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Chronic stable angina overview Chronic stable angina Microchapters Alternative Therapies for Refractory Angina Guidelines for Asymptomatic Patients Chronic stable angina overview On the Web Angina pectoris, commonly known as angina, is chest pain due to ischemia (a lack of blood and subsequent lack of oxygen supply) of the heart muscle. It is most often due to obstruction or spasm of the coronary arteries (the heart's blood vessels). Coronary artery disease, also referred to as atherosclerosis of the coronary arteries, is the most common cause of angina. The term derives from the Greek ankhon ("strangling") and the Latin pectus ("chest") meaning "a strangling feeling in the chest". In angina pectoris, symptomatic onset may include chest discomfort indicated by a feeling of tightness, heaviness, or pain in the chest cavity. Chronic stable angina is a form of chest pain characterized by an insufficient blood flow to the myocardium of the heart to match myocardial energy demands (ischemia). The term angina was originally derived from the Greek word ankhon and the Latin word pectus, which when combined, loosely translates as "a strangling feeling in the chest". Attempts to classify this disease state began as early as the 4th century B.C., when Lucius Annaeus Seneca first described the symptoms he was experiencing as "to have any other malady is to be sick; to have this is to be dying". Throughout history many renowned researchers and health care professionals have contributed to the understanding, definition, and recognition of angina. Chronic Stable Angina Angina pectoris is a sensation of chest discomfort that is often described as: a feeling of tightness, heaviness, or pain. Angina pectoris is a characteristic of coronary heart disease. When it occurs chronically, this is referred to as stable angina. Walk Through Angina Walk through angina is the appearance of anginal chest discomfort early in the course of exertion which subsequently subsides despite continued exertion. Mixed or variable threshold angina pectoris is a syndrome in which there is substantial variation in the magnitude of physical activity that induces anginal chest pain. Nocturnal angina is the occurrence of anginal discomfort either during the first hours of sleep or during the early morning hours. It is speculated that discomfort caused during the first hours of sleep is due to increased venous return, whereas the discomfort caused during the early morning hours is due to increased vascular tone. Postprandial angina pectoris is anginal chest discomfort that occurs following meals. It is thought to be due to an increase in vascular tone or a reduction in coronary blood flow. Cardiac Syndrome X Cardiac syndrome X is angina associated with objective evidence of myocardial ischemia in the absence of epicardial coronary artery disease. Syndrome X has been hypothesized to be a disorder of the coronary microvasculature rather than the large caliber epicardial coronary arteries. Coronary vasospasm is a multi-factorial, transient, and abrupt reduction of luminal diameter of an epicardial coronary artery due to inappropriate constriction of coronary smooth muscle that can generate distal ischemia. This may occur spontaneously or in the context of angioplasty, particularly if denudation of the endothelium or dissection occurs. In addition, the vasospasm can either be focal or multifocal (which compromises more than one vessel). Differentiating Chronic Stable Angina from Urgent Conditions Stable angina must be differentiated from unstable angina and acute coronary syndromes. If the pattern of angina is stable, this is termed chronic stable angina. If the magnitude, threshold or frequency of chest pain accelerates, this is termed an acute coronary syndrome. The primary causes of myocardial ischemia in chronic stable angina are: fixed epicardial stenosis, spasm of the epicardial artery and/or microvascualar disease. The causation of angina is not mutually exclusive. Two or more causes may coexist in the same patient. Epidemiology and Demographics Coronary artery disease (CAD) remains the single leading cause of death in the United States. Stable angina is the initial manifestation of ischemic heart disease in approximately 50% of these patients. The average mortality in patients with stable angina ranges from 1-3%. However, the prognosis varies widely depending on various factors such as: the duration and severity of symptoms, resting ECG abnormalities, abnormal left ventricular function and associated comorbidities. Pretest probability is defined as the probability of the target disorder before the result of a diagnostic test is known. A number of studies have emphasized the importance of pretest probability of coronary artery disease (CAD). Once a thorough patient history and physical examination is complete, it is important to assess the probability of underlying CAD, as this helps both the physician and the patient to determine the next step in the diagnosis and treatment. In patients with chronic stable angina, the strongest predictors contributing to underlying significant CAD include: the age, gender and type of pain (typical, atypical) experienced. Ischemic heart disease remains as the number one cause of mortality in developed countries. The prognosis of stable angina varies widely depending on severity of symptoms, extent of atherosclerosis and presence of other risk factors and co-morbidities. The presence of impaired left ventricular function is associated with a poor prognosis. Reduced LV function, number and location of stenoses, workload in METs calculated using Duke score are the strongest predictors of survival in patients with chronic stable angina. History and Symptoms The name 'angina pain' can be thought of as a misnomer as patients often describe the sensation as discomfort rather than physical pain. The best method to characterize this discomfort/pain is through the 'PQRST system'. Among patients with chronic stable angina, the physical examination may be asymptomatic or characteristically normal. Patients that present with left ventricular dysfunction are associated with a poorer prognosis than patients who do not present with dysfunction. All patients should be examined carefully for the presence of rales and other signs of heart failure. The majority of patients present with history of either, chest pain or discomfort categorized as: typical or atypical. Typical presentation would include pain or discomfort in the front or anterior precordium. Atypical presentation can be more convoluted in presentation and involve a wide range of symptoms. For example, an atypical patient may present with dyspnea instead of chest pain and this is termed an angina equivalent. In addition to the historical presentation of chest pain or discomfort, the patient history should be extensively evaluated to include an assessment of cardiovascular risk factors. Physical examination may be normal or asymptomatic. In some cases, a physical examination may reveal heart failure. Additional findings can be important in understanding the onset of the condition. For instance, the presence of peripheral vascular disease may be associated with an increased risk of coronary artery disease (CAD). Test Selection Guideline for the Individual Basis Criteria for test selection hinges largely on the current disease state of the individual patient and subsequent level of fitness for testing. Potential diagnostic testing modalities include: exercise ECG, ECG at rest, exercise echocardiography, echocardiography at rest, and stress scintigraphy. In patients with chronic stable angina, initial laboratory investigations are used to: identify potential causes of ischemia, establish risk factors, and determine the overall prognosis for the patient. An initial laboratory test can provide a wide variety of clinical information. For instance, low hemoglobin levels can cause ischemia. Therefore, assessing hemoglobin as a part of complete blood count provides prognostic information. Biomarkers, such as troponin and CK-MB, are used to exclude myocardial injury. In assessment for risk factor stratification, all patients with ischemic heart disease are recommended to have a a standard round of blood work conducted including fasting plasma glucose levels and a complete lipid profile. Serum creatinine is used to assess renal dysfunction due to associated hypertension or diabetes and remains a negative prognostic factor. In patients with chronic stable angina, an elevation in fasting glucose independently predicts the adverse outcome. Recent research on NT-pro-BNP has demonstrated the ability to predict long-term mortality in patients with chronic stable angina independent of age, ventricular ejection fraction and other risk factors. A resting 12-lead ECG is performed and recorded in all patients with suspected angina pectoris. However, a normal resting ECG does not exclude the diagnosis of ischemia. Abnormalites commonly observed on resting ECG include: ST-segment changes, left ventricular hypertrophy (LVH), left branch bundle blockage (LBBB), signs of coronary artery disease (CAD) such as previous myocardial infarction (MI) or abnormal repolarization patterns. An ECG recorded during pain helps to identify an underlying vasospasm. In patients with chronic stable angina, exercise ECG is more sensitive and specific to identify inducible ischemia and to diagnose coronary artery disease. ECG abnormalities associated with MI include: down sloping of ST-segment depression or elevation, accompanying angina that occurs at a low workload during early stages of exercise and persistent for more than 3-minutes after exercise. The reliability of diagnosis is shown to improve with the evaluation of ST changes in relation to heart rate. Bruce protocol or treadmill (expressed in terms of METs) or bicycle ergometer (expressed in terms of watts) are used to detect MI. Exercise ECG test must be terminated on the achievement of maximal predicted heart rate and/or if the patient becomes symptomatic or develops pain with significant ST-segment changes. Exercise ECG test also provides prognostic stratification to evaluate the response to medical therapy or revascularization. Routine chest x-ray examination is important in the evaluation of patients with signs or symptoms of congestive heart failure, valvular heart disease, pericardial disease, or aortic dissection/aneurysm. The presentation of cardiomegaly, characterized by pulmonary congestion on a chest x-ray, is indicative of a poor prognosis for the patient. Myocardial Perfusion Scintigraphy with Pharmacologic Stress Pharmacologic stress testing using myocardial perfusion scintigraphy or echocardiography can be employed in patients with known or suspected angina pectoris who are unable to perform adequate exercise tests. These patients often owe their ineligibility status to associated conditions such as: peripheral vascular disease, musculoskeletal disorders, diseases of the lower extremities, severe obesity, or deconditioning. Pharmacologic stress testing is achieved with the infusion of either dobutamine in incremental dose, which acts by increasing myocardial oxygen consumption and thereby mimic effect of exercise, or with the use of coronary vasodilators such as adenosine or dipyridamole, which acts by differentiating regions based on perfusion. Stress imaging is of great value in the evaluation of patients with low pretest probability of CAD. However, in patients with LBBB, perfusion scintigraphy is shown to have poor diagnostic accuracy. Myocardial Perfusion Scintigraphy with Thallium In patients with baseline ECG abnormalities,a myocardial perfusion test can be used to localize the region of ischemia. Thallium-201 and technetium-99m are the two radio-labeled agents that are frequently used for the assessment of myocardial perfusion. Myocardial uptake of thallium-201 chloride is directly proportional to the regional myocardial blood flow and is dependent on the presence of viable myocardium. In patients with known CAD, a normal thallium stress test without a perfusion defect is indicative of a benign process and associated with excellent prognosis. Patients with a normal thallium scan are at low risk for CAD and subsequent coronary angiography is indicated only if the patient has a high probabilty Duke treadmill score. Contraindications for thallium stress test include the presence of arrhythmia, acute myocarditis, severe aortic stenosis and acute MI within the past 2 days. Echocardiography is useful to evaluate ventricular function and detect ischemia induced regional wall motion abnormality that occurs at rest, during exercise or with pharmacologic stress test. As a testing modality, two-dimensional echocardiography is often coupled with other testing modalities to detect regional wall motion abnormalities that most frequently occur during induced myocardial ischemia associated with coronary artery disease (CAD). Potential paired testing modalities include: upright treadmill exercise, supine bicycle ergometry, pacing, and pharmacologic stress, particularly with dobutamine. Patients with CAD may respond more adversely to testing modalities than their counterparts. Often, an adverse outcome such as the inability to perform a bicycle ergometry test or exercise treadmill protocol can be characterized as a poor prognostic factor. Stress echocardiography is echocardiography that is paired with different forms of stressors, such as exercise or pharmacological. Exercise stress echocardiography is the preferred stress echocardiography modality. However, it is not suitable for all patients and may not be feasible in populations that do not meet a minimum level of fitness. In patients who are ineligible for exercise stress echocardiography, pharmacological stress echocardiography can be a useful alternative. Common pharmacological stressors include: adenosine, dipyridamole, and dobutamine. As a testing modality, exercise echocardiography is noted as more sensitive, more specific and has a higher predictive value than exercise ECG. Exercise echocardiography can be helpful in the evaluation of regional wall motion response, location and extent of ischemia during stress in patients with MI. During exercise, the normal myocardium is hyperdynamic while in patients with MI, the ischemic myocardium is either akinetic or hypokinetic. Positron Emission Tomography Ambulatory ST Segment Monitoring Ambulatory ECG monitoring (Holter monitor) is used to detect major arrhythmias and myocardial ischemia occurring during normal activities. Ambulatory ECG monitoring adds very little prognostic value in patients with chronic stable angina, however, does play a role in the detection of major arrhythmias in patients with chronic stable angina and suspected vasospastic angina. Electron Beam Tomography The extent of coronary artery calcification directly correlates to the area of atheromatous plaque. Hence in patients with chest pain, coronary artery calcium (CAC) scoring is one of the factor to be considered in the risk assessment for coronary artery disease. The methods used for detection and quantification of CAC include electron beam computed tomography (EBCT) and multi-detector computed tomography (MDCT). Agatston score is a computed software that is commonly used to measure CAC based on the density and area of calcified plaques. Cardiac Magnetic Resonance Imaging Cardiac magnetic resonance imaging (CMRI) is a non-invasive test that is useful in the evaluation of overall coronary anatomy and function. CMRI also helps in the identification of inflammation, neovascularization and fibrous cap. It, therefore, holds the potential for plaque characterization. Coronary angiography is a gold standard test in the evaluation of severity of coronary artery disease and the possibility for revascularization. Coronary angiography is indicated in patients with a high pretest probability of CAD and in symptomatic patients with inconclusive initial noninvasive tests. Provocative testing with ergonovine during angiography may be useful in patients with vasospastic angina. Major complications such as death, MI and stroke associated with routine angiography is as low as 0.1% - 0.2%. Treatment of chronic stable angina aims at minimizing symptoms, reducing recurrent ischemia, improving the quality of life and improving prognosis by preventing MI and death. Treatment options include lifestyle modification, pharmacotherapy and revascularization that help in slowing the disease progression, preserving the endothelial function and preventing thrombosis. Patients with double-vessel CAD and with normal LV function may be started on initial medical management and in non-responders, PCI may be considered. However, the decision of PCI versus CABG depends on the coronary anatomy, LV function and the need for complete revascularization. Patients with triple-vessel CAD or left main disease or reduced left ventricular function, CABG is the mainstay of management. However, in cases of mild symptoms or preserved LVEF in patients with triple-vessel disease, initial pharmacologic therapy or PCI may be tried. The goal of the management of chronic stable angina is to improve the quality of life by decreasing the severity and frequency of symptoms and to decrease premature cardiovascular death caused by myocardial infarction or development of heart failure. The mainstays of the treatment of chronic stable angina are patient education, lifestyle changes and medical therapy. In patients with chronic stable angina, immediate symptomatic relief is achieved with short-acting sublingual nitrates and long term symptom relief is achieved with beta blockers as first line therapy, or calcium channel blockers and long-acting nitrates when beta blockers are contraindicated. Drugs that improve the quality of life and are associated with a better prognosis include: low dose aspirin, beta-blockers and ACEIs. Dipyridamole is a pyrimidopyrimidine derivative with poor anti-thrombotic efficacy and therefore not recommended for anti-platelet therapy in patients with chronic stable angina. Dipyridamole may also exacerbate anginal symptoms due to coronary steal phenomenon. Thienopyridines, such as clopidogrel and ticlopidine, selectively inhibit ADP-induced platelet aggregation and are used as an alternative to aspirin in patients with significant risk of arterial thrombosis. In patients with chronic stable angina, nitrates remain the mainstay of therapy. Organic nitrates are therapeutic precursors of endothelium-derived relaxing factor that produce their beneficial effects both, by decreasing myocardial oxygen requirements and by improving myocardial perfusion. The most commonly used nitrates are nitroglycerin, isosorbide dinitrate and isosorbide mononitrate. Short acting nitrates, such as sublingual nitroglycerin, are best suited to treat acute episodes of angina and are effective when used for situational prophylaxis. Long-acting nitrates help to reduce the frequency and severity of angina and may increase exercise tolerance in patients with stable angina. Nitrates at therapeutic doses do not affect coronary vascular resistance, thereby reducing the risk of myocardial ischemia due to coronary steal phenomena that is consistent with the use of dipyridamole and other short acting dihydropyridines. In patients with stable angina, beta blockers are used as a first line of therapy for both, symptomatic relief and the prevention of ischemic events. The physiologic mechanism of benefit of this therapy is a marked reduction in myocardial oxygen consumption by reducing the heart rate and myocardial contractility. Selective beta-1 blockers are preferred to non-selective beta-blockers due to fewer associated side effects. The most commonly used selective beta-1 blockers are metoprolol, atenolol, and bisoprolol. Calcium Channel Blockers Calcium channel blockers (CCBs) consist of three sub-classes namely, dihydropyridines (e.g., nifedipine), phenylalkylamines (e.g., verapamil) and modified benzothiazepines (e.g., diltiazem). The beneficial anti-anginal effects of CCB include: reduction in the afterload consequent to systemic vasodilation as well as epicardial vessel vasodilation, enhancement of the coronary collateral flow with subsequent sub-endocardial perfusion due to the inhibition of calcium influx via L-type channels. Long-acting calcium channel blockers are an effective antianginal agent and are considered to be the first choice in post-MI patients with a contraindication to beta-blocker. Long-acting CCBs are also specifically used to control symptoms in patients with vasospastic angina. However short-acting CCBs, such as nifedipine, are avoided due to an increased risk of myocardial infarction and mortality. Potassium Channel Openers Nicorandil has both, anti-anginal effects due to nitrate-like and ATP-sensitive potassium channel activating properties and provides cardio-protective effects as well. Therefore, nicorandil usage in addition to standard anti-anginal therapy may be indicated in patients who are intolerant to beta-blocker therapy or in whom CCB monotherapy or combination therapy CCB is unsuccessful. Newer Anti-anginal Agents Ranolazine is a one of the newer FDA approved anti-anginal medication for management of chronic stable angina. Perhexiline is another anti-anginal, primarily used in Australia and New Zealand, being studied for use in the United States and UK. In patients with chronic stable angina, other effective agents with anti-anginal and anti-ischemic properties are ivabradine, trimetazidine and molsidomine. Patients diagnosed with syndrome X and hypertension may have microvascular angina characterized by a reduced coronary vasodilator reserve and increased sympathetic drive. ACE inhibition in such patients may attenuate sympathetic coronary vasoconstriction, normalize thallium perfusion defects and reduce exercise-induced ischemia with subsequent increased myocardial oxygen supply. Based on the recent AHA and ESC guidelines, the recommended goal blood pressure in patients with atherosclerotic coronary vascular disease is less than 130/80 mm Hg. Statins by inhibiting HMG-CoA reductase subsequently reduce serum cholesterol levels and have been shown to be effective in the primary prevention of various hyperlipidemias and secondary prevention of ischemic heart disease. The most commonly used statins are simvastatin, atorvastatin, pravastatin and rosuvastatin. The incidence of major cardiovascular mortality was reduced by 30% with the use of simvastatin and pravastatin in patients with coronary artery disease and therefore may be used for both primary and secondary prevention. However, there are no trials specifically performed on patients with stable angina but they form a significant portion in other major trials studying the efficacy of lipid-lowering drugs on the overall mortality from cardiovascular events. In patients with low HDL and high triglycerides as an adjunctive to statin therapy, fibrates or niacin may be used. The goal of the treatment of chronic stable angina is to reduce the symptoms, delay the progression of atherosclerosis, and prevent cardiovascular events. In order to achieve these goals, lifestyle modifications and medical therapy are the first line treatment. Revascularization is done to increase survival in specific conditions where the stenosis of the coronary arteries is anatomically and functionally significant and the symptoms are refractory to medical therapy. There are currently two well-established revascularization approaches for the treatment of chronic stable angina caused by coronary atherosclerosis: CABG and PCI. Since the introduction of coronary artery bypass surgery in 1967 and percutaneous transluminal coronary angioplasty (PTCA) in 1977, research has supported the effective usage of both strategies for treatment of patients with chronic stable angina. However, as with any treatment method, both methodologies have weaknesses. The choice between PCI and CABG is based upon anatomy and other factors such as left ventricular function and the presence or absence of diabetes. In general, PTCA is reserved for single or some cases of two vessel disease, while CABG is reserved for patients with two or three vessel disease or left main disease. With the availability of drug-eluting stents, PCI is increasingly being performed for many lesions including more complex ones. Percutaneous coronary intervention for coronary artery disease first began in 1977, as a valuable mode of revascularization, wherein at the point of coronary stenosis a catheter-borne balloon is inflated to relieve the stenosis. Coronary artery bypass surgery, also coronary artery bypass graft (CABG, pronounced "cabbage") surgery, and colloquially heart bypass or bypass surgery is a surgical procedure performed to relieve angina and reduce the risk of death from coronary artery disease. Arteries or veins from elsewhere in the patient's body are grafted to the coronary arteries to bypass atherosclerotic narrowings and improve the blood supply to the coronary circulation supplying the myocardium (heart muscle). This surgery is usually performed with the heart stopped, necessitating the usage of cardiopulmonary bypass; techniques are available to perform CABG on a beating heart, so-called "off-pump" surgery. PCI vs Medical Therapy An increased risk of mortality and morbidity is associated with untreated coronary artery disease. The main aim of therapy in patients with chronic stable angina is to alleviate symptoms, delay the progression of atherosclerosis, reduce the incidence of adverse coronary events and improve prognosis. This may be achieved with either initial medical therapy or with initial revascularization that includes percutaneous coronary intervention or coronary artery bypass grafting. Medical therapy alleviates symptom and improves prognosis; however, on the contrary, revascularization procedures provide symptomatic relief but generally does not improve mortality. CABG vs Medical Therapy It is well established that revascularization with CABG has shown to provide better symptomatic relief and improved survival rates in comparison to medical therapy in some patients with stable angina. However, the long term benefit of CABG is limited by the progression of atherosclerosis in other unbypassed vessels and stenosis of the graft itself. PCI and CABG vs Medical Therapy The Mass and Mass-II trials directly compared the effect of medical therapy, CABG and PCI for the management of chronic stable angina. However, there are a few reservations to the application of results from these studies as they did not include the current optimal strategies of therapy. PCI vs CABG PCI and CABG have become the standard of care in the management of patients with symptomatic coronary artery disease. Patients with multi-vessel disease, the overall mortality and freedom from myocardial infarction appear to be similar in both the treatment strategies; however, the need for repeat revascularization is significantly higher in patients who initially underwent PCI secondary to a higher incidence of restenosis. Alternative Therapies for Refractory Angina Transmyocardial Revascularization (TMR) As the survival of patients with primary coronary events continue to increase, the number of patients presenting with refractory ischemia despite maximal medical therapy and unsuitable for further traditional revascularization techniques also continues to rise. Transmyocardial revascularization (TMR) is one of the emerging techniques that has been studied in many randomized trials and has shown to reduce the incidence of recurrent angina, increase exercise tolerance time and improve quality of life. TMR can be performed using either a laser beam or a percutaneous approach. However, only laser TMR is currently FDA approved. Spinal Cord Stimulation (SCS) In patients with refractory angina, spinal cord stimulation (SCS) is used to provide analgesia in the region of radiation of anginal-pain with the help an implanted device consisting of a stimulating electrode tip that extends into the dorsal epidural space, usually at the C7-T1 level. Enhanced External Counter Pulsation (EECP) Enhanced external counter pulsation (EECP) is another alternative therapy in the management of refractory angina. Most data from observational studies have demonstrated significant improvement in the exercise tolerance and reduction in the frequency of anginal symptoms as well as the use of nitroglycerin among patients treated with EECP. Ongoing follow-up of the patient with chronic stable angina is necessary to monitor symptoms and to optimize antianginal therapy. It is generally recommended that these patients be evaluated every 4-6 months during first year of diagnosis/initiation of therapy and annually thereafter. Based upon clinical judgement, if the patient is poorly responsive to therapy, if the episodes are severe or frequent, or if the patient is fragile with multiple co-morbidities, they may need to be seen more frequently. During a follow-up visit, the patient should be asked about the frequency and severity of their anginal symptoms, their level of exercise capacity, whether they have been able to modify his/her risk factors, how well they are tolerating and complying with the therapy and whether he/she has developed new illnesses or co-morbidities. Cardiac rehabilitation, also called cardiac rehab (CR), is a medically supervised program to help cardiac patients recover quickly and improve their overall well being. The main goal of rehabilitation is to help patients understand their disease and inculcate a regimen to stabilize and reduce, or even reverse the progression of cardiovascular disease. Cardiac rehab is often divided into phases that involve monitored exercise, counseling, emotional support, and education about lifestyle changes to reduce the risks of heart problems. It also helps reverse limitations experienced by patients who have suffered the adverse patho-physiologic and psychological consequences of cardiac events, thus, also helping patients to return to work early. Traditionally, cardiac rehabilitation has been provided to lower-risk patients who could exercise without physical limitations. However, rapid evolution in the management of CAD has now changed the demographics of the patients, so that, even patients with recent revascularization can be candidates for rehabilitation training. The 1989 Surgeon General’s report, which assessed numerous case-control and cohort studies, reported that smoking increased cardiovascular disease mortality by 50%. Cigarette smoking, likely due to the hemodynamic consequences of sympathetic neural stimulation and systemic catecholamine release, plays an important role in the pathogenesis of coronary artery disease. Cigarette smoking also forms a major risk factor for acute cardiovascular events as it relates to an associated increase in blood coagulability. Hence, cigarette smoking is an important reversible risk factor in the pathogenesis of CAD and cessation of which improves prognosis and is associated with a substantial decrease in the risk of mortality. In patients with stable angina pectoris, nicotine replacement therapy has shown to be potentially beneficial despite the associated cardiovascular risks of nicotine, such as increase in heart rate with a small rise in blood pressure. Nicotine replacement therapy may be initiated as early as 2–3 days after acute myocardial infarction or cardiac arrhythmias. Additionally, nicotine patches have been used successfully in high-risk patients without any adverse effects such as aggravation of MI or arrhythmia. Obesity is directly associated with the development of coronary artery disease (CAD) risk factors such as: hypertension, diabetes, reduced levels of HDL-C and elevated levels of triglyceride. Research has demonstrated that CAD risk factors contribute to a strong, graded, J-shaped univariable relationship between BMI and cardiovascular disease mortality. This increased mortality, when adjusted for age, self-reported smoking status, total cholesterol, and systolic blood pressure, maintained significant hazard ratios. Hence, in obese patients with CAD, weight reduction and/or dietary interventions may be warranted to reduce the incidence of above-mentioned risk factors and prevent future coronary events. Weight reduction is strongly recommended in patients with a BMI greater than 30 kg/m2 and in patients with increased waist circumference (greater than 102 cms for men and 89 cms for women), characteristic of truncal obesity. Based on the plasma lipid abnormalities, adequate dietary modification may also be indicated. Based on an individual's ability to exercise and severity of the symptoms, physical activity may be indicated as a treatment. As a treatment, increased physical activity has demonstrated improvements in an individual's sustained exercise duration, reduced the frequency of symptoms and also provided beneficial effects on blood pressure, diabetes and the overall lipid profile. Before the initiation of an exercise regimen, an exercise test is indicated as a useful guide to assess the level of tolerance. In patients with established coronary artery disease, the recommended goal for total cholesterol is 130 mg/dl and LDL-C is 100 mg/dl, while the HDL-C and triglyceride concentrations serve as preferred markers for risk assessment. In patients with CAD, a fasting lipid-profile may be repeated at 5 year intervals to assess the overall risk of cardiovascular mortality and morbidity. Based on the individual’s lipid abnormalities, necessary dietary interventions and/or lipid-lowering agents are suggested to prevent the risk of future coronary events. A Mediterranean diet consisting of fruits, vegetables, lean meat and fish has also been shown to be beneficial. Omega-3 fatty acid supplementation may be indicated in patients with stable angina for secondary prevention, as it has been shown to reduce elevated triglycerides and also reduce the risk of sudden cardiac death. Fish consumption once a week has also been associated with reduced risk of mortality from coronary artery disease and, for this reason, is strongly recommended. The risk of progression of atherosclerosis is proportional to the increase in elevated blood pressure, hyperglycemia and dyslipidemia. Therefore, the control of hypertension, hyperglycemia and other features of metabolic syndrome deserves special attention in the prevention of mortality and morbidity due to coronary artery disease. In patients with established CAD, concomitant diabetes and/or renal dysfunction, the blood pressure goal is 130/80-85 and the decision to lower blood pressure depends on the total cardiovascular risk and the extent of target organ damage. Close monitoring and lifestyle changes may be indicated in low-risk patients without documented target organ damage. However, in high-risk patients with a sustained SBP of ≥140 mm Hg and/or DBP ≥90 mm Hg, the goal is to lower blood pressure less than 140/90 with the help of combined drug therapy and life style modification. Anti-hypertensive therapies that have shown to significantly reduce cardiovascular mortality and morbidity in patients with coronary artery disease include diuretics, beta-blockers, ACEIs, ARBs and calcium channel blockers. Diabetes is one of the major modifiable risk factors for coronary artery disease. Maintaining a good glycemic control has been demonstrated to delay the disease progression in patients with impaired glycemic control and further prevent microvascular complications. In type 1 diabetics, appropriate insulin therapy and concomitant dietary modification may be required. 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Jul 30, 2012. According to the University of Chicago's Center for Peripheral Neuropathy ( UCCPN), nearly 60 percent of diabetics have some sort of nerve damage ( UCCPN, 2010). This damage is often. Both alcohol and tobacco aggravate nerve pain and can cause nerve damage when used for long periods of time. Jun 5, 2015. This symptom is called peripheral neuropathy. Meaning your peripheral nerves in feet are damaged. The symptom aggravates when you have carbohydrate rich/ sugary food items. Even though there is no quick remedy for this issue but there are control measures to improve health condition. They are. 1. Some peripheral neuropathy patients feel tremendous burning pain. They don't like warm. But they like cold. "They like cold so much that they will walk in snow or. Cetuximab-induced hypomagnesaemia aggravates peripheral sensory neurotoxicity caused by oxaliplatin. peripheral neuropathy at the beginning of Cmab therapy, Looking for online definition of Peripheral edema in the Medical Dictionary? Peripheral edema explanation free. What is Peripheral edema? Meaning of. Peripheral nerve injury of the upper extremity commonly occurs in patients who participate in recreational (e.g., sports) and occupational activities. Home » Upper and Lower Limb » Weak Legs (Loss of Strength in One or Both Legs) Causes Weak Legs (Loss of Strength in One or Both Legs) Causes. Posted by. Stretching Exercises. Novak (2004) suggests that tightnesses in the following muscles can contribute to upper extremity disorders such as radial tunnel. Hereditary sensory neuropathy type I (HSN1). Center for Peripheral Neuropathy. University of Chicago; 5841 South Maryland Ave, MC 2030; Chicago, IL 60637 ; The definition of chronic kidney disease (CKD) is based on the presence of kidney damage (ie albuminuria) or decreased kidney function (ie glomerular. Find patient medical information for L-CARNITINE on WebMD including its uses, effectiveness, side effects and safety, interactions, user ratings and. Peripheral neuropathy is a disorder that occurs when your peripheral nerves malfunction because they're damaged. Peripheral neuropathy is a condition in which nerve damage triggers a burning, tingling or numb sensation in your hands and feet. The specific cause can be. Jul 19, 2015. Patients experiencing neuropathy symptoms, including those of diabetic peripheral neuropathy, not only have to manage pain but also sleep disturbances. Here. For others, sleep disturbances can aggravate neuropathy symptoms. For example, sleep deprivation can lower your pain threshold and make. Entitlement to service connection for peripheral neuropathy of the bilateral lower extremities as secondary to service-connected pes planus with osteoarthritis of the feet. 2. Entitlement to service connection for bilateral knee disabilities as secondary to service-connected pes planus with osteoarthritis of the feet. 3. Entitlement. Pathology, causes, and genetics of Alzheimer’s disease Peripheral neuropathy: A disorder that results from damage to the peripheral nerves. Symptoms: Numbness, weakness, loss of balance, & pain. Learn more here. Apr 16, 2016. Vitamin B deficiency. Low vitamin B12 (folate) may cause nerve damage and peripheral neuropathy, and has been linked to Parkinson's and peripheral neuropathy. A vitamin B6 deficiency can aggravate or even cause neuropathic pain. Magnesium deficiency. Magnesium protects nerves against damage. Cerebellar ataxia. Drug- and toxin-induced cerebellar ataxia: Phenytoin and other anticonvulsants (carbamazepine, barbiturates, gabapentin. The central nervous system includes the brain and spinal cord. Peripheral nerves are located outside the brain and spinal cord. They carry information between your. Good nutrition is helpful in avoiding many diseases, including peripheral neuropathy. Discovery the best neuropathy diet, and common supplements for neuropathy. Oct 29, 2014. Peripheral nerves are highly specialized and can cause a wide range of sensory, motor, and autonomic symptoms, making peripheral neuropathies hard to diagnose and hard to treat.1. There are more than 100 known types of peripheral neuropathy. Common acquired causes include diabetes, injury, Learn the risk factors and symptoms of peripheral neuropathy, nerve damage that is a common diabetes complication. Abstract: In order that the eye may satisfactorily perform its duties as an organ of vision, it is essential that the media should be optically transparent. Chapter 50 – Vibration VIBRATION. Michael J. Griffin. Vibration is oscillatory motion. This chapter summarizes human responses to whole-body vibration. Hiatal Hernia: An Overlooked Cause of Disease. By Dr Cliff Fruithandler DC. Hiatal Hernia has been one of my favourite conditions to treat. One of my. Sep 20, 2010. Obtain Relief from Peripheral Neuropathy by Using Natural Remedies. ( NewsTarget) Peripheral neuropathy is a condition which describes damage to the peripheral nervous system, which transmits information from the brain and. * A vitamin B6 deficiency can aggravate or even cause neuropathic pain. Peripheral neuropathy occurs when nerves malfunction because they're damaged or destroyed. You'll notice a tingling, numbness, or weakness. Types of Peripheral Neuropathy – Inflammatory. Peripheral neuropathy; Muscle pain, numbness or tingling; Tingling, numbness and pain in feet, legs, hands and arms; Obstructive Sleep Apnea Is Associated With Diabetic Peripheral Neuropathy @ Diabetes Causes Obstructive Sleep Apnea ★★ Diabetic Ed The 3 Step Trick that Reverses Diabetes Permanently in As Little as 11 Days.[ DIABETES CAUSES. Aim Obstructive sleep apnea increases in diabetes and morbid obesity. We tested a hypothesis that circulating autoantibodies in adult type 2 diabetes which increase in association with morbid obesity are Williamsburg Neuropathy Solutions, Williamsburg, Virginia. 751 likes. Helping men and women with Peripheral Neuropathy. Contact us by calling: (757). • The effect of lower-limb ischemia on the severity of neuropathy was examined in 48 diabetic patients with peripheral vascular disease. The severity of the vas Photophobia is a symptom of abnormal intolerance to visual perception of light. As a medical symptom, photophobia is not a morbid fear or phobia, but an. Nerve Report: 2017 Release. Don’t try anything before you read. We Tested 100 Peripheral Neuropathy Brands. You Will Be Shocked At What We Found Genetic Variants and Methylation Dysfunction Dr. J Dunn The recent advances in genetic research have finally reached a point where we can begin to look at. Learn about restless legs syndrome, including common causes, treatments, and home remedies. We go through the best symptom-relieving tips here. Michigan Diabetic Neuropathy Screening Instrument diabetic peripheral neuropathy diabetes mellitus driver's license. Michigan neuropathy screening instrument safe driving. a b s t r a c t. Although the effect of lower extremity pathology and surgical intervention on automobile driving function has been a topic of contemporary interest, we are unaware of any analysis of the. ★★ Pregnancy Diabetes ★★ ::The Foods to avoid with neuropathy – Can neuropathy go away? Depends. It depends on what the cause of neuropathy is. In majority of cases you can improve symptoms by. Feb 23, 2017. The damage is caused by the toxic effect of a certain medicines on the peripheral nerves (nerves that are not in the brain or spinal cord). There may be damage to the axon part of the nerve cell, which interferes with nerve signals. Most commonly, many nerves are involved (polyneuropathy). This usually. Learn all about heel pain, the causes, signs and symptoms, diagnosis, treatment options, home care and prevention. Frequently heel pain is triggered by. Have an L4-L5-S1 bulge/herniation, Happened last Nov. and nothing has help so far. The only relief I get is when im home laying in bed on my side but. More Neuropathy Articles ... - Botox For Diabetic Neuropathy: Diabetic neuropathy is a type of nerve damage that can occur if you have diabetes. High blood sugar can injure nerve fibers throughout your body. ★ Diabetic Polyneuropathy Icd 9 ★ :: Type 2 Diabetes Yeast Infections - The 3 Step Trick that Reverses D... - Norvasc Causes Peripheral Neuropathy: Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. In humans, experience with intentional overdosage of NORVASC is limited. Single oral doses of amlodipine maleate equiva... - Diabetic Neuropathy Demyelinating Axonal: The incidence of peripheral neuropathy is not known, but it is a common feature of many systemic diseases. Diabetes and alcoholism are the most common. The peripheral neu- ropathy may be symmetric, focal, or multifocal. Mixed forms are also seen. Chr... - Agent Neuropathy Orange Peripheral: AGENT ORANGE AND PERIPHERAL NEUROPATHY. What is peripheral neuropathy? Peripheral neuropathy is a nervous system condition that causes numbness, tingling, and muscle. There are many ways for dioxin, the toxic contaminant in Agent Orange, to enter the... - How Do You Diagnose Peripheral Neuropathy: Peripheral neuropathy — Comprehensive overview covers diagnosis, causes and treatment of this often painful disorder. Learn about peripheral neuropathy causes such as diabetes, alcohol, medication, shingles, vitamin deficiency, autoimmune diseases, a... - Vitamin B1 And Peripheral Neuropathy: What does vitamin D have to do with neuropathy? New research is giving us insights into the effects that a lack of this important vitamin could. Peripheral neuropathy caused by long-term alcohol abuse is a horrible form of suffering for those who mus...	2	8	1	0	1	0.535485	2	2,190
What the Anesthesiologist Should Know before the Operative Procedure As a group, patients undergoing ophthalmic surgery have a low risk of developing perioperative cardiac complications, but frequently have associated medical conditions associated with the extremes of age. Nitrous oxide (N2O) can increase intraocular pressure and cause blindness in patients who recently had a medical gas injected into the eye (a treatment for retinal detachment). To avoid this complication, N2O should not be used for patients who have had SF6 injected within the previous 4 weeks or C3F8 injected within the previous 3 months. 1. What is the urgency of the surgery? What is the risk of delay in order to obtain additional preoperative information? Most ophthalmic operations are elective. As a general rule medical conditions should be optimized before ophthalmic surgery. Emergent: Chemical burn, central retinal artery occlusion, and acute glaucoma (unresponsive to medication) are ophthalmic emergencies and require operations as soon as possible to improve the chance of maintaining vision in the affected eye. Urgent: Ruptured globe is considered an urgent case. Surgery should generally be performed within 24 hours of injury to reduce the chance of endophthalmitis from developing. Detached retinas are also considered to require urgent repairs if the macula is attached to the retina. In this situation surgery is usually performed within 24 hours of the diagnosis to reduce the risk of the macula detaching. (Macular detachment is associated with a poorer visual outcome.) However, surgery for a ruptured globe or a detached retina can generally be delayed until acute medical conditions are optimized. Elective: Most other eye operations are elective and can be delayed if necessary until the patient is optimized for surgery. 2. Preoperative evaluation The goals of a focused history and physical (H&P) are to establish a good doctor-patient relationship, assess patient risks, psychologically and physically prepare the patient for surgery, inform the patient about the risks and benefits of anesthesia, document this informed consent, assist in ensuring the correct site is operated upon, and plan for perioperative management. A good H&P will reduce the risk of perioperative delay, cancellation, and optimize perioperative care. Medical conditions should be optimized before elective ophthalmic surgery. Medical problems frequently encountered in adults include hypertension, diabetes, use of antithrombotic agents, coronary artery disease, congestive heart failure, COPD, arrhythmias, and implanted cardiac devices. Infants and children frequently present with complications of prematurity and congenital abnormalities. “Routine” preoperative labwork and electrocardiography (ECG) has not been shown to improve perioperative outcome (at any age) for low-risk surgery. Therefore, preoperative labwork and ECG are only warranted for specific medical conditions. Although there are guidelines, currently there are no nationally agreed upon preoperative lab recommendations. The guidelines we use at our institution (Massachusetts Eye & Ear Infirmary) for low-risk surgery include electrolytes for diuretic use, preoperative blood sugar for diabetics, and repeat blood sugar(s) for insulin-dependent diabetics on the day of surgery, INR for patients who took warfarin within 4 days or less before surgery, BUN/creatinine for renal dysfunction, LFTs, CBC, PT/INR, PTT for severe liver disease, and ECG for patients with cardiac disease. Because most eye operations are elective, most medically unstable conditions should be optimized before surgery. Delaying surgery may be indicated if the patient has acute respiratory illness, hypertension that is unevaluated or unresponsive to medication (systolic BP>180, diastolic BP>110), exacerbation of COPD or CHF, or a new clinically signficant arrhythmia. 3. What are the implications of co-existing disease on perioperative care? b. Cardiovascular system Acute or unstable cardiac conditions should generally be stabilized before eye surgery. Baseline coronary artery disease or cardiac dysfunction Goals of management are to minimize stress responses (e.g., tachycardia, hypertension) and maintain cardiovascular stability. A focused history is the most important method for detecting cardiovascular diseases. A preoperative ECG may be useful (as a baseline) for patients with known or suspected cardiac disease but most patients with stable cardiovascular disease can undergo ophthalmic surgery without other specialized cardiac testing. Delaying surgery or requesting additional preoperative evaluation for cardiac conditions is indicated for unstable cardiac conditions, such as MI within 30 days (7 days if additional myocardium shown not to be at risk), unstable angina, unstable CHF, unstable severe arrhythmias, and, if general anesthesia is required, undiagnosed murmurs. Other unstable cardiovascular conditions such as recent CVA or TIA may also warrant delaying surgery and obtaining additional medical evaluation. Hypertension (HTN) is a common problem in the elderly. The goal is to maintain the patient’s blood pressure (BP) in their therapeutic range such as systolic BP (SBP) <180 and diastolic BP (DBP) <110. Patients undergoing elective eye surgery with undiagnosed and untreated HTN should generally be delayed until their BP is evaluated and treated by an internist. Some patients who are anxious will have SBP> 180 and/or diastolic BP> 110 on the day of surgery despite having well-controlled BP preoperatively and are compliant with antihypertensive medication (“white coat syndrome”). For these (adult) patients, it is appropriate to administer a small dose(s) of a benzodiazine (e.g., midazolam 0.5-1 mg IV) or, if no contraindication, a beta blocker (e.g., lopressor 5 mg IV) or smooth muscle dilator (e.g., hydralazine 5-10 mg IV). Sedatives must be give judiciously so that intraoperatively, patients are aware of their surroundings and can respond to verbal commands. Allow sufficient time for the initial dose of sedative and/or antihypertensive agent to have an effect (e.g., 5-10 minutes midazolam and lopressor, 20 minutes hydralazine) before giving an additional dose. One study demonstrated treating diastolic HTN between 110-130 preoperatively on the day of surgery until BP was controlled vs cancelling surgery and making the patient return at a later date when BP was controlled showed no difference in outcomes. Patients with pacemakers and implanted cardiac defibrillators (ICDs) should be identified far enough in advance of surgery to confirm the device will continue to function appropriately in the perioperative period. Although these devices only occasionally fail unexpectedly, there are recommendations that before any surgical procedure these devices be checked. This check should include identification of the device (e.g., pacemaker? ICD? brand? model?), implanted date, date of last interrogation (our current guidelines; 6 months for pacemakers, 3 months for ICDs), has adequate perioperative battery life, the generator and leads are functioning appropriately, how the generator will respond to a magnet, and in the case of an ICD, if there have been any recent therapies for arrhythmias. (Recent therapy could increase the risk of device discharging during eye surgery, causing the patient to move.) In addition it is prudent to question the patient about any recent episodes of syncope, near syncope, and shortness of breath. (These could be signs of device malfunction or worsening underlying disease.) Patients with ICDs should also be asked about episodes of recent (known) device discharge. If present, and the device is left active intraoperatively, the patient will be at increased risk of the device delivering therapy and possibly causing patient movement. Adults with undiagnosed murmurs, or moderate or greater severity aortic stenosis, not reevaluated within the previous 12 months should have a preoperative echocardiogram evaluation to rule out significant aortic stenosis, mitral stenosis, a VSD, or an ASD before receiving general anesthesia. Children and adults with complex cardiac abnormalities, even if repaired, should receive a cardiology evaluation before undergoing general anesthesia. If general anesthesia is required in individuals with complex cardiac abnormalities or MAC or general anesthesia is required for patients with single chamber physiology, consideration should be given to performing anesthesia and surgery in a center that has experience with caring for individuals with complex congenital cardiac abnormailities. Perioperative risk reduction strategies Continue most cardiac and HTN medications up to and including the day of surgery. (Hold diuretics on the day of surgery unless required for CHF.) It is recommended to continue warfarin and other antithrombotic agents (e.g., clopidogrel [Plavix] and aspirin) for patients prescribed these medications undergoing cataract surgery. For vitrectomies and other eye operations, preoperative consultation between the ophthalmologist and patient’s internist or cardiologist is the best method to asses the perioperative risk of bleeding and develop a perioperative management strategy. Patients who had a drug eluting cardiac stent placed within the previous 12 months, or a bare metal cardiac stent within the previous 4-6 weeks, are at high risk of stent clotting if clopidogrel and/or aspirin is stopped within these periods. Elective surgery requiring stopping these medications should be delayed during these periods. If surgery is urgent and the risk of bleeding is considered to be moderate to high, generally clopidogrel is stopped and aspirin is continued perioperatively. A cardiology consultation should be considered if these drugs need to be stopped before the times outlined above. Do not administer eye drops that can exacerbate HTN (e.g., NeoSynephrine) until BP is well controlled (e.g., SBP <180, DBP <110). Administer a small additional dose of anti-anxiety and antihypertensive agents only as needed. Avoid or treat measures that increase pulse rate and BP (e.g. anxiety, pain, full bladder). If the patient is having eye pain request the surgeon to administer additional local anesthesia. For patients with a history of CHF undergoing MAC, minimize time supine. Consider having the head of the bed slightly elevated, or having the bed in reverse trendelenberg position. Determine by history, physical exam, and information from the patient’s electrophysiology lab, that pacemakers and ICDs are functioning appropriately preoperatively, and has adequate battery life to function into the perioperative period. Patients with appropriately functioning pacemakers can be operated on with no changes in routine management if a monopolar electrosurgical instrument (e.g. Bovie) is not used. (Rare for ophthalmic procedures) ICDs are commonly left active during eye operations if Bovie not used, the ICD has not delivered therapy recently, and the surgeon and anesthesia staff are warned that if an arrythmia is detected, the ICD can delivered electrical therapy with subsequent patient movement within 6-15 seconds. If indicated, most (but not all) ICDs can be temporarily inactivated by placing a magnet over the generator (after have working external defibrillator immediately in room). Preoperatively check with patient’s ICD lab, or manufacturer, how to inactivate and reactivate ICD if this might be necessary. Significant valvular lesions should be ruled out preoperatively for patients requiring general anesthesia. If general anesthesia is required in individuals with complex cardiac abnormalities, or M.A.C. or general anesthesia is required for patients with single chamber physiology, these patients should be evaluated by a cardiologist preoperatively and consideration should be given to performing anesthesia and surgery in a center that has experience with caring for individuals with complex congenital cardiac abnormailities. An acute respiratory condition (e.g., URI), or unstable chonic condition (e.g., asthma or COPD) should be ruled out by history and physical exam. For adults undergoing local anesthesia with MAC, it should be determined if the patient can lie flat for the duration of the procedure without movement or coughing. Be aware that the rare patient with pulmonary artery hypertension, will be at increased isk of morbidity and mortality if GA required. Preoperative consultation wilth a pulmonologist is recommended if GA might be required. Be aware that infants and children born prematurely with bronchopulmonary dysplasia have an increased risk of preoperative respiratory complications that may be compounded by acute pulmonary conditions Perioperative risk reduction strategies After discussion with the ophthalmologist, consider delaying surgery for acute or unstable pulmonary conditions until optimized. This might mean delaying surgery a few days to several weeks. For patients with mild asthma, a preoperative bronchodilator or nebulizer treatment may be useful. Exacerbation of severe or chronic pulmonary problems may require management by the patient’s primary care physician or pulmonologist. Patients with a history of kidney disease should have preoperative electrolytes and renal function tests if general anesthesia may be required. These tests should be repeated preoperatively on the day of surgery if the patient receiving dialysis and general anesthesia may be required. Ensure no unstable GI conditions. Inquire about a history of postoperative nausea or vomiting (PONV). Perioperative risk reduction strategies Patients requiring dialysis should be scheduled for surgery whenever possible the day after dialysis. Patients with significant kidney disease should have IV fluids that do not contain potassium. For patients with fluid restrictions the IV infusion rate should be appropriately maintained. If general anesthesia is required, be aware succinyl choline can increase serum potassium 0.5-1.0 mEq/L. Cis-atracurium may be the intermediate muscle relaxant of choice because of its nonrenal elimination and minimal hemodynamic effect. Confirm that the patient has complied with institution’s NPO guidelines before administering sedation or general anesthesia. Consider administering antiemetic(s) such as odansetron and/or dexamethasone to reduce risk of PONV if general anesthesia is required or patient has a history of PONV with MAC. Consider adding third antiemetic (e.g., scopolamine patch) and/or using TIVA techniques if patient has a significant history of PONV. Inquire about history of seizures, CVA, TIA, weakness, chronic pain, tremor, anxiety, claustrophobia, and dementia. Perioperative risk reduction strategies Request patient to continue antiseizure, chronic pain, and other essential neurologic medications to time of surgery with sip(s) water. Plan with surgeon preoperatively most appropriate anesthesia technique (e.g., MAC? GA?). If MAC, consider restraining head with tape, maintain verbal contact, reassure patient if necessary, and hold patient’s hand if patient desires. If patient is anxious, consider using clear drape, elevate drape allowing air to circulate onto patient’s face. g. Additional systems/conditions which may be of concern in a patient undergoing this procedure and are relevant for the anesthetic plan (eg. 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? As a general rule, most essential medications (e.g., most antihypertensives, cardiac, pulmonary, and antiseizure medications) are continued on their normal schedule with a sip(s) water until the time of surgery. (See more detailed recommendations below.) Some herbal medications (e.g., Ginko, ginseng). and many NSAIDs have some antithrombotic properties. h. Are there medications commonly seen in patients undergoing this procedure and for which should there be greater concern? For patients taking clopidogrel (Plavix) or other thienopyridines, or aspirin, it is important to ascertain the reason these drugs are being taken. If the patient had a cardiac stent placed within the previous year and these drugs are stopped, it may increase the risk of clotting of the stent. (See recommendations in Cardology section above.) Patients who have taken tamsulosin (Flomax) may have a floppy iris syndrome requiring use of iris hooks to perform cataract surgery and increase the length of surgery slightly. i. What should be recommended with regard to continuation of medications taken chronically? Continue most cardiac, antihypertensive, pulmonary, and antiseizure medications on schedule up to and including the day of surgery. Medications may be taken with sips of water. (Hold diuretics on the day of surgery unless required for CHF.) Request the patient to bring inhaler(s) to hospital. See recommendation regarding clopidogrel (Plavix), other thienopyridines, and aspirin above. Recent guidelines recommend continuing warfarin in therapeutic doses for cataract surgery and other procedures on superficial structures. Some studies suggest the risk of significant bleeding is small if warfarin is continued up to the day of surgery for a vitrectomy. However, there is concern by many retinal surgeons about the possibility of a significant bleeding complication in this situation. For patients who do stop warfarin several days preoperatively, and who are at moderate to high risk of developing a thrombotic complication, recent guidelines suggest considering administration of a low molecular weight heparin for several days preoperatively, with the last dose approximately 24 hours before surgery, and resuming warfarin the evening of or morning following surgery. Essential renal, neurologic (e.g., antiseizure medications), and psychiatric medications should also be continued up to the time of surgery. j. How To modify care for patients with known allergies – Ester anesthetics are avoided for patients with allergies to this class of drug (e.g., procaine [Novocain], tetracaine, chloroprocaine) and amide anesthetics (e.g., lidocaine, bupivacaine) are substituted. k. Latex allergy- If the patient has a sensitivity to latex (eg. rash from gloves, underwear, etc.) nonlatex containing gloves are used, and drugs with latex caps are removed (not punctured) when drawing up medications. The operating room staff is informed and only with latex free products are used. l. Does the patient have any antibiotic allergies- [Tier 2- Common antibiotic allergies and alternative antibiotics] Allergic reaction to antibiotics are noted and communicated to the surgeon. If the patient has a reaction to a penicillin derivative, and an antibiotic is required, another class of antibiotic is administered (e.g., clindamycin). m. Does the patient have a history of allergy to anesthesia? For patients with history of, significant risk factor for, or close family member history of malignant hyperthermia (MH) Consider regional anesthesia If general anesthesia required Ensure MH cart is available Avoid succinylcholine and inhalational agents if general anesthesia required History of sensitivity or allergic reaction to local anesthesia Determine if sensitivity likely to be epinephrine, possibly previously mixed with local anesthesia. If so, avoid epinephrine. If allergic to local anesthetic (usually ester based), use different class drug (e.g., amide). Also see above. 5. What laboratory tests should be obtained and has everything been reviewed? Preoperative labwork and ECG are only warranted for specific medical conditions. Guidelines in use (at our institution) for low-risk (eye) surgery include electrolytes for diuretic use, preoperative blood sugar for all diabetics and repeat blood sugar(s) for insulin-dependent diabetics on the day of surgery, INR for patients who took warfarin within 5 days of surgery, BUN/creatinine for renal dysfunction, LFTs, CBC, PT/INR, PTT for severe liver disease, and ECG for patients with history of cardiac disease. Hemoglobin levels: Only indicated if concerned about severe preoperative anemia (rare) Electrolytes: Indicated if taking diuretics and/or has kidney disease and GA possible. Coagulation panel: Indicated for history of bleeding diathesis. Day of surgery INR (fingerstick if possible) for patients who took warfarin 4 days or less before surgery. Imaging: Not routinely indicated. Other tests: Not routinely indicated. Intraoperative Management: What are the options for anesthetic management and how to determine the best technique? Regional anesthesia of the orbit (usually with sedation during block) and general anesthesia are the two options for providing analgesia and eye akinesia during orbital surgery. Commonly used techniques for orbital regional anesthesia include topical eye drops (mostly used for cataract surgery), extraconal block (sometime referred to as peribulbar block), intraconal block (retrobulbar block), and sub-Tenon’s block. Regional anesthesia (with or without sedation) and MAC Regional anesthesia of the orbit (topical or block), usually with sedation for needle blocks, are the most common methods of providing analgesia for adults undergoing procedures on the globe. Regional anesthesia (with MAC) Benefits: Low risk of side effects (e.g., prolonged sedation, PONV, sore throat) Drawbacks: Small risk of injury to eye and surrounding structures, small risk of systemic spread and cardiovascular instability. Increased risk of minor bleeding (e.g. skin hematoma, and conjunctiva bleeding) if taking antithrombotics. Contraindicated if infection at injection site. Issues: Need cooperative motionless patient. Not appropriate for patients who cannot lie flat for duration of procedure (e.g., has orthopnea, severe claustrophobia, severe sleep apnea,, or dementia) Slowing of heart rate from block (oculocardiac reflex) common, usually self-limited. Must be prepared to resuscitate from complications of block. (Self-inflating bag/mask, oxygen, airways, atropine, crash cart must be immediately available.) Limited access to head and neck during procedure if oversedated. Fire risk if Fio2 0.50 or greater administered around face (recommend starting Fio2 0.30 or less during surgery) CO2 can build up under drapes and cause restlessness (can dissipate CO2 by having mouth and nose exposed. If draped, have flows of at least 10 L/min of compressed air or air/oxygen mixture, or use vacuum tubing to remove CO2 buildup) b. General Anesthesia Benefits: Patient immobility and anesthesia. Drawbacks: PONV, longer time until fit for discharge, sore throat, higher risk of postoperative confusion in elderly, higher risk of cardiovascular and respiratory complications. Other issues: Must ensure patient immobility during procedure (movement can result in damage to eye). Airway concerns: Must ensure secure airway during intraorbital surgery. c. Monitored Anesthesia Care (See Regional Anesthesia above) 6. What is the author's preferred method of anesthesia technique and why? Regional anesthesia is preferred over general anesthesia because of reduced risk of PONV, reduced time to be street ready postoperatively, no sore throat, reduced risk of cardiovascular and respiratory complications, and reduced medicolegal liability from patient movement if awake. What antibiotic is given prophylactically? None routinely. Antibiotic administered only if surgeron requests it. What do I need to know about the surgical technique to optimize anesthetic care? Nitrous oxide (N20) can increase intraocular pressure and cause blindness in patients who recently had a medical gas injected into the eye. (A treatment for retinal detachment) To avoid this complication N20 should not be used for patients who have had SF6 injected within the previous 4 weeks, or C3F8 injected within the previous 3 months. Body motion during intraocular surgery can be disastrous. Every effort should be made to prevent movement during introcular surgery. Need to wait until surgeon marks eye before performing orbital block for patients having Toric lens implanted. What can I do intraoperatively to assist the surgeon and optimize patient care? Maintain normotension, prevent patient movement. What is the most common intraoperative complications and how can it be avoided/treated? Oculocardiac reflex (vagally mediated bradycardia). Avoid by minimizing traction on extraoccular muscles, consider prophylactic orbital block. Treat with anticholinergic (e.g., glycopyrrolate or atropine), orbital block. b. If the patient is intubated, are there any special criteria for extubation? To reduce the risk of straining on the endotracheal tube, many patients are extubated “deep” if they meet commonly used criteria for extubation (e.g., no signficant muscle paralysis by nerve stimulator, respiratory rate 10-18, adequate tidal volume, normothermic, no difficulty with airway or respiratory status anticipated). c. Postoperative management What analgesic modalities can I implement? Frequently acetaminophen is all that is needed for analgesia after minor eye operations (e.g., cataracts). Narcotic are usually required after orbital surgery and sometimes required after other types of ophthalmic surgery. Ketorolac should be considered for procedures likely to cause moderate or severe pain after discussion with surgeon about drug’s mild antithrombotic properties. What level bed acuity is appropriate? Most patients are discharged home on the day of surgery. Infants born prematurly (less than 36 weeks) and are less than 60 weeks gestational age are admitted overnight and monitored continuously with oximeter. What are common postoperative complications, and ways to prevent and treat them? Serious postoperative complications related to anesthesia are rare after ophthalmic surgery. Patients undergoing general anesthesia can have PONV, sore throat, and somnolence. PONV can be reduced by prophylactic antiemetics (e.g. odansetron and dexamethasone) and a TIVA techniques. Somnolence can be reduced by short actiong anesthethic agents (e.g., propofol, desflurane, remifentanil infusion). What's the Evidence? Feldman, MA, Patel, A. “Anesthesia for eye, ear, nose and throat surgery. In Miller's Anesthesia”. 2010. pp. 2378-88. (Good general review on the subject of anesthesia for ophthalmologic surgery.) Schein, OD, Katz, J, Bass, EB. “The value of routine preoperative medical testing before cataract surgery. Study of medical testing for cataract surgery”. N Engl J Med. vol. 20. 2000. pp. 168-175. (Important paper giving evidence "routine lab & EKG" do not improve perioperative outcomes for cataract surgery.). “ASA practice advisory for preanesthesia evaluation”. Anesthesiology. vol. 116. 2012. pp. 522-38. (Updated advisory of what preoperative testing is likely to be useful.) Weksler, N, Klein, M, Szendro, G. “The dilemma of immediate preoperative hypertension; to treat and operate, or postpone surgery”. J Clin Anesth. vol. 15. 2003. pp. 179-83. (Provides evidence that treating hypertension preoperatively on the day of surgery for patients with diastolic BP 110-130 had no worse outcome than canceling surgery, admitting patient and treating patient for hypertension, and performing surgery at a later date for surgery.) “ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery”. JACC. vol. 50. 2007. pp. e159-241. (Excellent general advisory on preoperative cardiac evaluation.) Douketis, JD, Berger, PB, Dunn, AS. “The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines”. Chest. vol. 133. 2008. pp. 299S-339S. (Excellent review of the literature. Gives evidence that continuing aspirin and warfarin [in therapeutic levels] perioperatively does not increase the risk of serious perioperative bleeding complications for cataract surgery.) Rozner, MA. “Implantable cardiac pulse generators: Pacemakers and cardioverter-defibrillators. In Miller's Anesthesia”. 2010. pp. 1389-409. (Excellent review on perioperative management of pacemakers, ICDs, and implanted cardiac devices for CHF.) Hart, RH, Vote, BJ, Borthwick, JH. “Loss of vision caused by expansion of intraocular perfluoropropane C3F8 gas during nitrous oxide anesthesia”. J Ophthalmol. vol. 134. 2002. pp. 761-3. (Case reports of nitrous oxide causing blindness in patients who had C3F8 gas bubble for retinal detachment.) Astrom, S, Kjellgren, D, Monestam, E. “Nitrous oxide anesthesia and intravitreal gas tamponade”. Acta Anaesthesiol Scand. vol. 47. 2003. pp. 361-2. (Case report of nitrous oxide causing blindness in patients who had SF6 gas bubble for retinal detachment.) 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: - g. Additional systems/conditions which may be of concern in a patient undergoing this procedure and are relevant for the anesthetic plan (eg. 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 (eg. rash from gloves, underwear, etc.) nonlatex containing gloves are used, and drugs with latex caps are removed (not punctured) when drawing up medications. The operating room staff is informed and only with latex free products are used. - l. Does the patient have any antibiotic allergies- [Tier 2- Common antibiotic allergies and alternative antibiotics] - 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? - a. Neurologic: - b. If the patient is intubated, are there any special criteria for extubation? - c. Postoperative management	2	15	0	0	2	0.463913	2	6,825
