficulties, psychomotor retardation, pseudobulbar palsy, and gait dysfunction [symptoma.com] Common dementia signs and symptoms include: Memory loss Impaired judgement Difficulties with abstract thinking Faulty reasoning Inappropriate behavior Loss of communication skills Disorientation to time and place Gait, motor, and balance problems Neglect [helpguide.org] Caring for people with dementia is stressful and demanding, and caregivers may become depressed and exhausted, often neglecting their own mental and physical health. [msdmanuals.com] […] cardioembolism, vasculitis Chronic: atherosclerosis, CADASIL Hemorrhage Hypertension Vascular malformation: AVM, aneurysm Cerebral amyloid angiopathy: sporadic, hereditary Treatment of established symptoms (Tertiary amelioration) Cognitive: amnesia, aphasia, neglect [web.archive.org] In 2012, he developed gait disturbance and mild amnesia. One year later, his gait disturbance worsened, and he developed urinary incontinence. [ncbi.nlm.nih.gov] Her last neuropsychological testing revealed a stable pattern of amnesia. Figure 1. MRI showing bilateral thalamic infarctions. [web.archive.org] ‘Severe amnesia’ was previously an exclusion criteria for bvFTD; however, 10% of pathologically confirmed cases have reported memory symptoms at the time of the initial clinical evaluation, with some showing severe amnesia. [doi.org] A physician should suspect VaD in a patient with cognitive dysfunction which follows a neurologic episode/deficit. The workup should commence with a detailed history eliciting onset and progression of cognitive and neuropsychiatric symptoms as well as a history of atherosclerotic conditions like angina pectoris. A detailed neurological and psychiatric assessment is essential. The Mini-Mental Status Exam (MMSE) is likely to reveal patchy cognitive deficits in VaD compared to global deficits in AD . Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria provide the guidelines to help in the diagnosis of VaD . Laboratory tests are performed to exclude other etiologies of dementia. They include a complete blood count (CBC), erythrocyte sedimentation rate (ESR), blood glucose levels, thyroid, liver, and kidney function tests, vitamin B12 levels, and Venereal Disease Research Laboratory (VDRL) test for syphilis. In addition, other tests like human immunodeficiency virus (HIV) testing, and tests to rule out autoimmune diseases should be ordered. Neuroimaging with computed tomography (CT) and magnetic resonance imaging (MRI) help to confirm the diagnosis with MRI being considered the gold standard. A vascular cause of dementia mainly can be excluded if CT and MRI do not demonstrate any cerebrovascular pathology. MRI findings in VaD include multiple white matter infarcts or lesions in the periventricular white matter, lacunar infarcts, and atrophy of the hippocampal or entorhinal cortical areas. Positron emission tomography (PET) helps in the identification of VaD and differentiates it from AD . Cerebral angiography is only indicated prior to carotid endarterectomy and is likely to show beading of the cortical blood vessels. Other tests which may be performed include an electrocardiogram, echocardiography, Holter monitoring, and carotid Doppler studies. There are no pharmacological agents with a regulatory approval for its treatment or prevention. [ncbi.nlm.nih.gov] Similarly, no single prognosis can be given, being largely dependent on the underlying cause and the degree to which successful treatment can be initiated. Promoted articles (advertising) [radiopaedia.org] Prognosis for People With Vascular Dementia If the conditions that cause vascular dementia go untreated, the prognosis is not good. [webmd.com] There are a variety of etiologies that contribute to the development of vascular cognitive impairment and VaD, and these are often associated with other dementia-related pathologies such as Alzheimer disease. [ncbi.nlm.nih.gov] SIDAM: a structured interview for the diagnosis of dementia of the Alzheimer type, multi-infarct dementia and dementias of other etiology according to ICD-10 and DSM III-R. Psychol Med. 1991 ; 21 :225-236. [doi.org] Author information 1 Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. [email protected] 2 Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands. [email protected] 3 Department of Neurology, [ncbi.nlm.nih.gov] The Epidemiology of Vascular Dementia, Geriatrics, Prof. Craig Atwood (Ed.), ISBN: 978-953-51-0080-5, InTech. O’Brien, J. and Markus, H. (2014). Vascular risk factors and Alzheimer’s disease. BMC Medicine, 12(1). [verywellhealth.com] CONCLUSIONS: An imbalance in pro-oxidant and anti-oxidant defenses is apparently involved in the pathophysiology of the AD and MD groups. [ncbi.nlm.nih.gov] Similarly, the effects of lipids and lipid-lowering therapy on preventing or treating dementia remain unclear; the few trials that have assessed lipid-lowering therapy for preventing (two trials) or treating (four trials) dementia found no evidence to [ncbi.nlm.nih.gov] It describes the difficulty of making a firm diagnosis and the importance of stroke prevention. [web.archive.org] Prevention Early detection and accurate diagnosis are important, as vascular dementia is at least partially preventable. [en.wikipedia.org] - Ramos AR, Dib SI, Wright CB. Vascular Dementia. Curr Transl Geriatr Exp Gerontol Rep. 2013;2(3): 188-195. - Kalaria RN. Cerebrovascular disease and mechanisms of cognitive impairment: evidence from clinicopathological studies in humans. Stroke. 2012;43:2526–2534. - Gorelick PB, Scuteri A, Black SE, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American heart association/American stroke association. Stroke. 2011;42:2672–2713. - van Straaten ECW, Scheltens P, Knol DL, et al. Operational definitions for the NINDS-AIREN criteria for vascular dementia: an interobserver study. Stroke. 2003;34:1907–1912. - Jellinger KA. Morphologic diagnosis of “vascular dementia” – a critical update. J Neurol Sci. 2008;270:1–12 - Ying H, Jianping C, Jianquing Y, et al. Cognitive variations among vascular dementia subtypes caused by small, large or mixed vessel disease. Arch Med Sci. 2016;12(4):747-753. - Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189-198. - American Psychiatric Association. Diagnostic and Statistical Manual of Mental disorders (5th ed.). Washington, DC. American Psychiatric Association; 2013. - Nagata K, Maruya H, Yuya H, et al. Can PET data differentiate Alzheimer's disease from vascular dementia?. Ann N Y Acad Sci. 2000;903:252-261.	2	6	0	0	1	0.91625	1	2,628
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
Basic Nutritional Support Heart and Cholesterol Finally, a Healthy Energy Drink for you and your kids! Chronic Fatigue Syndrome By Ronald Steriti, ND, PhD Chronic Fatigue Syndrome (CFS) is defined as debilitating fatigue and associated symptoms last-ing at least 6 months. Even though the Centers for Disease Control (CDC) officially recognized chronic fatigue syndrome in 1988, it remains a controversial issue. Chronic Fatigue Syndrome is closely related to another chronic condition, fibromyalgia (FMS). Muscle pain is the prominent symptom of fibromyalgia. However, preliminary studies by the Centers for Disease Control reveal that, for those individuals whose chronic fatigue does not significantly improve after a 5-year duration, the most prominent symptom changes from fatigue to muscle pain The criteria for diagnosing chronic fatigue syndrome was officially defined by the Centers for Disease Control (CDC) in 1988. They have recently revised their definition. The Oxford criteria differs slightly. The British criteria insists upon the presence of mental fatigue, while the American criteria includes a requirement for several physical symptoms, reflecting the belief that CFS has an underlying immune or infectious pathology. [1, 2] The CDC Criteria defines Chronic Fatigue Syndrome as: clinically evaluated, unexplained, persistent or relapsing fatigue that is: of new or definite onset; not a result of ongoing exertion; not alleviated by rest; and results in a substantial reduction in previous levels of occupational, social, or personal activity. Four or more of the following symptoms that persist or recur during 6 or more consecutive months of illness and that do not predate the fatigue: · Self-reported impairment of short-term memory or concentration · Sore throat · Tender lymph nodes · Muscle pain · Multi-joint pain without swelling or redness · Headaches of a new type, pattern, or severity · Unrefreshing and/or interrupted sleep Exclusion criteria includes: · Active, unresolved, or suspected disease that is likely to cause fatigue · Psychotic, melancholic or bipolar depression (but not uncomplicated major depression) · Psychotic disorders, Dementia, Anorexia or bulemia nervosa · Alcohol or other substance misuse · Severe obesity The Oxford (British) Criteria defines Chronic Fatigue Syndrome as: Severe disabling fatigue of at least six months duration that: affects both physical and mental functioning; and was present for more than 50% of the time. Other symptoms, particularly myalgia and sleep and mood disturbances, may be present. Exclusion criteria includes: · Active, unresolved, or suspected disease that is likely to cause fatigue · Psychotic, melancholic or bipolar depression (but not uncomplicated major depression) · Psychotic disorders, Dementia, Anorexia or bulemia nervosa Although the symptoms listed above are the official diagnostic criteria, many patients with chronic fatigue syndrome present with a variety of other symptoms, including: · Pain is almost universal in chronic fatigue · Chemical sensitivities · Secondary infections, including Candida and viral infections · Cognitive impairment, including short-term memory loss, difficulty concentrating, word searching, and math problems · Digestive disturbances, such as chronic constipation or diarrhea · Night sweats or spontaneous daytime sweats, unaccompanied by fever · Headaches, migraines · Weakness (paresis), muscle fatigue and pain (fibromyalgia) · Premenstrual syndrome (PMS) · Sleep disorders, including excessive sleep (hypersomnia), light sleep or an inability to sleep for more than an hour (hyposomnia), disturbing nightmares · A period of 1-3 hours after awakening during which they are too exhausted to get out of bed (dysania) · Cystitis (inflammation of the urinary bladder), particularly interstitial cystitis in which urine cultures are negative · Vision and eye problems, including sensitivity to light (photophobia), dry eyes, tunnel vision, night blindness and difficulty focusing An initial office exam may also find the following signs: · Low blood pressure, particularly on standing (orthostatic hypotension) · Low oral temperatures (less than 97˚ F) · Slightly elevated oral temperatures (less than 100˚ F), which are part of persistent flu-like symptoms. · Increased heart rate (tachycardia) · A positive Romberg test (unsteadiness when standing with eyes closed) Conventional Lab Tests Doctors usually perform the following labs when attempting to diagnose a patient with CFS: · Complete blood count (CBC) with differential · Chemistry panel · Erythrocyte Sedimentation Rate (ESR), a marker of inflammation Optional tests include: · Anti-nuclear antibodies (ANA) and rheumatoid factor (RF). These are tests for rheumatoid arthritis and systemic lupus erythematous (SLE) · Thyroid tests (T3, T4, TSH) · Adrenal tests (AM and PM cortisol levels) · Lyme titers and HIV serology Specific tests that support (but do not necessarily confirm) a diagnosis of chronic fatigue include: · Tests for viral infections, such as cytomegalovirus, Epstein-Barr virus, Human herpes virus 6, and coxsackie virus · Immune system tests, including low natural killer (NK) cell counts, elevated interferon alpha, tumor necrosis alpha, interleukins 1 and 2, T cell activation, altered T4/T8 cell ratios, low T cell suppressor cell (T8) count, fluctuating B and T cell counts, antinuclear antibodies, immunoglobin deficiency, antithyroid antibodies · Exercise testing may show decreased cortisol levels after exercise, decreased cerebral blood flow after exercise, inefficient glucose utilization, and erratic breathing patterns Research into the cause(s) of chronic fatigue syndrome touches upon a vast array of systems and etiologies. Several lab tests, in addition to those mentioned above may be helpful in guiding appropriate treatment. These would include: · Functional assessments of the adrenal gland, including measurements of cortisol, DHEA, and DHEA-S · Assessments of oxidative stress · Homocysteine levels · C-reactive protein, a sensitive marker of inflammation · Toxin analysis, including heavy metals, pesticides, and organic chemicals Possible Causes of Chronic Fatigue There is a considerable amount of research into the cause of chronic fatigue syndrome. Many researchers propose that there may be several different mechanisms that underly CFS. The possible causes of CFS fall into a few broad categories: · Immune system activation, particularly by viruses · Oxidative stress, glutathione deficiency · Endocrine dysfunction, including adrenal fatigue, thyroid deficiency and hypothalamic-pituitary axis abnormalities · Neurotransmitter deficiencies · Drug-induced fatigue As you will see from the following discussion, many of these causes are inter-related. For instance, oxidative stress can cause immune dysfunction through the nitric oxide and peroxynitrate systems. The immune system is also greatly influenced by the endocrine system (and the hormones involved, including DHEA, melatonin). For many people (and physicians) chronic fatigue syndrome is very confusing. In this article we will present current research on each of the components followed by a section on natural therapies that have been shown to be effective. The Immune System and Chronic Fatigue Syndrome Viruses and CFS Symptoms of CFS resemble a post-viral state and, for this reason, chronic viral conditions have been thought to contribute to CFS in some patients. Several viruses have been associated with CFS, including: · Herpes virus, particularly human herpes virus 6 (HHV-6) · Epstein-Barr virus (a herpes virus which causes infectious mononucleosis) · Cytomegalovirus (a herpes virus) · Coxsackievirus B1 and B4 Chronic viral infections have a detrimental impact on the body through several mechanisms: · Chronic viral infections cause the immune system to be activated in an effort to fight the infection · Chronic infections are a cause of inflammation in the body A primary strategy for chronic fatigue syndrome is to support the immune system in fighting viral infections. The Immune System The immune system is a complex system of cells and chemical messengers that work together to keep the body clear of pathogenic infections. The components specifically involved in viral immunity include: · Antigens (viruses) attach to T-helper cells which secrete a variety of chemical messengers (including interferon and interleukin-2) that activate NK cells, macrophages, cytotoxic T cells, and memory B cells. · Interferon is a group of glycoproteins that activate macrophages to form Natural Killer (NK) cells · NK cells lyse (split apart) cells that contain viruses. · Interleukin-2 stimulates proliferation of B and T cytotoxic cells. · Cytotoxic T cells are formed to attack specific antigens (viruses). An article published in the journal of Clinical Infectious Disease measured natural killer cell activity in 50 healthy individuals and 20 patients with clinically defined chronic fatigue immune dysfunction syndrome (CFIDS). The patients were divided into three groups based on severity of the clinical status. NK cell activity decreased with the increasing severity of the clinical condition. Researchers have found that human herpes virus 6 targets and kills NK cells. Supplements that have been shown to increase NK cell activity include beta-carotene, vitamin E, zinc, and DHEA. The herbs echinacea and ginseng have been shown to increase NK cell activity in CFS patients (see the Natural Therapies section). Viruses that “Fool” the Immune System There are two different types of T-helper cells which defend against different organisms: · T-helper 1 (Th1) cells target intracellular pathogens (organisms that invade cells), such as viruses. Interleukin-12 (IL-12) stimulates Th1 activation. · T-helper 2 (Th2) cells target organisms that are found outside of cells. T-helper 2 cells are involved in humoral or antibody-mediated immunity and are triggered by interleukin-10 (IL-10) which is stimulated by bacteria, parasites, toxins, and allergens. Each of the T-helper cells are activated by different cytokines (see Table). In health, there is a balance between Th1 and Th2 activity. When presented with an acute infection, the Th1 system predominates (and Th2 is supressed). In chronic infections, the Th2 system predominates leading to antibody production. Table: Cytokine profiles and functions of T helper cells Viruses, especially herpes viruses (like Epstein-Barr virus, cytomegalovirus, and human herpes virus 6) make proteins that mimic IL-10 which activates the Th2 system. Unfortunately, Th2 activation suppresses T-helper 1 (Th1) activity, particularly cytotoxic T cells and natural killer (NK) cells which are the main defense against viruses. In this way the viruses are able to “fool” the immune system and remain untouched by the bodies natural defenses. Addressing the two different types of T-helper cells has been the focus of work be Paul Cheney, MD. His protocols are are designed to stimulate Th1 and inhibit Th2. Several nutritional supplements, including essential fatty acids, vitamin A, vitamin E, DHEA and melatonin, have been found to have beneficial effects of the Th1:Th2 ratio (see the Natural Therapies section below). Infection and Inflammation A new theory has been published by Dr. Martin L. Pall (Professor of Biochemistry and Basic Medical Sciences at Washington State University). The theory involves a chain of events: · Chronic infections that often precede CFS act to induce excessive production of inflammatory cytokines. · Inflammatory cytokines induce nitric oxide synthase (iNOS) which synthesizes excessive amounts of nitric oxide · Nitric oxide reacts with superoxide to produce the potent oxidant peroxynitrite (nitrogen dioxide). · Peroxynitrite acts to increase the levels of both nitric oxide and superoxide which react to produce more peroxynitrite In this way, once peroxynitrite levels are elevated, they may act to continue the elevation, thus producing a self-sustaining vicious cycle. It is this cycle, according to the theory, that maintains the chronic symptoms of CFS and it is this cycle, therefore, that must be interrupted to effectively treat this condition. Figure: Peroxynitrate metabolism Breaking the infection-inflammation cycle Breaking the chain of inflammation caused by chronic viral infections would require a three-part protocol: · First, the underlying viral infection should be addressed with antiviral supplements (such as ginseng, echinacea and lactoferrin) and those that shift the Th1:Th2 ratio (such as essential fatty acids and vitamin E). · Second, inflammation should be reduced with anti-inflammatory agents (such as essential fatty acids and curcumin). · Third, the nitric oxide system should be supported with supplements such as arginine, vitamin B2 (riboflavin), vitamin B3 (niacin), and folate. Supplements that Support the Immune System Ginseng and Echinacea Commission E, the group of scientists that advises the German government about herbs, endorses ginseng "as a tonic to combat feelings of lassitude and debility, lack of energy and ability to concentrate, and during convalescence." Ginseng is highly prized in China as an herb that increases energy. The higher grades are extremely expensive. Most of the studies on ginseng have focused on its use in enhancing sports performance. Echinacea has become very popular in the United States as “the herb” to take for colds and flus. Echinacea has strong antiviral properties and has been shown to increase NK cell production. [10, 11] An article published in the journal Immunopharmacology found that both echinacea and ginseng (at concentrations greater or equal to 0.1 or 10 mcg/kg, respectively) significantly enhanced NK-function in patients with chronic fatigue syndrome or the acquired immunodeficiency syndrome. Essential Fatty Acids The use of essential fatty acids in chronic fatigue syndrome is controversial due to the results of one negative study. It has been proposed that essential fatty acids play a role in chronic fatigue syndrome. One possible mechanism is that viruses, as part of their attack strategy, may reduce the ability of cells to make 6-desaturated essential fatty acids. [14, 15] The use of essential fatty acids for post-viral fatigue syndrome was examined in a double blind, placebo-controlled study of 63 adults. The patients had been ill for one to three years after an apparent viral infection, suffering from severe fatigue, myalgia and a variety of psychiatric symptoms. The patients received either placebo or a preparation containing linoleic, gamma-linolenic (GLA), eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) over a 3-month period (eight 500-mg capsules per day). Participants were asked to assess their improvement at months 1 and 3. The treatment group showed continual improvement, whereas many in the placebo group reverted towards baseline. Table: Improvement with essential fatty acid treatment The essential fatty acid composition of their red cell membrane phospholipids was analyzed at the first and last visits. The essential fatty acid levels were abnormal at the baseline and corrected by active treatment. The authors concluded that essential fatty acids provide a rational, safe and effective treatment for patients with post-viral fatigue syndrome. A follow-up study of 50 patients diagnosed with chronic fatigue syndrome found no significant difference between the placebo group and those treated with Efamol marine (a combination of Evening Primrose Oil and Marine Fish Oil that contains linoleic acid, GLA, EPA and DHA) In addition, no difference was seen in red cell membrane lipids between the patients and control group. These results sharply contrasted the previous study by Behan et al. Essential fatty acids have been shown to have an effect on the ratio of T-helper 1 and 2 cells. High dietary intake of linoleic acid results in high tissue production of prostaglandin E2, which in turn causes inhibition of the proliferation and cytokine production of Th1 cells, mediators of cellular immunity. A study examined the effects on the immune system of either a low-fat diet or a high-fat diet containing coconut oil (rich in saturated fatty acids), safflower oil (rich in omega-6 EFAs), or fish oil (rich in omega-3 EFAs) as the main fat sources on mice. The ratio of production of Th1- to Th2-type cytokines was lower for lymphocytes from mice fed the safflower oil or fish oil diets. Although all fatty acids decreased IL-2 production in a concentration-dependent manner, saturated fatty acids were the least potent and omega-3 EFAs the most potent inhibitors, with omega-6 EFAs falling in between in terms of potency. The authors concluded that EFAs act to inhibit production of Th1-type cytokines with little effect on Th2-type cytokines with omega-3 EFAs being particularly potent. Essential fatty acids are named “essential” because they play a vital role in health. Essential fatty acids are found in healthy oils, such as fish, flax, borage, and perilla. Unfortunately fatty acids are damaged by heat and many people are deficient due to the high heats used to process packaged foods. Fatty acid metabolism requires several nutritional cofactors. These include L-carnitine (to move fats in an out of cells), vitamin E (which protects fats against oxidation), and NADH (which breaks fats down to form energy). Each of these nutrients have been studied for use in chronic fatigue syndrome. The amino acid L-carnitine is used in the body to transport fats across cell membranes. Carnitine is synthesized in the body from lysine (an essential amino acid that has antiviral properties) and methionine (an amino acid involved in homocysteine metabolism). L-carnitine is often included in weight-loss supplements to aid in moving fats. L-carnitine is also known to boost energy levels. [20, 21] Several studies have found deficiencies of carnitine in patients with CFS, while more recent studies have contradicted these findings: · A study of 35 CFS patients (27 females and 8 males) found significantly lower serum total carnitine, free carnitine and acylcarnitine levels, and that higher serum carnitine levels correlated with better functional capacity. · Another study found low levels of acylcarnitine in both Japanese and Swedish patients with chronic fatigue syndrome. · A recent study of 25 women with CFS and 25 healthy controls in The Netherlands, however, found no difference in carnitine levels. A clinical trial of carnitine for the treatment of CFS found clinical improvement in 12 of 18 patients. The greatest improvement occurred between weeks four and eight of treatment. One patient was unable to complete the trial due to the development of diarrhea. Vitamin E is a powerful antioxidant that is found in vegetable oils. Vitamin E works to protect the fat-soluble parts of the body, such as LDL cholesterol. Recent research in mice has found that vitamin E may enhance Th1 cytokines, possibly as a result of reduced prostaglandin E2 (PGE2, an inflammatory compound) production. NADH (reduced B-nicotanimide dinucleotide) is a coenzyme molecule formed from vitamin B3 (niacin). NADH donates its hydrogen in many reactions throughout the body. It is involved in oxidative phosphorylation (the production of ATP, the energy molecule of the body), fatty acid oxidation (the breakdown of fats to make energy), and in carbohydrate metabolism. A recent randomized, double-blind, placebo-controlled crossover study examined the use of NADH with chronic fatigue syndrome. Twenty-six eligible patients diagnosed with CFS received either 10 mg of NADH or placebo for a 4-week period. Eight of 26 (31%) responded favorably to NADH in contrast to 2 of 26 (8%) to placebo. Based upon these encouraging results the authors decided to conduct a larger study to establish its efficacy in CFS. NADH (5 to 10 mg per day) is most effective when taken in the morning 30 minutes before breakfast. Vitamin A plays a role in the development of T-helper and B cells. Vitamin A deficiency impairs innate immunity by diminishing the function of neutrophils, macrophages, and natural killer cells. Although vitamin A does play a role in balancing Th1 and Th2 function, it does so by down-regulating Th1 cell IFN-gamma secretion directly, decreasing activated antigen presenting cell (APC) function, and promoting Th2 cell growth and/or differentiation. Therefore, although vitamin A is an important nutrient for immune function, chronic fatigue syndrome patients should avoid excessively high doses. [29-33] Whey protein is perhaps the oldest and most well-known supplement used by athletes and body builders. In recent years, scientists have begun to investigate the health benefits of proteins to improve immunity and prevent diseases. Whey has recently been shown to have significant antiviral properties (with much of the research on it’s ability to increase glutathione levels and inhibit HIV). [34, 35] Whey protein is comprised of four major protein fractions and six minor protein fractions. The major protein fractions are beta-lactoglobulin, alpha-lactalbumin, bovine serum albumin, and immunoglobulins. Each of these components have important disease-fighting effects. Lactoferrin, in particular, has been shown to have significant antiviral activity. [36-38] DHEA and Melatonin DHEA (dehydroepiandrosterone) is the most prevalent hormone produced by the adrenal glands. It circulates in the bloodstream as DHEA sulfate (DHEAS) and is converted into other hormones, including estrogen and testosterone. Melatonin is a natural hormone that regulates the human biological clock. Levels of melatonin are lower during the day and higher at night. Melatonin is commonly used before bed to aid in sleep. An article published in the journal Immunology described a study of the immune effects of DHEA and melatonin in mice infected with a leukemia retrovirus that caused AIDS. Treatment with DHEA or melatonin alone, as well as together, prevented the reduction of B- and T-cell proliferation as well as of Th1 cytokine secretion caused by retrovirus infection. Supplementation also suppressed the elevated production of Th2 cytokines stimulated by retrovirus infection. Arginine is made in the body from glutamic acid, and is therefore considered semi-essential. Arginine stimulates the first step in the urea cycle, which rids the body of nitrogenous waste. Arginine is concentrated in muscles, where it is responsible for the high energy compounds guanidophosphate, phosphoarginine and creatine. An article published in the European Journal of Clinical Investigation described a study of the effects of L-arginine on NK cell function in 20 subjects with chronic fatigue syndrome and 21 healthy individuals. Arginine was found to increase NK activity in the healthy subjects but not those with CFS. Further investigation, however, found that the effect of arginine on NK cell activity was mediated by nitric oxide. That is, the increase in NK activity induced by arginine was blocked by the addition of an inhibitor of inducible nitric oxide synthase. NK activity was increased by incubation with a nitric oxide donor. The authors concluded that a dysfunction in the nitric oxide mediated NK cell activation may exist in CFS patients. Caution Arginine has been found to promote the growth of Herpes simplex, especially if lysine levels are low. Both lysine and arginine contribute to immunity and have antiviral properties. Proteins (meats, fish and cheese) usually contain slightly more lysine than arginine, with eggs containing equal amounts. Supplementation with equal amounts of lysine and arginine is recommended for those considering this therapy. One 500 mg capsule of each can be taken once or twice daily. Antioxidants and CFS Free radical damage (oxidative stress) is probably the most significant cause of biologic aging. Free radicals are unstable molecules that damage cells and are implicated in most diseases associated with aging. Antioxidants are the bodies natural defense against free radical-induced cell damage. Recent studies have shown that oxidative stress plays a role in the development of chronic fatigue syndrome. [41-43] Exercise has been shown to increase the production of oxidants. Fortunately, regular endurance exercise results in adaptations in the skeletal muscle antioxidant capacity, which protects myocytes (muscle cells) against the deleterious effects of oxidants and prevents extensive cellular damage. [44, 45] A study of the oxygen delivery to muscles in patients with CFS found that oxygen delivery and oxidative metabolism was significantly reduced in CFS patients after exercise, when compared with sedentary controls. The issue of exercise in chronic fatigue syndrome is a topic of debate. Many women with CFS were active athletically. There is some overlap between CFS symptoms and overtraining syndrome. Physical exercise is sometimes recommended for those with CFS. Unfortunately, for some people with CFS even minimal exercise can cause extreme fatigue. The antioxidant theory offers a novel explanation for this situation and provides several powerful therapies for those who enjoyed an active lifestyle before the chronic fatigue symptoms developed. Elevated Homocysteine Levels and CFS Homocysteine is a toxic intermediate molecule formed in the body during cellular damage. Homocysteine, although toxic itself, is normally metabolized into other nutrients that are beneficial to the body, including cysteine, taurine and glutathione. Homocysteine is so toxic to the body that many consider it to be much worse than cholesterol. A study of 12 women who fulfilled the criteria for both fibromyalgia and chronic fatigue syndrome found that, in all the patients, the homocysteine levels were increased in the cerebrospinal fluid (CSF). There was a significant positive correlation between CSF homocysteine and B12 levels and fatigue-ability, as rated on the Comprehensive Psychopathological Rating Scale. The authors concluded: “increased homocysteine levels in the central nervous system characterize patients fulfilling the criteria for both fibromyalgia and chronic fatigue syndrome”. Homocysteine and glutathione metabolism are related in biochemical pathways that involve cysteine, glutamine, glycine and GABA (see Figure). Figure: Glutathione metabolism Antioxidant Therapy for Chronic Fatigue Syndrome Glutathione and N-Acetyl Cysteine Glutathione is a peptide-like molecule naturally synthesized in the body from three amino acids: L-glutamic acid, L-cysteine, and glycine. Glutathione is one of the body’s most important and powerful antioxidants. Glutathione also attaches to toxic molecules, which are then eliminated from the body (detoxification). An article published in the journal Medical Hypothesis proposed that glutathione, an antioxidant essential for lymphocyte function, may be depleted in chronic fatigue syndrome patients. Glutathione is needed for both the immune system and for aerobic muscular contraction. The authors proposed that glutathione depletion by an activated immune system also causes the muscular fatigue and myalgia associated with chronic fatigue syndrome. Cysteine is a precursor to glutathione. It has been hypothesized that glutathione and cysteine metabolism may play a role in skeletal muscle wasting and muscle fatigue. The combination of abnormally low plasma cysteine and glutamine levels, low natural killer (NK) cell activity (with a resulting susceptibility to viral infection), skeletal muscle wasting or muscle fatigue, and increased rates of urea production defines a complex of abnormalities that is tentatively called "low CG syndrome." These symptoms are found in patients with HIV infection, cancer, major injuries, sepsis, Crohn's disease, ulcerative colitis, chronic fatigue syndrome, and to some extent in over-trained athletes. N-acetyl-cysteine is a precursor of glutathione that has been shown to be helpful against viruses (most of the research has been with HIV and Hepatitis infections). [51, 52] Coenzyme Q10 has long been prescribed for CFS patients. CoQ10 is a potent antioxidant that aids in metabolic reactions including the process of forming ATP, the molecule the body uses for energy. Virtually every cell in the body contains CoQ10. It is concentrated in the mitochondria, the area of the cells where energy is produced. Judy presented a study of 20 female patients with CFS that required bed rest following mild exercise and 20 healthy controls. Eighty percent of the CFS patients were found to be deficient in CoQ10 which further decreased following mild exercise or over the course of normal daytime activity. After three months of CoQ10 supplementation (100 mg per day) exercise tolerance (400 kg-meters of work) more than doubled. All patients had improved. Ninety percent had reduction and/or disappearance of clinical symptoms, and 85 percent had decreased post-exercise fatigue. [21, 53] Coenzyme Q10, 100 mg taken 3 times a day, often helps victims of severe chronic fatigue syndrome. Folate plays a role in many key biochemical reactions in the body. Folic acid is involved in homocysteine metabolism (with vitamins B6 and B12). It is needed to form glutamate (a precursor of glutathione), and is involved in DNA replication. Folate is also needed to make SAMe (S-adenosyl methionine), a natural supplement which affects (and may improve) mood. An article published in the journal Neurology described a study in which serum folate levels were measured in 60 patients with chronic fatigue syndrome. Researchers found that 50% had values below 3.0 micrograms/L (the normal values are 2-20). The authors concluded that some patients with CFS are deficient in folic acid. Most people do not consume the recommended amount of folic acid in their diet. Mild folic acid deficiencies are common in Western societies, and women taking birth control pills are at higher risk. It is recommended that women who are or could become pregnant should take 400-800 mcg per day to reduce the risk of birth defects. Most nutritionally-oriented doctors recommend that everyone take 400 mcg of folic acid per day. Glutamine is a conditionally essential amino acid that is needed during periods of excessive stress. Glutamine is the preferred energy for enterocytes, the cells lining the gastrointestinal tract. An article published in the British Journal of Sports Medicine described a study of athletes during an intense training period before the 1992 Olympics. The athletes were divided into three groups who differed in training fatigue and were considered separately. Group A (21 track and field athletes) had no lasting fatigue; group B (12 judo competitors) reported heavy fatigue at night but recovered overnight to continue training; group C (18 track and field athletes, one rower) had chronic fatigue and had been unable to train normally for at least several weeks. Plasma amino acid analysis showed that group A had a normal amino acid pattern, and both groups B and C had decreased plasma glutamine (average 33%) with, especially in group B, decreased histidine, glucogenic, ketogenic, and branched chain amino acids. Ten athletes in group C presented with infection. After three weeks of additional protein intake, virtually all the low glutamine levels increased to above 500 micromol/L. Total amino acids increased, and the amino acid pattern normalized. Six of the ten athletes on this protein intake returned to increased training within the three weeks. Glutamine is a non-essential amino acid that supplies energy to the brain. It has been found to be helpful in reducing fatigue, improving exercise endurance, alleviating hypoglycemia, and strengthening the immune system. One or two grams may be used as needed and is often recommended before exercise. Insomnia, however, may occur if glutamine is consumed too close to bedtime. CFS and The Endocrine System The Hypothalamus-Pituitary-Adrenal Axis The HPA axis refers to the hypothalamus, pituitary, and adrenal glands which are part of the endocrine system. The hypothalamus secretes several hormones that control the pituitary gland. The pituitary gland is considered the “master gland” of the endocrine system because it secretes hormones that control other glands (including the ovaries, testes, adrenals, and thyroid glands). A major role of the HPA axis is to restrain the immune system and prevent tissue damage. Reciprocal interactions between the HPA axis and immune system constitutes a new endocrine feedback loop that has given rise to the field of neuroendocrine immunology. "Many experts now think that chronic fatigue syndrome may be an example of the hypothalamus failing to properly regulate the brain’s influence on the immune system," says Jay Lombard, M.D., assistant clinical professor of neurology at Weill Medical College of Cornell University in New York City and co-author of The Brain Wellness Plan. It has been proposed that CFS is a mild form of Addison’s disease (which may be referred to as adrenal insufficiency, adrenal fatigue or hypoadrenalism). The following evidence is presented: [58-60] · Many of the symptoms of chronic fatigue syndrome overlap those of Addison’s disease (adrenal failure). · Improvement in CFS patients has occurred after supplementation with mineralocorticoids (fludrocortisone), low-dose hydrocortisone (cortisol), and licorice (an old herbal remedy for Addison’s disease). Cortisol is the main glucocorticoid secreted the adrenal glands. It has two main functions: · Cortisol increases blood glucose levels during periods of stress (the “fight or flight response”) by mobilizing carbohydrates, lipids and protein. It also stimulates the breakdown of fats to release energy. Cortisol inhibits the effects of insulin and decreases the rate of glucose use by cells. · Glucocorticoids, including cortisol, are anti-inflammatory. They inhibit histamine secretion, inhibit lymphocyte production, and stabilize macrophage lysosomes. Cortisol production by the adrenal glands follows a diurnal rhythm: They are elevated in the morning and lower in the evening (during sleep). People under stress often have no diurnal variation in their cortisol levels. An article published in the journal Neuropsychobiology described a study in which morning and evening serum cortisol and ACTH concentrations, and diurnal changes in hormone levels, were measured in 30 patients with chronic fatigue syndrome (CFS) but without concurrent depressive disorder and a control group of 15 matched healthy volunteers. The diurnal change in cortisol levels was significantly less in CFS than in controls. In CFS subjects, evening levels of cortisol correlated significantly with measures of general health and physical functioning, while diurnal change in cortisol was positively correlated with measures of functional improvement over the past year and current social functioning. An article published in the Journal Clinical Endocrinology Metabolism described a study of cortisol levels in thirty CFS patients and 72 normal volunteers. Compared to normal subjects, CFS patients demonstrated significantly reduced basal evening glucocorticoid levels and low 24-hour urinary free cortisol excretion, but elevated basal evening ACTH concentrations. There was increased sensitivity to ACTH, but a reduced maximal response. The authors concluded that primary adrenal insufficiency or a pituitary source is unlikely, and that the data was compatible with a mild central adrenal insufficiency secondary to either a deficiency of CRH (a secretion of the hypothalamus) or some other central stimulus to the pituitary-adrenal axis. One study measured the morning and evening salivary cortisol levels obtained on consecutive days in the first 3 days of the menstrual cycle in 14 patients with chronic fatigue syndrome, 26 community cases of ICD-10 current depressive episodes and 131 healthy community controls. The mean evening cortisol was significantly lower in the chronic fatigue syndrome patients compared to controls with depression and healthy controls. Chronic fatigue syndrome patients without psychiatric disorder had significantly lower morning salivary cortisol levels compared to controls. An article published in the Journal of Affective Disorders described a study in which cortisol levels were measured in 10 patients with CFS, 15 patients with major depression, and 25 healthy controls. Baseline circulating cortisol levels were highest in the depressed, lowest in the CFS, and intermediate between the two in the control group. Prolactin responses to the selective serotonin-releasing agent d-fenfluramine were lowest in the depressed, highest in the CFS, and intermediate between both in the healthy group. The authors concluded that depression is associated with hypercotisolemia and reduced central serotonin neurotransmission and suggest that CFS may be associated with hypocortisolemia and increased 5-HT function. One interesting study measured the size of the adrenal glands in eight CFS patients that had evidence of adrenal hypofunction (determined by a subnormal resonse to an ACTH stimulation test). The right and left adrenal gland bodies were reduced by over 50% in the CFS subjects indicative of significant adrenal atrophy in a group of CFS patients with abnormal endocrine parameters. Natural Supplements to Support Adrenal Function DHEA (dehydroepiandrosterone) is a hormone secreted from the adrenal glands. It is a precursor of the sex hormones (estrogen and testosterone). DHEA-S has recently been shown to have beneficial effects on memory, stress, anxiety, sleep and depression. Therefore, the deficiency of DHEA-S might be related to the symptoms in patients with CFS. DHEA has been reported to improve energy levels in chronic fatigue patients. One study showed the value of DHEA and vitamin C infusion treatment in the control of chronic fatigue syndrome. A study of 15 subjects with CFS, 15 subjects with major depression, and 11 healthy subjects found that DHEA and DHEA-S levels were significantly lower in the CFS compared to the healthy group. DHEA-S levels, but not DHEA, were lower in the depressives. The authors concluded that DHEA has a potential role both therapeutically and as a diagnostic tool, in CFS. Another study of DHEA levels in 22 CFS patients and 14 healthy controls found normal basal DHEA levels, but a blunted serum DHEA response curve to ACTH (adreno-corticotropic hormone) injection. ACTH normally stimulates the adrenal glands to secrete DHEA. The authors concluded that endocrine abnormalities play a role in CFS and that a relative glucocorticoid deficiency might contribute to the overall clinical picture in CFS. Licorice is highly valued as a medicinal herb by the Chinese and is an ingredient in almost all of the Chinese patent herbal formulas. Licorice has a sweet taste and helps combat fatigue. The active constituent in licorice, glycyrrhizin, stimulates the production of hormones, including cortisone, and stimulates the production of interferon, which boosts immunity. Licorice is an old herbal remedy that was used medically for Addison’s disease and adrenal insufficiency. [72, 73] Licorice should be used with care since it is well-known to increase blood pressure. Two to four 500 mg capsules can be taken twice a day. Licorice may also be consumed as a tea (one cup in the morning). Orthostatic hypotension is defined as an excessive fall in blood pressure on standing, usually greater than 20/10 mmHg. It is considered to be a manifestation of abnormal blood pressure regulation due to a variety of causes. Hypotension, particularly orthostatic hypotension, is a common symptom in chronic fatigue patients. Many people with CFS have chronic low blood pressure (the normal is 120/80 mmHg), which is made even worse on standing. This may be a particular problem in the morning, when standing can cause dizziness. Exercise or a heavy meal may exacerbate the symptoms. Syncope is a loss of consciousness and postural tone caused by diminished cerebral blood flow. Syncope often occurs during the morning shower, perhaps due to the vasodilating effect of hot water. There are several mechanisms that govern blood pressure. Upon standing, a large amount of blood pools in the veins of the legs and trunk. The transient decrease in venous return to the heart results in a low blood pressure. The body responds with a sympathetic-mediated release of catacholamines (norepinephrine and epinephrine) that increase heart rate contraction and vasoconstricts the arteries. With continued standing, antidiuretic hormone (ADH) is secreted which activates the renin-angiotensin-aldosterone system subsequently causing sodium and water retention and an expansion of the circulating blood volume. There are many causes of orthostatic hypotension, including: · Hypovolemia (low blood volume) induced by excessive use of diuretic agents (e.g., loop diuretics such as furosemide, bumetanide, and ethacrynic acid) and relative hypovolemia due to vasodilator therapy with nitrate preparations and calcium antagonists (verapamil, nifedipine, or diltiazem) or with angiotensin converting enzyme (ACE) inhibitors. · Histamine, a key player in allergic reactions, induces vasodilation and hypotension. · Potassium deficiency (hypokalemia) impairs the reactivity of vascular smooth muscle and may limit the increase in peripheral vascular resistance on standing. · The adrenocortical hypofunction of Addison’s disease may lead to orthostatic hypotension in the absence of adequate salt intake. · Several classes of drugs reversibly impair autonomic reflexes and reduce blood pressure on standing as an important adverse effect. These include many drugs used to treat psychiatric disorders such as the monoamine oxidase inhibitors (MAOIs) (isocarboxazid, phenelzine, and tranylcypromine) used to treat depression; the tricyclic antidepressants (nortriptyline, amitriptyline, desipramine, imipramine, and protriptyline) or tetracyclic antidepressants; and the phenothiazine antipsychotic drugs (chlorpromazine, promazine, and thioridazine). Other drugs that may produce orthostatic hypotension are quinidine, l-dopa, barbiturates, and alcohol. Vasopressin is a hormone secreted by the posterior pituitary gland that is also called antidiuretic hormone (ADH) because its principle effect is to cause retention of water by the kidneys. Vasopressin has several effects on the body in addition to the effect on water retention: · Vasopressin causes vasoconstriction of blood vessels which can increase blood pressure · Vasopressin induces secretion of ACTH in the anterior pituitary which stimulates cortisol production in the adrenal glands · Vasopressin also has a role in memory. Vasopressin is made from several amino acids, including cysteine, tyrosine, proline, glycine and arginine. Vaspressin secretion is affected by several stimuli, including: · Increased secretion of ADH is diagnosed as syndrome of inappropriate antidiuretic hormone (SIADH) and can be caused by: o Increased osmotic water pressure o Decreased extracellular fluid volume o Nicotine; Morphine, barbiturates, chlorpropramide, clofibrate, carbamazepine, angiotensin II o Pain, emotion, stress, exercise, standing o Nausea and vomiting · Decreased secretion of ADH can be caused by: o Decreased osmotic water pressure or Increased extracellular fluid volume o Butophanol, oxilorphan o Diabetes insipidus is decreased ADH or insensitivity to ADH which results in the passage of large amounts of dilute urine (polyuria) and thirst (polydipsia). Several studies have linked problems with vasopressin to chronic fatigue: [74, 75] · One study of 19 patients with chronic fatigue syndrome and 19 healthy controls found that patients with chronic fatigue syndrome had a reduced ACTH response to vasopressin infusion and a more rapid cortisol response to the infusion. · Another study of nine patients with postviral fatigue syndrome found low baseline levels and an erratic secretion of arginine vasopressin in the patients with postviral fatigue syndrome. · An article published in the journal Biological Psychiatry described a study of chronic fatigue syndrome patients which found that the combination of CRH and desmopressin (a synthetic analog of vasopressin) normalized the pituitary-adrenal response to CRH. The most common form of vasopressin available in the United States is lysine vasopressin made by Sandoz Pharmaceuticals in the form of a nasal spray called Diapid (Lypressin). Many people are experimenting with Diapid to help increase their memory. It may also be of use in chronic fatigue syndrome. Sodium is known to increase blood pressure and cardiac patients are usually placed on sodium-restricted diets. Chronic fatigue syndrome patients, however, often have hypotension. One study examined the use of sodium chloride (1200 mg) in a sustained-release formulation for 3 weeks in 22 patients with CFS and orthostatic hypotension. Of these 22 patients, 10 redeveloped orthostatic hypotension, while 11 did not show an abnormal response to the test and reported an improvement of CFS symptoms. However, those CFS patients who again developed an abnormal response to tilt-test had a significantly reduced plasma renin activity compared both with healthy controls and with those 11 chronic fatigue patients who improved after sodium chloride therapy. The testing of the renin levels of chronic fatigue syndrome patients that did not respond to sodium chloride is an important distinction in this study. As discussed earlier, orthostatic hypotension can be due to a several factors. The focus of this study was on adrenal hypofunction with inadequate salt intake. Those that did not respond to the salt intake had a reduction in renin, which increases blood pressure. Figure: The Renin-Angiotensin-Aldosterone System Sodium restriction has become a popular for those with high blood pressure (and associated increased cardiovascular risk factors). Chronic fatigue syndrome patients with low blood pressure and orthostatic hypotension do not need to restrict dietary sodium intake. Using sodium therapeutically should be done under the care of a well-trained and knowledgeable physician or cardiologist. Neurotransmitters and CFS Deficiencies in brain hormones and neu-rotransmitters are also known to cause low levels of energy. Catecholamines are neurotransmitters that are primarily secreted during times of stress. The principal catecholamines found in the body include norepinephrine, epinephrine, and dopamine. They are formed from the amino acid tyrosine. Figure: Tyrosine Metabolism Supplements That Support Neurotransmitter Function A study of the catecholamine production was performed on rats after swimming for a period of 8 hours. There was a decreased production of catecholamines after swimming. In the presence or L-tyrosine, there is at first an activation of noradrenaline synthesis, followed by a gradual normalization (on the 7th day) of adrenaline formation. One study examined the alterations in metabolism of catecholamines (adrenaline, noradrenaline, their precursors DOPA and dopamine, and their acid metabolites vanillyl mandelic acid) in sportsmen after development of acute fatigue as a result of the test physical loading. The authors found that excretion of catecholamines and their precursors was decreased for a long time after development of chronic fatigue in the resting state and the increase in excretion of the substances studied was not observed after physical loading. An article published in the journal Medical Science of Sports Exercise described a study of the effects of tyrosine on exercise tolerance and brain neurochemistry of mice. Tyrosine injections improved maze performance and prevented increase of levels of serotonin (5-HT) in the hypothalamus that follows exercise. Tyrosine administration significantly improved food consumption, cognitive behavior, and activity performance. The authors concluded that tyrosine may improve exercise tolerance and delay fatigue. An article published in the journal Brain Research Bulletin described a study of the effects of tyrosine on a group of 21 cadets during a demanding military combat training course. Ten subjects received five daily doses of a protein-rich drink containing 2 grams of tyrosine, and 11 subjects received a carbohydrate rich drink with the same amount of calories (255 kcal). The group supplied with the tyrosine-rich drink performed better on a memory and a tracking task than the group supplied with the carbohydrate-rich drink. In addition, the supplementation of tyrosine decreased systolic blood pressure. No effects on mood were found. The authors concluded that these findings suggest that supplementation with tyrosine may, under operational circumstances characterized by psychosocial and physical stress, reduce the effects of stress and fatigue on cognitive task performance. The amino acids phenylalanine or tyrosine, taken in daily doses of 1500 mg, can boost epinephrine and norepinephrine levels. Caution phyenylalanine and tyrosine should not be taken by those using MAO inhibitors and should be used with caution in those on thyroid medication (Synthroid). Magnesium is involved primarily with muscle relaxation. Acetylcholine is the neurotransmitter with calcium and magnesium regulating the amount of acetylcholine released. Calcium causes muscular contraction, while magnesium causes muscular relaxation. Magnesium deficiency causes neuromuscular irritability with muscle tightness and spasm and nerve conduction problems. It also affects the heart and cause hypertension or hypotension. Magnesium deficiency is a common cause of premenstrual cramping, and also causes fatigue. An article published in Lancet described a randomized, double-blind, placebo-controlled study of 20 patients with CFS. The CFS patients were found to have lower red cell magnesium concentrations. In a clinical trial, 32 CFS patients received either placebo or intramuscular magnesium sulfate every week for 6 weeks. Patients treated with magnesium claimed to have improved energy levels, better emotional state, and less pain, as judged by changes in the Nottingham health profile. Red cell magnesium returned to normal in all patients on supplemental magnesium but in only 1 patient on placebo. The authors concluded that these results show that magnesium may have a role in CFS. One study, however, found no difference in red blood cell magnesium concentrations in samples from 89 patients with CFS when compared to age and sex matched group selected from the normal population. A magnesium-loading test on six patients found no evidence of deficiency. A study of 97 chronic fatigue patients (chronic fatigue syndrome, fibromyalgia or/and spasmophilia) was conducted in Belgium. An IV loading test showed a magnesium deficit in 44 patients. After magnesium supplementation in 24 patients, the loading test showed a significant decrease in magnesium retention. Mean values of magnesium in the serum, red blood cell, and urine showed no significant difference between patients with or without magnesium deficiency. Serum magnesium levels were found to be significantly lower in the patients with spasmophilia (muscle cramps, twitching and spasms) than in the other patients. A study of 93 patients with unexplained chronic fatigue (54% with CFS) examined the relationship between magnesium deficiency and oxidative stress. Magnesium deficient patients (47%) had lower total antioxidant capacity in plasma, which was related to serum albumin. Magnesium deficient patients whose magnesium body stores did not improve after oral supplementation with magnesium (10 mg/kg/day) had persistently lower blood glutathione levels. The authors concluded that magnesium supplementation was followed by an improvement in magnesium body stores, in serum vitamin E, and its interrelated stage of lipid peroxidation. Magnesium plays a crucial role in metabolism. It is needed for activating B vitamins, relaxing muscles, and forming ATP, the energy molecule. Fatigue, muscle cramps and constipation are signs a magnesium deficiency. Normal concentrations of magnesium in blood do not rule out the diagnosis of the nervous form of primary chronic magnesium deficiency. The diagnosis of magnesium deficiency requires an oral magnesium load test. Most people do not consume enough magnesium in their diet. Magnesium is often paired with calcium as they work together and compete for absorption. Determining the proper ratio of calcium to magnesium is important, but can be determined readily. Taking too much magnesium often leads to diarrhea. An easy method would be to begin with one capsule of magnesium once or twice a day. The dose is increased until the stools become watery, then backed off to maintain a normal consistency of stools. Tryptophan and 5-HTP Tryptophan is the precursor for the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT), which is involved in fatigue and sleep. It is present in bound and free form in the blood, where the concentration is controlled by albumin binding to tryptophan. Figure: Tryptophan Metabolism Several older studies found that tryptophan was helpful in chronic fatigue. [90, 91] A recent study found that plasma-free tryptophan was significantly decreased in CFS patients. Tryptophan was banned for use as a supplement by the FDA following several deaths due to contaminated batches. Many companies are now making 5-HTP as a substitute for tryptophan. It has become a popular supplement used for depression. Unfortunately, 5-HTP is not as safe as tryptophan, particularly because it bypasses the enzyme tryptophan hydroxylase. As such, it can be converted into serotonin in peripheral tissue instead of in the brain. For this reason Life Extension Foundation recommends against the use of 5-HTP. Life Extension also encourages the FDA to reconsider its ban on tryptophan. Of particular concern to those that are considering supplementing with 5-HTP is that abnormally high levels (which can be achieved by supplementation or by prolonged exercise) can cause central fatigue. [93, 94] The following drugs are associated with side effects of chronic fatigue syndrome. Table: Medications that may cause fatigue Source: Physicians Desk Reference. Compiled by www.HolisticOnline.com There are currently no prescription medications approved by the FDA for use in chronic fatigue syndrome. There are, however, quite a number of medications that are used to treat the various symptoms of Chronic Fatigue Syndrome. Many are recommended for effects that may be unrelated the their primary use. These may include anti-depressants, anti-fungals, anti-histamines, anti-virals, CNS depressants (or stimulants), immunoglobulins, cardiac medications, anti-inflammatories, anti-convulsants, corticoids, and expectorants. Ampligen is an experimental anti-viral medication currently in phase III testing for the treatment of CFS. It is considered a “second generation interferon.” In clinical trials conducted outside the US, over 50% of test subjects taking Ampligen showed both physical and mental improvement of symptoms. Unfortunately, most of the study groups were too small for the results to be published in the scientific literature. Hemisherx, the drug manufacturer is hoping the current research trials will provide enough hard data to meet the criteria of FDA approval. Hydrocortisone is an anti-inflammatory that can be taken orally or administered topically. An article published in the journal Lancet described a study of 218 patients with chronic fatigue syndrome that received hydrocortisone (5 or 10 mg daily) for one month and placebo for one month. Self-reported fatigue scores for patients on hydrocortisone fell by 7.2 points, compared with 3.3 points for those on placebo. One researcher, however, concluded that although hydrocortisone treatment was associated with some improvement in symptoms, the degree of adrenal suppression precludes its practical use for CFS. Deprenyl, a MAO inhibitor Deprenyl or Derprenil, is also known as Eldepryl (Selegiline). It is an MAO-B inhibitor that is commonly used in Parkinson’s disease, in combination with levodopa or levodopa and carbodopa. Deprenyl inhibits the breakdown of dopamine by monoamine oxidase B (MAO-B). An article published in the journal Neuropsychobiology described a 6-week clinical trial of selegiline in 25 patients with chronic fatigue syndrome (CFS). Participants received placebo for two weeks, then 5 mg selegiline per day for two weeks, followed by two 5 mg tablets for two weeks. A significant improvement in tension/anxiety, vigor and sexual relations was found as compared with placebo. The authors concluded that selegiline has a small but significant therapeutic effect in CFS. Chronic Fatigue Syndrome is debilitating fatigue and associated symptoms lasting at least 6 months. The cause of CFS is as yet undetermined, but it may be triggered by infectious agents (especially viruses), stress, vitamin deficiencies, immunologic dysfunction, neurotransmitter deficits, adrenal or thyroid deficiency. 1. Ginseng (500 mg twice a day) has been found to enhance NK function in CFS patients. Ginseng is commonly used to help increase energy levels. 2. Echincea (500 mg twice a day) supports the immune system and has been found to enhance NK function in CFS patients. 3. Essential fatty acids may be of benefit in chronic fatigue. 4. Acetyl-L-carnitine (1000 to 2000 mg a day), Vitamin E (400 IU a day), and NADH (5 mg 2 times a day) support fat metabolism and may increase energy. 5. Whey protein should be considered as a source of amino acids and to enhance immunity and boost glutathione levels. 6. Lactoferrin (300 mg three times daily) has been shown to have significant antiviral properties and may be useful in chronic fatigue syndrome. 7. Glutathione (500 mg per day), and its precursors Glutamine (one gram per day) and N-Acetyl Cysteine (500 mg per day) are important antioxidants. Glutamine should not be taken at night as it may cause insomnia. 8. Vitamin B6, B12, folic acid (800 mcg per day) and trimethylglycine should be considered if homocysteine levels are elevated. SAMe (200 to 800 mg a day), a methyl donor, may be beneficial for symptoms of depression. 9. Coenzyme Q10 (100 mg 3 times a day) may be helpful in CFS for increased energy. 10. DHEA and melatonin can be considered based on appropriate lab testing. 11. Licorice (250 mg three times a day) may help with fatigue, particularly when it’s related to adrenal insufficiency. Care should be taken as high doses of licorice may increase blood pressure. 12. The amino acids phenylalanine or tyrosine, taken in daily doses of 1500 mg, will help to boost levels of brain hormones and neurotransmitters. 13. Magnesium may be deficient in 80% of all Americans and may be of particular importance in chronic fatigue. Everyone should consider supplementing with 500 mg of magnesium daily. Up to 3 grams of magnesium may be taken. Doseage should be reduced if an unwanted laxative effect occurs. 14. Few, if any, supplements contain sodium due to its adverse effect on blood pressure. Substituting sea salt for sodium chloride (common table salt) may be beneficial for those not on a sodium-restricted diet. 1. Reid, S., et al., Chronic fatigue syndrome. Bmj, 2000. 320(7230): p. 292-6. 2. Harrison, Harrison's Textbook of Internal Medicine. 1999. 3. Verillo, E.F. and L.M. Gellman, Chronic Fatigue Syndrome. 1997, New York: St Martin's Griffin. 4. Manian, F.A., Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response? Clin Infect Dis, 1994. 19(3): p. 448-53. 5. Buchwald, D., et al., Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome. J Rheumatol, 1997. 24(2): p. 372-6. 6. Ojo-Amaize, E.A., E.J. Conley, and J.B. Peter, Decreased natural killer cell activity is associated with severity of chronic fatigue immune dysfunction syndrome. Clin Infect Dis, 1994. 18 Suppl 1: p. S157-9. 7. Lusso, P., et al., Infection of natural killer cells by human herpesvirus 6. Nature, 1993. 362(6419): p. 458-62. 8. Pall, M.L., Elevated, sustained peroxynitrite levels as the cause of chronic fatigue syndrome. Med Hypotheses, 2000. 54(1): p. 115-25. 9. Bahrke, M.S. and W.R. Morgan, Evaluation of the ergogenic properties of ginseng: an update. Sports Med, 2000. 29(2): p. 113-33. 10. Sun, L.Z., N.L. Currier, and S.C. Miller, The American coneflower: a prophylactic role involving nonspecific immunity. J Altern Complement Med, 1999. 5(5): p. 437-46. 11. Currier, N.L. and S.C. Miller, Natural killer cells from aging mice treated with extracts from Echinacea purpurea are quantitatively and functionally rejuvenated. Exp Gerontol, 2000. 35(5): p. 627-39. 12. Currier, N.L. and S.C. Miller, Echinacea purpurea and melatonin augment natural-killer cells in leukemic mice and prolong life span. J Altern Complement Med, 2001. 7(3): p. 241-51. 13. See, D.M., et al., In vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients. Immunopharmacology, 1997. 35(3): p. 229-35. 14. Horrobin, D.F., Post-viral fatigue syndrome, viral infections in atopic eczema, and essential fatty acids. Med Hypotheses, 1990. 32(3): p. 211-7. 15. Gray, J.B. and A.M. Martinovic, Eicosanoids and essential fatty acid modulation in chronic disease and the chronic fatigue syndrome. Med Hypotheses, 1994. 43(1): p. 31-42. 16. Behan, P.O., W.M. Behan, and D. Horrobin, Effect of high doses of essential fatty acids on the postviral fatigue syndrome. Acta Neurol Scand, 1990. 82(3): p. 209-16. 17. Warren, G., M. McKendrick, and M. Peet, The role of essential fatty acids in chronic fatigue syndrome. 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Wong, Chronic fatigue syndrome: oxidative stress and dietary modifications. Altern Med Rev, 2001. 6(5): p. 450-9. 42. Richards, R.S., et al., Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome. Redox Rep, 2000. 5(1): p. 35-41. 43. Fulle, S., et al., Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome. Free Radic Biol Med, 2000. 29(12): p. 1252-9. 44. Powers, S.K., L.L. Ji, and C. Leeuwenburgh, Exercise training-induced alterations in skeletal muscle antioxidant capacity: a brief review. Med Sci Sports Exerc, 1999. 31(7): p. 987-97. 45. McCully, K.K., et al., Reduced oxidative muscle metabolism in chronic fatigue syndrome. Muscle Nerve, 1996. 19(5): p. 621-5. 46. McCully, K.K. and B.H. Natelson, Impaired oxygen delivery to muscle in chronic fatigue syndrome. Clin Sci (Lond), 1999. 97(5): p. 603-8; discussion 611-3. 47. McCully, K.S., Homocysteine and vascular disease. Nat Med, 1996. 2(4): p. 386-9. 48. Regland, B., et al., Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome. Scand J Rheumatol, 1997. 26(4): p. 301-7. 49. Bounous, G. and J. Molson, Competition for glutathione precursors between the immune system and the skeletal muscle: pathogenesis of chronic fatigue syndrome. Med Hypotheses, 1999. 53(4): p. 347-9. 50. Droge, W. and E. Holm, Role of cysteine and glutathione in HIV infection and other diseases associated with muscle wasting and immunological dysfunction. Faseb J, 1997. 11(13): p. 1077-89. 51. Sprietsma, J.E., Cysteine, glutathione (GSH) and zinc and copper ions together are effective, natural, intracellular inhibitors of (AIDS) viruses. Med Hypotheses, 1999. 52(6): p. 529-38. 52. Weiss, L., E. Hildt, and P.H. Hofschneider, Anti-hepatitis B virus activity of N-acetyl-L-cysteine (NAC): new aspects of a well-established drug. Antiviral Res, 1996. 32(1): p. 43-53. 53. Judy, W. in 37th Annual Meeting of the American College of Nutrition. 1996. 54. Jacobson, W., et al., Serum folate and chronic fatigue syndrome. Neurology, 1993. 43(12): p. 2645-7. 55. Kingsbury, K.J., L. Kay, and M. Hjelm, Contrasting plasma free amino acid patterns in elite athletes: association with fatigue and infection. Br J Sports Med, 1998. 32(1): p. 25-32; discussion 32-3. 56. Torpy, D.J. and G.P. Chrousos, The three-way interactions between the hypothalamic-pituitary-adrenal and gonadal axes and the immune system. Baillieres Clin Rheumatol, 1996. 10(2): p. 181-98. 57. Neeck, G. and L.J. Crofford, Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome. Rheum Dis Clin North Am, 2000. 26(4): p. 989-1002. 58. Baschetti, R., Overlap of chronic fatigue syndrome with primary adrenocortical insufficiency. Horm Metab Res, 1999. 31(7): p. 439. 59. Baschetti, R., Chronic fatigue syndrome: a form of Addison's disease. J Intern Med, 2000. 247(6): p. 737-9. 60. Jeffcoate, W.J., Chronic fatigue syndrome and functional hypoadrenia--fighting vainly the old ennui. Lancet, 1999. 353(9151): p. 424-5. 61. Jefferies, W.M., Mild adrenocortical deficiency, chronic allergies, autoimmune disorders and the chronic fatigue syndrome: a continuation of the cortisone story. Med Hypotheses, 1994. 42(3): p. 183-9. 62. MacHale, S.M., et al., Diurnal variation of adrenocortical activity in chronic fatigue syndrome. Neuropsychobiology, 1998. 38(4): p. 213-7. 63. Demitrack, M.A., et al., Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. J Clin Endocrinol Metab, 1991. 73(6): p. 1224-34. 64. Strickland, P., et al., A comparison of salivary cortisol in chronic fatigue syndrome, community depression and healthy controls. 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Characterization of CFS patients with special reference to their response to a new vitamin C infusion treatment. In Vivo, 1996. 10(6): p. 585-96. 70. Scott, L.V., et al., Differences in adrenal steroid profile in chronic fatigue syndrome, in depression and in health. J Affect Disord, 1999. 54(1-2): p. 129-37. 71. De Becker, P., et al., Dehydroepiandrosterone (DHEA) response to i.v. ACTH in patients with chronic fatigue syndrome. Horm Metab Res, 1999. 31(1): p. 18-21. 72. Baschetti, R., Chronic fatigue syndrome and liquorice. N Z Med J, 1995. 108(998): p. 156-7. 73. Baschetti, R., Liquorice and chronic fatigue syndrome. N Z Med J, 1995. 108(1002): p. 259. 74. Parker, A.J., S. Wessely, and A.J. Cleare, The neuroendocrinology of chronic fatigue syndrome and fibromyalgia. Psychol Med, 2001. 31(8): p. 1331-45. 75. Peroutka, S.J., Chronic fatigue disorders: an inappropriate response to arginine vasopressin? Med Hypotheses, 1998. 50(6): p. 521-3. 76. 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Galimov, [Catecholamines, their precursors and metabolites in human fatigue after exertion]. Vopr Med Khim, 1977(3): p. 369-75. 82. Avraham, Y., et al., Tyrosine improves appetite, cognition, and exercise tolerance in activity anorexia. Med Sci Sports Exerc, 2001. 33(12): p. 2104-10. 83. Deijen, J.B., et al., Tyrosine improves cognitive performance and reduces blood pressure in cadets after one week of a combat training course. Brain Res Bull, 1999. 48(2): p. 203-9. 84. Owasoyo, J.O., D.F. Neri, and J.G. Lamberth, Tyrosine and its potential use as a countermeasure to performance decrement in military sustained operations. Aviat Space Environ Med, 1992. 63(5): p. 364-9. 85. Cox, I.M., M.J. Campbell, and D. Dowson, Red blood cell magnesium and chronic fatigue syndrome. Lancet, 1991. 337(8744): p. 757-60. 86. Hinds, G., et al., Normal red cell magnesium concentrations and magnesium loading tests in patients with chronic fatigue syndrome. Ann Clin Biochem, 1994. 31(Pt 5): p. 459-61. 87. Moorkens, G., et al., Magnesium deficit in a sample of the Belgian population presenting with chronic fatigue. Magnes Res, 1997. 10(4): p. 329-37. 88. Manuel y Keenoy, B., et al., Magnesium status and parameters of the oxidant-antioxidant balance in patients with chronic fatigue: effects of supplementation with magnesium. J Am Coll Nutr, 2000. 19(3): p. 374-82. 89. Durlach, J., et al., Neurotic, neuromuscular and autonomic nervous form of magnesium imbalance. Magnes Res, 1997. 10(2): p. 169-95. 90. Lieberman, H.R., et al., Mood, performance, and pain sensitivity: changes induced by food constituents. J Psychiatr Res, 1982. 17(2): p. 135-45. 91. Lieberman, H.R., et al., The effects of dietary neurotransmitter precursors on human behavior. Am J Clin Nutr, 1985. 42(2): p. 366-70. 92. Vassallo, C.M., et al., Decreased tryptophan availability but normal post-synaptic 5-HT2c receptor sensitivity in chronic fatigue syndrome. Psychol Med, 2001. 31(4): p. 585-91. 93. Castell, L.M., et al., The role of tryptophan in fatigue in different conditions of stress. Adv Exp Med Biol, 1999. 467: p. 697-704. 94. Blomstrand, E., et al., Effect of sustained exercise on plasma amino acid concentrations and on 5-hydroxytryptamine metabolism in six different brain regions in the rat. Acta Physiol Scand, 1989. 136(3): p. 473-81. 95. Cleare, A.J., et al., Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial. Lancet, 1999. 353(9151): p. 455-8. 96. McKenzie, R., et al., Low-dose hydrocortisone for treatment of chronic fatigue syndrome: a randomized controlled trial. Jama, 1998. 280(12): p. 1061-6. 97. Natelson, B.H., et al., Single-blind, placebo phase-in trial of two escalating doses of selegiline in the chronic fatigue syndrome. Neuropsychobiology, 1998. 37(3): p. 150-4. The next step, after you have been diagnosed with a disease, is to find out what is the specific cause, and then choose supplements that address it. Phone consults are my specialty. Please call my at (239) 659-2684 to schedule a consultation. I recommend that you make an informed choice, and the goal of this web site is to provide you with the information to make a wise choice when it comes to your health and wellness. As you can see, I don't sell any vitamins on this web site. There are thousands of vitamin stores that will sell you whatever vitamin you want, and many of them offer discounts. If you are interested in some high-quality basic nutritional supplements, I recommend visiting the Store You will find my recommendations for a multiple, tasty chewable fiber wafers, high-potency probiotics, and fish oils. Good luck in your journey towards health and wellness!! Unfortunately, that would be a clear violation of FDA regulations. Also, one of the most important aspect of naturopathy is: "Treat the person, not the disease". This is a profound statement, and many people have spent thousands of dollars on vitamins listed in books or web sites for a specific disease. This is what I call "vending machine medicine". It rarely works! The solution is to find a naturopathic physician, such as myself, to assist you.	2	38	0	0	7	0.985201	7	18,161