The most common early warning signs of a thyroid problem include unexplained tiredness, constipation, dry skin, body temperature problems, weight gain, hoarseness, and mood imbalances. These symptoms may seem unrelated, but when taken together, can amount to thyroid concerns. That being said, while symptoms of an illness, condition, or disease are usually the motivator to get you to the doctor, they’re not always the best indicator for what may actually be ailing you. Looking out for particular symptoms and getting regular checkups if you have a family history of a particular disease, such as thyroid problems, GI disorders, high blood pressure, or certain cancers, is most certainly a good idea. But in the case of thyroid issues specifically, blood tests are the most accurate way to get a truly reliable picture of what’s going on. In other words, although it’s important to recognize and understand the symptoms, they’re not very predictive when it comes to diagnosing hypothyroidism — low levels of thyroid hormone production in the butterfly-shaped gland at the front of your neck. (In this article, we’re focused on hypothyroid, or underactive thyroid, rather than hyperthyroid, or overactive thyroid/too much thyroid hormone.) There are a number of different possible symptoms of hypothyroidism, but having one or two of those symptoms is not a reliable indicator that you have a thyroid problem, largely because many hypothyroidism symptoms overlap with symptoms of other conditions (some of which, like IBS and other digestive disorders, are more common or more likely). In fact, hypothyroidism only affects about 1% of the population, while IBS (irritable bowel syndrome) affects closer to 15% of the population [1, 2]. So what are early warning signs of thyroid problems? Let’s go over what to look out for, the tests that will be most indicative of a problem, and what to do if your levels are normal but you’re still experiencing symptoms of hypothyroid. What Are Early Warning Signs of Thyroid Problems? As we already mentioned, many of the symptoms we’re about to enumerate can also be symptoms of other diseases or conditions. So it’s important to understand that displaying one, two, or even three symptoms from this list doesn’t necessarily mean you have a thyroid condition. Importantly, the more symptoms you have from this list, the greater the likelihood that your issue is in fact with your thyroid, especially if you’re experiencing fouror more of these symptoms [3 Trusted SourcePubMedGo to source]. Early warning signs of a thyroid disorder or reduced thyroid function, in order of prevalence, include: For example, Hashimoto’s thyroiditis is an autoimmune condition that directly affects the thyroid and can lead to hypothyroidism. It’s the most common cause of hypothyroidism in the United States [7 Trusted SourcePubMedGo to source]. Your healthcare provider should be looking at your whole picture of health, including family history, other related illnesses, and above all, requesting labs so that you can have a very concrete idea of the state of your endocrine system and whether or not you’re making enough hormones. Blood Tests for Thyroid Health Because the most common symptoms of hypothyroidism overlap with other health challenges, it’s important to dig a little bit deeper than the symptoms to get to the root cause. Screening for symptoms can be useful in younger populations, but for the elderly, especially for women over 60 — which represent 47.4% of all autoimmune hypothyroid patients — it’s not a useful tool [3 Trusted SourcePubMedGo to source]. Importantly, no individual symptom can help predict whether or not a person is in need of HRT or other thyroid meds. Measuring TSH (thyroid-stimulating hormone), free T4 (thyroxine), and TPO (thyroid peroxidase) antibodies through bloodwork is the best way to verify if your symptoms could be attributable to thyroid dysfunction. From there, you can determine whether or not your levels are low enough to merit taking medication, or if something else might be going on that’s affecting your energy levels, skin, and digestion. While medical tests like blood work aren’t always the best predictors for every disease, in the case of thyroid hormone levels, blood work is actually the gold standard and very reliable. It’s worth getting labs done if you have any suspicion at all that you might have hypothyroidism. This type of blood work is relatively inexpensive, and knowing your levels is an important jumping-off point for next steps. It’s also a great way to avoid taking unnecessary medication. Furthermore, all prescription drugs come with potential side effects, and thyroid medications are no different. Taking them when they’re not actually needed increases your risk of experiencing side effects, and for no good reason. If you’re truly hypothyroid, you will benefit from thyroid medications and should take them. But if you have normal thyroid levels or subclinical hypothyroidism, there’s no reason for a healthcare professional to shoehorn you into a diagnosis and over-treat the problem with meds just because some of the symptoms line up. It’s important to know your body and to notice if symptoms begin to crop up that don’t have an obvious explanation. Many symptoms point to more than one disease or dysfunction, so while knowing which symptoms to look out for is a good idea, it’s also critical to know when it’s time to ask your doctor for blood work. What are early warning signs of thyroid problems? The big ones to look out for are unexplained tiredness, constipation, cold intolerance, weight gain, hoarseness, mood imbalances, and muscle weakness. The more of these you have, the more likely it is that you have a thyroid problem. But blood work is the only way to know for certain if you have clinically low levels of thyroid hormone. If you’ve been told that your thyroid hormone ranges are normal or subclinical but you still have lots of symptoms, you should seek a second opinion before beginning HRT or other thyroid med regimens. It’s not only possible but likely that your symptoms are gut-related and could be addressed with dietary changes and probiotics. If you’re looking for assistance to get you on the right track toward better understanding your whole health picture, reach out to our clinic. We’d love to help you. The Ruscio Institute has developed a range of high-quality formulations to help our patients and audience. If you’re interested in learning more about these products, please click here. Note that there are many other options available, and we encourage you to research which products may be right for you. Carlé A, Pedersen IB, Knudsen N, Perrild H, Ovesen L, Andersen S, et al. Hypothyroid Symptoms Fail to Predict Thyroid Insufficiency in Old People: A Population-Based Case-Control Study. Am J Med. 2016 Oct;129(10):1082–92. DOI: 10.1016/j.amjmed.2016.06.013. PMID: 27393881. Trusted SourcePubMedGo to source Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid. 2012 Dec;22(12):1200–35. DOI: 10.1089/thy.2012.0205. PMID: 22954017. Trusted SourcePubMedGo to source Chiovato L, Magri F, Carlé A. Hypothyroidism in context: where we’ve been and where we’re going. Adv Ther. 2019 Sep 4;36(Suppl 2):47–58. DOI: 10.1007/s12325-019-01080-8. PMID: 31485975. PMCID: PMC6822815. Trusted SourcePubMedGo to source Chanasumon N, Sriphojanart T, Suchonwanit P. Therapeutic potential of bimatoprost for the treatment of eyebrow hypotrichosis. Drug Des Devel Ther. 2018 Feb 22;12:365–72. DOI: 10.2147/DDDT.S156467. PMID: 29503529. PMCID: PMC5826207. Trusted SourcePubMedGo to source Cryer B, Redfern JS, Goldschmiedt M, Lee E, Feldman M. Effect of aging on gastric and duodenal mucosal prostaglandin concentrations in humans. Gastroenterology. 1992 Apr;102(4 Pt 1):1118–23. PMID: 1551520. Trusted SourcePubMedGo to source Siegel B, Weihe E, Bette M, Nüsing RM, Flores-de-Jacoby L, Mengel R. The effect of age on prostaglandin-synthesizing enzymes in the development of gingivitis. J Periodont Res. 2007 Jun;42(3):259–66. DOI: 10.1111/j.1600-0765.2006.00942.x. PMID: 17451546. Trusted SourcePubMedGo to source Qian H, Luo N, Chi Y. Aging-shifted prostaglandin profile in endothelium as a factor in cardiovascular disorders. J Aging Res. 2012 Feb 13;2012:121390. DOI: 10.1155/2012/121390. PMID: 22500225. PMCID: PMC3303603. Trusted SourcePubMedGo to source Burgos N, Toloza FJK, Singh Ospina NM, Brito JP, Salloum RG, Hassett LC, et al. Clinical Outcomes After Discontinuation of Thyroid Hormone Replacement: A Systematic Review and Meta-Analysis. Thyroid. 2021 May;31(5):740–51. DOI: 10.1089/thy.2020.0679. PMID: 33161885. PMCID: PMC8110016. Trusted SourcePubMedGo to source Livadas S, Bothou C, Androulakis I, Boniakos A, Angelopoulos N, Duntas L. Levothyroxine replacement therapy and overuse: A timely diagnostic approach. Thyroid. 2018 Nov 30; DOI: 10.1089/thy.2018.0014. PMID: 30351232. Trusted SourcePubMedGo to source Han CJ, Yang GS. Fatigue in Irritable Bowel Syndrome: A Systematic Review and Meta-analysis of Pooled Frequency and Severity of Fatigue. Asian Nurs Res (Korean Soc Nurs Sci). 2016 Mar;10(1):1–10. DOI: 10.1016/j.anr.2016.01.003. PMID: 27021828. Trusted SourcePubMedGo to source Frändemark Å, Jakobsson Ung E, Törnblom H, Simrén M, Jakobsson S. Fatigue: a distressing symptom for patients with irritable bowel syndrome. Neurogastroenterol Motil. 2017 Jan;29(1). DOI: 10.1111/nmo.12898. PMID: 27401139. Trusted SourcePubMedGo to source Saito YA, Schoenfeld P, Locke GR. The epidemiology of irritable bowel syndrome in North America: a systematic review. Am J Gastroenterol. 2002 Aug;97(8):1910–5. DOI: 10.1111/j.1572-0241.2002.05913.x. PMID: 12190153. Trusted SourcePubMedGo to source Ribichini D, Fiorini G, Repaci A, Castelli V, Gatta L, Vaira D, et al. Tablet and oral liquid L-thyroxine formulation in the treatment of naïve hypothyroid patients with Helicobacter pylori infection. Endocrine. 2017 Sep;57(3):394–401. DOI: 10.1007/s12020-016-1167-3. PMID: 27848196. Trusted SourcePubMedGo to source Bugdaci MS, Zuhur SS, Sokmen M, Toksoy B, Bayraktar B, Altuntas Y. The role of Helicobacter pylori in patients with hypothyroidism in whom could not be achieved normal thyrotropin levels despite treatment with high doses of thyroxine. Helicobacter. 2011 Apr;16(2):124–30. DOI: 10.1111/j.1523-5378.2011.00830.x. PMID: 21435090. Trusted SourcePubMedGo to source Centanni M, Gargano L, Canettieri G, Viceconti N, Franchi A, Delle Fave G, et al. Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis. N Engl J Med. 2006 Apr 27;354(17):1787–95. DOI: 10.1056/NEJMoa043903. PMID: 16641395. Trusted SourcePubMedGo to source Wang B, Xu Y, Hou X, Li J, Cai Y, Hao Y, et al. Small intestinal bacterial overgrowth in subclinical hypothyroidism of pregnant women. Front Endocrinol (Lausanne). 2021 May 24;12:604070. DOI: 10.3389/fendo.2021.604070. PMID: 34108932. PMCID: PMC8181748. Trusted SourcePubMedGo to source Talebi S, Karimifar M, Heidari Z, Mohammadi H, Askari G. The effects of synbiotic supplementation on thyroid function and inflammation in hypothyroid patients: A randomized, double‑blind, placebo‑controlled trial. Complement Ther Med. 2020 Jan;48:102234. DOI: 10.1016/j.ctim.2019.102234. PMID: 31987229. Trusted SourcePubMedGo to source Ng QX, Peters C, Ho CYX, Lim DY, Yeo W-S. A meta-analysis of the use of probiotics to alleviate depressive symptoms. J Affect Disord. 2018 Mar 1;228:13–9. DOI: 10.1016/j.jad.2017.11.063. PMID: 29197739. Trusted SourcePubMedGo to source Maes M, Leunis J-C. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuro Endocrinol Lett. 2008 Dec;29(6):902–10. PMID: 19112401. Trusted SourcePubMedGo to source Altobelli E, Del Negro V, Angeletti PM, Latella G. Low-FODMAP Diet Improves Irritable Bowel Syndrome Symptoms: A Meta-Analysis. Nutrients. 2017 Aug 26;9(9). DOI: 10.3390/nu9090940. PMID: 28846594. PMCID: PMC5622700. Trusted SourcePubMedGo to source Marum AP, Moreira C, Saraiva F, Tomas-Carus P, Sousa-Guerreiro C. A low fermentable oligo-di-mono saccharides and polyols (FODMAP) diet reduced pain and improved daily life in fibromyalgia patients. Scand J Pain. 2016 Aug 22;13:166–72. DOI: 10.1016/j.sjpain.2016.07.004. PMID: 28850525. Trusted SourcePubMedGo to source I care about answering your questions and sharing my knowledge with you. Leave a comment or connect with me on social media asking any health question you may have and I just might incorporate it into our next listener questions podcast episode just for you! Transform your health Every product is science-based, validated by real-world use, and personally vetted by Dr. Ruscio, DNM, DC.	2	9	5	0	0	0.992584	5	3,565
Congenital Malformations, Deformations, and Chromosomal Abnormalities (Q00-Q99) Refer to ICD-10 guidelines and sample cases to correctly report congenital anomalies. By Chandra Stephenson, CPC, COC, CPB, CPCO, CPMA, CPC-I, CIC, CCS, CANPC, CEMC, CFPC, CGSC, CIMC, COSC An estimated one in 33 infants globally is born with a congenital anomaly. In 2010, congenital anomalies accounted for approximately 270,000 neonatal deaths in 193 countries. Congenital anomalies — commonly referred to as birth defects — include congenital malformations, deformations, and chromosomal abnormalities. Heart defects, neural tube defects, and Down syndrome are the most common congenital anomalies. Source: Congenital Anomalies, World Health Organization Patients are most often diagnosed and treated for congenital anomalies during the neonatal period, but an individual may be diagnosed and treated at any age. Some congenital anomalies can produce long-term disabilities that require a lifetime of care. To understand and correctly report congenital anomalies using ICD-10, refer to guidelines in ICD-10-CM Official Guidelines for Coding and Reporting, chapter 17, to code sample cases: Congenital anomalies may be the principal or first-listed diagnosis during an encounter, or they may be reported as an additional diagnosis, depending on the circumstances of the encounter. Example 1: Amanda returns to Dr. Adams’ office with her parents to discuss her upcoming surgery to repair her left-sided cleft lip. Q36.9 Cleft lip, unilateral Example 2: John presents to Dr. Smith’s office complaining of fatigue. John has non-mosaicism Down syndrome. R53.83 Other fatigue Q90.0 Trisomy 21, nonmosaicism Manifestations that are not an inherent component of the congenital anomaly should be separately reported. Example 1: Melissa is seen for difficulty swallowing associated with her cleft palate. Q35.9 Cleft palate, unspecified Example 2: Michael was diagnosed with a subglottic web of the larynx. During a follow-up evaluation for this condition, Dr. Jones noted a cardiac murmur upon examination and has ordered an EKG. Q31.0 Web of larynx R01.1 Cardiac murmur, unspecified If the congenital anomaly has been corrected, a personal history code should be reported to identify the history of the anomaly, when applicable. NOTE: If a congenital anomaly requires multiple procedures before correction is complete, the anomaly is considered to still exist until all planned procedures are performed, and the provider feels the anomaly has been corrected. (This guideline is found in the excludes notes section of the applicable personal history codes.) Example 1: Alex presents for her one-year, post-op visit following ventricular septal defect repair. Z87.74 Personal history of (corrected) congenital malformations of heart and circulatory system Example 2: Shannon is seeing Dr. Williams for follow-up on her tetralogy of Fallot. Shannon has undergone one surgery to begin repair and Dr. Williams anticipates Shannon will need two additional surgeries before repair is complete. Q21.3 Tetralogy of Fallot When a congenital anomaly is identified at birth, the birth encounter should first list the appropriate Z38 code, followed by the appropriate codes from categories Q00-Q99 to identify the anomaly(s). Example: Following vaginal delivery of a single liveborn infant in the hospital, Dr. Patel noted webbing between the toes of the neonate’s left foot. Z38.00 Single liveborn infant, born in hospital, delivered vaginally Q70.32 Webbed toes, left foot Although there are few specific guidelines for the reporting of congenital anomalies, understanding those guidelines is essential for proper coding of encounters. Chandra Stephenson, CPC, COC, CPB, CPCO, CPMA, CPC-I, CIC, CCS, CANPC, CEMC, CFPC, CGSC, CIMC, COSC, is a consultant who started out in healthcare 10 years ago. She has worked in a centralized billing office, a family practice office, a cardiology office, as a billing and coding instructor at a local technical college, and as a coding and compliance auditor. She enjoys conducting audits, researching coding and compliance issues, developing coding tools, and providing practitioner education. She is a member of the AAPC National Advisory Board and the Indianapolis, local chapter. Latest posts by Renee Dustman (see all) - CMS Reports OPPS Hospital Claim Issues - January 20, 2017 - Coding Glaucoma Preventive Screening - January 20, 2017 - Dear Trump Administration: A Vision for the Future of Healthcare - January 18, 2017	4	3	0	0	9	0.456951	9	1,038
The federal government provides a program of basic health care insurance for older and disabled individuals called Medicare. Practically everyone who has a work history and is sixty-five and older is eligible for Medicare, even those who continue working after age sixty-five. The federal and state governments together also provide a comprehensive medical benefits program, called Medicaid, for qualified low-income people. Medicare and Medicaid are not the same, though some older people qualify for both. Medicaid coverage rules vary from state to state, but Medicare is the same all over the United States. The questions that follow examine Medicare and Medicaid, as well as private “Medigap” insurance commonly used to supplement Medicare coverage. The section then turns to long-term care benefits under public programs and under private long-term care Since Medicare and Medicaid came into being in 1965, they have been revised many times. More revisions are certain. Current information is available from your local Social Security Administration office. Other groups such as the American Association of Retired Persons, local legal services programs, senior centers, and area agencies on aging also provide useful information. Q. What is the basic structure of the Medicare program? A. The Health Care Financing Administration, a branch of the U.S. Department of Health and Human Services, is the federal agency responsible for administering the Medicare program. Regular Medicare has two main parts. The hospital insurance part, or “Part A,” covers medically necessary care in a hospital, skilled nursing facility, or psychiatric hospital, home health care, and hospice care. “Part B,” or the medical insurance benefits part, covers medically necessary physician’s services, no matter where you receive them, outpatient hospital care, many diagnostic tests, and a variety of other medical services and supplies not covered by Part A.The exact coverage rules and limitations are complex. The actual coverage determinations and payments to providers of care are handled by insurance companies under contract with Medicare. These insurance companies are referred to as “fiscal intermediaries” under Part A and “carriers” under Part B. They determine the appropriate fee for each service. That is why regular Medicare is referred to as a “fee for service” Medicare beneficiaries also have the option of joining a Managed Care Organization (MCO) or care option permitted under “Medicare + Choice.” Managed care organizations provide or arrange for all Medicare covered services and generally charge a fixed monthly premium and small or no co-payments. They may also offer benefits not covered by Medicare, such as preventive care, for little or no additional cost. Denials of Benefits Never accept a denial of benefits without further questioning. Unfair denials of Medicare benefits occur with surprising frequency. Medicare beneficiaries who appeal unfair denials have a substantial likelihood of success on appeal. Your appeal rights are Q. What does Medicare cost me? A. Part A coverage is provided free to all individuals sixty-five and older who are eligible for social security (even if they are still working). If you are not eligible for social security benefits, you can enroll in Part A after age sixty-five, but you will have to pay a sizable monthly premium. Part B is available to all Part A enrollees for a monthly premium that changes yearly. The Social Security Administration office can tell you the cost of the current premium. Under both Parts A and B, beneficiaries must pay certain deductibles and coinsurance payments, depending on the type of service, unless you are enrolled in a managed care organization. “Deductibles” are payments you must make before Medicare coverage begins. “Co-insurance payments” are percentages of covered expenses that you are responsible for paying. These amounts can change from year to year. If you meet certain income and resource tests, your state’s Medicaid program will assist you in paying your share of Medicare costs. The income and resource tests are more generous than the limits for regular Medicaid eligibility, so even if you are not eligible for Medicaid, you may still be eligible for help as a “Qualified Medicare Beneficiary” (QMB) or a “Specified Low-Income Medicare Beneficiary” (SLMB). Q. I will turn sixty-five soon, but I do not plan to retire then. Am I still going to be able to receive Medicare benefits? A. Yes, but you must file a written application. This can be done in two different ways. Your “initial” enrollment period begins three calendar months before your sixtyfifth birthday month, and extends three months beyond your birthday month. You can enroll at any time during this seven-month period. Your benefits will begin on the first day of the month in which you turn sixty-five. If you do not enroll during this time, you can enroll during the “general” enrollment period, which runs from January 1 to March 31 of each year. However, you will pay a higher monthly premium if you delay enrollment beyond your initial enrollment If you are working and are covered by your employer’s health insurance program, or if you are covered under your spouse’s plan, Medicare is the secondary payer after the other insurance pays. If you haven’t enrolled in Medicare and you lose the other insurance, you may sign up for the Medicare program during a “special” seven-month enrollment period that begins the month the other program no longer covers you. To make sure you receive maximum coverage without penalty, talk to your employer’s benefits office or your local Social Security Administration office. Q. Is Medicare only for older adults? A. No. In addition to older social security recipients, younger persons who have received social security disability benefits for more than twenty-four months are eligible, as well as certain persons with kidney disease. Protecting Your Rights When You Contact Public Agencies Remember to note the name of the person with whom you speak, the date of your conversation, and the content of the conversation. This is useful if you later need to challenge the information provided. Signing Up for Medicare Enrolling in Medicare is no problem for most people. Everyone who is turning sixty-five and applying for social security or railroad retirement benefits is automatically enrolled in Medicare Part A. If you are receiving these benefits before turning sixty-five, you should receive a Medicare card prior to the month you turn sixty-five. The Medicare benefits normally begin on the first of the month in which you turn sixty-five. If you are under sixty-five and receiving disability benefits, your enrollment in Medicare will begin automatically as soon as you have been receiving benefits for twentyfour months.If you are planning to work beyond age sixty-five and are covered by your employer’s health insurance program, you must still file a written application through your local Social Security Administration office. Q. What does Medicare Part A (hospital insurance) cover? A. Medicare Part A helps pay for medically necessary hospital care, skilled nursing care, home health care, and hospice care as described below: 1. Hospitalization. This includes: · a semiprivate room and board, · general nursing, · the cost of special care units, such as intensive care or coronary care units, · drugs furnished by the hospital during your stay, · blood transfusions, · lab tests, X-rays and other radiology services, · medical supplies and equipment, · operating and recovery room costs, and · rehabilitation services. The coverage period for hospitalization is based upon a “benefit period.” A benefit period begins the first time you receive inpatient hospital care. It ends when you have been out of a hospital and have not received skilled nursing care for sixty days in a row. A subsequent hospitalization begins a new benefit period. On the first day of hospitalization during a benefit period, the patient is responsible for a sizable inpatient hospital deductible ($776 during 2000). If you are hospitalized more than once during a benefit period, the deductible does not have to be paid for the other hospitalizations during the same benefit period. After the deductible, Part A pays for all covered services through the sixtieth day of hospitalization. From the sixty-first through ninetieth day, coverage continues but the patient is responsible for a daily co-insurance payment. After the ninetieth day, Medicare covers up to sixty extra days (called “reserve days”) during the lifetime of the patient. The patient pays a sizable co-insurance payment during reserve days. If psychiatric hospitalization is needed, Part A helps pay for a lifetime maximum of 190 days of inpatient care in a participating psychiatric hospital. 2. Skilled Nursing Facility inpatient care following a hospitalization of at least three days. Your condition must require on a daily basis skilled nursing or skilled rehabilitation services, which, as a practical matter, can only be provided in a skilled nursing facility. You must be admitted within a short time (usually thirty days) after you leave the hospital, and the skilled care you receive must be based on a doctor’s Most nursing home residents do not require the level of nursing services considered skilled by Medicare. Consequently, Medicare pays for relatively little nursing home care. In addition, not every nursing home participates in Medicare or is a skilled nursing facility. Ask the hospital discharge staff or nursing home staff if you are unsure of the facility’s status.The coverage period for skilled nursing facility services is limited to 100 days. In a benefit period, Medicare pays for all covered services for the first twenty days. For days twenty-one through 100, the patient is responsible for a sizable coinsurance payment. Medicare helps pay only for “skilled” nursing home care. Medicare does not pay for “custodial” care. However, the distinction is often fuzzy, and many Medicare denials based on a finding of custodial care can be successfully appealed. Generally, care is considered custodial when it is primarily for the purpose of helping the resident with daily living needs, such as eating, bathing, walking, getting in and out of bed, and taking medicine. Skilled nursing and rehabilitation services are those that require the skills of technical or professional personnel such as registered nurses, licensed practical nurses, or therapists. Care that is generally non-skilled may nevertheless be considered skilled when, for example, medical complications require the skilled management and evaluation of a care plan, observation of a patient’s changing condition, or patient education services. 3. Home Health Care. Medicare covers part-time or intermittent skilled nursing care; physical, occupational, and speech therapy services; medical social services; part-time care provided by a home health aide; and medical equipment for use in the home. Both Part A and Part B of Medicare cover some home health care. Medicare does not cover medications for patients living at home, nor does it cover general household services or services that are primarily custodial. To be eligible for home health care services you must meet four conditions, presented in simplified terms here. First, you must be under the care of a physician who determines you need home health care and sets up a plan. Second, you must be home bound, although you need not be bedridden. Third, the care you need must include intermittent skilled nursing, physical therapy, or speech therapy. Finally, your care must be provided by a Medicare-participating home health care agency. The coverage period for home health care is unlimited with no deductible or coinsurance payment (except for durable medical equipment) as long as you continue to meet all four conditions. 4. Hospice Care A hospice is an agency or organization that provides primarily pain relief, symptom management and supportive services to people with terminal illness. Hospice services may include physician or visiting nurse services, individual and family psychological support, inpatient care when needed, care from a home health aide, medications, medical/social services, counseling, and respite care for family To be eligible for hospice care, a patient must have a doctor certify that he or she is terminally ill (defined as a life expectancy of six months or less); the patient must choose to receive hospice care instead of standard Medicare benefits; and the hospice must be a The coverage period for hospice care consists of two ninety-day periods, followed by a thirty-day period, and when necessary, an indefinite extension. There are certain coinsurance payments required under the hospice benefit, but no deductibles. Q. What does Medicare Part B (medical insurance) cover? A. Medicare Part B covers a wide range of outpatient and physician expenses regardless of where they are provided–at home, in a hospital or nursing home, or in a private office. Covered services include: · doctors’ services, including some services by chiropractors, dentists, podiatrists, and · outpatient hospital services, such as emergency room services or outpatient clinic care, radiology services, and ambulatory surgical services; · diagnostic tests, including X-rays and other laboratory services, as well as some mammography and pap smear screenings; · durable medical equipment, such as oxygen equipment, wheelchairs, and other medically necessary equipment that your doctor prescribes for use in your home; · kidney dialysis; · ambulance services to or from a hospital or skilled nursing facility; · certain services of other practitioners who are not physicians, such as clinical psychologists or social workers; · many other health services, supplies and prosthetic devices that are not covered by Medicare Part A (Part B also covers some home health services.) Medicare does not cover: · routine physical examinations; · most routine foot care and dental care; · examinations for prescribing or fitting eyeglasses or hearing aids; · prescription drugs that do not require administration by a physician; · most cosmetic surgery; · immunizations except for certain persons at risk; · personal comfort items and services; · any service not considered “reasonable and necessary.” Recently, Medicare Part B began covering certain preventive services under certain circumstances. These services include: · certain vaccinations such as those for flu, pneumonia, and hepatitis B; · prostate cancer screenings; · pap smear and pelvic examination; · diabetes monitoring; · colorectal cancer screening; and · bone mass measurements. A. For Part B benefits, you must pay a $100 annual deductible. Then Medicare generally pays 80 percent of Medicare-approved amounts for covered services for the rest of the year. You pay the other 20 percent of the approved amount. There is no cap on the patient’s share of the cost. If you are a Medicaid recipient or a qualified Medicare beneficiary (QMB), then your physician must accept “assignment.” If a physician or other provider charges you more than the Medicare-approved amount, then your liability depends on whether the provider accepts assignment. “Accepting assignment” means that the provider agrees to accept the Medicare-approved amount as payment in full. This means that your liability is limited to the annual deductible and 20 percent co-payment. If the provider does not accept assignment, generally you must pay for any excess charge over the Medicare-approved amount, but only up to certain limits. The government presently sets the limit on physician’s charges at 115 percent of the Medicare-approved fee schedule. Doctors who charge more than these limits may be fined, and you should get a refund from the doctor. Here is an example of the difference accepting assignment can make: Mrs. Jones sees Dr. Brown on June 1 for medical care. She has already paid her $100 annual deductible for covered Part B medical care this year. Dr. Brown charges $230 for the visit. The Medicare-approved amount for such services are $200. If Dr. Brown accepts assignment, Mrs. Jones must pay a · $40 co-payment (that is, 20 percent of the $200 approved). If Dr. Brown does not accept assignment, Mrs. Jones must pay: · $40 plus the $30 excess charge. Her Payment = $70. Note that Dr. Brown’s actual charge ($230) is within 115 percent of the Medicare approved amount ($200) and is therefore permissible Doctors and suppliers who agree to accept assignment under Medicare on all claims are called Medicare participating doctors and suppliers. You can get a directory of Medicare participating doctors and suppliers from your Medicare carrier. The directory is also available for your use in Social Security Administration offices, state and area agencies on aging, and in most hospitals. Q. How are Medicare claims filed and paid? A. For Part A benefits, the provider submits the claim directly to Medicare’s fiscal intermediary (the insurance company). The provider will charge you for any deductible or co-insurance payment you owe. For Part B claims, doctors, suppliers and other providers are required to submit your Medicare claims to the Medicare carrier (the insurance company) in most cases, even if they do not take assignment. The provider will charge you directly for any deductible, co-insurance, or excess charge you owe. If you belong to a Medicare participating Managed Care Organization (MCO), there are usually no claim forms to be filed, nor any deductible or co-payment for any covered services, or the amount is small. Signing Up for Medicare Part B If you are receiving Part A coverage, you will automatically be enrolled for Part B coverage as well. If you don’t want Part B coverage, you must notify the Social Security Administration. Also, anyone sixty-five and older can buy Part B coverage. Enrollment periods are similar to those for Part A. Your Part B premium will be deducted from your monthly social security check. Q. What if I disagree with a Medicare decision? How can I appeal? A. You have the right to appeal all decisions regarding coverage of services or the amount Medicare will pay on a claim. If your claim has been denied in whole or in part, it is usually a good idea to appeal, especially if the basis of denial is unclear. A surprisingly high percentage of denials are reversed on appeal. In any case, the appeal will make clear the reason for the denial. Medicare Parts A and B have different procedures for appealing and several steps in the appeal process. After the initial levels of review, Parts A and B both include the option of a hearing before an administrative law judge and even review by a federal court if sufficient amounts of money are at stake. Key tips in appealing Medicare decisions: · Denials by any Part A provider (hospital, nursing home, home health care agency, or hospice): Do not accept oral denials. You should be given a written notice of non coverage from the provider explaining why the provider believes Medicare will not pay for the services. This is not an official Medicare determination. You should ask the provider to get an official Medicare determination. The provider must file a claim on your behalf to the Medicare fiscal intermediary if you ask for an official determination. If you still disagree, you may make use of several additional appeal steps if minimum threshold amounts of money are in dispute. · Hospital coverage denials: Hospital coverage decisions are normally made by Peer Review Organizations (PROs). PROs are groups of doctors and other health care professionals under contract with the federal government to review care given to Medicare patients. When you are admitted to the hospital, you will receive a notice called An Important Message From Medicare that explains the role of PROs and describes your appeal rights. If you disagree with a PRO decision, the initial review will occur very quickly, usually within three days. You cannot be required to pay for hospital care until third day after you receive a written denial of Medicare coverage. · Part B coverage denials: These decisions will be made by the Medicare carrier. After your doctor, supplier, or other provider sends in a Part B claim, Medicare will send you a notice called Evaluation of Your Medicare Part B Benefits. The notice tells you what charges were made and the amount Medicare approved and paid. It also shows the amount of any copayments, deductibles, or excess charges that you are responsible for paying. The notice gives the address and telephone number for contacting the carrier and an explanation of your appeal rights. You have six months from the date of the decision to ask the carrier to review it. If you still disagree, you may make use of several additional appeal steps if minimum threshold amounts of money are in dispute. Always be conscious of time limits for filing appeals (normally sixty days from the date of the notice). You may lose your rights if you wait too long. You may want to get assistance with your appeal from a legal services office or a private attorney, particularly if large medical bills are involved. Nonlawyer volunteers and non lawyer staff members of legal service programs help a number of people with benefit appeals without charging Q. Do I need any other insurance coverage besides Medicare? A. Yes. Most older persons need to purchase a supplemental (or “Medigap”) insurance policy to cover some of the costs not covered by Medicare. However, there are exceptions, In addition, if you can afford it, you may also want to consider purchasing a longterm care insurance policies, because Medicare and Medigap policies do not cover longterm care. Long-term-care insurance is discussed in the next section. Q. Who doesn’t need a Medigap policy? A. While most people need Medigap coverage, you may already have enough coverage without it if you belong to one of the four groups below: 1. If you are already covered by Medicaid, you do not need a Medigap policy. Medicaid covers the gaps in Medicare and more. 2. If you are not eligible for Medicaid, but your income is low, you may be eligible for help in paying Medicare costs under the Qualified Medicare Beneficiary (QMB) program. Under QMB the government will pay your Medicare Part B premiums and provide supplemental coverage equivalent to a Medigap policy if your income and assets fall below a qualification amount (one that is more generous than Medicaid’s). To apply contact the local office of your state Medicaid program. 3. If you get retiree health coverage through a former employer or union, you may not need Medigap insurance. But this coverage may not provide the same benefits as Medigap insurance and may not have to meet the federal and state rules that apply to Medigap. Examine the coverage, costs, and stability of your coverage to determine whether it is a better option than Medigap. 4. If you belong to an HMO, you probably do not need a Medigap policy, since HMO coverage is normally comprehensive. But do not be too quick to give up your Medigap coverage if you are just joining a Medicare HMO. If you can afford it, keep it long enough to be sure you are satisfied with the HMO. If you become dissatisfied with the HMO, you have the right to disenroll from it at any time. But if you have already given up you Medigap coverage, you may not be able to get it again or get the same price. Q. How do I find a good Medigap policy? A. Since 1992, all Medigap insurance has had to conform to standardized benefit plans. There are ten possible standardized plans, identified as Plan A through Plan J. Plan A is a core package and is available in all states. The other nine plans have different combinations of benefits. Check with your state department of insurance for additional information. Many states provide buyers guides. Purchase only one Medigap policy. Multiple policies will almost always provide overlapping coverage for which you will pay twice but receive the benefit of only once. In evaluating policies, decide which features would best meet your health needs and financial situation. Prescription drug coverage, for example, may be right for you if you are on continuing maintenance medications, even though such coverage may be expensive. When you compare policies of the same type (A through J), remember that benefits are identical for plans of the same type. For example, all type G plans have essentially the same benefits. However, the premiums and potential for premium increases may differ greatly. Q. When should I get a Medigap policy? A. Buy a Medigap policy at or near the time your Medicare coverage begins, because during the first six months that you are sixty-five or older and enrolled in Medicare Part B, companies must accept you regardless of any health conditions you have, and they cannot charge you more than they charge others of the same age. After this one-time period, you may be forced to pay much higher premiums for the same policy due to your health status. During this open enrollment period, companies may still exclude pre-existing conditions during the first six months of the policy. Different enrollment rules apply to persons under sixty-five who are eligible for Medicare because of disability. Q. What if I have an “old” Medigap policy and am considering a replacement? Is that a good idea? A. If you have a Medigap policy that pre-dates the standardized plans (before 1992), you may not need to switch policies, especially if you are satisfied. Some states have special regulations allowing beneficiaries to convert older policies to a standard Medigap plan. Check with your state insurance department or health insurance counseling service for Beware of illegal sales practices. Both federal and state laws govern the sale of Medigap insurance. These laws prohibit high pressure sales tactics, fraudulent or misleading statements about coverage or cost, selling a policy that is not one of the approved standard policies, or imposing new waiting periods for replacement policies. If a sales agent offers you a policy that duplicates coverage of your existing policy, the duplication must be disclosed to you in writing. If you feel you have been mislead or high pressured, contact your state insurance department, your state’s health insurance counseling program, or the federal Medicare Hotline at 1-800-MEDICARE (1-800-633- EVALUATING AMEDIGAP POLICY Obtain a free copy of the booklet Guide to Health Insurance for People with Medicare from your local Social Service Security Administration or from the Consumer Information Center, Department 70, Pueblo, CO 81009 (719) 948-3334 or at the website at www.pueblo.gsa.gov. This guide: · explains how Medigap insurance works; · explains the ten standardized plans; · tells how to shop for Medigap insurance; · lists addresses and phone numbers of state insurance departments of state insurance departments and state agencies on aging. Most states offer free insurance counseling Q. What is Medicaid? A. Medicaid is a medical assistance program for poor older or disabled persons whose income and assets fall below certain levels set by federal and state law. Unlike Medicare, which offers the same benefits to all enrollees regardless of income, Medicaid is managed by individual states, and the benefits and eligibility vary from state to state. Q. Is it possible to receive both Medicare and Medicaid? A. Yes, if you qualify for both programs. Even if you do not qualify for Medicaid, the Medicaid program may still assist you in paying for all or part of the Medicare premium, deductibles and co-insurance payments if you meet the special income and resource tests under the “Qualified Medicare Beneficiary” (QMB) program or the “Specified Low-Income Medicare Beneficiary” (SLMB) program. Q. If I qualify for Medicaid, what sorts of services do I get? A. Medicaid covers a broad spectrum of services. Certain benefits are mandated by federal law. They include: · inpatient and outpatient hospital services doctors’ · nurse practitioners’ services inpatient nursing home care · home health care services · laboratory X-ray charges. Other services may include private duty nursing; services from podiatrists, optometrists and chiropractors; mental health services; personal care in your home; dental care; physical therapy and other rehabilitation; prescription medications; dentures; eyeglasses; and more. In all cases, you may receive these service only from a Medicaidparticipating provider. As with Medicare, providers may choose whether or not to participate in Medicaid, and they must meet certain standards. Some states have contracted with managed care organizations to provide comprehensive care to Medicaid-eligible individuals. Qualifying for Medicaid Medicaid programs in each state have different standards to determine whether needy individuals are eligible for assistance. All states require that older adults be at least age sixty-five, blind or disabled, and that they meet income and asset tests. In most states, persons eligible for Supplemental Security Income (SSI) or Temporary Assistance to Needy Families (TANF) are automatically covered. Most states also cover some people whose income falls below a certain level after they “spend down” their income on medical bills. Medicaid eligibility rules are so complicated that it is advisable for older persons with low incomes or with high medical expenses to talk with someone with expertise in Medicaid–such as a legal services lawyer, paralegal, or social worker, or a private attorney experienced in handling Medicaid issues. Q. Does owning a home disqualify me from Medicaid? A. No. All states exempt your home as an asset as long as you or your spouse lives in it. If you must leave your home in order to receive nursing home care or other long-term care, the state may still exempt it, but state asset exemption rules differ from state to state and can be complex. Besides your home, all states allow you to keep a very limited amount of cash and personal property. Q. What does Medicaid cost me? A. Medicaid does not require you to pay premiums or deductibles like Medicare. Providers may not charge Medicaid patients additional fees beyond the Medicaid reimbursement amount. However, states are permitted to impose a nominal deductible charge or other form of cost-sharing for certain categories of services and prescription drugs. No Medicaid recipient may be denied services by a participating provider because of the patient’s inability to pay the charge. Individuals whose income or assets exceed the state’s permissible Medicaid amount may be eligible for Medicaid only after “spending down” their income or assets to a poverty level by incurring medical expenses. These “spend down” amounts can be very high, especially for nursing home residents whose income far exceeds the Medicaid eligibility level but who face enormous monthly expenses for care. Q. How do I apply for Medicaid? A. Contact the state or local agency that handles the Medicaid program. Its name will vary from place to place. It may be called Social Services, Public Aid, Public Welfare, Human Services, or something similar. You can also call your local agency on aging or senior center for information. When you apply, you will have to document your financial need in detail, as well as your residency. The application form can be lengthy and complex, but the Medicaid agency can help you complete it. If you are homebound, a Medicaid worker can be sent to your home to help you apply. If you are in a hospital or other institution, a staff social worker should be made available to help you apply. Don’t let inability to get to the public agency keep you from seeking assistance. Since the start of benefits is linked to your date of application, it is important to establish an application date as soon as you need Medicaid assistance. Almost any written request with your signature may be enough to establish your application date, even if you have not yet completed the full application form. The effective date can be retroactive, up to three months. Q. How are Medicaid claims filed and paid? A. Medicaid providers always bill Medicaid directly. The state Medicaid program reimburses providers according to the state’s particular reimbursement formula. Providers cannot charge you additional amounts for covered services, but states may opt to charge you small deductibles or fees for certain items such as prescriptions. Q. If I disagree with a decision made by my Medicaid program, what can I A. You have the right to appeal all decisions that affect your Medicaid eligibility or services. When a decision about your Medicaid coverage is made, you should receive prompt written notice of the decision. This will include an explanation of how you can appeal the decision. The appeal process includes a right to a fair hearing before a hearing officer. You may need a lawyer or public benefits specialist experienced in Medicaid law. Q. What federal programs will pay for long-term care in a nursing home? A. Medicare does not pay for a significant amount of nursing home care. Coverage of skilled nursing care, as described above under “Medicare,” is narrowly defined and limited to twenty days of full coverage and a maximum of eighty additional days with a large co-insurance payment. Medicaid, on the other hand, pays a substantial portion of the nation’s nursing home bill (over 40 percent). Medicaid, however, pays only when most other funds have been depleted. Medicaid will cover nursing home expenses if your condition requires nursing home care, the home is certified by the state Medicaid agency, and you meet income and other eligibility requirements to receive this benefit. Many persons who normally are not eligible for Medicaid become eligible after a period of time in a nursing home. This happens because the high cost of nursing home care forces many individuals to spend down their assets and income to a level that qualifies them for Medicaid in many states. The rules and availability of this option vary from state to state. The Department of Veterans Affairs (VA) pays for some nursing home care for veterans in VA facilities and private facilities, but the benefit is limited to the extent that resources and facilities are available. Priority is given to veterans with medical problems related to their military service, and to very old veterans of wartime service, and very poor veterans. Contact your local VA office for more information. Q. What if I don’t want to live in a nursing home? Are home care services available under Medicare or Medicaid? A. Yes, but to a limited extent. The home health care benefit under Medicare focuses mainly on skilled nursing and therapeutic services needed on a part-time or intermittent basis. The benefit is described above under “Medicare.” Medicaid home health care is usually quite limited, too. But in addition to home health, several state Medicaid programs also provide “personal care” services to Medicaideligible individuals who need help with normal activities of daily living, such as dressing, bathing, toileting, eating, and walking. Many states also have instituted Medicaid “waiver” programs that allow the state to use Medicaid dollars for home and community based services that would not normally be covered under Medicaid. These waiver programs usually target persons who would otherwise have to live in a nursing home. Some of the services covered under Medicaid waiver programs include personal care, adult day care, housekeeping services, care coordination and management, and respite care. Respite care enables primary care-givers to take a break from their responsibilities. Check with your local office on aging or department of human services about the options available in your Q. What happens if my husband needs nursing home care but I am still able to live independently? Will all our income and assets have to be used for his support before Medicaid will help pay expenses? A. If your spouse resides in or may be entering a nursing home, Medicaid has special rules that allow the spouse remaining in the community (community spouse) to keep more income and assets than permitted under the regular eligibility rules. The specifics vary from state to state, but the general structure is as follows: The community spouse can keep all income, no matter how much, that belongs exclusively to the community spouse. Joint income is another story. The state may require all or part of joint income to help pay nursing home expenses, depending upon the particular state’s rules. Most of the income of the nursing home spouse is considered available to pay for nursing home care. However, a portion of the nursing home spouse’s income may be kept by the community spouse as a “minimum monthly maintenance needs allowance” if the community spouse’s income is below a spousal allowance figure set by the state. States must establish a spousal allowance of at least 150 percent of the poverty level for a twoperson household. Thus, for 2000, this calculation results in a minimum spousal allowance of $1406 per month that could be kept by the community spouse (Alaska and Hawaii have higher figures). States also permit the community spouse to keep a shelter allowance, if shelter costs (rent, mortgage, taxes, insurance and utilities) exceed a specified amount. Assets or resources are treated quite differently. The state applies a two-step rule. First, Medicaid counts all resources owned by either spouse. This inventory will exclude a few resources. The excluded resources are: your home, household goods, personal effects, an automobile, and a burial fund of up to $1,500. Second, from the total countable resources, Medicaid permits the community spouse to keep one-half, as long as the one-half falls between a specified floor and ceiling amount, adjusted yearly. If the one-half falls below the floor (about $16,824 in 2000), the community spouse may keep more of the couple’s resources up to the floor amount. If the one-half exceeds the ceiling (about $84,120 in 2000), the excess will be considered available to pay for the cost of nursing home care. Thus, the community spouse is permitted to keep no more than the ceiling amount even if it equals far less than half of the Another special rule applies to your home. Even though your home is an excluded resource, the state, in limited circumstances, can place a lien against your home equal to the amount of nursing home expenses paid. The rules are complicated and vary by state; the advice of a lawyer experienced in Medicaid law is advisable. Moreover, almost all these rules have hardship exceptions in special circumstances. Q. If I have assets that exceed my state’s Medicaid eligibility requirements, can I transfer these to my children or to a trust in order to qualify? After all, these are assets I intend to leave to my children when I die. A. The law on transferring assets before making a Medicaid application is complex. Such transfers can result in a period of ineligibility for Medicaid benefits. Several strategies are available to shelter or preserve some of your assets, but there are a number of legal, financial, ethical, and practical consequences to any such transfer of property. Anyone considering such transfer should seek advice from a lawyer experienced in Medicaid law. Q. Must children pay for parents in nursing homes? A. There is no legal obligation for children to pay for their parents’ care. Only a spouse may be held legally responsible to help pay for the cost of nursing home care, and as a practical matter, the responsibility is often difficult to enforce against an unwilling spouse. If Medicaid enters the picture, the special rules for spousal responsibility described above will apply. Children sometimes feel pressured to help pay for a parent’s nursing home cost because of the shortage of nursing home beds, especially Medicaid covered beds. Some nursing homes give preference to admitting “private pay” patients over Medicaid patients because private-pay rates are often higher than the amount Medicaid pays. While admission priority for private pay patients is permissible in some states, it is illegal in others. In all states, federal law prohibits nursing homes from requiring a private payment from families, or a period of private payment, prior to applying for Medicaid coverage. Federal law also prohibits nursing homes from requiring patients to waive their rights to Medicare and/or Medicaid. Q. What is long-term care insurance? A. Long-term care insurance helps pay for nursing home care and usually home care services for a period of two or more years. Long-term care insurance is still a relatively new type of private insurance, so the features of this type of insurance continue to change frequently. For example, newer policies may cover assisted living facilities, adult day care, respite care, or other long – term care services. Most individual policies are available for purchase only to persons between ages fifty and eighty-four, and a medical screening of applicants is typically required. Not every older person needs or can afford a long-term care insurance policy. Policies are appropriate for those with substantial income and assets to protect, and who desire to buy this form of protection against the potential costs of long-term care. Most long-term care policies are structured as indemnity policies. That is, they pay up to a pre-set cap for each day of a covered service. The specific provisions of these policies should be closely examined before purchasing one, since the possible conditions and limitations on coverage can be complex. How much health insurance do I need? Some people covered by Medicare think they need several additional policies to cover Medicare gaps, specific diseases, and long-term care. That is probably not a good strategy. Chances are the policies would duplicate too many benefits to justify the cost. That is why insurance companies are no longer permitted to sell duplicate Medicare supplement policies. The consumer may purchase only one of the A-J policies. The best recommendation for someone on Medicare, who is not also on Medicaid, is to purchase one good “Medigap” policy, and possibly one long-term care insurance policy if you can comfortably afford the cost of a good long-term care policy. Lower income persons are likely to qualify for Medicaid if they need long-term care, so purchasing private long-term care insurance may be a waste of money. Q. How are the costs of a long-term care policy determined? A. The cost of the premium is determined in part by your age, the extent of coverage you purchase, and your health history. Age is clearly the single greatest factor because the risk of needing long-term care increases significantly with age. The premium for a seventy-five year old can be double or triple that for a sixty-five year old. Q. How do I evaluate a long-term care policy? A. Compare more than one policy side by side. Your state’s insurance department should have names of companies offering long-term care insurance. Many states are beginning to set minimum standards and consumer protection guidelines for these policies. In addition, federal law provides favorable tax treatment of federally qualifies long-term are policies — that is, policies that meet minimum federal standards. Guides for evaluating long-term care insurance may be available from your state insurance department or state office on aging. Keep in mind the following tips in evaluating policies: · Make sure your policy will pay benefits for all levels of care in a nursing home, including custodial care. · A good policy will pay benefits for assisted living and home care, including in-home personal care. Personal care refers generally to help with activities of daily living, such as dressing, bathing, toileting, eating, and walking. · Consider whether the amount of daily benefits will be adequate now and in the future. Many policies give you a range of daily benefit amounts to choose from. Make sure the policy has an “inflation adjustor” under which benefits increase by a certain percentage each year to keep pace with coverage. The “right” amount depends in part on the amount of assets you have to protect inflation. · Do not assume that more years of coverage is always better. Some policies offer benefit options of six, seven, or more years. It is possible to buy too much coverage. · Avoid policies that exclude coverage of pre-existing conditions for a lengthy period. Six months is considered a reasonable exclusion period for pre-existing conditions. · Policies should allow payment of nursing home or home health benefits without requiring a prior period of hospitalization as a condition of coverage. · Most policies impose waiting periods that restrict the starting time of benefits after you begin receiving nursing home care or home care–twenty to ninety days is a common waiting period. A longer waiting period will lower the premium cost. First day coverage will increase your premium. · Be sure your policy covers victims of Alzheimer’s disease and other forms of dementia. About half the residents of nursing homes suffer some form of dementia. · Be sure that the premium remains constant over the life of the policy and that the policy is guaranteed renewable for life. · Buy a policy only from a company that is licensed in your state and has agents physically present in your state. Out-of-state mail order policies often leave you powerless to remedy problems if anything goes wrong.	2	9	1	0	0	0.557308	1	9,908
What does a bulging fontanelle mean? A tense or bulging fontanelle occurs when fluid builds up in the brain or the brain swells, causing increased pressure inside the skull. When the infant is crying, lying down, or vomiting, the fontanelles may look like they are bulging. What causes large anterior fontanelle? The most common causes of a large anterior fontanel or delayed fontanel closure are achondroplasia, hypothyroidism, Down syndrome, increased intracranial pressure, and rickets. What is the ICD 10 code for bulging fontanelle? Bulging anterior fontanelle should be coded to R68. 1 Nonspecific symptoms peculiar to infancy when it meets the criteria in ACS 0001 Principal diagnosis or ACS 0002 Additional diagnoses. What are the 4 fontanelles? The fontanelles include: - Anterior fontanelle (also called soft spot). This is the junction where the 2 frontal and 2 parietal bones meet. The anterior fontanelle remains soft until about 18 months to 2 years of age. - Posterior fontanelle. This is the junction of the 2 parietal bones and the occipital bone. Can a large anterior fontanelle be normal? It is normal for infants to have these soft spots, which can be seen and felt on the top and back of the head. Fontanelles that are abnormally large may indicate a medical condition. A wide fontanelle occurs when the fontanelle is larger in size than expected for the age of the baby. What happens if the anterior fontanelle closes early? A condition in which the sutures close too early, called craniosynostosis, has been associated with early fontanelle closure. Craniosynostosis results in an abnormal head shape and problems with normal brain and skull growth. Premature closure of the sutures may also cause the pressure inside of the head to increase. At what age do fontanelles close? The posterior fontanelle usually closes by age 1 or 2 months. It may already be closed at birth. The anterior fontanelle usually closes sometime between 9 months and 18 months. The sutures and fontanelles are needed for the infant’s brain growth and development. What is the ICD 10 code for bulging fontanelles? ICD-10 code bulging fontanelels 2017 ICD-10-CM Diagnosis Code Q03.1 Atresia of foramina of Magendie and Luschka When to consider an abnormal fontanel in an infant? An abnormal fontanel in an infant can indicate a serious medical condition. Therefore, it is important to understand the wide variation of normal, how to examine the fontanels, and which diagnoses to consider when an abnormality is found. What is the average size of the anterior fontanel? The anterior fontanel is the largest and most important for clinical evaluation. The average size of the anterior fontanel is 2.1 cm, and the median time of closure is 13.8 months. The most common causes of a large anterior fontanel or delayed fontanel closure are achondroplasia, hypothyroidism, Down syndrome, increased intracranial pressure, What are the clinical features of bulging fontanelles? Clinical features include occipital bossing, progressive head enlargement, bulging of anterior fontanelle, papilledema, ataxia, gait disturbances, nystagmus, and intellectual compromise. (from menkes, textbook of child neurology, 5th ed, pp294-5)	4	7	0	0	4	0.364628	4	788
1 This publication contains summary information on causes of death for all doctor certified deaths for Australia in 2012. 2 In order to complete a death registration, the death must be certified by either a doctor using the Medical Certificate of Cause of Death, or by a coroner. Approximately 85-90% of deaths each year are certified by a doctor. The remainder are reported to a coroner. 3 In the full Causes of Death dataset the pattern of cause distribution is impacted by the certifier type. Table 1 below presents 2011 data disaggregated by certifier type to demonstrate the chapter by chapter coverage achieved by the doctor certified dataset compared with the full Causes of Death dataset. Table 1. Selected underlying causes of death - 2011(a)(b) Proportion by cause \|Cause of death and ICD-10 code \| \|Infectious and parasitic diseases (A00-B99) \| \|Neoplasms (C00-D48) \| \|Blood and immunity disorders (D50-D89) \| \|Endocrine, nutritional and metabolic diseases (E00-E90) \| \|Mental and behavioural disorders (F00-F99) \| \|Diseases of the nervous system (G00-G99) \| \|Diseases of the eye and adnexa (H00-H59) \| \|Diseases of the ear and mastoid process (H60-H95) \| \|Diseases of the circulatory system (I00-I99) \| \|Diseases of the respiratory system (J00-J99) \| \|Diseases of the digestive system (K00-K93) \| \|Diseases of the skin and subcutaneous tissue (L00-L99) \| \|Diseases of the musculoskeletal system and connective tissue (M00-M99) \| \|Diseases of the genitourinary system (N00-N99) \| \|Pregnancy and childbirth (O00-O99) \| \|Conditions originating in the perinatal period (P00-P96) \| \|Congenital and chromosomal abnormalities (Q00-Q99) \| \|Ill-defined causes (R00-R99) \| \|External causes (V01-Y98) \| \|Total doctor certified deaths \| \|Total coroner certified deaths \| \|Total deaths \| \|. . not applicable \| \|- nil or rounded to zero (including null cells) \| np not available for publication but included in totals where applicable, unless otherwise indicated \|(a) Data cells with small numbers have been randomly assigned to protect the confidentiality of individuals. As a result, some totals will not equal the sum of their components. Cells with a zero value have not been affected by confidentialisation. \| \|(b) Causes of death data for 2011 are preliminary and subject to a revisions process. See 3303.0 Causes of Death, Australia, 2011, Technical Note: Causes of Death Revisions 2009 and 2010. \| 4 Reportable deaths that were certified by a coroner will be included in the full Causes of Death, Australia (cat. no. 3303.0) publication to be released in 2014. This publication will present causes of death for all deaths in 2012, whether certified by a doctor or coroner. 5 The registration of deaths is the responsibility of the eight individual state and territory Registrars of Births, Deaths and Marriages. As part of the registration process, information about the cause of death is supplied by the medical practitioner certifying the death or by a coroner. Other information about the deceased is supplied by a relative or other person acquainted with the deceased, or by an official of the institution where the death occurred. The information is provided to the Australian Bureau of Statistics (ABS) by individual Registrars for coding and compilation into aggregate statistics. In addition, the ABS supplements this data with information from the National Coroners Information System (NCIS). The following diagram shows the process undertaken in producing cause of death statistics for Australia. 6 The doctor certified deaths data presented in this publication will also be included in the Causes of Death, Australia (cat. no. 3303.0) publication, to be released 2014. The Causes of Death publication also includes deaths which have been certified by a coroner, and therefore presents the full causes of death dataset. 7 A Glossary is also available which details definitions of terminology used throughout this publication. SCOPE AND COVERAGE 8 The statistics in this publication relate to the number of doctor certified deaths that were registered, not those that actually occurred, in the years shown. Scope of Causes of Death statistics 9 The scope for each reference year of death registrations includes: - deaths registered in the reference year and received by the ABS in the reference year - deaths registered in the reference year and received by ABS in the first quarter of the subsequent year - deaths registered in the years prior to the reference year but not received by ABS until the reference year or the first quarter of the subsequent year, provided that these records have not been included in any statistics from earlier periods. Death records received by ABS during the March quarter 2013 which were initially registered in 2012 (but for which registration was not fully completed until 2013) were assigned to the 2012 reference year. Any registrations relating to 2012 which were received by ABS from April 2013 were assigned to the 2013 reference year. Approximately 4% to 6% of deaths occurring in one year are not registered until the following year or later. Prior to 2007, the scope for the reference year of the Death Registrations collection included: - deaths registered in the reference year and received by ABS in the reference year - deaths registered in the reference year and received by ABS in the first quarter of the subsequent year - deaths registered during the two years prior to the reference year but not received by ABS until the reference year. Coverage of causes of death statistics Ideally, for compiling annual time series, the number of events (deaths) should be recorded and reported as those occurring within a given reference period such as a calendar year. However, due to lags in registration of events, not all deaths are registered in the year that they occur. Therefore, the occurrence event is approximated by the ABS through the addition of the event on a state/territory register of deaths. Also, some additions to the register can be delayed in being received by the ABS from a Registrar (processing or data transfer lags). In effect there are 3 dates attributable to each death registration: - the date on which the death occurred (date of occurrence) - the date on which the death is registered with the state and territory registry (date of registration); and - the month and year in which the registered event is lodged with the ABS (reference year). From 2007 onwards, 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, a death may occur in December 2011, but the death may not be registered until January 2012. Information about the death is then provided to the ABS in April of 2012. This death would have a date of occurrence of December 2011, a date of registration in January 2012, and a reference year of 2012. The ABS Causes of Death - Doctor Certified collection includes all doctor certified deaths that occurred and were registered in Australia, including deaths of persons whose usual residence is overseas. Deaths of Australian residents that occurred outside Australia may be registered by individual Registrars, but are not included in ABS deaths or causes of death statistics. The current scope of the statistics includes: - all deaths being registered for the first time - deaths in Australia of temporary visitors to Australia - deaths occurring within Australian Territorial waters - deaths occurring in Australian Antarctic Territories or other external territories (excluding Norfolk Island) - deaths occurring in transit (i.e. on ships or planes) if registered in the State of 'next port of call' - deaths of Australian Nationals overseas who were employed at Australian legations and consular offices (i.e. deaths of Australian diplomats while overseas), where able to be identified - deaths that occurred in earlier reference periods that have not been previously registered (late registrations). The scope of the statistics excludes: - still births / fetal deaths (detailed information on these deaths will be released in 2014) - repatriation of human remains where the death occurred overseas - deaths overseas of foreign diplomatic staff (where these are able to be identified) - deaths occurring on Norfolk Island. A range of socio-demographic data are available in the ABS Causes of Death - Doctor Certified collection. Standard classifications used in the presentation of causes of death statistics include age, sex, birthplace, multiple birth and Indigenous status. Statistical standards for social and demographic variables have been developed by the ABS. Where these are not published in the Causes of Death publication or data cubes, they can be sourced on request from the ABS. Australian Statistical Geography Standard (ASGS) The ABS has developed a new standard classification for geography, the Australian Statistical Geography Standard (ASGS). The ASGS provides a common framework of statistical geography and thereby enables the production of statistics which are comparable and can be spatially integrated. ABS causes of death statistics are coded to mesh blocks and can be produced for aggregates of these, for example, Statistical Areas, Sections of State and State. The ASGS has been applied to causes of death data since the 2011 reference period. For further information about the ASGS refer to the Australian Statistical Geography Standard (ASGS) (cat. no. 1270.0.55.001). Prior to 2011, causes of death data were coded to the Australian Standard Geographical Classification (ASGC). For further information about the ASGC refer to the Australian Standard Geographical Classification (ASGC) (cat. no. 1216.0). International Classification of Diseases (ICD) The International Classification of Diseases (ICD) is the international standard classification for epidemiological purposes and is designed to promote international comparability in the collection, processing, classification, and presentation of causes of death statistics. The classification is used to classify diseases and causes of disease or injury as recorded on many types of medical records as well as death records. The ICD has been revised periodically to incorporate changes in the medical field. Currently the ICD 10th revision is used for Australian causes of death statistics. ICD-10 is a variable-axis classification meaning that the classification does not group diseases only based on anatomical sites, but also on the type of disease. Epidemiological data and statistical data are grouped according to: - epidemic diseases - constitutional or general diseases - local diseases arranged by site - developmental diseases For example, a systemic disease such as septicaemia is grouped with infectious diseases; a disease primarily affecting one body system, such as a myocardial infarction is grouped with circulatory diseases; and a congenital condition such as spina bifida is grouped with congenital conditions. For further information about the ICD refer to the WHO International Classification of Diseases (ICD) The ICD 10th Revision is also available online 2012 MORTALITY CODING The extensive nature of the ICD enables classification of causes of death at various levels of detail. In this publication, data is presented at the ICD-10 chapter level, as well as 3 character codes. To enable the reader to see the relationship between the various summary classifications used in this publication, all tables show in brackets the ICD-10 codes which constitute the causes of death covered. Updates to ICD-10 The Updating and Revision Committee (URC), a WHO advisory group on updates to ICD-10, maintains the cumulative and annual lists of approved updates to the ICD-10 classification. The updates to ICD-10 are of numerous types including addition and deletion of codes, changes to coding instructions and modification and clarification of terms. The cumulative list of ICD-10 updates can be found online The ABS uses the Medical Mortality Data System (MMDS), software for automated cause of death coding. The MMDS applies ICD rules to all death records, diseases and conditions listed on the death certificate. Approximately 70-80% of records are coded using the MMDS without manual intervention. State and Territory Data Causes of death statistics for states and territories in this publication have been compiled in respect of the state or territory of usual residence of the deceased, regardless of where in Australia the death occurred and was registered. Deaths of persons usually resident overseas which occur in Australia are included in the state/territory in which their death was registered. Statistics compiled on a state or territory of registration basis are available on request. Aboriginal and Torres Strait Islander deaths The ABS Death Registrations collection identifies a death as being Indigenous where the deceased is identified as being of Aboriginal and/or Torres Strait Islander origin through the death registration process. Detailed explanatory notes regarding the data quality of this variable can be found in Explanatory Notes 29-36 of the Deaths, Australia, 2011 (cat. no. 3302.0) DEATHS BY TYPE OF CERTIFIER For deaths registered in 2012, 88.3% were certified by a doctor. The remainder were reported to, and certified by, a coroner. SPECIFIC ISSUES FOR 2012 DATA As outlined below, the following issues should be taken into account by users when analysing the 2012 doctor certified causes of death data. 34 Dementia (F01,F03) Since 2006, there has been a substantial increase in the number of deaths coded to Dementia (F01,F03). Updates to the coding instructions in ICD-10 has resulted in the assignment of some deaths shifting from Cerebrovascular diseases (I60-I69) to Vascular dementia (F01). In addition, changes to the Veterans’ Entitlements Act 1986 and Military Rehabilitation and Compensation Act 2004, and a subsequent promotional campaign targeted at health professionals, now allow for death from vascular dementia of veterans or members of the defence forces to be related to relevant service. This is believed to have had an effect on the number of deaths attributed to dementia. STANDARDISED DEATH RATES (SDR) 35 Standardised death rates (SDRs) enable the comparison of death rates between populations with different age structures by relating them to a standard population. The current standard population is all persons in the Australian population at 30 June 2001. SDRs are expressed per 1,000 or 100,000 persons. For 2010 deaths data onwards, the ABS has implemented a new set of principles for the use of direct age standardisation in production of mortality rates. See the Deaths, Australia, 2010 (cat. no 3302.0) Explanatory Notes 39-42 and Appendix 1: Principles on the use of direct age-standardisation for further information. CONFIDENTIALISATION OF DATA 36 Data cells with small values have been randomly assigned to protect confidentiality. As a result some totals will not equal the sum of their components. Cells with 0 values have not been affected by confidentialisation. EFFECTS OF ROUNDING 37 Where figures have been rounded, discrepancies may occur between totals and sums of the component items. 38 ABS products and publications are available free of charge from the ABS website. Click on Statistics to gain access to the full range of ABS statistical and reference information. For details on products scheduled for release in the coming week, click on the Future Releases link on the ABS homepage. 39 The ABS' publications draw extensively on information provided freely by individuals, businesses, governments and other organisations. The efforts of Registries of Births, Deaths and Marriages to improve the data quality, coverage and timeliness of death registration information, processes and systems are noted and valued by the ABS. Their continued cooperation is very much appreciated; without it, the wide range of statistics published by the ABS would not be available. Information received by the ABS is treated in strict confidence as required by the Census and Statistics Act 1905.	4	23	0	0	6	0.513084	6	3,375
What is an ICD Code? The system known as an ICD-Code began in the 1850s as the International List of Causes of Death. When the World Health Organization was created in 1948, it adopted responsibility for the code, publishing its sixth edition while adding causes of morbidity to the list. The International Statistical Classification of Diseases and Related Health Problems, normally shortened to simply ICD, is a list of diseases classified by signs, symptoms, and causes. This system allows any health condition to be classified with a code of up to six digits. Having an international standardized coding system for diseases gives doctors or statisticians a resource for more accurate analysis of population health, the incidence and prevalence of various diseases, as well as the storage and retrieval of vital medical information. The Current ICD Code Currently, the ICD in its tenth edition, with an eleventh set to be completed by 2015. Work first began on the ICD-10 in 1983 and ended in 1992 with the new code implemented the following year. The Centers for Disease Control and Prevention (CDC) began using the updated code in 1999; however, some U.S. medical organizations like Medicare and Medicaid services will continue to use the ICD-9 until 2013. The United States ICD-Code System There is a U.S. specific version of the ICD-10, referred to as the ICD-10-CM. This clinical modification of the international code expands each designation from three digits to six, allowing for continued growth as medical discoveries are made, as well as greater distinction and accuracy. This raises the number of possible codes from 13,600 to approximately 69,000. What is the ICD Code for Mesothelioma? Though the tenth version has replaced the ninth in many areas of the world, the ICD-9-CM is still in use in some parts of the United States. Under that system, malignant pleural mesothelioma (chest) is assigned the code 163, peritoneal mesothelioma (abdomen) is assigned 158, and tumors of the heart such as pericardial mesothelioma are assigned 164. In the ICD-10’s second chapter, mesothelioma falls under the broad category of malignant neoplasms, specifically those of the mesothelial and soft tissue. The mesothelial tissue is that which surrounds and protects vital organs, allowing them to maneuver and operate properly. Overall malignant mesothelioma has the designation of C45, with its types classified as follows: - Pleural mesothelioma – C45.0 - Peritoneal mesothelioma – C45.1 - Pericardial mesothelioma – C45.2 - Mesothelioma of other sites – C45.7 - Mesothelioma, unspecified – C45.9	4	2	0	0	1	0.63506	1	605
Needle EMG is the recording and study of electrical activity of muscles using a needle electrode. Neurologists use EMGs to test the electrical activity of a skeletal muscle to provide a medical diagnosis on a patient. Although these are common procedures but coding them incorrectly can not only cause billing problems but often lead to audits. The Centers for Medicare & Medicaid Services (CMS) outlines clearly its recommendations for EMG billing in the Federal Register (issue of October 31, 1997, Vol. 62, No. 211, page 59090), which covers some common questions like how many muscles should/need to be studied per limb in order to use the limb EMG codes or which code should be used when performing a limited study of a specific muscle and whether it can be used multiple times. Here are some tips which can clarify EMG billing confusions and help in maximizing your EMG reimbursements: 1. When choosing an EMG code, count the limbs and identify the specific muscles the physician has tested. The first set of EMG CPT codes 95860-95864 are used on the basis of this analysis. To report these codes, the physician must evaluate extremity muscles innervated by three nerves (for example, radial, ulnar, median, tibial, peroneal or femoral but not sub-branches) And a minimum of five muscles studied per limb. For example: If a physician performs EMG test on a patient’s right leg and meets the minimum testing requirements (five muscles innervated by three nerves each), then he should report CPT 95860. A single unit of 95860, 95861, 95863 or 95864 includes all muscles of five or more tested in a particular extremity(ies). In other words, one should report only a single unit of 95860-95864 per session: You cannot bill additional units for more than five muscles per extremity. CPT 95865 is used for needle examination of the larynx and CPT 95866 is used for needle examination of the hemidiaphragm. If fewer than five muscles are tested then CPT 95870 (Needle electromyography; limited study of muscles in one extremity or non-limb (axial) muscles (unilateral or bilateral), other than thoracic paraspinal, cranial nerve supplied muscles or sphincters) should be used. 2. The next set of CPT codes are 95867-95868 which describes the EMG study of muscles supplied by the cranial nerve, either unilaterally or bilaterally. If the answer to your question is yes, then CPT 95867 (Needle electromyography; cranial nerve supplied muscle[s], unilateral) OR CPT 95868 (Needle electromyography; cranial nerve supplied muscles, bilateral) should be used depending upon the test performed by the physician. For example: A physician monitors the RLN (Recurrent Laryngeal Nerve) during a total thyroidectomy, he should assign the CPT 95868 for a bilateral EMG. It is important to note that Codes 95867 and 95868 should not be reported together, nor should modifier -50 (bilateral procedure) be attached to CPT 95868. 3. Are studies performed on thoracic paraspinals other then those at T1 and T2? Then one must report CPT 95869 (Needle electromyography; thoracic paraspinal muscles). Code 95869 is exclusively used to study thoracic paraspinal muscles between T3 and T11. One unit can be billed, despite the number of levels studied or whether unilateral or bilateral. 95869 cannot be reported with 95860-95864 if only the T1 and/or T2 levels are studied with an upper extremity. This code should be used if the examinations are confined to distal muscles only, such as intrinsic foot or hand muscles. 4. Is the study performed on fewer than five muscles per extremity, then CPT 95870 should be used. This code should only be used when the muscles tested do not fit more appropriately under any other CPT code. Code 95870 can be billed at one unit per extremity (one limb, arm or leg), when fewer than five muscles are examined. For example: If a physician tests 3 muscles on the right arm and 4 muscles on the left arm, then code 95870 can be reported twice. This code can also be used for examining non-limb (axial) muscles (e.g. intercostal, abdominal wall, cervical and lumbar paraspinal muscles (unilateral or bilateral)) regardless of the number of level tested. However, it should not be billed when the paraspinal muscles corresponding to extremity are tested, and when the extremity codes 95860, 95861, 95863, or 95864 are reported. 5. The last in row is code 95872 which is (Needle electromyography using single fiber electrode, with quantitative measurement of jitter, blocking and/or fiber density, any/all sites of each muscle studied). This code should be used when a physician studies the action potentials (APs) from individual muscle fibers. One should report one unit of 95872 for each muscle the physician tests. The physician will generally test at least two muscles (one test serves as a “control”), so you will report a minimum of two units of service. When reporting CPT 95872, the physician must document the muscle(s) tested and the test results. Keep these tips handy when coding and billing EMG studies. As always, please consult your payer guidelines and state regulations for any specific rules. For recent changes in Nerve Conduction Study Codes 2013, please visit our latest blog post	4	11	36	0	2	0.611579	38	1,239
Z45.0 is a non-specific and non-billable ICD-10 code code, consider using a code with a higher level of specificity for a diagnosis of encounter for adjustment and management of cardiac device. The code is not specific and is NOT valid for the year 2023 for the submission of HIPAA-covered transactions. Category or Header define the heading of a category of codes that may be further subdivided by the use of 4th, 5th, 6th or 7th characters. Specific Coding for Encounter for adjustment and management of cardiac device Non-specific codes like Z45.0 require more digits to indicate the appropriate level of specificity. Consider using any of the following ICD-10 codes with a higher level of specificity when coding for encounter for adjustment and management of cardiac device: Pacemakers and Implantable Defibrillators An arrhythmia is any disorder of your heart rate or rhythm. It means that your heart beats too quickly, too slowly, or with an irregular pattern. Most arrhythmias result from problems in the electrical system of the heart. If your arrhythmia is serious, you may need a cardiac pacemaker or an implantable cardioverter defibrillator (ICD). They are devices that are implanted in your chest or abdomen. A pacemaker helps control abnormal heart rhythms. It uses electrical pulses to prompt the heart to beat at a normal rate. It can speed up a slow heart rhythm, control a fast heart rhythm, and coordinate the chambers of the heart. An ICD monitors heart rhythms. If it senses dangerous rhythms, it delivers shocks. This treatment is called defibrillation. An ICD can help control life-threatening arrhythmias, especially those that can cause sudden cardiac arrest (SCA). Most new ICDs can act as both a pacemaker and a defibrillator. Many ICDs also record the heart's electrical patterns when there is an abnormal heartbeat. This can help the doctor plan future treatment. Getting a pacemaker or ICD requires minor surgery. You usually need to stay in the hospital for a day or two, so your doctor can make sure that the device is working well. You will probably be back to your normal activities within a few days. [Learn More in MedlinePlus] - FY 2023 - No Change, effective from 10/1/2022 through 9/30/2023 - FY 2022 - No Change, effective from 10/1/2021 through 9/30/2022 - FY 2021 - No Change, effective from 10/1/2020 through 9/30/2021 - FY 2020 - No Change, effective from 10/1/2019 through 9/30/2020 - FY 2019 - No Change, effective from 10/1/2018 through 9/30/2019 - FY 2018 - No Change, effective from 10/1/2017 through 9/30/2018 - FY 2017 - No Change, effective from 10/1/2016 through 9/30/2017 - FY 2016 - New Code, effective from 10/1/2015 through 9/30/2016 (First year ICD-10-CM implemented into the HIPAA code set)	4	2	0	0	4	0.746624	4	668
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] most commonly the legs. Nonspecific 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. 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. Those genetic factors include deficiencies with antithrombin, protein C, and protein S, the mutation of factor V Leiden, and the property of having a non-O blood type. 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. Prevention options for at-risk individuals include early and frequent walking, calf exercises, anticoagulants, aspirin, graduated compression stockings, and intermittent pneumatic compression. Anticoagulation is the standard treatment; typical medications include low-molecular-weight heparin or a vitamin K antagonist. Wearing graduated compression stockings appears to reduce the risk of post-thrombotic syndrome. The rate of DVTs increases from childhood to old age; in adulthood, about one in 1000 adults is affected per year. - 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. Phlegmasia cerulea dolens is a very large and dangerous type of DVT. 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, tinged blue in color, and swollen, 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 roughly 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 "chronic" has been applied to symptomatic DVT that persists longer than 10 to 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 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 preventive measures are recommended. 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 antiplatelet 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. Following the completion of warfarin long term aspirin is useful to prevent re occurrence. 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 people's risks of DVTs, it also increased people's risks of major bleeding. The review thus recommended the need to balance risks and benefits. The 2012 ACCP guidelines for nonsurgical patients[h] recommend anticoagulation for the acutely ill in cases of elevated risk when neither bleeding nor a high risk of bleeding exists. 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 nonorthopedic surgery include early walking, mechanical prophylaxis (intermittent pneumatic compression or graduated compression stockings), and drugs (low-molecular-weight heparin and low-dose-unfractionated heparin) 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 low-molecular-weight heparin (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 hypercoagulable state, a likely adaptation against fatal postpartum hemorrhage. Additionally, pregnant women with genetic risk factors are subject to a roughly three to 30 times increased risk for VTE. Preventative treatments for pregnancy-related VTE in hypercoagulable 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. Evidence however does not support that these stockings reduce the risk of post-thrombotic syndrome nor do they 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 are 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 is 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 DVT, 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 are 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 breastfeed 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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Individual differences \| Methods \| Statistics \| Clinical \| Educational \| Industrial \| Professional items \| World psychology \| Biological: Behavioural genetics · Evolutionary psychology · Neuroanatomy · Neurochemistry · Neuroendocrinology · Neuroscience · Psychoneuroimmunology · Physiological Psychology · Psychopharmacology (Index, Outline) Radiology is the specialty directing medical imaging technologies to diagnose and sometimes treat diseases. Originally it was the aspect of medical science dealing with the medical use of electromagnetic energy emitted by X-ray machines or other such radiation devices for the purpose of obtaining visual information as part of medical imaging. Radiology that involves use of x-ray is called roentgenology. Wilhelm Conrad Roentgen first discovered x-radiation on 8 November 1895 at the Physical Institute of Wuerzburg University. He named the radiation he had discovered "X-radiation". This term is still in use today in the anglo-american region. His work was first published in a meeting protocol of the Wuerzburg Physical-Medical Society in the 1895 volume; the article was submitted by W.C. Roentgen on 28 December 1895. Today, following extensive training, radiologists direct an array of imaging technologies (such as ultrasound, computed tomography (CT) and magnetic resonance imaging) to diagnose or treat disease. Interventional radiology is the performance of (usually minimally invasive) medical procedures with the guidance of imaging technologies. The acquisition of medical imaging is usually carried out by the radiographer or radiologic technologist. Outside of the medical field, radiology also encompasses the examination of the inner structure of objects using X-rays or other penetrating radiation. As a medical specialty, radiology can be classified broadly into Diagnostic radiology and Therapeutic radiology. - Diagnostic radiology is the interpretation of images of the human body to aid in the diagnosis or prognosis of disease. It is divided into subfields by anatomic location and in some cases method: - Chest radiology. - Abdominal & Pelvic radiology. Sometimes together termed "Body Imaging." - Interventional radiology uses imaging to guide therapeutic and angiographic procedures. Also known as Vascular & Interventional radiology. - Neuroradiology is the sub-specialty in the field of brain, spine, head, and neck imaging. - Interventional Neuroradiology uses imaging to guide therapeutic and angiographic procedures in the head, neck and spine. - Musculoskeletal radiology is the sub-specialty in the field of bone, joint, and muscular imaging. - Pediatric radiology. - Mammography Subdivision of radiology that images the breast tissue. - Nuclear Medicine is a subdivision of radiology that uses radioisotopes in the characterization of lesions and disease processes, and often yields functional information. - A Radiologist is a subspecialty physician trained in all areas of diagnostic radiology. Board certification is earned through the American Board of Radiology (ABR). - Nuclear Medicine, Interventional radiology, Neuroradiology and Pediatric radiology have optional subspecialty Board qualifications under the American Board of Radiology. - Certification in Nuclear Medicine alone can be earned as a non-radiologist physician through the American Board of Nuclear Medicine. - Therapeutic radiology utilizes radiation (radiation therapy) for therapy of diseases such as cancer. - While originally encompassed within radiology, radiation oncology is now a separate field. - Radiation Oncology specialty certification is earned through the American Board of Radiology. Acquisition of radiological imagesEdit Patients have the following procedures to provide images for Radiological decisions to be made. Projection (plain) radiographyEdit Radiographs (or Roentgenographs, named after the discoverer of X-rays, Wilhelm Conrad Roentgen (1845-1923)) are often used for evaluation of bony structures and soft tissues. An X-Ray machine directs electromagnetic radiation upon a specified region in the body. This radiation tends to pass through less dense matter (air, fat, muscle, and other tissues), but is absorbed or scattered by denser materials (bones, tumors, lungs affected by severe pneumonia). In Film-Screen Radiography, radiation which has passed through a patient then strikes a cassette containing a screen of fluorescent phosphors and exposes x-ray film. Areas of film exposed to higher amounts of radiation will appear as black or grey on X-ray film while areas exposed to less radiation will appear lighter or white. In Computed Radiography (CR), the x-rays passing through the patient strike a sensitized plate which is then read and digitized into a computer image by a separate machine. In Digital Radiography the x-rays strike a plate of x-ray sensors producing a digital computer image directly. While all three methods are currently in use, the trend in the U.S. is away from film and toward digital imaging. Plain radiography was the only imaging modality available during the first 50 years of Radiology. It is still the first study ordered in evaluation of the lungs, heart and skeleton because of its wide availability, speed and relative low cost. - Main article: Fluoroscopy Fluoroscopy and angiography are special applications of X-ray imaging, in which a fluorescent screen or image intensifier tube is connected to a closed-circuit television system, which allows real-time imaging of structures in motion or augmented with a radiocontrast agent. Radiocontrast agents are administered, often swallowed or injected into the body of the patient, to delineate anatomy and functioning of the blood vessels, the genitourinary system or the gastrointestinal tract.Two radiocontrasts are presently in use. Barium (as BaSO4) may be given orally or rectally for evaluation of the GI tract. Iodine, in multiple proprietary forms, may be given by oral, rectal, intraarterial or intravenous routes. These radiocontrast agents strongly absorb or scatter X-ray radiation, and in conjunction with the real-time imaging allows demonstration of dynamic processes, such as peristalsis in the digestive tract or blood flow in arteries and veins. Iodine contrast may also be concentrated in abnormal areas more or less than in normal tissues and make abnormalities (tumors, cysts, inflammation) more conspicuous. Additionally, in specific circumstances air can be used as a contrast agent for the gastrointestinal system and carbon dioxide can be used as a contrast agent in the venous system; in these cases, the contrast agent attenuates the X-ray radiation less than the surrounding tissues. CT scanning Edit - Main article: Computed tomography CT imaging uses X-rays in conjunction with computing algorithms to image the body. In CT, an X-ray generating tube opposite an X-ray detector (or detectors) in a ring shaped apparatus rotate around a patient producing a computer generated cross-sectional image (tomogram). CT is acquired in the axial plane, while coronal and sagittal images can be rendered by computer reconstruction. Radiocontrast agents are often used with CT for enhanced delineation of anatomy. Intravenous contrast can allow 3D reconstructions of arteries and veins. Although radiographs provide higher spatial resolution, CT can detect more subtle variations in attenuation of X-rays. CT exposes the patient to more ionizing radiation than a radiograph. Spiral Multi-detector CT utilizes 8,16 or 64 detectors during continuous motion of the patient through the radiation beam to obtain much finer detail images in a shorter exam time. With computer manipulation these images can be reconstructed into 3D images of carotid, cerebral and coronary arteries. Faster scanning times in modern equipment has been associated with increased utilization. The first CT scanner in North America was installed at the Mayo Clinic in Rochester, MN in 1972. - Main article: Ultrasound Medical ultrasonography uses ultrasound (high-frequency sound waves) to visualize soft tissue structures in the body in real time. No ionizing radiation is involved, but the quality of the images obtained using ultrasound is highly dependent on the skill of the person (ultrasonographer) performing the exam. Ultrasound is also limited by its inability to image through air (lungs, bowel loops) or bone. The use of ultrasound in medical imaging has developed mostly within the last 30 years. The first ultrasound images were static and two dimensional (2D), but with modern-day ultrasonography 3D reconstructions can be observed in real-time; effectively becoming 4D. Because ultrasound does not utilize ionizing radiation, unlike radiography, CT scans, and nuclear medicine imaging techniques, it is generally considered safer. For this reason, this modality plays a vital role in obstetrical imaging. Fetal anatomic development can be thoroughly evaluated allowing early diagnosis of many fetal anomalies. Growth can be assessed over time, important in patients with chronic disease or gestation-induced disease, and in multiple gestations (twins, triplets etc.). Color-Flow Doppler Ultrasound measures the severity of peripheral vascular disease and is used by Cardiology for dynamic evaluation of the heart, heart valves and major vessels. Stenosis of the carotid arteries can presage cerebral infarcts (strokes). DVT in the legs can be found via ultrasound before it dislodges and travels to the lungs (pulmonary embolism), which can be fatal if left untreated. Ultrasound is useful for image-guided interventions like biopsies and drainages such as thoracentesis). It is also used in the treatment of kidney stones (renal lithiasis) via lithotripsy. Small portable ultrasound devices now replace peritoneal lavage in the triage of trauma victims by directly assessing for the presence of hemorrhage in the peritoneum and the integrity of the major viscera including the liver, spleen and kidneys. Extensive hemoperitoneum (bleeding inside the body cavity) or injury to the major organs may require emergent surgical exploration and repair. - Main article: Magnetic resonance imaging MRI uses strong magnetic fields to align spinning atomic nuclei (usually hydrogen protons) within body tissues, then uses a radio signal to disturb the axis of rotation of these nuclei and observes the radio frequency signal generated as the nuclei return to their baseline states. The radio signals are collected by small antennae, called coils, placed near the area of interest. An advantage of MRI is its ability to produce images in axial, coronal, sagittal and multiple oblique planes with equal ease. MRI scans give the best soft tissue contrast of all the imaging modalities. With advances in scanning speed and spatial resolution, and improvements in computer 3D algorithms and hardware, MRI has become an essential tool in musculoskeltal radiology and neuroradiology. One disadvantage is that the patient has to hold still for long periods of time in a noisy, cramped space while the imaging is performed. Claustrophobia severe enough to terminate the MRI exam is reported in up to 5% of patients. Recent improvements in magnet design including stronger magnetic fields (3 teslas), shortening exam times, wider, shorter magnet bores and more open magnet designs, have brought some relief for claustrophobic patients. However, in magnets of equal field strength there is often a trade-off between image quality and open design. MRI has great benefit in imaging the brain, spine, and musculoskeletal system. The modality is currently contraindicated for patients with pacemakers, cochlear implants, some indwelling medication pumps, certain types of cerebral aneurysm clips, metal fragments in the eyes and some metallic hardware due to the powerful magnetic fields and strong fluctuating radio signals the body is exposed to. Areas of potential advancement include functional imaging, cardiovascular MRI, as well as MR image guided therapy. Nuclear medicine Edit - Main article: Nuclear medicine Nuclear medicine imaging involves the administration into the patient of radiopharmaceuticals consisting of substances with affinity for certain body tissues labeled with radioactive tracer. The most commonly used tracers are Technetium-99m, Iodine-123, Iodine-131 and Thallium-201. The heart, lungs, thyroid, liver, gallbladder, and bones are commonly evaluated for particular conditions using these techniques. While anatomical detail is limited in these studies, nuclear medicine is useful in displaying physiological function. The excretory function of the kidneys, iodine concentrating ability of the thyroid, blood flow to heart muscle, etc. can be measured. The principal imaging device is the gamma camera which detects the radiation emitted by the tracer in the body and displays it as an image. With computer processing, the information can be displayed as axial, coronal and sagittal images (SPECT images). In the most modern devices Nuclear Medicine images can be fused with a CT scan taken quasi-simultaneously so that the physiological information can be overlaid or co-registered with the anatomical structures to improve diagnostic accuracy. PET scanning also falls under "nuclear medicine." In PET scanning, a radioactive biologically-active substance, most often Fluorine-18 Fluorodeoxyglucose, is injected into a patient and the radiation emitted by the patient is detected to produce multi-planar images of the body. Metabolically more active tissues, such as cancer, concentrate the active substance more than normal tissues. PET images can be combined with CT images to improve diagnostic accuracy. The applications of nuclear medicine can include bone scanning which traditionally has had a strong role in the work-up/staging of cancers. 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The custom Radiology Search, compiled from hundreds of peer-reviewed radiology sites, covers diagnostic radiology, radiation oncology, nuclear medicine, physics, engineering, computer science, and imaging technologies. - Radiological Society of North America - huge amount of information on radiology, including links to the online journals Radiology and Radiographics Advance practice nursing - Audiology - Dentistry - Dietetics - Emergency medical services - Epidemiology - Medical technology - Midwifery - Nursing - Occupational therapy - Optometry - Osteopathic medicine - Pharmacy - Physical therapy (Physiotherapy) - Physician - Physician assistant - Podiatry - Psychology - Public health - Respiratory therapy - Speech and language pathology Physician specialties: Anesthesiology - Dermatology - Emergency medicine - General practice (Family medicine) - Internal medicine - Neurology - Nuclear medicine - Occupational medicine - Pathology - Pediatrics - Physical medicine and rehabilitation (Physiatry) - Preventive medicine - Psychiatry - Radiation oncology - Radiology - Surgery Medical subspecialties: Allergy and immunology - Cardiology - Endocrinology - Gastroenterology - Hematology - Infectious disease - Intensive care medicine (Critical care medicine) - Medical genetics - Nephrology - Oncology - Pulmonology - Rheumatology \|This page uses Creative Commons Licensed content from Wikipedia (view authors).\|	2	13	0	0	1	0.518717	1	17,569
- Macular degeneration Macular degeneration Classification and external resources Picture of the fundus showing intermediate age-related macular degeneration. ICD-10 H35.3 ICD-9 362.50 DiseasesDB 11948 MedlinePlus 001000 eMedicine article/1223154 MeSH D008268 Age-related macular degeneration (AMD) is a medical condition which usually affects older adults and results in a loss of vision in the center of the visual field (the macula) because of damage to the retina. It occurs in “dry” and “wet” forms. It is a major cause of blindness and visual impairment in older adults (>50 years). Macular degeneration can make it difficult or impossible to read or recognize faces, although enough peripheral vision remains to allow other activities of daily life. Starting from the inside of the eye and going towards the back, the three main layers at the back of the eye are the retina, which contains the nerves; the choroid, which contains the blood supply; and the sclera, which is the white of the eye. The macula is the central area of the retina, which provides the most detailed central vision. In the dry (nonexudative) form, cellular debris called drusen accumulate between the retina and the choroid, and the retina can become detached. In the wet (exudative) form, which is more severe, blood vessels grow up from the choroid behind the retina, and the retina can also become detached. It can be treated with laser coagulation, and with medication that stops and sometimes reverses the growth of blood vessels. Although some macular dystrophies affecting younger individuals are sometimes referred to as macular degeneration, the term generally refers to age-related macular degeneration (AMD or ARMD). Age-related macular degeneration begins with characteristic yellow deposits (drusen) in the macula, between the retinal pigment epithelium and the underlying choroid. Most people with these early changes (referred to as age-related maculopathy) have good vision. People with drusen can go on to develop advanced AMD. The risk is considerably higher when the drusen are large and numerous and associated with disturbance in the pigmented cell layer under the macula. Recent research suggests that large and soft drusen are related to elevated cholesterol deposits and may respond to cholesterol-lowering agents. Central geographic atrophy, the “dry” form of advanced AMD, results from atrophy to the retinal pigment epithelial layer below the retina, which causes vision loss through loss of photoreceptors (rods and cones) in the central part of the eye. No medical or surgical treatment is available for this condition, however vitamin supplements with high doses of antioxidants, lutein and zeaxanthin, have been suggested by the National Eye Institute and others to slow the progression of dry macular degeneration and, in some patients, improve visual acuity. Neovascular or exudative AMD, the “wet” form of advanced AMD, causes vision loss due to abnormal blood vessel growth (choroidal neovascularization) in the choriocapillaris, through Bruch's membrane, ultimately leading to blood and protein leakage below the macula. Bleeding, leaking, and scarring from these blood vessels eventually cause irreversible damage to the photoreceptors and rapid vision loss if left untreated. Only about 10% of patients suffering from macular degeneration have the wet type. Macular degeneration is not painful, and this may allow it to go unnoticed for some time. Signs and symptoms - Pigmentary alterations - Exudative changes: hemorrhages in the eye, hard exudates, subretinal/sub-RPE/intraretinal fluid - Atrophy: incipient and geographic - Visual acuity drastically decreasing (two levels or more) ex: 20/20 to 20/80. - Preferential hyperacuity perimetry changes (for wet AMD) - Blurred vision: Those with nonexudative macular degeneration may be asymptomatic or notice a gradual loss of central vision, whereas those with exudative macular degeneration often notice a rapid onset of vision loss. - Central scotomas (shadows or missing areas of vision) - Distorted vision (i.e., metamorphopsia) - A grid of straight lines appears wavy and parts of the grid may appear blank. Patients often first notice this when looking at mini-blinds in their home. - Trouble discerning colors; specifically dark ones from dark ones and light ones from light ones. - Slow recovery of visual function after exposure to bright light - A loss in contrast sensitivity. Macular degeneration by itself will not lead to total blindness. For that matter, only a very small number of people with visual impairment are totally blind. In almost all cases, some vision remains. Other complicating conditions may possibly lead to such an acute condition (severe stroke or trauma, untreated glaucoma, etc.), but few macular degeneration patients experience total visual loss. The area of the macula comprises only about 2.1% of the retina, and the remaining 97.9% (the peripheral field) remains unaffected by the disease. Interestingly, even though the macula provides such a small fraction of the visual field, almost half of the visual cortex is devoted to processing macular information. The loss of central vision profoundly affects visual functioning. It is not possible, for example, to read without central vision. Pictures that attempt to depict the central visual loss of macular degeneration with a black spot do not really do justice to the devastating nature of the visual loss. This can be demonstrated by printing letters 6 inches high on a piece of paper and attempting to identify them while looking straight ahead and holding the paper slightly to the side. Most people find this difficult to do. There is a loss of contrast sensitivity, so that contours, shadows, and color vision are less vivid. The loss in contrast sensitivity can be quickly and easily measured by a contrast sensitivity test performed either at home or by an eye specialist. Similar symptoms with a very different etiology and different treatment can be caused by Epiretinal membrane or macular pucker or leaking blood vessels in the eye. Causes and risk factors - Aging: Approximately 10% of patients 66 to 74 years of age will have findings of macular degeneration. The prevalence increases to 30% in patients 75 to 85 years of age. - Family history: The lifetime risk of developing late-stage macular degeneration is 50% for people that have a relative with macular degeneration, versus 12% for people that do not have relatives with macular degeneration, a fourfold higher risk. Researchers from the University of Southampton reported October 7, 2008 that they had discovered six mutations of the gene SERPING1 that are associated with AMD. Mutations in this gene can also cause hereditary angioedema. - Macular degeneration gene: The genes for the complement system proteins factor H (CFH), factor B (CFB) and factor 3 (C3) have been determined to be strongly associated with a person's risk for developing macular degeneration. CFH is involved in inhibiting the inflammatory response mediated via C3b (and the alternative pathway of complement) both by acting as a cofactor for cleavage of C3b to its inactive form, C3bi, and by weakening the activecomplex that forms between C3b and factor B. C-reactive protein and polyanionic surface markers such as glycosaminoglycans normally enhance the ability of factor H to inhibit complement. But the mutation in CFH(Tyr402His) reduces the affinity of CFH for CRP and probably also alters the ability of factor H to recognise specific glycosaminoglycans. This change results in reduced ability of CFH to regulate complement on critical surfaces such as the specialised membrane at the back of the eye and leads to increased inflammatory response within the macula. In two 2006 studies at Yale Department of Epidemiology and Public Health and the Department of Ophthalmology and Visual Sciences, Moran Eye Center at the University of Utah School of Medicine, another gene that has implications for the disease, called HTRA1 (encoding a secreted serine protease), was identified. The mitochondrial genome (mtDNA) in humans is contained on a single circular chromosome 16,569 basepairs around, and each mitochondrion contains 5 to 10 copies of the mitochondrial chromosome. There are several essential genes in mtDNA that are involved in replication and translation, along with some genes that are crucial for the machinery that converts metabolic energy into ATP. These include NADH dehydrogenase, cytochrome c oxidase, ubiquinol/cytochrome c oxidoreductase, and ATP synthase, as well as the genes for unique ribosomal RNA and transfer RNA particles that are required for translating these genes into proteins. There are specific diseases associated with mutations in some of these genes. Below is one of the affected genes and the disease that arises from its mutation. - Mutation of the ATP synthase gene: Retinitis pigmentosa (RP) is a genetically linked dysfunction of the retina and is related to mutation of the adenosine triphosphate (ATP) synthase gene 615.1617 - Stargardt's disease (STGD, also known as juvenile macular degeneration) is an autosomal recessive retinal disorder characterized by a juvenile-onset macular dystrophy, alterations of the peripheral retina, and subretinal deposition of lipofuscin-like material. A gene encoding an ATP-binding cassette (ABC) transporter was mapped to the 2-cM (centiMorgan) interval at 1p13-p21 previously shown by linkage analysis to harbor the STGD gene. This gene, ABCR, is expressed exclusively and at high levels in the retina, in rod but not cone photoreceptors, as detected by in situ hybridization. Mutational analysis of ABCR in STGD families revealed a total of 19 different mutations including homozygous mutations in two families with consanguineous parentage. These data indicate that ABCR is the causal gene of STGD/FFM. - Drusen: CMSD studies indicate that drusen are similar in molecular composition to plaques and deposits in other age-related diseases such as Alzheimer's disease and atherosclerosis. While there is a tendency for drusen to be blamed for the progressive loss of vision, drusen deposits can be present in the retina without vision loss. Some patients with large deposits of drusen have normal visual acuity. If normal retinal reception and image transmission are sometimes possible in a retina when high concentrations of drusen are present, then, even if drusen can be implicated in the loss of visual function, there must be at least one other factor that accounts for the loss of vision. - Arg80Gly variant of the complement protein C3: Two independent studies published in the New England Journal of Medicine and Nature Genetics in 2007 showed that a certain common mutation in the C3 gene which is a central protein of the complement system is strongly associated with the occurrence of age-related macular degeneration. The authors of both papers consider their study to underscore the influence of the complement pathway in the pathogenesis of this disease. - Hypertension: Also known as high blood pressure. - Cardiovascular status: High cholesterol, obesity. - High fat intake is associated with an increased risk of macular degeneration in both women and men. Fat provides about 42% of the food energy in the average American diet. A diet that derives closer to 20-25% of total food energy from fat is probably healthier. Reducing fat intake to this level means cutting down greatly on consumption of red meats and high-fat dairy products such as whole milk, cheese, and butter. Eating more cold-water fish (at least twice weekly), rather than red meats, and eating any type of nuts may help macular degeneration patients. - Oxidative stress: It has been proposed that age-related accumulation of low-molecular-weight, phototoxic, pro-oxidant melanin oligomers within lysosomes in the retinal pigment epithelium may be partly responsible for decreasing the digestive rate of photoreceptor outer rod segments (POS) by the RPE. A decrease in the digestive rate of POS has been shown to be associated with lipofuscin formation - a classic sign associated with macular degeneration. - Fibulin-5 mutation: Rare forms of the disease are caused by geneic defects in fibulin-5, in an autosomal dominant manner. In 2004, Stone et al. performed a screen on 402 AMD patients and revealed a statistically significant correlation between mutations in Fibulin-5 and incidence of the disease. Furthermore, the point mutants were found in the calcium binding sites of the cbEGF domains of the protein. There is no structural basis for the effects of the mutations. - Race: Macular degeneration is more likely to be found in Caucasians than in people of African descent. - Exposure to sunlight especially blue light: There is conflicting evidence as to whether exposure to sunlight contributes to the development of macular degeneration. A recent study in the British Journal of Ophthalmology on 446 subjects found that it does not. Other research, however, has shown that high-energy visible light (HEV) may contribute to age-related macular degeneration. - Smoking: Smoking tobacco increases the risk of macular degeneration by two to three times that of someone who has never smoked, and may be the most important modifiable factor in its prevention. A review of previous studies found that "the literature review confirmed a strong association between current smoking and AMD. ... Cigarette smoking is likely to have toxic effects on the retina." - Deletion of CFHR3 and CFHR1: Deletion of the complement factor H-related genes CFHR3 and CFHR1 protects against age-related macular degeneration. Early work demonstrated that a family of immune mediators was plentiful in drusen. complement factor H (CFH) is an important inhibitor of this inflammatory cascade and a disease-associated polymorphism in the CFH gene strongly associates with AMD. Thus an AMD pathophysiological model of chronic low grade complement activation and inflammation in the macula has been advanced. Lending credibility to this has been the discovery of disease-associated genetic polymorphisms in other elements of the complement cascade including complement component 3 (C3). The role of retinal oxidative stress in the etiology of AMD by causing further inflammation of the macula is suggested by the enhanced rate of disease in smokers and those exposed to UV irradiation. Mitochondria are a major source of oxygen free radicals that occur as a byproduct of energy metabolism. Mitochondrial gene polymorphisms, such as that in the MT-ND2 molecule, predicts wet AMD. A powerful predictor of AMD is found on chromosome 10q26 at LOC 387715. An insertion/deletion polymorphism at this site reduces expression of the ARMS2 gene though destabilization of its mRNA through deletion of the polyadenylation signal. ARMS2 protein may localize to the mitochondria and participate in energy metabolism, though much remains to be discovered about its function. Other gene markers of progression risk includes Tissue Inhibitor of Metalloproteinase 3 (TIMP3) suggesting a role for intracellular matrix metabolism in AMD progression. Variations in cholesterol metabolising genes such as the hepatic lipase (LIPC), cholesterol ester transferase (CETP), lipoprotein lipase (LPL) and the ABC-binding cassette A1 (ABCA1) correlate with disease progression, Early stigmata of disease, drusen, are rich in cholesterol, offering face validity to the results of genome wide association studies Fluorescein angiography allows for the identification and localization of abnormal vascular processes. Optical coherence tomography is now used by most ophthalmologists in the diagnosis and the followup evaluation of the response to treatment by using either Avastin or Lucentis, which are injected into the vitreous of the eye at various intervals. Treatments for wet AMD Until recently, no effective treatments were known for wet macular degeneration. However, new drugs, called anti-angiogenics or anti-VEGF (anti-Vascular Endothelial Growth Factor) agents, can cause regression of the abnormal blood vessels and improvement of vision when injected directly into the vitreous humor of the eye. The injections have to be repeated on a monthly or bi-monthly basis. Examples of these agents include ranibizumab (trade name Lucentis), bevacizumab (trade name Avastin, a close chemical relative of ranibizumab) and pegaptanib (trade name Macugen). In November 2011 the FDA approved aflibercept (trade name Eylea) for treatment of wet AMD. Bevacizumab is not approved for intra-ocular use, but is approved for other systemic indications. Pegaptanib (Macugen) has benefits in neovascular AMD and has approval for such use. Worldwide, bevacizumab has been used extensively despite its "off label" status. The cost of ranibizumab (Lucentis) is approximately US$2000 per treatment while the cost of bevacizumab (Avastin) is approximately US$150 per treatment. Both drugs are made by Genentech. In the UK NICE institute issued guidelines for the treatment of wet AMD in the NHS. NICE only approved use of ranibizumab (trade name Lucentis) for wet AMD in the NHS in England. NHS hospitals and Primary Care Trusts in England are required to follow NICE guidance. Consuming omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid) has been correlated with a reduced progression of early ARMD, and in conjunction with low glycemic index foods, with reduced progression of advanced ARMD. A Cochrane Database Review of publications to 2007 found that the use of vitamin and mineral supplements, alone or in combination, by the general population had no effect on age-related macular degeneration, a finding echoed by another review. A 2006 Cochrane Review of the effects of vitamins and minerals on the slowing of ARMD found that positive results mainly came from a single large trial in the United States (the Age-Related Eye Disease Study), with funding from the eye care product company Bausch & Lomb who also manufactured the supplements used in the study, and questioned the generalization of the data to any other populations with different nutritional status. The review also questioned the possible harm of such supplements, given the increased risk of lung cancer in smokers with high intakes of beta-carotene, and the increased risk of heart failure in at-risk populations who consume high levels of vitamin E supplements. Because peripheral vision is not affected, people with macular degeneration can learn to use their remaining vision to partially compensate. Assistance and resources are available in many countries and every state in the U.S. Classes for "independent living" are given and some technology can be obtained from a state department of rehabilitation. Adaptive devices can help people read. These include magnifying glasses, special eyeglass lenses, computer screen readers, and TV systems that enlarge reading material. Video cameras can be fed into standard or special-purpose computer monitors, and the image can be zoomed in and magnified. These systems often include a movable table to move the written material. Text of internet articles can be copied and pasted into a word processing program, the font size increased. A white background can be difficult for a person with ARMD to read, so the background color can be changed to black, and the font color to white. In Windows, this can be done with the key combination Left-alt Left-shift Print Screen. In Mac OS X, this kind of visual inversion can be enabled systemwide via the Universal Access panel of System Preferences (located under the Apple menu at the extreme left of all menubars). Text-to-speech and other assistive options are also available there. Amsler Grid Test The Amsler Grid Test is one of the simplest and most effective methods for patients to monitor the health of the macula. The Amsler Grid is, in essence, a pattern of intersecting lines (identical to graph paper) with a black dot in the middle. The central black dot is used for fixation (a place for the eye to stare at). With normal vision, all lines surrounding the black dot will look straight and evenly spaced with no missing or odd looking areas when fixating on the grid's central black dot. When there is disease affecting the macula, as in macular degeneration, the lines can look bent, distorted and/or missing. 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A “gold standard” for medical coding is now an acknowledged need. However, the well-documented phenomenon of coder variability makes the generation of such a standard a challenge. A method is needed to efficiently generate a consensus view of how to code any given medical record. The Delphi Method, a consensus-generating methodology, is one such method. In this study, we demonstrate how a modified version of the Delphi Method can be used to create a gold standard for medical record coding. We demonstrate that, compared to more traditional methods, the Delphi Method reduces undercoding and is less susceptible to problems due to limitations in human cognitive ability. Finally, we describe an implementation of the Delphi Method as an online gaming environment. We discuss why a gaming environment is an ideal method for generating consensus cases and describe the benefits of this gaming environment to the greater coding community. Multiple studies have shown that medical coders will frequently differ in the number and type of codes they apply to medical charts. This is true for ICD-9-CM and ICD-10 coding1–3 and CPT (Current Procedural Terminology) codes, including E&M coding.4, 5 Coder variability is a significant challenge in developing any standard of “correctness” for medical coding. This is especially true for a gold standard that would be used to evaluate computer-assisted coding (CAC) systems. A gold standard, like any kind of measurement system, must be valid, meaning that the measurements derived from the system must be an actual reflection of the thing being measured (in this case the correctness of the coding system), and reliable, meaning that the measurements derived from the gold standard must be consistent, with the same measurements obtained each time the system is used under the same conditions.6 Coder variability undermines both of these standards. A typical method for creating a gold standard is to identify experts in the task under study (in this case medical coding experts), have them perform some reference task independently (code a set of medical records), and then use some resolution protocol to resolve differences in task output. For example, Resnik and colleagues (2006) had two experts code 720 radiology notes and then had a third expert code those notes when the first two experts disagreed. The gold standard for any radiology note in this study became the codes applied to notes that were agreed on by two of the three experts. Resnik and colleagues found that for 94 percent of the notes, two of the three coders agreed on all the CPT codes that should be applied.7 At first, the amount of agreement obtained in this study seems remarkable, especially in light of previous studies showing significant coder variability. However, a question can be raised about this kind of method for creating a gold standard. Radiology notes happen to be a particularly simple form of medical documentation.8 Their simple structure and relatively limited vocabulary make them amenable to automation. This would also tend to reduce the amount of variance among medical coders working with these documents since both the number and variety of codes that could be applied to each note is small. Under these conditions, it is a reasonable possibility that the amount of agreement obtained was simply an artifact of the kinds of documents coded and the low threshold used to determine if coders agreed that a code should apply. (In fact, in the simple case, where only one code should be applied to a note and there are only two possible codes that could logically be applied, the chances that two out of three coders will agree on which of the two codes actually apply is 100 percent.) Would the codes generated as the gold standard in that study be reliably generated again if different experts were used? Can this technique be used for other, more complicated kinds of medical documentation? Also, developing a gold standard by having expert coders independently generate codes is a method that is vulnerable to all the well-documented limitations of human information processing,9, 10 limitations that contribute to the observed variability between medical coders. The alternative is to develop a method that incorporates techniques that specifically compensate for these limitations. One possibility, a modified version of the Delphi Method, is discussed in the next section. The Delphi Method Linstone and Turoff define the characteristics of the Delphi Method as follows: - Receiving input from a variety of experts about a topic of interest, typically anonymously - Obtaining this input in a structured way (e.g., a questionnaire, an opinion on a defined problem, a set of rating scales) - Evaluating the input by using a set of criteria, and filtering and summarizing it if necessary - Presenting this evaluation to the experts again and giving them an opportunity to comment on it and change their input based on the evaluation - Evaluating this second round of input and presenting this second evaluation to the experts - Iteratively repeating the process until the opinions of the experts are stable and, in some instances, have converged on a consensus opinion11 Since its development in the 1950s at the RAND Corporation, the Delphi Method has been used for a wide range of applications including project estimation, risk analysis, and technology projections.12 However, to date it has not been used for the more structured task of medical coding. Yet the fact that medical coding is a complicated task without a generally agreed-upon “solution” makes it a candidate for this approach. A straight application of the Delphi Method could be used to create a gold standard, but there are potential problems with this. Traditionally, comments made by other experts have been used as part of the information received by participants. This feedback is used to reach a consensus by persuading some participants to change their positions on the topic in question. But presenting other participants’ comments is a cumbersome process, and the potential variability of these comments, coupled with the fact that persuasion through written discourse is a complicated and difficult-to-control interaction, could have a deleterious effect on the reliability of the Delphi Method. The Delphi Method of Medical Coding To address the concerns raised above, we modified the Delphi Method to make it more streamlined and less susceptible to bias. The Delphi Method of Medical Coding (DMMC), a patent-pending process developed by Artificial Medical Intelligence, consists of three steps: - Multiple coders are presented with identical sets of medical records and are asked to code them as they would in a normal clinical setting. This first stage is used to identify the universe of possible codes that could reasonably be applied to a chart. For each record, the codes are consolidated across coders into a single set so that every code that was generated by at least one coder is represented once in the set. One consolidated set of codes is created for each medical record reviewed. - The consolidated sets of codes gathered in step 1 are then presented to a second set of coders along with the associated medical records that were used in step 1. The second group of coders is asked to make a simple yes/no decision about each code. Specifically, should this code be applied to the associated record or not? - For each code, the percentage of coders who decided that the code should apply to the associated record is calculated. Then comparing that percentage to some a priori criterion (either a fixed percentage or some derived statistic, for example, one derived from a binomial distribution), one of three decisions is made about the code: a. The code should be applied to the chart (and hence should be part of the gold standard) because the percentage of coders who voted “yes” (or the statistic derived from this percentage) exceeds some criterion. b. The code should not be applied to the chart because the percentage of coders who voted “no” (or the associated statistic) exceeds some criterion. c. The code is indeterminate, meaning that a consensus either for or against applying the code to a chart cannot be derived. A Pilot Study That Used the DMMC To explore the effectiveness of the DMMC, we ran a pilot study. During phase 1, six coders, all with coding certification and hospital coding experience, were presented with five inpatient records. The records were e-mailed to the coders with the instruction to code the records as they normally would using whatever coding resources (manuals, encoders, etc.) they usually employ. Coders entered the codes into a spreadsheet and mailed them back to the experimenter. Consolidated sets were obtained for each record. During step 2, the consolidated sets and associated medical records were presented to seven additional coders. The order in which the medical records were presented was randomized with the constraint that no coder received the medical records in the same sequence. Coders were again instructed to use whatever resources they would normally use but were requested not to consult with other coders. Coders were provided with a simple form with the codes from each consolidated set pre-entered. Next to each code were two boxes, one for “yes” and one for “no.” They were instructed to check the “yes” box if they felt the code should apply and the “no” box if they felt the code should not apply. Coders were also provided the opportunity to write additional codes that they felt should be applied to the record but were not listed in the consolidated set. Only one coder chose to do this, adding three additional codes, but this was done for only one record. Because of this, these additional codes were excluded from the final analysis. How does the pattern of agreement between coders change when making simple yes/no judgments compared with the more traditional methods where coders independently generate codes? Figure 1 shows the level of agreement between coders during step 1 of the DMMC. Coders at this step of the method perform a task very similar to the task used to create a gold standard in the study by Resnik and colleagues.13 We divided the codes into the following three categories: codes in which two-thirds or more of the coders generated the code for the record, codes in which one-third or fewer of the coders generated the code for the record, and codes in which between one-third and two-thirds of the coders generated the code for the record. If consensus is assumed to occur when two-thirds of the coders agree that a code should or should not be applied to a record, then the level of agreement in step 1 seems to be quite high: consensus is obtained for 91 percent of the codes, a percentage similar to the one obtained by Resnik and colleagues.14 Figure 2 shows the pattern of agreement among coders during step 2 of the DMMC. Codes were again divided into three categories. However, this time agreement was determined by the percentage of coders voting “yes.” It might seem that the level of agreement actually declines when voting on codes as opposed to generating codes. We assume that codes for which the level of agreement is between one-third and two-thirds of the coders have an ambiguous status in that it is not clear whether they should or should not be applied to the associated chart. The percentage of codes that fall into this middle category increases by almost 67 percent, from 9 to 15 percent, between step 1 and step 2. But to conclude that voting on codes amplifies disagreements between coders is to miss the broader point about what is really taking place. This is shown in Figure 3. The figure shows that the number of coders agreeing that any one code should be applied to a medical record increases between step 1 and step 2. Also, a greater number of codes were applied by a larger number of coders in step 2. The average percentage of coders that agree that any given code should be applied to a record increased between step 1 and step 2 from 49 percent to 61 percent (p < .05). At the same time, the number of outliers drops dramatically once a list of “potential” codes is provided. It would appear that one of the reasons coders seem to agree more often in step 1 (and in traditional methods for producing gold standards) is that they simply did not think of certain codes that could have been applied. An implication of this is that traditional methods for producing gold standards are susceptible to undercoding problems. Presenting coders with a list of codes that they need to vote on as opposed to requiring coders to generate codes reduces this source of error. Although the current study is only a pilot, it suggests that the method of creating a gold standard by having coders independently generate codes and then using a resolution protocol to resolve differences has significant limitations. At a minimum, such a method is likely to result in gold standards with significant amounts of undercoding. The DMMC represents an alternative. Agreement is dependent on independent judgments on the applicability of codes rather than independent generation of the codes themselves. Because the former task is easier, it eliminates a significant source of error and, as the current study suggests, results in more completely coded gold standards. Traditionally, the number of experts used to create gold standards has been small. However, using small sample sizes increases the likelihood of variability, reducing the reliability of the standard. This suggests that significantly increasing the numbers of coders who participate in the creation of a coding standard is desirable. One way to do this is to implement the DMMC as an online game like the one developed by Artificial Medical Intelligence, called The Coding Game, a registered trademark of Artificial Medical Intelligence.15 In this game, coders perform both the task of entering codes and defining the universe of possible applicable codes (step 1) and the task of voting on the applicability of codes (step 2), just as is done in the DMCC, but as a competition. The coders receive points based on the correspondence between their responses and consensus of coders participating in the game. Online games that produce useful output as a byproduct are part of the emerging field of human-based computation.16 Online games have been shown to be effective means of accomplishing other tasks including labeling images17 and collecting common-sense knowledge.18 As with other online games, coders are motivated to participate for several reasons: - The game is engaging and fun to play. - It allows coders to demonstrate their skills and receive a rating. - Coders can win prizes and cash based on their performance. The Coding Game will produce a national gold standard for medical coding based on the responses of potentially thousands of coders. It will simultaneously be able to produce a quantitative score that will measure a coder’s ability to code, based on the gold standard. It can be adapted to audit coding at individual hospitals and could even be used to do new coding of medical records. The game is also adaptable to any coding system, including ICD-9, ICD-10, and CPT. Because it implements the DMMC, it inherits all the advantages of this methodology that have been demonstrated in this study. We believe that an online game like The Coding Game is the most effective, robust, and economical way to create a coding gold standard that can be used to evaluate CAC solutions, coders, and hospital coding. M. Elliott Familant, PhD, is chief technical officer of Artificial Medical Intelligence in Eatontown, NJ. Stuart Covit is executive vice president of marketing and administration of Artificial Medical Intelligence in Eatontown, NJ. Andrew B. Covit, MD, is chief executive officer of Artificial Medical Intelligence in Eatontown, NJ. - Office of Inspector General, Office of Healthcare Inspections. Department of Veterans Affairs. March 19, 1993. Available from the Department of Veterans Affairs Web site at http://www.va.gov/oig/54/reports/no37.htm (retrieved August 13, 2007). - Morris, W. C., D. T. Heinze, H. R. Warner, Jr., A. Primack, A. E. Morsch, and R. E. Sheffer. “Assessing the Accuracy of an Automated Coding System in Emergency Medicine.” Proceedings of the 2000 AMIA Annual Symposium (pp. 595–599). Philadelphia: Hanley & Belfus, 2000. - Nilsson, G., H. Petersson, H. Ahlfeldt, and L. E. Strender. “Evaluation of Three Swedish ICD-10 Primary Care Versions: Reliability and Ease of Use in Diagnostic Coding.” Methods of Information in Medicine 39 (2000): 325–331. - Morris, W. C., D. T. Heinze, H. R. Warner, Jr., A. Primack, A. E. Morsch, and R. E. Sheffer. “Assessing the Accuracy of an Automated Coding System in Emergency Medicine.” - King, M. S., M. S. Lipsky, and L. Sharp. “Expert Agreement in Current Procedural Terminology Evaluation and Management Coding.” Archives of Internal Medicine 162, no. 3 (2002): 316–320. - Cook, T. D., and D. T. Campbell. Quasi-Experimentation: Design and Analysis for Field Settings. Chicago, IL: Rand McNally, 1979. - Resnik, P., M. Niv, M. Nossal, G. Schnitzer, J. Stoner, A. Kapit, et al. “Using Intrinsic and Extrinsic Metrics to Evaluate Accuracy and Facilitation in Computer Assisted Coding.” Computer-Assisted Coding Software Standards Workshop. Arlington, VA: AHIMA, 2006. - Lai, J., and J. Vergo. “MedSpeak: Report Creation with Continuous speech Recognition.” Proceedings of CHI ’97 (pp. 431–438). Atlanta, GA: ACM Press, 1997. - Norman, D. A. The Psychology of Everyday Things. New York: Harper & Row, 1988. - Reason, J. T. Human Error. New York: Cambridge University Press, 1990. - Linstone, H. A., and M. Turoff. The Delphi Method: Techniques and Applications. 2002. Available at the Delphi Method: Techniques and Applications Web site at http://is.njit.edu/pubs/delphibook/index.html (retrieved August 13, 2007). - Resnik, P., M. Niv, M. Nossal, G. Schnitzer, J. Stoner, A. Kapit, et al. “Using Intrinsic and Extrinsic Metrics to Evaluate Accuracy and Facilitation in Computer Assisted Coding.” - Familant, M. E. United States Patent No. 44617. 2007. - Kosorukoff, A. “Human-based Genetic Algorithm.” IEEE Transactions on Systems, Man, and Cybernetics (2001): 3464–3469. - von Ahn, L., and L. Dabbish. “Labeling Images with a Computer Game.” ACM CHI (2004): 319–326. - von Ahn, L., M. Kedia, and M. Blum. (2006). “Verbosity: A Game for Collecting Common-Sense Knowledge.” ACM Conference on Human Factors in Computing Systems, CHI Notes (2006): 75-78. Kikano, G. E., M. A. Goodwin, and K. C. Stange. “Evaluation and Management Services: A Comparison of Medical Record Documentation with Actual Billing in a Community Family Practice.” Archives of Family Medicine 9, no. 1 (2000): 68–71. Morsch, M., D. Heinze, and D. Byrd. “Factors in Deploying Automated Tools for Clincal Abstraction and Coding.” IT in Health Care: Sociotechnical Approaches. Second International Conference. Portland, OR: IT in Health Care, 2004. Norman, D. A. “Categorization of Action Slips.” Psychological Review 88 (1981): 1–15. Zuber, T. J., C. E. Rhody, T. A. Muday, et al. “Variability in Code Selection Using the 1995 and 1998 HCFA Documentation Guidelines for Office Services.” Journal of Family Practice 49, no. 7 (2000): 642–645. Article citation: Perspectives in Health Information Management, CAC Proceedings; Fall 2008	3	18	1	0	0	0.165269	1	4,314