The 10th release of the International Classification of Diseases (ICD-10) is the latest edition to the system of codes that classifies every disease or health problem around the world. The previous edition was released about four decades ago and hence this release was seen as a sweeping change in the medical coding world. ICD-10 provides a unique platform for practicing physicians and other healthcare professionals and has become the new standard for clinical data, claims processing, clinical documentation, and public health reporting. The benefits of ICD-10 transition begin with enhanced clinical documentation which enables physicians to analyze patient details, thereby lead to better care coordination and health outcomes. ICD-9 has approximately 13000 diagnosis codes which are in numeric form only ICD-10 has about 68000 alphanumeric diagnosis codes with 19 times as many procedure codes and 5 times as many diagnosis codes as ICD-9 Even though most healthcare providers have successfully transitioned towards ICD-10, there are still a few others who have either not implemented it properly, or are in the process of doing so. In case you are still not sure whether to make the transition or not, go through the following benefits of ICD-10 implementation to arrive at a conclusion - 1. Fair Pay: The new ICD-10 coding system is more granular in nature. This allows physicians to accurately report the complexity of the care provided and differentiate between chronic patients and those who come for routine check-ups. Under the ICD-9 system this distinction would have been lost. As a result, the customers can be charged as per the treatment provided, thereby leading to better transparency in payment procedures. 2. Greater Efficiency: By implementing ICD-10, a huge amount of data will be generated and can be mined for the betterment of public health. It allows governments and healthcare officials to track and respond to global health threats faster while comparing practices with the international community. Areas of injury research and trauma services evaluation have also witnessed a marked improvement in classifying the nature of injuries and correlating them with the proper cause, treatment, and outcome. 3. Lesser Fraud: Adoption of ICD-10 will result in fewer fraudulent and exaggerated claims, which increases the cost of medical care and health insurance premiums. The conversion to ICD-10 will eventually result in better patient care and more accurate reimbursement for providers as well. 4. Improved Healthcare Quality: With ICD-9, the main focus was on improving reimbursements. But the ICD-10 coding setup supports a performance-based payment system rather than aiming at returns. This will change the way healthcare functions currently and will improve the overall quality of care being provided. 5. Setting Health Policy: Since most of the world is using the ICD-10 code set, health officials can use the data to compare public health trends with global pandemics. This will help in setting-up better health policies across the world. 6. Performance Monitoring: The upgrade to ICD-10 will improve a provider's ability to monitor services and resource utilization, analyze healthcare costs, monitor outcomes, and measure performance. Greater detail on procedure types will allow providers to evaluate their own performance as compared to their peers, and take the necessary steps towards improvement. 7. Improved Quality in Clinical Documentation: The ICD-10 coding system is very much dependent on clinical documentation. Since thousands of diagnosis codes are added to ICD-10, the precision of the codes depend on clinical documents. So, with the implementation of ICD-10, quality of clinical documentation will improve. 8. Improving Relationships: An upgrade to ICD-10 helps healthcare providers improve their relations with providers and vendors as well. Providers can partner with payers for coding improvements. Both payers and providers can collaborate and help to improve the reimbursement processes, thereby improving their revenue stream and satisfaction. While ICD-10 is necessary to be implemented, healthcare providers should also ensure that it is executed properly, failing to which more problems might arise for the practitioners. Here are a few Do's and Don'ts of ICD-10 implementation - Conduct Training for the Coding Team: ICD-10 requires comprehensive training sessions for the medical coders. The training sessions must have case-based exercises which induce them to think logically and act independently when they start coding Choose the Right Technology: Many healthcare IT companies have launched several tools to aid the ICD-10 implementation process. It is important that one chooses the correct tool which suits their requirement Be Aware of the Latest ICD-10 Updates: Updates to ICD-10 are being made frequently and it is important that you stay updated with the latest changes happening in the industry to keep up with the ICD implementation Update Your Clients: Your clients must be regularly updated about the ICD-10 initiatives taken by you. Share your various plans, ideas, or even shortcomings which will show them your commitment towards ICD-10 Don't do it in a Hurry: Plan a proper ICD-10 implementation plan and work accordingly. The more it is delayed the riskier it is to work at the last minute. Let things happen as planned so that you get enough time to fix any problems arising during the implementation and integration process Don't Leave Everything to the Coders: The ICD coding system demands a lot of groundwork to be done before the actual implementation. The ICD transition must be a combined effort of the transition management team, IT team, and the medical billing team Flatworld Solutions has been providing medical billing and coding services for over 17 years now. Our highly qualified team of medical billing specialists is adequately trained and well versed with the benefits of integrating ICD-10 codes. We provide high-quality services to clients around the world at very competitive prices. If you have any such requirement or would like to know about how Flatworld's ICD-10 knowledge can positively impact your practice, feel free to contact us or talk to one of our representatives and we will get back to you within 24 hours. 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Textbook of Psychiatry/Psychotic Disorders Schizophrenia and Related Psychotic Disorders - 1 Introduction - 2 Clinical Manifestations and Definition of Terms - 3 Specific Types of Primary Psychotic Disorders - 4 Schizophrenia - 4.1 Conceptual History and Diagnostic Classification - 4.2 Current classification – ICD 10/ DSM-IV-TR - 4.3 Epidemiology and Risk Factors - 4.4 Genetic Considerations - 4.5 Pathology - 4.6 Etiopathological Theories - 4.7 Clinical Diagnosis - 4.8 Differential Diagnosis - 4.9 Treatment - 4.10 Prognosis - 5 Schizophreniform Disorder - 6 Brief Psychotic Disorder - 7 Schizoaffective Disorder - 8 Delusional Disorder - 9 Shared Psychotic Disorder (Folie à Deux) - 10 References Psychosis, a syndrome with many causes, traditionally refers to an impaired ability to distinguish between false and real perceptions and beliefs. Schizophrenia is the prototypical psychotic disorder. The most common psychotic symptoms are positive symptoms such as abnormal perceptions (including illusions and hallucinations), false beliefs, including a wide variety of delusional thoughts (e.g., paranoid delusions, delusions of reference, grandiose, somatic, etc.), and disorganized thinking. In addition, patients with schizophrenia might have prominent negative symptoms such as affective flattening, alogia (decreased thought/speech production), and avolition, together with amotivation, anhedonia and social isolation. Disorganized or bizarre behavior is a separate symptom dimension of the disorder. Affective symptoms can also be present and cognitive and social deficits are common. This chapter focuses on primary psychotic disorders, as illustrated by schizophrenia, meaning that the clinical picture of psychosis is not deemed to be secondary to other processes. It is important to note that in addition to the primary psychoses a number of psychiatric and somatic conditions affecting the brain homeostasis can produce psychotic symptoms. Patients with personality disorders (PDs) can present with overt psychotic symptoms in response to stress (e.g., paranoid PD, schizotypal PD, borderline PD). Schizoid PD is considered a risk factor and might precede Schizophrenia and Delusional Disorder. With regards to mood disorders, severe psychotic depression can present with mood congruent (e.g., nihilistic delusions, delusional guilt) and/or auditory hallucinations making critical and negative comments. At the opposite end of the spectrum, severe mania can present with grandiose and religious delusions, delusions of special powers, and auditory hallucinations (God’s or angelic voices). Late life psychosis can be present in the later stages of dementia disorders. Conditions that affect the brain structure, either acutely [e.g., rapidly growing brain tumors, traumatic brain injury, strokes, infectious/inflammatory processes such as tertiary syphilis, multiple sclerosis or systemic lupus erythematosus (SLE)], or chronically [e.g., nutrient and vitamin deficiencies such as B12, niacin deficiency (pellagra), etc.] can present with a variety of psychotic symptoms. Last but not least, a number of drugs (prescribed and illicit) can be associated with psychotic symptoms either during treatment/intoxication or withdrawal. This chapter will first review the definitions of the different types of psychotic symptoms, as the basis for the discussion about the approach (including initial assessment as well as short and long-term treatment plans) to a patient with a generic psychotic syndrome. For the remainder of the chapter schizophrenia is used as the foundation for the discussion of clinical diagnosis, differential diagnosis, epidemiology, pathophysiology, genetics and treatment. Pertinent details of schizophrenia-related disorders will be discussed (compared and contrasted whenever the case) within the confines of the broader schizophrenia mainframe. Clinical Manifestations and Definition of Terms - Positive Symptoms are thought of as an excess of normal function. Overvalued misperceptions that become illusions and hallucinations and overvalued ideas that become delusions (fixed ideas) are classical examples of positive symptoms. - Negative Symptoms refer to a lack of what is considered to be normal function. Normally, a degree of volitional ability is expected; therefore decreased or absent volition (avolition) is a negative symptom. Similarly, a lack of motivation (amotivation), a lack of ability to enjoy things (anhedonia), or decreased ability to engage in social activities (social isolation) are other classical negative symptoms. - Catatonia refers to two extreme (and fundamentally opposite) states. Agitated catatonia refers to a state of excessive, extreme behavioral agitation (not in response to internal stimuli), while catatonic immobility refers to extreme negativism (the patient actively resists any attempts to have his extremities or whole body moved) or catalepsy (waxy flexibility). Other catatonic symptoms include posturing (assuming strange body postures), grimacing, mannerisms, stereotyped movements, echolalia (where the patient repeats in parrot-like fashion the words of another person), and echopraxia (where the patient imitates in mirror-like fashion the movements of another person). - Disorganized thinking (formal thought disorder) refers to an alteration in the thought process. Normally the flow of thinking is coherent, linear and goal directed. In psychotic patients the associations may be loose to the point of being non-existent. The psychotic patient’s thought form may present with tangentiality (ideas are only marginally connected) or circumstantiality (the patient responds to questions moving in gradually more focused, concentric circles until eventually reaching the answer). In extreme cases, even the structure of the sentence might be lost which results in word salad. - Disorganized behavior refers to the patient difficulty to complete most goal oriented activities. A range of behaviors have been described: actively responding to inner stimuli (e.g., talking to oneself or shouting for no apparent reason), aimless, repetitive movements and activities, poor ability to maintain one’s basic hygiene and perform routine actives of daily living (which often results in a disheveled appearance, and poor grooming and hygiene), or uncensored public sexual activity (being naked, or masturbating in public). - Active phase refers to a period of time when a combination of the above symptoms are prominently manifested. - Prodromal and residual phases refer to periods of time of attenuated symptoms that either precede (prodromal) or follow (residual) the active phase period. - Cognitive Symptoms: Memory (more specifically working memory), attention, concentration, processing speed, problem solving (executive functioning), and social cognition are a few of the many cognitive domains shown to be impaired in schizophrenia. - Insight is a multidimensional concept referring to awareness of illness, specific symptoms and their consequences, as well as need for treatment. Insight refers to the patient’s ability to understand that some of his or her non-reality based experiences (usually hallucinatory experiences and delusional representations) are secondary to having schizophrenia rather than reality. Awareness and attribution of both current and past symptoms represent specific aspects of insight. Additional dimensions of insight include a more global understanding of the diagnosis and need for treatment. Approach to the Patient with Acute Psychosis The following major issues should be kept in the forefront: - What is the most accurate diagnosis? - Is there a treatable or reversible component to the psychosis? - Is the patient safe? - Can the physician help to alleviate the positive symptoms? - Can the physician help to alleviate the negative, cognitive symptoms and insight deficits to improve social/functional outcomes? The history should clarify the onset (acute versus gradual), tempo (slow/protracted versus rapid), chronology, course (persistent versus episodic), and type of symptoms. Onset and tempo An acute or subacute onset of psychosis may represent delirium, psychosis due to a general medical condition, or a substance induced psychosis and should trigger the search for intoxication, infection, or metabolic derangement. According to the Diagnostic and Statistical Manual of Mental Disorders IV Text Revision (DSM-IV-TR) a diagnosis of schizophrenia requires the presence of a combination of prominent positive, negative, disorganized thinking (formal thought disorder), catatonia, or behavior type of symptoms for at least a month (active phase), with a total duration of the episode (including active phase, and some type of prodromal or residual symptoms) for at least 6 months and resulting in social and occupational dysfunction. A schizophrenia-like presentation that lasts more than a month but less than 6 months would be more appropriately diagnosed as schizophreniform disorder. Brief psychotic disorder should be diagnosed when the total duration of symptoms is shorter than a month. Schizoaffective disorder trumps schizophrenia if in addition to stand alone episodes of psychotic symptoms there is also a long history of affective symptoms, and the affective symptoms occurred for a longer time than the psychotic symptoms. Refers to the temporal rapport between the different symptoms. Clarifying what started and what followed are essential in ruling out phenomenologically overlapping disorders. If it is determined that the psychotic symptoms followed a medical condition or drug (prescribed or illicit) psychotic disorder due to a general medical condition, substance induced psychotic disorder, or delirium need to be considered first. Mood disorder with psychotic symptoms is diagnosed if the history shows that psychotic symptoms always occurred in the context of already present, and most often severe affective (depressive and manic) symptoms. A clearly episodic course is most times indicative of a primary affective disorder. Unfortunately, schizophrenia tends to be chronic, with some level of residual symptoms following the active phase for most patients. However, for schizophrenia, after one year since the onset of the acute phase symptoms, DSM allows for a number of course based specifiers including: single episode with partial/total remission, episodic with/without inter-episode residual symptoms, and continuous. Physical and Neurological Examination A thorough general and neurological examination is recommended. General physical examination Is recommended to first rule out a systemic disease that may be responsible for the psychotic syndrome. A number of non-specific physical abnormalities including an arched palate, narrow or wide–set eyes or subtle ear malformations are more frequently reported in patients with schizophrenia than in the general population. For patients treated with antipsychotics a physical exam will document the general state of health and is important to exclude side effects of medication. Side effects include orthostatic hypotension, hypersalivaton (secondary to clozapine), anticholinergic syndrome (dry mouth, and tachycardia secondary to anticholinergics), hyperprolactinemia (lactation secondary to D2 antagonism), and metabolic syndrome (most common with clozapine and olanzapine). Is recommended to rule out neurological conditions that may present with psychotic manifestations; of note, abnormal focal neurological signs are not typically found in primary psychotic disorders. Such findings should prompt the clinician to do a more extensive neurological work-up. In addition, a neurological exam is necessary to exclude the presence of soft neurological signs and abnormal involuntary movements. Soft (neurological) signs, while not pathognomonic, are frequently seen in schizophrenia, where "soft" denotes the absence of a clearly localized ("hard") central nervous pathology that can explain the observed deficits. They include: - Sensory function integration abnormalities include poor audio—visual integration, astereognosis (the inability to identify an object by touch without visual input), and agraphaesthesia (the inability to recognize writing on the skin purely by the sensation of touch). - Motor function integration abnormalities might include balance and gait abnormalities, poor coordination, intention tremor, finger—thumb opposition difficulties. In addition, a number of abnormal involuntary movements have been classically described in chronic schizophrenia (before the neuroleptic age) but have been much more prevalent since the introduction of antipsychotic dopamine antagonist drugs. These include: - Akathisia, which refers to low amplitude, high frequency movement typically involving the lower extremities. The patient reports a feeling of intolerable restlessness, specifically manifested as a need to continuously move one’s feet. The patient cannot stop pacing (paces in place when asked to sit or stand without walking), - Dystonia, which refers to a high amplitude, low frequency, spastic type of movement, typically involving an isolated muscle group, e.g., oculopharogyric crisis (eyes turned upwards), torticollis (neck turned sideways), laryngeal spasm (rare but serious as it might result in asphyxia), opisthotonus (arched back, rare, painful) - Dyskinesia, which refers to low amplitude, repetitive, moderate frequency, pseudo-parkinsonian movements that may involve any muscle group but most typically involve the fingers, hands, toes, feet, lips and lower face muscles (including perioral and mandibular muscles) - Tremor, which refers to a low amplitude, high frequency, repetitive movement. Tremor of the hands and fingers can be spontaneous or can be elicited by asking the patient to put his arms in a horizontal position and stretch his fingers. In addition, a parkinsonian pill rolling tremor may also be observed. In patients taking lithium a fine tremor(very low amplitude, very high frequency) may be seen. Mental Status Examination (MSE) - Appearance: disheveled or bizarre appearance may be a clue to underlying psychosis. Impaired reality testing commonly results in poor grooming and hygiene. - Attitude: paranoid patients may be unwilling to co-operate during an interview, while very psychotic patients my be unable to engage with the interviewer. - Motor behavior: posturing, repetitive gestures, extreme psychomotor agitation (without any apparent precipitants or retardation) can indicate a catatonic presentation. Alternatively, the patient may present with psychomotor agitation in response to overwhelming internal stimuli (e.g., loud, demeaning voices or threatening visions) or because of severe paranoid ideation. - Mood: patient’s reported mood can vary from good to depressed or afraid. - Affect: paranoid patients present with guarded affect, eyes scanning the room, and a closed up body language. - Speech/thought process: can be vague, circumstantial or overtly disorganized. At times nonsensical neologisms, word salad, clang (rhyming, nonsensical associations) are present. - Thought content: may be positive for delusional ideation (most common ideas of references and paranoid delusions). In addition, the patient may harbor suicidal and violent thoughts due to his persistent psychotic symptoms or, at times, related to concomitant depressive symptoms. - Perceptual disturbances: auditory hallucinations can be commanding and order the patient to kill himself or other people. When visual hallucinations are present they tend to be unpleasant as a rule and are often overtly terrifying. - Insight and Judgement: judgement is mostly impaired and the patient has very limited, if any, insight. - Cognition: with the possible exception of decreased attention, other cognitive deficits may not be obvious during a cursory MSE. In schizophrenia neuropsychological testing routinely reveals deficits in working memory, executive functioning, social functioning, processing speed, verbal fluency, and/or reaction time abnormalities. Unfortunately, the ability to test for these deficits routinely in clinical practice is limited by the lack of good, time efficient screening cognitive instruments for schizophrenia and related disorders. There are no tests that can rule in a diagnosis of schizophrenia or related disorders. The role of laboratory investigations are to rule out substance induced disorders and general medical conditions that can present with a psychotic syndrome; to establish a baseline and monitor physiological functions that can be affected by, or can affect the metabolism of psychotropic medications; and monitor drug levels when necessary. Investigations to exclude a substance induced disorder or general medical condition: - urine or blood toxicology screen: should be performed routinely in all patients presenting with new onset or exacerbated psychotic symptoms, as a number of illicit drugs can cause/worsen psychosis (e.g., hallucinogens, cocaine, stimulants, marijuana). - Complete blood cell count (CBC): blood dyscrasias can point to an underlying vitamin deficit that may manifest with psychosis (e.g., pernicious or megaloblastic anaemia as a sign of vitamin B12/folate deficits) - Rapid plasma reagin (RPR): done to rule out (tertiary) syphilis - Thyroid panel: indicated when there is a clinical suspicion for hypo or hyperthyroidism - Brain Imaging: - Structural brain imaging (CT or MRI) is indicated to rule out other brain pathologies (e.g., multiple strokes, demyelination, masses). Neuroimaging studies do not show a pattern of findings specific for schizophrenia or related disorders and may be normal early in the course of the disease. As schizophrenia progresses, enlarged ventricles and diffuse cortical atrophy becomes apparent. MRI scans may also show atrophy of the parahippocampal gyrus, dorsolateral prefrontal cortex, mesolimbic system, the anterior cingulate cortex, and planum temporalis asymmetry reversal or generalized reductions in grey and white matter. - Functional brain imaging studies (PET and functional MRI) demonstrate abnormalities in the same regions. However, none of these changes are pathognomonic for schizophrenia or related disorders. A liver function panel and chemistry panel (to document renal function) are recommended to establish a baseline for physiological functions that can affect the metabolism of psychotropic medications. Other tests that may be indicated to monitor side effects of psychotropic medication include a blood glucose level, a lipid panel, and an ECG (as some antipsychotics have the potential of prolonging the QTc interval). A prolactin level should only be measured when prolactinemia is suspected on clinical grounds. The following drug levels need monitoring: lithium (0.7 to 1.2 mEq/L), carbamazepine (5 to 12 mcg/mL), and valproic acid (50 to 100 mcg/mL). A clozapine level above 350 ng/mL is recommended to establish compliance and has been shown to correlate with improved efficacy for refractory schizophrenia. There is no clear evidence of a therapeutic range for other antipsychotics. Specific Types of Primary Psychotic Disorders General Considerations and Differential Diagnosis When a patient presents with a psychotic syndrome the first order of business is to establish if the presenting symptoms are due to another psychiatric or somatic condition. In other words, a psychotic syndrome is classified as "primary psychosis" only after other possible underlying pathologies have been ruled out. In terms of somatic contributors, the main suspects should include processes that may affect the brain either acutely or chronically, in which case a diagnosis of psychotic disorder due to a general medical condition is appropriate. A substance induced psychotic disorder should be diagnosed if there is a likely cause and effect relationship between a substance (including medication, OTC products or illicit drugs) and the psychotic presentation. Psychiatric underlying pathologies include severe depressive and bipolar disorder, which may present with mood congruent psychotic features. As discussed, under stress, some personality disorders may present with transient psychotic symptoms. The differential diagnosis between different primary psychotic disorders should take into account the type and duration of symptoms. Virtually identical symptoms are seen in schizophrenia, brief psychotic disorder, and schizophreniform disorder. The symptom duration differentiates brief psychotic disorder (1 day to <1 month) from schizophreniform disorder (1 month <6 months) and schizophrenia (>6 months). Delusional disorder is differentiated from schizophrenia based on prominent, non-bizarre delusions without any other associated symptoms. When distinct psychotic episodes are present but affective symptoms account for the majority of the clinical presentation a diagnosis of schizoaffective disorder should be considered. Conceptual History and Diagnostic Classification - 1853: Morel’s curious cases of Démence Précoce: Bénédict Morel introduces the concept of Démence Précoce, literally "early dementia", described a distinct syndrome affecting teenagers and young adults. The syndrome is characterized by bizarre behavior and mental function, withdrawal and self neglect starting in adolescence. - 1868: Kahlbaum’s Katatonie: Karl Ludwig Kahlbaum and Ewald Hecker publish Die Gruppierung der psychischen Krankheiten (The Classification of Psychiatric Diseases). By considering the longitudinal course of psychiatric symptoms in addition to the clinical presentation Kahlbaum and Hecker were the first to describe and name a number of psychiatric syndromes including cyclothymia, dysthymia, paranoia, catatonia, and hebephrenia. Kahlbaum’s Katatonie was characterized by stereotyped movements, outbursts of excitement and stupor. - 1870: Ewald Hecker’s hebephrenia and cyclothymia: Hecker differentiates between hebephrenia, a disorder that begins in adolescence with erratic behavior followed by a rapid decline of all mental functions, and cyclothymia, a cyclical mood disorder. - 1891: Arnold Pick reports on a case of a psychotic disorder which he calls Dementia Praecox - 1893: Emil Kraepelin’s Dementia Praecox: Kraepelin new classification of mental disorders distinguishes between dementia praecox and mood disorder (termed manic depression and including both unipolar and bipolar depression). - Dementia Praecox: A "sub-acute development of a peculiar simple condition of mental weakness occurring at a youthful age." - Distinct from catatonia and dementia paranoides. - Kraepelin’s concept relied heavily on course (chronic versus episodic) and prognosis - 1899: hebefrenia, catatonia and dementia paranoides as subtypes of dementia praecox. - 1919: Kraepelin writes that "it is becoming increasingly clear that we cannot distinguish satisfactorily between these two illnesses and this brings home the suspicion that our formulation of the problem may be incorrect." - 1908: Eugen Bleuler’s Schizophrenia gk. skhizein "to split"+ phren (gen. phrenos) "diaphragm, heart, mind", where "split mind" referred to being split off from reality and unable to distinguish what is real from what is not real. Of note, Bleuler never implied that people with schizophrenia have split personalities; he proposed the term of schizophrenia to describe the separation of function between personality, thinking, memory, and perception. - Bleuler 4 A's: flattened Affect, Autism, impaired Association of ideas and Ambivalence. - Bleuler proposal for a new name also stemmed from his dissatisfaction with the implications of dementia praecox label. Bleuler noted that schizophrenia was NOT a dementia, as some of his patients improved. - 1887 – 1967: Kurt Schneider described the first rank symptoms (FRS), thought to be specific for schizophrenia psychosis. He included thought insertion/broadcast/withdrawal, made feelings/impulses/actions/somatic sensations (a type of delusion), third person auditory hallucinations (running commentary or arguments), delusional perception, and thought echo (echo de la pensee or gendankenlautwerden) – a type of hallucination. Only 58% of patients with a diagnosis of schizophrenia experience at least one FRS, while 20% never experience FRS. Furthermore, 10% of patients with a diagnosis of schizophrenia experience FRS. - Modern positive and negative symptoms based classification systems: - Positive symptoms include distortions or excesses of normal functioning such as, hallucinations, delusions, disorganized thinking and speech, and inappropriate affect. Frequently hallucinations are auditory in nature; rarely they may be visual, tactile or olfactory. Delusions are fixed false beliefs held despite negative evidence, and are not consistent with cultural norms. Types include persecutory, referential, somatic, grandiose, etc. Positive symptoms are generally more responsive to treatment than negative symptoms. - Negative symptoms involve a decrease or absence of normal behavior. They include affective flattening, impoverishment of speech and language, avolition, amotivation, lack of interest, anhedonia, and social isolation. - Modern classifications: - Andreasen's Positive and Negative Symptoms Type - Crow Type I and II: - Type I – positive symptoms, good response to treatment, relatively better outcome - Type II – negative symptoms, poorer response to treatment, relatively poor outcome, MRI changes. Current classification – ICD 10/ DSM-IV-TR Common ICD/DSM types: - Paranoid schizophrenia: - Prominent delusions, auditory hallucinations - Usually minimal thought disorder or negative symptoms - Catatonic schizophrenia is characterized by prominent psychomotor symptoms e.g., violent excitement, posturing, waxy flexibility, automatic obedience, perseveration, stupor. - Residual schizophrenia or "defect state", when positive symptoms give way to negative symptoms. - Simple schizophrenia refers to insidious development of negative symptoms without positive symptoms DSM IV only: - Disorganized schizophrenia: mainly thought disorder, and negative symptoms, without prominent positive or affective symptoms. ICD 10 only: - Hebephrenic schizophrenia: affective abnormality, thought disorder, mannerisms. May have chronic course. Epidemiology and Risk Factors The life time prevalence of schizophrenia is between 0.5-1.5% in the general population and is one of the ten leading causes of disability worldwide. Of note, this 1 in 100 rate has been shown to be remarkably constant across different historical periods and across different cultures. The annual incidence is reported to be in the range of 0.5 to 5 per 10,000. The onset of schizophrenia is usually between the ages of 20-45. Most times, the course of the disorder is chronic and characterized by a gradual, progressive deterioration. However partial or complete recovery is reported to occur for 30-60% of patients following a first episode of schizophrenia.* About 20-40% of patients with schizophrenia attempt suicide at least once during their lifetime, and about 10-15% die of suicide. The prevalence in males and females is equal. The following risk factors have been reported for schizophrenia: - Men tend to be diagnosed earlier than women (males age 15-25 years, females age 25 – 35 years) - Seasonality: winter birth excess - Schizoid and schizotypal personality disorders - A family history of schizophrenia or major affective disorders - A family with a high level of expressed emotions (EE) - Schizophrenia tends to be more frequent in urban areas and in developed countries - Lower socioeconomic status - Schizophrenia is more frequent in recent immigrants (deprivation, stress of immigration may increase risk) The rate of schizophrenia is increased in families with affected members. Mode of Transmission is unknown and likely to be multi-factorial, possibly polygenic. 70% of the heritability of schizophrenia is genetic. Adoption studies have shown an increased incidence of schizophrenia spectrum disorders among adopted offspring of schizophrenic parents. When one parent has schizophrenia there is a twelve fold increase in the risk of developing the disorder; with one affected sibling there is a 9 fold increase in risk; for monozygotic, identical twins the rate of concordance is around 50%. Working memory appears to be heritable and showed significant associations with DISC1, reelin, and AKT1 in schizophrenia. While there are no structural or functional brain changes specific to schizophrenia or other psychotic disorders a number of abnormalities are reported. Enlarged ventricles, deep cortical sulci, diffuse gray and white matter loss, increased neuronal density, decreased synapse density, and an overall decrease in brain size have been reported in schizophrenia studies using structural brain imaging (CT, structural and diffusion sensor MRI studies) or postmortem observations. Smaller frontal and temporal lobes, lower volume hippocampus, thalamus, corpus callosum, and anterior cingulate, as well as larger caudate and putamen have been reported in schizophrenia. Decreased activation in dorsolateral prefrontal cortex (during working memory task), and increased activation of the superior temporal gyrus (during auditory hallucinations) have been also reported in functional brain imaging (fMRI and PET) studies. Impaired fetal or neonatal brain development may sow the seeds for the onset of psychotic symptoms in later life. Patients with schizophrenia have a lower than average IQ, and often subtle/soft neurological signs. A number of parental risk factors have been reported including multiparity, maternal bleeding during pregnancy, small baby size for gestational age, increased paternal age, and severe stress to mother during first trimester. In addition, the following environmental risk factors have been associated with increased risk of developing psychotic illness later in life: late winter birth, prenatal exposure to famine, in-utero exposure to analgesics, and cannabis use. - P50 sensory gating deficits: following an auditory stimulus schizophrenia patients fail to gate a subsequent stimulus that follows closely (within the normal 50 msec suppression). - Reduced P300 evoked response potential (ERP) [oddball deficit paradigm]: schizophrenia patients fail to respond to an odd ball stimulus administered during a series of otherwise identical stimuli. - Prepulse Inhibition (PPI) Paradigm. - Hypothesis: excessive DA activity in mesolimbic and cortical brain regions. Schizophrenia is the result of a dopaminergic hyper-salient state - Supporting evidence: - Postmortem studies: increase DA receptors in schizophrenia - HVA (dopamine metabolite) in plasma, CSF and severity of psychosis/response to neuroleptics - DA Agonists - Amphetamines release DA at synapses and cause positive symptoms (in people who do not have schizophrenia) - L-dopa increases central DA concentrations and causes positive symptoms - DA Antagonists: All effective antipsychotics are D2 receptor antagonists; efficacy correlates with D2 occupancy - Amphetamines and L-dopa do not produce negative symptoms - Antipsychotics are ineffective in 30% of patients - Antipsychotics block D2 receptors instantly but antipsychotic effect not evident for days - Hypothesis: serotonin excess - LSD and psilocybin are potent 5HT receptor agonists and cause positive symptoms of schizophrenia (in people who do not have schizophrenia) - Atypical antipsychotics are potent 5HT2 receptor antagonists - Limitations: LSD produces visual hallucinations which are uncommon in schizophrenia Excitatory amino acids (EAAs): glutamate and aspartate - Hypothesis: EAAs deficit - Phenylcyclidine (PCP), which antagonizes EAA receptors, can produce positive and negative symptoms in people without schizophrenia - Glutamate agonists (e.g., glycine), may be modestly therapeutic in schizophrenia - Freud: delusions as a way of making sense of a disturbed internal world ("I need to respond with aggression to protect myself as everyone is attacking me"). - Klein: failure to resolve the paranoid/schizoid position - Cameron: loss of conceptual boundaries - Goldstein: concrete thinking - Difficulties in filtering sensory input (see also electrophysiological findings) - Probably more important in precipitating schizophrenia than causing it - Lidz’s marital schism/marital skew - Bateson’s double bind theory - High expressed emotion - Social adversity in childhood and fetal life associated with risk of developing schizophrenia and other psychoses later in life - Risk factors for psychoses later in life (in developed countries): - households receiving social welfare benefits - single-parent households - low socioeconomic status - rented apartments According to DSM-IV Schizophrenia is diagnosed when the patient presents with a combination of positive (delusions and hallucinations) and negative symptoms, which have been present for at least 6 months and have resulted in significant dysfunction. It is also accepted that disorganized speech/behavior and/or catatonic symptoms, when combined with other positive or negative symptoms, can count toward a diagnosis of schizophrenia. Schizophrenia is a diagnosis of exclusion; in other words, it is required that there are no other medical, psychiatric, or substance-induced conditions that would explain the patient’s diagnosis better than schizophrenia. Early in the disease course, other etiologies of psychosis should be excluded. These include treatable conditions such as tertiary syphilis, vitamin deficiencies, brain tumor, drug and medication intoxication, chronic infection, and mood disorders. While neuroimaging studies (CT and MRI) do not show a single specific pattern with schizophrenia or related disorders and may be normal early in the course of the disease a screening CT is recommended for patients with a first episode of primary psychosis, especially for late or acute onsets. An affective psychosis (mania or depression with psychotic features) should be ruled out if affective symptoms preceded psychotic symptoms or are dominating the clinical picture at the time of presentation. A diagnosis of schizoaffective disorder is appropriate if historically the course has been dominated by affective symptoms and there are at least some episodes of "pure" psychosis i.e., independent of the affective background. Symptom duration will separate brief psychotic disorder (<1 month), schizophereniform disorder (<6 months), and schizophrenia (>6 months). Hospitalization is recommended if the acute psychotic symptoms result in danger to self or others or significant impairment. Traditionally, dopamine 2 (D2) antagonists (blockers), most often labelled as first generation (typical) neuroleptics, have been the pillar of schizophrenia treatment. - D2 blockers, by decreasing the presumably excessive mesolimbic dopamine, have established efficacy for positive psychotic symptoms; however, due to concomitant blockade of the frontostriatal dopamine pathway, where dopamine is presumably decreased all along in schizophrenia, they do not improve (and in some cases can worsen) negative, cognitive symptoms, and/or functional/social outcomes. - Due to an alteration of the physiological dopamine/acetylcholine ratio in the basal ganglia these drugs also have a number of extra-pyramidal adverse effects (EPSEs) both short term (acute dystonia, dyskinesia, akathisia) and long term (parkinsonism and tardive diskinesia). - Finally, following a dopamine blockade in the tuberoinfundibular system, there is a prolactin increase with common sexual side effects, including decreased sexual interest, sexual difficulties, lactation and (in men) gynaecomastia. - The side effects of typical neuroleptics can be stigmatizing and are a major reason for non-adherence to treatment. Some of the above issues have been resolved with the advent of the second generation antipsychotics (SGA) or atypical neuroleptics, a drug class that tends to share the mechanism of D2 and 5HT2 (serotonin) antagonism. We say "tends to share" rather than "share the characteristic" as the second generation drugs show a number of differences in terms of both receptor profile and affinities. To illustrate, the prototypical atypical neuroleptic is clozapine, a drug that has strong D4 and 5HT2A antagonism but only partial D2 antagonism. - SGAs have fewer EPSEs and tend to be better for negative symptoms than typicals (not increasing negative symptoms). - Some of the atypicals (e.g., olanzapine, clozapine) increase the risk for metabolic adverse effects including significant weight gain, diabetes and dyslipidemia. - Clozapine is recommended for treatment resistant schizophrenia. - Generally SGAs, with the exception of olanzapine and clozapine, are first line treatments. This preference is based more on better tolerability (less EPSEs and cognitive adverse effects) than greater efficacy. On a case by case basis first generation antipsychotics (FGAs) may represent a reasonable alternative. Perphenazine and molindone efficacy and overall tolerability has been shown to be similar to SGAs. General prescribing principles: - Initial management may include use of sedative medication such as lorazepam. - IM medication may be required in a very disturbed, involuntary patient. - Depot (long-acting) neuroleptics are indicated when treatment adherence is problematic. - Polypharmacy is common yet not supported by evidence. - The goal of treatment is stability on monotherapy at the lowest effective dose. Psychological (Individual and Family Interventions) - Good evidence: - Education of patient and carers - Reduction of high expressed emotion: shown to affect relapse rates - Supportive, solution oriented psychotherapy - Unclear benefit: - Cognitive behavioral therapy - Cognitive and functional rehabilitation - Self–help unclear - Good evidence: - Regular intensive case management - Unclear benefit: - As needed case management - Consumer based organizations 15-25% of patients diagnosed with schizophrenia have one episode and no residual impairment. 25-40% have recurrent episodes and no residual impairment. 5-10% have recurrent episodes and develop significant non-progressive impairment. 30-40% have recurrent episodes and develop significant progressive impairment. Therefore, the majority of patients do not recover fully BUT DO NOT have a chronic unremitting course. There is little evidence that antipsychotics have altered the course of illness for most patients. However, evidence suggests that prolonged psychosis which is untreated has a bad prognosis. Suicide rate is up to 15%. Good prognostic factors: - Female gender - Older age of onset - Higher socioeconomic status - Living in a developing (as opposed to developed) country - Good premorbid personality - No previous psych history - Good education and employment record - Acute onset, affective symptoms, good adherence to medication. Predicting risk of suicide: - Acute exacerbation of psychosis - Depressive symptoms - History of attempted suicide - Male gender - Command auditory hallucinations Clinical Manifestations and Diagnosic Considerations The clinical presentation is identical to schizophrenia, however impairment in function is not a requirement. The required duration of symptoms is of at least a month but less than 6 months. If symptoms persist for longer than 6 months it is appropriate to change the diagnosis to schizophrenia. The diagnosis requires for other pathologies that may be responsible for the clinical manifestations (e.g., medical and drug use) to be ruled out before a diagnosis of schizophreniform disorder is made. It is not clear if schizophreniform disorder is a different disorder or just a more acute, better prognosis type of schizophrenia. With good prognostic features: - Good premorbid level of function - Abrupt onset - Absence of flat affect Without good prognostic features: when less than 2 of the above features are present The prevalence is low overall. There may be differences between developed countries (estimated around 0.2%) and developing countries (estimated around 1%). - Hospitalization is recommended if the acute psychotic symptoms result in danger to self or others or significant impairment. - Acute psychosis should be treated with antipsychotics. Second generation antipsychotics, with the exception of olanzapine, are preferred first line. - Treatment should be continued for one year and reassessed after. - Supportive and solution oriented psychotherapy is beneficial. About one third of the patients recover. The rest of the patients initially diagnosed with schizophreniform disorder progress to schizophrenia or schizoaffective disorder. Brief Psychotic Disorder Clinical Manifestations and Diagnosic Considerations Phenomenologically there is no difference between brief psychotic disorder (BPD), schizophreniform disorder, and schizophrenia. The difference between these three diagnoses is based on symptom duration. As indicated by its name, the duration of symptoms in BPD are brief: more than 1 day but less than 1 month. When the symptoms last longer than a month but less than 6 months the diagnosis changes to schizophreniform disorder. The psychotic symptoms should not be part of a pre-existing medical, drug induced, or primary psychiatric condition (including other psychotic or mood disorders). DSM-IV-TR specifiers include: - With marked stressor(s) (brief reactive psychosis) - Without marked stressor(s) - With postpartum onset: when onset of symptoms is within 4 weeks postpartum Rare overall but more frequent in developing countries compared to developed countries. Hospitalization is recommended if the acute psychotic symptoms result in danger to self or others or significant impairment. Neuroleptics for short term treatment should be considered on a case by case basis. By definition full remission of symptoms and return to prior level of functioning is expected within a month. Clinical Manifestations and Diagnostic Considerations The patient presents with symptoms of schizophrenia, mania, depression or a combination of mood and psychotic symptoms. The history is significant for at least one distinct episode of psychosis not overlapping with mood symptoms and a relative temporal predominance of mood symptoms. Differential diagnoses should include drug induced and medical conditions with secondary psychotic symptoms. While patients with schizophrenia can experience mood symptoms their duration is relatively short relative to the total duration of illness. When the psychotic symptoms represent a culmination of a severe mood episode a diagnosis of mood disorders (i.e., bipolar and major depression) with psychotic features should also be included in the differential. Unclear but possibly less common than schizophrenia. Hospitalization is recommended if the acute psychotic symptoms result in danger to self or others or significant impairment. Antipsychotics are recommended for acute psychotic symptoms. Second generation antipsychotics (SGA), excluding olanzepine, should be considered as first line. Mood stabilizers including lithium, valproic acid, and carbamazepine, or SGA are recommended for acute manic symptoms. A neuroleptic-mood stabilizer combination may work better than either agent alone, and augmenting a neuroleptic with lithium or valproic acid should be considered as an augmentation strategy in cases of poor response to neuroleptic monotherapy. Antidepressants should be used conservatively for depressive symptoms. Close monitoring is required as an antidepressant can precipitate a manic switch in a patient with schizoaffective disorder. Better than schizophrenia but not as good as mood disorders. Clinical Manifestations and Diagnostic Considerations The patient presents with non-bizarre delusional beliefs but most often the mental status examination is otherwise fairly normal. The delusional ideas are restricted to a specific subject and do not contaminate other mental processes. Other psychotic symptoms may include olfactory/gustatory hallucinations, which may be prominent and are closely related to the main delusional themes. If prominent auditory/visual hallucinations are present a diagnosis of schizophrenia rather than delusional disorder may be more appropriate. Associated symptoms are rare but may include mood or anxiety symptoms. When present, such symptoms are often secondary to the delusional beliefs (e.g., "of course I feel anxious with the NSA following me around the clock"). Other conditions (medical, drug induced, other primary psychiatric disorders, including other psychotic or mood disorders) cannot better explain the clinical picture. - Erotomanic type: the patient erroneously believes that another person is in love with him/her - Grandiose type: the patient erroneously believes that he/she possesses enormous wealth, power, authority, knowledge, or has a special relationship to a deity or famous person - Jealous type: the patient erroneously believes that his/her partner is unfaithful - Persecutory type: the patient erroneously that he/she is targeted for punishment or retaliation - Somatic type: the patient erroneously believes that he/she has a medical condition or body deformity that is overlooked or misdiagnosed - Mixed type: delusions characteristic of more than one of the above types but without any one dominating theme - Unspecified type Rare. According to DSM-IV-TR estimated around 0.03% in the general population; 1-2% of all inpatient psychiatric admissions. The most common subtype is the persecutory type. Variable: the jealous type may wane and wax or remit; the persecutory type is often chronic. Clinical Manifestations and Diagnostic Considerations Mental status examination is significant for non-bizarre delusions but otherwise is within normal limits. There are minimal associated mood or anxiety symptoms; if present such symptoms appear secondary to the tenaciously held delusional beliefs. History is significant for a close relationship with another person who presents with similar delusional beliefs and meets criteria for a psychotic disorder. The patient who first presents with delusional symptoms is designated as the "primary," the "secondary" follows. Also, usually, the primary is dominant in his/her relationship with the secondary, who acts as a more passive recipient. For example, a parent with schizophrenia and chronic paranoid delusions about FBI surveillance may be the primary while his/her child, who only recently started to believe that indeed there are FBI cameras hidden on their property, is the secondary. Other diagnoses, including medical or drug induced disorders as well as other psychotic or mood disorders, should be excluded if folie à deux is to be diagnosed. Rare overall but statistics may be misleading due to under-reporting. Preliminary data suggest an increased prevalence in women. Hospitalization is recommended if the acute psychotic symptoms result in danger to self or others or significant impairment. Usually removing the secondary from the primary's environment is sufficient to promote complete remission of symptoms. In addition, the primary's condition should be treated as indicated. Interestingly, a remission of the primary's symptoms is followed by the remission of the secondary's delusional beliefs. When the secondary is separated from the primary the prognosis is good. - Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR. PsychiatryOnline.com Online ISBN 0-89042-334-2. Accessed 03/01/2011 - Kapur S.Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia.Am J Psychiatry. 2003 Jan;160(1):13-23 - Wicks S, Hjern A, Gunnell D, et. Social adversity in childhood and the risk of developing psychosis: a national cohort study. Am J Psychiatry. 2005 Sep;162(9):1652-7 - APA Practice Guidelines Guideline Watch (September 2009): Practice Guideline for the Treatment of Patients With Schizophrenia.PsychiatryOnline.com Online ISBN 0-89042-336-9. Accessed 03/01/2011	2	18	2	0	3	0.621053	5	9,826
- gastrointestinal stromal tumors (GIST) - esophageal cancer - stomach cancer (also called gastric cancer) - liver cancer (also called hepatocellular carcinoma, HCC, and hepatoma) - gallbladder cancer - pancreatic cancer - colorectal cancer (also called colon cancer, bowel cancer, and rectal cancer) - anal cancer \|Tumors: digestive system neoplasia\| \|GI tract\|\|Upper GI tract\|\|Esophagus\|\|Squamous cell carcinoma · Adenocarcinoma\| \|Stomach\|\|Gastric carcinoma · Signet ring cell carcinoma · Gastric lymphoma (MALT lymphoma) · Linitis plastica\| \|Lower GI tract\| \|Small intestine\|\|Duodenal cancer (Adenocarcinoma)\| \|Appendix\|\|Carcinoid · Pseudomyxoma peritonei\| \|Colon/rectum\|\|colorectal polyp: Peutz-Jeghers syndrome · Juvenile polyposis syndrome · Familial adenomatous polyposis/Gardner’s syndrome · Cronkhite–Canada diseaseneoplasm: Adenocarcinoma · Familial adenomatous polyposis ·Hereditary nonpolyposis colorectal cancer\| \|Anus\|\|Squamous cell carcinoma\| \|Upper and/or lower\|\|Gastrointestinal stromal tumor · Krukenberg tumor (metastatic)\| \|Accessory\|\|Liver\|\|malignant: Hepatocellular carcinoma (Fibrolamellar) · Hepatoblastomabenign: Hepatocellular adenoma · Cavernous hemangiomahyperplasia: Focal nodular hyperplasia · Nodular regenerative hyperplasia\| \|Biliary tract\|\|bile duct: Cholangiocarcinoma · Klatskin tumorgallbladder: Gallbladder cancer\| \|Pancreas\|\|exocrine pancreas: Adenocarcinoma · Pancreatic ductal carcinomaPancreatoblastoma\| \|Peritoneum\|\|Primary peritoneal cancer\| Gastrointestinal stromal tumor Signs and symptoms Patients present with trouble swallowing, gastrointestinal hemorrhage or metastases (mainly in the liver). Intestinal obstruction is rare, due to the tumor’s outward pattern of growth. Often, there is a history of vague abdominal pain or discomfort, and the tumor has become rather large by time the diagnosis is made. Generally, the definitive diagnosis is made with a biopsy, which can be obtained endoscopically, percutaneously with CT or ultrasound guidance or at the time of surgery. As part of the analysis, blood tests and CT scanning are often undertaken. A biopsy sample will be investigated under the microscope. The histopathologist identifies the characteristics of GISTs (spindle cells in 70-80%, epitheloid aspect in 20-30%). Smaller tumors can usually be found to the muscularis propria layer of the intestinal wall. Large ones grow, mainly outward, from the bowel wall until the point where they outstrip their blood supply and necrose (die) on the inside, forming a cavity that may eventually come to communicate with the bowel lumen. When GIST is suspected—as opposed to other causes for similar tumors—the pathologist can use immunohistochemistry (specific antibodies that stain the molecule CD117 (also known as c-kit) —see below). 95% of all GISTs are CD117-positive (other possible markers include CD34, desmin, vimentin and others). Other cells that show CD117 positivity are mast cells. If the CD117 stain is negative and suspicion remains that the tumor is a GIST, the newer antibody DOG-1 (Discovered On GIST-1) can be used. Also sequencing of Kit and PDGFRA can be used to prove the diagnosis. Barium fluoroscopic examinations (upper GI series and small bowel series (small bowel follow-through)) and CT are commonly used to evaluate the patient with upper abdominal pain. Both are adequate to make the diagnosis of GIST, although small tumors may be missed, especially in cases of a suboptimal examination. Small GISTs appear as intramural masses. When large (> 5 cm), they most commonly grow outward from the bowel. Internal calcifications may be present. As the tumor outstrips its blood supply, it can necrose internally, creating a central fluid-filled cavity that can eventually ulcerate into the lumen of the bowel or stomach. The tumor can directly invade adjacent structures in the abdomen. The most common site of spread is to the liver. Spread to the peritoneum may be seen. In distinction to gastric adenocarcinoma or gastric/small bowel lymphoma, malignant adenopathy (swollen lymph nodes) is uncommon (<10%). GISTs are tumors of connective tissue, i.e. sarcomas; unlike most gastrointestinal tumors, they are non-epithelial. 70% occur in the stomach, 20% in the small intestine and less than 10% in the esophagus. Small tumors are generally benign, especially when cell division rate is slow, but large tumors disseminate to the liver, omentum and peritoneal cavity. They rarely occur in other abdominal organs. Some tumors of the stomach and small bowel referred to as leiomyosarcomas (malignant tumor of smooth muscle) would most likely be reclassified as GISTs today on the basis of immunohistochemical staining. GISTs are thought to arise from interstitial cells of Cajal (ICC), that are normally part of the autonomic nervous system of the intestine. They serve a pacemaker function in controlling motility. Most (50-80%) GISTs arise because of a mutation in a gene called c-kit. This gene encodes a transmembrane receptor for a growth factor termed scf (stem cell factor). The c-kit/CD117 receptor is expressed on ICCs and a large number of other cells, mainly bone marrow cells, mast cells, melanocytes and several others. In the gut, however, a mass staining positive for CD117 is likely to be a GIST, arising from ICC cells. The c-kit molecule comprises a long extracellular domain, a transmembrane segment, and an intracellular part. Mutations generally occur in the DNA encoding the intracellular part (exon 11), which acts as a tyrosine kinase to activate other enzymes. Mutations make c-kit function independent of activation by scf, leading to a high cell division rate and possibly genomic instability. It is likely that additional mutations are “required” for a cell with a c-kit mutation to develop into a GIST, but the c-kit mutation is probably the first step of this process. The tyrosine kinase function of c-kit is vital in the therapy for GISTs, as described below. Although some families with hereditary GISTs have been described, most cases are sporadic. In GIST cells, the c-kit gene is mutated approximately 85% to 90% of the time. 35% of the GIST cells that do not have a mutated c-kit (“wild-type”) do have a mutation in another gene, PDGFR-α (platelet derived growth factor receptor alpha), which is a related tyrosine kinase. Mutations in the exons 11, 9 and rarely 13 and 17 of the c-kit gene are known to occur in GIST. D816V point mutations in c-kit exon 17 are responsible for resistance to targeted therapy drugs like imatinib mesylate. Mutations in c-kit and PDGFrA are mutually exclusive. Tumor size, mitotic rate, and location can be used to predict the risk of recurrence in GIST patients. Tumors Surgery is the mainstay of therapy for non-metastatic GISTs. Lymph node metastases are rare and routine removal of lymph nodes is typically not necessary. Wide margins are not necessary. Laparoscopic surgery, a minimally invasive type of abdominal surgery using telescopes and specialized instruments, has been shown to be effective for removal of these tumors without needing large incisions. Until recently, GISTs were notorious for being resistant to chemotherapy, with a success rate of <5%. Recently, the c-kit tyrosine kinase inhibitor imatinib, a drug initially marketed for chronic myelogenous leukemia, was found to be useful in treating GISTs, leading to a 40-70% response rate in metastatic or inoperable cases. Data presented at the 2007 ASCO meeting showed that adjuvant treatment with imatinib following surgical resection of GIST tumors can significantly reduce the risk of disease recurrence (6% recurrence on imatinib vs. 17% without therapy at 12 months). The optimal duration of adjuvant therapy is currently unknown; trials are ongoing evaluating treatment durations of 1, 2, and 3 years. Patients who develop resistance to imatinib may respond to the multiple tyrosine kinase inhibitor sunitinib (marketed as Sutent). The effectiveness of imatinib and sunitinib depend on the genotype. Therapy for GIST is best directed by physicians familiar with the disease. Such doctors, specifically surgeons and medical oncologists, are found at major cancer centers. Esophageal cancers are typically carcinomas which arise from the epithelium, or surface lining, of the esophagus. Most esophageal cancers fall into one of two classes: squamous cell carcinomas, which are similar to head and neck cancer in their appearance and association with tobacco and alcohol consumption, and adenocarcinomas, which are often associated with a history of gastroesophageal reflux disease and Barrett’s esophagus. Signs and symptoms Dysphagia and Odynophagia are the most common symptoms of esophageal cancer. Dysphagia (difficulty swallowing) is the first symptom in most patients. Odynophagia (painful swallowing) may be present. Fluids and soft foods are usually tolerated, while hard or bulky substances (such as bread or meat) cause much more difficulty. Substantial weight loss is characteristic as a result of poor nutrition and the active cancer. Pain, often of a burning nature, may be severe and worsened by swallowing, and can be spasmodic in character. An early sign may be an unusually husky or raspy voice. The presence of the tumor may disrupt normal peristalsis (the organised swallowing reflex), leading to nausea and vomiting, regurgitation of food, coughing and an increased risk of aspiration pneumonia. The tumor surface may be fragile and bleed, causing hematemesis (vomiting up blood). Compression of local structures occurs in advanced disease, leading to such problems as upper airway obstruction and superior vena cava syndrome. Fistulas may develop between the esophagus and the trachea, increasing the pneumonia risk; this condition is usually heralded by cough, fever or aspiration. If the disease has spread elsewhere, this may lead to symptoms related to this: liver metastasis could cause jaundice and ascites, lung metastasis could cause shortness of breath, pleural effusions, etc. Barrett’s esophagus is considered to be a risk factor for esophageal adenocarcinoma. - There are a number of risk factors for esophageal cancer. Some subtypes of cancer are linked to particular risk factors: - Age. Most patients are over 60, and the median in US patients is 67. - Sex. It is more common in men. - Heredity. It is more likely in people who have close relatives with cancer. - Tobacco smoking and heavy alcohol use increase the risk, and together appear to increase the risk more than either individually. - Gastroesophageal reflux disease (GERD) and its resultant Barrett’s esophagus increase esophageal cancer risk due to the chronic irritation of the mucosal lining (adenocarcinoma is more common in this condition, while all other risk factors predispose more for squamous cell carcinoma). - Human papillomavirus (HPV) - Corrosive injury to esophagus by swallowing strong alkalines (lye) or acids. - Particular dietary substances, such as nitrosamine. - A medical history of other head and neck cancers increases the chance of developing a second cancer in the head and neck area, including esophageal cancer. - Plummer-Vinson syndrome (anemia and esophageal webbing) - Tylosis and Howel-Evans syndrome (hereditary thickening of the skin of the palms and soles). - Radiation therapy for other conditions in the mediastinum. - Celiac disease predisposes towards squamous cell carcinoma. - Obesity increases the risk of adenocarcinoma fourfold. It is suspected that increased risk of reflux may be behind this association. - Drinking large quantities of hot beverages, especially hot brewed teas - Alcohol consumption in individuals predisposed to alcohol flush reaction. - Risk appears to be less in patients using aspirin or related drugs (NSAIDs). - The role of Helicobacter pylori in progression to esophageal adenocarcinoma is still uncertain, but, on the basis of population data, it may carry a protective effect. It is postulated that H. pylori prevents chronic gastritis, which is a risk factor for reflux, which in turn is a risk factor for esophageal adenocarcinoma. - According to the National Cancer Institute, “diets high in cruciferous (cabbage, broccoli, cauliflower) and green and yellow vegetables and fruits are associated with a decreased risk of esophageal cancer.” - Moderate coffee consumption is associated with a decreased risk. - According to one Italian study of “diet surveys completed by 5,500 Italians”—a study which has raised debates questioning its claims among cancer researchers cited in news reports about it—eating pizza more than once a week appears “to be a favorable indicator of risk for digestive tract neoplasms in this population.” Endoscopy and radial endoscopic ultrasound images of submucosal tumour in mid-esophagus. Although an occlusive tumor may be suspected on a barium swallow or barium meal, the diagnosis is best made with esophagogastroduodenoscopy (EGD, endoscopy); this involves the passing of a flexible tube down the esophagus and visualising the wall. Biopsies taken of suspicious lesions are then examined histologically for signs of malignancy. Additional testing is usually performed to estimate the tumor stage. Computed tomography (CT) of the chest, abdomen and pelvis, can evaluate whether the cancer has spread to adjacent tissues or distant organs (especially liver and lymph nodes). The sensitivity of CT scan is limited by its ability to detect masses (e.g. enlarged lymph nodes or involved organs) generally larger than 1 cm. FDG-PET (positron emission tomography) scan is also being used to estimate whether enlarged masses are metabolically active, indicating faster-growing cells that might be expected in cancer. Esophageal endoscopic ultrasound (EUS) can provide staging information regarding the level of tumor invasion, and possible spread to regional lymph nodes. The location of the tumor is generally measured by the distance from the teeth. The esophagus (25 cm or 10 inches long) is commonly divided into three parts for purposes of determining the location. Adenocarcinomas tend to occur distally and squamous cell carcinomas proximally, but the converse may also be the case. Most tumors of the esophagus are malignant, only about 0.5% are benign. A very small proportion (under 10%) is leiomyoma (smooth muscle tumor) or gastrointestinal stromal tumor (GIST). Malignant tumors are generally adenocarcinomas, squamous cell carcinomas, and occasionally small-cell carcinomas. The latter share many properties with small-cell lung cancer, and are relatively sensitive to chemotherapy compared to the other types. Self-expandable metallic stents are used for the palliation of esophageal cancer. Esophageal cancer affecting the lower esophageus. Insets show the tumor in more detail both before and after placement of a stent. The treatment is determined by the cellular type of cancer (adenocarcinoma or squamous cell carcinoma vs other types), the stage of the disease, the general condition of the patient and other diseases present. On the whole, adequate nutrition needs to be assured, and adequate dental care is vital. If the patient cannot swallow at all, a stent may be inserted to keep the esophagus patent; stents may also assist in occluding fistulas. A nasogastric tube may be necessary to continue feeding while treatment for the tumor is given, and some patients require a gastrostomy (feeding hole in the skin that gives direct access to the stomach). The latter two are especially important if the patient tends to aspirate food or saliva into the airways, predisposing for aspiration pneumonia. Surgery is possible if the disease is localised, which is the case in 20–30% of all patients. If the tumor is larger but localised, chemotherapy and/or radiotherapy may occasionally shrink the tumor to the extent that it becomes “operable”; however, this combination of treatments (referred to as neoadjuvant chemoradiation) is still somewhat controversial in most medical circles. Esophagectomy is the removal of a segment of the esophagus; as this shortens the length of the remaining esophagus, some other segment of the digestive tract (typically the stomach or part of the Colon or jejunum]) is pulled up to the chest cavity and interposed. If the tumor is unresectable or the patient is not fit for surgery, palliative esophageal stenting can allow the patient to tolerate soft diet. Endoscopic Therapy for Localized Disease There is accumulating data that endoscopic therapy is a safe, less invasive, and effective therapy for very early esophageal cancer. The candidates for endoscopic therapy are Stage 1 patients with tumors invading into the lamina propria (T1 mucosal) or submucosa (T1 submucosal) that do not have regional or distant metastasis. Patients with carcinoma in-situ or high-grade dysplasia can also be treated with endoscopic therapy. Submucosa cancers with increased risk of nodal metastases may not be as amenable to curative therapy. The two forms of endoscopic therapy that have been used for Stage 0 and I disease are endoscopic mucosal resection (EMR) and mucosal ablation using photodynamic therapy, Nd-YAG laser, or argon plasma coagulation. EMR Endoscopic Mucosal Resection has been advocated for early cancers (that is, those that are superficial and confined to the mucosa only) and has been shown to be a less invasive, safe, and highly effective nonsurgical therapy for early squamous cell esophageal cancer. Preliminary reports also suggest its safety and efficacy for early adenocarcinoma arising in Barrett’s esophagus. The prognosis after treatment with endoscopic mucosal resection is comparable to surgical resection. This technique can be attempted in patients, without evidence of nodal or distant metastases, with differentiated tumors that are slightly raised and less than 2 cm in diameter, or in differentiated tumors that are ulcerated and less than 1 cm in diameter. The most commonly employed modalities of endoscopic mucosal resection include strip biopsy, double-snare polypectomy, resection with combined use of highly concentrated saline and epinephrine, and resection using a cap. The strip biopsy method for endoscopic mucosal resection of esophageal cancer is performed with a double-channel endoscope equipped with grasping forceps and snare. After marking the lesion border with an electric coagulator, saline is injected into the submucosa below the lesion to separate the lesion from the muscle layer and to force its protrusion. The grasping forceps are passed through the snare loop. The mucosa surrounding the lesion is grasped, lifted, and strangulated and resected by electrocautery. The endoscopic double-snare polypectomy method is indicated for protruding lesions. Using a double-channel scope, the lesion is grasped and lifted by the first snare and strangulated with the second snare for complete resection. Endoscopic resection with injection of concentrated saline and epinephrine is carried out using a double-channel scope. The lesion borders are marked with a coagulator. Highly concentrated saline and epinephrine are injected (15–20 ml) into the submucosal layer to swell the area containing the lesion and elucidate the markings. The mucosa outside the demarcated border is excised using a high-frequency scalpel to the depth of the submucosal layer. The resected mucosa is lifted and grasped with forceps, trapping and strangulating the lesion with a snare, and then resected by electrocautery. A fourth method of endoscopic mucosal resection employs the use of a clear cap and prelooped snare inside the cap. After insertion, the cap is placed on the lesion and the mucosa containing the lesion is drawn up inside the cap by aspiration. The mucosa is caught by the snare and strangulated, and finally resected by electrocautery. This is called the “band and snare” or “suck and cut” technique. The resected specimen is retrieved and submitted for microscopic examination for determination of tumor invasion depth, resection margin, and possible vascular involvement. The resulting “ulcer” heals within 3 weeks. Although most lesions treated in the esophagus have been early squamous cell cancers, endoscopic snare resection can also be used to debulk or completely treat polypoid dysplastic or malignant lesions in Barrett’s esophagus. In a preliminary report from Germany, EMR was performed as primary treatment or adjunctive therapy following photodynamic therapy for early adenocarcinomas in Barrett’s esophagus. The “suck and cut” technique (with and without prior saline injection) was used as well as the “band and cut” technique. Although all tumors were resected without difficulty, 12.5% developed bleeding (which was managed successfully by endoscopic therapy). Eighty-one percent of the lesions were completely resected. The other lesions were also treated with other endoscopic techniques. While this report suggests it is feasible to completely resect local, circumscribed, early adenocarcinomas arising in Barrett’s esophagus, the relative safety and efficacy of EMR in conjunction with photodynamic therapy is unknown. The major complications of endoscopic mucosal resection include postoperative bleeding and perforation and stricture formation. During the procedure, an injection of 100,000 times diluted epinephrine into the muscular wall, along with high frequency coagulation or clipping can be applied to the bleeding point for hemostasis. It is important to administer acid-reducing medications to prevent postoperative hemorrhage. Perforation may be prevented with sufficient saline injection to raise the mucosa containing the lesion. The “non-lifting sign” and complaints of pain when the snare strangulates the lesion are contrainidications of EMR. When perforation is recognized immediately after a procedure, the perforation should be closed by clips. Surgery should be considered in cases of endoscopic closure failure. The incidence of complication range from 0–50% and squamous cell recurrence rates range from 0–8%. Laser therapy is the use of high-intensity light to destroy tumor cells; it affects only the treated area. This is typically done if the cancer cannot be removed by surgery. The relief of a blockage can help to reduce dysphagia and pain. Photodynamic therapy (PDT), a type of laser therapy, involves the use of drugs that are absorbed by cancer cells; when exposed to a special light, the drugs become active and destroy the cancer cells. Chemotherapy depends on the tumor type, but tends to be cisplatin-based (or carboplatin or oxaliplatin) every three weeks with fluorouracil (5-FU) either continuously or every three weeks. In more recent studies, addition of epirubicin (ECF) was better than other comparable regimens in advanced nonresectable cancer. Chemotherapy may be given after surgery (adjuvant, i.e. to reduce risk of recurrence), before surgery (neoadjuvant) or if surgery is not possible; in this case, cisplatin and 5-FU are used. Ongoing trials compare various combinations of chemotherapy; the phase II/III REAL-2 trial – for example – compares four regimens containing epirubicin and either cisplatin or oxaliplatin and either continuously infused fluorouracil or capecitabine. Radiotherapy is given before, during or after chemotherapy or surgery, and sometimes on its own to control symptoms. In patients with localised disease but contraindications to surgery, “radical radiotherapy” may be used with curative intent. Patients are followed up frequently after a treatment regimen has been completed. Frequently, other treatments are necessary to improve symptoms and maximize nutrition. In general, the prognosis of esophageal cancer is quite poor, because so many patients present with advanced disease: The overall five-year survival rate (5YSR) is less than 5%. Individualized prognosis depends largely on stage. Those with cancer restricted entirely to the esophageal mucosa have about an 80% 5YSR, but submucosal involvement brings this down to less than 50%. Extension into the muscularis propria (muscular layer of the esophageus) has meant a 20% 5YSR and extension to the structures adjacent to the esophagus results in a 7% 5YSR. Patients with distant metastases (who are not candidates for curative surgery) have a less than 3% 5YSR. Of all patients undergoing surgery with curative intent, the 5YSR is only about 25%. But these statistics are getting better, as more patients are getting diagnosis earlier because of the awareness of Barrett’s Esophagus. Stomach or gastric cancer can develop in any part of the stomach and may spread throughout the stomach and to other organs; particularly the esophagus, lungs and the liver. Stomach cancer causes about 800,000 deaths worldwide per year.” Signs and symptoms Endoscopic image of linitis plastica, a type of stomach cancer where the entire stomach is invaded, leading to a leather bottle-like appearance with blood coming out of it. Stomach cancer is often asymptomatic or causes only nonspecific symptoms in its early stages. By the time symptoms occur, the cancer has generally metastasized to other parts of the body, one of the main reasons for its poor prognosis. Stomach cancer can cause the following signs and symptoms: - Indigestion or a burning sensation (heartburn) - Loss of appetite, especially for meat - Abdominal pain or discomfort in the upper abdomen - Nausea and vomiting - Diarrhea or constipation - Bloating of the stomach after meals - Weight loss - Weakness and fatigue Bleeding (vomiting blood or having blood in the stool) which will appear as black. This can lead to anemia. Dysphagia; this feature suggests a tumor in the cardia or extension of the gastric tumor in to the esophagus. These can be symptoms of other problems such as a stomach virus, gastric ulcer or tropical sprue and diagnosis should be done by a gastroenterologist or an oncologist. Infection by Helicobacter pylori is believed to be the cause of most stomach cancer while autoimmune atrophic gastritis, intestinal metaplasia and various genetic factors are associated with increased risk levels. It is not currently believed that diet has any role to play. In more detail, H. pylori is the main risk factor in 65–80% of gastric cancers, but in only 2% of such infections. Approximately ten percent of cases show a genetic component. In Japan and other countries bracken consumption and spores are correlated with incidence of stomach cancer, though causality has yet to be established. Gastric cancer shows a male predominance in its incidence as up to three males are affected for every female. Estrogen may protect women against the development of this cancer form. A very small percentage of diffuse-type gastric cancers (see Histopathology below) are thought to be genetic. Hereditary Diffuse Gastric Cancer (HDGC) has recently been identified and research is ongoing. However, genetic testing and treatment options are already available for families at risk. Some researchers showed a correlation between Iodine deficiency or excess, iodine-deficient goitre and gastric cancer; a decrease of the incidence of death rate from stomach cancer after implementation of the effective I-prophylaxis was reported too. The proposed mechanism of action is that iodide ion can function in gastric mucosa as an antioxidant reducing species that can detoxify poisonous reactive oxygen species, such as hydrogen peroxide. China being member of International Cancer Genome Consortium is leading efforts to map stomach cancer’s complete genome. To find the cause of symptoms, the doctor asks about the patient’s medical history, does a physical exam, and may order laboratory studies. The patient may also have one or all of the following exams: - Gastroscopic exam is the diagnostic method of choice. This involves insertion of a fibre optic camera into the stomach to visualize it. - Upper GI series (may be called barium roentgenogram) - Computed tomography or CT scanning of the abdomen may reveal gastric cancer, but is more useful to determine invasion into adjacent tissues, or the presence of spread to local lymph nodes. Abnormal tissue seen in a gastroscope examination will be biopsied by the surgeon or gastroenterologist. This tissue is then sent to a pathologist for histological examination under a microscope to check for the presence of cancerous cells. A biopsy, with subsequent histological analysis, is the only sure way to confirm the presence of cancer cells. Various gastroscopic modalities have been developed to increased yield of detect mucosa with a dye that accentuates the cell structure and can identify areas of dysplasia. Endocytoscopy involves ultra-high magnification to visualize cellular structure to better determine areas of dysplasia. Other gastroscopic modalities such as optical coherence tomography are also being tested investigationally for similar applications. A number of cutaneous conditions are associated with gastric cancer. A condition of darkened hyperplasia of the skin, frequently of the axilla and groin, known as acanthosis nigricans, is associated with intra-abdominal cancers such as gastric cancer. Other cutaneous manifestations of gastric cancer include tripe palms (a similar darkening hyperplasia of the skin of the palms) and the sign of Leser-Trelat, which is the rapid development of skin lesions known as seborrheic keratoses. - Gastric adenocarcinoma is a malignant epithelial tumor, originating from glandular epithelium of the gastric mucosa. It invades the gastric wall, infiltrating the muscularis mucosae, the submucosa and thence the muscularis propria. Histologically, there are two major types of gastric cancer (Lauren classification): intestinal type and diffuse type. - Intestinal type adenocarcinoma: tumor cells describe irregular tubular structures, harboring pluristratification, multiple lumens, reduced stroma (“back to back” aspect). Often, it associates intestinal metaplasia in neighboring mucosa. Depending on glandular architecture, cellular pleomorphism and mucosecretion, adenocarcinoma may present 3 degrees of differentiation: well, moderate and poorly differentiate. - Diffuse type adenocarcinoma (mucinous, colloid): Tumor cells are discohesive and secrete mucus which is delivered in the interstitium producing large pools of mucus/colloid (optically “empty” spaces). It is poorly differentiated. If the mucus remains inside the tumor cell, it pushes the nucleus at the periphery – “signet-ring cell”. If cancer cells are found in the tissue sample, the next step is to stage, or find out the extent of the disease. Various tests determine whether the cancer has spread and, if so, what parts of the body are affected. Because stomach cancer can spread to the liver, the pancreas, and other organs near the stomach as well as to the lungs, the doctor may order a CT scan, a PET scan, an endoscopic ultrasound exam, or other tests to check these areas. Blood tests for tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) may be ordered, as their levels correlate to extent of metastasis, especially to the liver, and the cure rate. Staging may not be complete until after surgery. The surgeon removes nearby lymph nodes and possibly samples of tissue from other areas in the abdomen for examination by a pathologist. TNM staging is used. Like any cancer, treatment is adapted to fit each person’s individual needs and depends on the size, location, and extent of the tumor, the stage of the disease, and general health. Cancer of the stomach is difficult to cure unless it is found in an early stage (before it has begun to spread). Unfortunately, because early stomach cancer causes few symptoms, the disease is usually advanced when the diagnosis is made. Treatment for stomach cancer may include surgery, chemotherapy, and/or radiation therapy. New treatment approaches such as biological therapy and improved ways of using current methods are being studied in clinical trials. Surgery is the most common treatment and is the only hope of cure for stomach cancer. The surgeon removes part or all of the stomach, as well as the surrounding lymph nodes, with the basic goal of removing all cancer and a margin of normal tissue. Depending on the extent of invasion and the location of the tumor, surgery may also include removal of part of the intestine or pancreas. Tumors in the lower part of the stomach may call for a Billroth I or Billroth II procedure. Endoscopic mucosal resection (EMR) is a treatment for early gastric cancer (tumor only involves the mucosa) that has been pioneered in Japan, but is also available in the United States at some centers. In this procedure, the tumor, together with the inner lining of stomach (mucosa), is removed from the wall of the stomach using an electrical wire loop through the endoscope. The advantage is that it is a much smaller operation than removing the stomach. Endoscopic submucosal dissection (ESD) is a similar technique pioneered in Japan, used to resect a large area of mucosa in one piece. If the pathologic examination of the resected specimen shows incomplete resection or deep invasion by tumor, the patient would need a formal stomach resection. Surgical interventions are currently curative in less than 40% of cases, and, in cases of metastasis, may only be palliative. The use of chemotherapy to treat stomach cancer has no established standard of care. Unfortunately, stomach cancer has not been especially sensitive to these drugs until recently, and historically served to palliatively reduce the size of the tumor and increase survival time. Some drugs used in stomach cancer treatment include: 5-FU (fluorouracil), BCNU (carmustine), methyl-CCNU (Semustine), and doxorubicin (Adriamycin), as well as Mitomycin C, and more recently cisplatin and taxotere in various combinations. The relative benefits of these drugs, alone and in combination, are unclear. Scientists are exploring the benefits of giving chemotherapy before surgery to shrink the tumor, or as adjuvant therapy after surgery to destroy remaining cancer cells. Combination treatment with chemotherapy and radiation therapy is also under study. Doctors are testing a treatment in which anticancer drugs are put directly into the abdomen (intraperitoneal hyperthermic chemoperfusion). Chemotherapy also is being studied as a treatment for cancer that has spread, and as a way to relieve symptoms of the disease. The side effects of chemotherapy depend mainly on the drugs the patient receives. Radiation therapy (also called radiotherapy) is the use of high-energy rays to damage cancer cells and stop them from growing. When used, it is generally in combination with surgery and chemotherapy, or used only with chemotherapy in cases where the individual is unable to undergo surgery. Radiation therapy may be used to relieve pain or blockage by shrinking the tumor for palliation of incurable disease While previous studies of multimodality therapy (combinations of surgery, chemotherapy and radiation therapy) gave mixed results, the Intergroup 0116 (SWOG 9008) study showed a survival benefit to the combination of chemotherapy and radiation therapy in patients with nonmetastatic, completely resected gastric cancer. Patients were randomized after surgery to the standard group of observation alone, or the study arm of combination chemotherapy and radiation therapy. Those in the study arm receiving chemotherapy and radiation therapy survived on average 36 months; compared to 27 months with observation. The usual outcome is poor, because only 10 – 20% of hepatocellular carcinomas can be removed completely using surgery. If the cancer cannot be completely removed, the disease is usually deadly within 3 to 6 months. This is partially due to late presentation with large tumours, but also the lack of medical expertise and facilities. This is a rare tumor in the United States. A new receptor tyrosine kinase inhibitor, sorafenib has been shown in a Spanish phase III clinical trial to add two months to the lifespan of late stage HCC patients with well preserved liver function. Signs and symptoms HCC may present with jaundice, bloating from ascites, easy bruising from blood cloting abnormalies. Hepatitis and excessive alcohol are the leading causes of HCC. Hepatocellular carcinoma, like any other cancer, develops when there is a mutation to the cellular machinery that causes the cell to replicate at a higher rate and/or results in the cell avoiding apoptosis. In particular, chronic infections of hepatitis B and/or C can aid the development of hepatocellular carcinoma by repeatedly causing the body’s own immune system to attack the liver cells, some of which are infected by the virus, others merely bystanders. While this constant cycle of damage followed by repair can lead to mistakes during repair which in turn lead to carcinogenesis, this hypothesis is more applicable, at present, to hepatitis C. Chronic hepatitis C causes HCC through the stage of cirrhosis. In chronic hepatitis B, however, the integration of the viral genome into infected cells can directly induce a non-cirrhotic liver to develop HCC. Alternatively, repeated consumption of large amounts of ethanol can have a similar effect. Besides, cirrhosis is commonly caused by alcoholism, chronic hepatitis B and chronic hepatitis C. The toxin aflatoxin from certain Aspergillus species of fungus is a carcinogen and aids carcinogenesis of hepatocellular cancer by building up in the liver. The combined high prevalence of rates of aflatoxin and hepatitis B in settings like China and West Africa has led to relatively high rates of heptatocellular carcinoma in these regions. Other viral hepatitides such as hepatitis A have no potential to become a chronic infection and thus are not related to hepatocellular carcinoma. Hepatocellular carcinoma (HCC) most commonly appears in a patient with chronic viral hepatitis (hepatitis B or hepatitis C, 20%) or with cirrhosis (about 80%). These patients commonly undergo surveillance with ultrasound due to the cost-effectiveness. In patients with a higher suspicion of HCC (such as rising alpha-fetoprotein and des-gamma carboxyprothrombin levels), the best method of diagnosis involves a CT scan of the abdomen using intravenous contrast agent and three-phase scanning (before contrast administration, immediately after contrast administration, and again after a delay) to increase the ability of the radiologist to detect small or subtle tumors. It is important to optimize the parameters of the CT examination, because the underlying liver disease that most HCC patients have can make the findings more difficult to appreciate. On CT, HCC can have three distinct patterns of growth: - A single large tumor - Multiple tumors - Poorly defined tumor with an infiltrative growth pattern A biopsy is not needed to confirm the diagnosis of HCC if certain imaging criteria are met. The key characteristics on CT are hypervascularity in the arterial phase scans, washout or de-enhancement in the portal and delayed phase studies, a pseudocapsule and a mosaic pattern. Both calcifications and intralesional fat may be appreciated. CT scans use contrast agents, which are typically iodine or barium based. Some patients are allergic to one or both of these contrast agents, most often iodine. Usually the allergic reaction is manageable and not life threatening. An alternative to a CT imaging study would be the MRI. MRI’s are more expensive and not as available because fewer facilities have MRI machines. More important MRI are just beginning to be used in tumor detection and fewer radiologists are skilled at finding tumors with MRI studies when it is used as a screening device. Mostly the radiologists are using MRIs to do a secondary study to look at an area where a tumor has already been detected. MRI’s also use contrast agents. One of the best for showing details of liver tumors is very new: iron oxide nano-particles appears to give better results. The latter are absorbed by normal liver tissue, but not tumors or scar tissue. In a review article of the screening, diagnosis and treatment of hepatocellular carcinoma, 4 articles were selected for comparing the accuracy of CT and MRI in diagnosing this malignancy. Radiographic diagnosis was verified against post-transplantation biopsy as the gold standard. With the exception of one instance of specificity, it was discovered that MRI was more sensitive and specific than CT in all four studies. Macroscopically, liver cancer appears as a nodular or infiltrative tumor. The nodular type may be solitary (large mass) or multiple (when developed as a complication of cirrhosis). Tumor nodules are round to oval, grey or green (if the tumor produces bile), well circumscribed but not encapsulated. The diffuse type is poorly circumscribed and infiltrates the portal veins, or the hepatic veins (rarely). Microscopically, there are four architectural and cytological types (patterns) of hepatocellular carcinoma: fibrolamellar, pseudoglandular (adenoid), pleomorphic (giant cell) and clear cell. In well differentiated forms, tumor cells resemble hepatocytes, form trabeculae, cords and nests, and may contain bile pigment in cytoplasm. In poorly differentiated forms, malignant epithelial cells are discohesive, pleomorphic, anaplastic, giant. The tumor has a scant stroma and central necrosis because of the poor vascularization. Important features that guide treatment include: – - spread (stage) - involvement of liver vessels - presence of a tumor capsule - presence of extrahepatic metastases - presence of daughter nodules - vascularity of the tumor MRI is the best imaging method to detect the presence of a tumor capsule. - Surgical resection to remove a tumor together with surrounding liver tissue while preserving enough liver remnant for normal body function. This treatment offers the best prognosis for long-term survival, but unfortunately only 10-15% of patients are suitable for surgical resection. This is often due to extensive disease or poor liver function. Resection in cirrhotic patients carries high morbidity and mortality. The expected liver remnant should be more than 25% of the total size for a non-cirrhotic liver, while that should be more than 40% of the total size for a cirrhotic liver. The overall recurrent rate after resection is 50-60%. - Liver transplantation to replace the diseased liver with a cadaveric liver or a living donor graft. Historically low survival rates (20%-36%). Recentimprovement (61.1%; 1996-2001), likely related to adoption of the Milan criteria at US transplantation centers. If the liver tumor has metastasized, the immuno-suppressant post-transplant drugs decrease the chance of survival. - Percutaneous ethanol injection (PEI) well tolerated, high RR in small (8 cm), presence of portal vein thrombus, tumors with portal-systemic shunt and patients with poor liver function. - Radiofrequency ablation (RFA) uses high frequency radio-waves to destroy tumor by local heating. The electrodes are inserted into the liver tumor under ultrasound image guidance using percutaneous, laparoscopic or open surgical approach. It is suitable for small tumors(<5 cm). A large randomised trial comparing surgical resection and RFA for small HCC showed similar 4 years-survival and less morbidities for patients treated with RFA. - Selective Internal Radiation Therapy can be used to destroy the tumor from within (thus minimizing exposure to healthy tissue). There are currently two products available, SIR-Spheres and TheraSphere The latter is an FDA approved treatment for primary liver cancer (HCC) which has been shown in clinical trials to increase survival rate of low-risk patients. SIR-Spheres are FDA approved for the treatment of metastatic colorectal cancer but outside the US SIR-Spheres are approved for the treatment of any non-resectable liver cancer including primary liver cancer. This method uses a catheter (inserted by a radiologist) to deposit radioactive particles to the area of interest. - Intra-arterial iodine-131–lipiodol administration Efficacy demonstrated in unresectable patients, those with portal vein thrombus. This treatment is also used as adjuvant therapy in resected patients (Lau at et, 1999). It is believed to raise the 3-year survival rate from 46 to 86%. This adjuvant therapy is in phase III clinical trials in Singapore and is available as a standard medical treatment to qualified patients in Hong Kong. - Combined PEI and TACE can be used for tumors larger than 4 cm in diameter, although some Italian groups have had success with larger tumours using TACE alone. - High intensity focused ultrasound (HIFU) (not to be confused with normal diagnostic ultrasound) is a new technique which uses much more powerful ultrasound to treat the tumour. Still at a very experimental stage. Most of the work has been done in China. Some early work is being done in Oxford and London in the UK. - Hormonal therapy Antiestrogen therapy with tamoxifen studied in several trials, mixed results across studies, but generally considered ineffective Octreotide (somatostatin analogue) showed 13-month MS v 4-month MS in untreated patients in a small randomized study; results not reproduced. - Adjuvant chemotherapy: No randomized trials showing benefit of neoadjuvant or adjuvant systemic therapy in HCC; single trial showed decrease in new tumors in patients receiving oral synthetic retinoid for 12 months after resection/ablation; results not reproduced. Clinical trials have varying results. - Palliative: Regimens that included doxorubicin, cisplatin, fluorouracil, interferon, epirubicin, or taxol, as single agents or in combination, have not shown any survival benefit (RR, 0%-25%); a few isolated major responses allowed patients to undergo partial hepatectomy; no published results from any randomized trial of systemic chemotherapy. - Cryosurgery: Cryosurgery is a new technique that can destroy tumors in a variety of sites (brain, breast, kidney, prostate, liver). Cryosurgery is the destruction of abnormal tissue using sub-zero temperatures. The tumor is not removed and the destroyed cancer is left to be reabsorbed by the body. Initial results in properly selected patients with unresectable liver tumors are equivalent to those of resection. Cryosurgery involves the placement of a stainless steel probe into the center of the tumor. Liquid nitrogen is circulated through the end of this device. The tumor and a half inch margin of normal liver are frozen to -190°C for 15 minutes, which is lethal to all tissues. The area is thawed for 10 minutes and then re-frozen to -190°C for another 15 minutes. After the tumor has thawed, the probe is removed, bleeding is controlled, and the procedure is complete. The patient will spend the first post-operative night in the intensive care unit and typically is discharged in 3 – 5 days. Proper selection of patients and attention to detail in performing the cryosurgical procedure are mandatory in order to achieve good results and outcomes. Frequently, cryosurgery is used in conjunction with liver resection as some of the tumors are removed while others are treated with cryosurgery. Patients may also have insertion of a hepatic intra-arterial artery catheter for post-operative chemotherapy. As with liver resection, your surgeon should have experience with cryosurgical techniques in order to provide the best treatment possible. There is a new drug Sorafenib which was originally used for Renal Cell Cancer that has shown promising results when used with Hepatocellular Cancer - Interventional radiology Agaricus blazei mushrooms inhibited abnormal collagen fiber formation in human hepatocarcinoma cells in an in vitro experiment. - Abbreviations: HCC, hepatocellular carcinoma; TACE, transarterial embolization/chemoembolization; PFS, progression-free survival; PS, performance status; HBV, hepatitis B virus; PEI, percutaneous ethanol injection; RFA, radiofrequency ablation; RR, response rate; MS, median survival. A systematic review assessed 12 articles involving a total of 318 patients with hepatocellular carcinoma treated with Yttrium-90 radioembolization. Excluding a study of only one patient, post-treatment CT evaluation of the tumor showed a response ranging from 29 to 100 % of patients evaluated, with all but two studies showing a response of 71 % or greater. The usual outcome is poor, because only 10 – 20% of hepatocellular carcinomas can be removed completely using surgery. If the cancer cannot be completely removed, the disease is usually fatal within 3 – 6 months. However, survival can vary, and occasionally people will survive much longer than 6 months. It is a rare cancer that is still being studied and thought to be related to gallstones building up, which also can lead to calcification of the gallbladder, a condition known as Porcelain gallbladder. Porcelain gallbladder is also rare. Some studies indicate that people with porcelain gallbladder have a high risk of developing gallbladder cancer, but other studies question this. The outlook is poor for recovery if the cancer is found after symptoms have started to occur. - Gender: Approx. twice more common in women than men, mostly between the ages of 50 and 60. - Obesity increases the risk for gallbladder cancer. It is common in north India and indigenous peoples of the Americas. - Primary carcinoma is linked to chronic cholecystitis and cholelithiasis. Signs and Symptoms - Steady pain in the upper right abdomen - Loss of appetite - Weight loss - Jaundice and vomiting due to obstruction - Early symptoms mimic gallbladder inflammation due to gallstones. Later, the symptoms may be that of biliary and stomach obstruction. Most tumors are adenocarcinomas, with a small percent being squamous cell carcinomas. The cancer commonly spreads to the liver, bile duct, stomach,and duodenum. Early diagnosis is not generally possible. People at high risk, such as women or Native Americans with gallstones, are evaluated closely. Transabdominal ultrasound, CT scan, endoscopic ultrasound, MRI, and MR cholangio-pancreatography (MRCP) can be used to diagnose. The most common and most effective treatment is surgical removal of the gallbladder (cholecystectomy) with part of liver and lymph node dissection. However, with gallbladder cancer’s extremely poor prognosis, most patients will die by one year following the surgery. If surgery is not possible, endoscopic stenting of the biliary tree can reduce jaundice and a stent in stomach may relieve vomiting. Chemotherapy and radiation may also be used with surgery. If gall bladder cancer is diagnosed after cholecystectomy for stone disease (incidental cancer), reoperation to remove part of liver and lymph nodes is required in most cases – this should be done as early as possible as these patients have the best chance of long term survival and even cure About 95% of exocrine pancreatic cancers are adenocarcinomas (M8140/3). The remaining 5% include adenosquamous carcinomas, signet ring cell carcinomas, hepatoid carcinomas, colloid carcinomas, undifferentiated carcinomas, and undifferentiated carcinomas with osteoclast-like giant cells. Exocrine pancreatic cancers are far more common than endocrine pancreatic cancers (also known as islet cell carcinomas), which make up about 1% of total cases. Signs and symptoms Pancreatic cancer is sometimes called a “silent killer” because early pancreatic cancer often does not cause symptoms, and the later symptoms are usually non-specific and varied. Therefore, pancreatic cancer is often not diagnosed until it is advanced. Common symptoms include: - Pain in the upper abdomen that typically radiates to the back (seen in carcinoma of the body or tail of the pancreas) - Loss of appetite and/or nausea and vomiting - Significant weight loss - Painless jaundice (yellow skin/eyes, dark urine) when a cancer of the head of the pancreas (about 60% of cases) obstructs the common bile duct as it runs through the pancreas. This may also cause pale-colored stool and steatorrhea. - Trousseau sign, in which blood clots form spontaneously in the portal blood vessels, the deep veins of the extremities, or the superficial veins anywhere on the body, is sometimes associated with pancreatic cancer. - Diabetes mellitus, or elevated blood sugar levels. Many patients with pancreatic cancer develop diabetes months to even years before they are diagnosed with pancreatic cancer, suggesting that new onset diabetes in an elderly individual may be an early warning sign of pancreatic cancer. - Clinical depression has been reported in association with pancreatic cancer, sometimes presenting before the cancer is diagnosed. However, the mechanism for this association is not known. Risk factors for pancreatic cancer include: - Age (particularly over 60) - Male gender - African-American ethnicity - Smoking. Cigarette smoking has a risk ratio of 1.74 with regard to pancreatic cancer; a decade of non-smoking after heavy smoking is associated with a risk ratio of 1.2. - Diets low in vegetables and fruits - Diets high in red meat - Diabetes mellitus is both risk factor for pancreatic cancer, and, as noted earlier, new onset diabetes can be an early sign of the disease. - Chronic pancreatitis has been linked, but is not known to be causal. The risk of pancreatic cancer in individuals with familial pancreatitis is particularly high. - Helicobacter pylori infection - Family history, 5–10% of pancreatic cancer patients have a family history of pancreatic cancer. The genes responsible for most of this clustering in families have yet to be identified. Pancreatic cancer has been associated with the following syndromes; autosomal recessive ataxia-telangiectasia and autosomal dominantly inherited mutations in the BRCA2 gene and PALB2 gene, Peutz-Jeghers syndrome due to mutations in the STK11 tumor suppressor gene, hereditary non-polyposis colon cancer (Lynch syndrome), familial adenomatous polyposis, and the familial atypical multiple mole melanoma-pancreatic cancer syndrome (FAMMM-PC) due to mutations in the CDKN2A tumor suppressor gene. - Gingivitis or periodontal disease - Australia and Canada being members of International Cancer Genome Consortium are leading efforts to map pancreatic cancer’s complete genome. It is controversial whether alcohol consumption is a risk factor for pancreatic cancer. Drinking alcohol excessively is a major cause of chronic pancreatitis, which in turn predisposes to pancreatic cancer, but “chronic pancreatitis that is due to alcohol doesn’t increase risk as much as other types of chronic pancreatitis.” Overall, the association is consistently weak and the majority of studies have found no association. Some studies suggest a relationship, with risk increasing with increasing amount of alcohol intake. Risk is greatest in heavy drinkers mostly on the order of four or more drinks per day. But there appears to be no increased risk for people consuming up to 30g of alcohol a day, so most of the U.S. consumes alcohol at a level that “is probably not a risk factor for pancreatic cancer.” Several studies caution that their findings could be due to confounding factors. Even if a link exists, it “could be due to the contents of some alcoholic beverages” other than the alcohol itself. One Dutch study even found that drinkers of white wine had lower risk. A pooled analysis concluded, “Our findings are consistent with a modest increase in risk of pancreatic cancer with consumption of 30 or more grams of alcohol per day.” Most patients with pancreatic cancer experience pain, weight loss, or jaundice. Pain is present in 80 to 85 percent of patients with locally advanced or advanced metastatic disease. The pain is usually felt in the upper abdomen as a dull ache that radiates straight through to the back. It may be intermittent and made worse by eating. Weight loss can be profound; it can be associated with anorexia, early satiety, diarrhea, or steatorrhea. Jaundice is often accompanied by pruritus and dark urine. Painful jaundice is present in approximately one-half of patients with locally unresectable disease, while painless jaundice is present in approximately one-half of patients with a potentially resectable and curable lesion. The initial presentation varies according to location of the cancer. Malignancies in the pancreatic body or tail usually present with pain and weight loss, while those in the head of the gland typically present with steatorrhea, weight loss, and jaundice. The recent onset of atypical diabetes mellitus, a history of recent but unexplained thrombophlebitis (Trousseau sign), or a previous attack of pancreatitis are sometimes noted. Courvoisier sign defines the presence of jaundice and a painlessly distended gallbladder as strongly indicative of pancreatic cancer, and may be used to distinguish pancreatic cancer from gallstones. Tiredness, irritability and difficulty eating due to pain also exist. Pancreatic cancer is usually discovered during the course of the evaluation of aforementioned symptoms. Liver function tests can show a combination of results indicative of bile duct obstruction (raised conjugated bilirubin, γ-glutamyl transpeptidase and alkaline phosphatase levels). CA19-9 (carbohydrate antigen 19.9) is a tumor marker that is frequently elevated in pancreatic cancer. However, it lacks sensitivity and specificity. When a cutoff above 37 U/mL is used, this marker has a sensitivity of 77% and specificity of 87% in discerning benign from malignant disease. CA 19-9 might be normal early in the course, and could be elevated due to benign causes of biliary obstruction. Imaging studies, such as computed tomography (CT scan) and Endoscopic ultrasound (EUS) can be used to identify the location and form of the cancer. However, percutaneous needle biopsy of the cancerous pancreatic tissue is necessary to establish a definitive diagnosis. Endoscopic ultrasound is often used to visually guide the needle biopsy procedure. In the September 2009 issue of the journal Cancer Prevention Research, scientists from the University of Texas M.D. Anderson Cancer Center identified microRNAs associated with pancreatic cancer from blood samples of pancreatic cancer patients, leading to a new and minimally invasive approach to early detection. Expression of higher levels of miR-155 circulating in blood was identified as a potential early stage biomarker, and expression of miR196a was shown to increase during disease progression. Using a panel of 4 miRNA biomarkers, miR-21, miR-210, miR-155, and miR-196a, the study achieved 64% sensitivity and 89% specificity in a sample of 28 pancreatic cancer patients and 19 healthy controls. According to the American Cancer Society, there are no established guidelines for preventing pancreatic cancer, although cigarette smoking has been reported as responsible for 20–30% of pancreatic cancers. The ACS recommends keeping a healthy weight, and increasing consumption of fruits, vegetables, and whole grains while decreasing red meat intake, although there is no consistent evidence that this will prevent or reduce pancreatic cancer specifically. In 2006 a large prospective cohort study of over 80,000 subjects failed to prove a definite association. The evidence in support of this lies mostly in small case-control studies. In September 2006, a long-term study concluded that taking Vitamin D can substantially cut the risk of pancreatic cancer (as well as other cancers) by up to 50%, but this study needs to evaluate fully the risks, costs and potential benefits of taking Vitamin D. Several studies, including one published on 1 June 2007, indicate that B vitamins such as B12, B6, and folate, can reduce the risk of pancreatic cancer when consumed in food, but not when ingested in vitamin tablet form. Treatment of pancreatic cancer depends on the stage of the cancer. The Whipple procedure is the most common surgical treatment for cancers involving the head of the pancreas. This procedure involves removing the pancreatic head and the curve of the duodenum together (pancreato-duodenectomy), making a bypass for food from stomach to jejunum (gasto-jejunostomy) and attaching a loop of jejunum to the cystic duct to drain bile (cholecysto-jejunostomy). It can only be performed if the patient is likely to survive major surgery and if the cancer is localized without invading local structures or metastasizing. It can therefore only be performed in the minority of cases. Spleen-preserving distal pancreatectomy can also be used as a method to remove a cancer running through centre of pancreas; this is invasive surgery, resulting in loss of body and tail.Cancers of the tail of the pancreas can be resected using a procedure known as a distal pancreatectomy. Recently, localized cancers of the pancreas have been resected using minimally invasive (laparoscopic) approaches. After surgery, adjuvant chemotherapy with gemcitabine has in several large randomized studies been shown to significantly increase the 5-year survival (from approximately 10 to 20%), and should be offered if the patient is fit after surgery(Oettler et al. JAMA 2007, Neoptolemos et al. NEJM 2004, Oettler et al. ASCO proc 2007) . There is a study being done currently by Washington University that is using interferon to treat the cancer, and it has boosted survival times somewhat further. Addition of radiation therapy is a hotly debated topic, with groups in the US often favoring the use of adjuvant radiation therapy, while groups in Europe do not, due to the lack of any large randomized studies to show any survival benefit of this strategy. Surgery can be performed for palliation, if the malignancy is invading or compressing the duodenum or colon. In that case, bypass surgery might overcome the obstruction and improve quality of life, but it is not intended as a cure. In patients not suitable for resection with curative intent, palliative chemotherapy may be used to improve quality of life and gain a modest survival benefit. Gemcitabine was approved by the United States Food and Drug Administration in 1998 after a clinical trial reported improvements in quality of life in patients with advanced pancreatic cancer. This marked the first FDA approval of a chemotherapy drug for a non-survival clinical trial endpoint. Gemcitabine is administered intravenously on a weekly basis. Addition of oxaliplatin (Gem/Ox) conferred benefit in small trials, but is not yet standard therapy., a recently published study ECOG 6201 failed to show superiority of GEMOX over gemcitabine alone (Poplin et al, JCO 2009, Louvet et al. JCO 2005). Fluorouracil (5FU) may also be included, however no large randomized study has shown significant survival benefit from this addition(Berlin et al. JCO 2002). One sofar unpublished trial has shown a significant benefit from adding capecitabine to gemcitabine (Cunningham et al. ASCO proc 2005), On the basis of a Canadian led Phase III Randomised Controlled trial involving 569 patients with advanced pancreatic cancer, the US FDA has licensed the use of erlotinib in combination with gemcitabine as a palliative regimen for pancreatic cancer. This trial compared the action of gemcitabine/erlotinib vs gemcitabine/placebo and demonstrated improved survival rates, improved tumor response and improved progression-free survival rates(Moore et al. JCO 2005). The survival improvement with the combination is on the order of less than four weeks, leading some cancer experts to question the incremental value of adding erlotinib to gemcitabine treatment. New trials are now investigating the effect of the above combination in the adjuvant and neoadjuvant setting. A trial of anti-angiogenesis agent bevacizumab as an addition to chemotherapy has shown no improvement in survival of patients with advanced pancreatic cancer(Kindler et al.). It may cause higher rates of high blood pressure, bleeding in the stomach and intestine, and intestinal perforations. Patients diagnosed with pancreatic cancer typically have a poor prognosis partly because the cancer usually causes no symptoms early on, leading to locally advanced or metastatic disease at time of diagnosis. Median survival from diagnosis is around 3 to 6 months; 5-year survival is less than 5%. With 37,170 cases diagnosed in the United States in 2007, and 33,700 deaths, pancreatic cancer has one of the highest fatality rates of all cancers and is the fourth highest cancer killer in the United States among both men and women. Although it accounts for only 2.5% of new cases, pancreatic cancer is responsible for 6% of cancer deaths each year. Pancreatic cancer may occasionally result in diabetes. Insulin production is hampered and it has been suggested that the cancer can also prompt the onset of diabetes and vice versa. Thus diabetes is both a risk factor for the development of pancreatic cancer and diabetes can be an early sign of the disease in the elderly. Invasive cancers that are confined within the wall of the colon (TNM stages I and II) are curable with surgery. If untreated, they spread to regional lymph nodes (stage III), where up to 73% are curable by surgery and chemotherapy. Cancer that metastasizes to distant sites (stage IV) is not curable, although chemotherapy can extend survival. Radiation is used with rectal cancer. On the cellular and molecular level, colorectal cancer starts with a mutation to the Wnt signaling pathway. When Wnt binds to a receptor on the cell, that sets in motion a chain of molecular events that ends with β-catenin moving into the nucleus and activating a gene on DNA. In colorectal cancer, genes along this chain are damaged. Usually, a gene called APC, which is a “brake” on the Wnt pathway, is damaged. Without a working APC brake, the Wnt pathway is stuck in the “on” position. Signs and symptoms The symptoms of colorectal cancer depend on the location of tumor in bowel and whether it has spread to elsewhere in the body (metastasis). Most of the symptoms may occur in other diseases as well, and hence none of the symptoms mentioned here is diagnostic of colorectal cancer. Symptoms and signs are divided into local, constitutional (affecting the whole body) and metastatic (caused by spread to other organs). Local symptoms are more likely if the tumor is located closer to the anus. There may be a change in bowel habit (new-onset constipation or diarrhea in the absence of another cause), and a feeling of incomplete defecation (tenesmus) and reduction in diameter of stool; tenesmus and change in stool shape are both characteristic of rectal cancer. Lower gastrointestinal bleeding, including the passage of bright red blood in the stool, may indicate colorectal cancer, as may the increased presence of mucus. Melena, black stool with a tarry appearance, normally occurs in upper gastrointestinal bleeding (such as from a duodenal ulcer) but is sometimes encountered in colorectal cancer when the disease is located in the beginning of the large bowel. A tumor that is large enough to fill the entire lumen of the bowel may cause bowel obstruction. This situation is characterized by constipation, abdominal pain, abdominal distension and vomiting. This occasionally leads to the obstructed and distended bowel perforating and causing peritonitis. Certain local effects of colorectal cancer occur when the disease has become more advanced. A large tumor is more likely to be noticed on feeling the abdomen, and it may be noticed by a doctor on physical examination. The disease may invade other organs, and may cause blood or air in the urine (invasion of the bladder) or vaginal discharge (invasion of the female reproductive tract). If a tumor has caused chronic occult bleeding, iron deficiency anemia may occur; this may be experienced as fatigue, palpitations and noticed as pallor (pale appearance of the skin). Colorectal cancer may also lead to weight loss, generally due to a decreased appetite. More unusual constitutational symptoms are an unexplained fever and one of several paraneoplastic syndrome. The most common paraneoplastic syndrome is thrombosis, usually deep vein thrombosis. Colorectal cancer most commonly spreads to the liver. This may go unnoticed, but large deposits in the liver may cause jaundice and abdominal pain (due to stretching of the capsule). If the tumor deposit obstructs the bile duct, the jaundice may be accompanied by other features of biliary obstruction, such as pale stools. Micrograph of a tubular adenoma (left of image), a type of colonic polyp and a precursor of colorectal cancer. Normal colorectal mucosa is seen on the right. H&E stain. The lifetime risk of developing colon cancer in the United States is about 7%. Certain factors increase a person’s risk of developing the disease. - Age. The risk of developing colorectal cancer increases with age. Most cases occur in the 60s and 70s, while cases before age 50 are uncommon unless a family history of early colon cancer is present. - Polyps of the colon, particularly adenomatous polyps, are a risk factor for colon cancer. The removal of colon polyps at the time of colonoscopy reduces the subsequent risk of colon cancer. - History of cancer. Individuals who have previously been diagnosed and treated for colon cancer are at risk for developing colon cancer in the future. Women who have had cancer of the ovary, uterus, or breast are at higher risk of developing colorectal cancer. - Family history of colon cancer, especially in a close relative before the age of 55 or multiple relatives. - Familial adenomatous polyposis (FAP) carries a near 100% risk of developing colorectal cancer by the age of 40 if untreated - Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome - Smoking. Smokers are more likely to die of colorectal cancer than non-smokers. An American Cancer Society study found that “Women who smoked were more than 40% more likely to die from colorectal cancer than women who never had smoked. Male smokers had more than a 30% increase in risk of dying from the disease compared to men who never had smoked.” - Diet. Studies show that a diet high in red meat and low in fresh fruit, vegetables, poultry and fish increases the risk of colorectal cancer. In June 2005, a study by the European Prospective Investigation into Cancer and Nutrition suggested that diets high in red and processed meat, as well as those low in fiber, are associated with an increased risk of colorectal cancer. Individuals who frequently eat fish showed a decreased risk. However, other studies have cast doubt on the claim that diets high in fiber decrease the risk of colorectal cancer; rather, low-fiber diet was associated with other risk factors, leading to confounding. The nature of the relationship between dietary fiber and risk of colorectal cancer remains controversial. - Physical inactivity. People who are physically active are at lower risk of developing colorectal cancer. - Virus. Exposure to some viruses (such as particular strains of human papilloma virus) may be associated with colorectal cancer. - Primary sclerosing cholangitis offers a risk independent to ulcerative colitis - Low levels of selenium. - Inflammatory bowel disease. About one percent of colorectal cancer patients have a history of chronic ulcerative colitis. The risk of developing colorectal cancer varies inversely with the age of onset of the colitis and directly with the extent of colonic involvement and the duration of active disease. Patients with colorectal Crohn’s disease have a more than average risk of colorectal cancer, but less than that of patients with ulcerative colitis. - Environmental factors. Industrialized countries are at a relatively increased risk compared to less developed countries that traditionally had high-fiber/low-fat diets. Studies of migrant populations have revealed a role for environmental factors, particularly dietary, in the etiology of colorectal cancers. - Exogenous hormones. The differences in the time trends in colorectal cancer in males and females could be explained by cohort effects in exposure to some gender-specific risk factor; one possibility that has been suggested is exposure to estrogens. There is, however, little evidence of an influence of endogenous hormones on the risk of colorectal cancer. In contrast, there is evidence that exogenous estrogens such as hormone replacement therapy (HRT), tamoxifen, or oral contraceptives might be associated with colorectal tumors. - Alcohol. Drinking, especially heavily, may be a risk factor. The WCRF panel report Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective finds the evidence “convincing” that alcoholic drinks increase the risk of colorectal cancer in men. The NIAAA reports that: “Epidemiologic studies have found a small but consistent dose-dependent association between alcohol consumption and colorectal cancer even when controlling for fiber and other dietary factors. Despite the large number of studies, however, causality cannot be determined from the available data.” “Heavy alcohol use may also increase the risk of colorectal cancer” (NCI). One study found that “People who drink more than 30 grams of alcohol per day (and especially those who drink more than 45 grams per day) appear to have a slightly higher risk for colorectal cancer.” Another found that “The consumption of one or more alcoholic beverages a day at baseline was associated with approximately a 70% greater risk of colon cancer.” One study found that “While there was a more than twofold increased risk of significant colorectal neoplasia in people who drink spirits and beer, people who drank wine had a lower risk. In our sample, people who drank more than eight servings of beer or spirits per week had at least a one in five chance of having significant colorectal neoplasia detected by screening colonoscopy.” Other research suggests that “to minimize your risk of developing colorectal cancer, it’s best to drink in moderation.” On its colorectal cancer page, the National Cancer Institute does not list alcohol as a risk factor: however, on another page it states, “Heavy alcohol use may also increase the risk of colorectal cancer” Drinking may be a cause of earlier onset of colorectal cancer. Colorectal cancer is a disease originating from the epithelial cells lining the colon or rectum of the gastrointestinal tract, as a result of mutations along the ‘Wnt signaling pathway. Some of the mutations are inherited, and others are acquired. The most commonly mutated gene in all colorectal cancer is the APC gene, which produces the APC protein. The APC protein is the “brake” on the β-catenin protein. Without APC, β-catinin moves into the nucleus, binds to DNA, and activates more proteins. (If APC isn’t mutated in colorectal cancer, then β-catinin itself is.) But it’s not enough for the Wnt-APC-beta-catinin signaling pathway to get stuck in the “on” position. Other mutations must occur for the cell to become cancerous. The TP53 protein, produced by the p53 gene, normally monitors cell division and kills cells if they have Wnt pathway defects. But eventually, a clone of cells gets a second mutation, in the p53 gene, and it transforms from a large adenoma into an invasive carcenoma. (Sometimes p53 isn’t mutated, but another protective protein named BAX is.) Another protein that’s supposed to kill cells when they become cancerous is TGF-β. But in at least half of colorectal cancers, TGF-β also has a deactivating mutation. (Sometimes TGF-β isn’t deactivated, but a downstream protein named SMAD is.) Some genes are oncogenes — they are overexpressed in colorectal cancer. For example, RAS, RAF, and PI3K, which normally encourage the cell to divide in response to growth factors, can become mutated with mutations that make them oversignal the cell. PTEN normally inhibits PI3K, but sometimes PTEN gets mutated. Endoscopic image of colon cancer identified in sigmoid colon on screening colonoscopy in the setting of Crohn’s disease. Colorectal cancer can take many years to develop and early detection of colorectal cancer greatly improves the chances of a cure. The National Cancer Policy Board of the Institute of Medicine estimated in 2003 that even modest efforts to implement colorectal cancer screening methods would result in a 29 percent drop in cancer deaths in 20 years. Despite this, colorectal cancer screening rates remain low. Therefore, screening for the disease is recommended in individuals who are at increased risk. There are several different tests available for this purpose. - Digital rectal exam (DRE): The doctor inserts a lubricated, gloved finger into the rectum to feel for abnormal areas. It only detects tumors large enough to be felt in the distal part of the rectum but is useful as an initial screening test. - Fecal occult blood test (FOBT): a test for blood in the stool. Two types of tests can be used for detecting occult blood in stools i.e. guaiac based (chemical test) and immunochemical. The sensitivity of immunochemical testing is superior to that of chemical testing without an unacceptable reduction in specifity. - Sigmoidoscopy: A lighted probe (sigmoidoscope) is inserted into the rectum and lower colon to check for polyps and other abnormalities. - Colonoscopy: A lighted probe called a colonoscope is inserted into the rectum and the entire colon to look for polyps and other abnormalities that may be caused by cancer. A colonoscopy has the advantage that if polyps are found during the procedure they can be immediately removed. Tissue can also be taken for biopsy. In the United States, colonoscopy or FOBT plus sigmoidoscopy are the preferred screening options Other screening methods - Double contrast barium enema (DCBE): First, an overnight preparation is taken to cleanse the colon. An enema containing barium sulfate is administered, then air is insufflated into the colon, distending it. The result is a thin layer of barium over the inner lining of the colon which is visible on X-ray films. A cancer or a precancerous polyp can be detected this way. This technique can miss the (less common) flat polyp. - Virtual colonoscopy replaces X-ray films in the double contrast barium enema (above) with a special computed tomography scan and requires special workstation software in order for the radiologist to interpret. This technique is approaching colonoscopy in sensitivity for polyps. However, any polyps found must still be removed by standard colonoscopy. - Standard computed axial tomography is an x-ray method that can be used to determine the degree of spread of cancer, but is not sensitive enough to use for screening. Some cancers are found in CAT scans performed for other reasons. - Blood tests: Measurement of the patient’s blood for elevated levels of certain proteins can give an indication of tumor load. In particular, high levels of carcinoembryonic antigen (CEA) in the blood can indicate metastasis of adenocarcinoma. These tests are frequently false positive or false negative, and are not recommended for screening, it can be useful to assess disease recurrence. - Genetic counseling and genetic testing for families who may have a hereditary form of colon cancer, such as hereditary nonpolyposis colorectal cancer (HNPCC) or familial adenomatous polyposis (FAP). - Positron emission tomography (PET) is a 3-dimensional scanning technology where a radioactive sugar is injected into the patient, the sugar collects in tissues with high metabolic activity, and an image is formed by measuring the emission of radiation from the sugar. Because cancer cells often have very high metabolic rate, this can be used to differentiate benign and malignant tumors. PET is not used for screening and does not (yet) have a place in routine workup of colorectal cancer cases. - Whole-Body PET imaging is the most accurate diagnostic test for detection of recurrent colorectal cancer, and is a cost-effective way to differentiate resectable from non-resectable disease. A PET scan is indicated whenever a major management decision depends upon accurate evaluation of tumour presence and extent. - Stool DNA testing is an emerging technology in screening for colorectal cancer. Pre-malignant adenomas and cancers shed DNA markers from their cells which are not degraded during the digestive process and remain stable in the stool. Capture, followed by PCR amplifies the DNA to detectable levels for assay. Clinical studies have shown a cancer detection sensitivity of 71%–91%. Carcinoembryonic antigen (CEA) is a protein found on virtually all colorectal tumors. CEA may be used to monitor and assess response to treatment in patients with metastatic disease. CEA can also be used to monitor recurrence in patients post-operatively. Gross appearance of a colectomy specimen containing two adenomatous polyps (the brownish oval tumors above the labels, attached to the normal beige lining by a stalk) and one invasive colorectal carcinoma (the crater-like, reddish, irregularly-shaped tumor located above the label). Gross appearance of a colectomy specimen containing one invasive colorectal carcinoma (the crater-like, reddish, irregularly-shaped tumor). Micrograph of an invasive adenocarcinoma (the most common type of colorectal cancer). The cancerous cells are seen in the center and at the bottom right of the image (blue). Near normal colon-lining cells are seen at the top right of the image. Histopathologic image of colonic carcinoid stained by hematoxylin and eosin. The pathology of the tumor is usually reported from the analysis of tissue taken from a biopsy or surgery. A pathology report will usually contain a description of cell type and grade. The most common colon cancer cell type is adenocarcinoma which accounts for 95% of cases. Other, rarer types include lymphoma and squamous cell carcinoma. Cancers on the right side (ascending colon and cecum) tend to be exophytic, that is, the tumour grows outwards from one location in the bowel wall. This very rarely causes obstruction of feces, and presents with symptoms such as anemia. Left-sided tumours tend to be circumferential, and can obstruct the bowel much like a napkin ring. Adenocarcinoma is a malignant epithelial tumor, originating from glandular epithelium of the colorectal mucosa. It invades the wall, infiltrating the muscularis mucosae, the submucosa and thence the muscularis propria. Tumor cells describe irregular tubular structures, harboring pluristratification, multiple lumens, reduced stroma (“back to back” aspect). Sometimes, tumor cells are discohesive and secrete mucus, which invades the interstitium producing large pools of mucus/colloid (optically “empty” spaces) – mucinous (colloid) adenocarcinoma, poorly differentiated. If the mucus remains inside the tumor cell, it pushes the nucleus at the periphery – “signet-ring cell.” Depending on glandular architecture, cellular pleomorphism, and mucosecretion of the predominant pattern, adenocarcinoma may present three degrees of differentiation: well, moderately, and poorly differentiated. Most colorectal cancer tumors are thought to be cyclooxygenase-2 (COX-2) positive. This enzyme is generally not found in healthy colon tissue, but is thought to fuel abnormal cell growth. Colon cancer staging is an estimate of the amount of penetration of a particular cancer. It is performed for diagnostic and research purposes, and to determine the best method of treatment. The systems for staging colorectal cancers depend on the extent of local invasion, the degree of lymph node involvement and whether there is distant metastasis. Definitive staging can only be done after surgery has been performed and pathology reports reviewed. An exception to this principle would be after a colonoscopic polypectomy of a malignant pedunculated polyp with minimal invasion. Preoperative staging of rectal cancers may be done with endoscopic ultrasound. Adjunct staging of metastasis include Abdominal Ultrasound, CT, PET Scanning, and other imaging studies. The most common staging system is the TNM (for tumors/nodes/metastases) system, from the American Joint Committee on Cancer (AJCC). The TNM system assigns a number based on three categories. “T” denotes the degree of invasion of the intestinal wall, “N” the degree of lymphatic node involvement, and “M” the degree of metastasis. The broader stage of a cancer is usually quoted as a number I, II, III, IV derived from the TNM value grouped by prognosis; a higher number indicates a more advanced cancer and likely a worse outcome. Details of this system are in the graph below: \|AJCC stage\|\|TNM stage\|\|TNM stage criteria for colorectal cancer\| \|Stage 0\|\|Tis N0 M0\|\|Tis: Tumor confined to mucosa; cancer-in-situ\| \|Stage I\|\|T1 N0 M0\|\|T1: Tumor invades submucosa\| \|Stage I\|\|T2 N0 M0\|\|Stage I T2 N0 M0 T2: Tumor invades muscularis propria\| \|Stage II-A\|\|T3 N0 M0\|\|T3: Tumor invades subserosa or beyond (without other organs involved)\| \|Stage II-B\|\|T4 N0 M0\|\|T4: Tumor invades adjacent organs or perforates the visceral peritoneum\| \|Stage III-A\|\|T1-2 N1 M0\|\|N1: Metastasis to 1 to 3 regional lymph nodes. T1 or T2.