Home Sleep Apnea Tests (HSAT) have increased in usage and based on recent estimates amount to about a third of all sleep apnea tests due to their cost-effectiveness and accessibility in comparison to in-lab, HCP-monitored Polysomnography testing. An HSAT is a preference for many patients since they can take the test at home in a more natural, relaxing and private environment that is also more likely to reflect the actual disease manifestation. Today, the vast majority of payers reimburse for HSAT and some recommend it as a first-line diagnosis for sleep apnea. However, coding and billing requirements differ from payer to payer. This article will outline some of the basics, but it is always best to check with your payer for their specific requirements With a few exceptions, licensed medical doctors, regardless of their specialty, can prescribe HSAT to patients who are suspected of having sleep apnea based on signs and symptoms and testing positive for high risk on validated instruments such as the STOP-BANG, Epworth Sleepiness, and DOISNORE 50 questionnaires. Physicians may also consider clinical symptoms such as atrial fibrillation and hypertension as signs for high pre-test probability, based on the most recent AASM guidelines.1 HST G CODES AND CPT CODES In 2007 the AASM published the “Clinical Guidelines for the Use of Unattended Portable Monitors in the Diagnosis of Obstructive Sleep Apnea in Adult Patients.”2 which differentiated the HSATs by type (defined by the AASM). In the following year, Medicare introduced the HCPCS Level II codes G0398, G0399, and G0400 which followed the AASM types. G codes are “carrier determined,” which means that payment is up to the discretion of the Medicare Administrative Contractors (MACs). G CODES / SLEEP TYPE CLASSIFICATION G0398 Home sleep study with type II portable monitor, unattended; minimum of 7 channels: EEG, EOG, EMG, ECG/heart rate, airflow, respiratory effort, and oxygen saturation. G0399 Home sleep study with type III portable monitor, unattended; minimum of 4 channels: 2 respiratory movement/airflow, 1 ECG/heart rate, and 1 oxygen saturation. G0400 Home sleep study with type IV portable monitor, unattended; minimum of 3 channels. In 2009, Centers for Medicare and Medicaid Services (CMS) issued a National Coverage Determination (NCD) which included the WatchPAT® as a covered test. Today, most CMS MACs request the use of G codes to report HSATs and request the use of G0400 to report WatchPAT.3 In 2011, the AMA added the CPT codes 95800 and 95801 to describe HSAT using peripheral arterial tone (i.e. WatchPAT®). Note that WatchPAT® records sleep time so CPT 95800, not 95801, should be used to report HSAT using WatchPAT®. Most commercial payers request the use of 95800 to report WatchPAT®. 95800 Sleep study, unattended, simultaneous recording; heart rate, oxygen saturation, respiratory analysis (e.g. by airflow or peripheral arterial tone), and sleep time. 95801 Sleep study, unattended, simultaneous recording; heart rate, oxygen saturation, respiratory analysis (e.g. by airflow or peripheral arterial tone). In 2017 AASM clarified their position in a guideline, noting that the types of classification fail to consider new technologies such as peripheral arterial tonometry (PAT). They proposed another classification scheme but acknowledged that it has not been utilized by many. The AASM concluded that devices that measure PAT, actigraphy, and oximetry are technically adequate to diagnose OSA, and therefore recommended that physicians use such HSATs to diagnose OSA.1 The bottom line is that there are multiple codes that can be used to report HSAT. Typically, CMS requests that WatchPAT® be reported with G0400 and commercial payers request 95800. Since HSAT may be reported by more than one code, it is best to refer to the payer’s medical policy to ensure you are reporting the correct code. In upcoming newsletter editions, we will explore additional topics including when to bill the global, technical, and professional components of the code, credentialing, and accreditation issues. - Kapur et al., Clinical Practice Guideline for Diagnostic Testing for Adult Obstructive Sleep Apnea: An American Academy of Sleep Medicine Clinical Practice Guideline, 13 J. CLIN. SLEEP MED. 479 (Mar. 15, 2017). - Clinical Guidelines for the Use of Unattended Portable Monitors in the Diagnosis of Obstructive Sleep Apnea in Adult Patients. JCSM Journal of Clinical Sleep Medicine, Vol. 3, No. 7, 2007. - CMS Pub 100-03 Medicare National Coverage Determinations (NCD) – Sleep Testing for Obstructive Sleep Apnea (OSA). Transmittal R103NCD March 3, 2009.	4	14	9	8	0	0.833249	17	1,093
The complement system consists of a series of soluble proteins derived from the liver that play a key role in eradication of foreign invaders. Activation of the system results in the production of the cytolytic membrane attack complex (MAC), leading to death of targeted cells via cell lysis. This system plays a key role in the prevention of infection by being involved in the recognition, opsonization and lysis of microorganisms and foreign pathogens. Complement activation can occur by one of three pathways: classical, lectin and alternate pathways. The classical pathway is initiated when C1q (a pattern recognition molecule) binds to immunoglobulin in immune complexes, to C-reactive protein on self or microbial surfaces, or directly to molecules expressed on microbial membranes. This complex activates C1r, which becomes enzymatically active and cleaves C1s. C1s then activates C2 and C4, releasing C2a, C2b, C4a, and C4b. C2b and C4b become joined to form C3 convertase, C4b2b. C2 is similar (and related) to complement factor B (CFB), while C4 is similar (and related) to C3. The C4b2b molecule is functionally similar to C3bBb. C5 is the fifth component of complement, which plays an important role in inflammatory and cell killing processes. This protein is composed of alpha and beta polypeptide chains that are linked by a disulfide bridge. An activation peptide, C5a, which is an anaphylatoxin that possesses potent spasmogenic and chemotactic activity, is derived from the alpha polypeptide via cleavage with a convertase. The C5b macromolecular cleavage product can form a complex with the C6 complement component, and this complex is the basis for formation of the membrane attack complex, which includes additional complement components. The C5 convertase cleaves C5 into its two active components C5a and C5b. The result of this cleavage is the release of a C5a fragment, a potent inflammatory molecule, and activation of C5b, which initiates the MAC. The MAC is initiated when the complement protein C5 convertase cleaves C5 into C5a and C5b. Another complement protein, C6, binds to C5b. The C5bC6 complex is bound by C7 and finally C8C8 alpha-gamma induces the polymerization of 10 to 16 molecules of C9 into the complex called MAC. Initiation of the lectin pathway occurs when pattern recognition molecules (any of mannose-binding lectin (MBL), L-ficolin, H-ficolin, or M-ficolin) bind to the exterior surfaces of bacteria. The alternative pathway is continuously activated by spontaneous hydrolysis of the internal thioester bond in C3 to form C3(H20). This molecule, although not cleaved, can fulfill the same role as C3b in C3 convertase. C3(H20) binds to CFB, and this complex is cleaved by the complement serine protease factor D (CFD), resulting in splitting of the CFB protein into Ba and Bb fragments. C3(H20)Bb is a C3 convertase, which splits C3 into C3a and C3b. Once produced by these means, C3b perpetuates the positive feedback loop described above, joining CFB to form more convertase enzyme. Newly cleaved C3b is also deposited on nearby surfaces. C3(H20)Bb is a less efficient enzyme than C3bBb, but is less easily inactivated by complement factor H (CFH) and its cofactor complement factor I (CFI). Tight regulation of the complement cascade is necessary to prevent immune mediated disease and off-target damage of non-infected host cells. The balance between complement activation and inhibition is mediated by a series of regulatory proteins. CFH is critical inhibitor of the complement pathway that ensures the system targets foreign rather than host cells by neutralizing activated complement proteins that adhere to normal host cells. AMD and Complement The leading cause of vision loss in industrialized countries is age-related macular degeneration and its prevalence is increasing with the aging of the population.1,2 The defect in AMD is thought to lie in the outer retina and retinal pigment epithelium, and genetic predisposition, age, ischemia and environmental factors may play a role in its development.3,4 Several recent studies have reported an association between AMD and key proteins in the complement cascade. For example, a variation in the gene encoding CFH, the key inhibitor of complement mediated damage to non-pathologic cells, produces a nearly fivefold increase in the risk of AMD for individuals who harbor the Y402H polymorphism.5-8 The products of complement activation have been detected in blood in AMD patients. Hendrik P. N. Scholl and colleagues found that C3d, CFB and CFD were significantly increased in patients with AMD.9 The presence of activation products in circulating blood indicates that the inflammation found in AMD is not limited to the retina, but is systemic. The extent of this systemic complement activation in AMD is currently unknown. Mutations in complement-related genes including CFB, C2 and C3 have been associated with AMD.10 However, mutations in the CFH gene appear to have the greatest link to AMD.5-8 The CFH gene forms part of the RCA (regulators of complement activation) gene cluster located in the 1q32 chromosomal region of the human genome. The Y402H genetic variant of CFH gene is commonly associated with AMD. Genetic studies suggest that there may be further variants in the region associated with altered risk that have not yet been uncovered. Local complement system in the human RPE-choroid complex has also been described. Cells within the neural retina, RPE and choroid demonstrated gene expression profiles consistent with replication of the complete cohort of complement components and regulatory proteins associated with both the classical and alternative pathways.11 Components of the complement system have also been identified in drusen.12,13 Druse in AMD contain almost all alternative complement pathway proteins, including CFH, C3, and the products of its activation and degradation, as well as the terminal pathway proteins C5, C6, C7, C8, C9, separately and in combination as the MAC. An implication of this hypothesis relates to the finding that homozygous individuals for the most common CFH risk allele (Y402H) tend to concurrently manifest raised levels of choroidal C-reactive protein, a serum biomarker for inflammation,14 and in patients with both problems an increased risk of AMD progression.15 Thus, since dysfunction of the local complement system is associated with AMD, the RPE-choroid complex is a potential location for the delivery of novel therapeutic agents that target the complement cascade. Current Role of Complement-Based Therapies A number of AMD therapies are being developed to target specific components of the complement cascade. Complement therapies also have the potential to work at an earlier stage in the disease process, preventing progression to late AMD. However, modulation of the complement cascade may adversely affect the body’s defense mechanisms. Hence, any new therapeutic modality must affect AMD without adversely affecting the body’s immunological function. The use of local complement component inhibitors minimizes potential systemic side effects of complement inhibition. However, local inhibition of complement via intravitreal injections may have a shorter half-life and more local adverse effects, and may not be feasible in a life-long disease such as AMD. Some companies are evaluating nucleic acid aptamers that are synthetically derived and demonstrate desirable therapeutic properties largely owing to their three-dimensional structure, high target specificity, and high binding affinity. Others are using monoclonal antibodies that are laboratory-engineered clones of immunoglobulins designed to bind to specific target cell surfaces. They inhibit specific molecules or activate the immune system. Monoclonal antibody-based complement inhibitors exhibit similar molecular recognition characteristics, but they also have the potential to provoke an immunogenic response, which does not occur with aptamer compounds. Some of the medications that are on the horizon and show potential in the management of AMD include: • Eculizumab (Soliris, Alexion Pharmaceuticals, Cheshire, Conn.) is an orphan drug that is marketed for intravenous treatment of paroxysmal nocturnal hemoglobinuria (PNH), and received FDA approval in 2007 as the only licensed monoclonal antibody that targets the complement system. The molecule has been humanized to minimize immunogenicity and increase drug half-life, but was originally derived from a murine C5 antibody. This drug binds to C5 and prevents downstream activation and formation of MAC. The drug is administered intravenously over six months; weekly dosing during the initial induction period followed by two weekly maintenance doses. The COMPLETE (Complement inhibition of systemic Eculizumab for the treatment of Non-Exudative Age-Related Macular Degeneration) study at Bascom Palmer (Yehoshua Z, et al IOVS 2012;53:ARVO E-Abstract 2046) is one of the first to study the use of systemic complement inhibition for the treatment of dry AMD. (See Retinal Insider, September 2012 for more on the COMPLETE Trial.) Their results involving 30 eyes of 30 patients at six months showed that systemic treatment with eclizumab did not decrease drusen volume. In the same study, systemic use of eclizumab did not decrease the growth rate of geographic atrophy. Their explanations for lack of treatment effect for GA in this population included the possibility that complement activation may have no role in growth of GA; or the study duration was too short; or a higher drug dose was needed; inadequate penetration into the eye; different complement target needed; or that they used an inappropriate endpoint. These results were from a single study and involved administering systemic medication in just 30 eyes of 30 patients, and the power of the study may not be adequate to appropriately assess the role of C5 inhibition in dry AMD. Further studies are indicated in assessing the role of eclizumab in dry AMD. • POT-4 (Alcon), a derivative of compstatin, is a potent C3 inhibitor that suppresses complement activation by preventing the formation of key elements within the proteolytic cascade, thus impeding local inflammation, upregulation of angiogenic factors and subsequent tissue damage. POT-4 is administered intravitreally, which may limit possible unwanted systemic effects. Early results of POT-4 suggest that it manifests a good safety profile and drug tolerability. (Kaushal S, et al IOVS 2009;50:ARVO e-abstract 5010.) It is currently in Phase II clinical trials. • ARC1905 (Ophthotech, New York, N.Y.) is an aptamer-based C5 inhibitor, blocking the cleavage of C5 into C5a and C5b fragments and is another intravitreally administered complement inhibitor being evaluated in AMD. Like POT-4, it is similarly selective for a centrally positioned component within the cascade, although exerting its effect further downstream. • FCFD4514S (Genentech) is an anti-factor D antibody being studied for the treatment of dry AMD. Blockage of the complement factors (such as factor D) that moderate the production of these end-products serves to attenuate complement activation, rather than shutting the system down completely. Anti-factor D is administered intravitreously and selectively inhibits CFD which is a key component of the amplification step of the alternatve pathway. It is currently in Phase II testing for dry AMD. • TA106 (Taligen Therapeutics; Alexion Pharmaceuticals, Cheshire, Conn.) is a CFB inhibitor, still in pre-clinical development, that is primarily being investigated as an inhaled formulation in the treatment of severe, chronic asthma refractory to current therapies and is recently being studied for macular degeneration.16 • JSM-7717 (EvaluatePharma) and JPE-1375 (Jerini AG; Berlin, Germany) are two peptidomimetic C5a receptor (which is pro-inflammatory) antagonists currently in preclinical assessment for AMD.17 Receptor antagonists competitively bind to the C5a receptor neutralizing interaction, and hence such drugs have the potential to suppress the inflammatory response without adversely affecting complement-related immunity and are being used in pre-clinical studies.18 • Intravenous administration of CR2-fH, a recombinant form of CFH, was associated with a reduction in CNV size and the physiological sequelea of CNV on retinal function. The effectiveness of this approach in a mouse model of laser-induced AMD was recently elucidated.19 This strategy involves the supplementation of wild-type CFH with a recombinant “protective” form of the protein in high-risk variant cases. In theory, such augmentation should be helpful in re-instituting homeostatic regulation of the alternative pathway of the complement system. This drug is being studied in animal models and is part of ongoing pre-clinical experiments. • C1INH (ViroPharma Inc., Exton, Pa.) received FDA approval for the treatment of hereditary angioneurotic edema in 2008. Mutations in the gene that encodes SERPING1, a C1-inhibitor (C1INH) may similarly play a role in the development of AMD.20 A recent study showed that C1INH is present in the human retina and choroid, and AMD affection status was correlated with increased levels of the protein in the choroid.20 This drug, although not being used clinically, has the potential to be used in AMD. Thus, there is substantial evidence now that the complement system plays a role in the pathogenesis of AMD, but its exact role is uncertain. A number of drugs are being developed that target various components of the complement cascade, predominantly the alternate complement pathway. The complement cascade remains as one of the many therapeutic targets in AMD, and our understanding of its role in AMD is still primitive. However, emerging drugs that target the complement cascade are promising and may play a vital role in the prevention and management of this condition in the future. Dr. Kaiser is a consultant to Alcon, Novartis, Genentech, Ophthotech, Allegra, Bayer, Regeneron and ArcticDx; he reports a financial interest in SKS Ocular, LLC. Contact him at Cole Eye Institute, 9500 Euclid Ave., Desk i3. Cleveland, Ohio 44195. Phone: (216) 444-6702, e-mail: [email protected]. 1. La Cour M, Kiilgaard JF, Nissen MH. Age-related macular degeneration: Epidemiology and optimal treatment. Drugs Aging 2002;19:101-133. 2. Klein R, Klein BE, Lee KE, Cruickshanks KJ, Gangnon RE. Changes in visual acuity in a population over a 15-year period: The Beaver Dam Eye Study. Am J Ophthalmol 2006;142:539-549. 3. Klein RJ, Zeiss C, Chew EY, et al. Complement factor H polymorphism in age-related macular degeneration. Science 2005;308:385-389. 4. Mori K, Horie-Inoue K, Kohda M, et al. Association of the HTRA1 gene variant with age-related macular degeneration in the Japanese population. J Hum Genet 2007;52:636-641. 5. Hageman GS, Anderson DH, Johnson LV et al. A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci USA 2005;102:7227-32. 6. Klein RJ, Zeiss C, Chew EY et al. Complement factor H polymorphism in age-related macular degeneration. Science 2005;308:385-9. 7. Edwards AO, Ritter RR, Abel KJ, Manning A, Panhuysen C, Farrer LA. Complement factor H polymorphism and age-related macular degeneration. Science 2005;308:421-4. 8. Haines JL, Hauser MA, Schmidt S et al. Complement factor H variant increases the risk of age-related macular degeneration. Science 2005;308:419-21. 9. Scholl HP, Charbel Issa P, Walier M, Janzer S, Pollok-Kopp B, Borncke F et al. Systemic complement activation in age-related macular degeneration. PLoS One 2008;3:e2593. 10. Yates JR, Sepp T, Matharu BK et al. Complement C3 variant and the risk of age-related macular degeneration. N Engl J Med 2007;357:553-61. 11. Anderson DH, Radeke MJ, Gallo NB et al. The pivotal role of the complement system in aging and age-related macular degeneration: Hypothesis re-visited. Prog Retin Eye Res 2010;29:95-112. 12. Hageman GS, Luthert PJ, Victor Chong NH, Johnson LV, Anderson DH, Mullins RF. An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch’s membrane interface in aging and age-related macular degeneration. Prog Retin Eye Res 2001;20:705-732. 13. Persson BD, Schmitz NB, Santiago C, Zocher G, Larvie M, Scheu U et al. Structure of the extracellular portion of CD46 provides insights into its interactions with complement proteins and pathogens. PLoS Pathog 2010; 6:e1001122. 14. Johnson PT, Betts KE, Radeke MJ, Hageman GS, Anderson DH, Johnson LV. Individuals homozygous for the age-related macular degeneration risk-conferring variant of complement factor H have elevated levels of CRP in the choroid. Proc Natl Acad Sci USA 2006;103:17456-61. 15. Robman L, Baird PN, Dimitrov PN, Richardson AJ, Guymer RH. C-reactive protein levels and complement factor H polymorphism interaction in age-related macular degeneration and its progression. Ophthalmology 2010;117:1982-88. 16. Taube C, Thurman JM, Takeda K et al. Factor B of the alternative complement pathway regulates development of airway hyperresponsiveness and inflammation. Proc Natl Acad Sci USA 2006;103:8084-8089. 17. Schnatbaum K, Locardi E, Scharn D et al. Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: Increased receptor specificity and in vivo activity. Bioorg Med Chem Lett 2006;16:5088;92. 18. Allegretti M, Moriconi A, Beccari AR et al. Targeting C5a: Recent advances in drug discovery. Curr Med Chem 2005;12:217-36. 19. Rohrer B, Long Q, Coughlin B et al. A targeted inhibitor of the alternative complement pathway reduces angiogenesis in a mouse model of age-related macular degeneration. Invest Ophthalmol Vis Sci 2009;50:3056-64. 20. Mullins RF, Faidley EA, Daggett HT, Jomary C, Lotery AJ, Stone EM. Localization of complement 1 inhibitor (C1INH/SERPING1) in human eyes with age-related macular degeneration. Exp Eye Res 2009;89:767-73.s.	2	7	2	0	4	0.427472	6	4,257
Depression ICD-10 is a World Health Organization medical classification for conditions that fall into the mental, behavioral and neurodevelopmental disorders space. Many conditions from mild to severe depression, seasonal affective disorder, and postpartum depression, among others, fall into this category – all with their individual Depression ICD-10 designations. Diagnosis is determined by the inclusion and severity of numerous symptoms based on the Diagnostic, and Statistical Manual of Mental Disorders fifth edition. Depression is often used in everyday speech to describe feelings of sadness or melancholy. While feeling sad is often a primary symptom of depressive disorders, the clinical features are much more complicated and their expression is much more severe. Depressive disorders can negatively impact careers, relationships, and even your willingness to live. Besides anxiety disorders, depressive disorders are the most common in the world. It is estimated that 9.5 percent of American adults will have a depressive disorder each year. The following are the most well-known depressive disorders as found in the International Statistical Classification of Diseases and Related Health Problems 10th Revision (Depression ICD-10). F32 Depressive Episode When someone describes depression, they are most likely referring to a depressive episode. An estimated 21 million adults in the United States have had at least one depressive episode. That is 8.4 percent of the adult American population. The prevalence of a depressive episode is much higher among females (10.5 percent) when compared to males (6.2 percent). Depression ICD-10 codes: Severe depression w/o psychotic symptoms Severe depression with psychotic symptoms Recurrent Depressive Disorder, Mild Recurrent Depressive Disorder, Moderate Recurrent Depressive Disorder, Severe without psychotic symptoms Recurrent Depressive Disorder, Severe with psychotic symptoms Seasonal Affective Disorder Dysthymia or Persistent Depressive Disorder Depression ICD-10 Criteria and Symptoms In the ICD-10, a depressive episode involves 10 symptoms. The first three are key symptoms. At least one of these symptoms must be present most of the time for at least two weeks: - Persistent sadness or low mood - Loss of interest or pleasure - Fatigue or low energy The next seven symptoms will determine the severity of the episode and the exact Depression ICD-10 code: - Disturbed sleep - Poor concentration or indecisiveness - Low self-confidence - Poor or increased appetite - Suicidal thoughts or acts - Agitation or slowing of movements - Guilt or self-blame The above seven symptoms should be present for a month or more for most of every day. F32.0 Mild Depression Mild depression is the presence of two or three symptoms F32.1 Moderate Depression Moderate depression is four to six symptoms F32.2 Severe Depression Without Psychotic Symptoms Severe depression is seven or more symptoms F32.3 Severe Depression With Psychotic Symptoms Same as F32.2 with the presence of psychotic symptoms, such as delusions and/or hallucinations. A lot of mental health disorders have depressive symptoms. It is easy to mistake them for a depressive episode if you don’t pay close attention. For example, bipolar disorder is made up of a depressive episode paired with a manic episode but they often occur months apart. If the client is currently feeling depressed, it can be easily misdiagnosed as only a depressive episode. In this case, it is critical to examine the client’s personal and family history. It is essential for clinicians to get the full picture of their clients for accurate diagnosis. F33 Recurrent Depressive Disorder As the name suggests, recurrent depressive disorder is a depressive episode that happens more than once. The recurrence of a depressive episode is approximately 35 percent after 15 years. There are not many restrictions for a recurrence. The first episode may occur at any age and happen again at any time. It may initially be diagnosed as a depressive episode but must be changed to recurrent if it happens more than once. The severity of the disorder is based on the most recent occurrence. For instance, if the current depressive episode is moderate, then it will be diagnosed as F33.1, recurrent depressive disorder, current episode moderate. This is true even if past episodes were more or less severe. Similar to a single depressive episode, other severity codes include F33.0, recurrent depressive disorder, current episode mild, and F33.2, recurrent depressive disorder, current episode severe without psychotic symptoms. F33.3 is severe with psychotic symptoms. F34.1 Dysthymia (Persistent Depressive Disorder) Dysthymia is now categorized as a persistent depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) and is slightly less severe than a depressive disorder but is usually longer lasting. An estimated 1.5 percent of American adults had persistent depressive disorder in the past year and 2.5 percent will experience it at some time in their lives. - Depressed mood for most of the day every day for at least 2 years - Three of the following symptoms: - Loss of interest or pleasure in enjoyable activities - Fatigue or low energy - Disturbed sleep - Poor concentration or indecisiveness - Low self-confidence or self-esteem - Feelings of hopelessness - Social withdrawal - Less talkative than before - Pessimistic about the future or ruminating about the past - Inability to cope with routine responsibilities Dysthymia may be confused with a recurring mild depressive episode but— unlike the DSM-5—the depression ICD-10 designates that dysthymia doesn’t reach the severity level of a mild depressive episode. Additionally, you can have periods of non-depressed mood but they can only rarely last more than a few weeks for an accurate dysthymia diagnosis Diagnostic note: In the Diagnostic, and Statistical Manual of Mental Disorders fifth edition (DSM-5) dysthymia and chronic major depressive disorder have been consolidated into one disorder but that is not the case in the depression ICD-10 and the upcoming ICD-11. F53.0 Postpartum Depression Postpartum depression (PPD) is a recent addition to the ICD-10. It affects approximately 10–15 % of mothers yearly. Depressive symptoms last more than 6 months for 25–50 percent of those affected. Criteria and PPD symptoms - The symptoms of postpartum depression are the same criteria as for a depressive episode except. - Onset of symptoms occurs up to 4 weeks after delivery of a baby. It should be noted that this diagnosis is a work in progress and many people believe that PPD is more complicated than a depressive episode that happens in the month after childbirth. Mothers (and some fathers) report issues such as a lack of infant attachment and feeling disconnected from their partner, but these are not included in the formal diagnosis of postpartum depression in the current depression ICD-10 or DSM-5. It is important to distinguish PPD from the “baby blues”. Up to 70 percent of all new mothers experience the “baby blues,” but the features are not as severe or long-lasting. Symptoms may include: crying for no apparent reason, irritability, and anxiety. These indicators usually clear up within a week or two post-pregnancy without treatment. What is Seasonal Affective Disorder (SAD)? Often discussed as the “winter blues”, SAD gets a lot of attention, especially in cold weather. It is estimated that 5 percent of Americans experience seasonal depression each year. It is identified in the DSM-5 as a major depressive disorder with seasonal patterns. The depression ICD-10, however, does not have its own category for SAD. Instead, it is often diagnosed under F33.9, major depressive disorder, recurrent, unspecified. Depression ICD-10 codes are one of the most frequently used diagnostic codes in the mental health space but can be easily misdiagnosed. Practice software that helps clinicians easily find Depression ICD-10 codes and transfer them to paperwork is a big advantage. TheraPlatform provides a painless lookup of depression ICD-10 codes and will auto-populate them to the relevant documentation, billing, and claims. It makes diagnosing mental disorders, such as depression, a much simpler task. - PTSD ICD-10 - Suicidal ideation ICD-10 - Adjustment disorders ICD-10 - The Ultimate Insurance Billing Guide for Therapists - The Ultimate Teletherapy E-book - Therapy Resources	4	8	0	0	13	0.970431	13	1,818
A stroke occurs when a blood vessel in the brain is blocked or bursts. Without blood and the oxygen it carries, part of the brain starts to die. The part of the body controlled by the damaged area of the brain can't work properly. Brain damage can begin within minutes. That's why it's so important to know the symptoms of stroke and to act fast. Quick treatment can help limit damage to the brain and increase the chance of a full Symptoms of a stroke happen quickly. A stroke may cause: If you have any of these symptoms, call 911 or other emergency services right away. See your doctor if you have symptoms that seem like a stroke, even if they go away quickly. You may have transient ischemic attack (TIA), sometimes called a mini-stroke. A TIA is a warning that a stroke may happen soon. Getting early treatment for a TIA can help prevent a stroke. There are two types of You need to see a doctor right away. If a stroke is diagnosed quickly—right after symptoms start—doctors may be able to use medicines that can help you recover better. The first thing the doctor needs to find out is what kind of stroke it is: ischemic or hemorrhagic. This is important, because the medicine given to treat a stroke caused by a blood clot could be deadly if used for a stroke caused by bleeding in the brain. find out what kind of stroke it is, the doctor will do a type of X-ray called a CT scan of the brain, which can show if there is bleeding. The doctor may order other tests to find the location of the clot or bleeding, check for the amount of brain damage, and check for other conditions that can cause symptoms similar to a stroke. For an ischemic stroke, treatment focuses on restoring blood flow to the brain. If you get to the hospital right away after symptoms begin, doctors may use a medicine that dissolves blood clots. Research shows that this medicine can improve recovery from a stroke, especially if given within 90 minutes of the first symptoms.1 Other medicines may be given to prevent blood clots and control symptoms. hemorrhagic stroke can be hard to treat. Doctors may do surgery or other treatments to stop bleeding or reduce pressure on the brain. Medicines may be used to control blood pressure, brain swelling, and other After either kind of stroke and after your condition is stable, treatment shifts to preventing other problems and future strokes. You may need to take a number of medicines to control conditions that put you at risk for stroke, such as high blood pressure or atrial fibrillation. Some people need to have a surgery to remove plaque buildup from the blood vessels that supply the brain (carotid arteries). The best way to get better after a stroke is to start stroke rehabilitation (rehab). The goal of stroke rehab is to help you regain skills you lost or to make the most of your remaining abilities. Stroke rehab can also help you take steps to prevent future strokes. You have the greatest chance of regaining abilities during the first few months after a stroke. So it is important to start rehab soon after a stroke and do a little After you have had a stroke, you are at risk for having another one. But you can make some important lifestyle changes that can reduce your risk of stroke and improve your overall Learning about stroke: Living with stroke: Health Tools help you make wise health decisions or take action to improve your health. ischemic stroke is caused by a blood clot that blocks blood flow to the brain. Low blood pressure may also cause an ischemic stroke, although this is less common. Low blood pressure results in reduced blood flow to the brain. It may be caused by narrowed or diseased arteries, a heart attack, a large loss of blood, or a severe infection. Some surgeries (such as endarterectomy) or other procedures (such as carotid artery stenting) that are used to treat narrowed carotid arteries may cause a blood clot to break loose, resulting in a stroke. hemorrhagic stroke is caused by bleeding in or around the Other less common causes include head or neck injuries, certain diseases, and radiation treatment for cancer in the neck or brain. If you have symptoms of a stroke, call 911 or other emergency services right away. General symptoms of a Symptoms can vary depending on whether the stroke is caused by a blood clot (ischemic stroke) or bleeding (hemorrhagic stroke), where the stroke occurs in the brain, and how bad it is. A stroke usually happens suddenly but may occur over hours. For example, you may have mild weakness at first. Over time, you may not be able to move the arm and leg on one side of your body. If several smaller strokes occur over time, you may have a more gradual change in walking, balance, thinking, or behavior. This is called multi-infarct dementia. It isn't always easy for people to recognize symptoms of a small stroke. They may mistakenly think the symptoms can be attributed to aging. Or the symptoms may be confused with those of other conditions that cause similar symptoms. When you have an ischemic stroke, the oxygen-rich blood supply to part of your brain is reduced. hemorrhagic stroke, there is bleeding in the After about 4 minutes without blood and oxygen, brain cells become damaged and may die. The body tries to restore blood and oxygen to the cells by enlarging other blood vessels (arteries) near If blood supply isn't restored, permanent damage usually occurs. The body parts controlled by those damaged cells cannot function. This loss of function may be mild or severe. It may be temporary or permanent. It depends on where and how much of the brain is damaged and how fast the blood supply can be returned to the affected cells. Life-threatening complications may also occur. This is why it's important to get treatment as soon as possible. depends on the location and amount of brain damage caused by the stroke, the ability of other healthy areas of the brain to take over for the damaged areas, and rehabilitation. In general, the less damage there is to the brain tissue, the less disability results and the greater the chances of a successful recovery. Stroke is the most common nervous-system–related cause of physical disability. Of people who survive a stroke, half will still have some disability 6 months after the stroke. You have the greatest chance of regaining your abilities during the first few months after a stroke. Regaining some abilities, such as speech, comes slowly, if at all. About half of all people who have a stroke will have some long-term problems with talking, understanding, and decision-making. They also may have changes in behavior that affect their relationships with family and friends. After a stroke, you (or a caregiver) may also notice: complications of a stroke, such as pneumonia, may develop right away or months to years after a stroke. Some long-term problems may be prevented with proper home treatment and medical follow-up. For more information, see Home Treatment. A risk factor is anything that makes you more likely to have a particular health problem. Risk factors for stroke that you can treat or change include: Risk factors you cannot change Call 911 or other emergency services now if you have signs of a stroke: Signs of a transient ischemic attack (TIA) are similar to signs of a stroke. But TIA symptoms usually disappear after 10 to 20 minutes, although they may last longer. There is no way to tell whether the symptoms are caused by a stroke or by TIA, so emergency medical care is needed for both conditions. Call your doctor right away if you: Call your doctor for an appointment if you: Doctors who can diagnose and treat stroke If you need surgery or have other health problems, other specialists may be consulted, such as a: Some hospitals have a stroke team made up of many different health professionals, such as a neurologist, a neuroradiologist, a physical therapist, an occupational therapist, a speech therapist, a rehabilitation doctor (physiatrist), a nurse, and a social worker. To prepare for your appointment, see the topic Making the Most of Your Appointment. The first test after a stroke is CT scan, a series of X-rays that can show whether there is bleeding in the brain. This test will show whether the stroke is ischemic or hemorrhagic. You may also have an MRI. Other initial tests recommended for ischemic stroke include: If it seems that you may have a narrowing of carotid artery, your doctor may want you to have a: If your doctor believes that the stroke may have been caused by a problem with your heart, an Holter monitoring or telemetry test may be done. Guidelines recommend that risk factors for heart disease also be assessed after a stroke to prevent disability or death from a future heart problem. This is because many people who have had a stroke also have coronary artery disease. Measures will be taken to stabilize your vital signs, including giving you medicines. Treatment includes efforts to control bleeding, reduce pressure in the brain, and stabilize vital signs, especially blood pressure. Your treatment will also focus on stroke. This may include: You may also need to make lifestyle changes such as quitting smoking, eating heart-healthy foods, and being more active. For more information, see Prevention. rehab program as soon as possible after a stroke increases your chances of regaining some of the abilities you possible to predict how much ability you will regain. The more ability you retain immediately after a stroke, the more independent you are likely to be when you are discharged from the hospital. If your doctor wants to find out how the stroke has affected your ability to reason, concentrate, or remember, you may have neuropsychological tests. rehab will be based on the physical abilities that were lost, your general health before the stroke, and your ability to participate. Rehab begins with helping you resume activities of daily living, such as eating, bathing, and dressing. For more information, see the topic If you are someone whose loved one has had a stroke, you can play an important role in that person's recovery by providing support and encouragement. If you get worse, your loved ones may need to move you to a care facility that can meet your needs, especially if your caregiver has his or her own health problems that make it difficult to properly care for you. It is common for caregivers to neglect their own health when they are caring for a loved one who has had a stroke. If your caregiver's health declines, the risk of injury to you and your caregiver may increase. You can help prevent a stroke if you control risk factors and treat other medical conditions that can lead to a These are some of the common risk factors for stroke: Your doctor will probably prescribe several medicines after you have had a stroke. Medicines to prevent blood clots are typically used, because blood clots can cause TIAs and strokes. The types of medicines that prevent clotting are: Cholesterol-lowering and blood-pressure–lowering medicines are also used to prevent TIAs and strokes. Anticoagulants such as warfarin (for example, Coumadin) prevent blood clots from forming and keep existing blood clots from getting bigger. You may need to take this type of medicine after a stroke if you have atrial fibrillation or another condition that makes you more likely to have another stroke. For more information, see the topic Atrial Fibrillation. Antiplatelet medicines keep platelets in the blood from sticking together. Statins lower cholesterol and can greatly reduce your risk of having another stroke. Statins even protect against stroke in people who do not have heart disease or high cholesterol.2 If you have high blood pressure, your doctor may want you to take medicines to lower it. Blood pressure medicines include: Medicines used to treat depression and pain may also be prescribed after a stroke. When surgery is being considered after a stroke, your age, prior overall health, and current condition are major factors in the decision. If you have serious blockage in the carotid arteries in your neck, you may need a carotid endarterectomy. During this surgery, a surgeon removes plaque buildup in the carotid arteries. The benefits and risks of this surgery must be carefully weighed, because the surgery itself may cause a stroke. Treatment for hemorrhagic stroke may include surgery to: Carotid artery stenting (also called carotid angioplasty and stenting) is sometimes done as an alternative to surgery to prevent stroke. In this procedure, a doctor threads a thin tube called a catheter through an artery in the groin and up to the carotid artery in your neck. The doctor then uses a tiny balloon to enlarge the narrowed portion of the artery and places a stent to keep the artery open. Carotid artery stenting is not as common as carotid endarterectomy, a type of surgery. The National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health, is the leading U.S. federal government agency supporting research on brain and nervous system disorders. It provides the public with educational materials and information about these disorders. This association provides information and referrals to local self-help groups for people who have had a stroke and for their families. Pamphlets and other information can be obtained by calling the Dallas office (toll-free). 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. Nursing Home Compare is a website with information about every Medicare- and Medicaid-certified nursing home in the country. The site allows you to search for nursing homes by name, city, county, state, or ZIP code. It also allows you to compare the quality of nursing homes using a five-star rating. The site also has information on alternatives to nursing homes, such as home care or assisted living. The Centers for Medicare and Medicaid Services (CMS) is a federal agency within the U.S. Department of Health and Human Services. CMS administers Medicare, Medicaid, and the Children's Health Insurance Program (CHIP). CMS also has other responsibilities, such as overseeing the health insurance portability standards, which include the Health Insurance Portability and Accountability Act of 1996 (HIPAA), and ensuring quality care standards in long-term care facilities and clinical laboratories. This organization supports and assists people who are providing long-term care at home. It also provides education, research, services, and advocacy. This association provides education, information, referrals, and research on stroke. Information specific to survivors, caregivers, family, women, and children is included. CitationsAdams HP Jr, et al. (2007). Guidelines for the early management of adults with ischemic stroke. Stroke, 38(5): 1655–1711. Also available online: http://stroke.ahajournals.org/content/38/5/1655.full.Adams RJ (2008). AHA/ASA science advisory: Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke, 39(5): 1647–1652. Also available online: http://stroke.ahajournals.org/content/39/5/1647.full.pdf.Other Works ConsultedAbbott AL (2009). Medical (nonsurgical) intervention alone is now best for prevention of stroke associated with asymptomatic severe carotid stenosis. Stroke, 40(10): e573–e583.Adams RJ, et al. (2003). Coronary risk evaluation in patients with transient ischemic attack and ischemic stroke. Circulation, 108(10): 1278–1290. Also available online: http://circ.ahajournals.org/content/108/10/1278.full.Brott TG, et al. (2010). Stenting versus endarterectomy for treatment of carotid-artery stenosis. New England Journal of Medicine, 363(1): 11–23.Connolly ES Jr, et al. (2012). Guidelines for the management of aneurysmal subarachnoid hemorrhage. Also available online: http://stroke.ahajournals.org/content/early/2012/05/03/STR.0b013e3182587839.full.pdf+html.Ederle J, et al. (2009). Randomized controlled trials comparing endarterectomy and endovascular treatment for carotid artery stenosis: A Cochrane systematic review. Stroke, 40(4): 1373–1380.Goldstein LB, et al. (2010). Guidelines for the primary prevention of stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. Published online December 2, 2010 (doi: 10.1161/STR.0b013e3181fcb238). Also available online: http://stroke.ahajournals.org/content/42/2/517.full.Guyatt GH, 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(2, Suppl): 7S–47S.International Carotid Stenting Study investigators (2010). Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): An interim analysis of a randomized controlled trial. Lancet, 375(9719): 985–997.Lansberg MG, et al. (2012). Antithrombotic and thrombolytic therapy for ischemic stroke. Antithrombotic therapy and prevention of thrombosis, 9th ed. American College of Chest Physicians evidence-based clinical practice guidelines. Chest, 141(2, Suppl): e601S–e636S. Also available online:Latchaw RE, et al. (2003). Guidelines and recommendations for perfusion imaging in cerebral ischemia. Stroke, 34(4): 1084–1104. Also available online: http://stroke.ahajournals.org/content/34/4/1084.full.Morgenstern LB, et al. (2010). Guidelines for the management of spontaneous intracerebral hemorrhage. Stroke, 41(9): 2108–2129. Also available online: http://stroke.ahajournals.org/content/41/9/2108.full.Skinner JS, Cooper A (2011). Secondary prevention of ischaemic cardiac events, search date May 2010. BMJ Clinical Evidence. Available online: http://www.clinicalevidence.com.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.Spence JD, et al. (2010). Effects of intensive medical therapy on microemboli and cardiovascular risk in asymptomatic carotid stenosis. Archives of Neurology, 67(2): 180–186.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.U.S. Preventive Services Task Force (2007). Screening for carotid artery stenosis. Available online: http://www.ahrq.gov/clinic/uspstf/uspsacas.htm.Wahlgren N, et al. (2008). Thrombolysis with alteplase 3-4.5 h after acute ischemic stroke (SITS-ISTR): An observational study. Lancet. Published online September 15, 2008 (doi:10.1016/S0140-6736(08)61339-2). January 3, 2013 E. Gregory Thompson, MD - Internal Medicine & Karin M. Lindholm, DO - Neurology To learn more visit Healthwise.org © 1995-2012 Healthwise, Incorporated. Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.	2	11	1	2	0	0.972898	3	4,725
\|Major endocrine glands. (Male left, female on the right.) 1. Pineal gland 2. Pituitary gland 3. Thyroid gland 4. Thymus 5. Adrenal gland 6. Pancreas 7. Ovary 8. Testes\| \|Classification and external resources\| - 1 Types of disease - 2 List of diseases - 2.1 Glucose homeostasis disorders - 2.2 Thyroid disorders - 2.3 Calcium homeostasis disorders and Metabolic bone disease - 2.4 Pituitary gland disorders - 2.5 Sex hormone disorders - 2.6 Tumours of the endocrine glands not mentioned elsewhere - 2.7 See also separate organs - 3 Endocrine emergencies - 4 See also - 5 References - 6 External links Types of disease Broadly speaking, endocrine disorders may be subdivided into three groups: - Endocrine gland hyposecretion (leading to hormone deficiency) - Endocrine gland hypersecretion (leading to hormone excess) - Tumours (benign or malignant) of endocrine glands Endocrine disorders are often quite complex, involving a mixed picture of hyposecretion and hypersecretion because of the feedback mechanisms involved in the endocrine system. For example, most forms of hyperthyroidism are associated with an excess of thyroid hormone and a low level of thyroid stimulating hormone. List of diseases Glucose homeostasis disorders - Diabetes mellitus - Thyroid cancer - Thyroid hormone resistance Calcium homeostasis disorders and Metabolic bone disease - Parathyroid gland disorders - Osteitis deformans (Paget's disease of bone) - Rickets and osteomalacia Pituitary gland disorders - Hypopituitarism (or Panhypopituitarism) - Pituitary tumors Sex hormone disorders - Disorders of sex development or intersex disorders - Hypogonadism (Gonadotropin deficiency) - Disorders of Puberty - Menstrual function or fertility disorders Tumours of the endocrine glands not mentioned elsewhere See also separate organs - Autoimmune polyendocrine syndromes - Incidentaloma - an unexpected finding on diagnostic imaging, often of endocrine glands In endocrinology, medical emergencies include diabetic ketoacidosis, hyperosmolar hyperglycemic state, hypoglycemic coma, acute adrenocortical insufficiency, phaeochromocytoma crisis, hypercalcemic crisis, thyroid storm, myxoedema coma and pituitary apoplexy. Emergencies arising from decompensated pheochromocytomas or parathyroid adenomas are sometimes referred for emergency resection when aggressive medical therapies fail to control the patient's state, however the surgical risks are significant, especially blood pressure lability and the possibility of cardiovascular collapse after resection (due to a brutal drop in respectively catecholamines and calcium, which must be compensated with gradual normalization). It remains debated when emergency surgery is appropriate as opposed to urgent or elective surgery after continued attempts to stabilize the patient, notably in view of newer and more efficient medications and protocols. - List of MeSH codes (C19) - ICD-10 Chapter IV: Endocrine, nutritional and metabolic diseases - List of ICD-9 codes 240-279: Endocrine, nutritional and metabolic diseases, and immunity disorders - "Endocrine Disorders". webmd. - "Diagnosing Hyperthyroidism: Overactivity of the Thyroid Gland". endocrineweb. - Savage, M W; P Mah; A Weetman; J Newell-Price (1 September 2004). "Endocrine emergencies". Postgraduate Medical Journal. 80 (947): 506–515. doi:10.1136/pgmj.2003.013474. - Brouwers, FM; Eisenhofer, G; Lenders, JW; Pacak, K (December 2006). "Emergencies caused by pheochromocytoma, neuroblastoma, or ganglioneuroma.". Endocrinology and metabolism clinics of North America. 35 (4): 699–724, viii. doi:10.1016/j.ecl.2006.09.014. PMID 17127142. - Tahim, AS; Saunders, J; Sinha, P (2010). "A parathyroid adenoma: benign disease presenting with hyperparathyroid crisis.". Case Reports in Medicine. 2010: 596185. doi:10.1155/2010/596185. PMC . PMID 21209735. - Newell, KA; Prinz, RA; Pickleman, J; Braithwaite, S; Brooks, M; Karson, TH; Glisson, S (August 1988). "Pheochromocytoma multisystem crisis. A surgical emergency.". Archives of surgery (Chicago, Ill. : 1960). 123 (8): 956–9. doi:10.1001/archsurg.1988.01400320042007. PMID 2899426. - Scholten, A.; Cisco, R. M.; Vriens, M. R.; Cohen, J. K.; Mitmaker, E. J.; Liu, C.; Tyrrell, J. B.; Shen, W. T.; Duh, Q.-Y. (2 January 2013). "Pheochromocytoma Crisis Is Not a Surgical Emergency". Journal of Clinical Endocrinology & Metabolism. 98 (2): 581–591. doi:10.1210/jc.2012-3020. PMID 23284003. - Phitayakorn, R; McHenry, CR (June 2008). "Hyperparathyroid crisis: use of bisphosphonates as a bridge to parathyroidectomy.". Journal of the American College of Surgeons. 206 (3): 1106–15. doi:10.1016/j.jamcollsurg.2007.11.010. PMID 18501807.	3	12	0	0	2	0.938727	2	1,312
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 Neuromuscular Electrical Stimulation (NMES) involves the use of a device which transmits an electrical impulse to the skin over selected muscle groups by way of electrodes. Also known as an electronic shock unit, this therapeutic electrical stimulator is designed for home use. The NMES causes muscles to contract as a form of exercise or physical therapy. As an adjunct to traditional physical therapy, NMES of healthy muscle is intended to strengthen or maintain muscle mass during or following periods of enforced inactivity, maintain or gain range of motion, facilitate voluntary muscle control, and temporaily reduce spasticity. This is often the result of chronic neuromuscular disorders such as cerebral palsy, spina bifida, club foot and some nonprogressive myopathies. POLICYNeuromuscular Electrical Stimulation (NMES) or electronic shock unit is covered only where nerve supply to the muscle is intact, including brain, spinal cord, and peripheral nerves and it is used for treatment of the following: High voltage pulsed current, also called electrogalvanic stimulation, may also be covered to reduce swelling and control pain. However, its use in the treatment of wounds and ulcers is investigational. Neuromuscular Electrical Stimulation (NMES) is considered investigational for treatment of the following: Neuromuscular stimulation may be necessary during the initial phase of treatment, but there must be an expectation of improvement in function, and must be used with appropriate therapeutic procedures (for example; 97110) to effect continued improvement. (A limited number of visits without a therapeutic procedure may be medically necessary for treatment of muscle spasm.) Standard treatment is 3 to 4 sessions a week for one month when used as adjunctive therapy or muscle retraining. The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language. Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting. POLICY HISTORY5/1998: Approved by Medical Policy Advisory Committee (MPAC) as part of comprehensive Physical Medicine policy 3/29/2000: Excerpted from Physical Medicine policy with clarifications 2/13/2002: Investigational definition added, Managed Care Requirements deleted, coding statement added to Code Reference section 5/2/2002: Type of Service and Place of Service deleted 8/19/2002: Hyperlinks deleted 10/18/2005: Code Reference section updated; "A diagnosis code(s) must be linked to one of the following HCPCS and/or CPT Procedure Code. All other diagnosis codes are not covered." deleted; ICD-9 Diagnosis: V54.01, V54.02, V54.09, V54.81, V54.89, 728.2 added: 274.0, 333.83, 723.5, 337.20-337.29, 342.00-342.92, 353.1, 354.0-354.8, 355.0-355.8, 457.0, 729.81, 782.3, 711.00-716.59, 718.20-718.49, 719.00-719.59, 720.0-720.89, 721.0-723.5, 724.01-724.79, 726.0-726.67, 727.81-728.11, 728.12, 728.2, 728.6, 728.71, 728.83, 728.85, 729.4, 729.5, 729.81-729.82, 782.3, 923.0-924.4 deleted; HCPCS: A4595, E0731 added 10/23/2006: Policy reviewed, no changes 9/30/2009: Code reference section updated. ICD-9 new diagnosis codes 813.46, 813.47 and 832.2 added to covered table. 09/01/2015: Code Reference section updated for ICD-10. 05/27/2016: Policy number L.8.03.401 added. 09/30/2016: Code Reference section updated to add the following new ICD-10 diagnoses: S03.00XA - S03.03XS, S03.40XA - S03.43XS, S99.001A - S99.001S, S99.002A - S99.002S, S99.009A - S99.009S, S99.011A - S99.011S, S99.021A - S99.021S, S99.031A - S99.031S, S99.041A - S99.041S, S99.091A - S99.091S, and S99.209D - S99.209S. SOURCE(S)Cognitive Remediation in Traumatic Brain Injury: Update and Issues, Achieves of Physical Medicine and Rehabilitation, vol. 74, Feb. 1993, pp. 204-213. Guidelines for Cognitive Rehabilitation, NeuroRehabilitation, August, 1992, pp. 62-67. Published Trials of Nonmedical and Noninvasive Therapies for Hip and Knee Osteoarthritis, Annals of Internal Medicine, Physical Therapy, vol. 121, Number 2, May 1990, pp. 133-140. Pulsed Current, Intermittent Pneumatic Compression, and Placebo Treatments, Physical Therapy, vol. 70, number 5, May 1990, pp. 279-286. Physical Medicine and Rehabilitation Practice Guidelines, Section DeFisiatria, Association Medica De Puerto Rico, First Edition, copyright 1995. American Physical Therapy Association American Occupational Therapy Association Board Certified Physical Medicine and Rehabilitation Physicians Licensed Physical Therapist Consultants Licensed Occupational Therapist Consultants Carrier Medical Directors PM&R Clinic Workgroup Hayes Medical Technology Directory Health Care Financing Administration Specialists and Consultant 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. Neuromuscular stimulator for scoliosis CPT copyright American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.	4	3	1	2	4	0.889465	7	1,619
- 1 What is lumbar spondylosis M47 816? - 2 What is lumbar spondylitis? - 3 What is the ICD 10 for lumbago? What is lumbar spondylosis M47 816? 816 is a billable ICD code used to specify a diagnosis of spondylosis without myelopathy or radiculopathy, lumbar region. A ‘billable code’ is detailed enough to be used to specify a medical diagnosis. What is lumbar spondylitis? As your body ages, the discs between the bones of the spine become stiffer and can break down. The bones also wear down and can grow bone spurs. When this condition is in the lower back, it’s called lumbar spondylosis. How do you code spondylosis? Assign code M47. 812, Spondylosis without myelopathy or radiculopathy, cervical region, for the final interpretation of degenerative changes of the cervical spine. What is lumbar spondylosis with radiculopathy? For patients suffering with lumbar (low-back) spondylosis the symptoms may include generalized aching, pain, or stiffness in the low back, including muscle spasms or tightness. If there is pressure on the spinal nerves you may have numbness, tingling, pain, or weakness in the legs also known as a radiculopathy. What is spondylosis without myelopathy or radiculopathy? Spondylosis with myelopathy refers to spondylosis that is injuring the spinal cord. Spondylosis without myelopathy refers to spondylosis without any injury to the spinal cord. Symptoms of myelopathy include numbness, tingling, and weakness. What is diagnosis code m5416? 16: Radiculopathy, lumbar region. What is lumbosacral spine? A lumbosacral spine x-ray is a picture of the small bones (vertebrae) in the lower part of the spine. This area includes the lumbar region and the sacrum, the area that connects the spine to the pelvis. This is the spine and the sacrum with the cervical (neck), thoracic (mid-back), and lumbar (lower back) vertebra. What is spondylosis without myelopathy? What does degenerative spondylosis of the lumbar spine mean? Lumbar spondylosis is an age-related degeneration of the vertebrae and disks of the lower back. These changes are often called degenerative disk disease and osteoarthritis. The common condition is marked by the breakdown of one or more of the disks that separate the bones of the spine. Is lumbar spondylosis the same as lumbar stenosis? Lumbar stenosis is the gradual narrowing of the spinal canal caused by age-related changes of the discs and facet joints in the lower back. This degenerative process is called spondylosis (spinal arthritis). What is diagnosis code k08.121 in the ICD 10? K08.121 is a valid billable ICD-10 diagnosis code for Complete loss of teeth due to periodontal diseases, class I . It is found in the 2021 version of the ICD-10 Clinical Modification (CM) and can be used in all HIPAA-covered transactions from Oct 01, 2020 – Sep 30, 2021 . What would be appropriate ICD-10-CM code for lumbar stenosis? M48.061 is a billable/specific ICD-10-CM code that can be used to indicate a diagnosis for reimbursement purposes. Short description: Spinal stenosis, lumbar region without neurogenic claud. What is the ICD 10 for lumbago? M54.40 is a valid billable ICD-10 diagnosis code for Lumbago with sciatica , unspecified side.	4	7	0	0	10	0.637973	10	873