\| \|Stage III-B\|\|T3-4 N1 M0\|\|N1: Metastasis to 1 to 3 regional lymph nodes. T3 or T4.\| \|Stage III-C\|\|any T, N2 M0\|\|N2: Metastasis to 4 or more regional lymph nodes. Any T.\| \|Stage IV\|\|any T, any N, M1\|\|M1: Distant metastases present. Any T, any N.\| Micrograph of a colorectal adenocarcinoma metastasis to a lymph node. The cancerous cells are at the top center-left of the image, in glands (circular/ovoid structures) and eosinophilic (bright pink). H&E stain. Dukes classification is an older and less complicated staging system, that predates the TMN system, and was first proposed by Dr. Cuthbert Dukes in 1932; it identifies the stages as: - A – Tumour confined to the intestinal wall - B – Tumour invading through the intestinal wall - C – With lymph node(s) involvement (this is further subdivided into C1 lymph node involvement where the apical node is not involved and C2 where the apical lymph node is involved) - D – With distant metastasis A few cancer centers still use this staging system. Most colorectal cancers should be preventable, through increased surveillance, improved lifestyle, and, probably, the use of dietary chemopreventative agents. Most colorectal cancer arise from adenomatous polyps. These lesions can be detected and removed during colonoscopy. Studies show this procedure would decrease by > 80% the risk of cancer death, provided it is started by the age of 50, and repeated every 5 or 10 years. As per current guidelines under National Comprehensive Cancer Network, in average risk individuals with negative family history of colon cancer and personal history negative for adenomas or Inflammatory Bowel diseases, flexible sigmoidoscopy every 5 years with fecal occult blood testing annually or double contrast barium enema are other options acceptable for screening rather than colonoscopy every 10 years (which is currently the Gold-Standard of care). Lifestyle and nutrition The comparison of colorectal cancer incidence in various countries strongly suggests that sedentarity, overeating (i.e., high caloric intake), and perhaps a diet high in meat (red or processed) could increase the risk of colorectal cancer. In contrast, a healthy body weight, physical fitness, and good nutrition decreases cancer risk in general. Accordingly, lifestyle changes could decrease the risk of colorectal cancer as much as 60-80%. A high intake of dietary fiber (from eating fruits, vegetables, cereals, and other high fiber food products) has, until recently, been thought to reduce the risk of colorectal cancer and adenoma. In the largest study ever to examine this theory (88,757 subjects tracked over 16 years), it has been found that a fiber rich diet does not reduce the risk of colon cancer. A 2005 meta-analysis study further supports these findings. The Harvard School of Public Health states: “Health Effects of Eating Fiber: Long heralded as part of a healthy diet, fiber appears to reduce the risk of developing various conditions, including heart disease, diabetes, diverticular disease, and constipation. Despite what many people may think, however, fiber probably has little, if any effect on colon cancer risk.” More than 200 agents, including the above cited phytochemicals, and other food components like calcium or folic acid (a B vitamin), and NSAIDs like aspirin, are able to decrease carcinogenesis in pre-clinical development models: Some studies show full inhibition of carcinogen-induced tumours in the colon of rats. Other studies show strong inhibition of spontaneous intestinal polyps in mutated mice (Min mice). Chemoprevention clinical trials in human volunteers have shown smaller prevention, but few intervention studies have been completed today. The “chemoprevention database” shows the results of all published scientific studies of chemopreventive agents, in people and in animals. Aspirin should not be taken routinely to prevent colorectal cancer, even in people with a family history of the disease, because the risk of bleeding and kidney failure from high dose aspirin (300 mg or more) outweigh the possible benefits. A clinical practice guideline of the U.S. Preventive Services Task Force (USPSTF) recommended against taking aspirin (grade D recommendation). The Task Force acknowledged that aspirin may reduce the incidence of colorectal cancer, but “concluded that harms outweigh the benefits of aspirin and NSAID use for the prevention of colorectal cancer”. A subsequent meta-analysis concluded “300 mg or more of aspirin a day for about 5 years is effective in primary prevention of colorectal cancer in randomised controlled trials, with a latency of about 10 years”. However, long-term doses over 81 mg per day may increase bleeding events. The meta-analysis by the Cochrane Collaboration of randomized controlled trials published through 2002 concluded “Although the evidence from two RCTs suggests that calcium supplementation might contribute to a moderate degree to the prevention of colorectal adenomatous polyps, this does not constitute sufficient evidence to recommend the general use of calcium supplements to prevent colorectal cancer.”. Subsequently, one randomized controlled trial by the Women’s Health Initiative (WHI) reported negative results. A second randomized controlled trial reported reduction in all cancers, but had insufficient colorectal cancers for analysis A scientific review undertaken by the National Cancer Institute found that vitamin D was beneficial in preventing colorectal cancer, which showed an inverse relationship with blood levels of 80 nmol/L or higher associated with a 72% risk reduction compared with lower than 50 nmol/L. The treatment depends on the staging of the cancer. When colorectal cancer is caught at early stages (with little spread) it can be curable. However, when it is detected at later stages (when distant metastases are present) it is less likely to be curable. Surgery remains the primary treatment while chemotherapy and/or radiotherapy may be recommended depending on the individual patient’s staging and other medical factors. Because colon cancer primarily affects the elderly, it can be a challenge to determine how aggressively to treat a particular patient, especially after surgery. Clinical trials suggest that “otherwise fit” elderly patients fare well if they have adjuvant chemotherapy after surgery, so chronological age alone should not be a contraindication to aggressive management. Surgeries can be categorised into curative, palliative, bypass, fecal diversion, or open-and-close. Curative Surgical treatment can be offered if the tumor is localized. - Very early cancer that develops within a polyp can often be cured by removing the polyp (i.e., polypectomy) at the time of colonoscopy. - In colon cancer, a more advanced tumor typically requires surgical removal of the section of colon containing the tumor with sufficient margins, and radical en-bloc resection of mesentery and lymph nodes to reduce local recurrence (i.e., colectomy). If possible, the remaining parts of colon are anastomosed together to create a functioning colon. In cases when anastomosis is not possible, a stoma (artificial orifice) is created. - Curative surgery on rectal cancer includes total mesorectal excision (lower anterior resection) or abdominoperineal excision. In case of multiple metastases, palliative (non curative) resection of the primary tumor is still offered in order to reduce further morbidity caused by tumor bleeding, invasion, and its catabolic effect. Surgical removal of isolated liver metastases is, however, common and may be curative in selected patients; improved chemotherapy has increased the number of patients who are offered surgical removal of isolated liver metastases. If the tumor invaded into adjacent vital structures which makes excision technically difficult, the surgeons may prefer to bypass the tumor (ileotransverse bypass) or to do a proximal fecal diversion through a stoma. The worst case would be an open-and-close surgery, when surgeons find the tumor unresectable and the small bowel involved; any more procedures would do more harm than good to the patient. This is uncommon with the advent of laparoscopy and better radiological imaging. Most of these cases formerly subjected to “open and close” procedures are now diagnosed in advance and surgery avoided. Laparoscopic-assisted colectomy is a minimally-invasive technique that can reduce the size of the incision and may reduce post-operative pain. As with any surgical procedure, colorectal surgery may result in complications including - wound infection, Dehiscence (bursting of wound) or hernia - anastomosis breakdown, leading to abscess or fistula formation, and/or peritonitis - bleeding with or without hematoma formation - adhesions resulting in bowel obstruction. A 5-year study of patients who had surgery in 1997 found the risk of hospital readmission to be 15% after panproctocolectomy, 9% after total colectomy, and 11% after ileostomy - adjacent organ injury; most commonly to the small intestine, ureters, spleen, or bladder - Cardiorespiratory complications such as myocardial infarction, pneumonia, arrythmia, pulmonary embolism etc Chemotherapy is used to reduce the likelihood of metastasis developing, shrink tumor size, or slow tumor growth. Chemotherapy is often applied after surgery (adjuvant), before surgery (neo-adjuvant), or as the primary therapy (palliative). The treatments listed here have been shown in clinical trials to improve survival and/or reduce mortality rate and have been approved for use by the US Food and Drug Administration. In colon cancer, chemotherapy after surgery is usually only given if the cancer has spread to the lymph nodes (Stage III). At the 2008 annual meeting of the American Society of Clinical Oncology, researchers announced that colorectal cancer patients that have a mutation in the KRAS gene do not respond to certain therapies, those that inhibit the epidermal growth factor receptor (EGFR)–namely Erbitux (cetuximab) and Vectibix (panitumumab). Following recommendations by ASCO, patients should now be tested for the KRAS gene mutation before being offered these EGFR-inhibiting drugs. In July 2009, the US Food and Drug Administration (FDA) updated the labels of two anti-EGFR monoclonal antibody drugs (panitumumab (Vectibix) and cetuximab (Erbitux)) indicated for treatment of metastatic colorectal cancer to include information about KRAS mutations. However, having the normal KRAS version does not guarantee that these drugs will benefit the patient. “The trouble with the KRAS mutation is that it’s downstream of EGFR,” says Richard Goldberg, MD, director of oncology at the Lineberger Comprehensive Cancer Center at the University of North Carolina. “It doesn’t matter if you plug the socket if there’s a short downstream of the plug. The mutation turns [EGFR] into a switch that’s always on.” But this doesn’t mean that having normal, or wild-type, KRAS is a fail-safe. “It isn’t foolproof,” cautions Goldberg. “If you have wild-type KRAS, you’re more likely to respond, but it’s not a guarantee.” Tumors shrink in response to these drugs in up to 40 percent of patients with wild-type KRAS, and progression-free and overall survival is increased. The cost benefit of testing patients for the KRAS gene could potentially save about $740 million a year by not providing EGFR-inhibiting drugs to patients who would not benefit from the drugs. “With the assumption that patients with mutated Kras (35.6% of all patients) would not receive cetuximab (other studies have found Kras mutation in up to 46% of patients), theoretical drug cost savings would be $753 million; considering the cost of Kras testing, net savings would be $740 million.” - Adjuvant (after surgery) chemotherapy. One regimen involves the combination of infusional 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) - 5-fluorouracil (5-FU) or Capecitabine - Leucovorin (LV, Folinic Acid) - Chemotherapy for metastatic disease. Commonly used first line chemotherapy regimens involve the combination of infusional 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) with bevacizumab or infusional 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with bevacizumab or the same chemotherapy drug combinations with cetuximab in KRAS wild type tumors - 5-fluorouracil (5-FU) or Capecitabine - UFT or Tegafur-uracil - Leucovorin (LV, Folinic Acid) - In clinical trials for treated/untreated metastatic disease. - Gefitinib and Erlotinib Radiotherapy is not used routinely in colon cancer, as it could lead to radiation enteritis, and it is difficult to target specific portions of the colon. It is more common for radiation to be used in rectal cancer, since the rectum does not move as much as the colon and is thus easier to target. Indications include: - Colon cancer - pain relief and palliation – targeted at metastatic tumor deposits if they compress vital structures and/or cause pain - Rectal cancer - neoadjuvant – given before surgery in patients with tumors that extend outside the rectum or have spread to regional lymph nodes, in order to decrease the risk of recurrence following surgery or to allow for less invasive surgical approaches (such as a low anterior resection instead of an abdomino-perineal resection) - adjuvant – where a tumor perforates the rectum or involves regional lymph nodes (AJCC T3 or T4 tumors or Duke’s B or C tumors) - palliative – to decrease the tumor burden in order to relieve or prevent symptoms - Sometimes chemotherapy agents are used to increase the effectiveness of radiation by sensitizing tumor cells if present. Bacillus Calmette-Guérin (BCG) is being investigated as an adjuvant mixed with autologous tumor cells in immunotherapy for colorectal cancer TroVax, a cancer vaccine, produced by Oxford BioMedica , is in Phase III trials for renal cancers, and phase III trials are planned for colon cancers. Treatment of liver metastases According to the American Cancer Society statistics in 2006, over 20% of patients present with metastatic (stage IV) colorectal cancer at the time of diagnosis, and up to 25% of this group will have isolated liver metastasis that is potentially resectable. Lesions which undergo curative resection have demonstrated 5-year survival outcomes now exceeding 50%. Resectability of a liver metastasis is determined using preoperative imaging studies (CT or MRI), intraoperative ultrasound, and by direct palpation and visualization during resection. Lesions confined to the right lobe are amenable to en bloc removal with a right hepatectomy (liver resection) surgery. Smaller lesions of the central or left liver lobe may sometimes be resected in anatomic “segments”, while large lesions of left hepatic lobe are resected by a procedure called hepatic trisegmentectomy. Treatment of lesions by smaller, non-anatomic “wedge” resections is associated with higher recurrence rates. Some lesions which are not initially amenable to surgical resection may become candidates if they have significant responses to preoperative chemotherapy or immunotherapy regimens. Lesions which are not amenable to surgical resection for cure can be treated with modalities including radio-frequency ablation (RFA), cryoablation, and chemoembolization. Patients with colon cancer and metastatic disease to the liver may be treated in either a single surgery or in staged surgeries (with the colon tumor traditionally removed first) depending upon the fitness of the patient for prolonged surgery, the difficulty expected with the procedure with either the colon or liver resection, and the comfort of the surgery performing potentially complex hepatic surgery. A study published in 2009 found that Aspirin reduces risk of colorectal neoplasia in randomized trials and inhibits tumor growth and metastases in animal models. The influence of aspirin on survival after diagnosis of colorectal cancer is unknown. Several reports including a prospective cohort of 1,279 people diagnosed with stages I-III (non-metastatic) colorectal cancer have suggested a significant improvement in cancer-specific survival in a subset of patients using aspirin. Cancer diagnosis very often results in an enormous change in the patient’s psychological wellbeing. Various support resources are available from hospitals and other agencies which provide counseling, social service support, cancer support groups, and other services. These services help to mitigate some of the difficulties of integrating a patient’s medical complications into other parts of their life. Survival is directly related to detection and the type of cancer involved. Survival rates for early stage detection is about 5 times that of late stage cancers. CEA level is also directly related to the prognosis of disease, since its level correlates with the bulk of tumor tissue. Micrograph of a colorectal villous adenoma. These lesions are considered pre-cancerous. H&E stain. The aims of follow-up are to diagnose in the earliest possible stage any metastasis or tumors that develop later but did not originate from the original cancer (metachronous lesions). The U.S. National Comprehensive Cancer Network and American Society of Clinical Oncology provide guidelines for the follow-up of colon cancer. A medical history and physical examination are recommended every 3 to 6 months for 2 years, then every 6 months for 5 years. Carcinoembryonic antigen blood level measurements follow the same timing, but are only advised for patients with T2 or greater lesions who are candidates for intervention. A CT-scan of the chest, abdomen and pelvis can be considered annually for the first 3 years for patients who are at high risk of recurrence (for example, patients who had poorly differentiated tumors or venous or lymphatic invasion) and are candidates for curative surgery (with the aim to cure). A colonoscopy can be done after 1 year, except if it could not be done during the initial staging because of an obstructing mass, in which case it should be performed after 3 to 6 months. If a villous polyp, polyp >1 centimeter or high grade dysplasia is found, it can be repeated after 3 years, then every 5 years. For other abnormalities, the colonoscopy can be repeated after 1 year. Routine PET or ultrasound scanning, chest X-rays, complete blood count or liver function tests are not recommended. These guidelines are based on recent meta-analyses showing that intensive surveillance and close follow-up can reduce the 5-year mortality rate from 37% to 30%. The American Cancer Society estimates that in 2009 about 5,290 new cases of anal cancer will be diagnosed in the United States (about 3,000 in women and 2,000 in men). It is typically found in adults, average age early 60s. In the United States, an estimated 710 people died of anal cancer in 2009. Symptoms of anal cancer include bloating and change in bowel habits, a lump near the anus, rectal bleeding, itching or discharge. Women may experience lower back pain due to pressure the tumor exerts on the vagina, and vaginal dryness. - Human papillomavirus examination of squamous cell carcinoma tumor tissues from patients in Denmark and Sweden showed a high proportion of anal cancers to be positive for the types of HPV that are also associated with high risk of cervical cancer (90% of the tumors from women, 100% of the tumors from homosexual men, and 58% of tumors from heterosexual men). In another study done, high-risk types of HPV, notably HPV-16, were detected in 84 percent of anal cancer specimens examined. - Sexual activity: Having multiple sex partners or having anal sex, due to the increased risk of exposure to the HPV virus. Homosexual and bisexual men are 17 times more likely to develop anal cancer than heterosexual men. - Smoking: Current smokers are several times more likely to develop anal cancer compared with nonsmokers. - Immunosuppression, which is often associated with HIV infection. - Benign anal lesions (inflammatory bowel disease (IBD), hemorrhoids, fistulae or cicatrices). Inflammation resulting from benign anal lesions, such as hemorrhoids and anal fistulas, has been considered to cause a predisposition to anal cancer. Since many, if not most, anal cancers derive from human papillomavirus infections, and since the HPV vaccine prevents infection by some strains of the virus and has been shown to reduce the incidence of potentially precancerous lesions, scientists surmise that HPV vaccination may reduce the incidence of anal cancer. - Anal Pap smears similar to those used in cervical cancer screening have been studied for early detection of anal cancer in high-risk individuals. Anal cancer is most effectively treated with surgery, and in early stage disease (i.e., localised cancer of the anus without metastasis to the inguinal lymph nodes), surgery is often curative. The difficulty with surgery has been the necessity of removing the anal sphincter, with concomitant fecal incontinence. For this reason, many patients with anal cancer have required permanent colostomies. In more recent years, physicians have employed a combination strategy including chemotherapy and radiation treatments to reduce the necessity of debilitating surgery. This “combined modality” approach has led to the increased preservation of an intact anal sphincter, and therefore improved quality of life after definitive treatment. Survival and cure rates are excellent, and many patients are left with a functional sphincter. Some patients have fecal incontinence after combined chemotherapy and radiation. Biopsies to document disease regression after chemotherapy and radiation were commonly advised, but are not as frequent any longer. Current chemotherapy active in anal cancer includes cisplatin and 5-FU. Mitomycin has also been used, but is associated with increased toxicity. Metastatic or recurrent disease Up to 10% of patients treated for anal cancer will develop distant metastatic disease. Metastatic or recurrent anal cancer is difficult to treat, and usually requires chemotherapy. Radiation is also employed to palliate specific locations of disease that may be causing symptoms. Chemotherapy commonly used is similar to other squamous cell epithelial neoplasms, such as platinum analogues, anthracyclines such as doxorubicin, and antimetabolites such as 5-FU and capecitabine. J.D. Hainsworth developed a protocol that includes Taxol and Carboplatinum along with 5-FU.	2	40	0	1	1	0.697162	2	24,272
The importance of ICD-10 codes One of the types of codes that appear on healthcare provider accounts is known as ICD-10 codes. These codes are used to inform medical schemes about what conditions their members were treated for so that claims can be settled correctly. ICD-10 stands for International Classification of Diseases and Related Health Problems (10th revision). It is a coding system developed by the World Health Organisation (WHO), that translates the written description of medical and health information into standard codes, e.g. J03.9 is an ICD-10 code for acute tonsillitis (unspecified) and G40.9 denotes epilepsy (unspecified). When you join a medical scheme, you choose and pay for a particular benefit option. This benefit option contains a basket of services that often has limits on the health services that will be paid for. Because ICD-10 codes provide accurate information on the condition you have been diagnosed with, these codes help the medical scheme to determine what benefits you are entitled to and how these benefits could be paid. This becomes very important if you have a PMB condition, as these can only be identified by the correct ICD-10 codes. Therefore, if the incorrect ICD-10 codes are provided, your PMB-related services might be paid from the wrong benefit (such as from your medical savings account), or it might not be paid at all if your day-to-day or hospital benefits limits have been exhausted. ICD-10 codes must also be provided on medicine prescriptions and referral notes to other healthcare providers (e.g. pathologists and radiologists) who are not all able to make a diagnosis. Therefore, they require the diagnosis information from your referring doctor so that their claim to your medical scheme can also be paid out of the correct pool of money. Important note: Medical schemes are obliged by law to treat information about members' conditions with the utmost confidentiality. They are not allowed to disclose even ICD-10 codes to any other party, including employers or family members. Responsibilities regarding PMB's Medical scheme beneficiaries PMBs are very good news for medical scheme beneficiaries and give them considerable rights as far as healthcare is concerned. However, as a consumer you also have certain responsibilities to ensure that PMBs work as well for you as they should. - First and foremost, educate yourself about your medical scheme's rules, the listed medication and treatments (formularies) for your specific condition, as well as who the Designated Service Providers (DSPs) are. - Obtain as much information as possible about your condition and the medication and treatments for it. If there is a generic drug available, do your own research to find out whether there are any differences between it and the branded drug. - Don't bypass the system: if you must use a GP to refer you to a specialist, then do so. Make use of your medical scheme's DSPs as far as possible. Stick with your scheme's listed drug for your medication unless it is proven to be ineffective. - Be a good consumer: ask questions and follow the complaints process if you are not treated fairly. - Make sure your doctor submits a complete account to the medical scheme. It is especially important that the correct ICD-10 code is reflected. - Follow up and check that your account is submitted within four months and paid within 30 days after the claim was received (accounts older than four months are not paid by medical schemes). Among other objectives, PMBs want to achieve appropriate healthcare, resulting in lower costs associated with complications and hospitalisation. When beneficiaries are properly taken care of and their illnesses managed, the need for expensive hospitalisation decreases. Medical schemes have a critical role to play in making PMBs work. - Schemes have to educate their beneficiaries about PMBs and the benefits that are included in them. - Schemes must inform their beneficiaries of their DSPs and keep them updated should any changes occur. - Schemes should empower their beneficiaries with information on matters such as the intricacies of rules and the formularies for specific conditions. - Medical schemes have to guarantee and ensure reasonable access and availability of DSPs. - The public sector cannot be designated as a DSP without the medical scheme ensuring that the necessary service will be available. Doctors do not usually have a direct contractual relationship with medical schemes. They merely submit their accounts and if the medical scheme does not pay, for whatever reason, the doctor turns to the beneficiary for the amount due. This does not mean that PMBs are not important to healthcare providers nor that they don't have a role to play in its successful functioning. - Doctors should familiarise themselves with ICD-10 codes and how they correspond with PMB codes. If you use the correct ICD-10 code your account will definitely be paid as PMBs enjoy guaranteed medical aid cover. - Consider on which option your patients are and what can realistically be covered before recommending a drug or treatment. - Alert patients to the fact that their condition is a PMB and encourage them to engage their medical scheme on the matter. - Keep proper clinical records of patients so that when a formulary drug or protocol is not effective, or causes adverse side-effects, you can justify your alternative recommendation. - Do not abuse PMBs. The result will be an unsustainable private healthcare system with unaffordable contribution increases. Abuse could compel government to consider alternative payment options in the private healthcare sector. - Allow your practice to be listed as a DSP. - The "payment in full" concept is there to ensure accessibility of healthcare services for medical scheme beneficiaries if the DSP is not available; it is not a reimbursement model. When do co-payments apply to PMBs? Co-payments can only be levied when members voluntarily choose not to go to a DSP for a specific service, and/or when beneficiaries voluntarily decide not to use protocol or formulary medication or treatments. Co-payments have to be specified in the medical scheme rules and may never be 100% of the cost of the service or medication. Schemes are also not allowed to recover co-payments from beneficiaries' savings accounts. Medical scheme beneficiaries Is my medical scheme obliged by law to provide cover for certain medical conditions? Yes, these are known as Prescribed Minimum Benefits (PMBs). They were introduced into the Medical Schemes Act to ensure that beneficiaries of medical schemes would not run out of benefits for certain conditions and find themselves forced to go to State hospitals for treatment. These PMBs cover a wide range of ±271 conditions, such as meningitis, various cancers, menopausal management, cardiac treatment and many others, including medical emergencies. However, take note that certain limitations could apply, such as the use of a Designated Service Provider and specified treatment standards. PMB diagnosis, treatment and care are not limited to hospitals. Treatment can be received wherever it is most appropriate, including a clinic, outpatient setting or even at home. Always check your benefits with your medical scheme and make sure you have the scheme's rules at your disposal. Is it true that schemes now also have to provide chronic medication? Yes, the list of PMBs includes 26 common chronic diseases in the Chronic Disease List (CDL) and other chronic conditions within the ±271 Diagnosis Treatment Pair (DTP) section. Medical schemes have to provide cover for the diagnosis, treatment and care of these diseases. However, you should remember that a medical scheme does not have to pay for diagnostic tests that establish that you are not suffering from a PMB condition. The treatment algorithms (guidelines for appropriate treatment) for each of the CDL chronic conditions have been published in the Government Gazette while the chronic diseases in the DTP section are guided by the public sector protocols. This assures you of good quality treatment and reassures your medical scheme that it will not have to pay for unnecessary treatment. Your doctor should know and understand most of the guidelines so that he or she can help you get the treatment you need for any of these conditions without incurring costs that your scheme does not cover. Why are some chronic illnesses covered and some not? The diseases that have been chosen are the most common, they are life-threatening, and are those for which cost-effective treatment would sustain and improve the quality of the member's life. Does my scheme need to do anything to ensure that the Designated Service Provider can treat me? The Council for Medical Schemes has been advising medical schemes to enter into contracts with any DSP they choose, especially State hospitals, to ensure that these providers can supply the necessary services. Many State hospitals have set up separate wards to serve beneficiaries whose treatment and hospital stay is paid for by their medical scheme and to whom the hospital can then afford to provide better service. Other schemes have made arrangements with private hospital and certain retail pharmacies to treat their beneficiaries. Can I be refused cover for the chronic conditions if I do not get authorisation or have certain tests? Yes, medical schemes can make a benefit conditional on you obtaining pre-authorisation or joining a benefit management programme. These programmes are aimed at educating members about the nature of their disease and equipping them to manage it in a way that keeps them as healthy as possible. For example, many schemes offer treatment through groups that manage diseases such as diabetes, and are equipped to give the medication and monitor that disease. Can my scheme insist that it will only fund treatment that follows the appropriate protocol? Yes. The minimum medicines for treatment of all PMB conditions have been published in the Government Gazette, and are known as treatment algorithms (benchmarks for treatment). Your scheme may decide for which medicines it will pay for each chronic condition, but the treatment may not be below the standards published in the treatment protocols. If your scheme's cover conforms to that standard and you and your doctor decide that you should rather use different medication, then you may have to pay a co-payment towards the cost of that medicine. Your medical scheme must, however, pay for the treatment if your doctor can prove that the standard medication is ineffective or detrimental to your condition. Your medical scheme may develop protocols to manage the use of benefits. Such protocols would specify, for example, types of tests, investigations and number of consultations. Members who might need more frequent or extra services than provided for in the protocols, can appeal to their scheme for these to be covered. The scheme's appeal process might include a motivation from the treating doctor that explains the clinical reasons for the additional services Can my scheme refuse to cover my medication if I need, or want, a brand other than that which the scheme says it will pay for? Yes, the medical scheme may refuse to cover a part of the expenses. Your scheme may draw up what is known as a formulary – a list of safe and effective medicines that can be prescribed to treat certain conditions. The scheme may state in its rules that it will only cover your medication in full if your doctor prescribes a drug on that formulary. Generally speaking, schemes expect their members to stick to the formulary medication. Often the medicines on the list will be generics – copies of the original brandname drug – that are less expensive but equally effective. If you want to use a brandname medicine that is not on the list, your medical scheme may foot only part of the bill and you will have to pay either the difference between the price of the medication you use and the one on the formulary, or a percentage co-payment as registered in the scheme rules. If you suffer from specific side-effects from drugs on the formulary, or if substituting a drug on the formulary with one you are currently taking affects your health detrimentally, you can put your case to your medical scheme and ask the scheme to pay for your medicine. You can also appeal to the scheme if the formulary drug is ineffective and does not have the desired effect. If your treating doctor can provide the necessary proof and the scheme agrees that you suffer from side-effects, or that the drug is ineffective, then the scheme must give you an alternative and pay for it in full. Can my scheme make me pay for a PMB from my savings account? No, the regulations state that schemes cannot use your medical savings account to pay for PMBs. Can my scheme make me pay a co-payment or levy on a PMB? No, your scheme cannot charge you a co-payment or levy on a PMB if you follow the scheme formulary and protocol. However, if your scheme appoints a Designated Service Provider (DSP) and you voluntarily use a different provider, your scheme may charge you the difference between the actual cost and what it would have paid if you had used the DSP or the percentage co-payment as registered in the scheme rules. Can schemes still set a chronic medicine limit? Yes, your scheme can set a limit for your chronic medicine benefit. Any chronic medication you claim for will then reduce that limit, regardless of whether or not it is one of the PMB chronic conditions. However, if you exhaust your chronic medicine limit, your scheme will have to continue paying for any chronic medication you obtain from its DSP for a PMB condition. Can medical schemes prescribe protocols and formularies? Schemes can most certainly prescribe treatment protocols in terms of PMBs to improve their risk management. However, should medical schemes make use of formularies, these must be developed on the basis of evidence-based medicine, taking cost-effectiveness and affordability into account while also being on par with the gazetted algorithms for chronic diseases and the public sector protocols for the Diagnosis Treatment Pairs. Is there a process to follow when the formulary is not effective for a specific patient? An appeals process is in place for a medical scheme member to request his or her scheme to carry the costs for treatment outside the scheme's formulary. It is very important that complete medical records are submitted in support of the request. As the treating doctor, it is your responsibility to record the patient's reaction to the formulary treatment, including all efforts that were made to determine correct dosages and/or other possible contributing factors. If the PMB codes do not always correspond with the ICD-10 codes, what do I do to ensure a correct account? The Council for Medical Schemes has compiled a guideline on how to reconcile the two sets of codes. However, whenever there are differences between the ICD-10 codes and PMB codes, the latter takes precedence. This guideline is available on the CMS website www.medicalschemes.com under the Regulatory Info menu as "Prescribed minimum benefit ICD-10 coding".	4	2	0	0	2	0.860412	2	3,059
Kidney Transplant Dx. Coding By: Gouri Pathare MBBS, CPC Kidney transplantation is a treatment option for most patients with End Stage Renal Disease (ESRD). The procedure may be deceased-donor (cadaveric) or living-donor transplantation. Living-donor renal transplants may be genetically related (living-related) or non-related (living-unrelated) transplants. Diabetes mellitus, hypertension, cystic kidney disease, urologic conditions, and external causes such as trauma and toxins, all may cause kidney failure. When kidneys cease to filter wastes and extra fluid from the bloodstream, renal failure is considered to be permanent and consideration must be given to hemodialysis and/or kidney transplantation. A common complication of kidney transplant is rejection of the transplanted organ. The body’s immune system, or defense mechanism, recognizes that something foreign is in the body and tries to destroy it When post-organ transplant patients present for care, the coder should review medical record documentation to determine whether the patient has any complications of the transplanted organ. Consider 996.81 Complications of transplanted kidney versus V42.7. Kidney replaced by transplant. Assign V42.7 only if there is no complication of the kidney transplant. Code V42.7 is never used with 996.81. V codes are status codes used to classify certain conditions that may have an impact on the patient’s health status. It is appropriate to assign 996.81 when the kidney transplant is being rejected by the patient, or if there are any other complications or diseases that affect the function of the transplant. You must assign two codes to completely describe the impact on the transplanted kidney. For example, if the patient presents with acute kidney injury and has a history of kidney transplant, the function of the patient’s kidney is affected. Hence, the coder would assign 996.81 and 584.9 Acute kidney failure, unspecified. Physicians may document in the medical record that a kidney transplant recipient also has chronic kidney disease (CKD). The coder should not assume that this kidney disease is a complication of the transplant, unless the physician documents the link. A kidney transplant may not fully restore function to the kidney, and some residual kidney disease could be present. Without the link provided by the physician, coders should report V42.7 with an additional code for the CKD. Physicians may also document in the medical record of the post-kidney transplant recipient ESRD. Coders should pay special attention to this diagnosis because the physician may be indicating a past history of ESRD. The kidney transplantation was initially performed to improve the patient’s kidney function, and it would be unlikely that patient would still have ESRD. Physician clarification is required, as the addition of 585.6 End stage renal disease is a major complication/comorbidity, and can significantly affect the MS-DRG assignment. ICD 10 Coding for Kidney Transplant Kidney transplant status Z94.0 Patients who have undergone kidney transplant may still have some form of chronic kidney disease because the kidney transplant may not fully restore kidney function. Therefore, the presence of CKD alone does not constitute transplant complication. Assign the appropriate N18 code for the patient’s CKD and code Z94.0, kidney transplant status. Complications of kidney transplant T86.1 Unspecified complications of kidney transplant T86.10 Kidney transplant rejection T86.11 Kidney transplant failure T86.12 Kidney transplant infection T86.13 Use additional code to specify infection. Other complications of Kidney transplant T86.19. Gouri Pathare MBBS, CPC, is a practicing medical professional with nearly 30 years of experience as an independent private medical practitioner in Mumbai, India, and has worked as a clinical specialist training coders for Episource India Pvt, Ltd., a United States-based KPO company. She was lecturer in Anatomy in Government Medical College.	4	2	0	0	9	0.932209	9	860
What is ICD code? The full form of ICD is the International Classification of Diseases. WHO created International Statistical Classification of Diseases and Related Health Problems (ICD), a medical classification list of codes to help develop a universal code for doctors and insurance companies worldwide. It contains codes for diseases and causes of injuries and deaths. The universal codes help doctors, and insurance companies keep a record of patients. What is the latest version of ICD? The latest version of ICD is the ICS-11 which WHO released a preview in 2019 with 55,000 codes for causes of death, diseases, and injuries. The new revision was designed to simplify the coding structure, so healthcare providers can more easily record medical conditions. This edition is also the first to be completely electronic, so it can integrate with electronic data sources and is free to download online for personal use. The ICD-11 will come into effect on 1 January 2022. The new revision will also include new chapters on sexual health and traditional medicine. Get a dose of health tips delivered for free ICD-10 code for Erectile Dysfunction N52.9 is the code for Erectile Dysfunction in 1CD-10. The ICD-10-CM code N52.9 might also be used to specify conditions or terms like arteriopathy impotence, cannot get an erection, cannot sustain an erection, complaining of erectile dysfunction, delayed erection, endocrine impotence, etc The code N52 is applicable to adult patients aged 15 through 124 years inclusive. It is clinically and virtually impossible to use this code on a patient outside the stated age range. In N52 there are different codes specifying different Erectile Dysfunctions based on their causes \|N52.0\|\|Vasculogenic erectile dysfunction\| \|N52.01\|\|Erectile dysfunction due to arterial insufficiency\| \|N52.02\|\|Corporo-venous occlusive erectile dysfunction\| \|N52.03\|\|Combined arterial insufficiency and corporo-venous occlusive erectile dysfunction\| \|N52.1\|\|Erectile dysfunction due to diseases classified elsewhere\| \|N52.2\|\|Drug-induced erectile dysfunction\| \|N52.3\|\|Postprocedural erectile dysfunction\| \|N52.31\|\|Erectile dysfunction following radical prostatectomy\| \|N52.32\|\|Erectile dysfunction following radical cystectomy\| \|N52.33\|\|Erectile dysfunction following urethral surgery\| \|N52.34\|\|Erectile dysfunction following simple prostatectomy\| \|N52.35\|\|Erectile dysfunction following radiation therapy\| \|N52.37\|\|Erectile dysfunction following prostate ablative therapy\| \|N52.8\|\|Other male erectile dysfunction\| \|N52.9\|\|Male erectile dysfunction, unspecified\| - Erectile dysfunction - Erectile dysfunction, organic - Erectile dysfunction, vasculopathic - The impotence of organic origin - Male erectile disorder - Vasculopathic erectile dysfunction - A disorder characterized by the persistent or recurrent inability to achieve or to maintain an erection during sexual activity. - An inability to have an erection of the penis adequate for sexual intercourse. - Erectile dysfunction (ed) is when a man has trouble getting or keeping an erection. Ed becomes more common as you get older. But male sexual dysfunction is not a natural part of aging. Some people have trouble speaking with their doctors about sex. But if you have ed, you should tell your doctor. Ed can be a sign of health problems. It may mean your blood vessels are clogged. It may mean you have nerve damage from diabetes. If you don’t see your doctor, these problems will go untreated. Your doctor can offer several new treatments for ed. For many men, the answer is as simple as taking a pill. Getting more exercise, losing weight, or stopping smoking may also help. - Inability to perform sexual intercourse. - The inability in the male to have a penile erection due to psychological or organ dysfunction. ICD-11 code and description for Erectile Dysfunction HA01.1 is the code for erectile dysfunction in ICD-11 Male erectile dysfunction is characterized by the inability or marked reduction in the ability in men to attain or sustain a penile erection of sufficient duration or rigidity to allow for sexual activity. The pattern of erectile difficulty occurs despite the desire for sexual activity and adequate sexual stimulation, has occurred episodically or persistently over a period of at least several months, and is associated with clinically significant distress. \|1\|\|HA40\|\|Aetiological considerations in sexual dysfunctions and sexual pain disorders\| \|2\|\|HA40.1\|\|Associated with psychological or behavioral factors, including mental disorders\| \|3\|\|HA40.2\|\|Associated with the use of psychoactive substance or medication\| \|4\|\|HA40.3\|\|Associated with lack of knowledge or experience\| \|5\|\|HA40.4\|\|Associated with relationship factors\| Associated with cultural factors Other specified aetiological considerations in sexual dysfunctions and sexual pain disorders Risk factors for Erectile dysfunction mentioned in ICD-11 There are many risk factors for Erectile dysfunction and those include - Heart disease ICD-10: I25.10 - Atherosclerosis ICD-10: I70.90 - High cholesterol ICD-10: E78.5 - High blood pressure ICD-10: R03.0 - Diabetes ICD-10: E11.9 - Obesity ICD-10: E66	4	2	0	0	7	0.861072	7	1,206
\|Pronunciation\|\|/ - , - /,\| Anesthesia or anaesthesia (from Greek "without sensation") is a state of controlled, temporary loss of sensation or awareness that is induced for medical purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), amnesia (loss of memory), and unconsciousness. A patient under the effects of anesthetic drugs is referred to as being anesthetized. Anesthesia enables the painless performance of medical procedures that would otherwise cause severe or intolerable pain to an unanesthetized patient, 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 patient remains fully conscious), or in combination with general anesthesia or sedation. Drugs can be targeted at peripheral nerves to anesthetize an isolated part of the body only, such as numbing a tooth for dental work or using a nerve block to inhibit sensation in an entire limb. Alternatively, 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 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 patient, the complexity (and stress) of the procedure itself, and the anaesthetic technique. Of these factors, the health of the patient 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 patient. 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 Tied closely to the concepts of amnesia and hypnosis is the concept of consciousness. Consciousness is the higher order process that synthesizes information. For instance, the "sun" conjures up feelings, memories and a sensation of warmth rather than a description of a round, orange warm ball seen in the sky for part of a 24‑hour cycle. Likewise, a person can have dreams (a state of subjective consciousness) 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 or 2 cases per 1000 have some consciousness termed "awareness during general anesthesia".:253 Anesthesia is unique in that it is not a direct means of treatment; rather, it allows others 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 a person'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, medical doctors and dentists who practice it are termed anesthesiologists. Ancillary healthcare workers involved in anesthesia provision have varying titles and roles depending on the jurisdiction, and include nurse anesthetists, anesthetic nurses, 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 patients' 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. 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.:1003–1009 Aside from the generalities of the patients 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 person undergoing anesthetic 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 or 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 person under anesthesia and a quicker recovery. A combination of drugs was later shown to result in lower odds of dying in the first 7 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 person 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::926–931 - 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 three to 18 months following thoracotomy and three to 1 months following caesarean. Low quality evidence was found three 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.:1639–1641 Spinal, epidural and caudal anesthesia 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 management 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 patient.: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 complications 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 a person'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 patient, 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.:969–986 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 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.:2805–2816 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. 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. 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. Early medieval Arabic writings mention anaesthesia by inhalation. Inhalational anesthetics were first used by Arabic physicians, such as Abulcasis, Avicenna and Ibn Zuhr in the 11th century. They used a sponge soaked with narcotic drugs and placed it on a patient's face. These Arabic physicians were the first to use an anaesthetic sponge. Arab/Persian physicians also introduced the use of preoperative anaesthetic compounds around the 9th century. 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 patient 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 patient 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 (1803–73) in Germany, chloroform was named and chemically characterized in 1834 by Jean-Baptiste Dumas (1800–84). 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. Its use spread quickly and gained royal approval in 1853 when John Snow gave it to Queen Victoria during the birth of Prince Leopold. During the 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. 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 culture 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). - "anaesthesia". Oxford English Dictionary (Online ed.). Oxford University Press. (Subscription or participating institution membership required.) - Miller RD (2010). 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Individual differences \| Methods \| Statistics \| Clinical \| Educational \| Industrial \| Professional items \| World psychology \| Fetal Alcohol Spectrum Disorders (FASD) describes a continuum of permanent birth defects caused by maternal consumption of alcohol during pregnancy, which includes, but is not limited to Fetal alcohol syndrome (FAS). Over time, as it became apparent through research and clinical experience that a range of effects (including physical, behavioral, and cognitive) could arise from prenatal alcohol exposure, the term Fetal Alcohol Spectrum Disorders, or FASD, was developed to include Fetal alcohol syndrome (FAS) as well as other conditions resulting from prenatal alcohol exposure. There are a number of other subtypes with evolving nomenclature and definitions based on partial expressions of FAS, including Partial Fetal Alcohol Syndrome (PFAS), Alcohol-Related Neurodevelopmental Disorder (ARND), Alcohol-Related Birth Defects (ARBD), and Fetal Alcohol Effect (FAE). The term Fetal Alcohol Spectrum Disorders is not in itself a clinical diagnosis but describes the full range of disabilities that may result from prenatal alcohol exposure. Currently, Fetal Alcohol Syndrome (FAS) is the only expression of prenatal alcohol exposure that is defined by the International Statistical Classification of Diseases and Related Health Problems and assigned ICD-9 and ICD-10 diagnoses. Since the original syndrome of Fetal Alcohol Syndrome (FAS) was reported in 1973, four FASD diagnostic systems that diagnose FAS and other FASD conditions have been developed in North America: - The Institute of Medicine's guidelines for FAS, the first system to standardize diagnoses of individuals with prenatal alcohol exposure, - The University of Washington's "The 4-Digit Diagnostic Code," which ranks the four key features of FASD on a Likert scale of one to four and yields 256 descriptive codes that can be categorized into 22 distinct clinical categories, ranging from FAS to no findings, - The Centers for Disease Control's "Fetal Alcohol Syndrome: Guidelines for Referral and Diagnosis," which established general consensus on the diagnosis FAS in the U.S. but deferred addressing other FASD conditions, and - Canadian guidelines for FASD diagnoses, which established criteria for diagnosing FASD in Canada and harmonized most differences between the IOM and University of Washington's systems. Each diagnostic system requires that a complete FASD evaluation include assessment of the four key features of FASD, described below. A positive finding on all four features is required for a diagnosis of FAS, the first diagnosable condition of FASD that was discovered. However, prenatal alcohol exposure and central nervous system damage are the critical elements of the spectrum of FASD, and a positive finding in these two features is sufficient for an FASD diagnosis that is not "full-blown FAS." Diagnoses are described in a following section. Key features of FASD Each of the key features of FASD can vary widely within one individual exposed to prenatal alcohol. While consensus exists for the definition and diagnosis of FAS across diagnostic systems, minor variations among the systems lead to differences in definitions and diagnostic cut-off criteria for other disgnoses across the FASD continuum. (The central nervous system (CNS) damage criteria particularly lack clear consensus.) A working knowledge of the key features is helpful in understanding FASD diagnoses and conditions, and each are reviewed with attention to similarities and differences across the four diagnostic systems. In terms of FASD, growth deficiency is defined as significantly below average height, weight or both due to prenatal alcohol exposure, and can be assessed at any point in the lifespan. Growth measurements must be adjusted for parental height, gestational age (for a premature infant), and other postnatal insults (e.g., poor nutrition), although birth height and weight are the preferred measurements. Deficiencies are documented when height or weight falls at or below the 10th percentile of standardized growth charts appropriate to the patient's population. Criteria for FASD are least specific in the IOM diagnostic system ("low birth weight..., decelerating weight not due to nutrition..., [or] disproportional low weight to height" p.4 of executive summary), while the CDC and Canadian guidelines use the 10th percentile as a cut-off to determine growth deficiency. The "4-Digit Diagnostic Code" allows for mid-range gradations in growth deficiency (between the 3rd and 10th percentiles) and severe growth deficiency at or below the 3rd percentile. Growth deficiency (at severe, moderate, or mild levels) contributes to diagnoses of FAS and PFAS, but not ARND or static encephalopathy. Growth deficiency is ranked as follows by the "4-Digit Diagnostic Code:" - Severe - Height and weight at or below the 3rd percentile. - Moderate - Either height or weight at or below the 3rd percentile, but not both. - Mild - Either height or weight or both between the 3rd and 10th percentiles. - None - Height and weight both above the 10th percentile. In the initial studies that discovered FAS, growth deficiency was a requirement for inclusion in the studies; thus, all the original patients with FAS had growth deficiency as an artifact of sampling characteristics used to establish criteria for the syndrome.