Which diseases and disorders rank among the work-related musculoskeletal diseases? Work-related musculoskeletal diseases (MSDs) include degenerative diseases of the spine and the joints, as well as of their muscular and other structures. MSDs are closely connected with inappropriate physical strains, which are still found in many occupations today. Work-related diseases and disorders of the musculoskeletal system are primarily degenerative diseases, that is, signs of wear and tear. They include, for example: These diseases and biomechanical strains can lead to pain, discomforts and functional restrictions in all regions of the body: In the context of discomforts and pain in the musculoskeletal system, those affected frequently refer to the following unspecific symptoms or pain syndromes: Damage to the musculoskeletal system also includes direct nerve and vascular disorders through mechanical influences: Work-related MSDs are frequently the result of heavy physical work or inappropriate physical strain. However, it should not be forgotten that heavy physical work can also lead to inappropriate strains, physical stress and diseases in other organ systems. These include the consequences of static pressure loads in body cavities, organs and compartments, such as hernias or consequences for the cardiovascular system, for example hypertension and varicose veins. It should not be forgotten that there is an increased risk of accidents with heavy physical work. For example, injuries during load handling, or when pushing and pulling, joint injuries, muscle injuries, tendon injuries, damage to nerves, or the consequences of fractures are all possible. Thereby, amputations also rank among the spectre of diseases. The spectrum of factors in the workplace environment that lead directly to disorders and diseases in the musculoskeletal system is wide. It comprises both biomechanical workloads through physical demands during work and the effect of physical and chemical factors as well as modifications through factors of work organisation and of the psychosocial situation or the employee's position in the company. Inappropriate biomechanical workload to the muscles, ligaments, tendons, tendon insertions, joints and joint structures is particularly important in the aetiology. However, it should be stressed that it is not simply high or extreme physical strains that bring about the corresponding inappropriate workload to the musculoskeletal system. An imbalance between reduced resilience, e.g. through a lack of training, through underload or through constitutional and dispositional conditions, and normal physical workload, can also lead to corresponding inappropriate physical workload. It is also known that not only adverse ergonomic work conditions but also factors such as work organisation, the arrangement of work contents, social structures, management behaviour, opportunities for development in the company and resulting psychosocial stresses can at least influence the advance (progression) of disorders in the musculoskeletal system. Along with work-related factors, it is also necessary to take account of individual factors in the emergence and development of disorders and/or of mainly degenerative diseases in the musculoskeletal system. Especially with lower back pain it is known that age, anthropometrics and a lack of fitness play their respective parts. There is no clear evidence on the factors of gender, consumption of alcohol and smoking. Genetic factors play a part in particular with differences in the increase in age-related degenerative changes. Experts assess individual psychosocial factors, such as depression, fear, feelings of stress, personality factors and coping strategies, differently. If a person belongs to a specific occupational group, e.g. they are a blue-collar worker, the risk of lower back pain is regarded as higher. Whereby these groups usually also have to cope with high physical demands and exposure in their work for longer periods of time. Here, physical work factors and psychosocial and personal factors mutually interact. The greater and more intensive physical demands or the impact of physical factors, the less significant are psychosocial and personal factors in the development of MSDs. For example, if a person has to lift and carry heavy loads, or if an employee is exposed intensively to whole-body vibrations, the lumbar spine is heavily stressed. In comparison, psychosocial and individual factors play a greater part if physical demands/exposures tend to be minor, e.g. with office work. For years, many publications have been available on the evidence of occupational risk factors as well as disorders and diseases of the musculoskeletal system. MSDs are one of the most important causes of work absence, outpatient and inpatient hospital treatment, rehabilitation and early retirement. Over one in four of all working days lost due to work absence and cases of work absence are results of these groups of diseases, as well as about half of all rehabilitation cases and over a quarter of all early retirements. According to an estimate for the year 2005, in Germany diseases of the musculoskeletal system and the connective tissues (Chapter M ICD 10) were responsible for approx. 98 million working days lost due to incapacity, loss of production in the amount of € 8.8 billion, or 0.4% of the gross national income, and a loss of gross value added of € 15.5 billion, or 0.7% of the gross national income. Not every disease of the musculoskeletal system that is defined in accordance with the International Classification of Diseases (ICD 10) is encountered frequently. Measured against the frequency of cases of working days lost due to work absence, some diseases tend to be rare. With both men and women, the disease that is most frequently found is the relatively unspecific diagnosis group M54 "Dorsalgia". Here there are over 100 cases of work absence per 1000 employed insured persons. Other frequent reasons for work absence are other diseases of the spine, diseases of the tendons and the tendon sheath, with men shoulder lesions and interior damage to the knee joints; here there are over 10 cases of work absence per 1000 employed insured persons. Other disk damage, osteoarthritis of the knee or hip and other forms of osteoarthritis only occasionally lead to cases of work absence (over 1 case per 1000 employed insured persons). Rarely found reasons for work absence are diseases such as fibromatoses or polyarthritis, rhizarthrosis (osteoarthritis of the carpometacarpal joint of the thumb) among others with less than 1 case of work absence per 1000 employed insured persons. MSDs have a particular effect on work. Craft occupations in particular as well as work in industry and the services sector are accompanied by a much higher risk of work absence through diseases of the musculoskeletal system. MSDs are socio-economically significant because they usually lead to functional impairment of the musculoskeletal system and therefore of the capabilities that a person can deploy at the workplace. Occupational activities always presuppose specific motor skills. This involves physical strength, motility, posture, speed, coordination and dexterity as well as stamina. Diseases of the musculoskeletal system regularly mean that motor demands such as the application of force, or taking up specific postures and carrying out specific movements can only be done with discomfort, if at all. Examples of this are lifting a load with lower back pain, or grasping a tool with carpal tunnel syndrome. In the pathogenetic model for the development of disorders and diseases of the musculoskeletal system, biomechanical strain plays an important part - but not the only one. If thrust forces have to be applied in combination with specific postures during an activity - e.g. high compression forces in the disk of the lumbar spine when lifting loads - great physical forces are generated in the musculoskeletal apparatus. The tensile, compression and shearing forces that occur here can change and traumatise the structure of the musculoskeletal system both acutely and in the long term. This biomechanical explanatory approach applies as well among others to the development of bursitis following external compressive strains, nerve damage through external pressure, inflammatory reactions of the tendons and tendon insertions after high and repetitive strains or articular effusions. The development of muscle pain is more complex. High mechanical strain on isometric or concentric contractions primarily triggers peripheral muscle fatigue. This type of strain is connected with the release of radicals and mechanically influenced membrane damage. This leads to the release of Ca2+ through extension-activated canals. An ATP deficiency or membrane damage is activated by proteases (proteolytic enzymes). With intensive dynamic (concentric) contractions, the consequence of high metabolic strain is lactic acid acidosis through a local O2 deficiency. In addition, extended physical exertion leads to exhaustion of the energy supplies in the muscles through depletion of an energy-rich compound in the muscle cells (ATP, glycogen, creatine phosphate). This releases radicals and inflammatory cytokines and interferes with the ion pumps. This in turn reduces the relaxing speed of the muscles. Contraction remains and spasms occur. Those affected experience the process as "muscle soreness" or "muscle pain". In the long term, the muscles adapt to the strain. This can be seen in fibre transformation (change to the protein isoforms and thus to the fibre types), hypertrophy (enlargement), splicing, neogenesis, atrophy (degrading of proteins), apoptosis (cell death of unwanted cells) and possibly in necrosis as well, that is, the unplanned, complete loss of fibres. This process is controlled both mechanically through the external cytoskeleton and channel proteins, which induce gene transcription, as well as autocrinously (mechano-growth factor, cytokines, interleukin-6, stress proteins). In addition, body hormones such as insulin and thyroxine, neurotransmitters such as acetylcholine and noradrenaline, testosterone and glucocorticoids influence muscle adaptation. For this reason, there are different hypotheses as to how muscle pains occur: the muscle spasm hypothesis assumes that an alpha-gamma coupling triggers a tone increase in the muscles. The compression of muscle vessels associated with this is claimed to cause local ischaemia and oedema. Nocireceptors are stimulated, neuralgetic and vasoneuroactive substances are released. The microtrauma hypothesis explains the development of muscle pain through the traumatisation of capillaries, muscle fibres, fascias and tendons on eccentric contractions. Nocireceptors are stimulated directly in a mechanical way. This process triggers pain cascades and actuates regeneration processes (prostaglandins, vasoneuroactive substances, bradykinin, 5-hydroxytryptamine, neuropeptides). In addition, the sympaticus hypothesis brings muscle pain in conjunction with the body's stress reaction. Activation of the sympathetic nerve system in the stress reaction is coupled with the release of catecholamine. A sympathetic-afferent coupling to nocireceptors or after sensitisation or traumatisation is also postulated. A sympathetic innervation of the intrafusal muscle spindle is claimed to lead to a tone increase in the muscles and thus to muscle pain. Finally, psycho-physical explanation models are included for the development of disorders of the musculoskeletal system through a neuroplastic damage model. Pain on movement is learned, or connected with the movement, so that a movement without actual damage is considered to be painful. This applies, for example, for lower arm complaints with highly repetitive work. The German Working group 1.7 "Belastungen des Muskel- und Skelettsystems" (Strain in the musculoskeletal system) has summarised which occupational demands and activities are associated with special strains for the musculoskeletal system, and published them in DGUV-I 240-460 (previously BGI 504.46) "Handlungsanleitung für die spezielle arbeitsmedizinische Vorsorge nach dem Berufsgenossenschaftlichen Grundsatz G 46 'Belastungen des Muskel- und Skelettsystems'" (Guidelines for special occupational medicine treatment in accordance with principle G 46 'Strains in the musculoskeletal system' of the employers' occupational liability scheme). The working group is part of the occupational medicine committee at the Statutory Social accident Insurance (DGUV) (AG "Gefährdungsbeurteilung" - "Risk assessment" working group). The definition of the categories of physical workloads was updated in the currently ongoing research project F 2333 (MEGAPHYS - "Multilevel risk assessment of physical exposures", a cooperation project between DGUV, BAuA and research partners). According to this, relevant activities and exposures that put strains in the musculoskeletal system are: Manual handling of (heavy) loads Work in constrained positions (forced postures) Manual work (working mainly using hands/arms) Using entire physical strength Physical workload through bodily movement Effect of mechanical vibrations In the ongoing cooperation project between the BAuA and the DGUV (MEGAPHYS, project F 2333 of the BAuA) the above-mentioned workload categories were re-classified in the following way (Ditchen et al 2015): Information on the risk assessment of physical workload situations can be found at another place on the BAuA website, or in the Risk assessment portal. In the last decades, physical exposure at work has on the whole been reduced. In spite of this, employees in service occupations, in agriculture and forestry and craft-based trades, plant operators and unskilled workers still state very often that they have to stand or walk during their work, move loads, carry out repetitive hand-arm movements, move people or are exposed to mechanical vibrations. This involves in particular work in the service sector. In addition, an increasing tendency to unsuitable postures and insufficient physical activity in sedentary occupations, e.g. in clerical occupations, can be seen.	2	7	0	0	1	0.94626	1	2,941
Cardiac output determined by electrical bioimpedance, also known as Thoracic Electrical Bioimpedance (TEB), is based upon the resistive changes in the thorax to an applied current. A special monitor is designed to measure impedance during the cardiac cycle after the introduction of a high-frequency, low-amplitude current using surface electrodes placed at the base of the neck and the lower chest. Since impedance changes are related to the flow of blood, both stroke volume and cardiac output can be derived. Related hemodynamic parameters such as cardiac index, index of contractility, acceleration index, thoracic fluid content and systemic vascular resistance can also be subsequently estimated. 1. Differentiation of cardiogenic from pulmonary causes of acute dyspnea when medical history, physical examination and standard assessment tools provide insufficient information, and the treating physician has determined that TEB hemodynamic data are necessary for appropriate management of the patient. 2. Optimization of Atrioventricular (A/V) interval for patients with A/V sequential cardiac pacemakers when medical history, physical examination and standard assessment tools provide insufficient information, and the treating physician has determined that TEB hemodynamic data are necessary for appropriate management of the patient. 3. Monitoring of continuous inotropic therapy for patients with terminal congestive heart failure, when those patients have chosen to die with comfort at home or for patients waiting at home for a heart transplant. 4. Evaluation for rejection in patients with a heart transplant as a predetermined alternative to a myocardial biopsy. Medical necessity must be documented should a biopsy be performed after TEB. 5. Optimization of fluid management in patients with congestive heart failure when medical history, physical examination and standard assessment tools provide insufficient information, and the treating physician has determined that TEB hemodynamic data are necessary for appropriate management of the patient. - TEB is non-covered when used for patients: a. With proven or suspected disease involving severe regurgitation of the aorta. b. With Minute Ventilation (MV) sensor-function pacemakers, since the device may adversely affect the functioning of that type of pacemaker. c. During cardiac bypass surgery. d. In the management of all forms of hypertension (with the exception of drug-resistant hypertension defined as failure to achieve goal blood pressure in patients who are adhering to full doses of an appropriate three-drug regimen that includes a diuretic). Note: This indication is subject to contractor discretion. - All other uses of TEB not otherwise specified remain non-covered. TrailBlazer Local Non-Covered Indications All forms of hypertension, including drug-resistant hypertension defined above. Notice: This LCD imposes diagnosis limitations that support diagnosis to procedure code automated denials. However, services performed for any given diagnosis must meet all of the indications and limitations stated in this policy, the general requirements for medical necessity as stated in CMS payment policy manuals, any and all existing CMS national coverage determinations, and all Medicare payment rules. As published in CMS IOM 100-08, Section 13.5.1, to be covered under Medicare, a service shall be reasonable and necessary. When appropriate, contractors shall describe the circumstances under which the proposed LCD for the service is considered reasonable and necessary under Section 1862(a)(1)(A). Contractors shall consider a service to be reasonable and necessary if the contractor determines that the service is: - Safe and effective. - Not experimental or investigational (exception: routine costs of qualifying clinical trial services with dates of service on or after September 19, 2000, which meet the requirements of the clinical trials NCD are considered reasonable and necessary). - Appropriate, including the duration and frequency that is considered appropriate for the service, in terms of whether it is: - Furnished in accordance with accepted standards of medical practice for the diagnosis or treatment of the patient’s condition or to improve the function of a malformed body member. - Furnished in a setting appropriate to the patient’s medical needs and condition. - Ordered and furnished by qualified personnel. - One that meets, but does not exceed, the patient’s medical need. - At least as beneficial as an existing and available medically appropriate alternative. Bill Type Codes Contractors may specify Bill Types to help providers identify those Bill Types typically used to report this service. Absence of a Bill Type does not guarantee that the policy does not apply to that Bill Type. Complete absence of all Bill Types indicates that coverage is not influenced by Bill Type and the policy should be assumed to apply equally to all claims. 12X, 13X, 18X, 21X, 22X, 23X, 71X, 73X, 77X, 85X Bill Type Note: Code 73X end-dated for Medicare use March 31, 2010; code 77X effective for dates of service on or after April 1, 2010. Contractors may specify Revenue Codes to help providers identify those Revenue Codes typically used to report this service. In most instances Revenue Codes are purely advisory; unless specified in the policy services reported under other Revenue Codes are equally subject to this coverage determination. Complete absence of all Revenue Codes indicates that coverage is not influenced by Revenue Code and the policy should be assumed to apply equally to all Revenue Codes. Note: TrailBlazer has identified the Bill Type and Revenue Codes applicable for use with the CPT/HCPCS codes included in this LCD. Providers are reminded that not all CPT/HCPCS codes listed can be billed with all Bill Type and/or Revenue Codes listed. CPT/HCPCS codes are required to be billed with specific Bill Type and Revenue Codes. Providers are encouraged to refer to the CMS Internet-Only Manual (IOM) Pub. 100-04, Claims Processing Manual, for further guidance. Revenue codes have not been identified for this procedure since it can be performed in a number of revenue centers within a hospital such as emergency room (450), operation room (360), or a clinic (510). Report this HCPCS codeunder the revenue center where it was performed. Providers are reminded to refer to the long descriptors of the Bioimpedance, cv analysis ICD-9-CM Codes That Support Medical Necessity The CPT/HCPCS codes included in this LCD will be subjected to “procedure to diagnosis” editing. The following lists include only those diagnoses for which the identified CPT/HCPCS procedures are covered. If a covered diagnosis is not on the claim, the edit will automatically deny the service as not medically necessary. Medicare is establishing the following limited coverage for CPT/HCPCS code 93701: Hypertrophic obstructive cardiomyopathy Other primary cardiomyopathies Secondary cardiomyopathy, unspecified Congestive heart failure, Unspecified Left heart failure Systolic Heart Failure Diastolic Heart Failure Combined systolic and diastolic heart failure Heart failure, unspecified Shortness of breath Adjustment of cardiac pacemaker Note: Providers should continue to submit ICD-9-CM diagnosis codes without decimals on their claim forms and electronic claims. Diagnoses That Support Medical Necessity ICD-9-CM Codes That DO NOT Support Medical Necessity Diagnoses That DO NOT Support Medical Necessity All diagnoses not listed in the “ICD-9-CM Codes That Support Medical Necessity” section of this LCD. - Documentation supporting medical necessity should be legible, maintained in the patient’s medical record, and made available to Medicare upon request. - The medical record must show that this modality contributed to the management of the patient The use of bioimpedance must be supported by documented changes in the clinical examination and provide for a level of clinical decision-making beyond the findings of the history and physical examination. - A separate report, i.e., separate from the Evaluation and Management (E/M) service documentation, should be available for review. The report should list: - Patient demographics including name, age, height, weight and vital signs. - Date of the study. - Referring physician. - Clinical diagnosis. - Specific reason for the study (as outlined in the “Indications and Limitations of Coverage and/or Medical Necessity” section of this policy). - Results of the cardiac output, cardiac index, thoracic volume, systemic vascular resistance and index of contractility. - Interpretation of the data. - The application of the data to the listed clinical problem. - Repeated measurements to monitor acute interventions will only be reimbursed once per day. - Cardiac output monitoring by TEB must be ordered by the treating physician who must document that its use aids in the management of the patient. Notice: This LCD imposes utilization guideline limitations. Despite Medicare’s allowing up to these maximums, each patient’s condition and response to treatment must medically warrant the number of services reported for payment. Medicare requires the medical necessity for each service reported to be clearly demonstrated in the patient’s medical record. Medicare expects that patients will not routinely require the maximum allowable number of services.	4	0	2	0	0	0.953909	2	1,940
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 Lyme disease (LD) is a multisystem inflammatory disease caused by the spirochete Borrelia burgdorferi and transmitted by the bite of an infected Ixodes scapularis (Northeastern U.S.) or Ixodes pacificus (Pacific coast, most common in Northern California) tick. The disease is characterized by stages, beginning with localized infection of the skin (erythema migrans), followed by dissemination to many sites. Diagnostic testing for Lyme disease is challenging and can lead to overdiagnosis and overtreatment. Manifestations of early disseminated disease may include lymphocytic meningitis, facial palsy, painful radiculoneuritis, atrioventricular (AV) 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 Lyme disease can be adequately treated with oral antibiotics, intravenous (IV) antibiotics are indicated in some patients with neurologic involvement or atrioventricular block. The following paragraphs describe the various manifestations of Lyme disease, therapies, and the various laboratory tests used to support the diagnosis of Lyme disease. 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 Lyme disease, 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. Usual treatment consists of 2 weeks of either oral (ambulatory setting) or IV (hospitalized patients) antibiotics. Cranial neuritis, most frequently Bell palsy, may present early in the course of disseminated Lyme disease, occasionally before the development of antibodies, such that a Lyme disease etiology may be difficult to rule in or out. While Bell 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, magnetic resonance imaging, 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 best be made 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 pleocytosis and elevated protein. Selective synthesis of anti-spirochetal antibodies can also be identified. A course of IV antibiotics with 2 weeks of ceftriaxone is suggested when CSF abnormalities are identified. A variety of peripheral nervous system manifestations of Lyme disease have also been identified. Symptoms of peripheral neuropathy include paresthesias or radicular pain with only minimal sensory signs. Patients typically exhibit electromyographic 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 block, tachyarrhythmias, and myopericarditis. Antibiotics are typically given, although no evidence has demonstrated hastened 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 of greater than 0.3 seconds. 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 immunoglobulin G (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 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 Lyme disease. 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 more 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 Lyme disease, both of these conditions lack joint inflammation, have normal neurologic 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 optimum method of testing for Lyme disease depends on the stage of the disease. Diagnostic testing may not be necessary when a diagnosis can be made clinically in patients with a recent tick bite or exposure and the presence of the characteristic rash of erythema migrans. While diagnosis of Lyme disease is generally based on the clinical picture and demonstration of specific antibodies (see next), polymerase chain reaction (PCR)‒based technology can detect the spirochete in the central nervous system (CNS) in cases of neuroborreliosis, in the synovial fluid of cases of Lyme arthritis, and rarely in skin biopsy specimens of those with atypical dermatologic manifestations. However, while PCR-based tests can identify organisms in skin biopsy specimens of patients with dermatologic manifestations (ie, erythema migrans), this diagnosis is typically made clinically and antibiotic therapy is started empirically. Similarly, diagnosis of Lyme arthritis is based on clinical and serologic studies without the need for synovial tissue or fluid. Finally, intrathecal antibody production is considered a more sensitive test than PCR-based cerebral spinal fluid (CSF) detection in patients with suspected neuroborreliosis. PCR may be clinically useful as a second approach in patients with a short duration of neurologic symptoms (<14 days) during the window between exposure and the emergence of detectable levels of antibodies in the CSF. PCR-based detection is typically not performed in the urine due to the variable presence of endogenous polymerase inhibitors that affect test sensitivity. 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 immunoglobulin M (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 Lyme disease may persist for months or years. Thus detection of IgG antibodies only indicates exposure, either past or present. In Lyme disease 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 patient's signs and symptoms. For example, patients with vague symptoms of Lyme disease, chronic fatigue syndrome, or fibromyalgia may undergo multiple serologic tests over many weeks to months in an effort to establish the diagnosis of Lyme disease. 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) recommend a two-tiered method for the serologic diagnosis of Lyme disease: (1) ELISA or immunofluorescence assay (IFA), followed by (2) a confirmatory Western blot (including both IgM and IgG when signs or symptoms have been present ≤30 days; IgG only if for symptoms >30 days). A negative ELISA or IFA may be followed by a later (eg, in 4 to 6 weeks) convalescent serum test when symptoms have been present 30 days or less. Other tests include: Polymerase Chain Reaction (PCR) In contrast to the above 2 serologic tests, which 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 (but may not be indicated with recent history of tick bite or exposure) 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. However, PCR-based direct detection of B burgdorferi in the blood may be useful for documenting Lyme carditis when results of serologic studies are equivocal. 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. Evaluation of the Chemoattractant CXCL13 CXCL13 is a B lymphocyte chemoattractant and has been reported to be elevated in acute neuroborreliosis and a potential marker for successful treatment. Treatment of Lyme Disease As noted above, treatment with IV antibiotics may be indicated only in 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 or penicillin. 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 Lyme disease. 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. Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests (LDTs) must meet the general regulatory standards of the Clinical Laboratory Improvement Act (CLIA). Laboratory testing for Lyme disease is available under the auspices of CLIA. Laboratories that offer LDTs must be licensed by CLIA for high-complexity testing. As of 2014, there were at least 70 approved commercial laboratories that perform serologic testing for Lyme disease. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of this test. Treatment of Lyme disease consists of oral antibiotics, except for the following indications: I. A 2- to 4-week course of intravenous (IV) antibiotic therapy may be considered medically necessary in patients with neuroborreliosis with objective neurologic complications of documented Lyme disease (see below for methods of documentation). 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 central nervous system (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 and may replace serologic documentation of infection in patients with a short duration of neurologic symptoms (<14 days) during the window between exposure and production of detectable antibodies. II. 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. III. A single 2- to 4-week course of IV antibiotic therapy may be considered medically necessary in the small subset of patients with well-documented Lyme arthritis who have such severe arthritis that it requires the rapid response associated with IV antibiotics. Documentation of Lyme arthritis may include PCR-based direct detection of B. burgdorferi in the synovial tissue or fluid when results of serologic studies are equivocal. IV. Intravenous antibiotic therapy is considered not medically necessary in the following situations: * Patients with symptoms consistent with chronic fatigue syndrome or fibromyalgia, in the absence of objective clinical or laboratory evidence for Lyme disease; V. Repeat or prolonged courses (greater than 4 weeks) of intravenous antibiotic therapy are considered not medically necessary. VI. Repeat PCR-based direct detection of B. burgdorferi is considered investigational in the following situations: * as a justification for continuation of IV antibiotics beyond 1 month in patients with persistent symptoms * as a technique to follow therapeutic response VII. PCR-based direct detection of B. burgdorferi in urine samples is considered investigational in all clinical situations. VIII. Genotyping or phenotyping of B. burgdorferi is considered investigational. IX. Other diagnostic testing is considered investigational including but not limited to "stand-alone" C6 peptide ELISA or determination of levels of the B lymphocyte chemoattractant CXCL13 for diagnosis or monitoring treatment. The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language. Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Nervous/Mental Conditions, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D: A. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and B. appropriate with regard to standards of good medical practice; and C. not solely for the convenience of the Member, his or her Provider; and D. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient. For the definition of Medically Necessary, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary. Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting. 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. 02/18/2015: Policy description updated regarding polymerase chain reaction and the evaluation of the Chemoattractant CXCL13. Medically necessary policy statement regarding PCR-based direct detection of B. burgdorferi in CSF samples updated to add "and may replace serologic documentation of infection" to the policy statement. Removed the following statement: PCR-based direct detection of B. burgdorferi in the blood when results of serologic studies are equivocal. Policy statement criteria on intravenous antibiotic therapy updated to state: Patients with symptoms consistent with chronic fatigue syndrome or fibromyalgia, in the absence of objective clinical or laboratory evidence for Lyme disease. Policy statements renumbered. 08/28/2015: Medical policy revised to add ICD-10 codes. 12/02/2015: Policy description updated regarding laboratory testing. Policy statements unchanged. Policy guidelines section updated to add medically necessary and investigative definitions. 05/26/2016: Policy number A.5.01.08 added. 01/01/2017: Code Reference section updated to add the following CPT codes: 87475, 87476, and 87477. 01/20/2017: Policy description updated regarding diagnostic tests. Investigational statement regarding C6 peptide ELISA updated to add "stand-alone." 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. CPT copyright American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.	2	10	4	6	0	0.606184	10	4,981
Geriatric medicine involves health concerns of the elderly population, and these cover a number of syndromes and conditions. Dementia, urinary incontinence, osteoarthritis, diabetes, cardiovascular diseases, cerebrovascular diseases, hypertension, hearing concerns, and hyperthyroidism are some of the major conditions. Geriatricians carry out various examinations and offer counseling sessions for their patients. Practitioners in this field also screen patients for various psychosocial concerns. Dementia Codes - Medical and Psychiatric Codes Dementia is a condition that affects a number of old people and it is defined as the progressive and severe impairment of one's brain function that interferes with one's normal functioning. Dementia is usually irreversible. It may be mild, moderate, severe or profound. The new codes for dementia are provided in ICD-10 Chapter V: Mental and Behavioural Disorders. These codes signify various types of dementia and include medical codes and psychiatric codes. When billing for dementia, service providers should give the correct diagnostic codes for medical conditions causing irreversible dementia such as: • Alzheimer's disease • Frontotemporal dementia • Multi-infarct dementia • Parkinson's disease with dementia • Huntington's disease • Senile degeneration of the brain • Mild cognitive impairment • Dementia with Lewy bodies • Pick's disease • Binswanger's disease • Creutzfeldt-Jakob disease • Multiple sclerosis • Unspecified cerebral degeneration • Memory loss and late effects of CVD Psychiatric codes signify uncomplicated senile dementia, presenile dementia, senile dementia with delusional features, senile dementia with depressive features, senile dementia with delirium, arteriosclerotic dementia, dementia without behavioral disturbances, and dementia with behavioral disturbances. When coding, it is necessary to indicate whether the dementia occurred with or without behavioral disturbances such as violent behavior, aggressive behavior, wandering off and more. Reversible types of dementia are treatable and are most often caused by conditions such as brain tumors, chronic alcoholism, infections, certain deficiencies, heavy-metal poisoning, hyperthyroidism and so on. Providers can bill for pharmacologic, physical, occupational, speech-language and other therapies that are provided for their dementia patients. Payers require that providers clearly enter their primary diagnosis as well as the secondary diagnosis that support the medical necessity of the services provided. In case the patient suffers from an illness or injury not related to their dementia, the physician's primary diagnosis recorded in the claim should reflect clearly the need for the billed service. Factors that Have an Impact on Reimbursement • CMS does not regard certain diagnostic codes as regular medical codes. As a result, these are not reimbursed at the usual rate, sometimes these are not paid at all. The provider has to have in-depth knowledge regarding the assignment of the correct primary and secondary diagnostic codes to ensure full reimbursement. • Reporting all professional services in all settings such as inpatient, outpatient, home and nursing facilities, correctly using the appropriate CPT five digit codes • Appropriate use of evaluation and management (E/M) codes or the five digit codes used to report non-procedural professional services. These codes should clearly highlight the complexity of the service provided. Tests such as gait and balance assessment, mini mental status exam, history, physical and family interview do not have their own CPT codes. So these are included under E/M. A physician's interaction with the patient includes screening, procedure visit and visit for discussing results. For effective reimbursement, the correct diagnostic and procedural codes have to be assigned for each of these visits. During screening, the physician identifies the condition for which the appropriate diagnostic code has to be assigned. Any new problem that requires a differential diagnosis has to be documented during the procedure visit. The provider has to also ascertain whether requirements for a higher level code are met. Additional documentation includes valid diagnostic codes to justify a comprehensive exam, codes to report any co-existing conditions such as diabetes, weight loss, delirium and so on. This is important with regard to using higher levels of E/M coding. In the case of a patient with multiple problems, the doctor will have to spend more time to complete the assessment. It is the visit's complexity that would justify billing for the highest level E/M. • 99205 - Level 5 comprehensive exam for new patient • 99215 - Level 5 comprehensive exam for established patient • 96116 - neurobehavioral status examination Codes to Use for Care Management Provided • First hour - 99358 • Each additional 30 minutes - 99359 • Telephone services - 99371-3 Tips for Accurate Coding Review of systems (ROS), history of present illness (HPI), family, physical examination, social medical history, medical decision making, time spent for discussion of counseling, and organizing care, all these have to be taken into account when assigning E/M codes. When coding for dementia, under no circumstances should a lower level of service be reported using a higher level code. If you are to receive due reimbursement, medical necessity of a provided service is of course the primary consideration. Individual requirements of the CPT codes used are also a major criterion. The level of service reported should have sufficient supporting documentation. Geriatric Medical Coding - Outsource Strategies International (OSI), a leading medical billing and coding company in the US, provides a comprehensive suite of medical billing and coding outsourcing services.	4	7	1	0	0	0.943804	1	1,140
\|Part of a series on\| \|Medical and psychological \|Social and cultural anthropology\| In medicine and medical anthropology, a culture-bound syndrome, culture-specific syndrome, or folk illness is a combination of psychiatric and somatic symptoms that are considered to be a recognizable disease only within a specific society or culture. There are no objective biochemical or structural alterations of body organs or functions, and the disease is not recognized in other cultures. The term culture-bound syndrome was included in the fourth version of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1994) which also includes a list of the most common culture-bound conditions (DSM-IV: Appendix I). Counterpart within the framework of ICD-10 (Chapter V) are the culture-specific disorders defined in Annex 2 of the Diagnostic criteria for research. More broadly, an epidemic that can be attributed to cultural behavior patterns or suggestion is sometimes referred to as a behavioral epidemic. As in the cases of drug or alcohol abuse or smoking, transmission can be determined by communal reinforcement as well as by person-to-person interactions. On etiological grounds, it can be difficult to distinguish the causal contribution of culture in disease from other environmental factors such as toxicity. A culture-specific syndrome is characterized by: - categorization as a disease in the culture (i.e., not a voluntary behaviour or false claim); - widespread familiarity in the culture; - complete lack of familiarity or misunderstanding of the condition to people in other cultures; - no objectively demonstrable biochemical or tissue abnormalities (signs); - the condition is usually recognized and treated by the folk medicine of the culture. Some culture-specific syndromes involve somatic symptoms (pain or disturbed function of a body part), while others are purely behavioral. Some culture-bound syndromes appear with similar features in several cultures, but with locally specific traits, such as penis panics. A culture-specific syndrome is not the same as a geographically localized disease with specific, identifiable, causal tissue abnormalities, such as kuru or sleeping sickness, or genetic conditions limited to certain populations. It is possible that a condition originally assumed to be a culture-bound behavioral syndrome is found to have a biological cause; from a medical perspective it would then be redefined into another nosological category. The American Psychiatric Association states the following: The term culture-bound syndrome denotes recurrent, locality-specific patterns of aberrant behavior and troubling experience that may or may not be linked to a particular DSM-IV diagnostic category. Many of these patterns are indigenously considered to be "illnesses," or at least afflictions, and most have local names. Although presentations conforming to the major DSM-IV categories can be found throughout the world, the particular symptoms, course, and social response are very often influenced by local cultural factors. In contrast, culture-bound syndromes are generally limited to specific societies or culture areas and are localized, folk, diagnostic categories that frame coherent meanings for certain repetitive, patterned, and troubling sets of experiences and observations. The term culture-bound syndrome is controversial since it reflects the different opinions of anthropologists and psychiatrists. Anthropologists have a tendency to emphasize the relativistic and culture-specific dimensions of the syndromes, while physicians tend to emphasize the universal and neuropsychological dimensions. Guarnaccia & Rogler (1999) have argued in favor of investigating culture-bound syndromes on their own terms, and believe that the syndromes have enough cultural integrity to be treated as independent objects of research. Some studies suggest that culture-bound syndromes represent an acceptable way within a specific culture (and cultural context) among certain vulnerable individuals (i.e. an ataque de nervios at a funeral in Puerto Rico) to express distress in the wake of a traumatic experience. A similar manifestation of distress when displaced into a North American medical culture may lead to a very different, even adverse outcome for a given individual and [his or] her family. The fourth edition of Diagnostic and Statistical Manual of Mental Disorders classifies the below syndromes as culture-bound syndromes: The fifth edition of Diagnostic and Statistical Manual of Mental Disorders classifies the below syndromes as culture-bound syndromes: \|Ataque de nervios\|\|Hispanic people as well as in the Philippines\| \|Khyâl cap\|\|Cambodians in the United States and Cambodia\| \|Ghost sickness\|\|Native American\| \|Nervios\|\|Latin America, Latinos in the United States\| \|Susto\|\|Latinos in the United States; Mexico, Central America and South America\| The 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD) classifies the below syndromes as culture-specific disorders: \|Dhat syndrome (dhātu), shen-kʼuei, jiryan\|\|India; Taiwan\| \|Koro, suk yeong, jinjin bemar\|\|South-east Asia, India, China\| \|Nervios, nerfiza, nerves, nevra\|\|Egypt; Greece; northern Europe; Mexico, Central and South America\| \|Pa-leng (frigophobia)\|\|Taiwan; south-east Asia\| \|Pibloktoq (Arctic hysteria)\|\|Inuit living within the Arctic Circle\| \|Susto, espanto\|\|Mexico, Central and South America\| \|Taijin kyofusho, shinkeishitsu (anthropophobia)\|\|Japan\| \|Ufufuyane, saka\|\|Kenya; southern Africa (among Bantu, Zulu, and affiliated groups)\| \|Uqamairineq\|\|Inuit living within the Arctic Circle\| \|Windigo\|\|Indigenous people of north-east America\| Within the contiguous United States, the consumption of kaolin has been proposed as a culture bound syndrome observed in African Americans in the rural south, particularly in areas in which the mining of kaolin is common. In South Africa, among the Xhosa people, the syndrome amafufunyana is commonly used to describe those believed to be possessed by demons or other malevolent spirits. Traditional healers in the culture usually perform exorcisms in order to drive off these spirits. Upon investigating the phenomenon, researchers found that many of the people claimed to be affected by the syndrome exhibited the traits and characteristics of schizophrenia. Vegetative-vascular dystonia can be considered an example of somatic condition formally recognised by local medical community in former Soviet Union countries, but not in Western classification systems. Its umbrella term nature as neurological condition also results in diagnosing neurotic patients as neurological ones, in effect substituting possible psychiatric stigma with culture-bound syndrome disguised as a neurological condition. - Cross-cultural psychiatry - Cross-cultural psychology - Hi-wa itck - Medical anthropology - Zen sickness - Diagnostic criteria for research, p. 213–225 (WHO 1993) - Porta, Miquel, ed. (2008). "Behavioral epidemic". A Dictionary of Epidemiology (5th ed.). Oxford University Press. p. 48. ISBN 978-0-19-157844-1. Retrieved 25 August 2013. - American Psychiatric Association (2000), Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision, American Psychiatric Pub, p. 898, ISBN 978-0-89042-025-6 - Perry, S. (2012, 13 January). The controversy over 'culture-bound' mental illnesses. Retrieved 27 January 2013 from MinnPost. - Prince, Raymond H. (2000) In Review. Transcultural Psychiatry: Personal Experiences and Canadian Perspectives. Canadian Journal of Psychiatry, 45: 431–437 - Jilek W.G (2001) Psychiatric Disorders: Culture-specific. International Encyclopedia of the Social and Behavioral Sciences. Elsevier Science Ltd. - Guarnaccia, Peter J. & Rogler, Lloyd H. (1999) Research on Culture-Bound Syndromes: New Directions. American Journal of Psychiatry 156:1322–1327, September - Schechter DS, Marshall RD, Salman E, Goetz D, Davies SO, Liebowitz MR (2000). Ataque de nervios and childhood trauma history: An association? Journal of Traumatic Stress, 13:3, 529–534. - Schechter DS, Kaminer, T, Grienenberger JF, Amat J (2003). Fits and starts: A mother-infant case study involving pseudoseizures across three generations in the context of violent trauma history (with Commentaries by RD Marshall, CH Zeanah, T Gaensbauer). Infant Mental Health Journal. 24(5), 510–28. - American Psychiatric Association (2000), Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision, American Psychiatric Pub, pp. 898–901, ISBN 978-0-89042-025-6 - What is MAL DE PELEA? Psychology Dictionary, Accessed 19 December 2014. - American Psychiatric Association (2013), Diagnostic and statistical manual of mental disorders, 5th ed., pp. 833–837, ISBN 978-0-89042-554-1 - South Med J. 1999;Feb 92 (2): 190-192. Chalk Eating in Middle Georgia: A Culture-Bound Syndrome of Pica? Grigsby, RK, Thyer, BA, Waller, RJ, Johnston, GA Jr - Niehaus DJ, Oosthuizen P, Lochner C, Emsley RA, Jordaan E, Mbanga NI, Keyter N, Laurent C, Deleuze JF, Stein DJ (March–April 2004). "A culture-bound syndrome 'amafufunyana' and a culture-specific event 'ukuthwasa': differentiated by a family history of schizophrenia and other psychiatric disorders". Psychopathology. Karger Publishers. 37 (2): 59–63. doi:10.1159/000077579. PMID 15057028.]] - Mikhaylov, B (2010). "P02-34 -Statistical issues of the psychiatric care in Ukraine". European Psychiatry. 25: 652. doi:10.1016/S0924-9338(10)70647-7. Retrieved October 2, 2016. - EPA-1025 - Integrative psychotherapy model of anxiety disorders Mykhaylov, B. et al. European Psychiatry , Volume 29 , 1 http://www.europsy-journal.com/article/S0924-9338(14)78319-1/abstract - Kleinman, Arthur (1991), Rethinking psychiatry: from cultural category to personal experience, New York: Free Press, ISBN 0-02-917441-4, retrieved 8 January 2011 - Landy, David, ed. (1977), Culture, Disease, and Healing: Studies in Medical Anthropology, New York: Macmillan, ISBN 978-0-02-367390-0 - John Launer (2003), "Folk illness and medical models", Q J Med, 96 (11): 875–876, doi:10.1093/qjmed/hcg136 - Simons, Rondald C; Hughes, Charles C, eds. (1985), The Culture-Bound Syndromes: Folk Illnesses and Anthropological Interest, Dordrecht, Holland: D. Reidel Publishing Co, ISBN 90-277-1858-X, retrieved 9 September 2010 Paperback ISBN 90-277-1859-8 - Rebhun, L.A (2004), "Culture-Bound Syndromes", in Ember, Carol R.; Ember, Melvin, Encyclopedia of Medical Anthropology: Health and Illness in the World's Cultures, New York: Klower Academic/Plenum Publishers, pp. 319–327, ISBN 0-306-47754-8, retrieved 9 September 2010 (Note: Different preview pages result in the full chapter being viewable from the title link). - Kirmayer, L. J. (2001), "Cultural variations in the clinical presentation of depression and anxiety: implications for diagnosis and treatment.", Journal of Clinical Psychiatry, 62: 22–30	2	15	6	2	1	0.666169	9	2,594
\|Coronavirus disease 2019\| \|Other names\|\|COVID, (the) coronavirus\| Transmission and life-cycle of SARS-CoV-2 causing COVID-19. \|Symptoms\|\|Fever, cough, fatigue, shortness of breath, vomiting, loss of taste or smell; some cases asymptomatic\| \|Complications\|\|Pneumonia, viral sepsis, acute respiratory distress syndrome, kidney failure, cytokine release syndrome, respiratory failure, pulmonary fibrosis, paediatric multisystem inflammatory syndrome, long COVID\| \|Usual onset\|\|2–14 days (typically 5) from infection\| \|Duration\|\|5 days to chronic\| \|Causes\|\|Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)\| \|Diagnostic method\|\|rRT‑PCR testing, CT scan, Rapid antigen test\| \|Prevention\|\|Vaccination, face coverings, quarantine, physical/social distancing, ventilation, hand washing\| \|Treatment\|\|Symptomatic and supportive\| \|Frequency\|\|618,520,614 confirmed cases\| \|Part of a series on the\| Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease quickly spread worldwide, resulting in the COVID-19 pandemic. Symptoms of COVID‑19 are variable, but often include fever, cough, headache, fatigue, breathing difficulties, loss of smell, and loss of taste. Symptoms may begin one to fourteen days after exposure to the virus. At least a third of people who are infected do not develop noticeable symptoms. Of those people who develop symptoms noticeable enough to be classed as patients, most (81%) develop mild to moderate symptoms (up to mild pneumonia), while 14% develop severe symptoms (dyspnoea, hypoxia, or more than 50% lung involvement on imaging), and 5% develop critical symptoms (respiratory failure, shock, or multiorgan dysfunction). Older people are at a higher risk of developing severe symptoms. Some people continue to experience a range of effects (long COVID) for months after recovery, and damage to organs has been observed. Multi-year studies are underway to further investigate the long-term effects of the disease. COVID‑19 transmits when people breathe air contaminated by droplets and small airborne particles containing the virus. The risk of breathing these is highest when people are in close proximity, but they can be inhaled over longer distances, particularly indoors. Transmission can also occur if splashed or sprayed with contaminated fluids in the eyes, nose or mouth, and, rarely, via contaminated surfaces. People remain contagious for up to 20 days, and can spread the virus even if they do not develop symptoms. COVID-19 testing methods to detect the virus's nucleic acid include real-time reverse transcription polymerase chain reaction (rRT‑PCR), transcription-mediated amplification, and reverse transcription loop-mediated isothermal amplification (RT‑LAMP) from a nasopharyngeal swab. Several COVID-19 vaccines have been approved and distributed in various countries, which have initiated mass vaccination campaigns. Other preventive measures include physical or social distancing, quarantining, ventilation of indoor spaces, covering coughs and sneezes, hand washing, and keeping unwashed hands away from the face. The use of face masks or coverings has been recommended in public settings to minimise the risk of transmission. While work is underway to develop drugs that inhibit the virus, the primary treatment is symptomatic. Management involves the treatment of symptoms, supportive care, isolation, and experimental measures. Main article: COVID-19 naming During the initial outbreak in Wuhan, the virus and disease were commonly referred to as "coronavirus" and "Wuhan coronavirus", with the disease sometimes called "Wuhan pneumonia". In the past, many diseases have been named after geographical locations, such as the Spanish flu, Middle East respiratory syndrome, and Zika virus. In January 2020, the World Health Organization (WHO) recommended 2019-nCoV and 2019-nCoV acute respiratory disease as interim names for the virus and disease per 2015 guidance and international guidelines against using geographical locations or groups of people in disease and virus names to prevent social stigma. The official names COVID‑19 and SARS-CoV-2 were issued by the WHO on 11 February 2020. The Director-General, Tedros Adhanom explained that CO stands for corona, VI for virus, D for disease, and 19 for 2019, the year in which the outbreak was first identified. The WHO additionally uses "the COVID‑19 virus" and "the virus responsible for COVID‑19" in public communications. Main article: Symptoms of COVID-19 The symptoms of COVID-19 are variable depending on the type of variant contracted, ranging from mild symptoms to critical and possibly fatal illness. Common symptoms include coughing, fever, loss of smell (anosmia) and taste (ageusia), with less common ones including headaches, nasal congestion and runny nose, muscle pain, sore throat, diarrhea, eye irritation, and toes swelling or turning purple, and in moderate to severe cases breathing difficulties. People with the COVID-19 infection may have different symptoms, and their symptoms may change over time. Three common clusters of symptoms have been identified: one respiratory symptom cluster with cough, sputum, shortness of breath, and fever; a musculoskeletal symptom cluster with muscle and joint pain, headache, and fatigue; a cluster of digestive symptoms with abdominal pain, vomiting, and diarrhea. In people without prior ear, nose, and throat disorders, loss of taste combined with loss of smell is associated with COVID-19 and is reported in as many as 88% of symptomatic cases. Of people who show symptoms, 81% develop only mild to moderate symptoms (up to mild pneumonia), while 14% develop severe symptoms (dyspnea, hypoxia, or more than 50% lung involvement on imaging) which requiring hospitalization and 5% of patients develop critical symptoms (respiratory failure, septic shock, or multiorgan dysfunction) requiring ICU admission. At least a third of the people who are infected with the virus do not develop noticeable symptoms at any point in time. These asymptomatic carriers tend not to get tested and can still spread the disease. Other infected people will develop symptoms later, called "pre-symptomatic", or have very mild symptoms and can also spread the virus. As is common with infections, there is a delay between the moment a person first becomes infected and the appearance of the first symptoms. The median delay for COVID-19 is four to five days possibly being infectious on 1-4 of those days. Most symptomatic people experience symptoms within two to seven days after exposure, and almost all will experience at least one symptom within 12 days. Most people recover from the acute phase of the disease. However, some people – over half of a cohort of home-isolated young adults identified in June, 2021 – continued to experience a range of effects, such as fatigue, for months even after recovery. This is the result of a condition called long COVID which can be described as a range of persistent symptoms that continue for weeks and/or months at a time. Long-term damage to organs has also been observed after the onset of COVID-19. Multi-year studies are underway to further investigate the potential long-term effects of the disease.The Omicron variant became dominant in the U.S. starting in December 2021. Symptoms with the Omicron variant are less severe as they are with other variants. COVID‑19 is caused by infection with a strain of coronavirus known as 'Severe Acute Respiratory Syndrome coronavirus 2' (SARS-CoV-2). Main article: Transmission of COVID-19 \|Transmission of COVID-19\| \|Other names\|\|Mode of spread of COVID-19\| \|Specialty\|\|Infection prevention and control\| \|Types\|\|Respiratory droplet, airborne transmission, fomites\| \|Prevention\|\|Face coverings, quarantine, physical/social distancing, ventilation, hand washing, vaccination\| COVID-19 is mainly transmitted when people breathe in air contaminated by droplets/aerosols and small airborne particles containing the virus. Infected people exhale those particles as they breathe, talk, cough, sneeze, or sing. Transmission is more likely the more physically close people are. However, infection can occur over longer distances, particularly indoors. Infectivity can begin four to five days before the onset of symptoms, although contact tracing typically begins only two to three days before symptom onset. Infected people can spread the disease even if they are pre-symptomatic or asymptomatic. Most commonly, the peak viral load in upper respiratory tract samples occurs close to the time of symptom onset and declines after the first week after symptoms begin. Current evidence suggests a duration of viral shedding and the period of infectiousness of up to ten days following symptom onset for people with mild to moderate COVID-19, and up to 20 days for persons with severe COVID-19, including immunocompromised people. Infectious particles range in size from aerosols that remain suspended in the air for long periods of time to larger droplets that remain airborne briefly or fall to the ground. Additionally, COVID-19 research has redefined the traditional understanding of how respiratory viruses are transmitted. The largest droplets of respiratory fluid do not travel far, but can be inhaled or land on mucous membranes on the eyes, nose, or mouth to infect. Aerosols are highest in concentration when people are in close proximity, which leads to easier viral transmission when people are physically close, but airborne transmission can occur at longer distances, mainly in locations that are poorly ventilated; in those conditions small particles can remain suspended in the air for minutes to hours.The number of people generally infected by one infected person varies, but it is estimated that the R0 ("R nought" or "R zero") number is around 2.5. The disease often spreads in clusters, where infections can be traced back to an index case or geographical location. Often in these instances, superspreading events occur, where many people are infected by one person. Main article: SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel severe acute respiratory syndrome coronavirus. It was first isolated from three people with pneumonia connected to the cluster of acute respiratory illness cases in Wuhan. All structural features of the novel SARS-CoV-2 virus particle occur in related coronaviruses in nature. Outside the human body, the virus is destroyed by household soap, which bursts its protective bubble. SARS-CoV-2 is closely related to the original SARS-CoV. It is thought to have an animal (zoonotic) origin. Genetic analysis has revealed that the coronavirus genetically clusters with the genus Betacoronavirus, in subgenus Sarbecovirus (lineage B) together with two bat-derived strains. It is 96% identical at the whole genome level to other bat coronavirus samples (BatCov RaTG13). The structural proteins of SARS-CoV-2 include membrane glycoprotein (M), envelope protein (E), nucleocapsid protein (N), and the spike protein (S). The M protein of SARS-CoV-2 is about 98% similar to the M protein of bat SARS-CoV, maintains around 98% homology with pangolin SARS-CoV, and has 90% homology with the M protein of SARS-CoV; whereas, the similarity is only around 38% with the M protein of MERS-CoV. Main article: Variants of SARS-CoV-2 The many thousands of SARS-CoV-2 variants are grouped into either clades or lineages. The WHO, in collaboration with partners, expert networks, national authorities, institutions and researchers, have established nomenclature systems for naming and tracking SARS-CoV-2 genetic lineages by GISAID, Nextstrain and Pango. The expert group convened by the WHO recommended the labelling of variants using letters of the Greek alphabet, for example, Alpha, Beta, Delta, and Gamma, giving the justification that they "will be easier and more practical to discussed by non-scientific audiences." Nextstrain divides the variants into five clades (19A, 19B, 20A, 20B, and 20C), while GISAID divides them into seven (L, O, V, S, G, GH, and GR). The Pango tool groups variants into lineages, with many circulating lineages being classed under the B.1 lineage. Several notable variants of SARS-CoV-2 emerged throughout 2020. Cluster 5 emerged among minks and mink farmers in Denmark. After strict quarantines and a mink euthanasia campaign, the cluster was assessed to no longer be circulating among humans in Denmark as of 1 February 2021. As of December 2021[update], there are five dominant variants of SARS-CoV-2 spreading among global populations: the Alpha variant (B.1.1.7, formerly called the UK variant), first found in London and Kent, the Beta variant (B.1.351, formerly called the South Africa variant), the Gamma variant (P.1, formerly called the Brazil variant), the Delta variant (B.1.617.2, formerly called the India variant), and the Omicron variant (B.1.1.529), which had spread to 57 countries as of 7 December. The SARS-CoV-2 virus can infect a wide range of cells and systems of the body. COVID‑19 is most known for affecting the upper respiratory tract (sinuses, nose, and throat) and the lower respiratory tract (windpipe and lungs). The lungs are the organs most affected by COVID‑19 because the virus accesses host cells via the receptor for the enzyme angiotensin-converting enzyme 2 (ACE2), which is most abundant on the surface of type II alveolar cells of the lungs. The virus uses a special surface glycoprotein called a "spike" to connect to the ACE2 receptor and enter the host cell. Following viral entry, COVID‑19 infects the ciliated epithelium of the nasopharynx and upper airways. One common symptom, loss of smell, results from infection of the support cells of the olfactory epithelium, with subsequent damage to the olfactory neurons. The involvement of both the central and peripheral nervous system in COVID‑19 has been reported in many medical publications. It is clear that many people with COVID-19 exhibit neurological or mental health issues. The virus is not detected in the central nervous system (CNS) of the majority of COVID-19 patients with neurological issues. However, SARS-CoV-2 has been detected at low levels in the brains of those who have died from COVID‑19, but these results need to be confirmed. While virus has been detected in cerebrospinal fluid of autopsies, the exact mechanism by which it invades the CNS remains unclear and may first involve invasion of peripheral nerves given the low levels of ACE2 in the brain. The virus may also enter the bloodstream from the lungs and cross the blood-brain barrier to gain access to the CNS, possibly within an infected white blood cell. Research conducted when Alpha was the dominant variant has suggested COVID-19 May cause brain damage. It is unknown if such damage is temporary or permanent, and whether Omicron has similar effects. Observed individuals infected with COVID-19 (most with mild cases) experienced an additional 0.2% to 2% of brain tissue lost in regions of the brain connected to the sense of smell compared with uninfected individuals, and the overall effect on the brain was equivalent on average to at least one extra year of normal ageing; infected individuals also scored lower on several cognitive tests. All effects were more pronounced among older ages. The virus also affects gastrointestinal organs as ACE2 is abundantly expressed in the glandular cells of gastric, duodenal and rectal epithelium as well as endothelial cells and enterocytes of the small intestine. The virus can cause acute myocardial injury and chronic damage to the cardiovascular system. An acute cardiac injury was found in 12% of infected people admitted to the hospital in Wuhan, China, and is more frequent in severe disease. Rates of cardiovascular symptoms are high, owing to the systemic inflammatory response and immune system disorders during disease progression, but acute myocardial injuries may also be related to ACE2 receptors in the heart. ACE2 receptors are highly expressed in the heart and are involved in heart function. A high incidence of thrombosis and venous thromboembolism occurs in people transferred to intensive care units with COVID‑19 infections, and may be related to poor prognosis. Blood vessel dysfunction and clot formation (as suggested by high D-dimer levels caused by blood clots) may have a significant role in mortality, incidences[spelling?] of clots leading to pulmonary embolisms, and ischaemic events within the brain found as complications leading to death in people infected with COVID‑19. Infection may initiate a chain of vasoconstrictive responses within the body, including pulmonary vasoconstriction – a possible mechanism in which oxygenation decreases during pneumonia. Furthermore, damage of arterioles and capillaries was found in brain tissue samples of people who died from COVID‑19. COVID‑19 may also cause substantial structural changes to blood cells, sometimes persisting for months after hospital discharge. A low level of blood lymphocytes may result from the virus acting through ACE2-related entry into lymphocytes. Another common cause of death is complications related to the kidneys. Early reports show that up to 30% of hospitalised patients both in China and in New York have experienced some injury to their kidneys, including some persons with no previous kidney problems. Autopsies of people who died of COVID‑19 have found diffuse alveolar damage, and lymphocyte-containing inflammatory infiltrates within the lung. Although SARS-CoV-2 has a tropism for ACE2-expressing epithelial cells of the respiratory tract, people with severe COVID‑19 have symptoms of systemic hyperinflammation. Clinical laboratory findings of elevated IL‑2, IL‑7, IL‑6, granulocyte-macrophage colony-stimulating factor (GM‑CSF), interferon gamma-induced protein 10 (IP‑10), monocyte chemoattractant protein 1 (MCP1), macrophage inflammatory protein 1‑alpha (MIP‑1‑alpha), and tumour necrosis factor (TNF‑α) indicative of cytokine release syndrome (CRS) suggest an underlying immunopathology. Interferon alpha plays a complex, Janus-faced role in the pathogenesis of COVID-19. Although it promotes the elimination of virus-infected cells, it also upregulates the expression of ACE-2, thereby facilitating the SARS-Cov2 virus to enter cells and to replicate. A competition of negative feedback loops (via protective effects of interferon alpha) and positive feedback loops (via upregulation of ACE-2) is assumed to determine the fate of patients suffering from COVID-19. Additionally, people with COVID‑19 and acute respiratory distress syndrome (ARDS) have classical serum biomarkers of CRS, including elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer, and ferritin. Systemic inflammation results in vasodilation, allowing inflammatory lymphocytic and monocytic infiltration of the lung and the heart. In particular, pathogenic GM-CSF-secreting T cells were shown to correlate with the recruitment of inflammatory IL-6-secreting monocytes and severe lung pathology in people with COVID‑19. Lymphocytic infiltrates have also been reported at autopsy. Multiple viral and host factors affect the pathogenesis of the virus. The S-protein, otherwise known as the spike protein, is the viral component that attaches to the host receptor via the ACE2 receptors. It includes two subunits: S1 and S2. S1 determines the virus-host range and cellular tropism via the receptor-binding domain. S2 mediates the membrane fusion of the virus to its potential cell host via the H1 and HR2, which are heptad repeat regions. Studies have shown that S1 domain induced IgG and IgA antibody levels at a much higher capacity. It is the focus spike proteins expression that are involved in many effective COVID‑19 vaccines. The M protein is the viral protein responsible for the transmembrane transport of nutrients. It is the cause of the bud release and the formation of the viral envelope. The N and E protein are accessory proteins that interfere with the host's immune response. Human angiotensin converting enzyme 2 (hACE2) is the host factor that SARS-CoV-2 virus targets causing COVID‑19. Theoretically, the usage of angiotensin receptor blockers (ARB) and ACE inhibitors upregulating ACE2 expression might increase morbidity with COVID‑19, though animal data suggest some potential protective effect of ARB; however no clinical studies have proven susceptibility or outcomes. Until further data is available, guidelines and recommendations for hypertensive patients remain. The effect of the virus on ACE2 cell surfaces leads to leukocytic infiltration, increased blood vessel permeability, alveolar wall permeability, as well as decreased secretion of lung surfactants. These effects cause the majority of the respiratory symptoms. However, the aggravation of local inflammation causes a cytokine storm eventually leading to a systemic inflammatory response syndrome. Among healthy adults not exposed to SARS-CoV-2, about 35% have CD4+ T cells that recognise the SARS-CoV-2 S protein (particularly the S2 subunit) and about 50% react to other proteins of the virus, suggesting cross-reactivity from previous common colds caused by other coronaviruses. It is unknown whether different persons use similar antibody genes in response to COVID‑19. The severity of the inflammation can be attributed to the severity of what is known as the cytokine storm. Levels of interleukin 1B, interferon-gamma, interferon-inducible protein 10, and monocyte chemoattractant protein 1 were all associated with COVID‑19 disease severity. Treatment has been proposed to combat the cytokine storm as it remains to be one of the leading causes of morbidity and mortality in COVID‑19 disease. A cytokine storm is due to an acute hyperinflammatory response that is responsible for clinical illness in an array of diseases but in COVID‑19, it is related to worse prognosis and increased fatality. The storm causes acute respiratory distress syndrome, blood clotting events such as strokes, myocardial infarction, encephalitis, acute kidney injury, and vasculitis. The production of IL-1, IL-2, IL-6, TNF-alpha, and interferon-gamma, all crucial components of normal immune responses, inadvertently become the causes of a cytokine storm. The cells of the central nervous system, the microglia, neurons, and astrocytes, are also involved in the release of pro-inflammatory cytokines affecting the nervous system, and effects of cytokine storms toward the CNS are not uncommon. There are many unknowns for pregnant women during the COVID-19 pandemic. Given that they are prone to have complications and severe disease infection with other types of coronaviruses, they have been identified as a vulnerable group and advised to take supplementary preventive measures. Physiological responses to pregnancy can include: However, from the evidence base, it is difficult to conclude whether pregnant women are at increased risk of grave consequences of this virus. In addition to the above, other clinical studies have proved that SARS-CoV-2 can affect the period of pregnancy in different ways. On the one hand, there is little evidence of its impact up to 12 weeks gestation. On the other hand, COVID-19 infection may cause increased rates of unfavourable outcomes in the course of the pregnancy. Some examples of these could be foetal growth restriction, preterm birth, and perinatal mortality, which refers to the foetal death past 22 or 28 completed weeks of pregnancy as well as the death among live-born children up to seven completed days of life. Unvaccinated women in later stages of pregnancy with COVID-19 are more likely than other patients to need very intensive care. Babies born to mothers with COVID-19 are more likely to have breathing problems. Pregnant women are strongly encouraged to get vaccinated. Further information: COVID-19 testing COVID‑19 can provisionally be diagnosed on the basis of symptoms and confirmed using reverse transcription polymerase chain reaction (RT-PCR) or other nucleic acid testing of infected secretions. Along with laboratory testing, chest CT scans may be helpful to diagnose COVID‑19 in individuals with a high clinical suspicion of infection. Detection of a past infection is possible with serological tests, which detect antibodies produced by the body in response to the infection. Main article: COVID-19 testing The standard methods of testing for presence of SARS-CoV-2 are nucleic acid tests, which detects the presence of viral RNA fragments. As these tests detect RNA but not infectious virus, its "ability to determine duration of infectivity of patients is limited." The test is typically done on respiratory samples obtained by a nasopharyngeal swab; however, a nasal swab or sputum sample may also be used. Results are generally available within hours. The WHO has published several testing protocols for the disease. Several laboratories and companies have developed serological tests, which detect antibodies produced by the body in response to infection. Several have been evaluated by Public Health England and approved for use in the UK. The University of Oxford's CEBM has pointed to mounting evidence that "a good proportion of 'new' mild cases and people re-testing positives after quarantine or discharge from hospital are not infectious, but are simply clearing harmless virus particles which their immune system has efficiently dealt with" and have called for "an international effort to standardize and periodically calibrate testing" In September 2020, the UK government issued "guidance for procedures to be implemented in laboratories to provide assurance of positive SARS-CoV-2 RNA results during periods of low prevalence, when there is a reduction in the predictive value of positive test results". Chest CT scans may be helpful to diagnose COVID‑19 in individuals with a high clinical suspicion of infection but are not recommended for routine screening. Bilateral multilobar ground-glass opacities with a peripheral, asymmetric, and posterior distribution are common in early infection. Subpleural dominance, crazy paving (lobular septal thickening with variable alveolar filling), and consolidation may appear as the disease progresses. Characteristic imaging features on chest radiographs and computed tomography (CT) of people who are symptomatic include asymmetric peripheral ground-glass opacities without pleural effusions. Many groups have created COVID‑19 datasets that include imagery such as the Italian Radiological Society which has compiled an international online database of imaging findings for confirmed cases. Due to overlap with other infections such as adenovirus, imaging without confirmation by rRT-PCR is of limited specificity in identifying COVID‑19. A large study in China compared chest CT results to PCR and demonstrated that though imaging is less specific for the infection, it is faster and more sensitive. In late 2019, the WHO assigned emergency ICD-10 disease codes U07.1 for deaths from lab-confirmed SARS-CoV-2 infection and U07.2 for deaths from clinically or epidemiologically diagnosed COVID‑19 without lab-confirmed SARS-CoV-2 infection. The main pathological findings at autopsy are: Further information: COVID‑19 vaccine, Workplace hazard controls for COVID‑19, Pandemic