[How to reference and link to summary or text] That is, growth deficiency is a key feature of FASD because growth deficiency was a criterion for inclusion in the original study that determined the definition of FAS. This reinforces assertions that growth deficiency and FAS facial features are less critical for understanding the disability of FASD than the neurobehavioral sequelae to the brain damage. FAS facial features Refinements in diagnostic criteria since 1975 have yielded three distinctive and diagnostically significant facial features known to result from prenatal alcohol exposure and distinguishes FAS from other disorders with partially overlapping characteristics. The three FAS facial features are: - A smooth philtrum - The divot or groove between the nose and upper lip flattens with increased prenatal alcohol exposure. - Thin vermilion - The upper lip thins with increased prenatal alcohol exposure. - Small palpebral fissures - Eye width shortens with increased prenatal alcohol exposure. Measurement of FAS facial features uses criteria developed by the University of Washington. The lip and philtrum are measured by a trained physician with the Lip-Philtrum Guide, a 5-point Likert Scale with representative photographs of lip and philtrum combinations ranging from normal (ranked 1) to severe (ranked 5). Palpebral fissure length (PFL) is measured in millimeters with either calipers or a clear ruler and then compared to a PFL growth chart, also developed by the University of Washington. All four diagnostic systems have agreed upon this method for determining FAS facial feature severity rankings. Ranking FAS facial features is complicated because the three separate facial features can be affected independently by prenatal alcohol. Central nervous system damage Central nervous system (CNS) damage is the primary key feature of any FASD diagnosis. Prenatal alcohol exposure, a teratogen, can damage the brain across a continuum of gross to subtle impairments, depending on the amount, timing, and frequency of the exposure as well as genetic predispositions of the fetus and mother. While functional abnormalities are the behavioral and cognitive expressions of the FASD disability, CNS damage can be assessed in three areas: structural, neurological, and functional impairments. All four diagnostic systems allow for assessment of CNS damage in these areas, but criteria vary. The IOM system requires structural or neurological impairment for a diagnosis of FAS, but also allows a "complex pattern" of functional anomalies for diagnosing PFAS and ARND. The "4-Digit Diagnostic Code" and CDC guidelines allow for a positive CNS finding in any of the three areas for any FASD diagnosis, but functional anomalies must measure at two standard deviations or worse in three or more functional domains for a diagnoses of FAS, PFAS, and ARND. The "4-Digit Diagnostic Code" also allows for an FASD diagnosis when only two functional domains are measured at two standard deviations or worse. The "4-Digit Diagnostic Code" further elaborates the degree of CNS damage according to four ranks: - Definite - Structural impairments or neurological impairments for FAS or static encephalopathy. - Probable - Significant dysfunction of two standard deviations or worse in three or more functional domains. - Possible - Mild to moderate dysfunction of two standard deviations or worse in one or two functional domains or by judgment of the clinical evaluation team that CNS damage cannot be dismissed. - Unlikely - No evidence of CNS damage. Structural abnormalities of the brain are observable, physical damage to the brain or brain structures caused by prenatal alcohol exposure. Structural impairments may include microcephaly (small head size) of two or more standard deviations below the average, or other abnormalities in brain structure (e.g., agenesis of the corpus callosum, cerebellar hypoplasia). Microcephaly is determined by comparing head circumference (often called occipitofrontal circumference, or OFC) to appropriate OFC growth charts. Other structural impairments must be observed through medical imaging techniques by a trained physician. Because imaging procedures are expensive and relatively inaccessible to most patients, diagnosis of FASD is not frequently made via structural impairments except for microcephaly. When structural impairments are not observable or do not exist, neurological impairments are assessed. In the context of FASD, neurological impairments are caused by prenatal alcohol exposure which causes general neurological damage to the central nervous system (CNS), the peripheral nervous system, or the autonomic nervous system. A determination of a neurological problem must be made by a trained physician, and must not be due to a postnatal insult, such as a high fever, concussion, traumatic brain injury, etc. All four diagnostic systems show virtual agreement on their criteria for CNS damage at the neurological level, and evidence of a CNS neurological impairment due to prenatal alcohol exposure will result in a diagnosis of FAS or PFAS, and functional impairments are highly likely. Neurological problems are expressed as either hard signs, or diagnosable disorders, such as epilepsy or other seizure disorders, or soft signs. Soft signs are broader, nonspecific neurological impairments, or symptoms, such as impaired fine motor skills, neurosensory hearing loss, poor gait, clumsiness, poor eye-hand coordination, or sensory integration dysfunction. Many soft signs have norm-referenced criteria, while others are determined through clinical judgment. When structural or neurological impairments are not observed, all four diagnostic systems allow CNS damage due to prenatal alcohol exposure to be assessed in terms of functional impairments. Functional impairments are deficits, problems, delays, or abnormalities due to prenatal alcohol exposure (rather than hereditary causes or postnatal insults) in observable and measurable domains related to daily functioning, often referred to as developmental disabilities. There is no consensus on a specific pattern of functional impairments due to prenatal alcohol exposure and only CDC guidelines label developmental delays as such, so criteria (and FASD diagnoses) vary somewhat across diagnostic systems. The four diagnostic systems list various CNS domains that can qualify for functional impairment that can determine an FASD diagnosis: - Evidence of a complex pattern of behavior or cognitive abnormalities inconsistent with developmental level in the following CNS domains - Sufficient for a PFAS or ARND diagnosis using IOM guidelines - Performance at two or more standard deviations on standardized testing in three or more of the following CNS domains - Sufficient for an FAS, PFAS or static encephalopathy diagnosis using 4-Digit Diagnostic Code - General cognitive deficits (e.g., IQ) at or below the 3rd percentile on standardized testing - Sufficient for an FAS diagnosis using CDC guidelines - Performance at or below the 16th percentile on standardized testing in three or more of the following CNS domains - Sufficient for an FAS diagnosis using CDC guidelines - Performance at two or more standard deviations on standardized testing in three or more of the following CNS domains - Sufficient for an FAS diagnosis using Canadian guidelines Ten Brain Domains A recent effort to standardize assessment of functional CNS damage has been suggested by an experienced FASD diagnostic team in Minnesota. The proposed framework attempts to harmonize IOM, 4-Digit Diagnostic Code, CDC, and Canadian guidelines for measuring CNS damage viz-a-viz FASD evaluations and diagnosis. The standardized approach is referred to as the Ten Brain Domains and encompasses aspects of all four diagnostic systems' recommendations for assessing CNS damage due to prenatal alcohol exposure. The framework provides clear definitions of brain dysfunction, specifies empirical data needed for accurate diagnosis, and defines intervention considerations that address the complex nature of FASD with the intention to avoid common secondary disabilities. The proposed Ten Brain Domains include: - Achievement, adaptive behavior, attention, cognition, executive functioning, language, memory, motor skills, sensory integration or soft neurological problems, social communication The Fetal Alcohol Diagnostic Program (FADP) uses unpublished Minnesota state criteria of performance at 1.5 or more standard deviations on standardized testing in three or more of the Ten Brain Domains to determine CNS damage. However, the Ten Brain Domains are easily incorporated into any of the four diagnostic systems' CNS damage criteria, as the framework only proposes the domains, rather than the cut-off criteria for FASD. Prenatal alcohol exposure Prenatal alcohol exposure is determined by interview of the biological mother or other family members knowledgeable of the mother's alcohol use during the pregnancy (if available), prenatal health records (if available), and review of available birth records, court records (if applicable), chemical dependency treatment records (if applicable), or other reliable sources. Exposure level is assessed as Confirmed Exposure, Unknown Exposure, and Confirmed Absence of Exposure by the IOM, CDC and Canadian diagnostic systems. The "4-Digit Diagnostic Code" further distinguishes confirmed exposure as High Risk and Some Risk: - High Risk - Confirmed use of alcohol during pregnancy known to be at high blood alcohol levels (100mg/dL or greater) delivered at least weekly in early pregnancy. - Some Risk - Confirmed use of alcohol during pregnancy with use less than High Risk or unknown usage patterns. - Unknown Risk - Unknown use of alcohol during pregnancy. - No Risk - Confirmed absence of prenatal alcohol exposure. Amount, frequency, and timing of prenatal alcohol use can dramatically impact the other three key features of FASD. While consensus exists that alcohol is a teratogen, there is no clear consensus as to what level of exposure is toxic. The CDC guidelines are silent on these elements diagnostically. The IOM and Canadian guidelines explore this further, acknowledging the importance of significant alcohol exposure from regular or heavy episodic alcohol consumption in determining, but offer no standard for diagnosis. Canadian guidelines discuss this lack of clarity and parenthetically point out that "heavy alcohol use" is defined by the National Institute on Alcohol Abuse and Alcoholism as five or more drinks per episode on five or more days during a 30 day period. "The 4-Digit Diagnostic Code" ranking system distinguishes between levels of prenatal alcohol exposure as High Risk and Some Risk. It operationalizes high risk exposure as a blood alcohol concentration (BAC) greater than 100mg/dL delivered at least weekly in early pregnancy. This BAC level is typically reached by a 55kg female drinking six to eight beers in one sitting. For many adopted or adult patients and children in foster care, records or other reliable sources may not be available for review. Reporting alcohol use during pregnancy can also be stigmatizing to birth mothers, especially if alcohol use is ongoing. In these cases, all diagnostic systems use an unknown prenatal alcohol exposure designation. A diagnosis of FAS is still possible with an unknown exposure level if other key features of FASD are present at clinical levels. Confirmed absence of exposure Confirmed absence of exposure would apply to planned pregnancies in which no alcohol was used or pregnancies of women who do not use alcohol or report no use during the pregnancy. This designation is relatively rare, as most patients presenting for an FASD evaluation are at least suspected to have had a prenatal alcohol exposure due to presence of other key features of FASD. While the four diagnostic systems essentially agree on criteria for Fetal Alcohol Syndrome (FAS), there are still differences when full criteria for FAS are not met. This has resulted in differing and evolving nomenclature for other conditions across the spectrum of FASD, which may account for such a wide variety of terminology. Most individuals with deficits resulting from prenatal alcohol exposure do not express all features of FAS and fall into other FASD conditions. The Canadian guidelines recommend the assessment and descriptive approach of the "4-Digit Diagnostic Code" for each key feature of FASD and the terminology of the IOM in diagnostic categories, excepting ARBD. Fetal Alcohol Syndrome or FAS is the only expression of FASD that has garnered consensus among experts to become an official ICD-9 and ICD-10 diagnosis. To make this diagnosis or determine any FASD condition, a multi-disciplinary evaluation is necessary to assess each of the four key features for assessment. Generally, a trained physician will determine growth deficiency and FAS facial features. While a qualified physician may also assess central nervous system structural abnormalities and/or neurological problems, usually central nervous system damage is determined through psychological, speech-language, and occupational therapy assessments to ascertain clinically significant impairments in three or more of the Ten Brain Domains. Prenatal alcohol exposure risk may be assessed by a qualified physician, psychologist, social worker, or chemical health counselor. These professionals work together as a team to assess and interpret data of each key feature for assessment and develop an integrative, multi-disciplinary report to diagnose FAS (or other FASD conditions) in an individual. Other FASD diagnoses Other FASD conditions are partial expressions of FAS, and here the terminology shows less consensus across diagnostic systems, which has led to some confusion for clinicians and patients. A key point to remember is that other FASD conditions may create disabilities similar to FAS if the key area of central nervous system damage shows clinical deficits in two or more of the Ten Brain Domains. Essentially, growth deficiency and/or FAS facial features may be mild or nonexistent in other FASD conditions, but clinically significant brain damage of the central nervous system is present. In these other FASD conditions, an individual may be at greater risk for adverse outcomes because brain damage is present without associated visual cues of poor growth or the "FAS face" that might ordinarily trigger an FASD evaluation. Such individuals may be misdiagnosed with primary mental health disorders such as ADHD or Oppositional Defiance Disorder without appreciation that brain damage is the underlying cause of these disorders, which requires a different treatment paradigm than typical mental health disorders. While other FASD conditions may not yet be included as an ICD or DSM-IV-TR diagnosis, they nonetheless pose significant impairment in functional behavior because of underlying brain damage. Partial FAS (PFAS) Previously known as Atypical FAS in the 1997 edition of the "4-Digit Diagnostic Code," patients with Partial Fetal Alcohol Syndrome have a confirmed history of prenatal alcohol exposure, but may lack growth deficiency or the complete facial stigmata. Central nervous system damage is present at the same level as FAS. These individuals have the same functional disabilities but "look" less like FAS. - Growth deficiency - Growth or height may range from normal to deficient - FAS facial features - Two or three FAS facial features present - Central nervous system damage - Clinically significant structural, neurological, or functional impairment in three or more of the Ten Brain Domains - Prenatal alcohol exposure - Confirmed prenatal alcohol exposure Alcohol-Related Neurodevelopmental Disorder (ARND) Alcohol-Related Neurodevelopmental Disorder (ARND) was initially suggested by the Institute of Medicine to replace the term FAE and focus on central nervous system damage, rather than growth deficiency or FAS facial features. The Canadian guidelines also use this diagnosis and the same criteria. While the "4-Digit Diagnostic Code" includes these criteria for three of its diagnostic categories, it refers to this condition as static encephalopathy. The behavioral effects of ARND are not necessarily unique to alcohol however, so use of the term must be within the context of confirmed prenatal alcohol exposure. ARND may be gaining acceptance over the terms FAE and ARBD to describe FASD conditions with central nervous system abnormalities or behavioral or cognitive abnormalities or both due to prenatal alcohol exposure without regard to growth deficiency or FAS facial features. - Growth deficiency - Growth or height may range from normal to minimally deficient - FAS facial features - Minimal or no FAS facial features present - Central nervous system damage - Clinically significant structural, neurological, or functional impairment in three or more of the Ten Brain Domains - Prenatal alcohol exposure - Confirmed prenatal alcohol exposure Fetal Alcohol Effects (FAE) This term was initially used in research studies to describe humans and animals in whom teratogenic effects were seen after confirmed prenatal alcohol exposure (or unknown exposure for humans), but without obvious physical anomalies. Smith (1981) described FAE as an "extremely important concept" to highlight the debilitating effects of brain damage, regardless of the growth or facial features. This term has fallen out of favor with clinicians because it was often regarded by the public as a less severe disability than FAS, when in fact its effects can be just as detrimental. Alcohol-Related Birth Defects (ARBD) Formerly known as Possible Fetal Alcohol Effect (PFAE), Alcohol-Related Birth Defects (ARBD) was a term proposed as an alternative to FAE and PFAE The IOM presents ARBD as a list of congenital anomalies that are linked to maternal alcohol use but have no key features of FASD. PFAE and ARBD have fallen out of favor because these anomalies are not necessarily specific to maternal alcohol consumption and are not criteria for diagnosis of FASD. The Canadian guidelines recommend that ARBD should not be used as an umbrella term or diagnostic category for FASD. - ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 Astley, S.J. (2004). Diagnostic Guide for Fetal Alcohol Spectrum Disorders: The 4-Digit Diagnostic Code. Seattle: University of Washington. PDF available at FAS Diagnostic and Prevention Network. Retrieved on 2007-04-11 - ↑ Ratey, J.J. (2001). A User's Guide to the Brain: Perception, Attention, and the Four Theaters of the Brain. New York: Vintage Books. ISBN 0-375-70107-9. - ↑ Clarren, S.K. (2005). A thirty year journey from tragedy to hope. Foreword to Buxton, B. (2005). Damaged Angels: An Adoptive Mother Discovers the Tragic Toll of Alcohol in Pregnancy. New York: Carroll & Graf. ISBN 0-7867-1550-2. - ↑ Jones, K.L., Smith, D.W, Ulleland, C.N., Streissguth, A.P. (1973). Pattern of malformation in offspring of chronic alcoholic mothers. Lancet, 1, 1267-1271. PMID 4126070 - ↑ 5.0 5.1 5.2 Clarren, S.K., & Smith, D.W. (1978). Fetal alcohol syndrome. New England Journal of Medicine, 298, 1063-1067. PMID 347295 - ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 6.14 6.15 Institute of Medicine (IOM), Stratton, K.R., Howe, C.J., & Battaglia, F.C. (1996). Fetal Alcohol Syndrome: Diagnosis, Epidemiology, Prevention, and Treatment. Washington, DC: National Academy Press. ISBN 0309052920 - ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 7.9 Fetal Alcohol Syndrome: Guidelines for Referral and Diagnosis (PDF). CDC (July 2004). Retrieved on 2007-04-11 - ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 Chudley A, Conry J, Cook J, et al (2005). Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis. CMAJ 172 (5 Suppl): S1–S21. - ↑ 9.0 9.1 9.2 9.3 Clinical growth charts. National Center for Growth Statistics. Retrieved on 2007-04-10 - ↑ Jones, K.L., & Smith D.W. (1975). The fetal alcohol syndrome. Teratology, 12(1), 1-10. - ↑ Astley, S.J., & Clarren, S.K. (1996). A case definition and photographic screening tool for the facial phenotype of fetal alcohol syndrome. Journal of Pediatrics, 129(1), 33-41. - ↑ Astley, S.J., Stachowiak, J., Clarren, S.K., & Clausen, C. (2002). Application of the fetal alcohol syndrome facial photographic screening tool in a foster care population. Journal of Pediatrics, 141(5), 712-717. - ↑ Lip-philtrum guides. FAS Diagnostic and Prevention Network, University of Washington. Retrieved on 2007-04-10 - ↑ 14.0 14.1 14.2 FAS facial features. FAS Diagnostic and Prevention Network, University of Washington. Retrieved on 2007-04-10 - ↑ Astley, Susan. Backside of Lip-Philtrum Guides (2004) (PDF). University of Washington, Fetal Alcohol Syndrome Diagnostic and Prevention Network. Retrieved on [[2007-04-11] - ↑ West, J.R. (Ed.) (1986). Alcohol and Brain Development. New York: Oxford University Press. - ↑ 17.0 17.1 FADP - Fetal Alcohol Diagnostic Program - ↑ 18.0 18.1 18.2 18.3 18.4 18.5 Lang, J. (2006). Ten Brain Domains: A Proposal for Functional Central Nervous System Parameters for Fetal Alcohol Spectrum Disorder Diagnosis and Follow-up. Journal of the FAS Institute, 4, 1-11. Can be downloaded at http://www.motherisk.org/JFAS_documents/JFAS_5012_Final_e12_6.28.6.pdf - ↑ U.S. Department of Health and Human Services. (2000). National Institute on Alcohol Abuse and Alcoholism. Tenth special report to the U.S> Congress on alcohol and health: Highlights frfom current research. Washington, DC: The Institute. - ↑ 20.0 20.1 20.2 Streissguth, A. (1997). Fetal Alcohol Syndrome: A Guide for Families and Communities. Baltimore: Brookes Publishing. ISBN 1-55766-283-5. - ↑ Malbin, D. (2002). Fetal Alcohol Spectrum Disorders: Trying Differently Rather Than Harder. Portland, OR: FASCETS, Inc. ISBN 0-9729532-0-5. - ↑ Smith, D.W. (1981). Fetal alcohol syndrome and fetal alcohol effects. Neurobehavioral Toxicology and Teratology, 3, 127. - ↑ Aase, J.M., Jones, K.L., & Clarren, S.K. (1995). Do we need the term FAE? Pediatrics, 95(3), 428-430. - ↑ Sokol, R.J., & Clarren, S.K. (1989). Guidelines for use of terminology describing the impact of prenatal alcohol on the offspring. Alcoholism: Clinical and Experimental Research, 13(4), 597-598. - SAMHSA Fetal Alcohol Spectrum Disorders Center of Excellence - U.S. Congressional Caucus on Fetal Alcohol Spectrum Disorders - NOFAS-UK \|This page uses Creative Commons Licensed content from Wikipedia (view authors).\|	2	4	2	0	1	0.841683	3	6,044
- 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
Doctors bill for their services using a coding system called Current Procedural Terminology (CPT) and International Classification of Diseases (ICD 10). Everything in the medical industry is represented by one of these codes. Procedures, exams, diagnostic studies, office visits, etc are all represented by a CPT code and an ICD 10 code. What is a CPT Code A CPT code is a 5 digit number code that describes every procedure or medical service that exists. CPT codes are defined and maintained by the American Medical Association. One of the main uses of these codes are for billing. Whenever a doctor performs a service or procedure, she or he chooses the most appropriate CPT codes. The medical industry calls this “coding”. Sometimes it can be difficult as there are many different codes that can be used for a procedure. Actually, many people make a living on determining the optimal code to bill for a procedure in just a specific medical specialty. A medical biller then submits these codes to an insurance company to get reimbursed for the services. What is an ICD 10 Code An ICD 10 code is a 7 digit diagnosis code system. It is an international classification system of diseases published by the World Health Organization. Any kind of medical condition is identified by this system. Each character means something. For example, the first character is the area of study – medical or surgical. The fourth character is the body part or region. CPT Codes for Vein Treatments Here are some of the most commonly used CPT codes for vein related treatments. - 36471 – sclerotherapy for spider veins - 36475 – radiofrequency ablation first vein treated - 36476 – radiofrequency ablation subsequent veins treated - 36478 – endovenous laser ablation first vein treated - 36479 – endovenous laser ablation subsequent veins treated - 36482 – Venaseal vein closure - 36483 – Venaseal vein closure subsequent veins treated - 37765 – stab phlebectomy - 93970 – ultrasound of both legs - 93971 – ultrasound of one leg ICD 10 Codes for Vein Related Diagnosis There are so many possible ICD 10 codes for vein related diagnosis, they are too many to list here. For example there are roughly 30 ICD 10 codes for just varicose veins. - I83.811 – Varicose veins of right lower extremity with pain - I83.812 – Varicose veins of right lower extremity with pain - I83.813 – Varicose veins of bilateral lower extremities with pain	4	14	2	0	2	0.575388	4	546
Methods \| Statistics \| Clinical \| Educational \| Industrial \| Professional items \| World psychology \| \|Neurofibromatosis type 1\| \|Classification and external resources\| Café au lait spot characteristic of NF1. \|ICD-10\|\|Q850 (ILDS Q85.010)\| \|eMedicine\|\|derm/287 neuro/248 oph/338 radio/474\| Neurofibromatosis type I (NF-1) is a tumor disorder that is caused by the mutation of a gene on chromosome 17 that is responsible for control of cell division. NF-1 causes tumors along the nervous system. NF-1 often comes with scoliosis (curvature of the spine), learning difficulties, eye problems, and epilepsy. NF-1 was formerly known as von Recklinghausen disease after the researcher (Friedrich Daniel von Recklinghausen) who first documented the disorder, is a human genetic disorder. Neurofibromatosis 1 is one of the most common single-gene disorders affecting neurologic function in humans. NF-1 is not to be confused with Proteus Syndrome, which is a separate disorder, although significant confusion remains in both the media and medical community regarding this fact. NF-1 is a developmental syndrome caused by germline mutations in neurofibromin, a gene that is involved in the RAS pathway (RASopathy). In diagnosis it may also be confused with Legius syndrome. Prenatal testing may be used to identify the existence of NF-1 in the fetus. For embryos produced via in vitro fertilisation, it is possible via preimplantation genetic diagnosis to screen for NF-1. The National Institute of Health (NIH) has created specific criteria for the diagnosis of NF-1. Two of these seven "Cardinal Clinical Features" are required for positive diagnosis. - Six or more café-au-lait spots over 5 mm in greatest diameter in pre-pubertal individuals and over 15 mm in greatest diameter in post-pubertal individuals. Note that multiple café-au-lait spots alone are not a definitive diagnosis of NF-1 as these spots can be caused by a number of other conditions. - Two or more neurofibromas of any type or 1 plexiform neurofibroma - Freckling in the axillary (Crowe sign) or inguinal regions - Optic glioma - Two or more Lisch nodules (pigmented iris hamartomas) - A distinctive osseous lesion such as kyphoscoliosis, sphenoid dysplasia - Thinning of the long bone cortex with or without pseudarthrosis. - A first degree relative (parent, sibling, or offspring) with NF-1 by the above criteria. - Discovered mutations of the NF1 gene, which is located at chromosome 17q11.2 NF-1 is a progressive and diverse condition, making the prognosis difficult to predict. The NF-1 gene mutations manifest the disorder differently even amongst people of the same family. This phenomena is called variable expressivity. For example, some individuals have no symptoms, while others may have a manifestation that is rapidly more progressive and severe. For many NF-1 patients, a primary concern is the disfigurement caused by cutaneous/dermal neurofibromas, pigmented lesions, and the occasional limb abnormalities. However, there are many more severe complications caused by NF-1, although some of them are quite rare. There is no cure for the disorder itself. Instead, people with neurofibromatosis are followed by a team of specialists to manage symptoms or complications. In progress and recently concluded medical studies on NF-1 can be found by searching the official website of the National Institute of Health. The following is a list of conditions and complications associated with NF-1, and, where available, age range of onset and progressive development, occurrence percentage of NF-1 population, method of earliest diagnosis, and treatments and related medical specialties. The progression of the condition is roughly as follows: - Congenital musculoskeletal disorders may or may not be present - Cutaneous conditions may be observed in early infancy - Small tumors may arise in the retina which can eventually lead to blindness - Learning disabilities may arise in preschool children - Neurofibromas may occur and cause many dependent neurological conditions and cutaneous and skeletal disfigurement - Depression and social anxiety may occur as a result of disabilities caused by the condition - Neurofibromas may transition into cancer which can be fatal The St. Louis Children's Hospital Neurofibromatosis Center maintains a comprehensive list of current NF research studies. Musculoskeletal abnormalities affecting the skull include Sphenoid bone dysplasia, Congenital Hydrocephalus and associated neurologic impairment. These abnormalities are non-progressive and may be diagnosed in the fetus or at birth. Disorders affecting the spine include: - In NF-1, there can be a generalized abnormality of the soft tissues in the fetus, which is referred to as mesodermal dysplasia, resulting in maldevelopment of skeletal structures. - Meningoceles and formation of cystic diverticula of the dura of the spine, unrelated to Spina bifida - Radiographically, Dural ectasia can lead to scalloping of the posterior vertebral bodies and to the formation of cystic diverticula of the dura of the spine (termed meningoceles. This meningocele is not related to spina bifida). - Focal scoliosis and/or kyphosis are the most common skeletal manifestation of NF-1, occurring in 20% of affected patients. Approximately 25% of patients will require corrective surgery. Facial bones and limbsEdit - Bowing of a long bone with a tendency to fracture and not heal, yielding a pseudarthrosis. The most common bone to be affected is the tibia, causing congenital pseudarthrosis of the tibia or CPT. CPT occurs in 2-4% of individuals with NF-1. Treatment includes limb amputation. - Malformation of the facial bones or of the eye sockets (lambdoid suture defects, sphenoid dysplasia) - Unilateral overgrowth of a limb. When a plexiform neurofibroma manifests on a leg or arm, it will cause extra blood circulation, and may thus accelerate the growth of the limb. This may cause considerable difference in length between left and right limbs. To equalize the difference during childhood, there is an orthopedic surgery called epiphysiodesis, where growth at the epiphyseal (growth) plate is halted. It can be performed on one side of the bone to help correct an angular deformity, or on both sides to stop growth of that bone completely. The surgery must also be carefully planned with regard to timing, as it is non-reversible. The goal is that the limbs are at near-equal length at end of growth. - Flat pigmented lesions of the skin called café au lait spots. These spots can grow from birth to 16 years and are nonprogressive after that. - Freckling of the axillae or inguinal regions. - Dermal neurofibroma, manifested as single or multiple firm, rubbery bumps of varying sizes on a person's skin. Age of onset is puberty. Progressive in number and size. Not malignant. Can be treated with CO2 lasers. Neurobehavioral developmental disorderEdit The most common complication in patients with NF-1 is cognitive and learning disability. These cognitive problems have been shown to be present in approximately 80% of children with NF-1 and have significant effects on their schooling and everyday life. These cognitive problems have been shown to be stable into adulthood and do not get worse unlike some of the other physical symptoms of NF-1. The most common cognitive problems are with perception, executive functioning and attention. Disorders include: - Attention deficit hyperactivity disorder has been shown to be present in approximately 38% of children with NF-1. - Speech and language delays have also been identified in approximately 68% of preschool children with NF1. - Math deficits. - Motor deficits are common. Motor deficits due to NF-1 are probably not cerebellar. - Spatial deficit. Lovastatin, normally used to treat hypercholesterolemia, is currently in phase one of clinical trial (NCT00352599). This drug has been shown to reverse spatial deficits in mice. - Asperger's Syndrome. Nervous system diseaseEdit The primary neurologic involvement in NF-1 is of the peripheral nervous system, and secondarily of the central nervous system. A neurofibroma is a lesion of the peripheral nervous system. Its cellular lineage is uncertain, and may derive from Schwann cells, other perineural cell lines, or fibroblasts. Neurofibromas may arise sporadically, or in association with NF-1. A neurofibroma may arise at any point along a peripheral nerve. A number of drugs have been studied to treat this condition. Neurofibroma conditions are progressive and include: - Plexiform neurofibroma: Often congenital. Lesions are composed of sheets of neurofibromatous tissue that may infiltrate and encase major nerves, blood vessels, and other vital structures. These lesions are difficult and sometimes impossible to routinely resect without causing any significant damage to surrounding nerves and tissue. - Solitary neurofibroma, affecting 8–12% of patients with NF-1. This occurs in a deep nerve trunk. Diagnosis by cross-sectional imaging (e.g., computed tomography or magnetic resonance) as a fusiform enlargement of a nerve. - Schwannomas, peripheral nerve-sheath tumors which are seen with increased frequency in NF-1. The major distinction between a schwannoma and a solitary neurofibroma is that a schwannoma can be resected while sparing the underlying nerve, whereas resection of a neurofibroma requires the sacrifice of the underlying nerve. - Nerve root neurofibroma. - Bones, especially the ribs, can develop chronic erosions (pits) from the constant pressure of adjacent neurofibroma or Schwannoma. Similarly, the neural foramen of the spine can be widened due to the presence of a nerve root neurofibroma or schwannoma. Surgery may be needed when NF-1 related tumors compress organs or other structures. Nerve sheath tumorEdit - Peripheral nerve sheath tumor. - Chronic pain, numbness, and/or paralysis due to peripheral nerve sheath tumor. Central nervous system diseaseEdit - Main article: Epilepsy - Occurrence. Epileptic seizures haven been reported in up to 7% of NF-1 patients. - Diagnosis. Electroencephalograph, magnetic resonance imaging, computed tomographic scan, single-photon emission CT and positron emission tomographic scan. - Etiology. Due to cerebral tumors, cortical malformation, mesial temporal sclerosis. - Therapy. Drug therapy (57% amenable) where not resistant (29%). - Main article: Glial tumor Intracranially, NF-1 patients have a predisposition to develop glial tumors of the central nervous system, primarily: Focally degenerative myelinEdit Another CNS manifestation of NF-1 is the so-called "unidentified bright object" or UBO, which is a lesion which has increased signal on a T2 weighted sequence of a magnetic resonance imaging examination of the brain. These UBOs are typically found in the Cerebral peduncle, pons, midbrain, globus pallidus, thalamus, and optic radiations. Their exact identity remains a bit of a mystery since they disappear over time (usually, by age 16), and they are not typically biopsied or resected. They may represent a focally degenerative bit of myelin. - Main article: Dural ectasia Within the CNS, NF-1 manifests as a weakness of the dura, which is the tough covering of the brain and spine. Weakness of the dura leads to focal enlargement terms dural ectasia due to chronic exposure to the pressures of CSF pulsation. Acetazolamide has shown promise as a treatment for this condition. Children with NF-1 can experience social problems, attention problems, social anxiety, depression, withdrawal, thought problems, somatic complaints, and aggressive behavior. Treatments include psychotherapy, antidepressants and cognitive behavioral therapy. - Frequency. A plexiform neurofibroma has a lifetime risk of 8–12% of transformation into a malignant tumor. - Diagnosis. MRI. - Treatment. Chemotherapy. - Mortality. Malignant nerve sheath tumor was the main cause of death (60%) in a study of 1895 patients with NF-1 from France in the time period 1980-2006 indicated excess mortality in NF-1 patients compared to the general population. The cause of death was available for 58 (86.6%) patients. The study found excess mortality occurred among patients aged 10 to 40 years. Significant excess mortality was found in both males and females. - Main article: Neurofibromin 1 The neurofibromin 1 geneEdit NF-1 is caused by a mutation of a gene on the long arm of chromosome 17 which encodes a protein known as neurofibromin (not to be confused with the disorder itself) which plays a role in cell signaling. The Neurofibromin 1 gene is a negative regulator of the Ras oncogene signal transduction pathway. It stimulates the GTPase activity of Ras. It shows greater affinity for RAS p21 protein activator 1, but lower specific activity. The mRNA for this gene is subject to RNA editing (CGA->UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. In 1989, through linkage and cross over analyses, neurofibromin was localized to chromosome 17. It was localized to the long arm of chromosome 17 by chance when researchers discovered chromosome exchanges between chromosome 17 with chromosome 1 and 22. This exchange of genetic material presumably caused a mutation in the neurofibromin gene, leading to the NF1 phenotype. Structure of the Neurofibromin geneEdit The Neurofibromin gene was soon sequenced and found to be 350,000 base pairs in length. However, the protein is 2818 amino acids long leading to the concept of splice variants. For example, exon 9a, 23a and 48a are expressed in the neurons of the forebrain, muscle tissues and adult neurons respectively. Homology studies have shown that neurofibromin is 30% similar to proteins in the GTPase Activating Protein (GAP) Family. This homologous sequence is in the central portion of neurofibromin and being similar to the GAP family is recognized as a negative regulator of the Ras kinase. Additionally, being such a large protein, more active domains of the protein have been identified. One such domain interacts with the protein adenylyl cyclase, and a second with collapsin response mediator protein. Together, likely with domains yet to be discovered, neurofibromin regulates many of the pathways responsible for overactive cell proliferation, learning impairments, skeletal defects and plays a role in neuronal development. Inheritance and spontaneous mutationEditThe mutant gene is transmitted with an autosomal dominant pattern of inheritance, but up to 50% of NF-1 cases arise due to spontaneous mutation. The incidence of NF-1 is about 1 in 3500 live births. Related medical conditionsEdit Mutations in the NF1 gene have been linked to NF-1, Juvenile myelomonocytic leukemia and Watson syndrome. A condition with a separate gene mutation but similar Café au lait spots is Legius syndrome which has a mutation on the SPRED1 gene. - Understanding NF1, Harvard Medical School - GeneReviews/NCBI/NIH/UW entry on Neurofibromatosis 1 - GeneReviews/NIH/NCBI/UW entry on Legius syndrome SPRED1 Sprouty-related, EVH1 domain-containing protein 1 - NF KONTAKT.be (a nonprofit organization providing information and resources for families, Schools and Health Care workers dealing with NF1, NF2, and tumour-related neurofibromatosis in Belgium and providing awareness and support of Neurofibromatosis in Europe) - ↑ - ↑ Legendre, Claire-Marie, Catherine Charpentier-Côté, Régen Drouin, and Chantal Bouffard (February 9, 2011). Neurofibromatosis Type 1 and the "Elephant Man's" Disease: The Confusion Persists: An Ethnographic Study. PLoS ONE 6 (2): e16409. - ↑ "British couple successfully screens out genetic disorder using NHS-funded PGD" by Antony Blackburn-Starza, June 9, 2008, BioNews 461 - ↑ "Are there any prenatal tests for the neurofibromatoses?" - ↑ Huson, Susan Mary; Hughes, Richard Anthony Cranmer (1994). The neurofibromatoses: a pathogenetic and clinical overview, London: Chapman & Hall. - ↑ Skelley, Tao Le, Vikas Bhushan, Nathan William. First aid for the USMLE step 2 CK, 8th, New York: McGraw-Hill Medical. - ↑ National Institute of Healthwebsite - ↑ "Neurofibromatosis 1: Current Issues in Diagnosis, Therapy, and Patient Management", by David Viskochil MD PhD, Mountain States Genetic Foundation, Denver 2010 - ↑ "Current Therapies for Neurofibromatosis Type 1", by Laura Klesse MD PhD, Mountain States Genetic Foundation, Denver 2010 - ↑ Neurofibromatosis, giant cafe-au-lait spot. AllRefer.com Health. URL accessed on 2010-07-27. - ↑ Hyman SL, Shores A, North KN (October 2005). The nature and frequency of cognitive deficits in children with neurofibromatosis type 1. Neurology 65 (7): 1037–44. - ↑ Hyman SL, Gill DS, Shores EA, et al. (April 2003). Natural history of cognitive deficits and their relationship to MRI T2-hyperintensities in NF1. Neurology 60 (7): 1139–45. - ↑ Thompson HL, Viskochil DH, Stevenson DA, Chapman KL (February 2010). Speech-language characteristics of children with neurofibromatosis type 1. Am. J. Med. Genet. A 152A (2): 284–90. - ↑ van der Vaart T, van Woerden GM, Elgersma Y, de Zeeuw CI, Schonewille M (June 2011). Motor deficits in neurofibromatosis type 1 mice: the role of the cerebellum. Genes Brain Behav. 10 (4): 404–9. - ↑ "Trial to Evaluate the Safety of Lovastatin in Individuals With Neurofibromatosis Type I (NF1)" - ↑ Vivarelli R, Grosso S, Calabrese F, et al. (May 2003). Epilepsy in neurofibromatosis 1. J. Child Neurol. 18 (5): 338–42. - ↑ Johnson NS, Saal HM, Lovell AM, Schorry EK (June 1999). Social and emotional problems in children with neurofibromatosis type 1: evidence and proposed interventions. J. Pediatr. 134 (6): 767–72. - ↑ "Mortality Associated with Neurofibromatosis 1: A Cohort Study of 1895 Patients in 1980-2006 in France ", May 4, 2011 - ↑ "neurofibromin 1" GeneCards - ↑ "Human Gene NF1 (uc002hgf.1) Description and Page Index" - ↑ 21.0 21.1 Goldberg NS, Collins FS (November 1991). The hunt for the neurofibromatosis gene. Arch Dermatol 127 (11): 1705–7. - ↑ 22.0 22.1 Marchuk DA, Saulino AM, Tavakkol R, et al. (December 1991). cDNA cloning of the type 1 neurofibromatosis gene: complete sequence of the NF1 gene product. Genomics 11 (4): 931–40. - ↑ 23.0 23.1 Gutmann DH, Giovannini M (2002). Mouse models of neurofibromatosis 1 and 2. Neoplasia 4 (4): 279–90. - ↑ Feldkamp MM, Angelov L, Guha A (February 1999). Neurofibromatosis type 1 peripheral nerve tumors: aberrant activation of the Ras pathway. Surg Neurol 51 (2): 211–8. - ↑ Hannan F, Ho I, Tong JJ, Zhu Y, Nurnberg P, Zhong Y (April 2006). Effect of neurofibromatosis type I mutations on a novel pathway for adenylyl cyclase activation requiring neurofibromin and Ras. Hum. Mol. Genet. 15 (7): 1087–98. - ↑ Ozawa T, Araki N, Yunoue S, et al. (November 2005). The neurofibromatosis type 1 gene product neurofibromin enhances cell motility by regulating actin filament dynamics via the Rho-ROCK-LIMK2-cofilin pathway. J. Biol. Chem. 280 (47): 39524–33. - ↑ Le LQ, Parada LF (July 2007). Tumor microenvironment and neurofibromatosis type I: connecting the GAPs. Oncogene 26 (32): 4609–16. - ↑ OMIM 162200 Nervous tissue tumors/NS neoplasm/Neuroectodermal tumor (ICD-O 9350–9589) (C70–C72, D32–D33, 191–192/225) \| PNS: NST\| \| note: not all brain tumors are of nervous tissue, and not all nervous tissue tumors are in the brain (see brain metastases)\| \|This page uses Creative Commons Licensed content from Wikipedia (view authors).\|	2	23	1	0	4	0.870618	5	4,835
JUMP \| 1969 WHO Classification \| 1986 Ramsay Definition \| CDC 1988 Definition (Holmes) \| Oxford 1991 Definition \| CDC 1994 Definition (Fukuda) \| 1994 London Definition \| 2003 Canadian Consensus Criteria (CCC) \| CDC 2005 Empiric Definition \| 2010 Revised Canadian Consensus Definition (CCC) \| 2011 International Consensus Criteria (ICC) \| NIH/IOM 2015 Definition (SEID) Since the first documented outbreak of a chronic fatigue-like illness over 200 years ago1, there has there been little evidence of progress in the treatment, diagnosis and social acknowledgement of a disease which affects as many as 2.5 million in the US alone2. Much of the debate about the illness, commonly referred to as CFS, ME or conflated to ME/CFS, is still mired in uncertainties about the nature of symptoms, causes and biological processes, and the presumed effectiveness and safety of so called biopsychosocial interventions such as cognitive behavioral therapy (CBT) and graded exercise therapy (GET). Over the years, although a number of formal definitions of the illness, called criteria, have guided clinical diagnosis and treatment of ME and CFS, determined government policy on research funding, even influenced public perceptions about its nature and severity, consensus between researchers, governments and even patients on which criteria is best suited is far from settled. The criteria for the illness actually define two distinct, partially overlapping, entities: Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS). Fundamental to the historical narrative of the illness, says Frank Twisk, is the reality that although ME and CFS are considered to be the same, the criteria define two distinct, partially overlapping, clinical entities3. In the video below, Leonard Jason presents his extensive research into the merits and weaknessses of ME/CFS definitions at the 2014 NIH P2P Workshop. Fundamental differences between ME and CFS Twisk goes on to define ME and CFS separately: Myalgic Encephalomyelitis (ME) is a neurological disease4,5 that has been described in the medical literature since 1934 under various names6, including epidemic neuromyasthenia and atypical poliomyelitis, often relating to outbreaks7,8,9. Characteristic symptoms of ME, classified as a disease of the nervous system by the WHO since 196910, are muscle weakness, neurological dysfunction, especially of cognitive, autonomic and neurosensory functions; variable involvement of the cardiac and other systems; a prolonged relapsing course; but above all general or local muscular fatigue after minimal exertion with prolonged recovery times (post-exertional malaise)2. According to commonly used criteria for CFS2 chronic fatigue must be accompanied by at least four out of eight symptoms, e.g., tender lymph nodes and muscle and joint pain. However, five of the eight minor symptoms, i.e., headaches, lymph node pain, sore throat, joint pain, and muscle pain, do not differentiate people with melancholic depression group from healthy controls15. Myalgic Encephalomyelitis (ME) is a neurological disease defined by the WHO, while the diagnosis Chronic Fatigue Syndrome (CFS) is primarily based upon a vague notion of chronic fatigue. Why it matters If the illness can be differentiated by symptom severity and functional impairment, in a sense so can the different criteria. For example, the Canadian Consensus Criteria (CCC) identifies a subset of ME/CFS patients with more functional impairments and physical, mental, and cognitive problems than the Fukuda Definition ((Jason LA, Brown A, Clyne E, Bartgis L, Evans M, Brown M. Contrasting Case Definitions for Chronic Fatigue Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Myalgic Encephalomyelitis. Evaluation & the health professions. 2012;35(3):280-304. doi:10.1177/0163278711424281. [Full Text])). 1969 WHO Classification 1986 Ramsay Definition CDC 1988 Definition (Holmes) Oxford 1991 Definition CDC 1994 Definition (Fukuda) 1994 London Definition Canadian Consensus Criteria (CCC) – 2003 2005 Empiric Definition 2010 Revised Canadian Consensus Criteria (RCCC) NIH/IOM 2015 Definition (SEID) 2011 International Consensus Criteria (ICC-ME) In the video below, Prof Leonard Jason explains why good definitional criteria are important for ME/CFS, and exposes the weakness of those definitions in use up to 2010. Benign Myalgic Encephalomyelitis was classified in 196910 as a neurological disease by the World Health Organisation in its International Classification of Disease (currently listed under Other disorders of brain:Postviral fatigue syndrome:WHO ICD 10 G93.3). Following the Royal Free Hospital outbreak in the UK, Wallis (1955) and Acheson (1959) made the earliest attempts to formally describe the disease, their descriptions focusing on the hallmark muscular and neurological symptoms, including ease of fatigability and potentially relapsing and remitting course. Acheson coined the term ‘Myalgic Encephalomyelitis’ (1956) reflecting the muscular, brain and CNS involvement thought characteristic of the disease. Then in 1986 Ramsay published a definition21 of this disease using the term myalgic encephalomyelitis and the term benign was dropped due to the seriousness of the disability created by the illness22. Ramsay’s criteria differentiated the disease into two main groups: symptoms at onset and symptoms in chronic state. He further differentiated the chronic state into three main groups: muscle phenomena, circulatory impairment, and cerebral dysfunction. Interestingly, fatigue was not a cardinal feature of Ramsay’s chronic state ME. 1990 Revised Ramsay Definition. In 1990, Ramsay collaborated with Dr Elizabeth Dowsett, to publish revisions to his definition, which emphasized an initial viral trigger, and also introduced the concept of prolonged recovery time23. Note, Ramsay’s Definition did not use validated criteria published in a peer review journal. For details of the criteria of 1986 and 1990 Ramsay Definitions, toggle the panels below. The first US chronic fatigue syndrome definition, the CDC 1988 Definition, perhaps better known as the Holmes Definition, introduced the term chronic fatigue syndrome in an attempt to better describe the symptom complex previously known as chronic Epstein-Barr virus syndrome.24 Guided by the US Centers for Disease Control and Prevention (CDC), the Holmes working group documented concern regarding the invalidity of Epstein-Barr virus serologic tests and the lack of a causal relationship between Epstein-Barr virus infection and some patients who had been diagnosed with the chronic Epstein-Barr virus syndrome. The 1988 definition was proposed for research purposes, as a basis for future epidemiologic and clinical studies, with the understanding that it did not necessarily define a single disease but a syndrome – a complex of potentially related symptoms that may have several causes. According to this case definition, individuals needed to report 6 or more months of persistent or relapsing, debilitating fatigue that does not resolve with bedrest. Also, participants were required to report at least 8 of 11 minor symptoms (fever or chills, sore throat, lymph node pain, muscle weakness, muscle pain, postexertional malaise, headaches of a new or different type, migratory arthralgia, neuropsychiatric complaints, sleep disturbance, and a sudden onset of symptoms). Participants were also required to report at least a 50% impairment of daily functioning, as compared to premorbid levels. The new definition shifted the focus of the disease away from Ramsay’s earlier work and in so doing omitted or under-emphasized many of its cardinal symptoms instead giving undue prominence to chronic fatigue. Another major concern was that the requirement of eight or more minor symptoms could inadvertently select for individuals with psychiatric problems25. For details of the CDC 1988 Definition (Holmes) criteria, toggle the panel below. In 1991, a small group of British psychosocial psychiatrists (Sharpe et al)26 created guidelines to facilitate their research into fatiguing conditions. The guidelines became known as the Oxford 1991 Definition and included CFS of unknown etiology and a subtype of CFS called post-infectious fatigue syndrome (PIFS), which “either follows an infection or is associated with a current infection.” However, in reality, this definition shifted the focus of the illness away from the biological entity described in Ramsay’s Definition (1986) and the London Definition (1994) towards a biopsychosocial model. The presence of mental fatigue is required to fulfill the criteria and symptoms are accepted that may suggest a psychiatric disorder27. Shortly after publication of the Oxford criteria Anthony David wrote: “British investigators have put forward an alternative, less strict, operational definition which is essentially chronic fatigue in the absence of neurological signs (but) with psychiatric symptoms as common associated features”31. Less specific criteria, based on the presence or absence of fatigue as the only mandatory symptom, increased the likelihood of patients with primary psychiatric disorders being included in trial cohorts labeled with CFS32,33,34. For details of the Oxford 1991 Definition criteria, toggle the panel below. The CDC 1994 Definition for CFS (1994), also known as the Fukuda Definition, was a US Centers for Disease Control and Prevention (CDC) initiative, primarily developed for research studies of CFS in adults. It is currently favored for use research and clinical diagnosis. The Fukuda Definition requires a person to experience 6 or more months of chronic fatigue of a new or definite onset, that is not substantially alleviated by rest, not the result of ongoing exertion, and results in substantial reductions in occupational, social, and personal activities. Because the Fukuda criteria only require four symptoms out of a possible eight, critical CFS symptoms such as postexertional malaise, and memory and concentration problems are not required of all patients. The Fukuda definition is regarded as less specific than the Holmes criteria which selected a group of patients with higher symptomatology and functional impairment35. Furthermore, these differences do not appear to be influenced by psychiatric variables, as they occurred in the absence of differences in rates of psychiatric comorbidity between the two groups35. Another criticism is that Fukuda lacks clinical application, that it is characterized by vaguely worded criteria that are lacking operational definitions and guidelines to assist health care professionals in their interpretation and application of the diagnostic tool36. Several investigations have contrasted the Holmes and Fukuda Definitions. In a study of 2,376 primary care patients, 1.2% of the sample were diagnosed with CFS by using the 1988 case definition (Holmes), compared to 2.6% using the 1994 case definition (Fukuda)37. Another study of 71 primary care patients with CFS found that participants meeting only the 1994 definition experienced a greater duration of illness than those meeting the 1988 definition38. In contrast, those in the 1988 group reported greater frequency of sore throats, joint pain, tender lymph nodes, headaches, and fever. Finally, the 1988 group was more likely to report a sudden illness onset and a greater reduction in premorbid activity levels than the 1994 group. For a full list of the CDC 1994 Definition (Fukuda) criteria, toggle the panel below. The 1994 London Definition, based on Dr Melvin Ramsay’s clinical description of ME, was developed on behalf of M.E. Action, now Action for M.E. (AfME), for research purposes. Although these criteria were an improvement over the Oxford criteria, their legitimacy has been compromised – they have never been published or submitted for peer review, nor have they been consistently defined or validated. The London Definition places an emphasis on exercise-induced muscle fatigue plus delayed recovery of muscle power after exertion ends, evidence of central nervous involvement and impaired circulation (also known as the diagnostic triad). Two versions of the London Definition appeared around 1993/94. Version 1 was devised for AFME. A truncated and inaccurate revision39, Version 2, published in the 1994 National Task Force Report40 did not include the exclusion diagnoses and the physical examination findings. Another subverted form of the London Definition, based on version 1, was used as secondary criteria in the PACE trial, after the application of the fatigue-based Oxford to exclude those with neurological symptoms, contrary to the original purpose of the original version41. So it should be noted that the only documented application of the London Definition, in the PACE trial, was to filter out serious illness and focus more on fatigue (as a psychological component). For a full list of each of the London Definition criteria, toggle the panels below. The Canadian Consensus Criteria (CCC)42 were written in 2003 by ME/CFS professionals for use in clinical practice. The CCC diverged from Fukuda by de-emphasizing fatigue as the sole major (compulsory) criteria, and elevating the importance of other cardinal symptoms, including post-exertional malaise, pain, sleep disturbances, and cognitive dysfunction. Jason et al. found that CCC captured many of the cardiopulmonary and neurological abnormalities which were not currently assessed by the Fukuda criteria15. Furthermore, Jason also found that CCC also selected cases with “less psychiatric co-morbidity, more physical functional impairment, and more fatigue/weakness, neuropsychiatric, and neurological symptoms” and individuals selected by these criteria were significantly different from psychiatric controls with CFS. 2010 Revised Canadian Consensus Definition (CCC). In 2010 the Revised Canadian Consensus Definition43 specified explicit rules for determining whether critical symptoms meet ME/CFS criteria and a questionnaire was developed to assess core symptoms. It was intended that these developments would lead to increased reliability of the Canadian case definition as well as more frequent use of these criteria by investigators. For a full list of the 2003 Canadian Consensus Criteria for ME/CFS, toggle the panel below. The CDC set out to address criticisms that Fukuda lacked standardized reproducible criteria with the publication of the CDC 2005 Empiric Definition44, also known as the Reeves Definition. The Reeves Definition assesses disability using the Medical Outcomes Survey Short-Form-36 (Ware, Snow, & Kosinski, 2000), assesses symptoms using the Symptom Inventory (Wagner et al., 2005), and assesses fatigue using the Multidimensional Fatigue Inventory (Smets, Garssen, Bonke, & DeHaes, 1995). An evaluation of the Reeves Definition compared 27 patients with a prior diagnosis of CFS with 37 patients diagnosed with a Major Depressive Disorder. The researchers reported that 38 percent of those with a diagnosis of a Major Depressive Disorder were misclassified as having CFS using the new CDC definition45. Leonard Jason criticized the diagnostic utility of the definition because it lacked sensitivity and specificity46. The purpose of rigour had not been achieved, and the Reeves Definition was never broadly implemented. For a full list of the Empiric Definition, toggle the panel below. Consistent with the neurological classification of ME in the World Health Organization’s International Classification of Diseases (ICD G93.3), the International Consensus Criteria (ICC-ME) were developed in 2011 by an International Consensus Panel consisting of clinicians, researchers, teaching faculty and an independent patient advocate. The ICC-ME defines myalgic encephalomyelitis (ME) as an acquired neurological disease with complex global dysfunctions. Pathological dysregulation of the nervous, immune and endocrine systems, with impaired cellular energy metabolism and ion transport are prominent features. The ICC-ME arose out of the Canadian Consensus Criteria (CCC), with some significant changes: - The 6-month waiting period before diagnosis is no longer required. - Less focus on fatigue. - Redefined ‘post exertional malaise’ and introduced the terminology ‘postexertional neuroimmune exhaustion’ (pene). For a full list of the ICC-ME criteria, toggle the panel below. The recently proposed NIH/IOM 2015 Definition2 (SEID) diagnostic criteria developed by the US Institute of Medicine (IOM) at the request of the Department of Health and Human Services (HHS) redefines CFS for clinical application. The IOM recommended that the name of the disease be changed from ME/CFS to Systemic Exertion Intolerance Disease (SEID). Also on Shoutout About ME: The IOM concluded that the term myalgic encephalomyelitis was inappropriate because there was a lack of evidence for encephalomyelitis (brain inflammation) in ME/CFS patients, and myalgia (muscle pain) was not a core symptom of the disease (this point is heavily disputed by researchers and patient groups). SEID was not intended to replace usage of ME. According to the IOM, “This name captures a central characteristic of the disease: the fact that exertion of any sort—physical, cognitive, or emotional—can adversely affect patients in many organ systems and in many aspects of their lives. The committee believes systemic exertion intolerance disease appropriately captures the complexity and severity of the illness.” The new criteria were not evaluated with data sets of patients and controls49. Findings suggest that the new criteria select more patients who have less impairment and fewer symptoms than several other criteria49. SEID may also categorize many individuals with major depressive disorder, as well as other medical illnesses50. As a result of omitting these exclusions, SEID increased the prevalence rate for the illness of 0.42 percent as defined by Fukuda, by 2.8 times50. For a full list of the NIH/IOM 2015 Definition (SEID) criteria for ME/CFS, toggle the panel below. - Lorusso L, Mikhaylova SV, Capelli E, Ferrari D, Ngonga GK, Ricevuti G (February 2009). Immunological aspects of chronic fatigue syndrome. Autoimmun Rev 8 (4): 287–91. doi:10.1016/j.autrev.2008.08.003. PMID 18801465. [Abstract] ↩ - Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Board on the Health of Select Populations; Institute of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington (DC): National Academies Press (US); 2015 Feb. [Abstract], [Full Report] ↩ ↩ ↩ ↩ - Twisk, FN. Accurate diagnosis of myalgic encephalomyelitis and chronic fatigue syndrome based upon objective test methods for characteristic symptoms. World J Methodol. 2015 June 26; 5(2): 68-87. [Full Text] ↩ - Dowsett EG, Ramsay AM, McCartney RA, Bell EJ. Myalgic encephalomyelitis – a persistent enteroviral infection?. Postgrad Med J. 1990;66:526-530. [PubMed], [Full Text] ↩ - Parish JG. Early outbreaks of ‘epidemic neuromyasthenia’. Postgrad Med J. 1978;54:711-717. [PubMed], [Full Text] ↩ - Acheson ED. The clinical syndrome variously called benign myalgic encephalomyelitis, Iceland disease and epidemic neuromyasthenia. Am J Med. 1959;26:569-595. ↩ - Gilliam AG. Epidemiological study on an epidemic, diagnosed as poliomyelitis, occurring among the personnel of Los Angeles County General Hospital during the summer of 1934. Washington, DC: United States Treasury Department Public Health Service Public Health Bulletin; 1938.pp.1-90. ↩ - Crowley N, Nelson M, Stovin S. Epidemiological aspects of an outbreak of encephalomyelitis at the Royal Free Hospital, London, in the summer of 1955. J Hyg (Lond). 1957;55:102-122. [PubMed] ↩ - Strickland PS, Levine PH, Peterson DL, O’Brien K, Fears T. Neuromyasthenia and chronic fatigue syndrome (CFS) in Northern Nevada/California: a ten-year follow-up of an outbreak. J Chronic Fatigue Syndr. 2001;9:3-14. [DOI] ↩ - International Classification of Diseases, Eighth Revision (ICD-8): I (Code 323): 158. Geneva: Switzerland; 1967. ↩ ↩ - Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, Jones JF, Dubois RE, Cunningham-Rundles C, Pahwa S. Chronic fatigue syndrome: a working case definition. Ann Intern Med. 1988;108:387-389.[PubMed] [DOI] ↩ - Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. 1994;121:953-959.[PubMed] [DOI] ↩ - Jason LA, Jessen T, Porter N, Boulton A, Njoku MG, Friedberg F. Examining types of fatigue among individuals with ME/CFS (DSQ 2009; 29). [Full Text] ↩ - Jason LA, Boulton A, Porter NS, Jessen T, Njoku MG, Friedberg F. Classification of myalgic encephalomyelitis/chronic fatigue syndrome by types of fatigue. Behav Med. 2010;36:24-31.[PubMed] [DOI] ↩ - Jason LA, Torres-Harding SR, Carrico AW, Taylor RR. Symptom occurrence in persons with chronic fatigue syndrome. Biol Psychol. 2002;59:15-27.[PubMed] [DOI] ↩ ↩ - Wessely S. Chronic fatigue syndrome. Summary of a report of a joint committee of the Royal Colleges of Physicians, Psychiatrists and General Practitioners. J R Coll Physicians Lond. 1996;30:497-504.[PubMed] ↩ - Lane RJ, Barrett MC, Taylor DJ, Kemp GJ, Lodi R. Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle. Neuromuscul Disord. 1998;8:204-209.[PubMed] [DOI] ↩ - Aslakson E, Vollmer-Conna U, Reeves WC, White PD. Replication of an empirical approach to delineate the heterogeneity of chronic unexplained fatigue. Popul Health Metr. 2009;7:17.[PubMed] [Full Text] ↩ - Wilson A, Hickie I, Hadzi-Pavlovic D, Wakefield D, Parker G, Straus SE, Dale J, McCluskey D, Hinds G, Brickman A. What is chronic fatigue syndrome? Heterogeneity within an international multicentre study. Aust N Z J Psychiatry. 2001;35:520-527.[PubMed] [DOI] ↩ - Ramsay AM. Encephalomyelitis in North West London. A disease simulating poliomyelitis and hysteria. Lancet 1957; 2: 1196-1200. ↩ - Ramsay MA. Myalgic encephalomyelitis and postviral fatigue states: The saga of royal free disease. 2nd ed. Gower; London, UK: 1988. [Exerpt] ↩ - Hyde BM, Goldstein JA, Levine P. The clinical and scientific basis of myalgic encephalomyelitis/chronic fatigue syndrome. Nightingale research foundation; Ottawa, ON: 1992. ↩ - Ramsay, A.M. & Dowsett, B. (1992) Myalgic encephalomyelitis, then and now, and epidemiological introduction. In B.M. Hyde, J. Goldstein & P. Levine (Eds.), The clinical and scientific basis of myalgic encephalomyelitis/chronic fatigue syndrome (pp. 81-84). Ottawa: Nightingale Research Foundation. ↩ - Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, et al. Chronic Fatigue Syndrome: A Working Case Definition. Ann Intern Med. 1988;108:387-389. doi:10.7326/0003-4819-108-3-387. [PubMed] [Full Text] ↩ - Katon W, Russo J. Chronic fatigue syndrome criteria. A critique of the requirement for multiple physical complaints. Archives of Internal Medicine. 152:1604–1609.doi:10.1300/J092v13n02_01. [PubMed] ↩ - Sharpe MC, Archard LC, Banatvala JE, et al. A report–chronic fatigue syndrome: guidelines for research. Journal of the Royal Society of Medicine. 1991;84(2):118-121. [PubMed], [Full Text] ↩ ↩ - Wyller, VB. The chronic fatigue syndrome–an update. Acta neurologica Scandinavica. Supplementum, 2007, 187: 7–14. doi:10.1111/j.1600-0404.2007.00840.x. PMID 17419822 [PubMed] ↩ - White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC, Baber HL, Burgess M, Clark LV, Cox DL, Bavinton J, Angus BJ, Murphy G, Murphy M, O’Dowd H, Wilks D, McCrone P, Chalder T, Sharpe M; PACE trial management group. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. 2011 Mar 5;377(9768):823-36. doi: 10.1016/S0140-6736(11)60096-2. Epub 2011 Feb 18. [PubMed], [Full Text] ↩ - Twisk FN, Maes M. A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS. Neuro Endocrinol Lett. 2009;30(3):284-99. [PubMed], [Full Text] ↩ - David AS (1991) Postviral syndrome and psychiatry. Br Med Bull. 47: 966–988. ↩ - David AS (1991) Postviral syndrome and psychiatry. Br Med Bull. 47: 966–988. ↩ - Jason LA, Brown A, Clyne E, Bartgis L, Evans M, Brown M. Contrasting Case Definitions for Chronic Fatigue Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Myalgic Encephalomyelitis. Evaluation & the health professions. 2012;35(3):280-304. doi:10.1177/0163278711424281. [Full Text] ↩ - Carruthers, B. M., van de Sande, M. I., De Meirleir, K. L., Klimas, N. G., Broderick, G., Mitchell, T., Staines, D., Powles, A. C. P., Speight, N., Vallings, R., Bateman, L., Baumgarten-Austrheim, B., Bell, D. S., Carlo-Stella, N., Chia, J., Darragh, A., Jo, D., Lewis, D., Light, A. R., Marshall-Gradisbik, S., Mena, I., Mikovits, J. A., Miwa, K., Murovska, M., Pall, M. L. and Stevens, S. (2011), Myalgic encephalomyelitis: International Consensus Criteria. Journal of Internal Medicine, 270: 327–338. doi: 10.1111/j.1365-2796.2011.02428.x. [PubMed], [Full Text] ↩ - Morris G, Maes M. Case definitions and diagnostic criteria for Myalgic Encephalomyelitis and Chronic fatigue Syndrome: from clinical-consensus to evidence-based case definitions. Neuro Endocrinol Lett. 2013;34(3):185-99. [PubMed], [Full Text] ↩ - Leonard A. Jason, Susan R. Torres-Harding, Renee R. Taylor, Adam W. Carrico, A Comparison of the 1988 and 1994 Diagnostic Criteria for Chronic Fatigue Syndrome. Journal of Clinical Psychology in Medical Settings, 2001. Vol. 8, No. 4, pp 337-343. [Abstract] [Full Text] ↩ ↩ - Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR, McCready W, Huang CF, Plioplys S., A community-based study of chronic fatigue syndrome. Arch Intern Med. 1999 Oct 11;159(18):2129-37. [PubMed] ↩ - Wessely S, Chalder T, Hirsch S, Wallace P, Wright D., The prevalence and morbidity of chronic fatigue and chronic fatigue syndrome: a prospective primary care study. Am J Public Health. 1997 Sep;87(9):1449-55. [PubMed] ↩ - Tiersky LA, Weisberg S, Zhang QW et al. Symptom frequency and severity in chronic fatigue syndrome. 2000. Unpublished manuscript. ↩ - Williams, Margaret. Ellen Goudsmit PhD and the “London” criteria : THE FACTS. MEActionUK, 2005. [article] ↩ - EG Dowsett, E Goudsmit, A Macintyre, C Shepherd, et al., London criteria for M.E., Report from The National Task Force on Chronic Fatigue Syndrome (CFS), Post Viral Fatigue Syndrome (PVFS), Myalgic Encephalomyelitis (ME). Westcare, 1994, pp. 96-98. [name-us.org] ↩ - Shepherd, C. London Criteria for M.E. – for website discussion. ME Association, 2011, [Article] ↩ - Carruthers, et al., ME/CFS: Clinical Working Case Definition, Diagnostic and Treatment Protocols, Journal of Chronic Fatigue Syndrome, Volume 11, Number 1 2003. Page 18-126. [Overview], [Full Report] ↩ - Jason, L.A., M. Evans, N. Porter, M. Brown and A. Brown et al., 2010. The Development of a Revised Canadian Myalgic Encephalomyelitis Chronic Fatigue Syndrome Case Definition. Am. J. Biochem. Biotechnol., 6: 120-135. [Abstract], [Full Text] ↩ - Reeves WC, Wagner D, Nisenbaum R, et al. Chronic Fatigue Syndrome – A clinically empirical approach to its definition and study. BMC Medicine. 2005;3:19. doi:10.1186/1741-7015-3-19. [Full Text] ↩ - Jason, Leonard A; Najar, Natasha; Porter, Nicole; Reh, Christy (2009). “Evaluating the Centers for Disease Control’s Empirical Chronic Fatigue Syndrome Case Definition“. Journal of Disability Policy Studies 20 (2): 93–100. doi:10.1177/1044207308325995. [Abstract], [Full Text] ↩ - Jason L., Evans M., Brown A., Brown M., Porter N., Hunnell J., Anderson V. & Lerch A. (2010). Sensitivity and Specificity of the CDC Empirical Chronic Fatigue Syndrome Case Definition. Psychology, 1, 9-16. doi: 10.4236/psych.2010.11002. [Abstract] ↩ - Reeves WC, Jones JF, Maloney E, et al. Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. Popul Health Metr 2007;5:5. [Full Text] ↩ - Jason LA, Najar N, Porter N, et al. Evaluating the Centers for Disease Control’s empirical chronic fatigue syndrome case definition. J Disabil Policy Stud 2009;20:93–100. [Abstract], [Full Text] ↩ - Jason, L. Sunnquist, M. Brown, A. McManimen, S. Furst, J. Reflections on the IOM’s systemic exertion intolerance disease. Pol Arch Med Wewn 2015 pii: AOP_15_067 [Abstract], [Full Text] ↩ ↩ - Jason, L.A.; Sunnquist, M.; Kot, B.; Brown, A. Unintended Consequences of not Specifying Exclusionary Illnesses for Systemic Exertion Intolerance Disease. Diagnostics 2015, 5, 272-286. [Abstract], [Full Text] ↩ ↩	2	20	4	1	4	0.67687	9	7,162