prevention, Non-pharmaceutical intervention, Preparations prior to COVID-19, COVID-19 surveillance, and COVID-19 apps Preventive measures to reduce the chances of infection include getting vaccinated, staying at home, wearing a mask in public, avoiding crowded places, keeping distance from others, ventilating indoor spaces, managing potential exposure durations, washing hands with soap and water often and for at least twenty seconds, practising good respiratory hygiene, and avoiding touching the eyes, nose, or mouth with unwashed hands. Those diagnosed with COVID‑19 or who believe they may be infected are advised by the CDC to stay home except to get medical care, call ahead before visiting a healthcare provider, wear a face mask before entering the healthcare provider's office and when in any room or vehicle with another person, cover coughs and sneezes with a tissue, regularly wash hands with soap and water and avoid sharing personal household items. The first COVID‑19 vaccine was granted regulatory approval on 2 December 2020 by the UK medicines regulator MHRA. It was evaluated for emergency use authorization (EUA) status by the US FDA, and in several other countries. Initially, the US National Institutes of Health guidelines do not recommend any medication for prevention of COVID‑19, before or after exposure to the SARS-CoV-2 virus, outside the setting of a clinical trial. Without a vaccine, other prophylactic measures, or effective treatments, a key part of managing COVID‑19 is trying to decrease and delay the epidemic peak, known as "flattening the curve". This is done by slowing the infection rate to decrease the risk of health services being overwhelmed, allowing for better treatment of active cases, and delaying additional cases until effective treatments or a vaccine become available. Main article: COVID-19 vaccine Prior to the COVID‑19 pandemic, an established body of knowledge existed about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). This knowledge accelerated the development of various vaccine platforms during early 2020. The initial focus of SARS-CoV-2 vaccines was on preventing symptomatic, often severe illness. In January 2020, the SARS-CoV-2 genetic sequence data was shared through GISAID, and by March 2020, the global pharmaceutical industry announced a major commitment to address COVID‑19. In 2020, the first COVID-19 vaccines were developed and made available to the public through emergency use authorization. Initially, most COVID-19 vaccines were two-dose vaccines, with the sole exception being the single-dose Janssen COVID-19 vaccine. However, immunity from the vaccines has been found to wane over time, requiring people to get booster doses of the vaccine to maintain immunity against COVID-19. The COVID‑19 vaccines are widely credited for their role in reducing the spread of COVID-19 and reducing the severity and death caused by COVID‑19. According to a June 2022 study, COVID-19 vaccines prevented an additional 14.4 to 19.8 million deaths in 185 countries and territories from 8 December 2020 to 8 December 2021. Many countries implemented phased distribution plans that prioritized those at highest risk of complications, such as the elderly, and those at high risk of exposure and transmission, such as healthcare workers.Common side effects of COVID-19 vaccines include soreness, redness, rash, inflammation at the injection site, fatigue, headache, myalgia (muscle pain), and arthralgia (joint pain), which resolve without medical treatment within a few days. COVID-19 vaccines are not associated with a higher risk of adverse effects during pregnancy or while breastfeeding. Serious adverse events associated COVID‑19 vaccines, such as allergic reactions, are generally rare but of high interest to the public. Because COVID-19 vaccines are relatively new, new claims about possible side effects are still being made, and sometimes reports conflict. Main article: Face masks during the COVID-19 pandemic The WHO and the US CDC recommend individuals wear non-medical face coverings in public settings where there is an increased risk of transmission and where social distancing measures are difficult to maintain. This recommendation is meant to reduce the spread of the disease by asymptomatic and pre-symptomatic individuals and is complementary to established preventive measures such as social distancing. Face coverings limit the volume and travel distance of expiratory droplets dispersed when talking, breathing, and coughing. A face covering without vents or holes will also filter out particles containing the virus from inhaled and exhaled air, reducing the chances of infection. But, if the mask include an exhalation valve, a wearer that is infected (maybe without having noticed that, and asymptomatic) would transmit the virus outwards through it, despite any certification they can have. So the masks with exhalation valve are not for the infected wearers, and are not reliable to stop the pandemic in a large scale. Many countries and local jurisdictions encourage or mandate the use of face masks or cloth face coverings by members of the public to limit the spread of the virus. Masks are also strongly recommended for those who may have been infected and those taking care of someone who may have the disease. When not wearing a mask, the CDC recommends covering the mouth and nose with a tissue when coughing or sneezing and recommends using the inside of the elbow if no tissue is available. Proper hand hygiene after any cough or sneeze is encouraged. Healthcare professionals interacting directly with people who have COVID‑19 are advised to use respirators at least as protective as NIOSH-certified N95 or equivalent, in addition to other personal protective equipment. The CDC recommends that crowded indoor spaces should be avoided. When indoors, increasing the rate of air change, decreasing recirculation of air and increasing the use of outdoor air can reduce transmission. The WHO recommends ventilation and air filtration in public spaces to help clear out infectious aerosols. Exhaled respiratory particles can build-up within enclosed spaces with inadequate ventilation. The risk of COVID‑19 infection increases especially in spaces where people engage in physical exertion or raise their voice (e.g., exercising, shouting, singing) as this increases exhalation of respiratory droplets. Prolonged exposure to these conditions, typically more than 15 minutes, leads to higher risk of infection. Displacement ventilation with large natural inlets can move stale air directly to the exhaust in laminar flow while significantly reducing the concentration of droplets and particles. Passive ventilation reduces energy consumption and maintenance costs but may lack controllability and heat recovery. Displacement ventilation can also be achieved mechanically with higher energy and maintenance costs. The use of large ducts and openings helps to prevent mixing in closed environments. Recirculation and mixing should be avoided because recirculation prevents dilution of harmful particles and redistributes possibly contaminated air, and mixing increases the concentration and range of infectious particles and keeps larger particles in the air. Main article: Hand washing Thorough hand hygiene after any cough or sneeze is required. The WHO also recommends that individuals wash hands often with soap and water for at least twenty seconds, especially after going to the toilet or when hands are visibly dirty, before eating and after blowing one's nose. When soap and water are not available, the CDC recommends using an alcohol-based hand sanitiser with at least 60% alcohol. For areas where commercial hand sanitisers are not readily available, the WHO provides two formulations for local production. In these formulations, the antimicrobial activity arises from ethanol or isopropanol. Hydrogen peroxide is used to help eliminate bacterial spores in the alcohol; it is "not an active substance for hand antisepsis." Glycerol is added as a humectant. Social distancing (also known as physical distancing) includes infection control actions intended to slow the spread of the disease by minimising close contact between individuals. Methods include quarantines; travel restrictions; and the closing of schools, workplaces, stadiums, theatres, or shopping centres. Individuals may apply social distancing methods by staying at home, limiting travel, avoiding crowded areas, using no-contact greetings, and physically distancing themselves from others. Many governments are mandating or recommending social distancing in regions affected by the outbreak. Outbreaks have occurred in prisons due to crowding and an inability to enforce adequate social distancing. In the United States, the prisoner population is ageing and many of them are at high risk for poor outcomes from COVID‑19 due to high rates of coexisting heart and lung disease, and poor access to high-quality healthcare. After being expelled from the body, coronaviruses can survive on surfaces for hours to days. If a person touches the dirty surface, they may deposit the virus at the eyes, nose, or mouth where it can enter the body and cause infection. Evidence indicates that contact with infected surfaces is not the main driver of COVID‑19, leading to recommendations for optimised disinfection procedures to avoid issues such as the increase of antimicrobial resistance through the use of inappropriate cleaning products and processes. Deep cleaning and other surface sanitation has been criticised as hygiene theatre, giving a false sense of security against something primarily spread through the air. The amount of time that the virus can survive depends significantly on the type of surface, the temperature, and the humidity. Coronaviruses die very quickly when exposed to the UV light in sunlight. Like other enveloped viruses, SARS-CoV-2 survives longest when the temperature is at room temperature or lower, and when the relative humidity is low (<50%). On many surfaces, including glass, some types of plastic, stainless steel, and skin, the virus can remain infective for several days indoors at room temperature, or even about a week under ideal conditions. On some surfaces, including cotton fabric and copper, the virus usually dies after a few hours. The virus dies faster on porous surfaces than on non-porous surfaces due to capillary action within pores and faster aerosol droplet evaporation. However, of the many surfaces tested, two with the longest survival times are N95 respirator masks and surgical masks, both of which are considered porous surfaces. The CDC says that in most situations, cleaning surfaces with soap or detergent, not disinfecting, is enough to reduce risk of transmission. The CDC recommends that if a COVID‑19 case is suspected or confirmed at a facility such as an office or day care, all areas such as offices, bathrooms, common areas, shared electronic equipment like tablets, touch screens, keyboards, remote controls, and ATMs used by the ill persons should be disinfected. Surfaces may be decontaminated with 62–71 per cent ethanol, 50–100 per cent isopropanol, 0.1 per cent sodium hypochlorite, 0.5 per cent hydrogen peroxide, 0.2–7.5 per cent povidone-iodine, or 50–200 ppm hypochlorous acid. Other solutions, such as benzalkonium chloride and chlorhexidine gluconate, are less effective. Ultraviolet germicidal irradiation may also be used, although popular devices require 5–10 min exposure and may deteriorate some materials over time. A datasheet comprising the authorised substances to disinfection in the food industry (including suspension or surface tested, kind of surface, use dilution, disinfectant and inocuylum volumes) can be seen in the supplementary material of. Self-isolation at home has been recommended for those diagnosed with COVID‑19 and those who suspect they have been infected. Health agencies have issued detailed instructions for proper self-isolation. Many governments have mandated or recommended self-quarantine for entire populations. The strongest self-quarantine instructions have been issued to those in high-risk groups. Those who may have been exposed to someone with COVID‑19 and those who have recently travelled to a country or region with the widespread transmission have been advised to self-quarantine for 14 days from the time of last possible exposure. A 2021 Cochrane rapid review found that based upon low-certainty evidence, international travel-related control measures such as restricting cross-border travel may help to contain the spread of COVID‑19. Additionally, symptom/exposure-based screening measures at borders may miss many positive cases. While test-based border screening measures may be more effective, it could also miss many positive cases if only conducted upon arrival without follow-up. The review concluded that a minimum 10-day quarantine may be beneficial in preventing the spread of COVID‑19 and may be more effective if combined with an additional control measure like border screening. Main article: Treatment and management of COVID-19 Although several medications have been approved in different countries as of April 2022, not all countries have these medications. Patients with mild to moderate symptoms who are in the risk groups can take nirmatrelvir/ritonavir (marketed as Paxlovid) or remdesivir, either of which reduces the risk of serious illness or hospitalization. In the US, the Biden Administration COVID-19 action plan includes the Test to Treat initiative, where people can go to a pharmacy, take a COVID test, and immediately receive free Paxlovid if they test positive. Highly effective vaccines have reduced mortality related to SARS-CoV-2; however, for those awaiting vaccination, as well as for the estimated millions of immunocompromised persons who are unlikely to respond robustly to vaccination, treatment remains important. The cornerstone of management of COVID-19 has been supportive care, which includes treatment to relieve symptoms, fluid therapy, oxygen support and prone positioning as needed, and medications or devices to support other affected vital organs. Most cases of COVID-19 are mild. In these, supportive care includes medication such as paracetamol or NSAIDs to relieve symptoms (fever, body aches, cough), proper intake of fluids, rest, and nasal breathing. Good personal hygiene and a healthy diet are also recommended. As of April 2020 the U.S. Centers for Disease Control and Prevention (CDC) recommended that those who suspect they are carrying the virus isolate themselves at home and wear a face mask.As of November 2020 use of the glucocorticoid dexamethasone had been strongly recommended in those severe cases treated in hospital with low oxygen levels, to reduce the risk of death. Noninvasive ventilation and, ultimately, admission to an intensive care unit for mechanical ventilation may be required to support breathing. Extracorporeal membrane oxygenation (ECMO) has been used to address respiratory failure, but its benefits are still under consideration. Some of the cases of severe disease course are caused by systemic hyper-inflammation, the so-called cytokine storm. See also: COVID-19 pandemic death rates by country The severity of COVID‑19 varies. The disease may take a mild course with few or no symptoms, resembling other common upper respiratory diseases such as the common cold. In 3–4% of cases (7.4% for those over age 65) symptoms are severe enough to cause hospitalisation. Mild cases typically recover within two weeks, while those with severe or critical diseases may take three to six weeks to recover. Among those who have died, the time from symptom onset to death has ranged from two to eight weeks. The Italian Istituto Superiore di Sanità reported that the median time between the onset of symptoms and death was twelve days, with seven being hospitalised. However, people transferred to an ICU had a median time of ten days between hospitalisation and death. Abnormal sodium levels during hospitalization with COVID-19 are associated with poor prognoses: high sodium with a greater risk of death, and low sodium with an increased chance of needing ventilator support. Prolonged prothrombin time and elevated C-reactive protein levels on admission to the hospital are associated with severe course of COVID‑19 and with a transfer to ICU. Some early studies suggest 10% to 20% of people with COVID‑19 will experience symptoms lasting longer than a month. A majority of those who were admitted to hospital with severe disease report long-term problems including fatigue and shortness of breath. On 30 October 2020, WHO chief Tedros Adhanom warned that "to a significant number of people, the COVID virus poses a range of serious long-term effects." He has described the vast spectrum of COVID‑19 symptoms that fluctuate over time as "really concerning". They range from fatigue, a cough and shortness of breath, to inflammation and injury of major organs – including the lungs and heart, and also neurological and psychologic effects. Symptoms often overlap and can affect any system in the body. Infected people have reported cyclical bouts of fatigue, headaches, months of complete exhaustion, mood swings, and other symptoms. Tedros therefore concluded that a strategy of achieving herd immunity by infection, rather than vaccination, is "morally unconscionable and unfeasible". In terms of hospital readmissions about 9% of 106,000 individuals had to return for hospital treatment within two months of discharge. The average to readmit was eight days since first hospital visit. There are several risk factors that have been identified as being a cause of multiple admissions to a hospital facility. Among these are advanced age (above 65 years of age) and presence of a chronic condition such as diabetes, COPD, heart failure or chronic kidney disease. According to scientific reviews smokers are more likely to require intensive care or die compared to non-smokers. Acting on the same ACE2 pulmonary receptors affected by smoking, air pollution has been correlated with the disease. Short term and chronic exposure to air pollution seems to enhance morbidity and mortality from COVID‑19. Pre-existing heart and lung diseases and also obesity, especially in conjunction with fatty liver disease, contributes to an increased health risk of COVID‑19. It is also assumed that those that are immunocompromised are at higher risk of getting severely sick from SARS-CoV-2. One research study that looked into the COVID‑19 infections in hospitalised kidney transplant recipients found a mortality rate of 11%. Men with untreated hypogonadism were 2.4 times more likely than men with eugonadism to be hospitalized if they contracted COVID-19; Hypogonad men treated with testosterone were less likely to be hospitalized for COVID-19 than men who were not treated for hypogonadism. Genetics plays an important role in the ability to fight off Covid. For instance, those that do not produce detectable type I interferons or produce auto-antibodies against these may get much sicker from COVID‑19. Genetic screening is able to detect interferon effector genes. Some genetic variants are risk factors in specific populations. For instance, and allele of the DOCK2 gene (dedicator of cytokinesis 2 gene) is a common risk factor in Asian populations but much less common in Europe. The mutation leads to lower expression of DOCK2 especially in younger patients with severe Covid. In fact, many other genes and genetic variants have been found that determine the outcome of SARS-CoV-2 infections. While very young children have experienced lower rates of infection, older children have a rate of infection that is similar to the population as a whole. Children are likely to have milder symptoms and are at lower risk of severe disease than adults. The CDC reports that in the US roughly a third of hospitalised children were admitted to the ICU, while a European multinational study of hospitalised children from June 2020, found that about 8% of children admitted to a hospital needed intensive care. Four of the 582 children (0.7%) in the European study died, but the actual mortality rate may be "substantially lower" since milder cases that did not seek medical help were not included in the study. Complications may include pneumonia, acute respiratory distress syndrome (ARDS), multi-organ failure, septic shock, and death. Cardiovascular complications may include heart failure, arrhythmias (including atrial fibrillation), heart inflammation, and thrombosis, particularly venous thromboembolism. Approximately 20–30% of people who present with COVID‑19 have elevated liver enzymes, reflecting liver injury. Neurologic manifestations include seizure, stroke, encephalitis, and Guillain–Barré syndrome (which includes loss of motor functions). Following the infection, children may develop paediatric multisystem inflammatory syndrome, which has symptoms similar to Kawasaki disease, which can be fatal. In very rare cases, acute encephalopathy can occur, and it can be considered in those who have been diagnosed with COVID‑19 and have an altered mental status. In the case of pregnant women, it is important to note that, according to the US Centers for Disease Control and Prevention, pregnant women are at increased risk of becoming seriously ill from COVID‑19. This is because pregnant women with COVID‑19 appear to be more likely to develop respiratory and obstetric complications that can lead to miscarriage, premature delivery and intrauterine growth restriction. Fungal infections such as aspergillosis, candidiasis, cryptococcosis and mucormycosis have been recorded in patients recovering from COVID‑19. Further information: Long COVID Some early studies suggest that 10–20% of people with COVID‑19 will experience symptoms lasting longer than a month. A majority of those who were admitted to hospital with severe disease report long-term problems, including fatigue and shortness of breath. About 5–10% of patients admitted to hospital progress to severe or critical disease, including pneumonia and acute respiratory failure. By a variety of mechanisms, the lungs are the organs most affected in COVID‑19. In people requiring hospital admission, up to 98% of CT scans performed show lung abnormalities after 28 days of illness even if they had clinically improved. People with advanced age, severe disease, prolonged ICU stays, or who smoke are more likely to have long-lasting effects, including pulmonary fibrosis. Overall, approximately one-third of those investigated after four weeks will have findings of pulmonary fibrosis or reduced lung function as measured by DLCO, even in asymptomatic people, but with the suggestion of continuing improvement with the passing of more time. After severe disease, lung function can take anywhere from three months to a year or more to return to previous levels. The risks of cognitive deficit, dementia, psychotic disorders, and epilepsy or seizures persists at an increased level two years after infection. See also: COVID-19 vaccine The immune response by humans to SARS-CoV-2 virus occurs as a combination of the cell-mediated immunity and antibody production, just as with most other infections. B cells interact with T cells and begin dividing before selection into the plasma cell, partly on the basis of their affinity for antigen. Since SARS-CoV-2 has been in the human population only since December 2019, it remains unknown if the immunity is long-lasting in people who recover from the disease. The presence of neutralising antibodies in blood strongly correlates with protection from infection, but the level of neutralising antibody declines with time. Those with asymptomatic or mild disease had undetectable levels of neutralising antibody two months after infection. In another study, the level of neutralising antibodies fell four-fold one to four months after the onset of symptoms. However, the lack of antibodies in the blood does not mean antibodies will not be rapidly produced upon reexposure to SARS-CoV-2. Memory B cells specific for the spike and nucleocapsid proteins of SARS-CoV-2 last for at least six months after the appearance of symptoms. As of August 2021, reinfection with COVID‑19 was possible but uncommon. The first case of reinfection was documented in August 2020. A systematic review found 17 cases of confirmed reinfection in medical literature as of May 2021. With the Omicron variant, as of 2022, reinfections have become common, albeit it is unclear how common. COVID-19 reinfections are thought to likely be less severe than primary infections, especially if one was previously infected by the same variant.[additional citation(s) needed] Several measures are commonly used to quantify mortality. These numbers vary by region and over time and are influenced by the volume of testing, healthcare system quality, treatment options, time since the initial outbreak, and population characteristics such as age, sex, and overall health. The mortality rate reflects the number of deaths within a specific demographic group divided by the population of that demographic group. Consequently, the mortality rate reflects the prevalence as well as the severity of the disease within a given population. Mortality rates are highly correlated to age, with relatively low rates for young people and relatively high rates among the elderly. In fact, one relevant factor of mortality rates is the age structure of the countries' populations. For example, the case fatality rate for COVID‑19 is lower in India than in the US since India's younger population represents a larger percentage than in the US. The case fatality rate (CFR) reflects the number of deaths divided by the number of diagnosed cases within a given time interval. Based on Johns Hopkins University statistics, the global death-to-case ratio is 1.06% (6,548,484/618,520,614) as of 3 October 2022. The number varies by region. A key metric in gauging the severity of COVID‑19 is the infection fatality rate (IFR), also referred to as the infection fatality ratio or infection fatality risk. This metric is calculated by dividing the total number of deaths from the disease by the total number of infected individuals; hence, in contrast to the CFR, the IFR incorporates asymptomatic and undiagnosed infections as well as reported cases. A December 2020 systematic review and meta-analysis estimated that population IFR during the first wave of the pandemic was about 0.5% to 1% in many locations (including France, Netherlands, New Zealand, and Portugal), 1% to 2% in other locations (Australia, England, Lithuania, and Spain), and exceeded 2% in Italy. That study also found that most of these differences in IFR reflected corresponding differences in the age composition of the population and age-specific infection rates; in particular, the metaregression estimate of IFR is very low for children and younger adults (e.g., 0.002% at age 10 and 0.01% at age 25) but increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85. These results were also highlighted in a December 2020 report issued by the WHO. An analysis of those IFR rates indicates that COVID‑19 is hazardous not only for the elderly but also for middle-aged adults, for whom the infection fatality rate of COVID-19 is two orders of magnitude greater than the annualised risk of a fatal automobile accident and far more dangerous than seasonal influenza. At an early stage of the pandemic, the World Health Organization reported estimates of IFR between 0.3% and 1%. On 2 July, The WHO's chief scientist reported that the average IFR estimate presented at a two-day WHO expert forum was about 0.6%. In August, the WHO found that studies incorporating data from broad serology testing in Europe showed IFR estimates converging at approximately 0.5–1%. Firm lower limits of IFRs have been established in a number of locations such as New York City and Bergamo in Italy since the IFR cannot be less than the population fatality rate. (After sufficient time however, people can get reinfected). As of 10 July, in New York City, with a population of 8.4 million, 23,377 individuals (18,758 confirmed and 4,619 probable) have died with COVID‑19 (0.3% of the population). Antibody testing in New York City suggested an IFR of ≈0.9%, and ≈1.4%. In Bergamo province, 0.6% of the population has died. In September 2020, the U.S. Centers for Disease Control and Prevention (CDC) reported preliminary estimates of age-specific IFRs for public health planning purposes. Main article: Gendered impact of the COVID-19 pandemic \|Percentage of infected people who are hospitalised\| \|Percentage of hospitalised people who go to Intensive Care Unit\| \|Percent of hospitalised people who die\| \|Percent of infected people who die – infection fatality rate (IFR)\| \|Numbers in parentheses are 95% credible intervals for the estimates.\| COVID‑19 case fatality rates are higher among men than women in most countries. However, in a few countries like India, Nepal, Vietnam, and Slovenia the fatality cases are higher in women than men. Globally, men are more likely to be admitted to the ICU and more likely to die. One meta-analysis found that globally, men were more likely to get COVID‑19 than women; there were approximately 55 men and 45 women per 100 infections (CI: 51.43–56.58). The Chinese Center for Disease Control and Prevention reported the death rate was 2.8% for men and 1.7% for women. Later reviews in June 2020 indicated that there is no significant difference in susceptibility or in CFR between genders. One review acknowledges the different mortality rates in Chinese men, suggesting that it may be attributable to lifestyle choices such as smoking and drinking alcohol rather than genetic factors. Smoking, which in some countries like China is mainly a male activity, is a habit that contributes to increasing significantly the case fatality rates among men. Sex-based immunological differences, lesser prevalence of smoking in women and men developing co-morbid conditions such as hypertension at a younger age than women could have contributed to the higher mortality in men. In Europe as of February 2020, 57% of the infected people were men and 72% of those died with COVID‑19 were men. As of April 2020, the US government is not tracking sex-related data of COVID‑19 infections. Research has shown that viral illnesses like Ebola, HIV, influenza and SARS affect men and women differently. In the US, a greater proportion of deaths due to COVID‑19 have occurred among African Americans and other minority groups. Structural factors that prevent them from practising social distancing include their concentration in crowded substandard housing and in "essential" occupations such as retail grocery workers, public transit employees, health-care workers and custodial staff. Greater prevalence of lacking health insurance and care of underlying conditions such as diabetes, hypertension, and heart disease also increase their risk of death. Similar issues affect Native American and Latino communities. On the one hand, in the Dominican Republic there is a clear example of both gender and ethnic inequality. In this Latin American territory, there is great inequality and precariousness that especially affects Dominican women, with greater emphasis on those of Haitian descent. According to a US health policy non-profit, 34% of American Indian and Alaska Native People (AIAN) non-elderly adults are at risk of serious illness compared to 21% of white non-elderly adults. The source attributes it to disproportionately high rates of many health conditions that may put them at higher risk as well as living conditions like lack of access to clean water. Leaders have called for efforts to research and address the disparities. In the UK, a greater proportion of deaths due to COVID‑19 have occurred in those of a Black, Asian, and other ethnic minority background. More severe impacts upon patients including the relative incidence of the necessity of hospitalisation requirements, and vulnerability to the disease has been associated via DNA analysis to be expressed in genetic variants at chromosomal region 3, features that are associated with European Neanderthal heritage. That structure imposes greater risks that those affected will develop a more severe form of the disease. The findings are from Professor Svante Pääbo and researchers he leads at the Max Planck Institute for Evolutionary Anthropology and the Karolinska Institutet. This admixture of modern human and Neanderthal genes is estimated to have occurred roughly between 50,000 and 60,000 years ago in Southern Europe. Biological factors (immune response) and the general behaviour (habits) can strongly determine the consequences of COVID‑19. Most of those who die of COVID‑19 have pre-existing (underlying) conditions, including hypertension, diabetes mellitus, and cardiovascular disease. According to March data from the United States, 89% of those hospitalised had preexisting conditions. The Italian Istituto Superiore di Sanità reported that out of 8.8% of deaths where medical charts were available, 96.1% of people had at least one comorbidity with the average person having 3.4 diseases. According to this report the most common comorbidities are hypertension (66% of deaths), type 2 diabetes (29.8% of deaths), ischaemic heart disease (27.6% of deaths), atrial fibrillation (23.1% of deaths) and chronic renal failure (20.2% of deaths). Most critical respiratory comorbidities according to the US Centers for Disease Control and Prevention (CDC), are: moderate or severe asthma, pre-existing COPD, pulmonary fibrosis, cystic fibrosis. Evidence stemming from meta-analysis of several smaller research papers also suggests that smoking can be associated with worse outcomes. When someone with existing respiratory problems is infected with COVID‑19, they might be at greater risk for severe symptoms. COVID‑19 also poses a greater risk to people who misuse opioids and methamphetamines, insofar as their drug use may have caused lung damage. In August 2020, the CDC issued a caution that tuberculosis (TB) infections could increase the risk of severe illness or death. The WHO recommended that people with respiratory symptoms be screened for both diseases, as testing positive for COVID‑19 could not rule out co-infections. Some projections have estimated that reduced TB detection due to the pandemic could result in 6.3 million additional TB cases and 1.4 million TB-related deaths by 2025. The virus is thought to be of natural animal origin, most likely through spillover infection. A joint-study conducted in early 2021 by the People's Republic of China and the World Health Organization indicated that the virus descended from a coronavirus that infects wild bats, and likely spread to humans through an intermediary wildlife host. There are several theories about where the index case originated and investigations into the origin of the pandemic are ongoing. According to articles published in July 2022 in Science, virus transmission into humans occurred through two spillover events in November 2019 and was likely due to live wildlife trade on the Huanan wet market in the city of Wuhan (Hubei, China). Doubts about the conclusions have mostly centred on the precise site of spillover. Earlier phylogenetics estimated that SARS-CoV-2 arose in October or November 2019. A phylogenetic algorithm analysis suggested that the virus may have been circulating in Guangdong before Wuhan. The possibility that the virus was accidentally released from a laboratory has also been under consideration. U.S intelligence agencies found that the virus was not developed as a biological weapon and that it is unlikely for it to have been genetically engineered. The first confirmed human infections were in Wuhan. A study of the first 41 cases of confirmed COVID‑19, published in January 2020 in The Lancet, reported the earliest date of onset of symptoms as 1 December 2019. Official publications from the WHO reported the earliest onset of symptoms as 8 December 2019. Human-to-human transmission was confirmed by the WHO and Chinese authorities by 20 January 2020. According to official Chinese sources, these were mostly linked to the Huanan Seafood Wholesale Market, which also sold live animals. In May 2020, George Gao, the director of the CDC, said animal samples collected from the seafood market had tested negative for the virus, indicating that the market was the site of an early superspreading event, but that it was not the site of the initial outbreak. Traces of the virus have been found in wastewater samples that were collected in Milan and Turin, Italy, on 18 December 2019. By December 2019, the spread of infection was almost entirely driven by human-to-human transmission. The number of COVID-19 cases in Hubei gradually increased, reaching sixty by 20 December, and at least 266 by 31 December. On 24 December, Wuhan Central Hospital sent a bronchoalveolar lavage fluid (BAL) sample from an unresolved clinical case to sequencing company Vision Medicals. On 27 and 28 December, Vision Medicals informed the Wuhan Central Hospital and the Chinese CDC of the results of the test, showing a new coronavirus. A pneumonia cluster of unknown cause was observed on 26 December and treated by the doctor Zhang Jixian in Hubei Provincial Hospital, who informed the Wuhan Jianghan CDC on 27 December. On 30 December, a test report addressed to Wuhan Central Hospital, from company CapitalBio Medlab, stated an erroneous positive result for SARS, causing a group of doctors at Wuhan Central Hospital to alert their colleagues and relevant hospital authorities of the result. The Wuhan Municipal Health Commission issued a notice to various medical institutions on "the treatment of pneumonia of unknown cause" that same evening. Eight of these doctors, including Li Wenliang (punished on 3 January), were later admonished by the police for spreading false rumours and another, Ai Fen, was reprimanded by her superiors for raising the alarm. The Wuhan Municipal Health Commission made the first public announcement of a pneumonia outbreak of unknown cause on 31 December, confirming 27 cases – enough to trigger an investigation. During the early stages of the outbreak, the number of cases doubled approximately every seven and a half days. In early and mid-January 2020, the virus spread to other Chinese provinces, helped by the Chinese New Year migration and Wuhan being a transport hub and major rail interchange. On 20 January, China reported nearly 140 new cases in one day, including two people in Beijing and one in Shenzhen. Later official data shows 6,174 people had already developed symptoms by then, and more may have been infected. A report in The Lancet on 24 January indicated human transmission, strongly recommended personal protective equipment for health workers, and said testing for the virus was essential due to its "pandemic potential". On 30 January, the WHO declared COVID-19 a Public Health Emergency of International Concern. By this time, the outbreak spread by a factor of 100 to 200 times. Italy had its first confirmed cases on 31 January 2020, two tourists from China. Italy overtook China as the country with the most deaths on 19 March 2020. By 26 March the United States had overtaken China and Italy with the highest number of confirmed cases in the world. Research on coronavirus genomes indicates the majority of COVID-19 cases in New York came from European travellers, rather than directly from China or any other Asian country. Retesting of prior samples found a person in France who had the virus on 27 December 2019, and a person in the United States who died from the disease on 6 February 2020. RT-PCR testing of untreated wastewater samples from Brazil and Italy have suggested detection of SARS-CoV-2 as early as November and December 2019, respectively, but the methods of such sewage studies have not been optimised, many have not been peer-reviewed, details are often missing, and there is a risk of false positives due to contamination or if only one gene target is detected. A September 2020 review journal article said, "The possibility that the COVID‑19 infection had already spread to Europe at the end of last year is now indicated by abundant, even if partially circumstantial, evidence," including pneumonia case numbers and radiology in France and Italy in November and December. As of 1 October 2021[update], Reuters reported that it had estimated the worldwide total number of deaths due to COVID‑19 to have exceeded five million. Main article: COVID-19 misinformation After the initial outbreak of COVID‑19, misinformation and disinformation regarding the origin, scale, prevention, treatment, and other aspects of the disease rapidly spread online. In September 2020, the US Centers for Disease Control and Prevention (CDC) published preliminary estimates of the risk of death by age groups in the United States, but those estimates were widely misreported and misunderstood. Humans appear to be capable of spreading the virus to some other animals, a type of disease transmission referred to as zooanthroponosis. Some pets, especially cats and ferrets, can catch this virus from infected humans. Symptoms in cats include respiratory (such as a cough) and digestive symptoms. Cats can spread the virus to other cats, and may be able to spread the virus to humans, but cat-to-human transmission of SARS-CoV-2 has not been proven. Compared to cats, dogs are less susceptible to this infection. Behaviours which increase the risk of transmission include kissing, licking, and petting the animal. The virus does not appear to be able to infect pigs, ducks, or chickens at all. Mice, rats, and rabbits, if they can be infected at all, are unlikely to be involved in spreading the virus. Tigers and lions in zoos have become infected as a result of contact with infected humans. As expected, monkeys and great ape species such as orangutans can also be infected with the COVID‑19 virus. Minks, which are in the same family as ferrets, have been infected. Minks may be asymptomatic, and can also spread the virus to humans. Multiple countries have identified infected animals in mink farms. Denmark, a major producer of mink pelts, ordered the slaughter of all minks over fears of viral mutations, following an outbreak referred to as Cluster 5. A vaccine for mink and other animals is being researched. Further information: COVID-19 drug development International research on vaccines and medicines in COVID‑19 is underway by government organisations, academic groups, and industry researchers. The CDC has classified it to require a BSL3 grade laboratory. There has been a great deal of COVID‑19 research, involving accelerated research processes and publishing shortcuts to meet the global demand. As of December 2020[update], hundreds of clinical trials have been undertaken, with research happening on every continent except Antarctica. As of November 2020[update], more than 200 possible treatments have been studied in humans. Further information: COVID-19 vaccine Modelling research has been conducted with several objectives, including predictions of the dynamics of transmission, diagnosis and prognosis of infection, estimation of the impact of interventions, or allocation of resources. Modelling studies are mostly based on compartmental models in epidemiology, estimating the number of infected people over time under given conditions. Several other types of models have been developed and used during the COVID‑19 including computational fluid dynamics models to study the flow physics of COVID‑19, retrofits of crowd movement models to study occupant exposure, mobility-data based models to investigate transmission, or the use of macroeconomic models to assess the economic impact of the pandemic. Further, conceptual frameworks from crisis management research have been applied to better understand the effects of COVID‑19 on organisations worldwide. Main article: COVID-19 drug repurposing research Repurposed antiviral drugs make up most of the research into COVID‑19 treatments. Other candidates in trials include vasodilators, corticosteroids, immune therapies, lipoic acid, bevacizumab, and recombinant angiotensin-converting enzyme 2. In March 2020, the World Health Organization (WHO) initiated the Solidarity trial to assess the treatment effects of some promising drugs: an experimental drug called remdesivir; anti-malarial drugs chloroquine and hydroxychloroquine; two anti-HIV drugs, lopinavir/ritonavir; and interferon-beta. More than 300 active clinical trials are underway as of April 2020. Research on the antimalarial drugs hydroxychloroquine and chloroquine showed that they were ineffective at best, and that they may reduce the antiviral activity of remdesivir. By May 2020[update], France, Italy, and Belgium had banned the use of hydroxychloroquine as a COVID‑19 treatment. In June, initial results from the randomised RECOVERY Trial in the United Kingdom showed that dexamethasone reduced mortality by one third for people who are critically ill on ventilators and one fifth for those receiving supplemental oxygen. Because this is a well-tested and widely available treatment, it was welcomed by the WHO, which is in the process of updating treatment guidelines to include dexamethasone and other steroids. Based on those preliminary results, dexamethasone treatment has been recommended by the NIH for patients with COVID‑19 who are mechanically ventilated or who require supplemental oxygen but not in patients with COVID‑19 who do not require supplemental oxygen. In September 2020, the WHO released updated guidance on using corticosteroids for COVID‑19. The WHO recommends systemic corticosteroids rather than no systemic corticosteroids for the treatment of people with severe and critical COVID‑19 (strong recommendation, based on moderate certainty evidence). The WHO suggests not to use corticosteroids in the treatment of people with non-severe COVID‑19 (conditional recommendation, based on low certainty evidence). The updated guidance was based on a meta-analysis of clinical trials of critically ill COVID‑19 patients. In September 2020, the European Medicines Agency (EMA) endorsed the use of dexamethasone in adults and adolescents from twelve years of age and weighing at least 40 kilograms (88 lb) who require supplemental oxygen therapy. Dexamethasone can be taken by mouth or given as an injection or infusion (drip) into a vein. In November 2020, the US Food and Drug Administration (FDA) issued an emergency use authorization for the investigational monoclonal antibody therapy bamlanivimab for the treatment of mild-to-moderate COVID‑19. Bamlanivimab is authorised for people with positive results of direct SARS-CoV-2 viral testing who are twelve years of age and older weighing at least 40 kilograms (88 lb), and who are at high risk for progressing to severe COVID‑19 or hospitalisation. This includes those who are 65 years of age or older, or who have chronic medical conditions. In February 2021, the FDA issued an emergency use authorization (EUA) for bamlanivimab and etesevimab administered together for the treatment of mild to moderate COVID‑19 in people twelve years of age or older weighing at least 40 kilograms (88 lb) who test positive for SARS‑CoV‑2 and who are at high risk for progressing to severe COVID‑19. The authorised use includes treatment for those who are 65 years of age or older or who have certain chronic medical conditions. In April 2021, the FDA revoked the emergency use authorization (EUA) that allowed for the investigational monoclonal antibody therapy bamlanivimab, when administered alone, to be used for the treatment of mild-to-moderate COVID‑19 in adults and certain paediatric patients. A cytokine storm can be a complication in the later stages of severe COVID‑19. A cytokine storm is a potentially deadly immune reaction where a large amount of pro-inflammatory cytokines and chemokines are released too quickly. A cytokine storm can lead to ARDS and multiple organ failure. Data collected from Jin Yin-tan Hospital in Wuhan, China indicates that patients who had more severe responses to COVID‑19 had greater amounts of pro-inflammatory cytokines and chemokines in their system than patients who had milder responses. These high levels of pro-inflammatory cytokines and chemokines indicate presence of a cytokine storm. Tocilizumab has been included in treatment guidelines by China's National Health Commission after a small study was completed. It is undergoing a Phase II non-randomised trial at the national level in Italy after showing positive results in people with severe disease. Combined with a serum ferritin blood test to identify a cytokine storm (also called cytokine storm syndrome, not to be confused with cytokine release syndrome), it is meant to counter such developments, which are thought to be the cause of death in some affected people. The interleukin-6 receptor (IL-6R) antagonist was approved by the FDA to undergo a Phase III clinical trial assessing its effectiveness on COVID‑19 based on retrospective case studies for the treatment of steroid-refractory cytokine release syndrome induced by a different cause, CAR T cell therapy, in 2017. There is no randomised, controlled evidence that tocilizumab is an efficacious treatment for CRS. Prophylactic tocilizumab has been shown to increase serum IL-6 levels by saturating the IL-6R, driving IL-6 across the blood-brain barrier, and exacerbating neurotoxicity while having no effect on the incidence of CRS. Lenzilumab, an anti-GM-CSF monoclonal antibody, is protective in murine models for CAR T cell-induced CRS and neurotoxicity and is a viable therapeutic option due to the observed increase of pathogenic GM-CSF secreting T cells in hospitalised patients with COVID‑19. Transferring purified and concentrated antibodies produced by the immune systems of those who have recovered from COVID‑19 to people who need them is being investigated as a non-vaccine method of passive immunisation. Viral neutralisation is the anticipated mechanism of action by which passive antibody therapy can mediate defence against SARS-CoV-2. The spike protein of SARS-CoV-2 is the primary target for neutralising antibodies. As of 8 August 2020, eight neutralising antibodies targeting the spike protein of SARS-CoV-2 have entered clinical studies. It has been proposed that selection of broad-neutralising antibodies against SARS-CoV-2 and SARS-CoV might be useful for treating not only COVID‑19 but also future SARS-related CoV infections. Other mechanisms, however, such as antibody-dependant cellular cytotoxicity or phagocytosis, may be possible. Other forms of passive antibody therapy, for example, using manufactured monoclonal antibodies, are in development. The use of passive antibodies to treat people with active COVID‑19 is also being studied. This involves the production of convalescent serum, which consists of the liquid portion of the blood from people who recovered from the infection and contains antibodies specific to this virus, which is then administered to active patients. This strategy was tried for SARS with inconclusive results. An updated Cochrane review in May 2021 found high certainty evidence that, for the treatment of people with moderate to severe COVID‑19, convalescent plasma did not reduce mortality or bring about symptom improvement. There continues to be uncertainty about the safety of convalescent plasma administration to people with COVID‑19 and differing outcomes measured in different studies limits their use in determining efficacy. Since the outbreak of the COVID‑19 pandemic, scholars have explored the bioethics, normative economics, and political theories of healthcare policies related to the public health crisis. Academics have pointed to the moral distress of healthcare workers, ethics of distributing scarce healthcare resources such as ventilators, and the global justice of vaccine diplomacies. The socio-economic inequalities between genders, races, groups with disabilities, communities, regions, countries, and continents have also drawn attention in academia and the general public. The use of social distancing and the wearing of surgical masks and similar precautions against COVID‑19 may have caused a drop in the spread of the common cold and the flu. ((cite web)): CS1 maint: url-status (link) We detected in total 65776 variants with 5775 distinct variants. As at 1 February 2021, we assess that the cluster 5 variant is no longer circulating among humans in Denmark. U07.2 – COVID-19, virus not identified – COVID-19 NOS – Use this code when COVID-19 is diagnosed clinically or epidemiologically but laboratory testing is inconclusive or not available. Use additional code, if desired, to identify pneumonia or other manifestations A key issue for epidemiologists is helping policy makers decide the main objectives of mitigation – e.g. minimising morbidity and associated mortality, avoiding an epidemic peak that overwhelms health-care services, keeping the effects on the economy within manageable levels, and flattening the epidemic curve to wait for vaccine development and manufacture on scale and antiviral drug therapies. To prevent the spread of germs, including COVID-19, CDC recommends washing hands with soap and water whenever possible because it reduces the amount of many types of germs and chemicals on hands. But if soap and water are not readily available, using a hand sanitizer with at least 60% alcohol can help you avoid getting sick and spreading germs to others.	2	36	1	0	2	0.635627	3	17,241
Data Set for the Reporting of Ear and Temporal Bone Tumors: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting. The ear and temporal bone has complex anatomy and several critical structures, including dura and temporal lobe, facial nerve, internal carotid artery, and internal jugular vein, all in very close proximity (Figure 1). (4) Thus, the treatment options for both benign and malignant neoplasms in this area may require functionally destructive and cosmetically disfiguring surgeries equivalent to radical oncologic resections. (5) A comprehensive macroscopic examination is important for identifying critical prognostic factors, such as the structures involved, extent of invasion, and proximity to the margins, often requiring clinical and radiologic correlation. (6) The 3-dimensional surgical resection specimens can be difficult to handle at macroscopic exam (Figure 2). Furthermore, specific guidelines for the pathologic examination and reporting of these specimens are largely lacking. Thus, an international collaborative effort as achieved by the ICCR is critical for tumors of the ear and the temporal bone to ensure international uniformity in pathologic examination and facilitate multi-institutional and cross-regional data collection for improved patient management. The ICCR data set provides guidelines for the reporting of the biopsy and resection specimens of benign and malignant primary tumors of the external auditory canal (EAC), middle ear, and inner ear. (59) Cutaneous malignancies of the pinna are excluded, because these are incorporated into the skin and melanoma data sets. (7) The ICCR data sets include core and noncore elements. The core elements are required and considered essential for the clinical management and prognosis or staging of the neoplasms, and usually supported by National Health and Medical Research Council evidence level III-2 (analysis of prognostic factors among persons in a single arm of a randomized control trial) and above. (8) The noncore elements are recommended as good clinical practice but may not be clinically validated or used in management decisions at this time. The ICCR data set includes the minimum reporting requirements for ear and temporal bone tumors while providing the flexibility to include additional elements (noncore) that may be needed at the local level. There is significant variation in the strength of the evidence available for various tumors of the ear and temporal bone, with most data derived from retrospective case series because of the rare nature of the primary neoplasms. A summary of the ICCR guidelines for the reporting of the tumors of the ear and the temporal bone is presented along with a discussion of the salient evidence and practical issues. DATA SET ELEMENTS Core (Required) Elements Operative Procedure.--Surgical resection of the ear and the temporal bone is a significant undertaking, requiring comprehensive preoperative planning, with the resection of functionally critical structures associated with high treatment-related morbidity and mortality. (5,9-12) The resection specimens are often anatomically complex. The anatomic and surgical terminology may also be unfamiliar. Thus, the surgical team should be strongly encouraged to provide orienting marks with sutures and/or diagrams to facilitate optimal orientation and margin assessment. Photographic documentation of the specimen received in the laboratory prior to inking and sectioning is strongly encouraged (Figure 3), because this can be useful for clinicopathologic correlation at the multidisciplinary team meetings. The most commonly seen resection specimens include the following. (6,11) Sleeve Resection.--This procedure is used for small tumors located along the lateral aspect of the EAC. The specimen usually includes the conchal bowl and the cartilaginous part of the ear canal lateral to the tympanic membrane. Lateral Temporal Bone Resection.--This procedure is used for more medially located tumors that are confined to the EAC without extension into the middle ear. The lateral temporal bone resection usually includes the cartilaginous and bony parts of the EAC, the tympanic membrane, and the contents of the middle ear. Subtotal Temporal Bone Resection.--This procedure is used for tumors that extend into the middle ear space and include the entire EAC (Figure 4), the contents of the middle ear, and the cochlear and vestibular structures. The internal carotid artery forms the medial limit of this resection as it passes through the petrous temporal bone. Radical or Total Temporal Bone Resection.--This radical procedure is indicated for tumors that involve the petrous apex and extend intracranially or into the infratemporal fossa. This procedure usually includes resection of the petrous part of the temporal bone, with or without the petrous carotid. The stylomastoid complex is also often included in this specimen. Portions of the dura and the facial nerve may also be present. These resections may also be accompanied by a parotidectomy and/or a neck dissection, depending upon the extent of the tumor. (13-15) In cases when a neck lymph node dissection is submitted together with a tumor specimen, a separate, linked data set for Nodal Excisions and Neck Dissection Specimens for Head & Neck Tumours would be completed. (60) The data set includes free text to encompass all procedure types if the standard surgeries are not performed (ie, curettage, partial, or extended procedures). Specimens Submitted.--This section is a corollary of the operative procedure and largely depends on identification of the type of surgical resection performed and documentation of the various structures included. Thus, it forms the cornerstone of further macroscopic examination. The main specimen would depend upon the type of surgical procedures described above and may be accompanied by the temporomandibular joint, dura, brain tissue, stylomastoid complex, facial nerve, or internal jugular vein, depending upon the extent of the tumor. (16) The regional lymphatic basins of the ear and temporal bone, such as the parotid and ipsilateral neck dissection, may also be included if nodal involvement is suspected clinically or radiologically or if an elective neck dissection is performed for a squamous cell carcinoma. (13-15,17) Tumor Site.--Documentation of the exact location of the tumor is important because it correlates with the patient outcome. (5,6,9,18,19) The location of the tumor usually guides the surgery, while also influencing local control, and thus, prognosis. (6,19) As an example, patients with well-localized lateral EAC tumors (Figure 4) tend to have a much better outcome with lower functional morbidity compared with those with middle ear involvement. The patient prognosis worsens with the involvement of the facial nerve, the petrous apex, and increasing proximity to the brain. (5,9,17-20) The tumor site can be readily identified in en bloc, well-oriented specimens. (6) However, this may not be possible in a curettage or an otherwise compromised specimen, which then requires correlation with the imaging findings, operative report, and/or discussion with the treating team. The ICCR data set does include a "not-specified" option, but as the information in these elements is vital to a comprehensive and clinically relevant pathology report that guides further adjuvant therapy, it should be used in rare instances only after all good-faith efforts to obtain the information have been thoroughly exhausted. Tumor Dimensions.--Accurate assessment of the tumor size largely depends upon the type of specimen and the extent of the disease. Although identification and macroscopic measurement of the tumor size may be easy in a localized tumor in a well-oriented specimen, it may be impossible in a curettage or debulking specimen. Furthermore, the size of the tumor may be underestimated in the main specimen in cases with an extensive tumor involving separately submitted tissues (such as dura, facial nerve, and stylomastoid complex). (6) In some cases, inclusion of imaging findings may help yield a more accurate size. An attempt should be made to measure the depth of invasion whenever possible, particularly for the various carcinomas, as this has been shown to be an adverse prognostic feature. (21,22) Histologic Tumor Type.--The histologic classification provides information regarding the behavior of the tumor (ie, benign versus malignant) and also the propensity to develop local, regional, or distant spread. All ear and temporal bone tumors should be classified according to the most recent edition of the World Health Organization (WHO) Classification of Head and Neck Tumours (Table 1). (23-29) It is not within the scope of this article to review the histologic features and the differential diagnoses of these lesions, but in general there are limited data because of the rare nature of the tumors. Also, there is limited prognostic experience for most entities. (23,29,30) Among these, squamous cell carcinoma of the EAC is most common and also demonstrates the worst prognosis (Figures 2 through 4). (18,24,30,31) Ceruminous adenoid cystic carcinoma may be indistinguishable from a primary parotid gland tumor, which may require parotidectomy for thorough evaluation. (32,33) However, because of the sometimes extensive surgery required, benign tumors are also included in the classification for the sake of completeness (Figure 5). Histologic Tumor Grade.--Histologic tumor grade and degree of differentiation inform the behavior, with poorly differentiated/high-grade neoplasms generally associated with a worse outcome and increased risk of regional nodal metastases as opposed to well-differentiated/low-grade tumors. (21) Among the tumors of the ear and temporal bone, a 3-tiered grading system has conventionally been used for squamous cell carcinoma and salivary gland neoplasms (Figure 6). (23) The World Health Organization grading system is applied to meningiomas. (34) At this time, no grading systems are used for the other neoplasms. (23) Extent of Invasion.--Macroscopic examination of the resection specimen guides tissue selection for histologic examination (Table 2). Macroscopic examination of the tumor extent, photographic documentation, and appropriate annotation of the blocks in a block key, although time and labor intensive, are a critical component of pathologic examination of these specimens. The specimens should be sectioned in a manner that provides the best cross sections of the various anatomic structures and the tumor while also demonstrating the relationship of the tumor to these structures (Figure 4). (6) Detecting and documenting the involvement of these structures, especially temporomandibular joint, stylomastoid complex, parotid gland, etc, are of prognostic significance. Thus, the cylindrical sleeve and lateral temporal bone resections should be cut in the sagittal plane from anterior to posterior, whereas the more complex subtotal and radical temporal bone resections may require a more comprehensive approach, including sagittal section of the ear canal and axial sections of the pinna and the soft tissues around the temporal bone. (6) Dimensions of the macroscopically visible tumor should be recorded. The various structures macroscopically involved by the tumor (Table 2), such as skin, aural cartilage, bone (Figure 7), temporomandibular joint, and the parotid gland (Figure 8), and accompanying structures, such as facial nerve, stylomastoid complex, internal jugular vein, dura (Figure 8, B), and brain, should be documented and sampled for histologic examination (31,34) because in many cases the bony and soft tissue structures are histologically indistinguishable. (32,35) A corollary of the macroscopic examination, the microscopic exam serves to confirm or identify the presence of the tumor in the structures/areas noted during the macroscopic examination. Although structures such as the brain parenchyma and the parotid can be readily recognized histologically, most of the soft tissue, bony, and neural structures in this area do not have distinctive histologic features and are indistinguishable from each other. The tissue response to invasion and destruction, such as ulceration, granulation tissue, desmoplasia, and sclerosis, may further confound the recognition of these structures histologically. However, documentation of the structures involved provides critical prognostic information and guides adjuvant radiotherapy and/or chemotherapy. (12,31,35-37) Bone/Cartilage Invasion.--Bone/cartilage invasion is ideally assessed both on macroscopic as well as histologic exam (Figures 5 and 7). Correlation with radiologic findings and operative report may be required to determine the clinical and imaging index of suspicion for bone involvement. (38,39) The extent of bone invasion is essential to stage (.9,17,19,20,35,40) Patients with cartilage/bone involvement will generally require adjuvant therapy and have a poorer prognosis. (5,12,21,35) Thus, it is strongly recommended that histologic sections be taken from the areas of maximum bone involvement (after appropriate decalcification). Perineural Invasion.--Perineural invasion is considered an independent adverse prognostic feature. (22,41,42) Patients with involvement of a large, named nerve (ie, facial) have a poor clinical outcome. (41) Histologic correlation of perineural invasion to a named nerve (facial nerve, glossopharyngeal nerve, tympanic nerve, and great superficial and deep petrosal nerves) requires specific orientation and documentation in the gross specimen and submitted block protocol. When a small biopsy contains lesional tissue only without nerves, "cannot be assessed" should be selected so as to alert the clinical team that perineural invasion is not reliably excluded and that appropriate radiologic correlation is essential. (38) Lymphovascular Invasion.--The prognostic significance of lymphovascular involvement has not been separately evaluated for ear and temporal bone tumors. However, it can be inferred from other head and neck tumors that it may be of prognostic significance. Use of standardized information collected in this fashion would facilitate additional research by multiple institutions. Margin Status.--Margin assessment is the most challenging component of evaluating en bloc resection specimens. (6) Meticulously resected tumors with negative skin, soft tissue, and bone margins carry the best prognosis. (10,19,30,43,44) Assessment of the deep soft tissue and bone margins is often more clinically significant than superficial skin margins (Figure 4). (41) Distance to the margins should be measured in millimeters both macroscopically as well as histologically. Thus, ideally, the margins should be sampled in a radial manner to facilitate measurement. Although the data set requires only the distance to the closest margin and the tissue type at the margin (skin, soft tissue, bone, or parotid), indicating the location (superior/ inferior, medial/lateral, anterior/posterior) of the closest margins should be considered a best practice in a well-oriented specimen. Proactive discussion with the surgical team is often essential when involved or close deep soft tissue or bone margins may not have been histologically examined because of intraoperative drilling/burring techniques. (6,11) Additional, critical margins around the styloid process and mastoid may also be resected and sent separately for pathologic evaluation. Not included in the data set, but suggested, is the pattern of invasion, because patients with squamous cell carcinoma with a dyscohesive, tentacular pattern of infiltration have a higher risk of recurrence compared with those with pushing borders. (22,45) Pathologic Staging.--Currently, there is no universally accepted staging system for tumors of the ear and the temporal bone. The pathologic T staging recommended (Table 2) is largely determined by modifications of the Pittsburgh staging system, (40,46) based on retrospective clinical and radiologic evidence of patients with squamous cell carcinoma of the EAC and temporal bone, whereas other staging systems are also recognized. (18) Interestingly, none of these systems include nodal metastases, although regional lymph node metastasis is associated with a worse prognosis. (10,20) Tumors of the inner ear are extremely rare, with some retrospective case series proposing radiologic staging systems for these neoplasms. (47) Curettage or debulking specimens are generally submitted for inner ear tumors. Thus, an accurate clinical staging is probably of greater significance than accurate pathologic staging. Disease-free and disease-specific survival data are limited; however, it would stand to reason that tumors that extend beyond the temporal bone to involve the dura, present with facial nerve palsy due to nerve involvement, and/or involve the petrous apex will carry significantly poorer prognosis. (12,23,41,48) Thus, although the Union for International Cancer Control 8th edition staging system for tumors of the ear and the temporal bone is not established, staging may inform standardized therapy rather than use as a prognostic tool. Importantly, only skin squamous cell carcinoma of the EAC is covered by the American Joint Commission (AJCC) on Cancer 8th-edition staging manual. (49) The lymph nodes within the parotid gland as well as those surrounding the parotid gland and neck nodes form the regional nodal drainage basin of the tumors of the EAC and the temporal bone. (11,15,50) When lymph nodes are included in any specimens from the head and neck, the ICCR has developed a linked but separate Nodal Excisions and Neck Dissection Specimens for Head & Neck Tumours Histopathology Reporting Guide, (60) which would be completed in conjunction with the Ear and Temporal Bone Tumours Histopathology Reporting Guide. (59) However, it is critical to distinguish direct extension into an intraparotid node from metastases to a lymph node with extranodal extension. The former should be accounted for in the pT stage and the latter in the pN stage. Correlation with macroscopic examination is helpful in this context. Documentation of the extranodal extension is important because it is associated with poor prognosis. (49,51) The most common metastases to the intraparotid lymph nodes are from cutaneous primary tumors (squamous cell carcinoma or melanoma) that rarely arise as primary salivary gland neoplasms. The ICCR recommends that the suffixes m (multiple tumors), r (recurrent tumors), and y (posttherapy tumors) as suggested by AJCC be used while staging tumors of the EAC and temporal bone. The suffixes indicate an aggressive biology and contribute to the prognostic information. (50) Noncore (Recommended) Elements Tumor Focality.--Identification of multifocal or bilateral tumors is important in the context of certain syndrome or inherited neoplasms. Separate data sets should be used for reporting each additional neoplasm. Paraganglioma, (52,53) schwannoma, (54) meningioma, (54) and endolymphatic sac tumor (55) may be multifocal/bilateral, raising the possibility of familial or syndromic association, and requiring appropriate clinical investigation or confirmation. Coexistent Pathology.--The ability to identify coexistent pathology depends largely on the type of specimen. Management and prognosis may also be complicated by the coexistent pathology. Presence of acute or chronic osteomyelitis presents challenges for adjuvant radiotherapy and chemotherapy. (56) Otitis media has been associated with poor survival. (10) Previous radiation (most often for nasopharyngeal carcinoma (57) or for recurrent cutaneous squamous cell carcinoma (50)) may alter histologic interpretation. Cholesteatoma is a common concurrent finding (Figure 9). Ancillary Testing.