The implantable cardioverter-defibrillator (ICD) is a surgically implanted electronic device that directs an electric charge directly into the heart to treat life-threatening arrhythmias. The implantable cardioverter-defibrillator is used to detect and stop life-threatening arrhythmias and restore a productive heartbeat that is able to provide adequate cardiac output to sustain life. The exact indications for the implantation of the device are controversial, but patients suffering from ventricular fibrillation (unproductive heartbeat), ventricular tachycardia (abnormally fast heartbeat), long QT syndrome (an inherited heart disease), or others at risk for sudden cardiac death are potential candidates for this device. A study by the National Institute for Heart, Lung, and Blood of the National Institutes of Health showed a significant increase in survival for patients suffering from ventricular arrhythmias when ICD implant is compared to medication. Several follow-up studies indicate that this may be due to the marked increase in survival for the sickest patients, generally defined as those having a heart weakened to less than 50% of normal, as measured by the ability of the left side of the heart to pump blood. Overall, studies have documented a very low mortality rate of 1–2% annually ICD implant is limited to patients that face the risk of sudden cardiac death from sustained ventricular arrhythmia, including ventricular tachycardia and ventricular fibrillation. Less than 1% of the more than 100,000 device implants done in the United States are performed on pediatric patients. Reduction in the risk of sudden cardiac death improves to less than 2% for both populations. Patients experiencing syncope (fainting) will be monitored with a cardiac monitor for arrhythmias. Following unsuccessful medical treatment for sustained ventricular arrhythmias, ICD implant will be indicated. Similar in structure to a pacemaker, an ICD has three main components: a generator, leads, and an electrode. The generator is encased in a small rectangular container, usually about 2 in (5 cm) wide and around 3 oz (85 g) in weight. Even smaller generators have been developed, measuring 1 in (2.5 cm) in diameter and weighing about 0.5 oz (14 g). The generator is powered by lithium batteries and is responsible for generating the electric shock. The generator is controlled by a computer chip that can be programmed to follow specific steps according to the input gathered from the heart. The programming is initially set and can be changed using a wand programmer, a device that communicates by radio waves through the chest of the patient after implantation. One or two leads, or wires, are attached to the generator. These wires are generally made of platinum with an insulating coating of either silicone or polyurethane. The leads carry the electric shock from the generator. At the tip of each lead is a tiny device called an electrode that delivers the necessary electrical shock to the heart. Thus, the electric shock is created by the generator, carried by the leads, and delivered by the electrodes to the heart. The decision of where to put the leads depends on the needs of the patient, but they can be located in the left ventricle, the left atrium, or both. According to the American College of Cardiology, more than 100,000 persons worldwide currently have an ICD. The battery-powered device rescues the patient from a life-threatening arrhythmia by performing a number of functions in order to reestablish normal heart rhythm, which varies with the particular problem of the patient. Specifically, if encountered with ventricular tachycardia, many devices will begin treatment with a pacing regimen. If the tachycardia is not too fast, the ICD can deliver several pacing signals in a row. When those signals stop, the heart may go back to a normal rhythm. If the pacing treatment is not successful, many devices will move onto cardioversion . With cardioversion, a mild shock is sent to the heart to stop the fast heartbeat. If the problem detected is ventricular fibrillation, a stronger shock called a defibrillation is sent. This stronger shock can stop the fast rhythm and help the heartbeat return to normal. Finally, many ICDs can also detect heartbeats that are too slow; they can act like a pacemaker and bring the heart rate up to normal. ICDs that defibrillate both the ventricles and the atria have also been developed. Such devices not only provide dual-chamber pacing but also can distinguish ventricular from atrial fibrillation. Patients that experience both atrial and ventricle fibrillations, or atrial fibrillation alone, that would not be controlled with a single-chamber device are candidates for this kind of ICD. ICD insertion is considered minor surgery, and can be performed in either an operating room or an electrophysiology laboratory. The insertion site in the chest will be cleaned, shaved, and numbed with local anesthetic. Generally, left-handed persons have ICDs implanted on the right side, and visa versa, to speed return to normal activities. Two small cuts (incisions) are made, one in the chest wall and one in a vein just under the collarbone. The wires of the ICD are passed through the vein and attached to the inner surface of the heart. The other ends of the wires are connected to the main box of the ICD, which is inserted into the tissue under the collarbone and above the breast. Once the ICD is implanted, the physician will test it several times before the anesthesia wears off by causing the heart to fibrillate and making sure the ICD responds properly. The doctor then closes the incision with sutures (stitches), staples, or surgical glue. The entire procedure takes about an hour. Immediately following the procedure, a chest x ray will be taken to confirm the proper placement of the wires in the heart. The ICD's programming may be adjusted by passing the programming wand over the chest. After the initial operation, the physician may induce ventricular fibrillation or ventricular tachycardia one more time prior to the patient's discharge, although recent studies suggest that this final test is not generally necessary. A short stay in the hospital is usually required following ICD insertion, but this varies with the patient's age and condition. If there are no complications, complete recovery from the procedure will take about four weeks. During that time, the wires will firmly take hold where they were placed. In the meantime, the patient should avoid heavy lifting or vigorous movements of the arm on the side of the ICD, or else the wires may become dislodged. After implantation, the cardioverter-defibrillator is programmed to respond to rhythms above the patient's exercise heart rate. Once the device is in place, many tests will be conducted to ensure that the device is sensing and defibrillating properly. About 50% of patients with ICDs require a combination of drug therapy and the ICD. Perioperative mortality demonstrates a 0.4–1.8% risk of death for primary non-thoracotomy implants. The ICD showed improved survival compared to medical therapy, improving by 38% at one year. There is a 96% survival rate at four years for those implanted with ICD. Less then 2% of patients require termination of the device, with a return to only medical therapy. Ventricular tachycardia can be successfully relieved by pacing in 96% of instances with the addition of defibrillation converting 98% of patients to a productive rhythm that is able to sustain cardiac output. Ventricular fibrillation is successfully converted in 98.6–98.8% of all cases. Atrial fibrillation and rapid ventricular response leads to erroneous fibrillation in as many as 11% of patients. Environmental conditions that can affect the functioning of the ICD after installation include: Environmental conditions often erroneously thought to affect ICDs include: Patients should also be instructed to memorize the manufacturer and make of their ICD. Although manufacturing defects and recalls are rare, they do occur and a patient should be prepared for that possibility. In general, if the condition of the patient's heart, drug intake, and metabolic condition remain the same, the ICD requires only periodic checking every two months or so for battery strength and function. This is done by placing a special device over the ICD that allows signals to be sent over the telephone to the doctor, a process called trans-telephonic monitoring. If changes in medications or physical condition occur, the doctor can adjust the ICD settings using a programmer, which involves placing the wand above the pacemaker and remotely changing the internal settings. One relatively common problem is the so-called "ICD storm," in which the machine inappropriately interprets an arrhythmia and gives a series of shocks. Reprogramming can sometimes help alleviate that problem. When the periodic testing indicates that the battery is getting low, an elective ICD replacement operation is scheduled. The entire signal generator is replaced because the batteries are sealed within the case. The leads can often be left in place and reattached to the new generator. Batteries usually last from four to eight years. Patients are treated with medical therapy to reduce the chance of arrhythmia. This alternative has been shown to have a higher rate of sudden death when compared to ICD over the initial three years of treatment, but has not been compared at five years. If the site of ventricular tachycardia generation can be mapped by electrophysiology studies, the aberrant cells can be removed or destroyed. Less then 5% of patients suffer peri-operative mortality with this cell removal. Gersh, Bernard J., ed. Mayo Clinic Heart Book. New York: William Morrow and Company, Inc., 2000. Gregoratos, Gabriel, et al. "ACC/AHA Guidelines for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices." Journal of the American College of Cardiologists 31, no. 5 (April 1998): 1175–1209. Moss, A. "Implantable Cardioverter-Defibrillator Therapy: The Sickest Patients Benefit Most." Circulation 101 (April 2000): 1638–1640. Sears, Samuel F. Jr., et al. "Fear of Exertion Following ICD Storm: Considering ICD Shock and Learning History." Journal of Cardiopulmonary Rehabilitation 21 (January/February 2001): 47. American Heart Association. National Center. 7272 Greenville Avenue, Dallas, TX, 75231-4596. (214) 373-6300. http://www.americanheart.org . North American Society of Pacing and Electrophysiology. 6 Strathmore Road, Natick, MA, 01760-2499. (508) 647-0100. http://www.naspe.org/index.html . "Implantable Cardioverter-Defibrillator." American Academy of Family Physicians. May 7, 2001. http://www.familydoctor.org/handouts/270.html . "Implantable Cardioverter-Defibrillators (ICDs)" North American Society of Pacing and Electrophysiology. 2000. http://www.naspe.org/your_heart/treatments/icds.html . Michelle L. Johnson, MS,JD Allison J. Spiwak, MSBME Electrophysiologists are specially trained cardiologists or thoracic surgeons who study and treat problems with the heart conduction system. In a hospital operating room, they often implant the ICD system and oversee the programming or reprogramming of the device. Electrophysiologists receive special continuing medical education to provide successful implantation. Implantation, follow-up, and replacement can be limited at any one institution, therefore an experienced well-trained electrophysiologist should perform these procedures.	3	8	2	0	0	0.717374	2	2,520
PATHOLOGY Brain tumours Remember that the skull is a rigid closed box. There are 3 compartments. Two are above the tentorium cerebelli (divided by the falx cerebri) and 1 below. There are 3 things inside the head: Blood, brain and CSF Brain: mixture of glial cells and neurones (equal volumes) Relatively small amount of blood inside the brain at any one time. Small volume of CSF and extracellular fluid. Very little space inside the head, when there is an expanding mass inside the head (whether this is tumour, haemorrhage, abscess or anything else) Pressure in adult is about 15mmHg. In newborn baby it is atmospheric pressure (because it is in connection with the outside) You can measure the intracranial pressure by doing a lumbar puncture and attaching a sphygmomanometer to it. Alternatively you can drill a small hole into the head and attach a transducer. As the volume expands the pressure stays more or less the same (however after a certain volume, the pressure expands rapidly). Eventually the pressure inside the head exceeds the cerebral perfusion pressure and you become brain dead. Neurological intensive care units frequently measure the intracranial pressure. Important to recognise it early. As a mass expands (e.g above the tentorium cerebelli) then it initially squashes the ventricles. Then it will eventually cause brain tissue to herniate to the other side. Finally, it will cause herniation of the brain stem (from one side to the other). This is important because the brainstem is supplied by small branches from the basilar artery. The basilar artery itself is anchored and can’t move. Therefore the vessels stretch and tear. This causes secondary haemorrhages which will cause death. Oedema and hydrocephalus Oedema: excess water in the extracellular space Hydrocephalus: excess water in the ventricular system Oedema Normally we don’t produce significant ECF in the brain because we don’t have lymphatics in the brain (and thus we would have no way of removing it). Additionally, the blood vessels in the brain have tight junctions and unless there is a pathological condition they do not allow fluid to getting across. Thus if breakdown in BBB, fluid gets out into the extracellular space, it builds up (due to lack of lymphatics) There are 2 reasons that you can get cerebral oedema: Vasogenic: tight junctions open. This can be due to trauma or a tumour. This is the one that is most amenable to treatment (putting patient on ventilator etc) Cytotoxic: Here there is a problem with the sodium potassium pump. This is dependent on oxygen and glucose. If this pump fails then sodium cant be pumped out of the cell. Thus water enters and it swells. This is seen in ischaemia. There is not much you can do in this situation. Hydrocephalus Causes: Loss of brain tissue, as you can’t have a vacuum in your skull, so CSF fills up the space. Commonest cause of this is Alzheimer’s where you have lost brain tissue. Termed hydrocephalus ex vacuo. Overproduction/blockage/reabsorption failure. Remember the anatomy of the ventricular system. You have the choroids plexus which produces the CSF. This is present throughout the ventricular system. The CSF flows from the lateral ventricles through the foramen of Monro to the third ventricle. It then flows via the cerebral aqueduct to the fourth ventricle. Then it can flow down the spinal cord or through the foramen of Luschke and the foramen of Megendie. It then flows around the superior saggital sinus to be reabsorbed by the arachnoid villi. This circulates about 3 times a day. You cannot stop CSF from being produced. Thus if there is a blockage then the pressure will rapidly rise and you will die from raised intracranial pressure quickly. Can produce too much CSF – choroids plexus papilloma/carcinoma. Note how the ventricles are equally enlarged (this is sign of papilloma/carcinoma) Circulation blockage – need to think of the anatomy and find out where the blockage is. (below scan does not show where the blockage is) (on right can see that there is blockage of the foramen of monro) Chiari malformation Note that there is a congenital defect where you have a small posterior fossa which is not large enough for the contents. You get these scan changes Treatment is with neurosurgery to decompress the area. Note that newborn infant is when there is the first presentation. Associated with spina bifida. Can also present in later life though (presenting with headaches, raised intracranial pressure etc) Brain tumours Primary brain tumours are reasonably rare. 10X more common to have secondary brain tumours (especially from lung, breast etc). This often occurs in the context of late stage disseminated disease. However, there may be the presentation of a single brain tumour met as the first presentation. They are common in children (as common as childhood leukaemia) Survival not improved in 60 years. 1 year median survival. Causes Not really known Maybe some familial, radiation, viral factors etc. (Most have no known cause) Some conditions have increased risk e.g neurofibromatosis, von-Hippel Lindau etc Not really any carcinoma sequence that we are aware of (e.g dysplasia, CIS etc). Don’t find incidental brain tumours (not known what the precancerous state is) Clinical presentation Raised intracranial pressure e.g headache. Especially worse in morning (because when lying down, venous drainage from head is not as good as when standing up), then it progresses to persisting throughout the day. Eventually patient begins to vomit (remember this is a cardinal feature of raised ICP). As vomiting persists the patient will begin to get drowsy (as the raised ICP is having an effect on cerebral perfusion). Then only matter of hours before coma Behavioural change not as common presentation now because all psychiatric patients have brain imaging. Seizure: first time patient has a seizure after the age of 4-5 then the patient has a brain tumour until proven otherwise. (this is because seizures are common in childhood and vast majority are not due to brain tumours – as child gets older and especially adult who gets this must get MRI – CT is useless, not good resolution) Neurological deficit – (as opposed to stroke, the deficit comes on gradually over time – as the tumour expands). - Classification Tend not to use term benign or malignant. Unlike other tumours in the body, ALL brain tumours are potentially lethal (irrespective of type and grade) due to raised ICP Major biological difference between infiltrating gliomas (these arise in the substance of the brain. They infiltrate the brain by following line of least resistance). These will kill you within a year. Tumours from the surface that push into the brain but don’t invade the brain tissue e.g pituitary or meningeal tumours are a very different entity. Easily treated The first type is referred to as of glial origin. Remember that neurones are post mitotic cells and thus you cannot get neuronal tumours. Glioma These tumours proliferate and invade adjacent brain tissue. They are capable of developing a new blood vessel for themselves. Astrocyte: scaffolding of the brain tissue, they support the brain. Also contribute to BBB and provide nutrition to the brain. They turnover regularly Oligodendrocytes: lay down myelin over the axons. Note neural development. You have proliferation, differentiation (the cells are very undifferentiated – can become astrocyte, oligodendrocyte or neurone). There is then migration to the site of the developing cortex. First the astrocytes go up. Then the neurones move up and they wrap themselves around the astrocytes (like a vine). Then they make connections to other cells. The cells then begin apoptosis (if this doesn’t occur then half their brain will be twice the size as the other) Sometimes there is arrested migration and you result in a double cortex In brain tumours the opposite occurs Glioma classification Astrocytoma, oligodendroglioma ependymoma (remember the ependymal cells are the cells which line the ventricles and contribute to the choroids plexus) Key thing is to remember that these are highly malignant and will kill you (only matter of time) Astrocytoma Two different groups: non-infiltrating and infiltrating Non infiltrating are juvenile pilocystic, subependymal giant cell and subependynoma Infiltrating include astrocytoma, anaplastic astrocytoma and glioblastoma multiforme. These infiltrate surrounding brain, show progression to higher grade and very difficult to remove (as they look like normal brain). Only on MRI is there a difference. Also problem as often presents late. The CT underestimates the tumour extent. The isolated tumour cells invade widely and it is impossible for the surgeon to remove it all (need to add a couple of cm into the perimeter of the apparent tumour) They never metastastise because there are no lymphatics in the brain (additionally they lack enzyme – metalloproteinase to invade blood vessels). However by contrast, secondaries can easily metastasise to the brain because can spread by blood If they do reoccur then they do so in the same place (however still cannot be removed as it invades the brain tissue) They are very leaky as they don’t have the normal tight junctions of normal brain. Thus they leak fluid into the extracellular space and cause brain oedema and raised ICP (which is how they kill you) Grade: Grade 1 = don’t progress to later grades and can often not present problems Grade 2 = hypercellular Grade 3 = has mitosis Grade 4 = has necrosis and neovascularisation. Progression is inevitable (except grade 1). You try to delay progression with surgery/chemotherapy/radiotherapy but not very effective. Can do surgery as below (you can use image guidance to locate the tumour amidst the surrounding brain. It has not helped mortality but it has helped reduce morbidity. - Extent of resection depends on the location (how much neurological deficit you will do by performing the procedure) Oligodendroglioma These are another form of glioma They have a unique genetic signature (1p 19q deletions). Those with this deletion respond much better to chemotherapy. Either way, all the patients with these brain tumours will end up with a highly malignant stage 4 glioma called a glioblastoma (most die within year). In summary, grade is very good predictor of survival. Additionally amount of neurological deficit is a good predictor. Glioma treatments Removal Biopsy is not a treatment. Maximum safe debulking of the tumour. Can also do craniotomy (where a portion of the skull is removed) and decompression Radiation: Conventional external beam can be used. However, internal beams can also be used. Chemotherapy Can also be used. Therapeutic resistance These tumours do so badly because radical resection is difficult (due to problem of removing brain tissue and resulting in severe neurological deficit/death) Radiotherapy constraints Tumour heterogeneity (i.e multiple cell lines are involved and therefore as you kill off one cell line, another takes its place) Blood tumour barrier (which makes it difficult for chemotherapy to act). CHILD BRAIN TUMOURS These are as frequent as leukaemia but are more devastating. The impact of treatment on the developing nervous system is a problem. There are psychological and neurological effects of the treatment on it. There may be endocrine effects (e.g damage to the pituitary glands). If you e.g operate on a spinal cord in a child < 2 then they will not grow beyond that length. Most adult brain tumours occur above tentorium while most child ones occur below the tentorium. Cerebellar astrocytoma Cystic and it is easily resected. No other Treatment is necessary. There is excellent long term survival. - Brainstem astrocytoma Same tumour, same histology but different location. Now very different prognosis. Impossible to resect. There are major neurologic deficits. There is low grade histology but LOCATION and NOT the grade dictates the outcome. Only palliative care is possible. Medulloblastoma This is a primitive neuroepidermal tumour (it is the equivalent of a nephroblastoma, retinoblastoma etc) Develops from the primitive developing cerebellum. They spread down the spinal cord through the CSF. There are small round cells (they look kind of like small cell carcinoma in the lungs) Treatment in a child over 2: resection (as much as you can) and radiotherapy to the spinal cord. Treatment under 2: intrathecal chemotherapy (not as effective) and resection as much as you can. However there are devastating neurological affects as the effects on the developing nervous system are extensive. NON GLIAL TUMOURS These arise from the structures that cover the brain (and structures around it) Meningioma. This pushes into the brain tissue but does not invade (unlike a glioma). Thus relatively easy to be removed. Pituitary adenoma Can produce too much or too little hormone Can also compress surrounding structures e.g optic nerve – remember that patients often do not notice visual field defects, cavernous sinus (remember, collection of veins), brainstem. Schwannoma These are tumours of the cranial nerves (except II). Remember that the optic nerve is covered by oligodendrocytes (which is why it is the only cranial nerve which is affected by MS). This is a schwannoma in the cerebello-pontine angle. Thus affecting 7th and 8th nerves. Thus probably complaining of deafness. This is a difficult area to operate (and may be left with a 7th nerve palsy afterwards) Note that if you get it on both sides you almost definitely have type 2 neurofibromatosis. Pinealoma Back of the brainstem is in a very inaccessible place of the brainstem, can press on back of brainstem damaging nerves so cannot have vertical gaze, cannot move up or down. makes sense – arises posteriorly from the brainstem – supplies the superior oblique – which is responsible for making the eye look down Also compresses the aqueduct of Sylvius – so patients get hydrocephalus. Cerebral haemangioblastoma: This is a vascular tumour which arises from stem cells that produce blood vessels It is associated with von-Hippel Lindau disease. Remember this is a disease where there is a mutation in a tumour suppressor gene – this causes them to be at increased risk of this as well as phaochromocytoma but most importantly renal cell carcinoma. Since it is very vascular, it is prone to bleed. Craniopharyngioma Benign tumour but due to where it is – right by the hypothalamus, it is very problematic Can be blind due to damage to pituitary stalk, they can have dwarfism due to damage to pituitary, diabetes insipidus due to damage to posterior pituitary etc. 4 C’s Childhood, cystic, calcified and cholesterol in cyst. Microscopically composed of remnants of Rathke’s pouch. - Stroke is the rapidly developing loss of brain function due to disruption of the normal blood supply to the brain You cannot manage a patient unless you can do a CT scan within 2 hours of the onset of symptoms. Scan needs to tell you if you have a haemorrhage or an infarct (this is only thing you need to initially know) Stroke units: need full work up within 3-4 hours Need early recognition with neuroimaging Early treatment with thrombolysis Need to have good prevention (with risk factor management). Remember that stroke risk is exactly the same as heart disease risk except heart disease is an additional factor. Neurorehabilitation is essential. Recovery after stroke takes at least 2 years. Thus cant give up. Need to make sure have access to speech therapy, physiotherapy etc. This makes a difference. Stroke is either an infarct or a haemorrhage. Infarct can be embolus or thrombus Haemorrhage can be intracerebral or subarachnoid. (you can get haemorrhages in other areas e.g extradural haemorrhages in trauma) Stroke incidence/mortality Declining mortality due to improved BP control (one of the main risk factors haemorrhagic stroke) and other risk factor management. Case fatality is also declining due to improved acute stroke care. The stroke events are less severe and there is an increased dx of mild cases (i.e picked up earlier) Frequency of stroke type Infarction is most common (65%) Haemorrhage is about 1/10 (of which half are subarachnoid haemorrhage and half are intracerebral haemorrhage). This is on the decline because of better BP control. TIA = 20%. (transient loss of unction within 20 mins. Platelets then break up and move on. However, important thing is that high chance of then developing infarct. (i.e warning sign). (traditional definition: hypocalcaemia (lack of Vitamin D) and phosphate retention (decrease in reabsorption) Thus secondary hyperparathyroidism and thus osteitis fibrosa cystica. Osteomalacia Due to less activation of vitamin D (I believe thus calcium decrease), Thus reduction in mineralization of bone Another cause is dialysis units which contain aluminum (bind osteoid and inhibit mineralization of bone) Can also be due to metabolic acidosis – get bone resorption and release of hydroxyapatite from the bone. (i.e you are releasing Ca2+ - another positive ion being exchanged for hydrogen, from the bone) Osteoporosis Usually due to steroid therapy (given to those with renal failure, especially those with glomerulonephritis) - Osteitis fibrosa cystica: Due to hypocalcaemia/phosphate retention and thus increased parathyroidism. Can also get amyloid deposition (B2 microglobulin) – associated with dialysis Paget’s disease (osteitis deformans) Epidemiology Can effect one bone but much more commonly it affects multiple bones. You get “collagen matrix madness” You have initial osteolytic phase (hence reduction in bone formation) Mixed phase: get both osteolytic and osteoblastic. However this is haphazardly laid down (which means that this is woven bone – see above) Osteoblastic activity prevails: thus you get gain in bone mass. Thus fibrosis of bone marrow and thickening of bone trabeculae (osteosclerotic phase – thus get mosaic pattern) Pathogenesis Unknown cause More common in whites Slow virus: paramyxovirus potentially implicated. Also genetic predisposition (18q is locus implicated in Paget’s disease) Morphology At late phase get sclerosis, thickening of bone mass. Especially affects skull and long bones Complications of Paget’s disease Fractures (because even though increase in bone mass, it is laid down quickly and haphazardly) Bone pain (due to fractures) Deformity (due to increased bone mass) Nerve or cord compression Deafness (due to compression of nerves) Osteoarthritis Heart failure (because have increase in vascularity of the bone – resulting in shunts) Rarely – can have malignant transformation (to osteosarcoma – makes sense, increase in proliferation) SUMMARY Abnormal matrix/osteoid: osteogenesis imperfecta (inherited) or acquired (osteoporosis) Abnormal mineralization: rickets/osteomalacia or renal osteodystrophy (I believe this is the main one, even though other 2 also) Abnormal parathyroid: osteitis fibrosa cystica Abnormal osteoclastic function: Paget’s disease or osteopetrosis (these 2 seem very similar, just seems to me like Paget’s difference is that the osteoblastic activity comes at the end rather than primarily) AVASCULAR NECROSIS (OSTEONECROSIS) This is due to infarction of bone and bone marrow. Due to ischaemia: (Can be vascular injury – usually tauma) thrombosis Steroids Radiation Alcoholism Idiopathic Major sites Head of femur and scaphoid bone. May be asymptomatic or associated with pain. If not treated then can predispose to severe osteoarthritis. Fractures/Tumours Fractures can be complete (where you get 2 fragments of bone) or incomplete (also called greenstick fractures. This is where the bone is cracked but not brocken into two pieces)* Often seen in young, immature bone (this is common in children) Theycan also be simple or compound. Simple = closed – the surrounding skin is intact Compound = open, the skin is broken and the bone may protrude through (thus risk of infection) They can be comminuted – where the bone is splintered into multiple bone fragments. They can be displaced – where the ends of the bone are not aligned . Spiral fracture = seen in twisting injury (common in dancers) Complicated = when there is injury to adjacent tissues (e.g blood vessels and nerves) Depressed fracture = commonly seen in the skull (where the fractures can compress underlying tissue – with risk of damaging the brain) Stress fracture (bone fracture after repetitive stress). E.g tibia, fibula and metatarsals (e.g athletes, dancers and army recruits) Pathologic fractures = fracture of a bone that has been damaged by disease. Pathological fracture Any condition that affects the bone, weakening it can result in this. Osteoporosis Osteomalacia Pagets disease Tumours (both primary or secondary) Congenial bone disorders e.g osteogenesis imperfecta. Fractures cont Incomplete simple fractures heal the most quickly. Communitated fractures are characterized by multiple fragments and so it will delay healing. Compound fractures communicate with the overlying skin and thus are more likely to become infected. Healing of bone You injure the blood vessels and thus you get haematoma formation (collection of blood) Then you get inflammatory phase (get neutrophils, then macrophages and then granulation tissue formation). This is called procallus (remember this is fibroblasts and blood vessels) (formation of granulation tissue at the site of the fracture) Osteoprogenitor cells give rise to osteoblasts which migrate to the site of the granulation tissue. They proliferate and produce osteoid. You get external callus bridges at the fracture site and outside of bone, internal callus bridges the fracture in he medullary cavity. You get ossification (need it to make the bone strong) This bone is formed quickly and thus it is woven bone. Therefore you need to replace it with lamellar bone. This is called remodeling. Factors that affect healing of bone fracture Type – e.g simple heals more quickly than comminuted and compound Alignment (if not aligned then impaired healing) Degree of immobilization – need it for callous formation (excessive movement stops this – this is why we use plaster of paris in fractures) Interposition of soft tissue Blood supply – because inflammatory phase involves tiny blood vessels. Steroids (because they are anti inflammatory – remember all healing is reduced with steroids) DM (due to lack of poor blood supply, poor function of macrophages and prone to infection) Nutrition – D for calcium deposition, C for function of fibroblasts. Infection Age – due to poor blood supply. Malignancy. Complications of fracture Delayed union Malunion Fibrous union (where you have fibrous tissue instead Non union (failure of 2 ends to meet) Aseptic necrosis (infarction of bone and bone marrow) Osteomyelitis (infection of bone and bone marrow) Treatment of fracture Immobilization (either internal fixation – plates/screws) External – plaster of paris. OSTEOMYELITIS This is inflammation of bone and marrow due to infection. Bacterial infection = most common cause. Mycobacteria (Tb), fungi, viruses and parasites Pathology Can spread from bloodstream to extra-osseus site Direct extension from neighbouring site Direct inoculation (e.g traumatic or surgical) Most common cause = staph aureus. E.coli, pseudomonas and klebsiella can occur in patients with GU infection and drug abusers. Patient with sicke cell disease are also prone to osteomyelitis – commonly due to salmonella. Strep B = most common in neonates. (Makes sense – just like it can cause neonatal meningitis) Many of the non haematogenous cases are caused by mixed flora and/or anaerobes. (Again, makes sense – spreading straight from outside world) The initial focus of inflammation (in children) is in the metaphysic (as this is the best vascularised part of the bone in children). Overall osteomyelitis is most common in children Most common (in adults) = vertebrae. When you have osteomyelitis you have necrosis of the bone (necrotic bony fragment is called sequestrum) Reactive bone formation The adjacent bone is trying to heal itself (termed involucrum) Clinical features Often a child (more common) Fever, malaise, bone pain and tenderness. Also reduced movement of limb. Dx Blood culture = best test Blood tests: increased WCC, ESR and C-reactive protein Radiography (can see lytic lesions but it takes time – changes are late) Either ultrasound or MRI = best dx Bone scan hot spot is useful and bone scintigraphy for difficult cases. Complications of ostemyletitis Abscess formation (called Brodie’s abscess) Continuous bone formation – (called Garres sclerosing osteomyelitis) Sinus tract formation – Can get chronic osteomyelitis Can get pathological fractures Can get amyloidosis (in the chronic condition) Bacteraemia. Tx of osteomyelitis Antibiotics and then PO May also need to do surgical drainage. Tuberculous ostemoyelitis It is rare in developed country. Occurs by haematogenous seeding from extra osseous sites. Most common site is the spine (Potts disease) Get granulomatous inflammation of affected bone (just like any Tb infection) Very difficult to tx. BONE TUMOURS Classification: Benign Malignant (primary or secondary) Most common tumour in tumours/young adults are primary benign bone tumours Most common in older adults = multiple myeloma and mets from other sites Metastatic tumours Common ones are carcinoma of breast, prostate, renal or bronchogenic lung carcinoma. The can be either osteolytic (bone destruction – either due to direct bone erosion or due to stimulation of osteoclasts by cytokines or osteosclerotic (e.g prostatic adenocarcinoma – can cause bone formation) Complications Pain Pathological fracture Replacement of bone marrow (can get anaemia, infection, bleeding etc) Hypercalcaemia (I imagine due to resorption of bone???) Nerve and spinal compression Myeloma There is primary malignant proliferation of plasma cells in the marrow. (see other lecture) Primary bone tumours Primary benign tumours = more common in children and young adults. Primary malignant tumours = more common in elderly. Accurate dx depends on clinical, radiologic and pathologic examination of lesion. Classification Can be bone-producing or cartilage producing (As well as others) Bone forming tumours Can be benign, malignant or locally aggressive (in between) Benign – can be osteoma or osteoid osteoma Locally aggressive (can be osteoblastoma) Malignant (ostesarcoma) Osteoma This is a benign bone forming tumour. Usually seen in craniofacial location. Probably a harmatoma (some people believe) Multiple association are associated with Gardners syndrome (type of FAP) Osteoid osteoma This is a benign bone forming tumour. Seen in young. (More prevelant in men) Painful (due to production of prostaglandin). Characteristically relieved by aspirin. Commonest in femur or tibia. Charectirsed by a nidus (small focus of blood vessel proliferation). In this site the cells produce prostaglandin (hence can be inhibited by aspirin, causing the pain to be relieved) Therapy = complete excision of nidus. Osteoblastoma This is a benign bone forming tumour. Seen in younger age. Most commonly seen in vertebral column No sclerotic reaction Pain is NOT relieved by aspirin Therapy – curettage/resection. Malignant tumours Ostesarcoma This is a malignant bone forming tumour. Has bimodal age distribution. Seen in young and elderly (i.e 2 peaks) Effects the end of the bones. Most arising from the metaphysic. This is because it is the most metabolically active part of the bone Pathogenesis of osteosarcoma Cabe sporadic or genetic (Rb, p16 and p3 have been implicated) Secondary osteosarcoma can be associated with radiation and pagets disease Clinical features of osteosarcoma Tenderness and/or pain in affected region. Fracture (since the bone is weakened – you can get a pathologic fracture) Distant mets – commonest is lung. Spread Can spread within medullary cavity Through the periosteum Can spread across epiphyseal plate (into the joints) Haematogenous. Osteosarcoma There are characteristic X-ray features in osteosarcoma. Codmans triangle and sunray speculation. Makes sense because this is a bone forming tumour – and thus the osteoid can be deposited perpendicular to the bone (Hence called sunray speculation). You get the codmans triangle due to lifting of the periosteum. Treatment Patients usually treated pre-operatively by chemotherapy and surgical resection. Prognosis = poor – due to early metastasis (60% 5 year survival rate) CARTILAGE PRODUCING TUMOURS Osteochondroma These are bony lesions with a cartilage cap. Seen in young patients - 40) This is a malignant tumour of cartilage This is the second most common primary malignant tumour of bone (half after osteosarcoma) Often associated with tiny calicifications Can occur de novo or from a previous benign tumour Axiel skeleton (bones of pelvis, shoulder, ribs and spine) are most common.. This is an aggressive tumour which can metastasize anywhere (lungs, kidney, liver and brain are most common) They are NOT sensitive to chemotherapy (only tx is resection). (Unlike osteosarcoma which can be sensitive to chemotherapy) Comparing osteosarcoma with chondrosarcoma: Osteosarcoma = 10-25 years and elderly (Chondrosarcoma = >40) Osteosarcoma = Affects long bones (chondrosarcoma = affects axial skeleton) Osteosarcoma = Sensitive to chemotherapy (chondrosarcoma = NOT sensitive to chemotherapy). Giant cell tumours (osteoclastoma) Occurs in adults (20-55). Affects the epiphyseal ends (rather than metaphysic) of long bones. There are stromal cells and multinucleated osteoclast like giant cells It is a locally aggressive tumour (with high recurrence), may also metastasise. May also cause haemorrhage which makes sense – since these are osteoclasts and are breaking down thte bone. (4% metastasise). (I.e this is a benign tumour but it may metastasise infrequently). Not easy to know whether it will metastasise or not based on histological indicators. Ewings sarcoma These are neuroectodermal Seen in children and young adults. Site is medullary cavity (rather than metaphysic or epiphysis) in the diaphysis of long bones, pelvis and ribs. There is a translocation involving chromosome 11 and 22. It is characterized by the proliferation of small blue cells (called this as there is very little cytoplasm and large nuclei). Note these are known as small round cells of childhood, i.e this is another neuroblastoma – e.g nephroblastoma, retinoblastoma, medulloblastoma – all characterized by these small blue cells.) Characteristic Xray is onion skinning. It is highly aggressive and chemotherapy resistant. With the advent of chemotherapy and surgery then survival has increased, but overall poor prognosis. Joints Joints can be synovial or non synovial. They are a type of connective tissue. Synovial - = movable joints e.g knee joints. Non synovial joints – allow very limited movement but structural movement (Cartilagenous – e.g intervertebral disks) and fibrous (e.g cranial sutures) Structure of synovial joints The articular surface is covered by haline cartilage – and the healing is poor. The cartilage acts as a shock absorber between the bones There are cells called chondrocytes which produce the matrix. They also produce enzymes which degrade the matrix. The matrix is made up of collagen type II (compare this to the collagen type one that is found in bone matrix), proteoglycans and water. The joint is surrounded by a capsule – which is rich in nerves (hence this is pain sensitive). The synovial joints are supported by ligaments and bursa (which is a fibrous sac that acts as a cushion to ease movement in areas that are subject to friction). The whole synovial cavity there is a synovial membrane The synovium lacks a basement membrane (therefore there is a quick exchange between blood and synovium). It contains 2 cell types. Type A synovial cells are macrophage-like and type B synovial cells are fibroblast like (and produce protein) The function of the synovial fluid is for lubrication and nourishment for the cartilage. Synovial fluid It is normally colourless and transparent WBC = males It is a oligoarthritis (i.e single joint is usually affected – unlike the polyarthritis in regular RA) Affects the large joints – especially the knees (unlike the small joints in RA) Lymphadenopathy and splenomegaly RF is usually negative but ANA is usually positive. RHEUMATIC FEVER Remember it is an acute or recurrent inflammatory disease which is usually secondary to group A strep. Joint disease – classically a migratory arthritis (Affects one joint, then moves to another etc) Usually affects large joints (knees, elbows etc) and pain There is usually no deformity SLE This is a systemic autoimmune disease There is usually minimal joint deformity. It results in a non erosive synovitis SERO-NEGATIVE SPONDYLOARTHRITIS A group of diseases with negative RF There is involvement of the sacroiliac joint and spine (sarcoilitis and spondylitis) Usually affects patients with HLA-B27 Ankylosing spondylitis, reactive arthritis (such as reiters syndrome and enteropathic arthritis) and psoriatc arthritis Ankylosing spondylitis (bamboo spine) This is a chronic inflammatory disorder of lumbar spinal and sacroiliac joints. There is fixation and fibrosis of the spine – (which is why it is called bamboo spine) Often affects young males. Most have HLA B27. They have autoantibodies directed at joint elements after infection. Peripheral arthritis, uveitis, aortic incompetence and amyloidosis can occur. Reiters disease/reactive arthritis It is an autoimmune reaction following especially Chlamydia infection Useful pneumonic = patient cant see, cant pee and cant bend the knee. Can also be due to salmonella, shigella, yersinia and campylobacter Defined by triad of arthritis (affecting knees, ankles and spine), urethritis or cervicitis and conjunctivitis Enteropathic arthritis This occurs with chronic inflammatory bowel diseases (UC/Crohns) (remember the non GI problems that these patients can get) It can also occur following a bowel infection – e.g after salmonella, shigella, yersinia and campylobacter Psoriatic arthritis Affects 5% of patients with psoriasis. Arthritis which affects the distal interphalangeal joints, ankles, knees and spine Again HLA-B27 is implicated INFECTIVE ARTHRITIS Haematogenous spread = most common Spread from adjacent infective foci – (e.g osteomyelitis) Direct inoculation – local trauma and insertion of surgical prosthesis Suppurative arthritis Staph aureus (most common in both young and old) Haemophilus influenza = in young children Gonoccocus (in healthy young sexually active individuals) Strep, E.coli, pseudomonas and salmonella can all be causes as well. Clinical features Acutely painful Sweollen joints Fever Decreased range of motion Increased WCC Joint aspiration Not really recommended as you can spread the infection. Yellow/green and purulent WBC > 50,000 Polymorphs = >75% (makes sense – as mostly bacterial) Gluocse < blood (makes sense – the bacteria are using up the glucose) Gram stain + culture = often positive TUBERCULOUS ARTHRITIS Spread from adjacent tuberculous osteomyelitis or haematogenous spread Spine = most commonly affected (Potts disease) followed by the hip. It can cross cartilage barriers (unlike other bacterial infections) There is a destructive arthritis and deformity There is granulomatous inflammation LYME DISEASE Transmitted by tic. Borrelia brgdoferi = pathogen. It can also cause arthritis. Remember skin manifestation – erythema migrans (seen at site of tic bite) Second stage = CNS and heart involvement Late stage = when you get destructive arthritis. GOUT ARTHRITIS (Note used to be called a disease of kings, because meat and wine cause it, which is more expensive) Males > females Peak incidence = in 5th decades ¼ arfamilial It is a disorder of purine metabolism which results in hyperucricaemia. Serum urate level is above 7mg/dl Hyperucricaemia can be primary or secondary Primary Can be due to undersecretion of uric acid (90%) Overproduction of uric acid Risk factors Age (rare before 30) Family history Alcohol consumption Obesity Meat etc Secondary gout Secondary – affects 10% of cases. Due to overproduction of uric acid usually associated with excessive breakdown of nucleic acids (e.g due to leukaemia, multiple myeloma and massive cell lysis that results from cytotoxic drug therapy). Renal undersecrteion (e.g renal failure, diuretics (Both thiazide and loop. Remember loop = hyperurcaemia, hypocalcaemia, hypokalaemia while thiazide = hypercalcaemia, hypocalaemia and hyperuricaemia. Potassium appearing = hyperkalaemia) Can also be due to an enzyme deficiency – (Hypoxanthine guanine phosphorybosyl transferase (HGPRT) – this is important in uric acid metabolism. Pathogenisis of gout You have deposition of urate crystals on the surface of the articular cartilage This results in interaction with leucocytes which result in degenerative changes. Classical joint affected = big toe. (Metacarpophalangeal joint of big toe). ¾ affecrting the ig toe with first attack. (Note that apparently external joints are more readily affeceted because these joints are more typically colder and therefore the uric acid is more readily able to precipitate). Sometimes there can be deposition of uric acid in tissue which results in tophus formation (gouty tophi) – commonly in ear lobe. (Remember, differential is calcinosis and I imagine also rheumatoid nodules?) They occur in chronic hyperuricaemia and is due to the deoposition of uric acid in tissue. Stages of gout You have an acute inflammatory arthritis and asymptomatic periods in between the attacks. Eventually it becomes a chronic inflammatory conditions You have chronic deposition of urate in and around the joints (Known as tophi) Complications of gout Interstitial nephritis Renal calculi (made of uric acid) Renal failure Diagnosis Need to examine aspirated synovial fluid. It will show needle shaped crystals and neutrophils. Can do synovial biopsy. Note that don’t put tissue in formalin container (as the crystals will dissolve in this, thus have to put it in alcohol). Treatment Colchicine (remember, this is a drug that binds to tubulin and causes damage to mitotic cells. Hence also used for cancer – and side effects = anaemia and neutropenia for this reason, it is killing rapidly dividing cells. However, it also inhibits uric acid deposition and for this reason it is used in gout). It is also an anti inflammatory effect – due to slowing down the immune response – I imagine this is again due to the white cells are rapidly dividing) Allopurinol (this inhibits uric acid synthesis) (It is a purine analogue that binds to the enyme. It is not useful for acute gout but is more useful for chronic treatment = to lower the uric acid levels in the plasma. It is commonly used in prophylaxis for patients who are receiving chemotherapy. Makes sense, as the chemotherapy is likely to increase the uric acid levels). PSEUDOGOUT Also known as chondrocalcinosis This is the deposition of calcium pyrophosphate on arcticular cartilage. (I.e different crystal deposition) Most commonly seen in over 50’s Classification They are classified into primary (idiopathic), hereditary and secondary (due to hyperparathyroidism, hypothyroidism, haemochromatosis and DM) Pathology Asymptomatic until the crystals are shed into the joint space (spontaneous or due to trauma) Unlike the crystals in gout, the crystals here are rhomboid in shape. Hypertrophic osteoarthropathy This is new bone formation at the distal ends of the long bones, especially the metacarpal and metatarsal bones. It is a syndrome of painful, swollen joints, cubbing of the digits and the above. (I believe it is clubbing with these other things associated) Rarely it appears as an idiopathic disorder but the main significance is that there is usually underlying disease – (usually bronchogenic carcinoma). TUMOURS OF THE SOFT TISSUE Extremely rare. They are tumours of mesenchymal origin. (mesenchyme is the conncentive tissue of fetal and developing organs which will develop into the stroma) and are classified based on their histological differentiation. They can be benign or malignant Pathogenesis Poorly understood but risk factors Radiation, viruses (e.g kaposis sarcoma) and genetic syndromes (e.g li fraumeni) Classification of soft tissue (benign and malignant) Tuours of adipose tissue = lipoma and liposarcoma Tumours of smooth uscle = leiomyoma and leiomyosarcoma Tumours of skeletal muscle = rhabdomyoma and rhabdomyosarcoma Fibrohistiocytic tumours = fibrous histiocytoma and malignant fibrous tumours Vascular tumours = haemangioma and angiosarcoma Peripheral nerve tumours = neurofibroma and malignant peripheral nerve sheath tumours Tumours of uncertain histiogenesis e.g synovial sarcoma (not does not originate from synovium – uncertain origin) More information about the soft tissue sarcomas Note – this is not that important, main thing is to know the prognosis. Malignant fibrous histiocytoma This is the most common malignant soft tissue tumour of adults. Usually occurs in deep soft tissues of an extremity. More common in adults over 50 Liposarcomas Second most common. Characterized by presence of lipoblasts Rhabdomyosarcoma Tumours with skeletal muscle differentiation Most common sarcomas of childhood/young Charactersed by rhabdomyoblasts Synovial sarcoma Typically affects young adults. Occur in proximity to joints but do not arise from the synovium. Pathogenesis of soft tissue sarcomas Need to know this Histologic type Tumour grade: (as any type) Degree of differentiation, cellularity, pleoorphism, number of mitoses, presence of necrosis Stage of tumour Location (the more superficial have a better prognosis) Dx Histologic examination Immunohistochemistry. Nearly all vimentin positive (remember from last year, vimentin in all sarcomas) Leiomyosarcoma (desmin and actin positive) Rhabdomyosarcoma (myoglobin positive) Molecular dx – some have specific genetic abnormality (e.g Ewings sarcoma – t(11;22) and synovial sarcoma = t(X;18). I.e specific. There are others as well. GISTS Remember these originate from the interstitial cells of cajal. Remember that most have mutations in c-kit (a protooncogene) and gleevec is a selective c-kit receptor inhibitor. Remember this is also used for CML (chronic myeloid leukaemia) Skin diseases There is a wide range of conditions – from inflammatory to neoplastic. It is a common reason for consultation to GP’s Skin neoplsms rarely poste threat to patients life. The exception is a melanoma. Pigmented skin lesions are common but they are not necessarily melanoma (e.g some squamous cell carcinoma can have melanocytes in it but it is not a melanoma). They may sometimes be clinically distinguished, but it may be difficult. Some benign lesions that form a tumour are not true lesions (e.g malformations, harmatomas, infection (i.e warts) or cysts. Structure of skin The layers from superficial to [email protected] Stratified squamous epithelium. This is specialized for keratin production and is exposed to UV light. It also contains melanocytes and Langerhans cells (which are specialized antigen presenting cells). Dermis Subcutaneous fat. Stratified squamous epithelium There is a layered, orderly maturation from the base to the surface. There is a basal layer of small dark round cells. The superficial layers flatten and acquire more abundant cytoplasm and produce keratin Dysplasia = showing disorderly maturation and abnormal cytological features. UV light (especially UV-B) causes DNA damage. Melanocytes These are neural crest in origin. They migrate at 6 weeks in utero to the skin. They produce melanin pigment and the melanin is transferred to adjacent squamous cells. The melanin protects the nucleus of squamous cells against UV damage to the DNA. (Hence this is the reason why in human evolution those that lived closer to the equator/hot countries developed darker skin (in order to protect themselves from skin cancer etc) Dermis This is a loose connective tissue which supports the epidermis. It contains: Fibrous and adipose connective tissue, blood and lymphatic vessels, nerves, smooth muscle (to control blood vessels, arrector pili – the smooth muscle that makes your hair stand on end – etc). Additionally there are inflammatory cells (lymphocytes, macrophages, mast cells etc) Skin appendages (e.g sweat glands, sebaceous glands, arrector pili etc) Can get tumours of any of these – they are generally benign. E.g can get haemangiomas, lyomyomas, neurofibromas, scwannomas, dermatomycomas, skin appendage tumours etc Skin appendages Pilo-sebaceous units e.g hair follicles and attached sebaceous glands. There are also sweat glands If the epidermis and superficial dermis is damaged/removed then the epidermis will regenerate from surviving skin appendage epithelium (Hence you can do a split skin graft and there can be regeneration. Additionally if you burn off the epidermis then it will regenerate, while if you burn off deeper layers then there is no regeneration) Skin tumours These may be benign or malignant May arise from epidermis (i.e squamous cell carcinoma), melanocytes (i.e malignant melanoma), appendages or the dermis (from any of its constituent elements e.g haemangioma, schwannoma etc) The treatment of benign lesions is usually cosmetic (or to exclude malignancy). Malignant tumours of the skin may be locally aggressive (i.e grow and destroy the area they are in). However only very rarely will they have the potential to metastasise. The exception to this, however is a melanoma. Also note that malignant skin tumours are usually primary and you ill only develop secondaries very late when there is a disseminated primary malignancy. Primary skin malignancy Squamous epithelium = much more common. They are basal cell carcinoma or squamous cell carcinoma. Collectively they are known as non-melanoma skin cancer. Melanocytes = much less common origin for malignancy. However if it is not identified early enough it poses significant risk for metastasis. Also other types of primary skin malignancy (from dermal elements – e.g lymphoma, appendages etc. These are rare though). NMSC may be locally invasive however they rarely cause metastasis or death. Melanoma however is more aggressive and the outcome depends on stage at dx. Skin malignancy = related to UV-B light exposure: Light skin, fair, red hair, pale eyes, tendency to freckling are prone to developing freckling. Outdoor work especially in areas in the equator SCC is related to cumulative exposure (you usually also see some other UV related skin damage) Most melanoma however is NOT related to cumulative exposure but instead to intense, intermittent exposures BCC appears to be intermediate UV-A is also important (which is used in sunbeds and to tx psoriasis patients). Epidemiology of skin cancer NMSK = commonest cancer but rarely causes death (I think). Melanoma on the other hand (although is much rarer) causes far more deaths (than NMSC) Epidemiology of NMSC Incidence is strongle linked to age. (most occurring >65 years old) Often multiple and usually in sun-exposed sites. I.e face, legs, ears, nose, scalp (in bald men) etc Small numbers will be on difficult areas to excise e.g eyelid, BCC is exceptionally rare cause of metastasis. SCC are uncommon cause of mets/death (however much more common than BCC). Mainstay of treatment is local excision. Basal cell carcinoma It is derived from squamous epidermis What characterizes it histologically are basal cells thataare palisading (i.e at the edge of the groups of tumour cells, the cells and nucli are arranged in parallel) Metastasis = incredibly rare There can e local invasion with lisk of local destruction. (especially near the nose and eye – termed a rodent ulcer) Different histological types are less or more prone to recurrence – and this guides treatment) Risk factors UV light (UV-B), radiation, immune suppression. Age and faire skin Treatment Surgical excision. Mohs micrographic surgery if high risk (this is where you take slices (you remove as much as you can see, then you takiceand look at them under the microscope, if you see tumour then you take another slice, wheras if you don’t then you stop).. Useful for tricky arlocal destruction eas, or recurrent tumours etc. Local destruction (cryotherapy, electrosurgery, radiotherapy etc) Topical treatment – with 5-fluorouracil (an antimetabolite) or imiquimod. (This is an immune modulating drug which is felt to help by altering immune targeting of the tumour) High risk cases require specialist treatment (e.g if difficult to define, recurrent, post radiation or large. As well as critical sites (mid face including eyes, nose etc) Invasive squamous cell carcinoma Derived from squamous epithelium of epidermis Shows differentiation towards keratin production. Metastasis can occur (but rare and late) Overall good prognosis If does metastasise then will go to regional lymph nodes. Poorer prognosis – if lip, deep tumours and arising in non-sun damaged skin (e.g genital area) Also poorer if arising from chronic ulcers or skin disease Tx = excision. (Tend not to do the cryotherapy, electrotherapy etc that you get with basal cell. Probably because more risk of spread/invasion?) Histological hallmark = keratinisation Risk factors By far, sun exposure = most important risk factor. Historic (chimneysweapers being at risk for scrotal SCC – due to hydrocarbons) Radiation treatment (over irradiated areas) Edge of old scars, burns, sinuses, chronic ulcers etc (Makes sense – as rapid turnover etc there) Genetic – e.g xeroderma pigmentosum (being unable to repair UV induced DNA damage – hence lots of skin cancer) and people with albianism (makes sense, as lack of protectivemelanin) Immunosupression – post transplant, HIV – related to specific HPV types (not the common HPV that causes warts (I imagine that this is because not immunosupressed individuals will not get infected by these HPV virii) Common HPV infection = NOT risk factor. Dysplastic epidermal lesions These show varying degrees of dyplasia but do not show invasion. They can develop into invasive SCC (but unlikely and long time) Tend to present as irregular crusted, keratotic lesions (or red patches) Actinic (solar) keratosis This is epithelium that shows dysplasia (ranging from mild to severe) but short of in situe SCC. Bowens disease This is the term for in situ squamous cell carcinoma (i.e full thickness dysplasia/ keratosis) This seems to be a rather flat lesion – which makes sense since it is a carcinoma in situ. Pigmented skin lesions Melanoma = typically pigmented. However not all melanomas are pigmented and not all pigmented skin are melanomas. (e.g BCC, keratosis etc). Vascular lesions are usually blue/red rather than brown Thus can be difficult to diagnose. Thus important to send all lumps and bumps to pathology. Benign melanocytic lesions Freckle - ephelisFreckle – ephelis This is a localised area of increased melanin production. It is induced by the sun but there are no increase in melanocytes Benign lentigo This is a flat lesion with increased numbers of melanocytes in the basal layer of the epidermis. They are fixed but may sometimes be promoted by long term sun exposure Melanocytic naevus (pigmented mole). This is a clonal proliferation of melanocytes as nests Naevus Naevus = benign proliferation of skin element (commonly refers to melanocytes – i.e mole) Implies a pigmented lesion which is present at birth Commonest example is melanocytic naevus (which may be congenital or aquired). Normally you stop producing naevi after 20 (if new naevi are formed after then you should be converned).. The lesions evolve with time – the location of the nests, amount of pigmentation and degree of nodularity typically change with time. They can be junctional (confined to basal layer), compound (basal layer and epidermis,. May be slightly raised) or intradermal (they are only in the epidermis, usually form raised areas) MALIGNANT MELANOMA Can be aggressive and life threatening Doesn’t cause high amount of deaths, but potentially easily recognised. Also even though it is more common in elderly, it does not infrequently affect the young. Usually associated with intense sun exposure not cumulative. Can arise in sites outside the skin. E.g eye (most common malignant tumour affecting the eye), meninges, mucosa etc. Does NOT always produce pigment (i.e can be amelontic). There has been a rise in incidence (with travel of fair skinned people to hot countries) as well as increased detection. It is an important dx (even if early – for insurance problems etc) Development Goes through stages. Goes through in situ (confined to epidermis) – which is always cured. (i.e in these they grow upwards into the epidermis) Some of the in situ tumours will invade into the dermis (and then into the subcutaneous fat). From there they can spread through the lymphatics to other sites (e.g skin, local lymph nodes) and by blood stream to liver, brain etc. Can also spread within skin and form satellite tumour nodules (which is why wide excision of invasive melanoma is therefore performed) Note that these tumours can be problematic, can be bizarre (e.g can excise melanoma, live 10 years and then present with a met) Prognostic factors Stage Most important If there are mets (lymph nodes or distant). Distant mets = very bad prognosis, lymph mets then poor prognosis If the melanoma hasn’t metastasised then thickness Breslow thickness If no mets (i.e only primary lesion) then the thickness of invasion becomes important. Best single thing for prognosis. 2mm thick (about half way through the dermis) then drops to 50% 5 year survival. Clarkes level of invasion This was related to the level of invasion (was used, but in reality corresponds to thickness. Other prognostic features Ulceration = bad, mitosis. Presence of tumour infiltrating lymphocytes then this is good. Histological classification Not that important because doesn’t have independent outcome in Superficial spreading (where an in situ component can be identified), nodular (invasive at the outset), acral (palms, soles and nails, rare but commonest form in black people – as they don’t get them elsewhere (I imagine because these areas are relatively unprotected, with paler skin), lentigo maligna melanoma (invasive melanoma developing in sun exposed skin on background of lentigo maligna) Also note lentigo maligna (hutchinson melanotic freckle) – this is a big flat pigmented lesion (related to chronic sun exposed skin – especially in face of elderly). Evolves towards in situ malignant melanoma (but low frequency will become this) Treatment of melanoma Primary excision of any suspicious lesion. (However don’t do incisional biopsies or shave/hit etc it, as it can alter the morphology) If it is melanoma then do re-excision to get clear margin. (As there is risk of satellites). The margin of clearance relates to tumour invasion. If more than 1mm in thickness then do sentinel lymph node biopsy (assessing for subclinical lymph node metastasis). Remember that purpose is to target the single lymph node that if one were to be involved you can targe it, rather than take out all the nodes and get lymphoedema.) – you inject blue die and radiolabel and see which nodes light up (nodes where tumour would have first spread – then remove them and check for metastatic deposits. (If doesn’t have met then unlikely that other nodes have met) Note that not therapeutic (possibly marginal). Mainly done for prognosis 1/3 of melanomas arise from preexiting melanocytic naevi however most don’t. Also note that any single naevi (even if they are strange, big etc) it is unlikely to become a melanoma. Also very rare families with high risk melanoma have unusual clinical features. E.g atypical multiple moles and melanoma syndrome (have dysplastic naevi). Risk factors: fair skin, tendancy to freckle and burn, blue eyes and red/blonde hair. Congenital naevi: risk depends on size (only significant if very large) Multiple dysplastic naevi (increased risk) No excess risk in typical sporadic naevi or small congenital naevi. Early detection Clinical suspicion A,B,C,D,E A = asymmetry B = border irregularity C= colour variation D = diameter >0.5cm E = expanding However most moles = harmless. Sequential photography may help. Other worrying singns = changing moles, new moles (beyond young adulthood), irregular outline, bleeding, ulceration and development of satellite lesions. Calcium metabolism Normal calcium homeostasis Remember that the bones that support us are not static. There is a constant turnover. We absorb calcium from the diet, it is present in the ECF, soft tissue and bone etc. We are constantly laying down calcium in the bone – as hydroxyapetite (as calcium phosphate) and we are absorbing the calcium from bone Also, it is removed by the kdieny. Bone is the resevoir of calcium (hence the reason why when you have disorders of calcium then it will affect bone). Calcium is bound in plasma. Half is free (1.1mmol) – this is the biologically active form About half is bound mostly to albumin (about 1 mmol). With total being about 2.4 (other bound in other proteins as well as bicarbonate and phosphate). This is another resevoir of calcium. Thus when albumin falls then the total calcium falls. (Most simple/cheap method of calcium measurement measures the total calcium). (However point of care testing – e.g in ICU, the blood gas analyser (in all the electrolytes – compared to lab result), then it measures free calcium – which is about half the total calcium). Note that no pathological conditions that give high albumin. Note that there are various formulas that you can use to correct the ionised calcium for when albumin falls. Also note that free calcium can be displaced from albumin by hydrogen ions. Thus in acidosis you will have higher calcium in the ionised fraction. In renal disease you get total fall in calcium. This is due to a combination of lack of vit D activation and phosphate increase (which causes fall in calcium) However note that renal disease can also cause metabolic alkalosis (which causes an increase in the proportion of free ionised calcium (I.e kind of like a correction, although not really as it is a disease process). Thus if a patient with renal failure develops tetany, confusion etc then don’t be immediately tempted to give calcium (as this may be due to the uraemia rather than the calcium as the free calcium may not as low as you may think it is – if patient wasn’t acidotic). Factors affecting plasma calcium concentration That is, the total concentration. Plasma albumin concentration (see above Dietry calcium intake/urinary loss Hormones + vitamins Parathyroid hormone Vitamin D (active – dihydroxy vitamin D) – depends on dietary intake and intestinal absorption Calcitonin. (Doesn’t have a big role in physiological regulation, but can be used exogenously to lower calcium) End organ function – e.g celiac disease (causing impaired absorption), renal disease (impair hydroxyilation of vit D), liver (the same, hydroxylation),parathyroid glands (e.g adenoma etc) Action of parathyroid hormone It is a protein that stimulates osteoclasts in bone. This results in bone resorption (which releases calcium AND phosphate from bone). In kidney – it activates 1 alpha hydroxylase – which results in hydroxylation of 25 hydroxy vit D to 1,25 hydroxy vit D. (Note that 25 hydroxy vit D is a kind of “storage form” of vitamin D – as there are much higher concentrations of it) It also enhance the reabsorption of calcium from the renal tubules, but it also inhibits phosphate reabsorption. This is significant because plasma calcium and phosphate are at a concentration close to saturation point. (Thus if you alter the concentration of one then it will precipitate – calcium and phosphate). Thus if you increase calcium AND phosphate in plasma then you will get calcium phosphate precipitation (especially in kidneys – resulting in nephrocalcinosis). Thus by increasing calcium but decrease phosphate then this does not happen. Thus overall effect is increase calcium conc and decrease in phosphate conc. Vit D structure and synthesis Remember you have vit D3 (generated through sunlight) Vit D2 – This comes from ergosterol (a plant source) (Vit D2 or D3 ) is then metabolized in the liver to 25-hydroxycholecalciferol (by 25hydroxylase) In the kidney it is metabolized to 1,25 dihydroxycholecalciferol (1,25 hydroxy vitamin D) – which is the active form. The half life of the 25 hydroxy form = several weeks while the 1,25 dihydroxy is only a few hours. Note that have to have very extensive liver disease before you will have fall in 25 hydroxy vit D. (Thus most patients with liver disease do not have fall in vit D). Note that there are other forms of vit D that are not biologically active. Note that anticonvulsants – e.g phenytoin will enhance the hydroxylation of 25 hydroxy vit D to number of non active forms. (Hence metabolic bone disease/osteomalacia can result. Control of calcium concentration Parathyroid glands release parathyroid hormone in response to lowered calcium level. This acts on bone to increase bone resorption (increase in calcium in phosphate). Thus by negative feedback it reduces parathyroid hormone level. Also acts on kidneys to increase conc of 1,25 vit D, increased calcium in tubules. The active Vit D will also increase calcium absorption. Disorders of bone Pyerparathyroidism Primary, secondary or tertiary. This increases Decreased bone mineralization Osteomalacia (in adults) and rickets (in children) E.g vit D deficiency and malabsorption. This is associated with low plasma calcium levels. Reduced bone matrix (type 1 collagen and proteoglycan remember) Osteoporosis Postmenopausal and senile osteoporosis. (also due to slight reduction in 1,25 vit D due to reduction in renal function) This does not cause a disturbance in plasma calcium levels. Disordered bone mineralization I.e Pagets disease of bone. Disorder of osteoclast and osteoblast function (these 2 cell types no longer work in tandem, hence disorgonisation of bone mineralization). BIOCHEMICAL INVESTIGATIONS TO DX METABOLIC BONE DISORDERS Plasma Calcium – should be measured with albumin. (So can interpret total albumin/free albumin levels etc.). Note how sample taken is important. (Ideally should take off tourniquet for 20 seconds before taking the sample (so that you don’t concentrate the vascular compartment – due to increased pressure causing movement of water out of vascular compartment) Phosphate (increases in patients with renal glomerular damage) – hence need to know what renal function is (either creatinine or urea). Alkaline phosphatase (bone isoenzmye) – marker of osteoblastic activity (remember that this is also in the liver and other places) PTH 25-OH vit D (don’t measure active vitamin D routinely due to the low levels of the active form, so more expensive) Urine Calcium and phosphate Pyridinoline and deoxypridinoline (markers of osteoclastic activity) – thus along with alk phos can have knowledge of osteoblastic and osteoclastic activity. How to investigate the disorders If plasma calcium is high – then look at plasma phosphate. If have normal then would suspect hyperthyroidism or hypervitaminosis (not sure why hyperthyroidism would cause this, but TFT’s would naturally be used to dx hyperthyroidism) If it was low then you would suspect hyperparathyroidism (makes sense – high calcium but low phosphate – which is what parathyroid hormone does). You would do an X-ray to look for cystic lesions (subperiosteal erosions in terminal phalynx – early sign, eventually can go on to get osteitis fibrosa cystica). Also naturally do PTH hormones. Can also be malignancy since some tumours can produce parathyroid like hormone. (Thus in this case the parathyroid hormone will be undetectable) If low calcium and low phosphate then differentials could be secondary hyperparathyroidism due to vitamin D deficiency (i.e low calcium that is then causing too much parathyroid hormone which decreases phosphate levels). Hence makes sense to measure the vitamin D levels. low calcium but normal/high phosphate suggests hypoparathyroidism (makes sense – not enough calcium reabsorpion and too much phosphate reabsorption) It can also due to renal failure (causing a secondary hyperparathyroidism) – in this case the calcium would be down, however the phosphate would be up due to decreased reabsorption. Clinical presentations of hypercalcaemia General Non specific ill health (malaise, weakness, vomiting). Most patients picked up through routine screening now. Psychiatric disturbances (“groans” Renal Polyuria and thus polydypsia (along with hypokalaemia, as inhibit concentration mechanisms) Renal stones and nephrocalcinosis (“stones”) – makes ses Bones Bone pain (“bones”) Abdominal (“abdominal moans”) Constipation (increases gastrin release) Duodenal ulceration Cardiac Dysarrhythmias – (Prolongation of latent phase I think?) Differential dx of hypercalcaemia Hypercalcaemia associated with low plasma phosphate Primary hyperparathyroidism (e.g adenoma), causing bone resorption and calcium goes up, and phosphate goes down Malignancy (ectopic hormone production – PTHrP) Tertiary hyperparathyroidism (after treatment of secondary hyperparathyroidism – because the hyperparathyroid glands have become autonomous – they may not be suppressed when the calcium returns back to normal) Normal plasma phosphate Hypervitaminosis D and thiazide diuretics (makes sense, they cause calcium reabsorption) Rarely – thyrotoxicosis, sarcoidosis, immobiliation with pagets disease of bone etc. Sarcoidosis and other macrophage disfunction disease are associated with increased activated vit D Primary hyperparathyroidism note Note suppression of other hyperparathyroid glands due to the single adenoma. Note the symptoms and hypertension are due to the hyperparathyroidism. Note that the calcium is not that high (because it isn’t in primary hyperparathyroidism – in malignancy it is usually much higher). Note that the albmin is a bit high (probably due to incorrect sampling technique) (and hence the calcium is actually a little lower) Note how the phosphate is at the lower end of the reference range (you would expect a higher phosphate for that calcium, hence you can dx hyperparathyroidism based on these results alone.) Also the alk phos is high end of reference range (because early in the dx). Note the parathyroid hormone is only slightly elevated. Note how even if PTH was e.g 10 and calcium was high you would still dx hyperparathyroidism. (I.e need to compare the results with each other) Note that post op the patient became hypoparathyroid. Note that the alk phos has probably rised because of immobilisation for a week. The reason he got hypoparathyroidism is because the other 3 parathyroid glands remain suppressed (after being suppressed by the adenoma). Thus need to maintain low normal calcium levels in order to reactivate the parathyroid glands. I.e DON’T be tempted to give calcium (unless very low) So patient became hypoparathyroid but then was going back to normal. Note how levels of calcium is very high and even lower phosphate (than previous example). Also note that when you get hypercalcaemia then you get polyuria and thus water depletion. (Thus note how the sodium and urea are elevated in conc) Also note that hypercalcaemia is frequently related to hypokalaemia (hence would think about correcting the low potassium). Also note the metabolic alkalosis (I believe this is secondary to the low potassium – possibly due to potassium leaving cells and H+ entering?) This is all due to ectopic hormone production (PTHrelated peptide) by breast carcinoma recurrence. Compare the 2 cases – note how in malignancy you get much higher calcium. Clinical features of hypocalcaemia Numbness and tingling of fingers and toes Muscle cramps/spasms Positive Trousseau’s sign (increase of 20 mm Hg over systolic pressure causing a claw like appearance the hand) and Chvosteks sign (when tapping the facial nerve you get contractions in the face) Laryngeal spasm and stridor Convulsions (mostly in newborn and infancy) Proximal myopathy (causing waddling gait – especially in children) Bone pain Psychiatric disturbances Cataracts Differential dx of hypocalcaemia Low plasma PTH concentration Idiopathic and acquired hypoparathyroidism High plasma PTH Secondary hyPERparathyroidism With low phosphate conc – due to Vit D deficiency (either nutritional, malabsorption – e.g coeliacs and anticonvulsant therapy – due to conversion into inactive forms) With high plasma phosphate – due to renal failure Note that these secondary causes – when treated can result in tertiary hyperparathyroidism (i.e going from low calcium to high calcium, but with the parathyroid hormone not changing) Pseudohypoparathyroidism – (see previous lecture) Miscellaneous conditions Renal tubular acidosis (not sure why) Acute pancreatitis – (main reason is due to low albumin – also because of dystrophic calcification?) Note the high urea due to renal failure Sodium – Would expect it to be low in person with renal failure (hence this is normal for someone with renal failure) Metabolic acidosis and hyperkalaemia (what you would expect) Phosphate retention and calcium falls The alk phos rises due to secondary hyperparathyroidism. Classical findings in someone with renal disease. Note low calcium and low phosphate. Urea is normal so not renal failure. Since the phosphate is low rather than high (which is what you would expect with primary hypoparathyroidism) this is a secondary hyperparathyroidism Since it is not due to renal failure, most likely cause is due to vit D deficiency. Additionally the raised alk phos gives a clue as to it being a hyperparathyroidism and that she has metabolic bone disease and osteomalacia. All this is worked out without having to measure the PTH and Vit D levels – which would take much longer. Note the high calcium and low phosphate is suggestive of a primary hyperparathyroidism. However the urine shows that the phosphate is low. Thus this is due to a phosphate deficiency (which has caused the metabolic bone disease and increase in calciu,) Summary of investigation of ostemalacia Osteoporosis – classification Primary Type 1 = postmenopausal Type 2 = senile Also idiopathic (which occurs in under 50s) Secondary Endocrine e.g cushings, hyperthyroidism and hyperparathyroidism (I understand cushings but not sure about the hyperthyroidism and especially the hyperparathyroidism, I would think this would cause osteitis fibrosa cystica) GI – malabsorption, liver disease (due to low calcium?) Malignancy – multiple myeloma (possibly because it causes invasion of the bone marrow) Drugs – steroids, anticonvulsants (again – due to vitamin D conversion to inactive forms) Bone turnover markers Note there are lots, but main ones for bone resorption are urine hydroxyproline and pyridinole while for bone formation then alkaline phosphotase (especially skeletal isoenzymes) General considerations in using biochemical markers Urinary markers are usually corrected for creatinine. Also need to be corrected by circardian rhythm and are affected by age, oestrogen etc. Summary of bone function level tests Note how phosphate is increased in someone with primary/tertiary but is variable in someone with secondary (as it is down in someone with renal failure, but decreased in someone with rickets/osteomalacia) Remember that in osteoporosis. (I believe that can be lower end calcium? But overall no metabolic disturbance I think) Pagets disease – you have normal but is very increased alk phos because of rapid bone turnover. (If increases again then suggestive of a complication of pagets disease – namely sarcoma) Also note that immobilisation can be associated with hypercalcaemia. Non-organ specific autoimmune disease Revision of tolerance Remember that tolerance = failure of immune system to respond to an antigen. Remember that this is a leaky process and the failure in self tolerance results in autoimmunity Maintenance of tolerance Central T cell tolerance (thymic education) Peripheral T cell tolerance (active regulation and absence of secondary signal/danger signal) B cell tolerance Thymus Remember you have positive selection (T cells that can bind to own HLA type are selected out – so you don’t waste time making T cells that cannot protect you from infection). Negative selection = where T cell receptors that bind strongly to the T cell receptor undergo elimination by apoptosis. Tolerance is a leaky process (thus everyone has some self reactive T cells). However there are mechanisms in the periphery to switch off the autoreactive T cells. Thus you need several signals (rather than just contact of the HLA molecule withn the peptide. Thus you need costimulation (e.g CD40-CD40-L). Also what is important is the danger signal (inflammation or infection – much easier to activate the T cells) – note this is what adjuvants try to do in vaccines (to try and drive the immune process) Activation is manifest by proliferation and maturation. However if they only get signal 1 they can either be anergic (“switched off” – but can be reversed) or apoptosis. (remember “cure” for autoimmune disease would be to drive the cells to apoptosis – but I believe all they can do so far is to push them to anergy, which doesn’t help). B cell tolerance They are kept under control mostly because T cell help is absent. However ther are other mechanisms where B cells can be silenced (don’t think I need to know much about this) Remember the simple diagram below, Even if cytotoxic cells/B cells are activated but if Thelper cells are not activated then there will be limited damage. Remember thate tolerance is leaky. Hence remember that there is a huge difference between autoimmune reactivity and autoimmune disease. In autoimmune disease you have tissue damage and organ dysfunction (while many people will have weakly active autoimmune reactivity and be free from disease) Mechanisms of autoimmunity Often we don’t know why it occurs. However some mechanisms we do understand. Released of sequestered antigen Antigens which the T cells are not used to seeing in the thymus are released (by other disease) and hence they are not tolerised and will react Important in eye and testis. Intraoccular antigens are generally not expressed in the periphery (generally not a problem because the cells don’t usually penetrate into the eye). However if you get penetrating trauma to one eye then you can get release of the antigens and autoimmunity reaction to both eyes. (Previously, if had trauma to eye, then had to quickly remove it to prevent blindness in both eyes. However now immunosupressants are used.) Also occurs in testicular tortion (testicular antigens can activate the immune system and can have both testis attacked, resulting in infertility) Alteration of self With infection or drug Best example is drug induced lupus. Some drugs e.g hydralazine (not a widely used drug for heart failure) can cause this. It alters the DNA (by binding to it) This can result in autoimmune reactivity In most patients it is an autoimmune reaction to the hydrazalazine. (so when you remove the drug, the drug induced lupus goes away) However in some there is binding to the DNA itself. (so that when you remove the drug, the drug induced lupus still remains) Molecular mimicry Some infectious agents are closely related to our antigens. (E.g strep A) hence cross reaction with own tissues Best example is rheumatic fever Antibodies that are made in strep cross react with heart (resulting in pancarditis), brain (chorea?) skin (subcutaneous nodules?) and joints Superantigen stimulation E.g Toxic shock syndrome – after this then it can overwhelm tolerance. Thus many people that recover are left with autoimmune disease. (Makes sense, even though you have recovery from the initial superactivation, you have so much disruption of the normal mechanisms of self tolerance that you subsequently get autoimmunity) Superantigens don’t have to be processed. Thus activate huge numbers of T cells. E.g TSS – (after staph, strep) Another example is Kawasaki syndrome (which some people believe to be due to superantigen activation). This tends to affect young children and effect the coronary artery which can cause MI (obviously concerning in such a young child). Additionally it can cause scalded skin. Also get generalised rash etc Infection of antigen presenting cell In the periphery the APC’s will usually be able to have signal 1 (self antigen + MHC class I (because they have made it through the negative selection) but not signal 2 (the costimulation – unless it is actually a true infectious process going on However if the APC itselt is infected by a virus then it can cause the costimulation. This is the mechanism that we believe type 1 DM occurs. (That there is a virus which infects the APC and causes activation of autoimmunity causing destruction of the beta cells of the Islet of Langarhans). Mutations in genes controlling immune response E.g ALPS (autoimmune lymphoproliferative syndrome) This is due to mutations in the FAS/FAS ligand. This is a key pathway in switching off the immune system. This pathway induces apoptosis. However if have mutation then once you switch on an immune response then you cant switch it off. (Hence get lymphadenopathy, hepatomegaly etc). Mechanisms of tissue injury Type 1 = IgE influenced. Forms basis for most allergy. However no known autoimmunity showing this mechanism yet. Type 2 = humoural immunity Type 3 = immune complexes Type 4 = cellular immune response. Also some that don’t fit neatly to this. Autoantibodies Remember presence doesn’t imply pathogenesis However usually easier to measure than T cell reactions E.g in hashimotos thyroiditis, the injury is actually T cell mediated, but the anti thyroid antibody is used for Dx (as easier to measure) Type II This is antibody mediated cytotoxicity Antibody binds, complement is activated and there is influx of inflammatory cells which leads to tissue damage. E.g anti GMB disease Lab tests: look for the specific antibodies. (variable efficacy e.g GBM is 100% sensitive, others less good). Note that complement consumption is often masked (wont see change in complement levels, because not that much is activated) Gold standard = immunoglobulin deposition on biopsy. Type III Immune complex deposition. Antibody binds to antigen (soluble or in tissue) Complement is activated. If it is not cleared then it may get lodged in tissue. E.g SLE and rheumatoid vasculitis Remember that people have a way of removing antibody complexes. This is by the complex binding to RBC’s which then go to the spleen. These are then stripped off by macrophages. Only when mechanism doesn’t work properly or it is overwhelmed, that you get immune complex disease When you get immune complexes in tissues then you get inflammatory cells that migrate into the tissue, causing tissue damage. Here you often find a fall in serum complex levels C3 and C4 especially. Also need to do CH100 to rule out complement deficiency Also will do specific antibody tests e.g ANF/ANA (screening test, then go with ENA) , RF (e.g rheumatoid arthritis), anti ds DNA (e.g lupus) and anti – ENA (I believe this is a group of antibodies, e.g anti ds DNA) Type IV One of commonest mechanism Delayed hypersensitivity. Antigen is presented to T cells, the T cell is activated and secretes chemokines Macrophages are activated by interferon and you get tissue injury E.g RA and cellular rejection in grafts Also what arises with granulomatous inflammation ORGAN SPECIFIC VS NON ORGAN SPECIFIC Organ specific e.g autoimmune thyroiditis, IDDM, pernicious anaemia, autoimmune hepatitis etc. Key is that the antigen that is targeted is specific to these organs. In non organ specific then the antigen is expressed throughout the body (and thus any organ can be effected) Non organ specific 3 main categories are rheumatoid disease (key thing is that it is not just an arthritis – but other effects) Also connective tissue disease (e.g SLE, scleroderma, polymyocytis, dermatomyositis, mixed connective tissue disease and Sjogrens syndrome) And third main one is primary vasculitis Also others e.g anti phospholipids syndrome VASCULITIS SHOULD BE COVERED IN NEXT LECTURE, IF NOT THEN COME BACK TO VASCULITIS, SIZES, GRANULOMA OR NO GRANULOMA USE OF LAB TESTS Remember they are useful to rule in, rule out or monitor disease activity. Remember that false positives and false negative results are common. Thus need to take history, have differential and have targeted tests. Detection of autoantibodies (skipped in lecture, probably not that important) Agglutination assays The antigen coated beads and serum If there is no antibody then it remains in suspension The antibody agglutinates to form a button (due to bridges that are formed between the beads) Simple and quick assay Indirect immunofluorescence Use slides with cultured cells. Patient serum is added and incubated on the slides. If there is antibody then it will stick to the nucleus of the cells. (I.e testing for ANF) Then use fluorescent anti humoural antibody against the antibody (and see if there is positive). Strong lighting in the nuclei is suggestive of lupus. (Need to do more specific tests to refine the dx) ELISA Antigen coated well, incubate patients serum, wash away excess Then use enzymed linked antibodies (that are then washed away again). The enzyme is used to catalyse a reaction with a colour change. (Thus the more antibody that has linked, the more reaction occurs) The intensity of the colour is suggestive of the level of antigen. (come back if time) RHEUMATOID ARTHRITIS Arthritis = most common presentation. However it can affect most tissues in the body Also note that some extraarticular features may occur alone (atypical presentation) Side note, very painful ulcers can occur due to vasculitis. Note that the arthritis is mainly due to T cell mediated immunity while the vasculitis and other extra articular is due to the immune complex deposition. Epidemiologyu Uncertain peak age 3:1 female male ratio 1% prevelance and 30/100,000 incidence (makes sense, much larger prevelance due to it being a chronic condition) There are genetic influences e.g HLA- DR4 (DR1 associated with Hispanic/jewish and asian popns) Presentations Acute polyarthritis = common presentation Will complain of inflammatory symptoms/signs. Mainly morning stiffness. (not really fever, although may have some low grade). Key difference between mechanical osteoarthrosis. Minimum of 6 weeks to get dx. Can be other presentations though. E.g slow monoarthritis, acute monoarthritis, local and systemic extra-articular disease Patterns of progression Most = polycyclic. (I.e relapsing remitting) Some have monocyclc (more benign – i.e have few episodes) Also progressive (where they have aggressive disease causing massive joint destruction) Note currently no way of knowing who will progress in what way. RA pathology Have chronic widespread synovitis Lymphocyte infiltration and hyperplastic synovium Pannus formation at synovial interface which can eat in (causing marginal erosions). This is an invasive type of altered connective tissue which eats its way into the the cartilage (goes on to destroy the joint). This can cause collapse of the bone and cause an irreversible deformity. Nodules Occur on the extensor surfaces in 20% of seropositive patients (I believe this is by definition seropositive) There is focal central fibrinoid necrosis. Thought to be due to a form of vasculitis They are small HARD nodules. Commonly occur by the elbow Rheumatoid vasculitis Can be small vessel – i.e nailfold infarcts and spinter haemorrhages. (They don’t tend to cause too many problems). (side note, remember that splinter haemorrhages can be cuased by trauma but also vasculitis. This is why RA, SLE, scleroderma and other connective tissue diseases can cause splinter haemorrhages. Also remember that infective endocarditis can cause this, which makes sense since infective endocarditis is a cause of vasculitis. Can also be medium vessel – i.e leg ulcers and neuropathy The vasculitis is generally immune complex mediated. It may also be ANCA psotive Rheumatoid factor This is an antibody to the Fc portion of IgG and is present in about half of patients with RA. However lots of weak positives (non specific) – e.g infection and especially older females Strong positive however is highly suggestive of RA. RA complications Felty’s syndrome Splenomegaly, RA and neutropenia Amyloidosis Remember, any chronic disease can cause amyloidosis Vasculitis (See above) Pulmonary disease Nodules, pleural effusion Interstitial fibrosis Obliterative bronchiolitis (small airways scar up and air cannot get in, most devastating) (Note that may not notice getting restless on exertion due to lack of mobility due to the arthritis) Occlar disease Keratoconjunctivitis sicca (conjunctivitis and keratosis – inflammation of the cornea that is associated with dry eyes/lack of tear production) Episcleritis (inflammation of the episclera, the layer in between the conjunctiva and the sclera). Scleritis (more severe, effecting the sclera, commonly in rheumatic conditions e.g RA, wegeners granulomatosis etc) Sleromalacia (Thinning of the sclera, exposing the choroids underneath, I believe this is the wost) The eye can perforate from damage to the eye wall. Making the diagnosis To rule in Clinical picture Rheumatoid factor and anti-CCP antibodies Xrays of hands and any affected joints. This is because erosions on Xray (see below) help to make dx even in the event of seronegative RA. Additionally it shows that the rheumatoid arthritis is an aggressive form. Rule out alternative dx ANF (to rule out the connective tissue diseases – e.g SLE, and follow up (i.e ENA I believe) ANCA to rule out vasculitis Also need to think about the seronegative arthritis (with Hx and exam) Also note that you can get transient arthritis in a viral arthritis (commonly following rubella in adult). Dx by history and serology. (Need to think about this, especially if the first line tests come up negative). Monitoring disease activity Clinical activity scores CRP (best non specific – used to monitor inflammation) ESR (but affected by lots of things, e.g NSAIDS, anaemia etc) FBC – anaemia (normocytic normochromatic (anaemia of chronic disease – check why), but may also see iron deficiency anaemia due to gastric irritation/bleeding from the medications that these patients are on). Monitor function of affected organs Serial RF = little benefit Immunology 2 CONNECTIVE TISSUE DISEASE This is rheumatoid arthritis (says rheumatoid disease, but I assume she means this) SLE Polymyositis Scleroderma and CREST Mixed connective tissue disease Sjogrens syndrome (Vasculitidies). Remember that there can be a lot of overlap between these diseases. However many have well defined syndromes Many respond to immunosupression. Notable exception is scleroderma. SLE Inflammatory multisystem disease Unknown aetiology Diverse clinical and lab abnormalities Variable course and prognosis (can range from arthritis/skin rash to life threatening and aggressive disease). (note about 5% of renal transplant lists are due to lupus) Multiple autoantibodies. Cytotoxic function (type 2 hypersensitivity to platelets, RBC’s etc) Immune complex deposition (type 3 hypersensitivity) I.e more than 1 mechanism of autoimmunity in this one disease. Other lupus This is classical lupus but there are others Drug-induced lupus (e.g hydralazine which results in loss of tolerance due to altered self – usually remit after removing the drug) Neonatal lupus (antibodies (IgG – remember, IgM cant cross the placenta as it is too large) from a mother with lupus may cross the placenta to induce lupus in the newborn. Typically takes form of skin rash and congenital heart block. Note that especially the anti Ro antibodies can bind to the conducting system (causing heart block and hearf failure – thus needed to treat with pacing). Latent lupus (those with serological evidence of lupus but don’t have symptoms – however may go on to develop lupus themselves. Additionally can result in neonatal lupus (if woman gets pregnant). However remember that vica versa (not all will get disease in those that have antibodies) Antiphospholipid syndrome (associated with thrombophilia, 30% of those with lupus have this, although may get on its own) End stage lupus (there is no more inflammation due to “burn out” of inflammation – but can still have renal failure etc. Thus steroids/immunosupression is not necessary (as no benefit, just giving toxicity) Epidemiology 9:1 female to male Peak age = 2nd – 3rd decade (young females = common) Large geographical incidence (America more than Scandinavia for example) Prevelance = about 50/100,000 Racial – black>white Genetic: some genetic factors such as complement deficiencies and problems in the mechanism for desposing immune complexes. (makes sense, if you don’t have a good mechanism to dispose of complexes then you are more likely to get lupus) Clinical features Inflammation of any organ, predominantly: Skin (classical rash = butterfly rash). (Remember it is one of the few rashes that goes up above the nose – rather than just the cheeks). Generally is not itchy or sore. Also classically photosensitive (so commonly after being in the sun it comes out) Note that another rash that they can get is discoid lupus. (can be chronic, slightly raised. Skin follicles plugged wth debris). Classically on biopsy then you can demonstrate immune complex along the dermo-epidermal junction) Also mouth ulcers etc Joints (usually). (Skin and joint manifestation is generally Kidneys (need potent immunosupression to prevent renal failure) Brain (cerebral manifestation is one of the most severe Serosal surfaces (can get pleural effusions and pericarditis) Immune cytopenias and haemolytic anaemia is common. (Remember, anyone with haemolytic anaemia should be tested for lupus) Note that skin manifestations only = cutaneous lupus. However this may be part of Renal pathology Many different types you can get. Focal segmental glomerulonephritis Focal proliferative glomerulonephritis Diffuse proliferative glomerulonephritis Membranous glomerulonephritis (glomerulonephrosis) Sclerosis. Morbidity and mortality Due to organ damage of disease itself However also significant morbidity/mortality due to the effects of immunosuppressant drugs. E.g those with renal lesion treated with high dose steroids and cyclophosphamide (alkylating agent that causes leucopenia and infertility) Common autoantibodies ANF = screening test. If positive then go on to do other tests (anti dsDNA) ENA (anti extractable nuclear antibodies) – especially Anti-Ro, Anti-La and Anti-Sm Antibodies to RBC, WBC and platelets (especially if have neutropenias, anaemias etc) Making the dx Clinical hx and exam. Uranalysis and urine microscopy (because patients may have silent renal failure) ANF (if negative then unlikely dx of SLE) If positive then go on to measure Anti-dsDNA Also anti-ENA (note that anti-sm is an especially specific test – although only found in 30% of those with lupus). Anti ro and anti la (found in other connective tissue disease, but support dx) Also need to assess function of potentially involved organs. Monitoring disease activity Function of affected organs FBC and ESR (remember that CRP = poor measure in SLE) Complement levels (level of consumption – remember there is type 3 hypersensitivity and thus could be lower levels of complement) Anti-dsDNA levels reflects disease activity. Examples 5 day old girl Rash Enlarged Liver & Spleen Severe hepatitis Normal heart rate Mother had mild SLE diagnosed 1999 (intrauterine infections e.g rubella, herpes etc would be differential The mild lupus is mother was key. Intrauterine viral antibodies were negative Infection screen negative Anti-Ro positive Anti-DNA negative Rapidly worsening liver failure Working diagnosis - Neonatal lupus Note that IgG tests are used for this. Remember that in most neonatal diseases you are looking for IgM (because IgG are mostly from the mother). However, since you are looking for a disease that has been transferred from the mother to the child you are looking for IgG. (mother) Mother had been well during pregnancy Never had systemic therapy for SLE Generally unwell Fatigue – anaemia (anaemia is common after pregnancy, but this was haemolytic anaemia, not expected after pregnancy) Joint pains ANF >1/400 S&H Anti-DNA 297iu/ml (Ref 50) (i.e this is a disease of the elderly) M and Black = more affected than F and white. Pathogenesis Very complicated and many interconnected pathologies Previous exposure to irradiation Exposure to asbestos, petroleum products, rubber or plastic products HH8 (not sure why, I know that this causes kaposis sarcoma, as far as multiple myeloma is concerned I am not too sure) Cytogenetics (e.g deletion of 13q or translocation of 4;14) Myeloma cells produce Il-6. This is important because it induces myeloma cell growth and induces osteoclast activation. Hence you get breakdown of the bone. (This makes sense, this is the reason why even if there is no direct infiltration of the myeloma cells, there is osteoclast activity and hence lytic lesions. E.g in the skull it is called a pepperpot skull The plasma cells secrete a MONOCLONAL Ig. Usually they are IgG or IgA (the other types are uncommon) In 2/3 of patients they have Bence Jones proteins. These are light chains of immunoglobulins that are found in the urine. They are able to be found in the urine because they are light chains (hence they can be filtered in the glomerulus) (possibly the reason why only 2/3 of patients have this is because the other 1/3 produce heavy chains?) Dx of MM Radiology You may see specific punched out lytic lesions (makes sense, since these would be due to the osteoclast activation) E.g (e.g note below the multiple lytic lesions in the metaphysic and diaphysis of the humerus and in the ribs. There is also a small fracture in the proximal metaphysic) Also note the pepper pot skull on the right You can see multifocal destructive lesions ( Bone marrow sampling (a bone marrow aspirate or biopsy) Serum and urine electrophoresis and immunoglobulin levels (You would have a monoclonal spike, urine electrophoresis would be the Bence Jones criteria I would imagine). Could also see multifocal destructive lesions (multiple punched out lytic lesions) They can soap bubble appearance Can also have pathologic fractures (makes sense, they have bony infiltration and lytic lesions) Note that you mal also get a diffuse osteoporosis (because of Il-6 secretion which results in infiltration of the bone even if there is no infiltration of the bone) Bone marrow sampling Can do a bone marrow aspirate or a bone marrow biopsy Normally plasma cells form about 10-20% of the bone marrow. (I think lecturer is saying that normally 10-30% but when there is multiple myeloma there is a greater percentage. Not sure. Remember the normal morphology of plasma cells. You have a nucleus which is pushed to one side and perinuclear clearing (because of golgi bodies - to make the immunoglobulins I believe) However, in multiple myeloma you can have abnormal cells e.g bi-nucleated, trinucleated or multi-nucleated forms. Can have immature blasts Intracytoplasmic inclusions (Russle bodies large eosinophilic cells) Immunohistochemistry (will see a single type of Ig – monoclonal remember). They can be either kappa or lambda (never both, usually kappa). Remember that they are the type of light chains?) Serum and urine analysis Monoclonal globulin spike on serum electrophoresis (note that small percentage, 1% secrete neither Bence Jones proteins or monoclonal spike) The absence of Ig or its components from blood or urine does NOT exclude myeloma (because of the 1% of the non secretors I would imagine) Clinical features of multiple myeloma CRAB (hypercalcaemia, renal failure, anemia and bone lesions) Infiltration of bones (hence bone lytic lesions) (the hypercalcaemia would cause hyperparathyroidism too I would imagine? Additionaly there would be il-6 secretion and therefore resulting in osteoclasts being activated also causing lytic lesions?) (Remember that a patient with back pain especially if it is unremitting even in the night then suspect MM. Additionally another feature that maybe present is tender ribcage) Hence get bone pain and pathologic fractures Hypercalcaemia – (due to resorption of bone I would imagine, Not all patients get this I believe it is 10%) Infiltration of bone marrow (hence the anaemia) Renal insufficiency (just due to amyloid or due to infiltration as well?) Infiltration of other organs is rare. Amyloidosis – AL chain. Recurrent infections This is the most common cause for death (renal failure being the second most common) This is due to a combination of decreased production of normal immunoglobulins (and hence there is particular risk from encapsulated organisms) (antibody mediated immunity) Additionally infiltration of the bone marrow causes leucopenia (and hence cell mediated immunity is also reduced) Hypercalcaemia Additional symptoms due to this (Bones, stones, groans and psychiatric moans remember) Lethargy, nausea, vomiting, abdominal pain (due to ulcers or pancreatitis I believe) Renal stones Depression (psychiatric moans) Bone lesions Amyloidosis Remember that you can get a AL type of a amyloidosis (it is the most common type of systemic amyloidosis I believe) It is a systemic amyloidosis with deposits in many places Remember from BED. It occurs with about 10% of MM patients and when you have this then generally very poor prognosis. Note however that most people with Al amyloid do not have MM (but probably some lymphproliferative disorder. Not known if they will eventually develop myeloma because the amyloid will usually kill the patient first. Dx = kidney (more invasive) or rectal biopsy (remember, rectal is often used I believe in systemic amyloidosis, possibly because it is a good and minimally invasive procedure) Then stained with congo red stain Complications associated with amyloid deposition Restrictive cardiomyopathy Enlargement of the tongue Athropathy (basically the same as arthritis) Tendency for prolonged bleeding (due to binding of clotting factor X by the amyloid fibril) Skin changes Renal failure This is the second most common cause of death The renal failure is multifactorial Obviously if the patient has amyloidosis then amyloid deposits can cause However myeloma kidney (myeloma cast nephropathy due to deposition of cast within the tubules) (just a feature that suggests myeloma I would imagine – I think just meaning direct invasion of the myeloma cells?) Light chain nephropathy (this is due to deposition of light chain in the glomeruli) Hypercalcaemia (causing renal calcinosis?) and hyperuricaemia Pyelonephritis (not sure the mechanism) Prognosis of multiple myeloma Very poor 6-12 months if untreated Median survival = 3 years if treated Causes of death = infection and renal failure. Treatment of multiple myeoma Currently it is not curable However, chemotherapy, steroids, and radiation may help Bisphosphonates are also used (I imagine as symptomatic therapy in order to prevent fractures and build up bone bulk) Thalidomide = tx for multiple myeloma (remember, it caused birt defects in women before, but now used again as a tx for this condition). Thalidomide used in combination with dexamethasone Bone marrow transplant (either autologous or allogenic can also be used) SOLITARY PLASTMACYTOMA This is like a multiple myeloma but it is a solitary tumor which is growing within the soft tissue or skeleton The serum immunoglobulin concentrations are within normal limits The patients are younger than patients with multiple myeloma It involves the spine, pelvis and femur Can present with a single symptomatic area of bone destruction. Plasma cells account for more than 15% in the bone marrow It may however progress to multiple myeoma (10-20 years later) Extra medullary plasmocytoma = often involved in the lung, oronosopharynx and nasal sinuses Extra-osseus lesions can be cured by local resection or chemotherapy. Progression to multiple myeloma is rare. (I believe the skeletal forms are worse because you are far more likely to progress to multiple myeloma) WALDENSTROMS MACROGLOBUMINAEMIA (apparently not that important) Just know a bit about it Occurs in the elderly and more in females The neoplastic cells this time produce IgM (whereas multiple myeloma usually produces IgG, but can produce others) and this is the reason why it is called macroglobuminaemia (as the immunoglobulins are large) Weakness and weight loss Lymphadenopathy, hepatosplenomegaly, autoimmune haemolysis and hyperviscosity syndrome Hyperviscosity syndrome = visual impairment due to distention of the retinal blood vessels. There can also be neurological symptoms, bleeding (due to macroglobulins binding to clotting factors and interfering with platelet function), cryoglobuminaemia and Raynauds phenomenon HEAVY CHAIN DISEAES These are monoclonal proliferations of B cells with increased production of heavy chains (kind of like amyloidosis in a way. Light chain production forms AL amyloidosis, while this is heavy chain disease) Note that this, amyloidosis and waldenstroms macroglobuminaemias are all types of paraproteinemias (which indicate an underlying immunoproliferative disorder). That is, excessive amounts of single monoclonal gammaglobulins. (Light chains – amyloidosis, heavy chains – heavy chain disease or full polymers – waldenstroms macroglobuminaemia) There can be production of alpha heavy chain disease, gamma heavy chain disease or mu heavy chain disease (more information about this in the lecture, come back to this in the very unlikely situation of having excess time) MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE This is the most common cause of monoclonal gammopathy 3% of adults >70 will have this. This is a monoclonal immunoglobulin spike in the serum or urine without evidence of MM or other disease It is asymptomatic and usually picked up incidentally The plasma cells form	2	14	0	0	3	0.655576	3	23,988
\|Page tools: Print Page Print All\| Death is the permanent disappearance of all evidence of life after birth has taken place. The definition excludes all deaths prior to live birth. For the purposes of the Deaths and Causes of Death collections of the Australian Bureau of Statistics (ABS), a death refers to any death which occurs in, or en route to Australia and is registered with a state or territory Registry of Births, Deaths and Marriages. Doctor Certified Deaths Deaths which were certified by a doctor or medical practitioner, which were not required to be referred to a coroner. External Causes of Death Deaths due to causes external to the body (for example suicide, transport accidents, falls, poisoning etc). Applicable ICD-10 codes are: V01-Y98. International Statistical Classification of Diseases and Related Health Problems. The purpose of the ICD is to permit the systematic recording, analysis, interpretation and comparison of mortality and morbidity data collected in different countries or areas and at different times. The ICD, which is endorsed by the World Health Organisation (WHO), is primarily designed for the classification of diseases and injuries with a formal diagnosis. See Explanatory Notes 18 - 22 for more information on ICD. Further information is also available from the WHO website. The condition of being mortal or subject to death. Multiple Causes of Death All morbid conditions, diseases and injuries entered on the death certificate. These include those involved in the morbid train of events leading to death which were classified as either the underlying cause, the immediate cause, or any intervening causes and those conditions which contributed to death, but were not related to the disease or condition causing death. For deaths where the underlying cause was identified as an external cause (injury or poisoning) multiple causes include circumstances of injury, the nature of injury as well as any other conditions reported on the death certificate. Natural Cause of Death Deaths due to diseases (for example diabetes, cancer, heart disease etc), which are not external or unknown. Other Territories include Jervis Bay Territory, previously included with the Australian Capital Territory, as well as Christmas Island and the Cocos (Keeling) Islands. The year that presented data refers to. For example, this publication presents data for the 2009 reference year, as well as some historical data for the 2008 reference year. From 2007, data for a particular reference year includes all deaths registered in Australia for the reference year that are received by the ABS by the end of the March quarter of the subsequent year. For example, data for the 2009 reference year includes all deaths registered in Australia for 2009 that were received by the ABS by the end of March 2010. See Explanatory Notes 6 - 14 for more information about scope and coverage. The sex ratio relates to the number of males per 100 females. The sex ratio is defined for total population, at birth, at death and among age groups by appropriately selecting the numerator and denominator of the ratio. State or Territory of Registration State or territory of registration refers to the state or territory in which the death was registered. It is the state or territory in which the death occurred, but is not necessarily the deceased's state or territory of usual residence. State or Territory of Usual Residence State or territory of usual residence refers to the state or territory in which the person lived, or intended to live, for a total of six months or more in a given reference year. Underlying Cause of Death The disease or injury which initiated the train of morbid events leading directly to death. Accidental and violent deaths are classified according to the external cause, that is, to the circumstances of the accident or violence which produced the fatal injury rather than to the nature of the injury. Unknown Cause of Death Deaths where it is unable to be determined whether the cause was natural or external. These documents will be presented in a new window.	3	6	0	0	2	0.316082	2	798
Managed care is an American health care plan that provides health insurance. Managed care plans include a contractual agreement between health care providers and medical facilities that provide the members of the care with a reduced cost of health services through simulative competition and streamlined administration care (Smith & Goodwin, 2017). Managed care aims at reducing the cost of health services to the members and attain an improved quality of care. Managed care as a method of service delivery, has encouraged the transfer of healthcare services to outpatient as well as other non-traditional settings of care. “Analysis of managed care, and discuss how it, as a delivery method, has facilitated the transfer of health services to outpatient and other nontraditional settings of care." Outpatient health care services are all categories of services rendered to the patients outside the traditional healthcare setting (hospital). These services are also referred to as ambulatory care including the wellness and preventive care services, diagnostic care, treatment as well as rehabilitation. With the approval of the Health Maintenance Organization Act in 1973, there is controlled costs in both public and private healthcare markets for service delivery (Smith & Goodwin, 2017). The managed costs by these organizations have influenced efficiency as well as effectiveness in the healthcare service industry because of the creation of the service providers across traditional and non-traditional health settings. Health providers operate with networks that encourage a vast assortment of services in non-traditional health settings through an explicit set of principles that would be used to select the most qualifying healthcare service, provider. Also, managed care plan focuses on preventative care services that are not offered in the MANAGED CARE ANALYSIS 3 hospitals/traditional health care settings only, but also non-traditional setting s like the community (Schwartz et al., 2018). Managed care plan providers establish the network plan for the plan. The amount of the cash needed depends on the rules posted by the network selected. Managed care plans have transferred healthcare services to outpatient and other non-traditional settings through the distribution of programs in various types like HMO, PPO, and POS. Health Maintenance Organization (HMO) is a type of managed care plan that only pays for care services within the network after choosing a primary physician who will be coordinating most of the health care services for you (Smith & Goodwin, 2017). Preferred Provider Organization (PPO) demands more payment in case one receives care within the network. However, this type of plan pays a portion of the healthcare service cost even if you go outside the system. Point of Service (POS) is a managed care plan that gives room for the client to choose either HMO or a PPO plan anytime they attend health facilities for medical care. These have encouraged channeling healthcare services to outpatient and other non-traditional health settings (Hall, Orentlicher, Bobinski, Bagley & Cohen, 2018). “Discuss the impact managed care has on the access, financing, and delivery of health care in the United States." Managed care plan essentially aims at reducing the cost of healthcare service delivery while enhancing the quality of care offered to the patients. Managed care have significantly influenced the affordability and accessibility of the healthcare services throughout the United States population. Managed care plans have provided fee-for-service as well as traditional indemnity insurance plans thus giving the physicians an opportunity to have incentives of delivering MANAGED CARE ANALYSIS 4 healthcare services of negligible worth to their patients (Hall, Orentlicher, Bobinski, Bagley & The managed care plan is the most common type of healthcare plan in the United States has primarily provided healthcare solution for people from low socio-economic backgrounds. The services are easily accessible and affordable. This is because managed care plans have encouraged immediate primary care services. People have been given the opportunity to care for their health at a considerable certainty level. Prescription management of the care services is improved because the health care network providers collaborate with the pharmaceutical agencies to make sure that the prescriptions are accessible at an affordable price (Schwartz et al., Managed care has significantly influenced the cost of healthcare services. It has lowered the prices of the services for those who have the insurance coverage. This is the major goal of the managed care system. However, the reduced costs don't sacrifice the quality of the services rendered. The reduced costs and enhanced quality of services have been achieved through the establishment of the network of service providers who offers care services as well as referrals (Schwartz et al., 2018). If people are loyal to their network care provider, procedures and services, are discounted. "Discuss managed care's role in promoting health." Managed care programs and systems are essential in promoting health. Especially, managed care programs have enhanced preventative care in the population as well as healthcare facilities. The managed health care plans are effective in controlling chronic diseases via preventative care (Smith & Goodwin, 2017). According to Frank, Glazer & McGuire (2017), managed care provides chances for public health improvement through a structured format. MANAGED CARE ANALYSIS 5 Because the primary aim of the managed care plan is to reduce the cost without sacrificing the quality of health care services, managed care organizations focus on population-based research that attempts to attain the most suitable public health outcomes. The managed care organization also provide civic education to its subscribers that offer insights about health incentives. Managed care along with the public health departments work collaboratively to provide health care services to the public. Therefore, it makes the duo get concerned with the population health, and its intervention systems that improve the health of the community (Frank, Glazer & Managed care aims at reducing the cost of health services to the members and attain an improved quality of care. Managed care as a method of service delivery, has encouraged the transfer of healthcare services to outpatient as well as other non-traditional settings of care. Outpatient health care services are all categories of services rendered to the patients outside the traditional healthcare setting (hospital). The managed costs by these organizations have influenced efficiency as well as effectiveness in the healthcare service industry because of the creation of the service providers across traditional and non-traditional health settings. Managed care have significantly influenced the affordability and accessibility of the healthcare services throughout the United States population. Managed care programs and systems are essential in promoting health. Specially, managed care programs have enhanced preventative care in the community as well as healthcare facilities. MANAGED CARE ANALYSIS 6 Frank, R. G., Glazer, J., & McGuire, T. G. (2017). Measuring adverse selection in managed health care. In Models of Health Plan Payment and Quality Reporting (pp. 29-57). Retrieved from https://www.worldscientific.com/doi/abs/10.1142/9789813202887_0002 Hall, M. A., Orentlicher, D., Bobinski, M. A., Bagley, N., & Cohen, I. G. (2018). Health care law and ethics. Wolters Kluwer Law & Business. Schwartz, P., Gao, W., Kreitman, J., Hamilton, G., Keleti, D., Michael, K. E., & Gelzer, A. D. (2018). Inverse Correlation of Decreased Opioid Utilization and Increased Medical Assisted Therapy in US Medicaid Managed Care. The value in Health, 21, S189. Retrieved from https://www.valueinhealthjournal.com/article/S1098-3015(18)31578- Smith, J., & Goodwin, N. (2017). Towards managed primary care: the role and experience of primary care organizations. Routledge. Retrieved from	2	4	1	1	0	0.685992	2	1,680
Heart: The hollow, muscular organ that maintains the circulation of the blood.Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint.Heart Failure: A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.Death: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.Heart Diseases: Pathological conditions involving the HEART including its structural and functional abnormalities.Heart Transplantation: The transference of a heart from one human or animal to another.Heart Defects, Congenital: Developmental abnormalities involving structures of the heart. These defects are present at birth but may be discovered later in life.Fetal Heart: The heart of the fetus of any viviparous animal. It refers to the heart in the postembryonic period and is differentiated from the embryonic heart (HEART/embryology) only on the basis of time.Death, Sudden, Cardiac: Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as CHEST PAIN and CARDIAC ARRHYTHMIAS, particularly VENTRICULAR TACHYCARDIA, can lead to the loss of consciousness and cardiac arrest followed by biological death. (from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., 2005)Heart Valves: Flaps of tissue that prevent regurgitation of BLOOD from the HEART VENTRICLES to the HEART ATRIA or from the PULMONARY ARTERIES or AORTA to the ventricles.Heart Atria: The chambers of the heart, to which the BLOOD returns from the circulation.Heart Block: Impaired conduction of cardiac impulse that can occur anywhere along the conduction pathway, such as between the SINOATRIAL NODE and the right atrium (SA block) or between atria and ventricles (AV block). Heart blocks can be classified by the duration, frequency, or completeness of conduction block. Reversibility depends on the degree of structural or functional defects.Brain Death: A state of prolonged irreversible cessation of all brain activity, including lower brain stem function with the complete absence of voluntary movements, responses to stimuli, brain stem reflexes, and spontaneous respirations. Reversible conditions which mimic this clinical state (e.g., sedative overdose, hypothermia, etc.) are excluded prior to making the determination of brain death. (From Adams et al., Principles of Neurology, 6th ed, pp348-9)Time Factors: Elements of limited time intervals, contributing to particular results or situations.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Fetal Death: Death of the developing young in utero. BIRTH of a dead FETUS is STILLBIRTH.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Heart Arrest, Induced: A procedure to stop the contraction of MYOCARDIUM during HEART SURGERY. It is usually achieved with the use of chemicals (CARDIOPLEGIC SOLUTIONS) or cold temperature (such as chilled perfusate).Heart Function Tests: Examinations used to diagnose and treat heart conditions.Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).Myocardial Contraction: Contractile activity of the MYOCARDIUM.Coronary Disease: An imbalance between myocardial functional requirements and the capacity of the CORONARY VESSELS to supply sufficient blood flow. It is a form of MYOCARDIAL ISCHEMIA (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels.Attitude to Death: Conceptual response of the person to the various aspects of death, which are based on individual psychosocial and cultural experience.Myocardial Infarction: NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.Myocytes, Cardiac: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).Hemodynamics: The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Ventricular Function, Left: The hemodynamic and electrophysiological action of the left HEART VENTRICLE. Its measurement is an important aspect of the clinical evaluation of patients with heart disease to determine the effects of the disease on cardiac performance.Cardiac Output, Low: A state of subnormal or depressed cardiac output at rest or during stress. It is a characteristic of CARDIOVASCULAR DISEASES, including congenital, valvular, rheumatic, hypertensive, coronary, and cardiomyopathic. The serious form of low cardiac output is characterized by marked reduction in STROKE VOLUME, and systemic vasoconstriction resulting in cold, pale, and sometimes cyanotic extremities.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Cardiomyopathy, Dilated: A form of CARDIAC MUSCLE disease that is characterized by ventricular dilation, VENTRICULAR DYSFUNCTION, and HEART FAILURE. Risk factors include SMOKING; ALCOHOL DRINKING; HYPERTENSION; INFECTION; PREGNANCY; and mutations in the LMNA gene encoding LAMIN TYPE A, a NUCLEAR LAMINA protein.Heart Arrest: Cessation of heart beat or MYOCARDIAL CONTRACTION. If it is treated within a few minutes, heart arrest can be reversed in most cases to normal cardiac rhythm and effective circulation.Cardiomyopathies: A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.Caspases: A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.Stroke Volume: The amount of BLOOD pumped out of the HEART per beat, not to be confused with cardiac output (volume/time). It is calculated as the difference between the end-diastolic volume and the end-systolic volume.Heart Failure, Systolic: Heart failure caused by abnormal myocardial contraction during SYSTOLE leading to defective cardiac emptying.Cardiomegaly: Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.Perfusion: Treatment process involving the injection of fluid into an organ or tissue.Heart, Artificial: A pumping mechanism that duplicates the output, rate, and blood pressure of the natural heart. It may replace the function of the entire heart or a portion of it, and may be an intracorporeal, extracorporeal, or paracorporeal heart. (Dorland, 28th ed)Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic.Cardiotonic Agents: Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE).Heart Injuries: General or unspecified injuries to the heart.Myocardial Reperfusion Injury: Damage to the MYOCARDIUM resulting from MYOCARDIAL REPERFUSION (restoration of blood flow to ischemic areas of the HEART.) Reperfusion takes place when there is spontaneous thrombolysis, THROMBOLYTIC THERAPY, collateral flow from other coronary vascular beds, or reversal of vasospasm.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Heart Septum: This structure includes the thin muscular atrial septum between the two HEART ATRIA, and the thick muscular ventricular septum between the two HEART VENTRICLES.Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.Prognosis: A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.Ventricular Dysfunction, Left: A condition in which the LEFT VENTRICLE of the heart was functionally impaired. This condition usually leads to HEART FAILURE; MYOCARDIAL INFARCTION; and other cardiovascular complications. Diagnosis is made by measuring the diminished ejection fraction and a depressed level of motility of the left ventricular wall.Rheumatic Heart Disease: Cardiac manifestation of systemic rheumatological conditions, such as RHEUMATIC FEVER. Rheumatic heart disease can involve any part the heart, most often the HEART VALVES and the ENDOCARDIUM.Heart Rate, Fetal: The heart rate of the FETUS. The normal range at term is between 120 and 160 beats per minute.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.Heart Valve Prosthesis: A device that substitutes for a heart valve. It may be composed of biological material (BIOPROSTHESIS) and/or synthetic material.Infant, Newborn: An infant during the first month after birth.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Mortality: All deaths reported in a given population.Risk Assessment: The qualitative or quantitative estimation of the likelihood of adverse effects that may result from exposure to specified health hazards or from the absence of beneficial influences. (Last, Dictionary of Epidemiology, 1988)Autopsy: Postmortem examination of the body.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Age Factors: Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time.United StatesVentricular Remodeling: The geometric and structural changes that the HEART VENTRICLES undergo, usually following MYOCARDIAL INFARCTION. It comprises expansion of the infarct and dilatation of the healthy ventricle segments. While most prevalent in the left ventricle, it can also occur in the right ventricle.Heart Failure, Diastolic: Heart failure caused by abnormal myocardial relaxation during DIASTOLE leading to defective cardiac filling.Receptors, Death Domain: A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.American Heart Association: A voluntary organization concerned with the prevention and treatment of heart and vascular diseases.Chronic Disease: Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care. (Dictionary of Health Services Management, 2d ed)Necrosis: The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.Cardiovascular Diseases: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.Mice, Inbred C57BLIncidence: The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from PREVALENCE, which refers to all cases, new or old, in the population at a given time.Oxygen Consumption: The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346)Caspase 3: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Cardiac Pacing, Artificial: Regulation of the rate of contraction of the heart muscles by an artificial pacemaker.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Autonomic Nervous System: The ENTERIC NERVOUS SYSTEM; PARASYMPATHETIC NERVOUS SYSTEM; and SYMPATHETIC NERVOUS SYSTEM taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the CENTRAL NERVOUS SYSTEM, especially the HYPOTHALAMUS and the SOLITARY NUCLEUS, which receive information relayed from VISCERAL AFFERENTS.Exercise Test: Controlled physical activity which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used.Natriuretic Peptide, Brain: A PEPTIDE that is secreted by the BRAIN and the HEART ATRIA, stored mainly in cardiac ventricular MYOCARDIUM. It can cause NATRIURESIS; DIURESIS; VASODILATION; and inhibits secretion of RENIN and ALDOSTERONE. It improves heart function. It contains 32 AMINO ACIDS.Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Hypoplastic Left Heart Syndrome: A condition caused by underdevelopment of the whole left half of the heart. It is characterized by hypoplasia of the left cardiac chambers (HEART ATRIUM; HEART VENTRICLE), the AORTA, the AORTIC VALVE, and the MITRAL VALVE. Severe symptoms appear in early infancy when DUCTUS ARTERIOSUS closes.Heart Septal Defects: Abnormalities in any part of the HEART SEPTUM resulting in abnormal communication between the left and the right chambers of the heart. The abnormal blood flow inside the heart may be caused by defects in the ATRIAL SEPTUM, the VENTRICULAR SEPTUM, or both.Heart Neoplasms: Tumors in any part of the heart. They include primary cardiac tumors and metastatic tumors to the heart. Their interference with normal cardiac functions can cause a wide variety of symptoms including HEART FAILURE; CARDIAC ARRHYTHMIAS; or EMBOLISM.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.National Heart, Lung, and Blood Institute (U.S.): Component of the NATIONAL INSTITUTES OF HEALTH. It conducts and supports research program related to diseases of the heart, blood vessels, lung, and blood; blood resources; and SLEEP WAKE DISORDERS. From 1948 until October 10, 1969, it was known as the National Heart Institute. From June 25, 1976, it was the National Heart and Lung Institute. Since October 1997, the NHLBI has also had administrative responsibility for the NIH Woman's Health Initiative.Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system.Ventricular Pressure: The pressure within a CARDIAC VENTRICLE. Ventricular pressure waveforms can be measured in the beating heart by catheterization or estimated using imaging techniques (e.g., DOPPLER ECHOCARDIOGRAPHY). The information is useful in evaluating the function of the MYOCARDIUM; CARDIAC VALVES; and PERICARDIUM, particularly with simultaneous measurement of other (e.g., aortic or atrial) pressures.Hospitalization: The confinement of a patient in a hospital.Models, Cardiovascular: Theoretical representations that simulate the behavior or activity of the cardiovascular system, processes, or phenomena; includes the use of mathematical equations, computers and other electronic equipment.Proto-Oncogene Proteins c-bcl-2: Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Sex Factors: Maleness or femaleness as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or effect of a circumstance. It is used with human or animal concepts but should be differentiated from SEX CHARACTERISTICS, anatomical or physiological manifestations of sex, and from SEX DISTRIBUTION, the number of males and females in given circumstances.Reactive Oxygen Species: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.Severity of Illness Index: Levels within a diagnostic group which are established by various measurement criteria applied to the seriousness of a patient's disorder.Risk: The probability that an event will occur. It encompasses a variety of measures of the probability of a generally unfavorable outcome.In Situ Nick-End Labeling: An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Systole: Period of contraction of the HEART, especially of the HEART VENTRICLES.Electrocardiography, Ambulatory: Method in which prolonged electrocardiographic recordings are made on a portable tape recorder (Holter-type system) or solid-state device ("real-time" system), while the patient undergoes normal daily activities. It is useful in the diagnosis and management of intermittent cardiac arrhythmias and transient myocardial ischemia.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Endocardium: The innermost layer of the heart, comprised of endothelial cells.Antigens, CD95: A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.DNA Fragmentation: Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS.Anti-Arrhythmia Agents: Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.Diastole: Post-systolic relaxation of the HEART, especially the HEART VENTRICLES.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Myocarditis: Inflammatory processes of the muscular walls of the heart (MYOCARDIUM) which result in injury to the cardiac muscle cells (MYOCYTES, CARDIAC). Manifestations range from subclinical to sudden death (DEATH, SUDDEN). Myocarditis in association with cardiac dysfunction is classified as inflammatory CARDIOMYOPATHY usually caused by INFECTION, autoimmune diseases, or responses to toxic substances. Myocarditis is also a common cause of DILATED CARDIOMYOPATHY and other cardiomyopathies.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Kaplan-Meier Estimate: A nonparametric method of compiling LIFE TABLES or survival tables. It combines calculated probabilities of survival and estimates to allow for observations occurring beyond a measurement threshold, which are assumed to occur randomly. Time intervals are defined as ending each time an event occurs and are therefore unequal. (From Last, A Dictionary of Epidemiology, 1995)Autophagy: The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.Heart Septal Defects, Ventricular: Developmental abnormalities in any portion of the VENTRICULAR SEPTUM resulting in abnormal communications between the two lower chambers of the heart. Classification of ventricular septal defects is based on location of the communication, such as perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical muscular defect.Propanolamines: AMINO ALCOHOLS containing the propanolamine (NH2CH2CHOHCH2) group and its derivatives.Isoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Ischemic Preconditioning, Myocardial: Exposure of myocardial tissue to brief, repeated periods of vascular occlusion in order to render the myocardium resistant to the deleterious effects of ISCHEMIA or REPERFUSION. The period of pre-exposure and the number of times the tissue is exposed to ischemia and reperfusion vary, the average being 3 to 5 minutes.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Heart-Assist Devices: Small pumps, often implantable, designed for temporarily assisting the heart, usually the LEFT VENTRICLE, to pump blood. They consist of a pumping chamber and a power source, which may be partially or totally external to the body and activated by electromagnetic motors.Animals, Newborn: Refers to animals in the period of time just after birth.