--Immunohistochemistry may be used to confirm a diagnosis (Figure 10), whereas additional testing may serve prognostic or therapeutic goals (eg, SDHB, PD-L1). (29,53,58) The ear and the temporal bone is a complex anatomic site that is affected by a wide variety of relatively uncommon benign and malignant neoplasms. There are limited guidelines regarding the prognostic factors and patient outcomes of the tumors affecting this region. The employment of an internationally standardized reporting data set should not only facilitate the examination of these specimens, but also data collection for future research and international benchmarking. Accepted for publication October 1, 2018. Published online November 30, 2018. The authors would like to express their appreciation to the sponsoring societies and organizations and give special thanks to Fleur Webster and Hannah B. Canlas for their exceptional organizational and editing contributions. The views expressed are those of the authors solely. (1.) Srigley J, Lankshear S, Brierley J, et al. Closing the quality loop: facilitating improvement in oncology practice through timely access to clinical performance indicators. J Oncol Pract. 2013;9(5):e255-e261. (2.) Ellis DW, Srigley J. Does standardised structured reporting contribute to quality in diagnostic pathology?: the importance of evidence-based datasets. Virchows Arch. 2016;468(1):51-59. (3.) The International Collaboration on Cancer Reporting Web site. http://www. iccr-cancer.org. Accessed April 21, 2018. (4.) Snell R. Clinical Anatomy by Regions. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012. (5.) Cristalli G, Manciocco V, Pichi B, et al. Treatment and outcome of advanced external auditory canal and middle ear squamous cell carcinoma. J Craniofac Surg. 2009;20(3):816-821. (6.) Allanson BM, Low TH, Clark JR, Gupta R. Squamous cell carcinoma of the external auditory canal and temporal bone: an update. Head Neck Pathol. 2018; 12(3):407-418. (7.) Scolyer RA, Judge MJ, Evans A, et al. Data set for pathology reporting of cutaneous invasive melanoma: recommendations from the international collaboration on cancer reporting (ICCR). Am I Surg Pathol. 2013;37(12):1797-1814. (8.) NHMRC standards and procedures for externally developed guidelines. Canberra, Australia: National Health and Medical Research Council. 2007. https://www.nhmrc.gov.au/guidelines-publications/nh56. Accessed August 2018. (9.) Madsen AR, Gundgaard MG, Hoff CM, et al. Cancer of the external auditory canal and middle ear in Denmark from 1992 to 2001. Head Neck. 2008; 30(10):1332-1338. (10.) Nakagawa T, Kumamoto Y, Natori Y, et al. Squamous cell carcinoma of the external auditory canal and middle ear: an operation combined with preoperative chemoradiotherapy and a free surgical margin. Otol Neurotol. 2006;27(2):242-248; discussion 249. (11.) Evans PHR, Montgomery PQ, Gullane PJ. Principles and Practice of Head and Neck Surgery and Oncology. 2nd ed. Boca Raton, FL: CRC Press; 2009. (12.) Gidley PW. Managing malignancies of the external auditory canal. Expert Rev Anticancer Ther. 2009;9(9):1277-1282. (13.) Rinaldo A, Ferlito A, Suarez C, Kowalski LP. Nodal disease in temporal bone squamous carcinoma. Acta Otolaryngol. 2005;125(1):5-8. (14.) Zanoletti E, Danesi G. The problem of nodal disease in squamous cell carcinoma of the temporal bone. Acta Otolaryngol. 2010;130(8):913-916. (15.) Kelder W, Ebrahimi A, Forest VI, Gao K, Murali R, Clark JR. Cutaneous head and neck squamous cell carcinoma with regional metastases: the prognostic importance of soft tissue metastases and extranodal spread. Ann Surg Oncol. 2012;19(1):274-279. (16.) Kollert M, Draf W, Minovi A, Hofmann E, Bockmuhl U. Carcinoma of the external auditory canal and middle ear: therapeutic strategy and follow up [in German]. Laryngorhinootologie. 2004;83(12):818-823. (17.) Moffat DA, Wagstaff SA, Hardy DG. The outcome of radical surgery and postoperative radiotherapy for squamous carcinoma of the temporal bone. Laryngoscope. 2005;115(2):341-347. (18.) Stell PM, McCormick MS. Carcinoma of the external auditory meatus and middle ear: prognostic factors and a suggested staging system. J Laryngol Otol. 1985;99(9):847-850. (19.) Yin M, Ishikawa K, Honda K, et al. Analysis of 95 cases of squamous cell carcinoma of the external and middle ear. Auris Nasus Larynx. 2006;33(3):251-257. (20.) Mazzoni A, Danesi G, Zanoletti E. Primary squamous cell carcinoma of the external auditory canal: surgical treatment and long-term outcomes. Acta Otorhinolaryngol ital. 2014;34(2):129-137. (21.) Wermker K, KluwigJ, Schipmann S, Klein M, Schulze HJ, Hallermann C. Prediction score for lymph node metastasis from cutaneous squamous cell carcinoma of the external ear. Eur J Surg Oncol. 2015;41(1):128-135. (22.) Brandwein-Gensler M, Teixeira MS, Lewis CM, et al. Oral squamous cell carcinoma: histologic risk assessment, but not margin status, is strongly predictive of local disease-free and overall survival. Am J Surg Pathol. 2005;29(2):167-178. (23.) Choi JY, Choi EC, Lee HK, Yoo JB, Kim SG, Lee WS. Mode of parotid involvement in external auditory canal carcinoma. J Laryngol Otol. 2003;117(12): 951-954. (24.) Sandison A, Thompson LDR. Tumours of the external auditory canal: squamous cell carcinoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ, eds. WHO Classification of Head and Neck Tumours. Lyon, France: IARC Press; 2017:263-264. (25.) Sandison A, Thompson LDR. Tumours of the external auditory canal: ceruminous adenoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ, eds. WHO Classification of Head and Neck Tumours. 4th ed. Lyon, France: IARC Press; 2017:265. (26.) Sandison A, Thompson LDR. Tumours of the external auditory canal: ceruminous adenocarcinoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ, eds. WHO Classification of Head and Neck Tumours. 4th ed. Lyon, France: IARC Press; 2017:264. (27.) Sandison A. Tumours of the middle and inner ear: aggressive papillary tumour. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ, eds. WHO Classification of Head and Neck Tumours. 4th ed. Lyon, France: IARC Press; 2017:266-267. (28.) Sandison A. Tumours of the middle and inner ear: endolymphatic sac tumour. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ, eds. WHO Classification of Head and Neck Tumours. 4th ed. Lyon, France: IARC Press; 2017:267-268. (29.) Thompson LDR. Update from the 4th edition of the World Health Organization Classification of Head and Neck Tumours: tumours of the ear. Head Neck Pathol. 2017;11(1):78-87. (30.) Shen W, Sakamoto N, Yang L. Prognostic models to predict overall and cause-specific survival for patients with middle ear cancer: a population-based analysis. BMC Cancer. 2014;14:554. (31.) Hosokawa S, Mizuta K, Takahashi G, et al. Carcinoma of the external auditory canal: histological and treatment groups. B-ENT. 2014;10(4):259-264. (32.) El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ, eds. WHO Classification of Head and Neck Tumours. 4th ed. Lyon, France: IARC Press; 2017. (33.) Crain N, Nelson BL, Barnes EL, Thompson LD. Ceruminous gland carcinomas: a clinicopathologic and immunophenotypic study of 17 cases. Head Neck Pathol. 2009;3(1):1-17. (34.) Leong SC, Youssef A, Lesser TH. Squamous cell carcinoma of the temporal bone: outcomes of radical surgery and postoperative radiotherapy. Laryngoscope. 2013;123(10):2442-2448. (35.) Ito M, Hatano M, Yoshizaki T. Prognostic factors for squamous cell carcinoma of the temporal bone: extensive bone involvement or extensive soft tissue involvement? Acta Otolaryngol. 2009;129(11):1313-1319. (36.) Perry A, Louis DN, Budka H, et al. Meningiom. In: Louis DN, Ohgaki H, Wiestler OD, et al, eds. World Health Organization Classification of Tumours of the Central Nervous System. Lyon, France: IARC Press; 2016:232-245. (37.) Rodriguez Paramas A, Gil Carrasco R, Arenas Britez O, Yurrita Scola B. Malignant tumours of the external auditory canal and of the middle ear [in Spanish]. Acta Otorrinolaringol Esp. 2004;55(10):470-474. (38.) Wang Z, Zheng M, Xia S. The contribution of CT and MRI in staging, treatment planning and prognosis prediction of malignant tumors of external auditory canal. Clin imaging. 2016;40(6):1262-1268. (39.) Gillespie MB, Francis HW, Chee N, Eisele DW. Squamous cell carcinoma of the temporal bone: a radiographic-pathologic correlation. Arch Otolaryngol Head Neck Surg. 2001;127(7):803-807. (40.) Moody SA, Hirsch BE, Myers EN. Squamous cell carcinoma of the external auditory canal: an evaluation of a staging system. Am J Otol. 2000;21(4):582-588. (41.) Higgins TS, Antonio SA. The role of facial palsy in staging squamous cell carcinoma of the temporal bone and external auditory canal: a comparative survival analysis. Otol Neurotol. 2010;31(9):1473-1479. (42.) Aivazian K, Ebrahimi A, Low TH, et al. Perineural invasion in oral squamous cell carcinoma: quantitative subcategorisation of perineural invasion and prognostication. J Surg Oncol. 2015;111(3):352-358. (43.) Schwager K, Pfreundner L, Hoppe F, Baier G, Willner J, Baier K. Carcinoma of the external ear canal and middle ear as interdisciplinary challenge for ear surgery and radiotherapy [in German]. Laryngorhinootologie. 2001;80(4):196-202. (44.) Nyrop M, Grontved A. Cancer of the external auditory canal. Arch Otolaryngol Head Neck Surg. 2002;128(7):834-837. (45.) Li Y, Bai S, Carroll W, et al. Validation of the risk model: high-risk classification and tumor pattern of invasion predict outcome for patients with low-stage oral cavity squamous cell carcinoma. Head Neck Pathol. 2013;7(3): 211-223. (46.) Arriaga M, Curtin H, Takahashi H, Hirsch BE, Kamerer DB. Staging proposal for external auditory meatus carcinoma based on preoperative clinical examination and computed tomography findings. Ann Otol Rhinol Laryngol. 1990;99(9, pt 1):714-721. (47.) Bambakidis NC, Megerian CA, Ratcheson RA. Differential grading of endolymphatic sac tumor extension by virtue of von Hippel-Lindau disease status. Otol Neurotol. 2004;25(5):773-781. (48.) Pfreundner L, Schwager K, Willner J, et al. Carcinoma of the external auditory canal and middle ear. Int J Radiai Oncol Biol Phys. 1999;44(4):777-788. (49.) Califano J, Lydiatt W, Nehal K, et al. Cutaneous squamous cell carcinoma of the head and neck. In: Amin MB, Edge S, Greene F, et al, eds. AJCC Cancer Staging Manual. 8th ed. Chicago, IL: Springer; 2017:171-181. (50.) Andruchow JL, Veness MJ, Morgan GJ, et al. Implications for clinical staging of metastatic cutaneous squamous carcinoma of the head and neck based on a multicenter study of treatment outcomes. Cancer. 2006;106(5):1078-1083. (51.) Liu J, Ebrahimi A, Low TH, et al. Predictive value of the 8th edition American Joint Commission Cancer (AJCC) nodal staging system for patients with cutaneous squamous cell carcinoma of the head and neck. J Surg Oncol. 2018; 117(4):765-772. (52.) Boedeker CC. Paragangliomas and paraganglioma syndromes. CMS Curr Top Otorhinolaryngol Head Neck Surg. 2011;10:Doc03. (53.) Boedeker CC, Hensen EF, Neumann HP, et al. Genetics of hereditary head and neck paragangliomas. Head Neck. 2014;36(6):907-916. (54.) Slattery WH. Neurofibromatosis type 2. Otolaryngol Clin North Am. 2015; 48(3):443-460. (55.) Michaels L. Origin of endolymphatic sac tumor. Head Neck Pathol. 2007; 1(2):104-111. (56.) Lim LH, Goh YH, Chan YM, Chong VF, Low WK. Malignancy of the temporal bone and external auditory canal. Otolaryngol Head Neck Surg. 2000; 122(6):882-886. (57.) Wang J, Xie B, Dai C. Clinical characteristics and management of external auditory canal squamous cell carcinoma in post-irradiated nasopharyngeal carcinoma patients. Otol Neurotol. 2015;36(6):1081-1088. (58.) Bauml J, Seiwert TY, Pfister DG, et al. Pembrolizumab for platinum- and cetuximab-refractory head and neck cancer: results from a single-arm, phase II study. J Clin Oncol. 2017;35(14):1542-1549. (59.) Thompson LDR, Gupta R, Sandison A, Wenig BM. Ear and Temporal Bone Tumours, Histopathology Reporting Cuide. 1st ed. Sydney, Australia: International Collaboration on Cancer Reporting; 2018. (60.) Bullock M, Beitler JJ, Carlson DL, et al. Nodal Excisions and Neck Dissection Specimens for Head & Neck Tumours, Histopathology Reporting Cuide. 1st ed. Sydney, Australia: International Collaboration on Cancer Reporting; 2018. Ruta Gupta, MD, MBBS, FRCPA; Ann Sandison, MD; Bruce M. Wenig, MD; Lester D. R. Thompson, MD From the University of Sydney, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia (Dr Gupta); the Department of Head and Neck and Oral Pathology, Guy's Hospital, London, United Kingdom (Dr Sandison); the Department of Pathology, Moffitt Cancer Center, Tampa, Florida (Dr Wenig); and the Department of Pathology, Southern California Permanente Medical Group, Woodland Hills Medical Center, Woodland Hills (Dr Thompson). The authors have no relevant financial interest in the products or companies described in this article. Corresponding author: Lester D. R. Thompson, MD, Southern California Permanente Medical Group, Woodland Hills Medical Center, Department of Pathology, 5601 De Soto Avenue, Woodland Hills, CA 91365 (email: [email protected]). Caption: Figure 1. An illustration of the complex anatomic relationships within the ear and temporal bone. Frequently, disfiguring or destructive surgery is required to remove benign or malignant tumors from these areas. Reproduced with permission from the International Collaboration on Cancer Reporting. Caption: Figure 2. A complex petrosectomy sample (A) showing orientation and serial sectioning after inking (B). Arrow points to (C) the histologic features of the tumor in relationship to the surrounding structures and margins (hematoxylin-eosin, original magnification X10). Caption: Figure 3. A well-oriented sample with sutures has been photodocumented to aid in section selection and correlation to margins and key anatomic structures. A, Left ear anterior-lateral. B, Left ear posterior-medial. Caption: Figure 4. A, A subtotal temporal bone resection with orientation and margins, serially sectioned. B, The black box section was submitted as a "megablock" (arrow), with identification of tumor on the blue inked canal margin (hematoxylin-eosin, original magnification X10). Caption: Figure 5. This benign middle ear adenoma (a neuroendocrine tumor) shows bone invasion of the ossicles, but it is still a benign neoplasm (hematoxylin-eosin, original magnification X400). Caption: Figure 6. An intermediate-grade, moderately differentiated, infiltrative squamous cell carcinoma is noted in this resection sample (hematoxylineosin, original magnification X400). Caption: Figure 7. This bone specimen has been decalcified, and upon histologic exam it demonstrates islands of invasive squamous cell carcinoma (hematoxylin-eosin, original magnifications X10 [A] and X200 [B]). Caption: Figure 8. A, Parotid gland invasion by a squamous cell carcinoma. B, Dural involvement by a squamous cell carcinoma is a significant finding in ear and temporal bone samples (hematoxylin-eosin, original magnifications X100 [A] and X400 [B]). Caption: Figure 9. There is a cholesteatoma intimately associated with a middle ear adenoma (hematoxylin-eosin, original magnification X200). Caption: Figure 10. A, An endolymphatic sac tumor shows fragments of bone and a delicate papillary architecture. B, CAIX yields a very strong membrane reactivity in this endolymphatic sac tumor, a characteristic finding for this neoplasm not seen in other ear and temporal bone primary tumors (hematoxylin-eosin, original magnification X200 [A]; original magnification X400 [B]). Table 1. World Health Organization Classification of the Histologic Types of the Tumors of the Ear and the Temporal Bonea Descriptor ICD-O Codes (b) Squamous cell carcinoma 8070/3 Ceruminous adenocarcinoma 8420/3 Ceruminous adenoid cystic carcinoma 8200/3 Ceruminous mucoepidermoid carcinoma 8430/3 Ceruminous adenoma 8420/0 Ceruminous pleomorphic adenoma Ceruminous syringocystadenoma papilliferum Middle ear adenoma (carcinoid) Middle ear adenocarcinoma Aggressive papillary tumor 8260/1 Endolymphatic sac tumor 8140/3 Vestibular schwannoma 9560/0 Meningioma 9530/0 (a) Reproduced with permission from the World Health Organization (WHO)/International Agency for Research on Cancer. (b) The morphology codes are from the International Classification of Diseases for Oncology (ICD/O). Behavior is coded /0 for benign tumors; /1 for unspecified, borderline, or uncertain behavior; /2 for carcinoma in situ and grade III intraepithelial neoplasia; and /3 for malignant tumors. Table 2. Pathologic Staging for Tumors of the Ear and Temporal Bone (pT) (a) pTx Assessment not possible on the submitted specimen pT1 Tumor limited to the EAC without bony erosion or evidence of soft tissue involvement pT2 Tumor with limited EAC bone erosion (not full thickness) or limited (<0.5 cm) soft tissue involvement pT3 Tumor eroding the osseous EAC (full thickness) with limited (<0.5 cm) soft tissue involvement, or tumor involving the middle ear and/or mastoid pT4 Tumor eroding the cochlea, petrous apex, medial wall of the middle ear, carotid canal, jugular foramen, or dura, or with extensive soft tissue involvement ([greater than or equal to] 0.5 cm), such as involvement of TMJ or styloid process, or evidence of facial paresis Abbreviations: EAC, external auditory canal; TMJ, temporomandibular joint. (a) Data derived from Moody et al40: Moody SA, Hirsch BE, Myers EN. Squamous cell carcinoma of the external auditory canal: an evaluation of a staging system. Am J Otol. 2000;21(4):582-588 and Arriaga et al46: Arriaga M, Curtin H, Takahashi H, et al. Staging proposal for external auditory meatus carcinoma based on preoperative clinical examination and computed tomography findings. Ann Otol Rhinol Laryngol. 1990;99(9, pt 1):714-721. \|Printer friendly Cite/link Email Feedback\| \|Author:\|\|Gupta, Ruta; Sandison, Ann; Wenig, Bruce M.; Thompson, Lester D.R.\| \|Publication:\|\|Archives of Pathology & Laboratory Medicine\| \|Date:\|\|May 1, 2019\| \|Previous Article:\|\|Data Set for the Reporting of Malignant Odontogenic Tumors: Explanations and Recommendations of the Guidelines From the International Collaboration...\| \|Next Article:\|\|Data Set for the Reporting of Mucosal Melanomas of the Head and Neck: Explanations and Recommendations of the Guidelines From the International...\|	2	6	1	0	3	0.289004	4	9,415
Fecal incontinence (FI), also known as anal incontinence, or in some forms encopresis, is a lack of control over defecation, leading to involuntary loss of bowel contents—including flatus (gas), liquid stool elements and mucus, or solid feces. FI is a sign or a symptom, not a diagnosis. Incontinence can result from different causes and might occur with either constipation or diarrhea. Continence is maintained by several interrelated factors, including the anal sampling mechanism, and usually there is more than one deficiency of these mechanisms for incontinence to develop. The most common causes are thought to be immediate or delayed damage from childbirth, complications from prior anorectal surgery (especially involving the anal sphincters or hemorrhoidal vascular cushions), altered bowel habits (e.g., caused by irritable bowel syndrome, Crohn's disease, ulcerative colitis, food intolerance, or constipation with overflow incontinence), and receptive anal sex. An estimated 2.2% of community dwelling adults are affected. \|Other names\|\|Faecal incontinence, bowel incontinence, anal incontinence, accidental bowel leakage\| \|Diagram showing normal anatomy of anal canal and rectum.\| Fecal incontinence has three main consequences: local reactions of the perianal skin and urinary tract, including maceration (softening and whitening of skin due to continuous moisture), urinary tract infections, or decubitus ulcers (pressure sores); a financial expense for individuals (due to cost of medication and incontinence products, and loss of productivity), employers (days off), and medical insurers and society generally (health care costs, unemployment); and an associated decrease in quality of life. There is often reduced self-esteem, shame, humiliation, depression, a need to organize life around easy access to a toilet and avoidance of enjoyable activities. FI is an example of a stigmatized medical condition, which creates barriers to successful management. People may be too embarrassed to seek medical help, and attempt to self-manage the symptom in secrecy from others. FI is one of the most psychologically and socially debilitating conditions in an otherwise healthy individual, but it is generally treatable. Management may be achieved through an individualized mix of dietary, pharmacologic, and surgical measures. Health care professionals are often poorly informed about treatment options, and may fail to recognize the effect of FI. - 1 Signs and symptoms - 2 Causes - 3 Pathophysiology - 4 Diagnostic approach - 5 Management - 6 Epidemiology - 7 History - 8 Society and culture - 9 Research - 10 See also - 11 References - 12 External links Signs and symptomsEdit FI affects virtually all aspects of peoples' lives, greatly diminishing physical and mental health, and affect personal, social and professional life. Emotional effects may include stress, fearfulness, anxiety, exhaustion, fear of public humiliation, feeling dirty, poor body-image, reduced desire for sex, anger, humiliation, depression, isolation, secrecy, frustration and embarrassment. Some people may need to be in control of life outside of FI as means of compensation. The physical symptoms such as skin soreness, pain and odor may also affect quality of life. Physical activity such as shopping or exercise is often affected. Travel may be affected, requiring careful planning. Working is also affected for most. Relationships, social activities and self-image likewise often suffer. Symptoms may worsen over time. FI is a sign or a symptom, not a diagnosis, and represents an extensive list of causes. Usually, it is the result of a complex interplay of several coexisting factors, many of which may be simple to correct. Up to 80% of people may have more than one abnormality that is contributing. Deficits of individual functional components of the continence mechanism can be partially compensated for a certain period of time, until the compensating components themselves fail. For example, obstetric injury may precede onset by decades, but postmenopausal changes in the tissue strength reduce in turn the competence of the compensatory mechanisms. The most common factors in the development are thought to be obstetric injury and after effects of anorectal surgery, especially those involving the anal sphincters and hemorrhoidal vascular cushions. The majority of incontinent persons over the age of 18 fall into one of several groups: those with structural anorectal abnormalities (sphincter trauma, sphincter degeneration, perianal fistula, rectal prolapse), neurological disorders (multiple sclerosis, spinal cord injury, spina bifida, stroke, etc.), constipation/fecal loading (presence of a large amount of feces in the rectum with stool of any consistency), cognitive and/or behavioral dysfunction (dementia, learning disabilities), diarrhea, inflammatory bowel diseases (e.g. ulcerative colitis, Crohn's disease), irritable bowel syndrome, disability related (people who are frail, acutely unwell, or have chronic/acute disabilities), and those cases which are idiopathic (of unknown cause). Diabetes mellitus is also known to be a cause, but the mechanism of this relationship is not well understood. The functioning of the anal canal can be damaged, traumatically or atraumatically. The resting tone of the anal canal is not the only factor which is important; both the length of the high pressure zone and its radial translation of force are required for continence. This means that even with normal anal canal pressure, focal defects such as the keyhole deformity can be the cause of substantial symptoms. External anal sphincter (EAS) dysfunction is associated with impaired voluntary control, whereas internal anal sphincter (IAS) dysfunction is associated with impaired fine tuning of fecal control. Lesions which mechanically interfere with, or prevent the complete closure of the anal canal can cause a liquid stool or mucous rectal discharge. Such lesions include piles (inflamed hemorrhoids), anal fissures, anal cancer or fistulae. Obstetric injury may tear the anal sphincters, and some of these injuries may be occult (undetected). The risk of injury is greatest when labor has been especially difficult or prolonged, when forceps are used, with higher birth weights or when an midline episiotomy is performed. Only when there is post operative investigation of FI such as endoanal ultrasound is the injury discovered. FI is a much under-reported complication of surgery. The IAS is easily damaged with an anal retractor (especially the Park's anal retractor), leading to reduced resting pressure postoperatively. Since the hemorrhoidal vascular cushions contribute 15% of the resting anal tone, surgeries involving these structures may affect continence status. Partial internal sphincterotomy, fistulotomy, anal stretch (Lord's operation), hemorrhoidectomy or transanal advancement flaps may all lead to FI post operatively, with soiling being far more common than solid FI. The "keyhole deformity" refers to scarring within the anal canal and is another cause of mucus leakage and minor incontinence. This defect is also described as a groove in the anal canal wall, and may occur after posterior midline fissurectomy or fistulotomy, or with lateral IAS defects. Rare causes of traumatic injury to the anal sphincters include military or traffic accidents complicated by pelvic fractures, spine injuries or perineal lacerations, insertion of foreign bodies in the rectum, and sexual abuse. Nontraumatic conditions causing anal sphincter weakness include scleroderma, damage to the pudendal nerves and IAS degeneration of unknown cause. Radiation induced FI may involve the anal canal as well as the rectum, when proctitis, anal fistula formation and diminished function of internal and external sphincter occur. Irradiation may occur during radiotherapy, e.g. for prostate cancer. Many people with FI have a generalized weakness of the pelvic floor, especially puborectalis. A weakened puborectalis leads to widening of the anorectal angle, and impaired barrier to stool in the rectum entering the anal canal, and this is associated with incontinence to solids. Abnormal descent of the pelvic floor can also be a sign of pelvic floor weakness. Abnormal descent manifests as descending perineum syndrome (>4 cm perineal descent). This syndrome initially gives constipation, and later FI. The pelvic floor is innervated by the pudendal nerve and the S3 and S4 branches of the pelvic plexus. With recurrent straining, e.g. during difficult labour or long term constipation, then stretch injury can damage the nerves supplying levator ani. The pudendal nerve is especially vulnerable to irreversible damage, (stretch induced pudendal neuropathy) which can occur with a 12% stretch. If the pelvic floor muscles lose their innervation, they cease to contract and their muscle fibres are in time replaced by fibrous tissue, which is associated with pelvic floor weakness and incontinence. Increased pudendal nerve terminal motor latency may indicate pelvic floor weakness. The various types of pelvic organ prolapse (e.g. external rectal prolapse, mucosal prolapse and internal rectal intussusception & solitary rectal ulcer syndrome) may also cause coexisting obstructed defecation. The rectum needs to be of a sufficient volume to store stool until defecation. The rectal walls need to be "compliant" i.e. able to distend to an extent to accommodate stool. Rectal sensation is required to detect the presence, nature and amount of rectal contents. The rectum must also be able to evacuate its contents fully. There must also be efficient co-ordination of rectal sensation and relaxation of the anal canal. If the sensory nerves are damaged, detection of stool in the rectum is dulled or absent, and the person will not feel the need to defecate until too late. Rectal hyposensitivity may manifest as constipation, FI, or both. Rectal hyposensitivity was reported to be present in 10% of people with FI. Pudendal neuropathy is one cause of rectal hyposensitivity, and may lead to fecal loading/impaction, megarectum and overflow FI. Normal evacuation of rectal contents is 90-100%. If there is incomplete evacuation during defecation, residual stool will be left in the rectum and threaten continence once defecation is finished. This is a feature of people with soiling secondary to obstructed defecation. Obstructed defecation is often due to anismus (paradoxical contraction or relaxation failure of the puborectalis).:38 Whilst anismus is largely a functional disorder, organic pathologic lesions may mechanically interfere with rectal evacuation. Other causes of incomplete evacuation include non-emptying defects like a rectocele. Straining to defecate pushes stool into the rectocele, which acts like a diverticulum and causes stool sequestration. Once the voluntary attempt to defecate, albeit dysfunctional, is finished, the voluntary muscles relax, and residual rectal contents are then able to descend into the anal canal and cause leaking.:37 \|Drug/mechanism of action\|\|Common examples\| \|Drugs altering sphincter tone\| \|Topical drugs applied to anus (reducing pressure)\| \|Drugs causing profuse diarrhea\| \|Tranquilisers/hypnotics (reducing alertness)\| Central nervous systemEdit Continence requires conscious and subconscious networking of information from and to the anorectum. Defects/brain damage may affect the central nervous system focally (e.g. stroke, tumor e.g. spinal cord lesions, trauma, multiple sclerosis) or diffusely (e.g. dementia, multiple sclerosis, infection, Parkinson's disease or drug-induced). FI (and urinary incontinence) may also occur during epileptic seizures. Dural ectasia is an example of a spinal cord lesion that may affect continence. Liquid stool is more difficult to control than formed, solid stool. Hence, FI can be exacerbated by diarrhea. Some consider diarrhea to be the most common aggravating factor. Orlistat is an anti-obesity (weight loss) drug that blocks the absorption of fats. This may give side effects of FI, diarrhea and steatorrhea. This may occur when there is a large mass of feces in the rectum (fecal loading), which may become hardened (fecal impaction). Liquid stool elements are able to pass around the obstruction, leading to incontinence. Megarectum (enlarged rectal volume) and rectal hyposensitivity are associated with overflow incontinence. Hospitalized patients and care home residents may develop FI via this mechanism, possibly a result of lack of mobility, reduced alertness, constipating effect of medication and/or dehydration. The mechanisms and factors contributing to normal continence are multiple and inter-related. The puborectalis sling, forming the anorectal angle (see diagram), is responsible for gross continence of solid stool. The IAS is an involuntary muscle, contributing about 55% of the resting anal pressure. Together with the hemorrhoidal vascular cushions, the IAS maintains continence of flatus and liquid during rest. The EAS is a voluntary muscle, doubling the pressure in the anal canal during contraction, which is possible for a short time. The rectoanal inhibitory reflex (RAIR) is an involuntary IAS relaxation in response to rectal distension, allowing some rectal contents to descend into the anal canal where it is brought into contact with specialized sensory mucosa to detect consistency. The rectoanal excitatory reflex (RAER) is an initial, semi-voluntary contraction of the EAS and puborectalis which in turn prevents incontinence following the RAIR. Other factors include the specialized anti-peristaltic function of the last part of the sigmoid colon, which keeps the rectum empty most of the time, sensation in the lining of the rectum and the anal canal to detect when there is stool present, its consistency and quantity, and the presence of normal rectoanal reflexes and defecation cycle which completely evacuates stool from the rectum and anal canal. Problems affecting any of these mechanisms and factors may be involved in the cause. Identification of the exact causes usually begins with a thorough medical history, including detailed questioning about symptoms, bowel habits, diet, medication and other medical problems. Digital rectal examination is performed to assesses resting pressure and voluntary contraction (maximum squeeze) of the sphincter complex and puborectalis. Anal sphincter defects, rectal prolapse, and abnormal perineal descent may be detected. Anorectal physiology tests assess the functioning of the anorectal anatomy. Anorectal manometry records the pressure exerted by the anal sphincters and puborectalis during rest and during contraction. The procedure is also able to assess sensitivity of the anal canal and rectum. Anal electromyography tests for nerve damage, which is often associated with obstetric injury. Pudendal nerve terminal motor latency tests for damage to the pudendal motor nerves. Proctography, also known as defecography, shows how much stool the rectum can hold, how well the rectum holds it, and how well the rectum can evacuate the stool. It will also highlight defects in the structure of the rectum such as internal rectal intussusception. Dynamic pelvic MRI, also called MRI defecography is an alternative which is better for some problems but not as good for other problems. Proctosigmoidoscopy involves the insertion of an endoscope (a long, thin, flexible tube with a camera) into the anal canal, rectum and sigmoid colon. The procedure allows for visualization of the interior of the gut, and may detect signs of disease or other problems that could be a cause, such as inflammation, tumors, or scar tissue. Endoanal ultrasound, which some consider to be the gold standard for detection of anal canal lesions, evaluates the structure of the anal sphincters, and may detect occult sphincter tears that otherwise would go unseen. Functional FI is common. The Rome process published diagnostic criteria for functional FI, which they defined as "recurrent uncontrolled passage of fecal material in an individual with a developmental age of at least 4 years". The diagnostic criteria are, one or more of the following factors present for the last 3 months: abnormal functioning of normally innervated and structurally intact muscles, minor abnormalities of sphincter structure/innervation (nerve supply), normal or disordered bowel habits, (i.e., fecal retention or diarrhea), and psychological causes. Furthermore, exclusion criteria are given. These are factors which all must be excluded for a diagnosis of functional FI, and are abnormal innervation caused by lesion(s) within the brain (e.g., dementia), spinal cord (at or below T12), or sacral nerve roots, or mixed lesions (e.g., multiple sclerosis), or as part of a generalized peripheral or autonomic neuropathy (e.g., due to diabetes), anal sphincter abnormalities associated with a multisystem disease (e.g., scleroderma), and structural or neurogenic abnormalities that are the major cause. There is no globally accepted definition, but fecal incontinence is generally defined as the recurrent inability to voluntarily control the passage of bowel contents through the anal canal and expel it at a socially acceptable location and time, occurring in individuals over the age of four. "Social continence" has been given various precise definitions for the purposes of research, however generally it refers to symptoms being controlled to an extent that is acceptable to the individual in question, with no significant effect on their life. There is no consensus about the best way to classify FI, and several methods are used. Symptoms can be directly or indirectly related to the loss of bowel control. The direct (primary) symptom is a lack of control over bowel contents which tends to worsen without treatment. Indirect (secondary) symptoms, which are the result of leakage, include pruritus ani (an intense itching sensation from the anus), perianal dermatitis (irritation and inflammation of the skin around the anus), and urinary tract infections. Due to embarrassment, people may only mention secondary symptoms rather than acknowledge incontinence. Any major underlying cause will produce additional signs and symptoms, such as protrusion of mucosa in external rectal prolapse. Symptoms of fecal leakage (FL) are similar, and may occur after defecation. There may be loss of small amounts of brown fluid and staining of the underwear. FI can be divided into those people who experience a defecation urge before leakage (urge incontinence), and those who experience no sensation before leakage (passive incontinence or soiling). Urge incontinence is characterized by a sudden need to defecate, with little time to reach a toilet. Urge and passive FI may be associated with weakness of the external anal sphincter (EAS) and internal anal sphincter (IAS) respectively. Urgency may also be associated with reduced rectal volume, reduced ability of the rectal walls to distend and accommodate stool, and increased rectal sensitivity. There is a continuous spectrum of different clinical presentations from incontinence of flatus (gas), through incontinence of mucus or liquid stool, to solids. The term anal incontinence often is used to describe flatus incontinence, however it is also used as a synonym for FI generally. It may occur together with incontinence of liquids or solids, or it may present in isolation. Flatus incontinence may be the first sign of FI. Once continence to flatus is lost, it is rarely restored. Anal incontinence may be equally disabling as the other types. Fecal leakage, fecal soiling and fecal seepage are minor degrees of FI, and describe incontinence of liquid stool, mucus, or very small amounts of solid stool. They cover a spectrum of increasing symptom severity (staining, soilage, seepage and accidents). Rarely, minor FI in adults may be described as encopresis. Fecal leakage is a related topic to rectal discharge, but this term does not necessarily imply any degree of incontinence. Discharge generally refers to conditions where there is pus or increased mucus production, or anatomical lesions that prevent the anal canal from closing fully, whereas fecal leakage generally concerns disorders of IAS function and functional evacuation disorders which cause a solid fecal mass to be retained in the rectum. Solid stool incontinence may be called complete (or major) incontinence, and anything less as partial (or minor) incontinence (i.e. incontinence of flatus (gas), liquid stool and/or mucus). In children over the age of four who have been toilet trained, a similar condition is generally termed encopresis (or soiling), which refers to the voluntary or involuntary loss of (usually soft or semi-liquid) stool. The term pseudoincontinence is used when there is FI in children who have anatomical defects (e.g. enlarged sigmoid colon or anal stenosis). Encopresis is a term that is usually applied when there are no such anatomical defects present. The ICD-10 classifies nonorganic encopresis under "behavioural and emotional disorders with onset usually occurring in childhood and adolescence" and organic causes of encopresis along with FI. FI can also be classified according to gender, since the cause in females may be different from males, for example it may develop following radical prostatectomy in males, whereas females may develop FI as an immediate or delayed consequence of damage whilst giving birth. Pelvic anatomy is also different according to gender, with a wider pelvic outlet in females. Several severity scales exist. The Cleveland Clinic (Wexner) fecal incontinence score takes into account five parameters that are scored on a scale from zero (absent) to four (daily) frequency of incontinence to gas, liquid, solid, of need to wear pad, and of lifestyle changes. The Park's incontinence score uses four categories: - 1 - those continent for solid and liquid stool and also for flatus. - 2 - those continent for solid and liquid stool but incontinent for flatus (with or without urgency). - 3 - those continent for solid stool but incontinent for liquid stool or flatus. - 4 - those incontinent to formed stool (complete incontinence). The fecal incontinence severity index is based on four types of leakage (gas, mucus, liquid stool, solid stool) and five frequencies (once to three times per month, once per week, twice per week, once per day, twice or more per day). Other severity scales include: AMS, Pescatori, Williams score, Kirwan, Miller score, Saint Mark's score and the Vaizey scale. FI may present with signs similar to rectal discharge (e.g. fistulae, proctitis or rectal prolapse), pseudoincontinence, encopresis (with no organic cause) and irritable bowel syndrome. \|Stool consistency\|\|Cause\|\|First line\|\|Second line\| \|Diarrhea\|\|Inflammatory\|\|Anti-inflammatory drugs\|\|Constipating drugs\| \|Solid\|\|Pelvic floor\|\|Biofeedback\|\|Sacral nerve stimulation\| \|Sphincter intact\|\|Sacral nerve stimulation\|\|Lavage\| \|Sphincter rupture\|\|Anal repair\|\|Sacral nerve stimulation/Neosphincter\| \|Rectal prolapse\|\|Rectopexy\|\|Perineal resection\| \|Soiling\|\|Keyhole defect\|\|Lavage\|\|PTQ implant\| FI is generally treatable with conservative management, surgery or both. The success of treatment depends upon the exact causes and how easily these are corrected. Treatment choice depends on the cause and severity of disease, and the motivation and general health of the person effected. Commonly, conservative measures are used together, and if appropriate surgery carried out. Treatments may be attempted until symptoms are satisfactorily controlled. A treatment algorithm based upon the cause has been proposed, including conservative, non-operative and surgical measures (neosphincter refers to either dynamic graciloplasty or artificial bowel sphincter, lavage refers to retrograde rectal irrigation). Conservative measures include dietary modification, drug treatment, retrograde anal irrigation, biofeedback retraining anal sphincter exercises. Incontinence products refer to devices such as anal plugs and perineal pads and garments such as diapers/nappies. Perineal pads are efficient and acceptable for only minor incontinence. If all other measures are ineffective removing the entire colon may be an option. Dietary modification may be important for successful management. Both diarrhea and constipation can contribute to different cases, so dietary advice must be tailored to address the underlying cause or it may be ineffective or counter productive. In persons with disease aggravated by diarrhea or those with rectal loading by soft stools, the following suggestions may be beneficial: increase dietary fiber; reduce wholegrain cereals/bread; reduce fruit and vegetables which contain natural laxative compounds (rhubarb, figs, prunes/plums); limit beans, pulses, cabbage and sprouts; reduce spices (especially chilli); reduce artificial sweeteners (e.g. sugar free chewing gum); reduce alcohol (especially stout, beer and ale); reduce lactose if there is some degree of lactase deficiency; and reduce caffeine. Caffeine lowers the resting tone of the anal canal and also causes diarrhea. Excessive doses of vitamin C, magnesium, phosphorus and/or calcium supplements may increase FI. Reducing olestra fat substitute, which can cause diarrhea, may also help. Pharmacological management may include anti-diarrheal/constipating agents and laxatives/stool bulking agents. Stopping or substituting any previous medication that causes diarrhea may be helpful in some (see table). There is not good evidence for the use of any medications however. In people who have undergone gallbladder removal, the bile acid sequestrant cholestyramine may help minor degrees of FI. Bulking agents also absorb water, so may be helpful for those with diarrhea. A common side effect is bloating and flatulence. Topical agents to treat and prevent dermatitis may also be used, such as topical antifungals when there is evidence of perianal candidiasis or occasionally mild topical anti-inflammatory medication. Prevention of secondary lesions is carried out by perineal cleansing, moisturization, and use of a skin protectant. Evacuation aids (suppositories or enemas) e.g. glycerine or bisacodyl suppositories may be prescribed. People may have poor resting tone of the anal canal, and consequently may not be able to retain an enema, in which case transanal irrigation (retrograde anal irrigation) may be a better option, as this equipment utilizes an inflatable catheter to prevent loss of the irrigation tip and to provide a water tight seal during irrigation. A volume of lukewarm water is gently pumped into the colon via the anus. People can be taught how to perform this treatment in their own homes, but it does require special equipment. If the irrigation is efficient, stool will not reach the rectum again for up to 48 hours. By regularly emptying the bowel using transanal irrigation, controlled bowel function is often re-established to a high degree in patients with bowel incontinence and/or constipation. This enables control over the time and place of evacuation and development of a consistent bowel routine. However, persistent leaking of residual irrigation fluid during the day may occur and make this option unhelpful, particularly in persons with obstructed defecation syndrome who may have incomplete evacuation of any rectal contents. Consequently, the best time to carry out the irrigation is typically in the evening, allowing any residual liquid to be passed the next morning before leaving the home. Complications such as electrolyte imbalance and perforation are rare. The effect of transanal irrigation varies considerably. Some individuals experience complete control of incontinence, and other report little or no benefit. It has been suggested that if appropriate, people be offered home retrograde anal irrigation. Biofeedback (the use of equipment to record or amplify and then feed back activities of the body) is a commonly used and researched treatment, but the benefits are uncertain. Biofeedback therapy varies in the way it is delivered, but it is unknown if one type has benefits over another. The role of pelvic floor exercises and anal sphincter exercises in FI is poorly determined. While there may be some benefit they appear less useful than implanted sacral nerve stimulators. These exercises aim to increase the strength of the pelvic floor muscles (mainly levator ani). The anal sphincters are not technically part of the pelvic floor muscle group, but the EAS is a voluntary, striated muscle which therefore can be strengthened in a similar manner. It has not been established whether pelvic floor exercises can be distinguished from anal sphincter exercises in practice by the people doing them. This kind of exercise is more commonly used to treat urinary incontinence, for which there is a sound evidence base for effectiveness. More rarely are they used in FI. The effect of anal sphincter exercises are variously stated as an increase in the strength, speed or endurance of voluntary contraction (EAS). Electrical stimulation can also be applied to the anal sphincters and pelvic floor muscles, inducing muscle contraction without traditional exercises (similar to transcutaneous electrical nerve stimulation, TENS). The evidence supporting its use is limited, and any benefit is tentative. In light of the above, intra-anal electrical stimulation (using an anal probe as electrode) appears to be more efficacious than intra-vaginal (using a vaginal probe as electrode). Rarely, skin reactions may occur where the electrodes are placed, but these issues typically resolve when the stimulation is stopped. Surgically implanted sacral nerve stimulation may be more effective than exercises, and electrical stimulation and biofeedback may be more effective than exercises or electrical stimulation by themselves. TENS is also sometimes used to treat FI by transcutaneous tibial nerve stimulation. In a minority of people, anal plugs may be useful for either standalone therapy or in concert with other treatments. Anal plugs (sometimes termed tampons) aim to block involuntary loss of fecal material, and they vary in design and composition. Polyurethane plugs were reported to perform better than those made of polyvinyl-alcohol. Plugs are less likely to help those with frequent bowel movements, and many find them difficult to tolerate. In women, a device that functions as an inflatable balloon in the vagina, has been approved for use in the United States. Surgery may be carried out if conservative measures alone are not sufficient to control incontinence. There are many surgical options, and their relative effectiveness is debated due to a lack of good quality evidence. The optimal treatment regime may be a both surgical and non-surgical treatments. The surgical options can be considered in four categories: restoration and improvement of residual sphincter function (sphincteroplasty, sacral nerve stimulation, tibial nerve stimulation, correction of anorectal deformity), replacement / imitation of the sphincter or its function (anal encirclement, SECCA procedure, non-dynamic graciloplasty, perianal injectable bulking agents), dynamic sphincter replacement (artificial bowel sphincter, dynamic graciloplasty), antegrade continence enema (Malone procedure), and finally fecal diversion (e.g. colostomy). A surgical treatment algorithm has been proposed. Isolated sphincter defects (IAS/EAS) may be initially treated with sphincteroplasty and if this fails, the person can be assessed for sacral nerve stimulation. Functional deficits of the EAS and/or IAS (i.e. where there is no structural defect, or only limited EAS structural defect, or with neurogenic incontinence) may be assessed for sacral nerve stimulation. If this fails, neosphincter with either dynamic graciloplasty or artificial anal sphincter may be indicated. Substantial muscular and/or neural defects may be treated with neosphincter initially. FI is thought to be very common, but much under-reported due to embarrassment. One study reported a prevalence of 2.2% in the general population. It affects people of all ages, but is more common in older adults (but it should not be considered a normal part of aging). Females are more likely to develop it than males (63% of those with FI over 30 may be female). In 2014, the National Center for Health Statistics reported that one out of every six seniors in the U.S. who lived in their own home or apartment had FI. Men and women were equally affected. 45–50% of people with FI have severe physical and/or mental disabilities. Risk factors include age, female gender, urinary incontinence, history of vaginal delivery (non-Caesarean section childbirth), obesity, prior anorectal surgery, poor general health and physical limitations. Combined urinary and fecal incontinence is sometimes termed double incontinence, and it is more likely to be present in those with urinary incontinence. Traditionally, FI was thought to be an insignificant complication of surgery, but it is now known that a variety of different procedures are associated with this possible complication, and sometimes at high levels. Examples are midline internal sphincterotomy (8% risk), lateral internal sphincterotomy, fistulectomy, fistulotomy (18-52%), hemorrhoidectomy (33%), ileo-anal reservoir reconstruction, lower anterior resection, total abdominal colectomy, ureterosigmoidostomy, and anal dilation (Lord's procedure, 0-50%). Some authors consider obstetric trauma to be the most common cause. While the first mention of urinary incontinence occurs in 1500 BC in the Ebers Papyrus, the first mention of FI in a medical context is unknown. For many centuries, colonic irrigation was the only treatment available. Stoma creation was described in 1776, FI associated with rectal prolapse in 1873 and anterior sphincter repair in 1875. During the mid 20th Century, several operations were developed for instances where the sphincters were intact but weakened. Muscle transpositions using the gluteus maximus or the gracilis were devised, but did not become used widely until later. End-to-end sphincteroplasty is shown to have a high failure rate in 1940. In 1971 Parks and McPartlin first describe an overlapping sphincteroplasty procedure. Biofeedback is first introduced in 1974. In 1975, Parks describes post anal repair, a technique to reinforce the pelvic floor and EAS to treat idiopathic cases. Endoanal ultrasound is invented in 1991, which starts to demonstrate the high number of occult sphincter tears following vaginal deliveries. In 1994, the use of an endoanal coil during pelvic MRI shows greater detail of the anal canal than previously. During the last 20 years, dynamic graciliplasty, sacral nerve stimulation, injectable perianal bulking agents and radiofrequency ablation have been devised, mainly due to the relatively poor success rates and high morbidity associated with the earlier procedures. Society and cultureEdit Persons with this symptom are frequently ridiculed and ostracized in public. It has been described as one of the most psychologically and socially debilitating conditions in an otherwise healthy individual. In older people, it is one of the most common reasons for admission into a care home. Persons who develop FI earlier in life are less likely to marry and obtain employment. Often, people will go to great lengths to keep their condition secret. It has been termed "the silent affliction" since many do not discuss the problem with their close family, employers or clinicians. They may be subject to gossip, hostility, and other forms of social exclusion. The economic cost has not received much attention. In the Netherlands, outpatients were reported to have total costs of €2169 annually, and over half of this was productivity loss in work. In the US, the average lifetime cost (treatment and follow-up) was $17,166 per person in 1996. The average hospital charges for sphincteroplasty was $8555 per procedure. Overall, in the US, the total charges associated with surgery increased from $34 million in 1998 to $57.5 million in 2003. Sacral nerve stimulation, dynamic graciloplasty and colostomy were all shown to be cost effective. 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Features of color reflection in psychogenic pain in patients with somatoform disorders during psychotherapeutic treatment. Somatoform disorders relate to 'minor' psychosomatic disorders where somatic symptoms cannot be explained by organic disorders or secondary consequences of other mental symptoms (International Classification of Diseases, 1994; Clinical Psychiatry, 1998). According to ICD-10 (F45) the 'somatoform disorders' class relates to section (F4) 'Neurotic, associated with stress and somatoform disorders'. This section includes: somatization disorder (F45.0), undifferentiated somatoform disorder (F45.1), hypochondriac disorder (F45.2), somatoform vegetative dysfunction (F45.3), chronic somatoform pain disorder (F45.4), other somatoform disorders (F45. 8), unspecified somatoform disorder (F45.9) (International Classification of Diseases, 1994; Clinical Psychiatry, 1998). Most often encountered are somatized disorder (F45.0), somatoform vegetative dysfunction (F45.3) and chronic somatoform pain disorder (F45.4). Relating to diagnostic criteria for somatized disorder are: the presence of many somatic symptoms presented over two or more years which have no adequate somatic explanation; constant expression of distrust in attending physicians in their attempts to convince the patient of the absence of any physical illness and refusal to follow their advice; the presence of symptoms whose consequence is disruption to social and family relations. Diagnostic criteria for somatoform vegetative dysfunction include the following symptoms: symptoms of vegetative excitation (heartbeat, blushing, and tremor having a chronic nature and causing anxiety); additional subjective symptoms relating to the body or system; concern with the given illness despite it being unconfirmed by examinations; lack of confirmation in the results of investigation into the structural or functional disturbance of the body or system (International Classification of Diseases, 1994; Clinical Psychiatry, 1998). An important distinguishing feature of somatoform disorders is special resistance to medicamental treatment and an expressed tendency to timing (V.G. Starshenbaum, 2003). Such patients submit with great difficulty to pharmacological treatment and require psychotherapeutic treatment. However, its effectiveness in much depends on an understanding of the nature of the psychophysiological state of the patients, and their perception and experience of the pain symptoms. This process is very complicated and may be viewed in the context of other forms of mental activity, one of which is the process of color reflection in pain. It is assumed that over the long history of human progress there have formed in the cultural tradition nonconcious associative links between color and its symbolic meaning (N.V. Serov, 1995). Sufficient attention has been devoted to the issues of using color in diagnostics and treatment (B.A. Bazima, 2001; M. Lyusher, 1996; E.I. Sokolova, 2007). At the same time, within the framework of applied methods associative links between color and the signs being studied are measured. Each color tint causes a determined shift in the psychophysiological state of the body (M. Lyusher, 1996; E.I. Sokolova, 2007). Thus, red color excites and activates, and blue calms and restrains. A classification was constructed according to the psychological action of colors on a person (G. Friling, K. Auer, 1995; L.D. Lebedeva, 2006). The authors categorised red, orange and yellow as stimulating or exciting colors. Colors from violet to blue-green--as a group of desintegrate or 'cold' colors causing processes of inhibition, removal of excitation and reduction in emotionality. Colors in the middle part of the spectrum (green, yellow-green, olive, etc.) aiding a person's immersion in his internal world were categorised as static or 'equalising'. 'Soft' or pastel tones (pale green, grey-blue, lilac, etc., that is, colors in the upper part of the spectrum) created a sensation of restraint and softness. Black and other colors with high intensity creating an oppressive impression--fear, anguish--were categorised as a group of dominating or 'oppressive' colors. In contradistinction to G. Friling and K. Auer (1995), A.M. Lugova (2007) put forward two groups of colors according to their psychological effect on a person: 1) an invigorating range which includes red-violet, red, red-orange, yellow-orange and yellow pure colors and their lightened shades; 2) a relaxing range--yellow-green, green, blue-green, blue, blue-violet and violet pure colors and their lightened shades. Moreover, a dependence was discovered between a preference or repugnance towards a color and the nature and intensity of the pain symptoms (G.A. Adashinskaia et al., 2003; 2005). Thus, for patients with neurogenic and somatogenic pain symptoms with high-intensity pain a preference was noted for black and grey colors, for those with mid-intensity pain--brown and red, and where there was no pain--yellow and green colors. For patients with psychogenic pain of high and medium intensity the color preferences were represented by yellow, violet and red colors; where there was no pain--by grey and green (V.I. Shchepin, 2001; G.A. Adashinskaia et al., 2003; 2005). The authors came to a conclusion about the presence of an associative link between color and pain sensation. To reduce stress and optimise the psychophysiological condition of the patients, methods of color therapy have of late been used. The integrated effect of light of the preferred color was accomplished via a visual analyser. At the same time, contemplation of a red, orange, and yellow background was associated with warmth which created an emotional lift; green and sky blue--with a state of calm; blue and violet caused a sensation of cold, black and dark red created a sombre mood (N.V. Serov, 2002; A.M. Lugova 2007). Apart from this, various psychotherapeutic methods are widespread based on active auto-suggestion during muscle relaxation and use of self-regulation processes (V.S. Lobzin, M.M. Reshetnikov, 1986; B.D. Karvasarsky, 1990; 2002; V.V. Kozlov, 2001; A.D. Titar, 2004). The basis of these methods is autogenic training (AT) developed by Shultz 1973. It was noted that during AT there arose spontaneous color images without any external influences in the form of inter-laced lines, 'cloudlike shadows', color spots, etc. (Karvasarsky B.D., 2002, p. 69-70). Using special exercises the patient was being learned to withstand the arising patterns and color spots emotionally and via working with them to regulate his psychophysiological state. The appearance of these images could be accompanied both by positive and also negative emotions. During autotraining the patient was trained to imagine only those images which caused positive emotions that were accompanied by optimisation of the psychophysiological condition (Karvasarsky B.D., 2002, p. 69-70). Thus, the use of psychorelaxation techniques permitted to improve the emotional and physical state. Thus, when applying relaxation methods with the use of corresponding color ranges the emotional state improved, work capacity increased, and the physical state was restored. However, their use was limited by the conditions of the hospitals or other medical establishments, and also the capabilities of the patients themselves to master methods of autogenic relaxation. If in the works of V.I. Shchepin (2001), N.V. Serov (2002), G.A. Adashinskaia (2003; 2005), A.M. Lugova (2007) et al. 'external' color influence on the psychophysiological state of patients was examined, then when applying relaxation methods a link was discovered between the psychoemotional state and color images (V.S. Lobzin, M.M. Reshetnikov, 1986; B.D. Karvasarsky, 1990; 2002; V.V. Kozlov, 2001; A.D. Titar, 2004). However, neither in these, nor in other works, has a study been made of the interrelationship between pain, anxiety and color images, and also the possibility to use this link to liquidate negative symptoms. Along with that it was possible to assume that the substitution of an 'external' color influence for the 'internal' one, arising during color reflection of the pain, would allow an increase in the effectiveness of psychotherapeutic treatment. Within the framework of the present work the study is proposed of the link between color images and the pain of patients with somatoform disorders during psychotherapeutic treatment using empatho-techniques based on synaesthetic mechanisms. In the given work we study synaesthesia between color images and pain. At the same time the patient in a condition of 'empathy' (concentration) in zones of pain localisation established a link between the pain and its color reflection. When concentrating attention on color images, their transformation was noted, accompanied by a decrease in the intensity of psychogenic pain up to its complete disappearance. The purpose of the present work consisted in the study of the interrelationship of color images and psychogenic pain of patients with somatoform disorders during psychotherapeutic treatment. 1) a state of concentration ('empathy') on zones of pain, sensitivity is reflected in color images; 2) during psychotherapeutic treatment positive transformation occurs of color images which is connected with a reduction of pain symptoms and an improvement of the psychophysiological state. Research was carried out for 39 people with somatoform disorders (9 men and 30 woman aged from 20 to 60 years old, with an average age of 40 years) (Group 1). The criteria for selecting patients were their complaints, typical for the given disorders and diagnosis of the attending physician. Amongst them 20 people had higher education (51%), 19 patients (49%) had post-secondary education. 