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Aging: The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.Cardiac Surgical Procedures: Surgery performed on the heart.Cell Line, Tumor: A cell line derived from cultured tumor cells.Caspase Inhibitors: Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.bcl-2-Associated X Protein: A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.Hypertrophy, Left Ventricular: Enlargement of the LEFT VENTRICLE of the heart. This increase in ventricular mass is attributed to sustained abnormal pressure or volume loads and is a contributor to cardiovascular morbidity and mortality.Infant Mortality: Postnatal deaths from BIRTH to 365 days after birth in a given population. Postneonatal mortality represents deaths between 28 days and 365 days after birth (as defined by National Center for Health Statistics). Neonatal mortality represents deaths from birth to 27 days after birth.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Heart Valve Prosthesis Implantation: Surgical insertion of synthetic material to repair injured or diseased heart valves.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Double-Blind Method: A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment.Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery.Ventricular Dysfunction: A condition in which HEART VENTRICLES exhibit impaired function.Ventricular Fibrillation: A potentially lethal cardiac arrhythmia that is characterized by uncoordinated extremely rapid firing of electrical impulses (400-600/min) in HEART VENTRICLES. Such asynchronous ventricular quivering or fibrillation prevents any effective cardiac output and results in unconsciousness (SYNCOPE). It is one of the major electrocardiographic patterns seen with CARDIAC ARREST.Caspase 8: A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see LINEAR MODELS) the relationship is constrained to be a straight line and LEAST-SQUARES ANALYSIS is used to determine the best fit. In logistic regression (see LOGISTIC MODELS) the dependent variable is qualitative rather than continuously variable and LIKELIHOOD FUNCTIONS are used to find the best relationship. In multiple regression, the dependent variable is considered to depend on more than a single independent variable.Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing MYOCARDIAL REPERFUSION INJURY.Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time.Stroke: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)Predictive Value of Tests: In screening and diagnostic tests, the probability that a person with a positive test is a true positive (i.e., has the disease), is referred to as the predictive value of a positive test; whereas, the predictive value of a negative test is the probability that the person with a negative test does not have the disease. Predictive value is related to the sensitivity and specificity of the test.Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Cardiac Catheterization: Procedures in which placement of CARDIAC CATHETERS is performed for therapeutic or diagnostic procedures.Death Domain Receptor Signaling Adaptor Proteins: Intracellular signaling adaptor proteins that bind to the cytoplasmic death domain region found on DEATH DOMAIN RECEPTORS. Many of the proteins in this class take part in intracellular signaling from TUMOR NECROSIS FACTOR RECEPTORS.Tachycardia: Abnormally rapid heartbeat, usually with a HEART RATE above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.Acute Disease: Disease having a short and relatively severe course.Heart Septal Defects, Atrial: Developmental abnormalities in any portion of the ATRIAL SEPTUM resulting in abnormal communications between the two upper chambers of the heart. Classification of atrial septal defects is based on location of the communication and types of incomplete fusion of atrial septa with the ENDOCARDIAL CUSHIONS in the fetal heart. They include ostium primum, ostium secundum, sinus venosus, and coronary sinus defects.BH3 Interacting Domain Death Agonist Protein: A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.Energy Metabolism: The chemical reactions involved in the production and utilization of various forms of energy in cells.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Reference Values: The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.Tachycardia, Ventricular: An abnormally rapid ventricular rhythm usually in excess of 150 beats per minute. It is generated within the ventricle below the BUNDLE OF HIS, either as autonomic impulse formation or reentrant impulse conduction. Depending on the etiology, onset of ventricular tachycardia can be paroxysmal (sudden) or nonparoxysmal, its wide QRS complexes can be uniform or polymorphic, and the ventricular beating may be independent of the atrial beating (AV dissociation).Echocardiography, Doppler: Measurement of intracardiac blood flow using an M-mode and/or two-dimensional (2-D) echocardiogram while simultaneously recording the spectrum of the audible Doppler signal (e.g., velocity, direction, amplitude, intensity, timing) reflected from the moving column of red blood cells.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Models, Animal: Non-human animals, selected because of specific characteristics, for use in experimental research, teaching, or testing.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor.Adrenergic beta-Agonists: Drugs that selectively bind to and activate beta-adrenergic receptors.Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Pacemaker, Artificial: A device designed to stimulate, by electric impulses, contraction of the heart muscles. It may be temporary (external) or permanent (internal or internal-external).Baroreflex: A response by the BARORECEPTORS to increased BLOOD PRESSURE. Increased pressure stretches BLOOD VESSELS which activates the baroreceptors in the vessel walls. The net response of the CENTRAL NERVOUS SYSTEM is a reduction of central sympathetic outflow. This reduces blood pressure both by decreasing peripheral VASCULAR RESISTANCE and by lowering CARDIAC OUTPUT. Because the baroreceptors are tonically active, the baroreflex can compensate rapidly for both increases and decreases in blood pressure.Atrial Fibrillation: Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.Reproducibility of Results: The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.Creatine Kinase: A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.Oxygen: An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.Vascular Resistance: The force that opposes the flow of BLOOD through a vascular bed. It is equal to the difference in BLOOD PRESSURE across the vascular bed divided by the CARDIAC OUTPUT.Anoxia: Relatively complete absence of oxygen in one or more tissues.Chi-Square Distribution: A distribution in which a variable is distributed like the sum of the squares of any given independent random variable, each of which has a normal distribution with mean of zero and variance of one. The chi-square test is a statistical test based on comparison of a test statistic to a chi-square distribution. The oldest of these tests are used to detect whether two or more population distributions differ from one another.Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx).Sinoatrial Node: The small mass of modified cardiac muscle fibers located at the junction of the superior vena cava (VENA CAVA, SUPERIOR) and right atrium. Contraction impulses probably start in this node, spread over the atrium (HEART ATRIUM) and are then transmitted by the atrioventricular bundle (BUNDLE OF HIS) to the ventricle (HEART VENTRICLE).Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.Caspase 9: A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.Fas Ligand Protein: A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Cytochromes c: Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.Receptors, Adrenergic, beta: One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Diuretics: Agents that promote the excretion of urine through their effects on kidney function.Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.Defibrillators, Implantable: Implantable devices which continuously monitor the electrical activity of the heart and automatically detect and terminate ventricular tachycardia (TACHYCARDIA, VENTRICULAR) and VENTRICULAR FIBRILLATION. They consist of an impulse generator, batteries, and electrodes.Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from DEATH, the physiological cessation of life and from MORTALITY, an epidemiological or statistical concept. Lazarus sign Lazarus taxon Near-death experience Premature burial Suspended animation The Lazarus Heart Hornby K, Hornby L, ... "Death following spontaneous recovery from cardiopulmonary arrest in a hospital mortuary: 'Lazarus phenomenon' in a case of ... About a minute after resuscitation ended, a nurse noticed a rhythm on the heart monitor and resuscitation was resumed. The ... Judith Johnson, 61, went into cardiac arrest at Beebe Medical Center in Lewes, Delaware, United States, in May 2007. She was ... May 27, 1942: Death due to heart attack. Chen Duxiu was born in the city of Anqing, in Anhui province. He was born to a wealthy ... In 1932, Chen was arrested by the government of the Shanghai International Settlement, where he had been living since 1927, and ... 1932 to 1937: Arrest by Kuomintang authorities and imprisonment. 1937 to 1942: Retires from public life. ... which had led to the deaths of thousands of Communists - now known as the Shanghai massacre of 1927, and because of his ... "Heart Attack Cited in Death of Louisiana Tech Running Back Tyrone Duplessis". KSLA.com. 2012-02-13. Retrieved 2013-04-05. " ... cardiac arrest (2013) † Davis was under contract when he died though did not play in a game due to his illness. †† Johnson was ... "Coroner: Northwestern State death from heart disease". USA Today. 2004-03-18. Retrieved 2015-09-20. "Arkansas Linebacker Found ... Each NFL player is listed with the team for which he last played before his death, rather than the team with which he spent ... Ramchand suffered three heart attacks in the two months preceding his death. He was admitted to the Hinduja Hospital in Mumbai ... In 1995, he recovered after suffering a cardiac arrest. ... on 1 September 2003, and, days before his death, asked the ... Gollapudi, Nagaraj (8 September 2003). "Former cricketers react to Ramchand's death". ESPNcricinfo. Retrieved 1 August 2016. ... "heart complications". "Gulabrai Ramchand". ESPNcricinfo. Retrieved 1 August 2016. "Wisden - GS Ramchand". ESPNcricinfo. ... ... puthiyathalaimurai.tv/arcot-mla-death-from-a-heart-attack Profile on Rajya Sabha website. ... He died from cardiac arrest on 18 July 2013. "List of MLAs from Tamil Nadu 2011" (PDF). Govt. of Tamil Nadu. Archived from the ... The noted cause of death was "acute heart failure". Before his arrest, Stefan Meier did not have a history of heart problems. ... In October 1941, Stefan Meier, after denunciation by a neighbor, was arrested again and sentenced by a Special Court of ... Half of these deaths come from heart failure which often develops from electrical heart rhythm problems such as atrial ... "cardiac arrest" is often confused with "sudden death" from ventricular fibrillation.) This sudden death rate is equal to the ... care and treatment of cardiac electrical diseases that lead to heart failure and sudden death. It includes national and ... The other half of these deaths occur suddenly due to an extreme and instantly fatal cardiac turbulence called ventricular ... Lacking proper glycogen storage, the horse's brain, heart muscle, and skeletal muscles cannot function, leading to rapid death ... Symptoms include general weakness, contracted tendons, hypoglycemic seizures, cardiac arrest, and sudden death. Horses that are ... It leads to abortion, stillbirths, or early death of affected animals. Glycogen is a molecular polymer of glucose used to store ... An abnormal heart rate can occur which can result in cardiac arrest and death. Common causes include kidney failure, ... Injecting potassium chloride into the heart muscle disrupts the signal that causes the heart to beat. This same amount of ... cardiac arrest in special situations: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and ... Among those who are in hospital, rates are between 1% and 2.5%. It increases the overall risk of death by at least ten times. ... The cause of death was heart disease. Worrell died in 1899 at the Kings County Hospital of burns she sustained while sleeping ... Police of the precinct had arrested her a number of times. Her sisters separated themselves from her years before because of ... Singh was arrested under sections 279 (rash and negligent driving) and 304A (causing death by negligence) of the Indian Penal ... Later the doctors said that his death occurred maybe due to heart attack. His funeral was held at 2pm on 4 June 2014 at his ... After the death of his father in 1969, his brothers took care of his education. He is the third child in the family. His family ... He was immediately rushed to the AIIMS hospital but later went into cardiac arrest. He was administered CPR but could not be ... Arrest made in ex-Sacred Heart Pioneers player Chauncey Hardy's death - ESPN "Chauncey Hardy: Former Sacred Heart Basketball ... Before his death he had 3 heart attacks. A day later, a man was arrested after he surrendered to police. He was put in custody ... Chauncey, a native of Middletown, Connecticut, previously played basketball for Sacred Heart University in Fairfield, ... Individual studies have indicated snus is correlated with death from heart attack and with heart failure. The European Union ... At higher doses, tachycardia, reflex bradycardia, arrhythmia or even cardiac arrest can occur in some individuals.[citation ... In contrast, since women traditionally are less likely to use snus, their rate of tobacco-related deaths in Sweden can be ... Asplund, Kjell (October 29, 2002). Snuffing, Smoking and the risk for heart disease and other vascular diseases (PDF) (3rd ed ... Some newspapers wrote that he had died of a heart attack, however others suggested that his death had been related to his ... Four years before, in 1933, Reza Pahlavi had arrested Davar's closest friend Teymourtash. Teymourtash died shortly afterward in ... His heart rate dropped ... leading to his death from a cardiac arrest ... a classic secondary response to raised intercranial ... Wroe, David (August 19, 2014). "Reza Barati: Two men arrested over death of asylum seeker at PNG detention centre". Retrieved ... In July 2014 a security guard and later a Salvation Army worker, both Papua-New Guinean, were arrested. Both men were charged ... Berati ... was struck from behind .... also kicked and had a rock dropped on his head, before dying of heart failure while ... He was found guilty and sentenced to death by hanging. Pister died in Landsberg Prison of an acute heart attack on 28 September ... Pister was arrested by the Americans in 1945; put on trial for war crimes by the American Military Tribunal at Dachau with 30 ... This train came to be known as the "Death Train". It took until 27 April for the train to arrive at Dachau with many aboard ... The coroner ruled Brinkamp's death to be attributed to a heart attack. Following his death, she inherited $5,000 from a life ... Authorities reported Vermilya had been ingesting the "white pepper" since her house arrest on October 28. By November 9, she ... The coroner, however, ruled her cause of death as "acute nephritis". Due to the unusually high number of deaths within the ... His death was determined to be caused by gastritis. Smith was still married at the time of his supposed nuptials to Vermilya. ... Death can occur rapidly following overdose as a result of respiratory arrest and paralysis of the heart. Calabar Bean Cymserine ... and death). Physostigmine may counteract GHB by producing a nonspecific state of arousal. However, not enough scientific ... induces neuronal cell death". Toxicology and Applied Pharmacology. 106 (1): 28-37. doi:10.1016/0041-008X(90)90102-Z. PMID ... The gas was designed to induce cardiac arrest, making the victim's death look like a heart attack. Stashynsky used the weapon ... In 1950 he was arrested for traveling without a ticket on public transportation to Lviv from his village. After agreeing to act ... 182-9 Echo of the Arrest of the Murderer Lev Rebet How the KGB organized the assassination of Bandera. (Як КДБ організовував ... ISBN 0-465-00312-5. Plokhy, Serhii (5 January 2017). "How a KGB Assassin Used the Death of His Child to Defect". POLITICO ... Since the ring has replaced her heart, she cannot remove it without risking death by cardiac arrest. She is also vulnerable to ... In the aftermath of the War of the Green Lanterns and the death of the rogue Guardian Krona, Atrocitus felt his rage dimming, ... where she is among the Red Lanterns who are overcome by the rage generated by the deaths of billions of beings within ... He forged Man-lung's signature to frame him, causing Man-lung to be arrested. He dies of a heart attack in the final episode ... After the death of his ex-wife, he marries Cheung Hok-wa. Ekin Cheng as Pau Man-lung (包文龍) Formerly an agent working for the ... His greed and ambition would inadvertently cause the deaths of Wong Lui's mother and Ching-lit. Amy Kwok as Wong Lui (黃蕾) The ... However, she soon opens her heart to Man-lung and his family when they show her kindness and acceptance, something she had been ... Myocardial infarction (a.k.a. heart attack) - A myocardial infarction is the death of a part of the heart which is typically ... There are several causes of sudden cardiac death and it is distinct from cardiac arrest. The leading cause of SCD in young ... American College of Cardiology American Heart Association Heart Rhythm Society Indian Heart Association National Heart ... Heart cancer - Cancer of the heart is very rare and those cancers tend to be benign. Myxoma - Most common tumor of the heart. ... Current passing through the heart produces an immediate cardiac arrest that also leads shortly to unconsciousness and death. It ... As early as 1853, he designed a lethal chamber that would gas animals to death relatively painlessly, and he founded the Model ... that produce unconsciousness or death through hypoxia or asphyxia. The process is not instantaneous. With percussive stunning, ... Gas stunning Percussive stunning Electrical stunning is done by sending an electric current through the brain and/or heart of ... Broken-hearted, he was placed under house arrest, and his death followed ten weeks later, on 31 December. Unamuno died while ... Millán Astray responded: "Death to intelligence! Long live death!" provoking applause from the Falangists. Pemán, in an effort ... Unamuno was removed from his position of rector of the University of Salamanca by Franco and placed under house arrest. He died ... He called the battle cry of the elite armed forces group named La Legión-"Long live death!"-repellent and suggested Astray ... "Heart condition caused White Rock Marathon runner's death", The Dallas Morning News, 2 March 2009. "Teacher dies from heart ... "New York City Marathon: Two Runners Are Dead From Cardiac Arrest", The New York Times, 7 November 1994. "A second runner, a man ... "Coach copes with wife's death", The Columbus Dispatch, 27 January 2004. "The Fit Man's Heart Threat", Men's Health, 23 August ... The most-frequent causes are: sudden cardiac death, triggered by a congenital or acquired heart disorder; exercise-associated ... ... was very frail and had to be carried. After Mok's troops apprehended them, Pol Pot was placed under house arrest.[ ... Heuveline's central estimate is 2.52 million excess deaths, of which 1.4 million were the direct result of violence. ... On 15 April 1998, Pol Pot died in his sleep, apparently of heart failure. His body was preserved with ice and formaldehyde ... Pol Pot had grown suspicious of Son Sen and in June 1997 ordered his death. Khmer Rouge cadres subsequently killed Son and 13 ... ... after the death of a girl thrown from an inflatable trampoline in Gorleston. ... A man and woman from Great Yarmouth have been arrested - ... Heart East Anglia On Air Now. Hearts Feel Good Weekend with ... A man and woman from Great Yarmouth have been arrested - after the death of a girl thrown from an inflatable trampoline in ... Two arrested after Gorleston inflatable death. 12 July 2018, 12:36 , Updated: 12 July 2018, 12:53 ... These celebrities who died of heart attacks are listed alphabetically and include the famous cardiac arrest victims hometown ... List of famous people who died of cardiac arrest, including photos, birthdates, professions, and other information. ... These notable heart attack deaths include modern and long-gone famous men and women, from politicians to religious leaders to ... Everyone on this list has cardiac arrest as a cause of death somewhere in their public records, even if it was just one ... Details of his death are still emerging, but friends and relatives say they have been concerned about Jacksons use of ... Iconic pop star Michael Jackson suffered a cardiac arrest and died on Thursday at the age of 50. ... Heart attacks are about twice as common as cardiac arrests, but a heart attack can progress to a cardiac arrest if not treated. ... and tissue death in part of the heart muscle. In contrast to cardiac arrest, heart attack patients may not lose consciousness. ... The store owner suffers a heart attack and dies.Is the younger man guilty of ... Trial begins in case of heart attack death Pushed, grocer went into cardiac arrest. ... "The medical examiner will testify the stress of that attack caused the man to have a heart attack," the prosecutor added. "He ... Flannery said the jury could resolve the case by answering a single question: "Did the death occur during that crime, during ... Study Highlights Heart-related deaths spike around Christmas, and the effect may not be because of the cold winter season. ... The mission of the Sudden Cardiac Arrest (SCA) Foundation is to prevent death and disability from sudden cardiac arrest. The ... DALLAS, TX - Heart-related deaths spike during Christmas, but the effect may have nothing to do with the cold winter season, ... Heart-related deaths spike around Christmas, and the effect may not be because of the cold winter season. ... ... claiming the companys products led to the death of his wife. ... Lawrence Harbaugh filed a GranuFlo heart attack lawsuit against ... Furthermore, a 2010 study by Fresenius examined the incidence of sudden death and cardiac arrest among patients. These results ... which increases the risk of adverse GranuFlo side effects including cardiac arrest and sudden cardiac death. It also places ... GranuFlo Cardiac Arrest Lawsuit Filed Against Fresenius. July 24, 2013. By: Jacky Gale Granuflo ... Quantitative troponin and death, cardiogenic shock, cardiac arrest and new heart failure in patients with non-ST-segment ... Quantitative troponin and death, cardiogenic shock, cardiac arrest and new heart failure in patients with non-ST-segment ... Quantitative troponin and death, cardiogenic shock, cardiac arrest and new heart failure in patients with non-ST-segment ... With no effective heartbeat, the brain and other vital organs are deprived of blood, leading to death within minutes. ... Cardiac arrest occurs when the heart suddenly stops functioning. ... Sudden Cardiac Arrest Cardiac arrest occurs when the heart ... Cardiac arrest is not a heart attack. The heart usually continues beating during a heart attack; however, cardiac arrest may ... Causes of Cardiac Arrest. Electrical signals in the heart synchronize heart function so that the heart beats properly and pumps ... ... the diagnostic test most often used to assess the electrical and muscular functions of the heart. ... Sudden Cardiac Arrest Foundations mission is to raise awareness about sudden cardiac arrest and help save lives through ... Sudden Cardiac Arrest Foundation is a non-profit organization with a 501(c)(3) tax-exempt status. All rights reserved. ... His 2014 research showed that the incidence of sudden cardiac arrest among athletes may be 1 in 50,000 - four times higher than ... James Gandolfinis Death Brings to Light Distinction Between a Heart Attack and Sudden Cardiac Arrest. June 20, 2013. AED ... Gandolfini suffered a heart attack or cardiac arrest. The investigation into cause of death is ongoing, but the head physician ... As mentioned above, cardiac arrest may occur as a result of a heart attack or coronary heart disease, but it can also be ... Heart attacks occur when there is a blockage of vessels in the heart limiting blood flow; however, the heart generally keeps ... Routinely implanting pager-size defibrillators in heart attack survivors to stop cardiac arrest reduces their chance of dying ... Effective Treatment for Heart Failure Possible Following Discovery of Heart Molecule. Significant Decrease in Heart Disease ... a history of heart attack and evidence of resulting heart weakness. Heart specialists called the results important, but some ... ATLANTA (AP) - Routinely implanting pager-size defibrillators in heart attack survivors to stop cardiac arrest reduces their ... Iran has issued an arrest warrant and asked Interpol for help in detaining President Donald Trump and dozens of others it ... Grant Imahara mourned by MythBusters co-stars after sudden death: My heart is broken. Yahoo Celebrity ... which represents the highest-level arrest request issued by Interpol. Local authorities generally make the arrests on behalf of ... TEHRAN, Iran (AP) - Iran has issued an arrest warrant and asked Interpol for help in detaining President Donald Trump and ... ... is when the heart stops beating suddenly and unexpectedly - possibly leading to sudden cardiac death. Read on to learn more ... Sudden Cardiac Arrest (SCA) / Sudden Cardiac Death (SCD). While heart disease is the leading cause of death in the United ... Protect This Heart Sudden Cardiac Arrest Enlarged Heart Long QT Syndrome Chain of Survival Heart Screenings Research * ... What causes sudden cardiac arrest in children?. There are two types of heart conditions that lead to sudden cardiac arrest in ... WebMD explains the difference between sudden cardiac arrest and a heart attack. ... Sudden cardiac death (SCD) is a sudden, unexpected death caused by a change in heart rhythm (sudden cardiac arrest). It is the ... SCD is responsible for half of all heart disease deaths.. How Is Sudden Cardiac Arrest Different from a Heart Attack?. Sudden ... Heart Disease and Sudden Cardiac Death. In this Article. In this Article In this Article * How Is Sudden Cardiac Arrest ... ... died from a heart attack ... and no drugs were found in his system ... TMZ has learned.The L.A. County Coroner… ... Dad Shares Update After Nude, Bloody Arrest. Hes Gonna Be Fine Ozzy Osbourne. Suing AEG Youre Making Me a Slave to Staples ... As for why he had a heart attack, were told there was evidence of heart disease. A source connected with the Coroner tells TMZ ... Sylvester Stallones son, Sage Stallone, died from a heart attack ... and no drugs were found in his system ... TMZ has learned ... Toronto police have arrested a fugitive who fled to Canada from the U.S. after he was convicted of reckless driving and driving ... How a death on Torontos streets strikes at the heart of what it means to be good. ... Toronto police arrest fugitive wanted in Wisconsin. Toronto police have arrested a fugitive who fled to Canada from the U.S. ... Toronto police have arrested a fugitive who fled to Canada from the U.S. after he was convicted of reckless driving and driving ... A male in his late teens has been arrested at his Scarborough-area home after a student of a similar age was stabbed in the ... How a death on Torontos streets strikes at the heart of what it means to be good. ... UPDATED: Teen arrested after Danforth and Greenwood stabbing. J.P. Moczulski for National Post ... A male in his late teens has been arrested at his Scarborough-area home after a student of a similar age was stabbed in the ... Dog the Bounty Hunter rushed to the hospital for heart emergency, months after wifes death. ... Arrest of Youcef Nadarkhanis Lawyer: A Bad Situation Made Worse. Arrest of Youcef Nadarkhanis Lawyer: A Bad Situation Made ... Nadarkhani was arrested in October 2009 for protesting the mandatory teaching of Islam at his childrens schools. His charges ... One aspect of Dadkhahs arrest which makes the situation so dire is the fact that now Iranian pastor Youcef Nadarkhani, who has ... TMZ has obtained Casey Johnsons death certificate.The certificate lists Caseys death as deferred. Shes listed as an ... Insane Nude, Bloody Arrest After Penthouse Meltdown Queen Latifah. Mom Dies. After Long Struggle with Heart Condition ... Casey Johnson Death Certificate. TMZ has obtained Casey Johnsons death certificate.. The certificate lists Caseys death as " ... Caseys cause of death is still unknown, but our sources say her frail medical condition -- including diabetes -- may have ... ... to patients with heart disease because of a ... Sex-Cult Story Is Much Deeper Than Allison Macks Arrest. ... to patients with heart disease because of a "potential increased risk of heart problems or death that can occur years later." ... As a result, the FDA has added a new warning about this increased risk of death in patients with heart disease, have advised ... However, based on these studies, the FDA is unable to determine why the risk of death is greater for patients with heart ... Heart Arrest. Death, Sudden. Death, Sudden, Cardiac. Heart Diseases. Cardiovascular Diseases. Death. Pathologic Processes. ... Heart Arrest Death, Sudden, Cardiac Procedure: Cardiopulmonary resuscitation (CPR) Drug: Epinephrine Drug: Atropine Drug: ... related to CPR interventions and the cause of arrest. The cause of arrest will be determined based on chart records, interview ... In-hospital Cardiac Arrest - Dynamics and State Transitions. The safety and scientific validity of this study is the ... Jarrid Wilsons wife shares Bible verse late husband sent before his death: Its speaking to my heart. ... Should the Secret Service Arrest Former Virginia Governor Terry McAuliffe?. Should the Secret Service Arrest Former Virginia ... hating liberals may want to become familiar with this law before issuing a threat against the President as they may be arrested ... ... we also used the Million Hearts cardiac arrest definition (10) and examined cardiac arrest deaths that had heart disease ... and heart failure death rates increased. Death rates attributable to diabetes-related heart disease and non-AMI ischemic heart ... Limiting cardiac arrest deaths to those defined as such by Million Hearts or to those defined as heart disease by using the ... We investigated heart disease death rates among all people in Maine during 1999-2017. We analyzed trends in heart disease death ... 2,200 per each stroke death annually; $2,100 for each heart disease death; and $91 for each cardiac arrest death. The ... Cardiac arrest gets little research funding despite huge death toll. By AMERICAN HEART ASSOCIATION NEWS ... The American Heart Associations 2017 Statistical Update does not rank cardiac arrest as a separate cause of death, but the ... Cardiac arrest is a leading cause of death in the U.S. but gets just a fraction of the governments funding for medical ... OccurPatientsRhythmsSurvivorsTreatment of Cardiac ArrestWent into cardiac arrestSymptomsPerson'sChestCall 911BlockageSuffer cardiac arrest each yearDefibrillatorsHeart's electricalSuddenlyNewsIncidenceResearchersLead to cardiac arrestCardiovascularSuffers from sudden cardiaRisk FactorsFramingham HeartCase of cardiac arrestSudden Cardiac Arrest FoSuffered from cardiac arrestCardiac arrest survival ratesFailureSurviveAthletesSurvival ratesOccurs when the electricalCoroner'sPrevent cardiacArteriesDisease deathsTrigger cardiac arrest - Mr. Flannery said the jury could resolve the case by answering a single question: "Did the death occur during that crime, during the assault? (baltimoresun.com) - however, cardiac arrest may occur as a result of a heart attack. (barnesjewish.org) - Cardiac arrest can also occur for no known reason. (barnesjewish.org) - Sudden cardiac arrest is not a heart attack (myocardial infarction) but can occur during a heart attack . (cdc.gov) - When this occurs, the heart is unable to pump blood and death will occur within minutes, if left untreated. (cdc.gov) - The Food and Drug Administration (FDA) has issued a warning advising prescribers to practice caution before prescribing the common antibiotic Biaxin, aka clarithromycin, to patients with heart disease because of a "potential increased risk of heart problems or death that can occur years later. (yahoo.com) - An estimated 359,400 cases of cardiac arrest occur in the United States outside of a hospital setting each year. (usatoday.com) - The SCA Risk Assessment is an interactive tool designed to help individuals estimate their risk of sudden cardiac arrest (SCA), a common cardiac arrhythmia that can occur abruptly and without warning. (hrsonline.org) - In fact, two-thirds of SCA deaths occur without any prior indications of heart disease. (hrsonline.org) - 2 - 4 How these data apply to approximately one-third of in-hospital cardiac arrests that occur in intensive care units (ICUs) is less clear. (cmaj.ca) - Even if it does not confer immortality, physicians should emphasize the benefits of exercise rather than perseverating on the rare cardiac death that happens to occur during an athletic event. (acc.org) - Most SIDS deaths occur in the winter. (medlineplus.gov) - If certain diseases occur during pregnancy, they may cause a baby to be born with heart block. (daviddarling.info) - Acute pulmonary cardiovascular strain" sounds like a naturally-occurring health event, but it's nothing more than severe strain on the heart and lungs -- something that might occur when an already out of shape person is restrained (within policy) by several men and a police dog while being intermittently beaten (within policy). (techdirt.com) - Although more research is needed to explain the spike in deaths, researchers suggest one possibility may be that patients hold back in seeking medical care during the holiday season. (sca-aware.org) - Another explanation may have to do with a terminally ill patients' will to live and hold off death for a day that is important to them. (sca-aware.org) - Furthermore, a 2010 study by Fresenius examined the incidence of sudden death and cardiac arrest among patients. (injurylawyer-news.com) - They confirmed that patients were six to eight times more likely to suffer cardiac arrest when using GranuFlo and NaturaLyte . (injurylawyer-news.com) - This warning is based on the results of a 10-year study of patients with coronary heart disease from a large clinical trial, named the CLARICOR trial, that first observed the issue. (yahoo.com) - Within the trial, there was an unexpected increase in deaths among patients with coronary heart disease who received a two-week course of Biaxin. (yahoo.com) - However, based on these studies, the FDA is unable to determine why the risk of death is greater for patients with heart disease . (yahoo.com) - As a result, the FDA has added a new warning about this increased risk of death in patients with heart disease, have advised prescribers to consider other antibiotics instead, and have added the startling study results to all Biaxin labels. (yahoo.com) - Patients with in-hospital cardiac arrest at St.Olavs Hospital (Trondheim, Norway) during the study period. (clinicaltrials.gov) - Coenzyme Q10 cut mortality rates in half when added to medical therapy for patients with severe heart failure, according to results of a clinical trial reported at Heart Failure 2013, the annual meeting for the Heart Failure Association of the European Society of Cardiology, in Lisbon, Portugal. (everydayhealth.com) - Of the 420 patients with severe heart failure from Europe, India, Malaysia and Australia in the study, those who took 100 milligrams of coenzyme Q10 three times a day along with their current medical therapy showed improvement in their heart failure symptoms, such as shortness of breath and fatigue. (everydayhealth.com) - To the surprise of researchers, the number of hospitalizations for heart failure was also lower - 29 patients compared with 55 among those treated with a placebo along with their regular medications. (everydayhealth.com) - Deaths from heart disease in patients who took coenzyme Q10 also were significantly lower over two years - only 18 deaths compared with 36 deaths in patients who received a placebo. (everydayhealth.com) - Professor Svend Aage Mortensen, from the Heart Center of Copenhagen University Hospital in Denmark, and other Q-SYMBIO Study investigators concluded that coenzyme Q10 supplementation not only improved survival for patients with severe heart failure but that the treatment was safe, with fewer reported side effects than standard treatments. (everydayhealth.com) - The new results with coenzyme Q10 supplementation offer hope for patients with severe heart failure. (everydayhealth.com) - Physicians should always watch out for OSA in their heart patients and treat it promptly when present. (inquirer.net) - It is powered by an implantable pulse generator, similar to a heart pacemaker device implanted in patients with heart blocks and very slow heart rates. (inquirer.net) - He musters a passel of recent research that suggests that the 'obsession' with lowering a patients' total cholesterol with statins, and a public health message that has made all sources of saturated fat verboten to the health-conscious, have failed to reduce heart disease. (sun-sentinel.com) - Search this state listing to locate a Mended Heart chapter offering support and encouragement to heart patients, families and caregivers. (healthfinder.gov) - This site focuses on educating heart patients about the various aspects of coping with heart disease, including topics such as coping with depression, lifestyle changes, cholesterol and nutrition. (healthfinder.gov) - The new study tested the rival drug, Praluent, for a longer time and in patients at higher risk - nearly 19,000 people who in the previous year had a heart attack or chest pain serious enough to put them in the hospital. (wandtv.com) - February 20, 2013 Dr. Sam Parnia researches the experiences of cardiac arrest patients in the time between when their hearts stop and when they are brought back to life. (npr.org) - Background - Given the high incidence of sudden death in patients with chronic heart failure (CHF) and the efficacy of implantable cardioverter-defibrillators, an appropriate tool for the prediction of sudden death is desirable. (ahajournals.org) - For prediction of sudden death, only survivors without heart transplantation (HTx) or a mechanical assist device and patients who died suddenly were analyzed. (ahajournals.org) - Mode of death was sudden in 44 patients (49%), whereas 31 patients (35%) had pump failure and 14 patients (16%) died from other causes. (ahajournals.org) - 2.11 (130 pg/mL), Kaplan-Meier sudden death-free survival rates were significantly higher in patients below (99%) compared with patients above (81%) this cutoff point ( P =0.0001). (ahajournals.org) - Conclusion - BNP levels are a strong, independent predictor of sudden death in patients with CHF. (ahajournals.org) - Up to 50% of total mortality in patients with chronic heart failure (CHF) is attributable to sudden death. (ahajournals.org) - 1-year mortality attributable to sudden death ranges from 2% to 4% for patients in NYHA classes I and II and from 5% to 12% for patients in NYHA classes III and IV. (ahajournals.org) - 1 Most sudden death events in ambulatory patients are caused by ventricular tachyarrhythmias. (ahajournals.org) - 1 Studies of cardiac arrest involving patients admitted to non-critical care beds showed that survival has not improved despite 40 years of medical advances. (cmaj.ca) - On the other hand, survival might be expected to be lower because critical care patients have a high disease burden and experience arrests despite aggressive preemptive life support. (cmaj.ca) - therefore, cardiac arrest in these patients implies cardiovascular collapse in addition to noncardiac illness (i.e., at least two-organ failure). (cmaj.ca) - We evaluated survival outcomes during a five-year follow-up period among adult patients who experienced cardiac or respiratory arrest in ICUs at four hospitals. (cmaj.ca) - This study is designed as a multi-center prospective observational study of newly diagnosed Heart Failure (HF) patients to test the hypothesis that additional Ejection Fraction (EF) recovery occurs between 90 and 180 days as Guideline Directed Medical Therapy (GDMT) is achieved. (clinicaltrials.gov) - The new study is consistent with earlier results that have indicated a potential heart health benefit from an occasional drink, but it amplifies the message since it involved millions of patients, said Dr. Allan Stewart, director of aortic surgery at Mount Sinai Hospital in New York City. (hon.ch) - The reduction of mortality from sudden cardiac arrest (SCA) in the setting of coronary heart disease (CHD) remains a major challenge, especially among patients with type 2 diabetes. (springer.com) - We summarize recent evidence that suggests that the increase in risk in patients with diabetes is not specific for SCA, as diabetes also is associated with a similar increase in risk for non-SCA CHD death and non-fatal myocardial infarction. (springer.com) - We also present previously published and unpublished data that demonstrates that both clinically-recognized microvascular and autonomic neuropathy also are associated with the risk of SCA among treated patients with diabetes, after taking into account prior clinically-recognized heart disease and other risk factors for SCA. (springer.com) - Sudden cardiac death in patients with diabetes. (springer.com) - 8% of those patients developed a heart arrhythmia, compared with 0.3% of patients in the control group. (cnn.com) - To determine whether hypertensive patients with ECG abnormalities and receiving hydrochlorothiazide diuretics were at increased risk of sudden death. (clinicaltrials.gov) - For example, withdrawing life support often doesn't lead to immediate cardiac arrest, and some patients don't die at all. (firstthings.com) - DCD requires the transfer of patients before or upon death to the operating room for organ procurement. (firstthings.com) - David Siscovick and co-workers interviewed 334 patients - or spouses of patients - who suffered cardiac arrest in the Seattle area. (thefreelibrary.com) - AstraZeneca's Farxiga, originally developed to treat diabetes, also lowered the risk of heart problems in heart failure patients who did not have diabetes. (yahoo.com) - Among 2,605 of such patients treated for 18 months, about 9% of those on Farxiga had worsening heart failure or heart-related death versus nearly 13% of those not given the drug. (yahoo.com) - But in the study, within one year of getting the implants, 26.7 percent of the dual-chamber patients died or were hospitalized with heart failure, compared with 16.1 percent of patients who got only backup pacemaking help. (ljworld.com) - A study earlier this year suggesting that millions of heart patients could benefit from defibrillators raised concerns about the costs. (ljworld.com) - The new study could help fine-tune which patients could get by with the cheaper models, said Dr. Sidney Smith, the American Heart Assn.'s chief science officer. (ljworld.com) - Smith noted the new study included many patients with mild heart failure and didn't address whether dual-chamber devices would be better than less costly ones for the sickest heart patients. (ljworld.com) - University of Sydney researchers are raising concerns over the need for informed decision making for genetic testing after a study published today finds patients at risk of inherited heart disease do not always understand test results or the impact results will have on their life. (news-medical.net) - Some heart disease patients face a higher risk of sudden cardiac death, which can happen when an arrhythmia -- an irregular heartbeat-- disrupts the normal electrical activity in the heart and causes the organ to stop pumping. (news-medical.net) - In an effort to hasten care for patients in cardiac arrest, researchers at the University of Minnesota are studying whether they can cram ambulances with the latest imaging and heart-lung bypass technology - a breakthrough that would make them better equipped than some small hospitals. (startribune.com) - In Paris, ambulances emblazoned with "reanimation" on their hoods carry heart-lung bypass pumps to take over when patients' hearts have stopped. (startribune.com) - And they'll need to figure out where to deploy the ambulances - finding gaps in and around the Twin Cities where patients who suffer cardiac arrest aren't getting to hospitals as quickly as others. (startribune.com) - But a 2016 study in Berlin found that patients receiving standard care were no more likely to suffer hemorrhages or deaths within seven days than those receiving mobile care. (startribune.com) - Rather than continue resuscitation efforts at emergency scenes indefinitely, medics in the consortium are trained to transport patients to the U for potential placement on bypass machines if three rounds of defibrillation fail to shock their hearts into normal rhythms. (startribune.com) - However, the consortium's approach has resulted in survival for more than 40 percent of patients whose hearts couldn't be restarted by defibrillation. (startribune.com) - Wilder Schaaf and colleagues reviewed 11 studies published between 1993 and 2011 that looked at mental health issues following cardiac arrests experienced outside of a hospital and found problems plaguing anywhere from 15 percent to 50 percent or more of patients. (lifescript.com) - Months to years after surviving cardiac arrest, about one-third of patients were depressed and nearly two-thirds were experiencing anxiety. (lifescript.com) - But treating mental illnesses in other types of heart patients has been shown to increase long-term survival while decreasing costs, according to independent research. (lifescript.com) - A range of tools can help patients achieve that goal, including peer support groups such as the Sudden Cardiac Arrest Survivor Network and smart-phone apps such as ICD Coach (in which Sears has a financial interest), he noted. (lifescript.com) - a satisfying news for heart patients as according to a latest discovery, a brief, immediate test can actually help detect fatal strokes from a few drops of blood. (counselheal.com) - These devices have tiny wires that connect to the heart and constantly monitor heart rhythms. (barnesjewish.org) - However, other heart rhythms are serious and increase risk for life-threatening conditions such as sudden cardiac arrest . (cardiosmart.org) - A procedure called ablation can prevent abnormal heart rhythms by destroying the heart tissue that causes them. (cardiosmart.org) - ATLANTA (AP) - Routinely implanting pager-size defibrillators in heart attack survivors to stop cardiac arrest reduces their chance of dying by a surprising one-third and could benefit millions of Americans, a major study found. (heart1.com) - Moss's study involved 1,232 heart attack survivors who also had diminished heart pumping power, a common consequence of the damage caused by a heart attack. (heart1.com) - ORLANDO, Fla. (AP) - A newer cholesterol drug, used with older statin medicines, modestly lowered heart risks and deaths in a big study of heart attack survivors that might persuade insurers to cover the pricey treatment more often. (wandtv.com) - The clinical characteristics of the arrests were determined by interviewing survivors and the next of kin of nonsurvivors, reviewing medical records, and analyzing postmortem data. (acc.org) - Here, five heart attack survivors share their very different experiences - and what they wish they'd realized sooner. (aarp.org) - One new study found that heart attack survivors benefited from a medicine long used to treat gout. (yahoo.com) - As a young woman Nelson, a social work major at Sacred Heart University in Fairfield, aided survivors of another tragedy - the 2012 shootings at Sandy Hook Elementary School in Newtown. (newstimes.com) - NEW YORK (Reuters Health) - A quarter of cardiac arrest survivors suffer long-term psychological problems such as anxiety, post-traumatic stress disorder and depression, a new review of research estimates. (lifescript.com) - Many long-term care issues for survivors are unknown, experts said, largely because only 10 percent of the 382,800 Americans who suffer cardiac arrest each year survive. (lifescript.com) - In reality, however, the long-term mental health state of many cardiac arrest survivors is not typically considered or assessed, the researchers write in their report, which appears in the journal Resuscitation. (lifescript.com) - Over a five-year period, survivors of cardiac arrest and similar events who did not show signs of PTSD lived three and a half times longer than those with ongoing trauma, according to a 2008 study by Dr. Karl-Heinz Ladwig, an epidemiologist at the Helmholtz Zentrum M�nchen in Germany. (lifescript.com) - In the long term, a reexamination of the current understanding of the causes, diagnosis, and treatment of cardiac arrest will be necessary to generate new knowledge that can be used to enable high-quality care across the continuum of care and overcome the longstanding plateau in cardiac arrest survival rates. (nap.edu) - What do sudden cardiac arrest symptoms look like for children? (simonsheart.org) - Sudden cardiac arrest does not always have symptoms. (simonsheart.org) - What Are the Symptoms of Sudden Cardiac Arrest? (cdc.gov) - In over half of the cases, however, sudden cardiac arrest occurs without prior symptoms. (cdc.gov) - Symptoms of heart failure arise from fluid accumulation and congestion, as well as reduced blood flow to parts of the body when the heart is no longer to pump blood efficiently. (everydayhealth.com) - Recommendations in the report, which are expected to be turned into a code of practice that will apply to any sports event in Singapore, state that athletes must be able to recognise warning symptoms of sudden cardiac arrest. (campusrock.sg) - Learn the symptoms and how acting fast can save your life and limit damage to your heart. (healthfinder.gov) - Loss of heart tissue due to a blockage can cause symptoms such as chest pain, shortness of breath, weakness, and even death. (onhealth.com) - Women may experience different heart attack signs and symptoms than men. (onhealth.com) - Instead, women commonly have a different set of heart attack symptoms. (onhealth.com) - Such symptoms in women cause delays in diagnosis if the symptoms are not considered as possible signs of heart disease. (onhealth.com) - If you or an individual develop symptoms of a heart attack, do not delay getting medical help. (onhealth.com) - The sooner heart attack symptoms are identified, the sooner the patient can be treated, maximizing the chance of a good outcome. (onhealth.com) - Almost all SIDS deaths happen without any warning or symptoms. (medlineplus.gov) - The symptoms and severity of heart block depend on which type you have. (daviddarling.info) - First-degree heart block rarely causes severe symptoms. (daviddarling.info) - First-degree heart block rarely causes any symptoms. (daviddarling.info) - The term sudden cardiac death refers to natural death from cardiac causes, heralded by abrupt loss of consciousness within one hour of the onset of acute symptoms. (news-medical.net) - Different strategies are available for preventing cardiac arrest, depending on a person's risk. (barnesjewish.org) - A person's risk of SCD is higher during the first 6 months after a heart attack . (cdc.gov) - THURSDAY, March 23, 2017 (HealthDay News) -- Having a drink each day may help protect a person's heart against disease, a large-scale study suggests. (hon.ch) - If needed, the AED can deliver an electric shock to the person's heart. (prweb.com) - The AED will broadcast a voice command that instructs the person operating the device to shock the unconscious person's heart. (prweb.com) - Both emergency response methods help improve a person's chance of surviving sudden cardiac arrest. (prweb.com) - Racing heart (feels like it is beating out of your chest). (simonsheart.org) - A male in his late teens has been arrested at his Scarborough-area home after a student of a similar age was stabbed in the neck and chest Friday morning near Danforth and Greenwood avenues. (nationalpost.com) - Hodge also noted that cardiac arrest is different from a heart attack, where a person is feeling chest pains, sweating, nausea and heaviness in the arms. (usatoday.com) - As blood accumulates, it can obstruct the heart's normal blood flow, leading to chest pain , heart attack and even sudden death. (heart.org) - As with men, women's most common heart attack symptom is chest pain or discomfort. (heart.org) - During a heart attack, an individual will experience shortness of breath, chest pain, and pain in the shoulder, arm, or neck area. (qualityhealth.com) - People have this idea of the Hollywood heart attack, which is a man squeezing his chest, the feeling of the balloon about to burst," says clinical cardiologist Malissa Wood, assistant professor of medicine at Harvard Medical School. (aarp.org) - Decreasing the time between cardiac arrest onset and the first chest compressions is critical. (nap.edu) - This blockage can damage or destroy some of the heart muscle. (simonsheart.org) - A heart attack is caused by a blockage in a blood vessel that interrupts the flow of blood causing an area of the heart muscle to die. (hrsonline.org) - A heart attack occurs when a blockage-such as clogged arteries-causes low blood flow to the heart. (qualityhealth.com) - His study, released Tuesday, suggests the implanted defibrillators should be much more widely used and considered for all who meet just two simple criteria: a history of heart attack and evidence of resulting heart weakness. (heart1.com) - Dr. Sidney Smith, research director of the American Heart Association, called the findings ``very impressive' but added, ``We are talking about a lot of people who would receive defibrillators. (heart1.com) - 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. (cdc.gov) - We place defibrillators in schools to reduce death from sudden cardiac arrest. (justgiving.com) - Drones to deliver heart defibrillators to cardiac arrest site Drone delivery service Flirtey announced on Tuesday that it is partnering with a Reno-based ambulance service to send out emergency equipment by air. (usatoday.com) - Drone delivery company Flirtey is partnering with Reno-based ambulance service REMSA to send out defibrillators by air as part of every response to a cardiac arrest emergency. (usatoday.com) - Chicago A new study has linked widely used, more sophisticated heart defibrillators with a slightly increased risk of hospitalization and death. (ljworld.com) - Located in the right atrium, it initiates the heart's electrical activity stimulating muscle contraction so the heart can pump blood to the body. (heart.org) - He also had a mutant variant of a gene associated with a condition known as Long QT syndrome 1, an inherited disorder of the heart's electrical activity that is associated with sudden cardiac death. (campusrock.sg) - Heart block is a problem that occurs with the heart's electrical system . (daviddarling.info) - Damage to the heart muscle or to the heart's electrical system causes acquired heart block. (daviddarling.info) - In contrast, sudden cardiac arrest occurs when the electrical system to the heart malfunctions and suddenly becomes very irregular. (cdc.gov) - Cardiac arrest happens suddenly. (heartandstroke.ca) - Plaque may also trap small blood clots, completely blocking a coronary artery suddenly, resulting in a heart attack. (onhealth.com) - Brian Hook, the U.S. special representative for Iran, dismissed the arrest warrant announcement during a news conference in Saudi Arabia on Monday. (yahoo.com) - The news came the day that the parents of the man arrested in the stabbing defended their son, claiming the killing was in self-defense . (nbclosangeles.com) - Our collective hearts are broken at the news of this tragedy," Easton Area School District Superintendent John Reinhart said Sunday. (mcall.com) - Tim Russert [NBC News' Washington bureau chief and the moderator of Meet the Press] died of sudden cardiac death. (baltimoresun.com) - If all of this is above board, it doesn't explain the deputies' pressing need to "secure" citizens' cell phone recordings, which was performed without a warrant in one case, and in the other, took the form of a nine-hour "house arrest" to ensure the footage didn't make its way to the news before the warrant arrived. (techdirt.com) - His 2014 research showed that the incidence of sudden cardiac arrest among athletes may be 1 in 50,000 - four times higher than the most frequently cited estimate of 1 in 200,000. (sca-aware.org) - 2015). 1 In hospital settings, annual cardiac arrests incidence is approximately 200,000 (Merchant et al. (nap.edu) - 1 The 2013 out-of-hospital cardiac arrest (OHCA) incidence statistic (395,000) includes patient of all ages and cardiac arrests events with both cardiac and non-cardiac (e.g., trauma, drowning, poisoning, and other related causes) etiologies. (nap.edu) - In this study, researchers analyzed trends in deaths in New Zealand, where Christmas occurs during the summer season when death rates are usually at a seasonal low - allowing researchers to separate any winter effect from a holiday effect. (sca-aware.org) - However, researchers note that the study did not track daily temperatures and New Zealand has an island climate, which almost eliminates the extremes of temperature that have been associated with heart-related death rates in previous studies. (sca-aware.org) - Researchers aren't sure exactly why there's such a disparity in funding from the National Institutes of Health, but say more is definitely needed considering about 450,000 Americans die each year from cardiac arrest. (heart.org) - The new analysis of funding from 2007 to 2016 is the first to evaluate the annual trend of NIH cardiac arrest research funding over time, researchers said. (heart.org) - NIH funds allocated for cardiac arrest have declined from $35.4 million to $28.5 million during the past decade, the researchers noted. (heart.org) - Drinking more than that increased the risk of many heart health problems, researchers found. (hon.ch) - For this study, researchers at the University of Cambridge and University College London investigated the potential link between alcohol consumption and 12 cardiovascular diseases by analyzing electronic health records for nearly 2 million adults with good heart health. (hon.ch) - The researchers found increased risks with newer models featuring pacemakers that supply electrical impulses to the upper and lower heart chambers. (ljworld.com) - The researchers halted the study early because of the poor results, which could translate into thousands of hospitalizations or deaths worldwide each year. (ljworld.com) - In a study published in November, for example, researchers found that a depressed patient recovering from a heart attack treated with psychotherapy and antidepressants during a six-month trial incurred - on average - $1,857 in medical costs, whereas a depressed patient who received no psychological treatments cost an average of $2,797 over the same time period. (lifescript.com) - Physicians responsible for the cardiovascular care of athletes must be guided by interpretation standards that distinguish normal ECG findings in athletes from ECG abnormalities requiring additional evaluation for conditions associated with sudden cardiac death," said Jonathan Drezner, who directs UW Medicine's Center for Sports Cardiology and is a team physician for the University of Washington Huskies and Seattle Seahawks. (sca-aware.org) - Increased efforts to address cardiovascular dis- and ischemic heart disease (not including acute myocardial infarction) ap- peared to drive the plateauing rates. (cdc.gov) - Bolton's son alleges that Fresenius concealed or misrepresented information about the risks associated with their hemodialysis treatments, and failed to adequately warn about the increased risk of cardiovascular injury and death. (aboutlawsuits.com) - Cardiovascular disease accounted for the majority of cardiac arrests. (acc.org) - exercise, control your diabetes) was carefully followed, eventual death remains certain, and some of that will be cardiovascular. (acc.org) - This study does an excellent job in demonstrating that cardiovascular death occurs during distance races, but that it is rare. (acc.org) - Among homeless individuals cardiovascular disease remains one of the major causes of death due to challenges in predicting initial risk, limited access to health care and difficulties in long-term management, according to a review published today in the Journal of the American College of Cardiology. (news-medical.net) - Here's what the report says contributed to Silva's death: "Acute intoxication, chronic alcoholism, severe abdominal obesity, chronic hypertension, acute pulmonary-cardiovascular strain. (techdirt.com) - Death is from the sequelae of severe chronic cardiovascular disease exacerbated by the effects of acute intoxication together with the sequelae of properly employed restraint procedures. (techdirt.com) - What Are the Risk Factors of Sudden Cardiac Arrest? (cdc.gov) - Risk factors for coronary artery disease include smoking , hypertension , family history of heart disease , and high cholesterol . (cdc.gov) - ease risk factors, chronic heart disease, and access to care are ne- cessary to continue the decrease in heart disease deaths in Maine. (cdc.gov) - Spontaneous Coronary Artery Dissection (SCAD) is a rare but potentially fatal disease that usually affects young women with no risk factors for heart disease . (heart.org) - Learn how you can lower your risk factors to improve your heart health. (healthfinder.gov) - You can prevent and control many coronary heart disease (CHD) risk factors with lifestyle changes and medicines. (healthfinder.gov) - Univariate risk factors of sudden death were log BNP ( P =0.0006), log N-terminal atrial natriuretic peptide ( P =0.003), LVEF ( P =0.005), log N-terminal BNP ( P =0.006), systolic blood pressure ( P =0.01), big endothelin ( P =0.03), and NYHA class ( P =0.04). (ahajournals.org) - Women should exercise, quit smoking , start exercising, and see their doctors for regular check-ups to monitor heart disease risk factors. (onhealth.com) - We determined risk factors for immediate (within 24 hours) and later death. (cmaj.ca) - There are a number of risk factors associated with heart attack. (mercola.com) - Keeping key risk factors for heart disease in check such as high blood pressure, high cholesterol, obesity and diabetes. (cardiosmart.org) - We, of course, encourage all our readers to regularly visit their doctors to screen for potential heart problems as well as consider how you can prepare your home or business in the case of cardiac arrest through AED training and the installation of an AED . (aed.com) - The devices, like the one given to Vice President Dick Cheney last summer, constantly check for abnormal beats and zap the heart back to normal in case of cardiac arrest. (heart1.com) - In the case of cardiac arrest, the system of care encompasses numerous facets including the public, EMS systems, health care systems, and hospitals. (nap.edu) - Adverse trends in hypertens- verse trends in HHD, heart failure, diabetes-related heart disease, ive heart disease, heart failure disease, diabetes-related heart disease, and non-AMI IHD. (cdc.gov) - Flattening rates appear to be driven by adverse trends in HHD, heart failure, diabetes-related heart disease, and non-AMI IHD. (cdc.gov) - Thompson i am a heart failure patient. (heart.org) - Adding the over-the-counter antioxidant supplement coenzyme Q10 to medical therapy dramatically improved survival rates for people with severe heart failure in a new study. (everydayhealth.com) - FRIDAY May 24, 2013 The first drug to cut deaths from heart failure in more than 10 years is not a miracle pharmacuetical, but a widely available over-the-counter nutritional supplement called coenzyme Q10, or CoQ10. (everydayhealth.com) - During heart failure, as the disease worsens,CoQ10 levels get lower and the heart gradually becomes starved for energy. (everydayhealth.com) - People more likely to experience heart failure as they age, and approximately 5.7 million Americans currently have the condition, a common complication of atrial fibrillation, or afib. (everydayhealth.com) - If you have heart failure and think coenzyme Q10 may be a good addition to your current medical therapy, be sure to talk to your doctor before taking it. (everydayhealth.com) - A clothespin-like device that reduces mitral valve leakage may offer a new treatment option to those seriously ill with heart failure. (everydayhealth.com) - It is linked with the development of difficult-to-treat high blood pressure, heart enlargement, heart failure, diabetes, accidents due to daytime sleepiness, memory lapses, irregular heartbeat and even sudden cardiac death (SCD). (inquirer.net) - Among his conditions, Mr Pradip had an enlarged heart and pre-existing cardiomyopathy, a disease of the heart muscle that can lead to heart failure. (campusrock.sg) - The complaint (PDF) was filed by the son of Harold Bolton, Sr. in the U.S. District Court for the District of Massachusetts on October 25, alleging that the fatal heart attack occurred as a result of Fresenius Medical Care's failure to provide proper warnings and instructions about the potential side effects of Granuflo and NaturaLyte . (aboutlawsuits.com) - The proportion of sudden death is higher in mild heart failure (NYHA classes I and II) compared with advanced stages (NYHA classes III and IV), whereas the proportion of fatal pump failure increases with the severity of disease. (ahajournals.org) - Congestive heart failure (CHF), or heart failure, is a condition when the heart cannot sufficiently pump oxygen-rich blood to supply the body's needs. (healthguideinfo.com) - When you have right-sided heart failure your heart is incapable of pumping enough blood to the lungs. (healthguideinfo.com) - Left-sided heart failure occurs when the heart is unable to pump enough blood throughout the body. (healthguideinfo.com) - Congestive heart failure commonly leads to this condition because the heart muscle is too weak to pump adequate amounts of blood to and from the lungs, as well as the rest of the body. (healthguideinfo.com) - Functional polymorphisms of the MMP-9 gene promoters have been shown in multivariate analysis to be an independent predictor of cardiac mortality regardless of the mechanism of heart failure. (clinicaltrials.gov) - Athletes with positive family history of premature heart disease or cardiac death, or hereditary cardiac conditions, should seek cardiac clearance before taking part in sports or competitions. (campusrock.sg) - Athletes who are concerned about their heart health should visit their pediatrician or pediatric cardiologist . (healthychildren.org) - Well-trained athletes and young people are at higher risk for first-degree heart block caused by an overly active vagus nerve . (daviddarling.info) - SINGAPORE: Bodybuilding champion Pradip Subramanian, who died after a celebrity Muay Thai match with YouTuber Steven Lim in 2017, had underlying heart conditions that placed him at a high risk of cardiac arrest, a coroner's court heard on Monday (Dec 30). (campusrock.sg) - While there is still much speculation over the circumstances of his death, the Los Angeles County Coroner's office declared it as a result of a cardiac arrest. (qualityhealth.com) - This disease can be a rather sudden killer (onset-to-death can be as little as two years), but the "contributing factors" listed on the coroner's report make no mention of the heavy physical strain put on Silva's body by the restraint efforts of nine law enforcement officers and a police dog. (techdirt.com) - The coronary arteries that arise from the aorta and supply blood to the heart consist of three layers. (heart.org) - A shunt can be an abnormal flow pattern of blood through the chambers of the heart or the large arteries leaving the heart. (heart.org) - Blockages in the coronary arteries of the heart can lead to heart attack. (heart.org) - Farthest along is inclisiran, tested in 1,561 people with heart disease from clogged arteries who still had high LDL, the bad form of cholesterol, despite taking standard drugs. (yahoo.com) - SCD is responsible for half of all heart disease deaths. (cdc.gov) - Since the 1950s, heart disease deaths have declined in the United States, but recent reports indicate a plateau in this decline. (cdc.gov) - Maine's age-adjusted heart disease death rate has typically been lower than that of the United States, and Maine was one of the first states where heart disease deaths declined below cancer deaths (8). (cdc.gov) - We computed a comparability ratio (coronary heart disease deaths recorded on death certificates divided by validated coronary heart disease deaths) to quantify agreement between death certificate determination and clinical judgment. (cdc.gov)	2	52	3	0	8	0.931184	11	25,530

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