32 patients (82%) were married, 2 patients (5%) divorced, and 5 people (13%) had not been married. The main complaints of the patients under study were cephalagia, spinal pains, and heart pain, etc. Also noted was discomfort in the area of the digestive tract, dyspepsia, irritable bowel syndrome, Da Costa's syndrome, etc. Vegetative disturbances were manifested by headaches, coldness in the extremities, and sweatiness. At the same time, a lasting or labile increase in arterial pressure was observed, an acceleration in the number of cardiac contractions, disturbances in breathing rhythms, a sensation of heaviness, and muscular tension. The indicated symptoms presented, as a rule, in combination with emotional conflict or psychosocial problems. Those pains experienced had no physical basis and were not confirmed by medical examinations. As a control group, 30 healthy people (20 women and 10 men aged from 18 to 60 years old, with an average age of 39 years) were taken (Group 2). Amongst them 85% of those studied were married and 15% had never married. Amongst the healthy subjects 68% had higher education, and 32% post-secondary education. Empatho-techniques were used as a psychotherapeutic method of treatment which allowed certain conditions to be achieved and created for the use of self-regulation processes (V.A. Ishinova et al., 2003; 2004; 2005; 2007). The method being used was applied to discover and study the dynamics of visual images when concentrating on pain. In the beginning the patient was asked to adopt a position comfortable to him (sitting or lying with eyes closed) and to concentrate on places of localised pain or physical discomfort. Under these conditions color spots spontaneously arose which were a color reflection of the physical sensation of pain. In the condition of 'empathy' there occurred the establishment of a link between physical sensations and color images. Empatho-techniques were used as a psychotherapeutic method which allowed the eradication of pain and the normalisation of the psychophysiological condition of the patients (Ishinova et al., 2003; 2004; 2005; 2007). The role of the psychotherapist came down to training the patient from session to session in the methods of 'empathy' in pain zones and the tracking of corresponding color images. Empatho-techniques consisted in the following. Initially the patient was asked to adopt a comfortable position (sitting or lying with eyes closed) and to concentrate on the places of localised pain or physical discomfort. Under these conditions the patients noted the spontaneous appearance of color images which were a color reflection of the physical pain sensation. In other words, in a state of 'empathy' a link was established between physical sensations and color images. According to the patients' self-reports, color images were noted in the form of achromatic, chromatic colors and their combinations. The color images received could appear in the form of achromatic ('a'), to which all shades from white to black were categorised; chromatic colors, which included: 1) red, orange and yellow, relating to the longwave part of the spectrum and designated by us with the letter 'l'; 2) yellow-green, green, and blue-green, relating to the mediumwave part of the spectrum and designated with the letter 'm'; 3) blue and violet colors relating to the shortwave part of the spectrum ('s'). Moreover, mixed chromatic and achromatic colors in various combinations ('al', 'als', 'alm', etc.) were assessed. At the same time, as attention was shifted from the pain to the color images, their transformation was noted, which was accompanied by a decrease in the intensity of the pain symptom and an improvement in the patient's condition. That is, as the pain intensity decreased, a transformation occurred in the color images: colors in the longwave part of the spectrum were replaced by colors in the mediumwave and shortwave parts of the spectrum that was typical for healthy people. During psychotherapeutic treatment the intensity of pain was assessed on the 'pain' scale from the SF-36 quality of life questionnaire. Also, each patient indicated which color corresponded to the pain he experienced. A change in color images was assessed according to the self-reports of each patient and the obtained data recorded in the research reports. Before beginning the sessions each patient was acquainted with the basis of the method and detailed instructions given on the procedure for the research. Additional methods of treatment were not used. The role of the psychotherapist amounted to training the patient from session to session in the methods of 'empathy' with zones of pain, and the ability to relate physical sensation with its color reflection and emotional condition. At the same time, as the removal of concentration of his attention from the intensity of the pain to color images progressed there was a transformation in them which was accompanied by a reduction in the expressiveness of the pain symptom and an improvement in emotional state. In other words, along with the transformation of color images there occurred also a transformation in the intensity of pain symptoms up to their complete disappearance. For assessment of the psychological status at the beginning and end of the course, the levels were determined of trait and state anxiety (TA and SA) using the self-assessment scales of Spielberg-Hanin (I.F. Dyakonov, 2005), and also quality of life using questionnaire MOS SF-36 (Medical Outcomes Study-Short Form) (A.A. Novik, T.I. Ionova, 2002). Special attention was paid to the pain measure which was determined according to the 'Pain' scale of the same survey. According to the authors of the method, the less the intensity of pain, the higher the measure on the 'Pain' scale, as with other measures in the MOS SF-36 questionnaire (A.A. Novik, T.I. Ionova, 2002). A summary assessment of the pain consisted of quantitative (intensity) and qualitative characteristics. To assess the intensity a scale was used where: 0--no pain; 1--very weak pain; 2--weak pain; 3--medium pain; 4--strong pain; 5--very strong pain. The qualitative characteristics were determined according to the degree of the pain's influence on role functionality: 1--did not hinder at all; 2--a little; 3 moderate; 4--strongly; 5--very strongly. Also studied were the dynamics of change in the physical, emotional, mental and social functioning whilst receiving psychological help according to the scales: physical functioning (PF), role physical functioning (RFF), general health (GH), vitality (V), social functioning (SF), role emotional functioning (REF) and mental health (MH). To assess the functional state of the central nervous system (CNS) an examination was carried out of the bioelectrical activity (BEA) of the brain. A record of the EEG was made on a 'Mitsar' 21-channel electroencephalograph in a state of calm wakefulness and during empathetic contact. Electrodes were placed according to the 10x20 international scheme. Assessment of the bioelectrical activity was performed visually according to the I.A. Svyatogor (2001) classification and using mathematical analysis. Statistical processing of the data obtained was carried out using the STATISTICA v 5.5 computer program for non-parametric parameters. At the same time, the Wilkinson (T) and Mann-Whitney (U) criteria were used, and also the Fisher precision method for a fourfold table (V.S. Genes, 1967). The research was conducted in three stages. At the first stage in the beginning of the course of psychotherapeutic treatment acquaintance was made with the patient's problem, his life and medical history, and psychodiagnostics performed. Also analysed was the patient's environment with the purpose of recording possible genetically conditioned illnesses. In this case, if the obtention of information was difficult, for example, due to age or the patient's state of health, conversations were held with his relatives and available records from clinics or hospitals studied. Also conducted at this stage was psychological testing of patients with SFD with the aim of discovering the level of anxiety, quality of life, and presence of pain symptoms. Apart from this, the functional condition of the central nervous system (CNS) was studied, assessed according to background and reactive patterns of brain BEA according to the classification developed by I.A. Svyatogor (2000; 2004), and also according to the spectra of power, amplitudes, and indexes of the main EEG components (delta, theta, alpha and beta ranges). Studied at the second stage in the psychotherapy process were the color images occurring when concentrating attention on pain. At the second stage in the psychotherapy process empatho-techniques were used to remove pain symptoms in patients with somatoform disorders. With a decrease in the intensity of pain changes were noted in the color images. All information obtained was recorded in the research reports. At the third stage at the end of the course a second study was carried out of the psychophysiological characteristics of the patients under examination. The number of sessions was determined by the nature of the change in psychophysiological measures, decrease in complaints, and improvement in wellbeing. The whole course of psychotherapy was performed in a period from one to two months with 1-2 sessions conducted per week, which corresponded on average to 12 sessions each with a duration of 45 minutes. Results and discussion At the beginning of the course patients with SFD had an average pain measure on the 'Pain' scale significantly (p < 0.05) lower (60.5 [+ or -] 9.2) than in the group of healthy subjects (82.15 [+ or -] 8.1) (Diag. 1; Table 1). Patients assessed their pain as having 'moderate' and 'strong' levels of intensity which 'a little' or 'moderately' limited their functioning in society (Diag. 1; Table 1). Distinct from patients with SFD, the healthy subjects on the 'Pain' scale either marked it as completely absent or as 'very weak pain' which related to physical discomfort not having a significant influence on their quality of life (Table 1; Diag. 1). Moreover, for the patients under study a high TA level was discovered (48.2 [+ or -] 3.3), which significantly (p < 0,05) distinguished them in comparison with the healthy subjects (35,67 [+ or -] 1,9) and a moderate SA level--32.5 [+ or -] 3.1 (the lower SA level for healthy subjects was 22.4 [+ or -] 1,8) (Diag. 2). An increased level of anxiety for patients with SFD against a background of expressed pain symptoms was accompanied by a low level of role functioning. So in comparison with the healthy subjects, patients with SFD had significantly lower (p < 0.001) values for role physical (48.5 [+ or -] 11.7) and emotional (50.1 [+ or -] 11.1) functioning, general health (58.3 [+ or -] 5.0) and vitality (47.9 [+ or -] 6.4). It can be assumed that the obtained deviations from normal values are a consequence of the patients' psychophysiological state which is characterised by sleep disruption, increased sensitivity, and the presence of pain symptoms and strong emotional stress that had a significant influence on physical functioning (83.8 [+ or -] 6.0), mental health (53.3 [+ or -] 6.8) and social functioning (73.4 [+ or -] 8.5) (Diag. 1; Table 1). [FIGURE 1 OMITTED] [FIGURE 2 OMITTED] Thus, patients with SFD assessed their quality of life significantly lower than healthy subjects. Anamnestic data from survey patients showed the presence of such personal traits as extreme affect resistance, tendency to fears, suspiciousness, anxiety, continually increased background mood in combination with a hunger for work, high activity, optimism and conflict in some, and sensitivity to offence, suspicion and vulnerability in others. At the same time, characteristic for them was the withdrawal from conflicts and tendency to social deprivation which was reflected in low measures on the 'social functioning' scale. Anamnestic data and results of psychological tests allow the assumption that the characteristics discovered are not only the consequence of illness but also of the personal traits of patients with SFD. During the use of empatho-techniques based on synaesthesia mechanisms, the character of the psychogenic pain's color reflection was studied in patients with SFD. Fifty seven sample observations were conducted during which a link was established between color images and psychogenic pain. At the same time, both 'pure' chromatic ('l', 'm', and 's') and 'pure' achromatic (from light-grey to black--'a') colors were detected, as also were combinations of these colors ('mixed' color images 'als', 'alm', 'lm', 'ls', etc). For this 57 sample observations were conducted during which an interrelationship was established between color images and psychogenic pain. At the same time, both 'pure' chromatic colors were detected ('l', 'm' and 's') and 'pure' achromatic (from white to black- 'a'), and also all possible combinations of these colors ('mixed' color images 'als', 'alm', 'lm', 'ls', etc.). In all, 15 variations of color images were identified. In all, 15 variants of color images were identified: variant 'a' was observed in 6 cases, 'l' in five cases, 1 case of variant 'm', 5-'s', 6-'al', 2-'am', 4 'as', 1-'lm', 5-'ls', 6-'alm', 3-'ams', 1-'lsm', 3 'lsam', and 3 'ms'. However, according to Fisher's Precision Method (FPM) at the beginning of the course where there were pain symptoms there were only 7-'a', l, s, al, ls, alm, als (Table 2)--significantly (p < 0.05) appearing color images. So for patients with SFD psychogenic pain was reflected in the following manner: red, orange, yellow (longwave part of the spectrum part of the spectrum), blue and violet (shortwave part of the spectrum), various shades from black to white (achromatic colors), combinations of red, orange and yellow with blue and violet (mixed colors in the longwave and shortwave parts of the spectrum), red, orange and yellow in combination with green and black-and-white (mixed colors in the longwave and shortwave parts of the spectrum and achromatic colors). From Table 2 it is clear that colors in the mediumwave part of the spectrum (green--'m') were not characteristic for patients SFD where there was psychogenic pain (Table 2). When concentrating on color images reflecting psychogenic pain their transformation was noted, which was accompanied by a reduction in the intensity of the pain right up to its complete disappearance. In conditions of no pain in all 10 color images variants were noted: 22-'a', 3-'l', 5-'m', 12-'s', 1-'al', 3-'am', 3-'as', 2 'lm', 3-'ls', 3-'ms'. During psychotherapeutic treatment a reduction was noted in pain symptoms up to their complete disappearance which was accompanied by a transformation of color images. Where there was a significant lack of psychogenic pain (p < 0.05) there were only three variants of color images (achromatic, mediumwave and shortwave colors) (Table 2). Longwave colors were not detected either in pure form or in combination with other colors (Table 2). Thus, the results obtained illustrated the interrelationship of color images with psychogenic pain which, as a rule, is accompanied by negative emotions (anxiety, irritation, etc.). It may be assumed that by influencing the transformation of color images and changing them in the optimal direction it is possible to reduce psychoemotional tension and optimise the psychophysiological state of patients. Distinct from patients with SFD, healthy subjects experiencing physical discomfort (30 sample observations) there were noted (p < 0.05) only two variants of color images--'a' and 'as' (achromatic--from black to white and a combination of achromatic with shortwave--from black to white with blue and violet colors). Where there was no physical discomfort, 'pure' achromatic and shortwave colors were noted, and also mixed--mediumwave with shortwave (green with blue and violet colors) (Table 3). When studying brain BEA it transpired that 12% did not exhibit deviations, 46% registered a reduction in the intensity of alpha and a strengthening of the intensity of pathological theta and beta components, and for 42% the absence of an alpha-component and the domination of a desynchronised EEG was noted. At the end of the course of psychotherapeutic treatment the psychophysiological state of patients had improved. So, for patients with SFD the intensity of pain symptoms significantly declined, which was reliably confirmed (p <0.001) by an improvement in the 'Pain' scale measure (80.4 [+ or -] 7.2) which approached the value for healthy subjects (82.15 [+ or -] 8.1) (Fig. 1; Tables 1 and 4). There was also a significant (p < 0.001) reduction in the level of TA and SA (Fig. 2). The improvement in the psychophysiological state of patients with SFD was reflected in the measures for their quality of life. The average value of the measures for all scales of the QL questionnaire at the end of the course had significantly improved (p < 0,001) in comparison with the initial values and approached the measures for healthy subjects (Fig. 1; Table 1 and 4). Also, there were no significant differences noted for the TA and SA measures which may bear testimony to the restoration of the psychophysiological state of patients in this group and in connection with this an improvement in role functioning. A significant improvement in psychological measures during psychotherapeutic treatment not always coincided with the normalisation of EEG patterns. Thus, with initial normal measures for BEA (12%) no changes were discovered. For subjects with moderate BEA deviations, in 73% there was noted a significant (p <0.05) increase in the intensity of the alpha-component against the background of a reduction in the intensity of theta- and beta-components, at the same time as for subjects with a desynchronised EEG the increase in intensity of the alpha-component was only noted in 40% of those studied. These data illustrated that despite the significant improvement in the psychological status of patients with SFD, normalisation of the functional state of the CNS according to brain BEA parameters was only observed in 73% and 40% of subjects with an initially changed FS CNS, and FS CNS was not changed where there were initial normal corticosubcortical interrelationships. Thus it can be assumed that the psychotherapeutic effect mechanism is based on the synaesthetic link between spontaneously transforming color images and pain during psychotherapeutic treatment. According to direction of the transformation it is possible preliminarily to assess the degree of influence of negative factors on the psyche of the subject, his reaction to the experienced state, and attitude to his condition. At the same time, a positive transformation may be observed which represents a process of change in color images in the optimal direction (colors in the longwave part of the spectrum reflecting pain and anxiety transform into colors in the medium- and shortwave parts of the spectrum and achromatic ones). The transformation process of color images is associated with the formation of patients' ability for self-regulation, which is accompanied by a reduction in psychoemotional tension and the disappearance of a feeling of discomfort at the somatic and emotional levels. 1. The psychological state of patients with somatoform disorders, by which we understand in the present study the levels of state and trait anxiety, and the intensity of psychogenic pain and variants of color reflection corresponding to it, significantly differ from those in healthy subjects. 2. Measures of bioelectrical activity for patients with SFD in 88% of cases differed from normal values. 3. Discovered deviations in the psychophysiological state of patients with SFD coincided with a low level of quality of life. 4. The psychotherapeutic treatment (empatho-techniques) method we used led to a reliable improvement in the psychological measures being studied. 5. Results of electrophysiological study showed that despite a significant improvement in the psychological status of patients with SFD, normalisation of the functional state of the CNS according to electroencephalography parameters was only observed in 73% of subjects with moderate changes in brain BEA and in 40% of subjects with expressed changes in brain BEA, and did not change where there were initially normal corticosubcortical interrelationships. 6. For the first time data was obtained bearing testimony to color reflection of psychogenic pain in patients with SFD and where there was physical discomfort in healthy subjects. Results of research in healthy people are presented for comparison with the data of patients with SFD on page 11 and in Table 3 and Diagrams 1 and 2. Seven variants of color reflection were reliably identified where there were pain symptoms inpatients with SFD. 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Nekotorye prostye metody kiberneticheskoi obrabotki dannykh diagnosticheskykh i fiziologicheskih issledovaniy [Some simple methods of cybernetic elaboration of data from diagnostic and physiologic studies]. Moskva: Nauka. Gureje O., Von Korff M., Simon G.E, & Gater, R. (1998) Persistent pain and well-being: a World Health Organization study in primary care. Journal of the American Medical Association, 280, 147--151. International classification of Diseases (ICD-10) (1994) The ICD 10 Classification of Mental and Behavioural Disorders/ Russian version edited by Yu. L. Nuller & S. Yu. Tsirkina. St.Petersburg: Ed. Overlaid. Ishinova V.A.. (2003). Sposob Ishinovoi V.A. korrektsii psikhosomaticheskikh i psikhoemotsionalnikh narusheniy [Method of V.A. Ishinova of Correction of Psychosomatic and Psychoemotional Alterations]. Patented in Russian Federation under No 2286806 Ishinova V.A. & Il'ina L.V. (2004). Empatotekhnika kak metod korrektsii psikhicheskogo sostoiania [Empatho-technique as a Method of Correction of Psychological State]. XIX Congress of the Russian Physiological Society named by I.P.Pavlov. Russia, Ekaterinburg. Ishinova V.A., Anan'ev V.A., Sviatogor I.A., Timofeeva L.L & Kuznetsov V.A. (2005). O nekotorikh tendentsiakh izmenenia bioelektricheskoi aktivnosti mozga v protsesse psikhoterapevticheskogo vozdeistvia [Some tendencies in changes of the bioelectrical brain activity during psychotherapeutic intervention]. Zhurnal Mezdunarodnaia Akademia, 21, 218-221. Ishinova V.A., Kashkarova O.E. & Kuznetsov V.A. (2007). Vlianie relaksatsionnykh metodov v protsesse psikhoterapevticheskogo lechenia patsientov s trevozhno-fobicheskimi i somatoformnymi rasstroistvami. [The influence of relaxation methods on the psychotherapeutic treatment of patients with anxiety, phobic and somatic alterations]. Zhurnal Terra Medica, 3, 18-23. Ishinova V.A. & Svyatogor I.A. (2008 a) Otsenka psikhophiziologicheskogo sostoyania pri dezadaptatsionnih narusheniyakh v protsesse psikhologicheskoy korrektsii. [The assessment of the psychophysiological state in disadaptative disturbances during psychocorrection] Proceedings of the International Conference of Donosology. p.292-293. Ishinova V.A., Reznikova T.N. & Svyatogor I.A.(2008 b) Izmenenie tsvetooschuscheniy u patsientov s psikhosomaticheskimi rasstroystvami v protsesse psikhoterapevticheskogo vozdeistvia. Proceedings of the III International Congress Psychosomatic Medicine 2008. p.54-55. Karvasarsky B.D. (2002) Psikhoterapevticheskaia entsiklopedia [Encyclopaedia of Psychotherapy]. St.Petersburg: Ed. Piter Kozlov V.V. (2001) Psikhotekhnologii izmenennykh sostoianiy soznania. Lichnostniy rost. Metody i tekhniki [Psychotechnology of Changed Consciousness. Personality growth. Methods and Techniques]. Moscow: Ed. Institut psikhoterapii. Kulakov S.A. (2002) Osnovy psikhosomatiki. [Basics of Psychosomatics]. St.Petersburg: Rech. Lebedeva L.D., Nikonorova Yu.V. & Tarakanova N.A. (2006). Entsiklopedia priznakov i interpretaciy v proektivnom risovanii i art-terapii. [Encyclopaedia of signs and interpretations in projective drawing and art therapy]. St.Petersburg: Rech. Lobzin V.S. & Reshetnikov M.M.(1986). Autogennaia trenirovka. [Autogennic training]. St.Petersburg: Ed. Meditsina. Lugova A.M. (2007) Sposob korrekcii psikhoemotsionalnogo sostoiania po metodu A.M. Lugovoi. [The Method of A.M.Lugova of Psychoemotional Correction]. Patented in Russian Federation under No 2313282. Lyusher M. & Sara D. (1996). Tsvet vashego kharaktera. Tayni pocherka. [The color of your character. The mystery of your handwriting]. Moscow: Veche Novits A.A. & Ionova T.I. (2002). Rukovodstvo po issledovaniyu kachestva zhizni v meditsine. [Handbook on life quality research in Medicine]. St.Petersburg: Neva Schepin V.I. (2001) Sposob uluchshenia funktsyi organizma [Method of Functional Improvement of the Organism]. Patented in Russian Federation under No 2161991. Schultz J. (1973) Das autogene Training. [The Autogenic Training]. 14th Edition.--Stutgart: Ed. Thieme Serov N.V. (2002) Svetotsvetovaya terapia. Smysl i znachenie tsveta: informatsia-tsvet-intellekt. [Color-light therapy: information--color--intellect]. St.Petersburg: Rech Sokolova E.I. (2007) Sposob Sokolovoi E.I. opredelenia psikhologii sostoiania lichnosti v zhiznennoi situatsii [The Method of E.I.Sokolova of Psychological Determination of the State of the Personality]. Patented in Russian Federation under No 2304985. Starshenbaum G.V. (2003). Dinamicheskaya psikhiatria i klinicheskaya psikhoterapia. [Dynamic psychiatry and clinical psychotherapy]. Moscow: Izdatelstvo vysshei shkoly psikhologii. Svyatogor I.A. (2000). Klassifikatsia EEG-patternov i ikh neirofiziologicheskaia interpretatsia pri dezadaptatsionnykh rasstroistvakh [The classification of EEG-patterns and its neurophysiologic interpretation in non-adaptative alterations]. Biologicheskaia obratnaia sviaz', 3, 10-19. Titar A.D., Titar E.T., Sinutin S.A. & Mishastiy A.A. (2004). Sposob psikhologicheskogo treninga, sposob obuchenia navykam obrazno-simvolnogo myshlenia, sposob obuchenia samoregulatsie psikhoemotsionalnogo sostoyania i ustroystvo dlia psikhologicheskogo treninga. [The Method of Psychological Training, of Learning Habits of Representative and Symbolic Thinking, of Learining Autoregulation of Psychoemotional State and Procedures for Psychological Training]. Patented in Russian Federation under No 2232606. Vera A. Ishinova (1), Irina A. Svyatogor (2) and Tatiana N. Reznikova (3) (1) Wallenberg Institute of Special Education and Special Psychology (2) Pavlov Institute of Physiology, Russian Academy of Sciences (3) Institute of the Human Brain, Russian Academy of Sciences (Russia) Correspondence concerning this article should be addressed to V.A. Ishinova, Saint Petersburg, 195256, Ul. Butlerova, d. 13, kv. 687 (Russia). E-mail: [email protected] Table 1 Average values of quality of life (QL) measures in scores for patients (n = 39) with somatoform disorders before and after psychotherapeutic treatment QL Mean value Before After p< Questionnaire (M) and psycho- psycho- Scales standard therapeutic therapeutic deviation therapy therapy (SD) PF M 83.8 94.4 SD 6.0 2.8 0.001 RPF M 48.5 87.8 SD 11.7 6.9 0.001 P M 60.5 80.4 SD 9.2 7.2 0.001 GH M 58.3 72.6 SD 5.0 4.7 0.001 V M 47.9 69.7 SD 6.4 5.8 0.001 SF M 73.4 90.4 SD 8.5 4.1 0.001 REF M 50.1 78.6 SD 11.1 9.5 0.001 MH M 53.3 75.6 SD 6.8 4.4 0.001 p<--level of significance according to Wilkinson criteria; M--mean value; SD--standard deviation; n--sample size. PF--physical functioning; RPF--role physical functioning; P--pain; GH--general health; V--vitality; SF--social functioning; REF -role emotional functioning; MH--mental health. Table 2 Reliable (p<0.05 according to FPM) frequency of occurrence of color patterns in % of patients with SFD where there is psychogenic pain and where it is absent (n = 57) Reliable occurrence Variants of of variants of color color reflection where reflection pain is present % Mean SD error % ([+ or -]) Achromatic (a) 10 4 4-22 Longwave (l) 9 4 3-10 Mediumwave (m) -- -- -- Shortwave (s) 9 4 3-10 Achromatic + longwave (al) 10 4 4-22 Longwave + shortwave (ls) 9 4 3-10 Achromatic + longwave + shortwave (als) 10 4 4-22 Achromatic + longwave + mediumwave (alm) Achromatic + longwave + mediumwave (alm) 10 4 4-22 Reliable occurrence Variants of of variants of color color reflection where reflection pain is absent % Mean SD error % ([+ or -]) Achromatic (a) 38 6 27-53 Longwave (l) -- -- -- Mediumwave (m) 9 4 3-10 Shortwave (s) 21 5 11-34 Achromatic + longwave (al) -- -- -- Longwave + shortwave (ls) -- -- -- Achromatic + longwave + shortwave (als) -- -- -- Achromatic + longwave + mediumwave (alm) Achromatic + longwave + mediumwave (alm) -- -- -- %--number of observations of the given color from the total number of observations; [+ or -]--mean error; SD (standard deviation)--indicates in which limits it is possible to expect reliable occurrence of the said attribute. Table 3 Reliable (p<0.05 according to FPM) frequency of occurrence of color patterns in % of healthy subjects with physical discomfort and where it is absent (n = 30) Reliable occurrence of variants of color Variants reflection of color where pain is reflection present Mean error % % ([degrees]) SD e Achromatic (a) 33 9 17-53 Longwave (l) -- -- -- Shortwave (s) -- -- -- Mediumwave + shortwave (ms) -- -- -- Achromatic + shortwave (as) 20 7 8-39 Reliable occurrence of variants of Variants color reflection of color where pain is absent reflection Mean error % % ([degrees]) SD Achromatic (a) 30 9 15-49 Longwave (l) -- - - Shortwave (s) 27 8 12-46 Mediumwave + shortwave (ms) 17 7 6-35 Achromatic + shortwave (as) -- - - %--number of observations of the given color from the total number of observations; [+ or -]--mean error; SD (standard deviation) indicates in which limits it is possible to expect reliable occurrence of the said attribute. Table 4 Average values of measures of quality of life (QL) scales in scores for patients with somatoform disorders after psychotherapeutic treatment and for healthy subjects Groups studied QL Mean value (M) Patients with Healthy Questionnaire and standard SFD (after subjects Scales deviation (SD) psychotherapeutic treatment) PF M 94.4 94.8 SD 2.8 2.9 RPF M 87.8 85.6 SD 6.9 8.8 P M 80.6 82.2 SD 7.0 8.1 GH M 72.6 72.4 SD 4.7 5.1 V M 69.7 71.3 SD 5.8 6.3 SF M 90.4 88.7 SD 4.1 5.7 REF M 78.6 79.5 SD 9.5 10.8 MH M 75.6 73.6 SD 4.4 5.1 Reliability determined by Mann-Whitney criteria (U) was not discovered. M--mean value; SD--standard deviation; n--sample size. PF--physical functioning; RPF--role physical functioning; P--pain; GH--general health; V--vitality; SF--social functioning; REF -role emotional functioning; MH--mental health. \|Printer friendly Cite/link Email Feedback\| \|Author:\|\|Ishinova, Vera A.; Svyatogor, Irina A.; Reznikova, Tatiana N.\| \|Publication:\|\|Spanish Journal of Psychology\| \|Date:\|\|Nov 1, 2009\| \|Previous Article:\|\|Salivary cortisol response to a psychosocial stressor on children diagnosed with attention-deficit/hyperactivity disorder: differences between...\| \|Next Article:\|\|Temporal stability and cross-national consistency of the dimensional structure of the sexual attraction questionnaire (SAQ).\|	2	28	0	0	6	0.88481	6	10,405
What Are The Stages Of Prostate Cancer Your healthcare provider uses the Gleason score and Grade Groups to stage prostate cancer based on its projected aggressiveness. To get this information, the pathologist: - Assigns a grade to each type of cell in your sample. Cells are graded on a scale of three to five . Samples that test in the one to two range are considered normal tissue. - Adds together the two most common grades to get your Gleason score . - Uses the Gleason score to place you into a Grade Group ranging from one to five. A Gleason score of six puts you in Grade Group 1 . A score of nine or higher puts you in Grade Group five . Samples with a higher portion of more aggressive cells receive a higher Grade Group. Recommended Reading: Is Zinc Good For The Prostate Definitions Of Disease Categories ICD codes used in the disease categories were the following : myocardial infarction , other coronary heart disease , cerebrovascular accident , arterial disease , heart failure , pneumonia , chronic lower respiratory disease , external causes , complications of diagnostic or surgical procedures , complications of therapeutic drug or vaccine usage , suicide , traffic accident , falls , other heart disease , gastrointestinal disease , dementia , diabetes , complications of heart disease , urinary system disease , symptoms , pulmonary circulation , nervous system disease , hypertensive disease , other bacterial disease , psychic disease , anemia , tumors other than prostate cancer , and prostate cancer . Causes Of Prostatitis Food Allergies Food allergies can cause prostate inflammation and prostatitis. Symptoms of food allergy can include abdominal pain, nausea, vomiting, as well as diarrhea. A food allergy is known as an immune system response, so its symptoms can affect the whole body. Besides, food allergy can lead to itchy skin, a sudden decrease in blood pressure, shortness of breath and difficulty swallowing. One reason why food allergy can be a cause of prostatitis is that some patients experience a flare-up of signs and symptoms when consuming certain foods. Some products such as pasta, breads as well as baked goods are commonly associated with food allergy. So, you should try a wheat-free diet to help determine whether or not wheat is the cause of your prostatitis. Besides, some other men reported that their symptoms become worse after they consume spicy or acidic foods. Keep reading this entire article to discover other causes of prostatitis that can make you experience some of the symptoms of prostatitis. Recommended Reading: What Is The Main Cause Of Prostate Enlargement What Is The Prostate The prostate is a small gland in men that helps make semen. Located just below the bladder in front of the rectum, it wraps around the tube that carries urine and semen out of the body. It tends to grow larger as you get older. If your prostate gets too large, it can cause a number of health issues. Donât Miss: Flomax No Sperm Vitamin And Mineral Supplements An inverse relationship was observed between sunlight, or UVB exposure, and incidence of prostate cancer , suggesting that vitamin D deficiency might increase prostate cancer risk development . Similarly, discoveries were made by Barnett and Beer who found that people living in âsunnyâ countries were at lower risk of developing secondary solid cancer after melanoma compared to people living in âless sunnyâ countries. The incidence of prostate cancer in African-American men is twice that of Caucasians, suggesting that race might play a role. There might be a role for vitamin D deficiency in this as UV radiation is blocked in darkly pigmented skin due to high melanin levels and this mechanism inhibits the conversion to vitamin D3 . Vitamin E is a vitamin which is fat soluble. Vegetable oils, egg yolks, and nuts are the important dietary sources of vitamin E. Tocopherols present in vitamin E have both potent cellular anti-oxidant with anticancer properties . Studies investigating the relationship between vitamin E and prostate cancer risk have shown contradicting results. The ATBC trial showed that in men who smoked supplementing daily vitamin E was not able to reduce the incidence of prostate cancer . In another large clinical trial , vitamin E supplementation did not show any benefit in 31,000 men with incident prostate cancer . Folate and vitamin B12 Also Check: What Age Do Males Get Prostate Cancer When Malignant Cancer Cells Form And Grow Within A Persons Breast Tissue Breast Cancer Occurs In fact, most people dont even know what it does. The earlier the detection of prostate cancer, the better the patients chance of survival is. The pancreas is located behind the stomach, so having pancreatic cancer doesnt involve a palpable mass that you can feel. Being armed with information is vital to begin the fight. If breast cancer is diagnosed at an early enough stage, its treatable. Here are 10 more facts about prostate cancer. Despite this, pancreatic cancer is among the deadliest types of cancer, which is why its extremely important to know and recogni. Although the percentage of cases in men is much lower than in women, male breast cancer accounts for a por. Find the information you need today. Whether you or someone y. It may grow slowly and its typically treatable. Treatment for bladder cancer depends on your overall health, progression of the c. Prostate cancer is a common type of cancer in men, according to the mayo clinic. Although the percentage of cases in men is much lower than in women, male breast cancer accounts for a por. Being armed with information is vital to begin the fight. Breast cancer is the second most common cancer found in women after skin cancer but that doesnt mean men arent at risk as well. But hearing the words can still be scary. The pancreas is an organ that releases enzymes involved with digestion, and hormones to regular blood sugar levels. Whether you or someone y. Dont Miss: Does Enlarged Prostate Affect Ejaculation Can A Poor Diet Cause Prostate Cancer The impact of diet isnt clear. Theres no definitive cause and effect connection between prostate cancer and diet. But there is some evidence that prostate cancer is associated with: Dairy: Men who eat a lot of dairy may be slightly more at risk for prostate cancer. High-fat or high-carb foods: Eating a lot of sugary or high-fat foods may increase your risk for prostate cancer. These foods can also cause obesity, which may change your hormone levels and promote inflammation. Processed meat: This includes foods like salami, bacon, and lunch meat. Theres evidence that eating these foods every day increases your prostate cancer risk. Alcohol: This includes beer, wine, and liquor. Theres growing evidence that alcohol can increase your risk for prostate cancer. Also Check: When To Get A Prostate Biopsy Major Causes Of Prostate Cancer Cancer that affects the prostate gland of the body is called prostate cancer. It is a small gland in the male body that is in the shape of a walnut. The sperm in the male body is transported and nourished by the seminal fluid produced by the prostate gland. Around 40,000 people die every year due to prostate cancer. Prostate cancer is very common in men. The growth of cancer is slow and usually, it is limited inside the prostate gland without causing any serious problem. Early detection can help in getting timely prostate cancer treatment. International Rates And Migration Prostate cancer exhibits an extraordinary amount of variation in its occurrence worldwide. For example, the incidence rate for African Americans is approximately 60-fold higher than the rate among men in Shanghai, China.6 Although part of this disparity is due to differences in diagnostic ascertainment and the prevalence of screening, mortality rates, which are less subject to such influences, also vary profoundly. For example, the mortality rate for African Americans from 1988 to 1992 was approximately 12 times higher than the mortality rate in Hong Kong. These differences notwithstanding, mortality is increasing faster in the westernizing parts of Asia than anywhere else in the world. Observation of Asian migrants, moreover, provides the most compelling argument for environmental influences linked to Western lifestyle as causal factors in prostate cancer. Japanese Americans have an incidence rate 43 times higher than their counterparts in Japan, and there are data indicating that migrants develop the high-risk pattern within one generation.6,7 Shimizu and colleagues reported that prostate cancer incidence rates in Los Angeles among migrants from Japan were similar regardless of whether men immigrated early or later in life.7 We interpret this to mean that environmental forces can accelerate the progression of latent tumors even late in life. You May Like: Can Prostate Cancer Metastasis To The Colon Painful Or Burning Urination Prostate cancer causes the gland to enlarge in size, affecting the normal flow of urine. Impedance to urine flow is the reason for painful micturition. It is also possible that painful urination occurs due to cancer spreading to surrounding structures. Prostate cancer is notorious for its nature of local invasion of surrounding structures like the urethra, bladder, and rectum. Burning during urination can be due to suppurative infection or side effects of the treatment of prostate cancer. The enlargement of the gland causes urinary obstruction and retention. Undue retention of urine inside the bladder can lead to infection of urethra and bladder leading to burning during urination. Antibiotics can relieve the situation for a while, but the doctor needs to start treating prostate cancer to avoid further risks and complications. Discussing this problem with your doctor is the best possible choice to ward off the complications of undiagnosed prostate cancer. Family history and genetics are major risk factors of prostate cancer, but lifestyle changes and diet can make these warning signs more conspicuous as obesity can worsen your condition of painful micturition. Page 1 of 14 Expert Review And References - American Cancer Society. Prostate Cancer Early Detection, Diagnosis, and Staging. 2019: . - Garnick MB . Harvard Medical School 2015 Annual Report on Prostate Diseases. 2015. - Hermanns T, Kuk C, Zlotta AR. Clinical presentation, diagnosis and staging. Nargund VH, Raghavan D, Sandler HM . Urological Oncology. Springer 2015: 40: 697-718. - Logothetis CJ, Kim J, Davis J, Kuban D, Mathew P, Aparicio A. Neoplasms of the prostate. Hong WK, Bast RC Jr, Hait WN, et al . Holland Frei Cancer Medicine. 8th ed. People’s Medical Publishing House 2010: 94: 1228-1254. - PDQ® Adult Treatment Editorial Board. Prostate Cancer Treatment Patient Version. Bethesda, MD: National Cancer Institute 2020: . - PDQ® Adult Treatment Editorial Board. Prostate Cancer Treatment Health Professional Version. Bethesda, MD: National Cancer Institute 2020: . Don’t Miss: Drinking Alcohol After Prostate Surgery Diagnostic Radiologic Procedure And Ultraviolet Light Exposure The radiation generated from X-ray, CT and nuclear imaging is ionizing radiation that penetrates the tissue to reveal the bodyâs internal organs. However, ionizing radiation can damage DNA, and although cells repair most of the damage, sometimes small area may remain altered consequently leading to DNA mutations that may contribute to cancer development years down the road. The first study investigating the connection between low-dose ionization radiation from diagnostic X-ray procedures and risk for prostate cancer reported that exposure to a hip/pelvic X-ray significantly increased prostate cancer risk independently of other known risk factors such as family history of cancer . However, unless men were exposed to high doses of radiation during cancer treatment in youth, any increase in the risk for cancer due to medical radiation appears to be slight. Considering that the increase in high-dose imaging has occurred only since 1980 and the effects of radiation damage typically take many years to appear, this may explain the weak association between ionizing radiation and prostate cancer risk observed thus far. Finally, exposure to solar UV radiation is inversely associated with both the incidence and mortality of prostate cancer . The biological explanation of this fact is based on the synthesis and physiological actions of vitamin D . Staging: The Tnm System Staging is done as part of the diagnosis process to determine how extensive your cancer is within your prostate and whether it has spread to lymph nodes or other organs. Prostate cancer is typically staged using the TNM system, which is based on: - The extent of the primary tumor - Whether the cancer has spread to nearby lymph nodes - The presence or absence of distant metastasis - Your PSA level at the time of diagnosis - Your Gleason score and the amount of cancer Using this information, prostate cancer is then grouped into stages I through IV, with stage I being the least advanced and stage IV being the most advanced. - Stage I: Cancer is confined to your prostate. Gleason score is 6 or below. PSA level is less than 10. - Stage II: The tumor is more advanced but does not extend beyond your prostate. - Stage III: The tumor extends beyond your prostate and may be in a seminal vesicle. Cancer has not spread to lymph nodes. - Stage IV: The tumor has spread to another part of your body, such as your bladder, rectum, lymph nodes or bones. Don’t Miss: How Early Can You Get Prostate Cancer Early Prostate Cancer Warning Signs Men Should Look Out For Prostate cancer affects one in eight men in the UK Men are being told to watch out for seven key signs that could signal that they have prostate cancer. The disease, which affects one in eight men in the UK, is largely symptomless, reports Leicestershire Live. Chances of survival are entirely dependent on when the disease is diagnosed, meaning the seven telltale signs could make all the difference. The call for wider awareness of prostate cancer comes as 100 percent of people diagnosed at its earliest stage survive for five years or more. About 78 percent of those diagnosed will survive for 10 or more years, but this all comes down to when a diagnosis is made. A key issue for late diagnosis is often linked to the fact that prostate cancer doesnt usually cause any symptoms in its early stages. This means men often wont get tested until it can be too late. However, experts say seven key signs can lead men towards an earlier diagnosis â and many are linked to urinating. Mainly centred around a change in urinary habits, this is more likely to mean an enlarged prostate than prostate cancer for a concerned man, but regardless, people are still urged to get it checked out. Over the years, many men will suffer issues with urination, some of which can be linked to prostate cancer. Things You Can Change: Diet And Lifestyle Men in western countries have much higher rates of prostate cancer than men in Asia. While no one can definitively explain this phenomenon, experts suspect differences in eastern and western diets are to blame. Poor eating habits and diets that heavily rely on fats and animal proteins can cause DNA damage and lead to cancer. Even men who are already at greater risk due to age, race or genetics can reduce their chances of developing prostate cancer by adopting healthy diets and lifestyles. Read Also: Is Peanut Butter Good For Prostate Etiology And Risk Factors The etiology of prostate cancer is the subject of numerous studies and remains largely unknown compared to other common cancers. The well-established prostate cancer risk factors are advanced age, ethnicity, genetic factors and family history . Other factors positively associated with prostate cancer include diet , obesity and physical inactivity, inflammation, hyperglycemia, infections, and environmental exposure to chemicals or ionizing radiation . Is Prostate Cancer Genetic Yes. Cancer including prostate cancer is caused by genetic changes. Some of these changes are inherited from family members. Others are acquired during your life due to age, exposures, diet, and lifestyle. You can end up with a gene change in two different ways: 1) Youre born with it. This is called an inherited” gene mutation. In other words, your father or mother had the same mutation and passed it to you. There are over 20 different genes associated with prostate cancer. Keep in mind that both womenandmen can have these mutations. 2) You acquired it at some point during your life. This is called an acquired gene mutation. This means you were born without the gene change, and it happened at some point during your life. Recommended Reading: Genetic Testing For Prostate Cancer Risk Further Treatments To Control The Cancer Your first treatment may help keep your cancer under control. But over time, the cancer may change and start to grow again. If this happens you might be offered other treatments, including: - more hormone therapy - clinical trials More hormone therapy If youve had hormone therapy on its own as a first treatment, you might be offered a chemotherapy drug called docetaxel . This may help some men to live longer, and can help to improve and delay symptoms. If youve already had docetaxel, you might be offered more docetaxel or another chemotherapy drug called cabazitaxel . This is a type of internal radiotherapy that may be an option if your cancer has spread to your bones and is causing pain. A radioactive liquid is injected into your arm and collects in bones that have been damaged by the cancer. It kills cancer cells in the bones and helps some men to live longer. It can also help to reduce bone pain and delay some symptoms, such as bone fractures. Read more about radiotherapy for advanced prostate cancer.	2	12	0	0	1	0.517121	1	3,669
What is valvular heart disease? Valvular heart disease icd 10 is the point at which any valve in the heart has harm or is ailing. There are a few reasons for valvular heart disease icd 10. - The ordinary heart has four chambers (both ways atria, and right and left ventricles) and four valves (Figure 1). - The mitral valve, additionally called the bicuspid valve, permits blood to move from the passed-on chamber to the left ventricle. - The tricuspid valve permits blood to move from the right chamber to the right ventricle. - The aortic valve permits blood to move from the passed-on ventricle to the aorta. - The pneumonic valve permits blood to move from the right ventricle to the aspiratory vein. The valves open and near control or direct the blood streaming into the heart and afterward away from the heart. Three of the heart valves are made out of three handouts or folds that cooperate to open and near permit blood to stream across the opening. The mitral valve just has two handouts. Solid heart valve handouts can completely open and close the valve during the heartbeat, yet sick valves could not completely open and close. Any valve in the heart can become unhealthy, yet the aortic valve is generally ordinarily impacted. Ailing valves can turn into “broken” where they don’t totally close; this is called disgorging. Assuming this occurs, blood spills once again into the chamber that it came from insufficient blood can be pushed forward through the heart. The other normal sort of heart valve condition happens while the launch of the valve is restricted and firm and the valve can’t open completely when blood is attempting to go through; this is called stenosis. In some cases the valve might be feeling the loss of a handout — this all the more generally includes the aortic valve. In the event that the heart valves are sick, the heart can’t really siphon blood all through the body and needs to work harder to siphon, either while the blood is spilling once more into the chamber or against a limited opening. This can prompt cardiovascular breakdown, unexpected heart failure (when the heart quits thumping), and demise. Realities About Valvular Heart Disease icd 10 - Around 2.5% of the U.S. populace has valvular heart disease icd 10, yet it is more normal in more seasoned grown-ups. Around 13% of individuals brought into the world before 1943 have valvular heart disease 10. - Rheumatic heart disease most regularly influences the mitral valve (which has just two flyers) or the aortic valve, however, any valve can be impacted, and beyond what one can be involved. - Bicuspid aortic valve (having just two pamphlets as opposed to the typical three) occurs in around 1% to 2% of the populace and is more normal among men. - In 2017, there were 3,046 passings because of rheumatic valvular heart disease icd 10 and 24,811 passings because of non-rheumatic valvular heart disease icd 10 in the United States. - Almost 25,000 passings in the U.S. every year are because of heart valve sickness from causes other than rheumatic disease. - Valvular heart disease icd 10 passings are all the more generally because of aortic valve sickness. Rates of Deaths Due to Valvular Heart Disease icd 10 by Valve, 2017 In 2017, 61% of passings from valvular heart disease icd 10 were because of aortic valve sickness and 15% of passings were brought about by mitral valve disease. As per a 2020 CDC investigation of grown-ups with CHDs, the predominance rate was 2.5% higher in guys than in females (51.3% vs. 48.8%, respectively). What causes valvular heart disease icd 10? There are a few reasons for valvular heart disease icd 10, including inborn circumstances (being brought into the world with it), contaminations, degenerative circumstances (wearing out with age), and conditions connected to different sorts of heart disease. - The rheumatic disease can occur after contamination from the microscopic organisms that cause strep throat isn’t treated with anti-toxins. The contamination can cause scarring of the heart valve. This is the most widely recognized reason for valve sickness around the world, yet it is considerably less normal in the United States, where most strep contaminations are dealt with ahead of schedule with anti-infection agents. It is, nonetheless, more normal in the United States among individuals brought into the world before 1943. - Endocarditis is a contamination of the internal coating of the heart brought about by a serious disease in the blood. The disease can choose the heart valves and harm the handouts. Intravenous medication use can likewise prompt endocarditis and cause heart valve sickness. - Intrinsic heart valve disease is distortions of the heart valves, like missing one of its pamphlets. The most usually impacted valve with an intrinsic imperfection is a bicuspid aortic valve, which has just two flyers instead of three. - Different kinds of heart disease: - Cardiovascular breakdown. Cardiovascular breakdown happens when the heart can’t siphon sufficient blood and oxygen to help different organs in your body. - Atherosclerosis of the aorta where it joins the heart. Atherosclerosis alludes to the development of plaque within the vein. Plaque is comprised of fat, calcium, and cholesterol. - A thoracic aortic aneurysm is a lump or expansion where the aorta connects to the heart. - A respiratory failure (otherwise called myocardial dead tissue or MI), can harm the muscles that control the opening and shutting of the valve. - Immune system disease, like lupus. - The Marfan disorder is a sickness of connective tissue that can influence heart valves. - Openness to high-portion radiation, which might prompt calcium stores on the valve. - The maturing system can cause calcium stores to foster on the heart valves, making them solid or thickened and less productive with age. What are the side effects of valvular heart disease icd 10? Heart valve disease can grow rapidly or over a significant stretch. At the point when valve disease grows all the more leisurely, there might be no side effects until the condition is very cutting-edge. At the point when it grows all the more unexpectedly, individuals might encounter the accompanying side effects: - Chest torment - Unsteadiness or blacking out - Quick weight gain - Unpredictable heartbeat How is valvular heart disease icd10 analyzed? The specialist might hear a heart mumble (an uncommon sound) while paying attention to your pulse. Contingent upon the area of the mumble, how it sounds, and its mood, the specialist might have the option to figure out which valve is impacted and what kind of issue it is (disgorging or stenosis). A specialist may likewise utilize echocardiography, a test that utilizations sound waves to make a film of the valves to check whether they are working accurately. How is valvular heart disease icd 10 treated? On the off chance that the condition is straightforward, it very well may be made do with prescriptions to treat the side effects. In the event that the valve is all the more genuinely unhealthy and causes more serious side effects, a medical procedure might be suggested. The sort of a medical procedure will rely upon the valve in question and the reason for the sickness. In certain circumstances, the valve should be supplanted by either opening the heart during a medical procedure or supplanting the valve without opening the heart during the medical procedure. To Know More About Hypertensive Heart Disease icd 10. Valvular Heart Disease pdf : Valvular Heart Disease icd 10 (FAQs) What is the ICD 10 code for valvular heart disease? ICD-10-CM I08. 9 is gathered inside Diagnostic Related Group(s) (MS-DRG v39.0): 306 Cardiac intrinsic and valvular problems with mcc. 307 Cardiac inborn and valvular problems without mcc. What is valvular heart disease? Valvular heart disease is the point at which any valve in the heart has harm or is ailing. There are a few reasons for valve infection. The typical heart has four chambers (both ways atria, and right and left ventricles) and four valves. What are the sorts of valvular heart disease? Kinds of valvular heart disease Valvular stenosis (limiting) The solidifying of heart valves can limit the size of the valve opening and confine blood stream. … Valvular prolapse (getting awkward) Prolapse is a condition when the valve folds (pamphlets) get awkward or structure a lump. … What is the most widely recognized type of valvular heart disease? Degenerative valve disease is the most widely recognized type of valvular heart disease in the United States, while rheumatic heart disease represents most valve pathology in agricultural countries. As the US populace ages, doctors are probably going to see more patients with degenerative valve issues. What are the symptoms of valve disease? A few actual indications of heart valve disease can include: Chest torment or palpitations (fast rhythms or skips) Windedness, trouble slowing down to rest, weariness, shortcoming, or powerlessness to keep up with normal movement level. Dazedness or blacking out. Enlarged lower legs, feet or midsection. Is valvular heart disease serious? Many individuals carry on with long and solid lives and never acknowledge they have a gentle valve issue. Be that as it may, left untreated, high-level valve sickness can cause a cardiovascular breakdown, stroke, blood clumps or passing because of abrupt heart failure. Is valvular heart disease perilous? Heart valve sickness alludes to any of a few circumstances that forestall at least one of the valves in your heart from working right. Left untreated, heart valve sickness can make your heart work harder. This can decrease your personal satisfaction and, surprisingly, become perilous. How long can you live with valvular heart disease? In non-industrial nations, it advances substantially more quickly and may prompt side effects in youngsters under 5 years old. Around 80% of patients with gentle side effects live for no less than 10 years after the determination. In 60% of these patients, the illness may not advance by any stretch of the imagination. How is valvular heart disease analyzed? An ECG can recognize broadened offices of your heart, heart disease and unusual heart rhythms. Chest X-beam. A chest X-beam can assist your PCP with deciding if the heart is expanded, which can show specific kinds of heart valve infections. A chest X-beam can likewise assist specialists with deciding the state of your lungs What is the ICD-10 code for valvular heart disease? ICD-10 code I34. 0 for Nonrheumatic mitral (valve) deficiency is a clinical grouping as recorded by WHO under the reach – Diseases of the circulatory framework.	2	8	0	0	4	0.900451	4	2,437
CNA EXAM 2.txt Home > Flashcards > Print Preview The flashcards below were created by user on FreezingBlue Flashcards . What would you like to do? CH 8: What structures are in the Upper Respiratory Tract? Nose, Pharynx (throat), Larynx (voice box) What is an epiglottis? lid over larynx prevents food from getting in What structures are in the Lower Respiratory Tract? - Trachea - windpipe - Right and left lung - Main stem bronchus - Right and left bronchus: Bronchi, Bronchioles, Alveoli What is the evolutionary process of the respiratory function? - -Traps foreign bodies in airway: Mucus, goblet cells, cilia and Helps prevents lung infection - Carries odor molecules: detected by olfactory sensors in nose & carried to brain and Moistens air - Airflow �hijacked� by larynx: Creates vast range of sound and Uniquely human communication What is the function of the respiratory system? - -Absorb oxygen from atmosphere: Fuel for cellular metabolism - -Expel carbon dioxide from body:Waste products of cellular metabolism, Accumulation results in respiratory acidosis - Breathing apparatus takes up most of space in face, neck, chest - Breathing requires huge expenditure of energy for the movement of the Diaphragm and Intercostal muscles What are the basics of Cellular Metabolism? - -Oxygen and Glucose go into cell. - -Energy in the form of ATP is produced. - -By products H2O, CO2 & heat leave cell. What are the respiratory pumps? diaphragm and intercostal muscles Describe the diaphragm? - Dome shaped muscle - Three sheets of crisscrossed muscle attached to ribs, spine & sternum - Separates thoracic cavity from abdominal cavity - Expiration-Center bulges from pressure in abdominal cavity at rest - Inspiration-Flattens and enlarges chest when contracted - Pleura creates seal that allows lungs to move with the diaphragm - Muscles contract in unison - Diaphragm pulls down and ribs pull upward - Rib cage swings up and out enlarging the chest Is Inspiration an active or inactive process? Is Expiration a passive or active process? Describe the lungs? - -two, Soft, stretchy and spongy �lites� - Right lung 3 �lobes� - Left lung 2 �lobes� - Scooped out area front and center cradles heart - lungs never quiet - Double sided serous membrane lining reduces friction - Visceral pleura wraps lung - Parietal pleura wraps inside of chest wall - Oily pleural fluid between layers allows lungs to slide in chest as we breath How much air is inspired and expired with each respiration 3/4 pint�about 15 pints/min. Describe Bronchial systems in lungs? - Bronchial system of increasingly smaller tubes traverse lungs - Appearance of upside down, hollowed out tree which forms the - R & L main stem bronchus - Wrapped in muscular coat - End in blind sacs �alveoli� - Structured like a cluster of grapes for increased surface area - 350,000,000 / lung - O2 & CO2 transferred across alveolar membrane - Each wrapped in capillary - 350 million alveola per lung - Area of a tennis court - Increases oxygen absorptive capacity - Pulmonary artery bring deoxygenated blood to alveolar capillaries - CO2 crosses into lumen - O2 crosses into capillaries - Pulmonary veins return oxygenated blood to heart - 1/5 to 1/10 of blood supply is in pulmonary circulation at any given time Describe Alveolar Circulation? - -very efficient - -O2 passes by diffusion: hi in air to low gradient in alveoli - -Crosses 2 ultra-thin membranes - -Alveoli one cell layer thick and Surfactant increases surface tension - -Capillary membrane one cell layer thick: Total 1/1000 mL What is automatic breathing? - Primitive respiratory center in brain - Medulla oblongata - Don�t have to think about breathing CH 40: Respiratory Disorders: What are the functions of the lungs? - Brings oxygen (O2) into the lungs - Removes carbon dioxide (CO2) from the body. What are respiratory disorders and illness? Anything that interferes with lung function and decreases the quality of life or threatens life. What is COPD? Chronic obstructive pulmonary disease (COPD) What does COPD affect? - the airways and alveoli become less elastic - the walls between the alveoli are destroyed - airway walls become inflamed - more mucus is secreted What are 3 COPD illnesses? - Chronic bronchitis What are the risk factors for COPD? - Smoking tobacco or marijuana - Exposure to second-hand smoke Does COPD have a cure? Describe Chronic Bronchitis? - Occurs after repeated episodes of bronchitis. - Inflammation of the bronchi. - Smoker�s cough in the morning is often the first symptom. What are the risk factors for chronic bronchitis? - Smoking is the major cause. - Infection, air pollution, and industrial dusts are risk factors. How is chronic Bronchitis treated? - Smoking cessation - Oxygen therapy and breathing exercises are often ordered. - Alveoli enlarge and become less elastic. - Air is trapped in the alveoli when exhaling. - O2 and CO2 exchange cannot occur in affected alveoli - Over inflation with stagnant air - The person has shortness of breath and a cough - Breathing is easier when upright and slightly forward - Tripod position What is barrel chest? occurs with people with emphysema. since air can't escape the alveoli in the lungs, the chest puffs out What are the risk factors for emphysema? - Smoking most common cause - Air pollution and industrial dusts are risk factors What is the treatment for emphysema? - Smoking cessation - Respiratory therapy - Reactive airway - Airway inflamed and narrow at bronchioles - Extra mucus production - Dyspnea - labored breathing - Wheezing and coughing - Pain and tightening in the chest What triggers Asthma? Allergies, smoke, pollutants, exertion or cold air. How is Asthma treated? - Severe attacks may require emergency care. - Repeated or undertreated attacks can damage the respiratory system. - Viral respiratory infection. - Flu season from November through March. - Most deaths occur in older persons. How do you treat the flu? - Relief of symptoms. How is the flu spread? - Coughing and sneezing - Standard Precautions are followed - Flu vaccine for prevention Who is recommended to have the flu vaccine as per the CDC? - 50 years of age and older - Chronic heart, lung, or kidney disease pts. - Immune system problems - Severe form of anemia - Will be more than 3 months pregnant during the flu season - Nursing center or assisted-living residents - Close contact with children 0 to 23 months - Alveolar infection - Microbial cause can be Bacteria, Viruses, Fungi and Parasites How are pneumonia microbes reaching the lungs? - Being inhaled - Carried in the blood Once infected with pneumonia causing microbes, what is out bodies response to infection? Inflammatory response: Affected tissues fill with fluid and Cannot exchange gases properly Who is at high risk to contract pneumonia? - Children under 2 years of age - Adults over 65 years of age - Older adults are at great risk of dying from the disease. What factors increase the risk for pneumonia? - Bed rest - Chronic diseases - Tube feedings What is the treatment for pneumonia? - Drugs for infection, breathing and pain - Increased fluid intake to treat fever and to thin secretions - Intravenous therapy and oxygen - Semi-Fowler�s position to ease breathing How can a CNA provide care for persons with pneumonia? - Vital signs - Standard Precautions are followed. - Isolation Precautions are used depending on the cause. - Mouth care is important. - Frequent linen changes. - Positioning - fowlers for breathing - Care blocks - Bacterial infection in the lungs. - May occur anywhere in body. - TB may be fatal if not treated. How is TB spread? - by airborne droplets Who is at risk for TB? - Risk is close, frequent contact with an infected person - Living in close, crowded areas - Country of origin - Poor nutrition - HIV infection What are the signs and symptoms of TB? - May be present in the body but cause no signs and symptoms. - Persons with active infection can spread the disease to others. - May lie dormant for decades - Chest x-rays and TB testing can detect the disease. What is the treatment of TB? - Drugs for TB. - Will require at least 2 drugs for a minimum of 6 months - May require 4 drugs for 9 months - DOT for some How are TB patients treated in hospital? - Standard Precautions and Isolation Precautions are needed - Isolation room in hospital - N95 mask - When sneezing, coughing or producing sputum must contain in tissue - Tissues are flushed down the toilet, placed in a biohazard bag, or placed in a paper bag and burned. - Hand washing after contact with sputum is essential. CH 34: Oxygen Administration: What are the factors affecting oxygenation? - respiratory system status-Organs, nerves and muscles of respiration must be intact for exchange of respiratory gases to occur - circulatory system functioning - blood must flow to and from heart - red blood cell count - need enough hemoglobin to pick up O2 - nervous system function - brain damage can slow respiration - aging - lung tissue weakens with age - exercise - more 02 needed with exercise - fever - O2 needs increase - pain - does it hurt to breath. also pain increases need for O2 - drugs - some depress respiratory centers in brain - smoking -causes lung cancer or COPD - allergies - sensitivity to substance causing body reactions - pollutant exposure - damage lungs - nutrition - need iron and vitamins to produce RBC - alcohol - depresses brain, reduces aspiration What is respiratory depression? slow weak respiration at a rate of fewer than 12 per minute What is respiratory arrest? when berathing stops What is hypoxia? when cells don't have enough oxygen. signs of restlessness, dizzy and disoriented What are some abnormal respirations? - tachypnea - rapid breathing - bradypnea - slow breathing - apnea - absence of breathing - hypoventilation - slow shallow irregular respirations - hyperventilation - rapid deeper respirations - dyspnea - painful or labored breathing - orthopnea - breathing comfortably on when sitting - kussmal - signal diabetic coma, deep and rapid - biots - rapid and deep followed by 30 seconds apnea. nervous system disorder - cheyne stokes - gradually increase in rate and depth then become shallow and slow and then apnea for 10-20 seconds Describe Oxygen therapy? - Oxygen is a drug and must be ordered by MD - Nursing Assistant can only administer at predetermined and preset rate - Check care plan for correct flow rate and delivery method What are the side effects of Oxygen? - Retinopathy of the newborn - Bronchial Pulmonary Dysplasia of the newborn (BPD) - Drying of respiratory tract mucosa - Skin breakdown under tubing and edges of delivery devices - Hypoventilation (breathing at slow rate. high CO2 in blood) in COPD patients In what ways can lack of oxygen alter our functioning? - Alteration in pulmonary function - Alteration in cardiac function - Alteration in neurological function - Alteration in musculoskeletal function What is a pulse oximetry? measures concentration of o2 in arterial blood What is orthopedic position? being placed in fowlers or semi fowlers to breath easier. What is atelectasis? collapse of a portion of the lung. What will lack of oxygen ultimately mean? - alteration in alveolar perfusion (passage of fluid thru vessels) - alteration in cellular respiration - cell death Describe Oxygen Therapy? - Delivery of oxygen from an extrinsic source - Controlled oxygen therapy will benefit any patients with impaired tissue oxygenation When is controlled oxygen therapy used? - Used to prevent or relieve hypoxia (deficiency in the amount of o2 reaching tissues) - Not a substitute for other treatments - Treatment of underlying cause - Restorative treatments - Adjunct treatments - Incentive Spirometry - TCDB - turn, cough, deep breath - Correct Positioning Describe Incentive Spirometry? - encourages people to inhale to a preset volume of air and then hold the breath for 3 seconds - Will benefit all post op patients - Requires teaching and coaching - Difficult for some people to follow instructions - Increases inspiratory volume - Prevents atelectasis (collapse of the lung) What are some oxygen sources? wall outlet, oxygen tank, oxygen concentrator (uses oxygen from air), liquid oxygen system (8 hours of use) How do you perform a TCDB? - Sit with your head slightly forward and your feet flat on the floor. - Turn head away from nurse - Breathe in deeply while splinting abdomen. - Hold your breath for a few seconds. - Cough twice, first to loosen mucus, then to bring it up. - Breathe in by sniffing gently. - Use strong tissues or paper towels to dispose of the mucus. What is therapeutic positioning for people with oxygen deficiencies? - Either High Fowlers or fowlers - Buttocks firmly into gatch of bed. - Spine is straight - Expands chest cavity - Often improves O2 saturations without supplemental oxygen - use of a foot board to keep but in gatch of bed What are some oxygen regulators? - Pressurized O2 Oxygen - Handle with care - Can achieve high flow rates of O2 What is an oxygen concentrator? - Concentrates atmospheric oxygen - Patient receives greater concentration than room air would deliver What are some oxygen delivery systems? - Nasal Cannula - Face Mask - Non-Re-breather Mask Describe nasal cannulas? - Most frequently used O2 delivery device - looks like snake teeth in nose and tubing wraps around ears and fastened under chin - Delivery range from 24% @ 1L/min to 44% @ 6L/min - Patient preference - Simple to use - Comfortable at low flow rate - Over 4 liters / min may cause drying of mucosa - May be used orally for mouth breathers Describe a simple face mask? - Short term oxygen therapy - covers whole nose and mouth - Delivers from 30% up to 60% @ 6 L/mn � 8 L/mn - May be uncomfortable - Contraindicated (should not be used) for CO2 retainers - Suitable for mouth breathers - Must remove mask to eat - May switch to NC for meals Describe a non-rebreather mask? - Delivers high concentrations of O2 - covers nose and mouth with a bag hanging off of it containing O2 - 80% to 90% at 10L/min - Must frequently check bag to insure inflation - Must remove mask to eat - NC will not deliver high concentrations Describe a Venturi Mask? - Precise delivery of high flow O2 rates - face mask with pointed end in all colors to show the amount of O2 given. - Flow device calibrates delivery - 24% @ 2L/mn up to 55% @ 14L/mn - May be used for carbon dioxide retainers How do you know if O2 is needed? - look for bluish skin and nail color - look for pallor and cyanosis (bluish discoloration of the skin) - look for an injury like broken ribs (side will be very bruised) or injury of the spine - Check for proper circulation in the feet - look for rib retractions during breathing to gage the amount of effort the patient is using to breath - look for the tripod position as it eases breathing - look for deformities that could labor breathing like scoliosis - look at body mass�those too thin or too big The person needs to rest after? pulmonary function tests CH 3: Ethics and Laws: What are is the function of ethics and laws? to protect patients and residents from harm What do Nurse practice acts involve? - Authorized duties (scope of practice) - Your training and job description - Safe delegation - A complex set of rules and standards of conduct - Knowledge of what is right conduct and wrong conduct. - Professional groups have codes of ethics. - Morals are involved. - Ethical problems involve making choices. - Ethical behavior involves choices or judgments about what should or should not be done. - Ethical behavior involves not being prejudiced or biased. - A boundary limits or separates something. - Helping relationships with patients, residents, and families have professional boundaries. - Professional boundaries separate helpful behaviors from behaviors that are not helpful. What is a boundary crossing? - a brief act or behavior outside of the helpful zone. - Over-involved or under-involved with person that you are caring for What is a boundary violation? an act or behavior that meets the caregivers needs, not the person�s. act is unethical. What are boundary signs? acts, behaviors, or thoughts that warn of a boundary crossing or violation. What are some boundary violations? - Abuse of any kind - Giving a lot of personal information about yourself - Keeping secrets with the person Are boundary violations and professional sexual misconduct a crime? Describe professional sexual misconduct? - An act, behavior, or comment that is sexual in nature. - Telling off color jokes - Making comments with a sexual message - Having more physical contact with a certain resident than with others - Touching a resident inappropriately - Flirting with, kissing or having a sexual relationship with a resident or family member - Suggesting a romantic relationship with a resident or family member - Laws tell you what you can and cannot do. - A law is a rule of conduct made by a government body. What are criminal laws? concerned with offenses against the public and society in general. What are civil laws? - concerned with relationships between people. - Torts are part of civil law. - Ethic concerned with what you should or should not do - Often addressed in law What is a tort? a wrong committed against a person or their property What are unintentional torts? - Acts in which harm was not intended. - Negligence: like giving someone a bath in too hot water which burns them - Malpractice: Negligence by a professional (licensed) person. What are intentional torts? Acts of malice like�done knowingly What are some examples of intentional torts? - Defamation: Injuring a person�s name & reputation by making false statements to a 3rd party - Libel: Making a false statement in print, writing or through pictures or drawings that harms a person - Slander: Spoken false statement that harms a person - False imprisonment: Unlawful restraint of a person and Restriction of freedom of movement - Invasion of privacy: Violating a persons right to privacy - HIPAA violation (protects patients privacy of health information) - Name or private affairs made public - Photograph published without consent - Fraud: Tricking, deceiving or fooling a person with the result of harming a person or their property - Assault and battery - Intentionally attempting or threatening to touch a person�s body with consent - The person fears bodily harm - �I�m going to tie you in that wheel chair if you try to get up again� - Touching a person without their consent - Person must consent to any procedure, treatment or other act that involves touching the body - Person have right to withdraw consent at any time - May be verbal �yes� or �okay� - May be a gesture: a nod or turning to the side for a back rub What is a person's right in regards to their body? - the right to decide what will be done to his or her body - Who can touch his or her body - What treatment may be given - If the person is unable to give consent, a responsible party or a legal representative gives informed consent. What is informed consent? - implies that the person clearly understands: - The reason for a treatment, procedure, or care measure - What will be done - How it will be done - Who will do it - The expected outcomes - Other treatment, procedure, or care options - The effects of not having the treatment, procedure, or care measure Can the nursing assistant be responsible for obtaining consent? no, but May witness signed consent in some agencies Can a CNA be present a will signing? - You can ethically and legally witness the signing of a will. - You can refuse to witness the signing of a will. - You must politely refuse to prepare a will. - Know your agency�s policy before you agree to witness a will. - If you are named in a will, don't witness it. - If you have questions, ask the nurse. What is abuse? intentional mistreatment or harm of a person Is reporting abuse mandatory? yes, Abuse is a crime. What are the elements of abuse? - Willful causing of injury - Unreasonable confinement - Depriving the person of the goods or services needed for physical, mental, or psychosocial well-being What is the role of health care workers in abuse? - it is their duty to protect against abuse of patients - Extends to persons in a coma. - The abuser is usually a family member or caregiver. - Both men and women are abusers. - Both men and women are abused. - Persons convicted of abuse, neglect, or mistreatment May not be allowed to be employed in long term care - Law of states, accrediting agencies & OBRA What is the nursing assistant registry? it tells of base, neglect or mistreatment done by any nursing assistant. Who are vulnerable populations of people who cant protect themselves from harm? - All children under 18 years of age - Persons 18 years old or older who have: - Disabilities or conditions that make them at risk to be wounded, attacked, or damaged. - Problems caring for or protecting themselves - Mental illnesses - Brain damage - Emotional disabilities - Physical disabilities - Developmental disability - Changes from aging Describe elder abuse? - Physical abuse - Verbal abuse - Involuntary seclusion - Financial exploitation or misappropriation - Emotional abuse - Sexual abuse What federal or state laws require the reporting of elder abuse? - State Ombudsman - Senior & Disabled Services Division (SDSD) - Contact information must be posted in clear view of general public What does child abuse and neglect involve? - A child 18 years old or younger - Any recent act or failure to act in the best interest of the child on the part of a parent or caregiver - The act or failure to act results in: - Serious physical injury - Emotional harm - Sexual abuse - Sexual exploitation - The act or failure to act presents a likely or immediate risk for harm What are the types of child abuse and neglect? - Physical abuse - Physical or emotional neglect - Sexual abuse - Child pornography - Child prostitution - Emotional abuse - Substance abuse Where is child abuse/neglect seen? - at every social level - The abuser usually is a household member. - Usually an abuser is someone the family knows. - All states require the reporting of suspected child abuse. AS a CNA what is your duty in regards to child abuse? - If you suspect child abuse, share your concerns with the nurse. - Give as much detail as you can. What is intimate partner abuse? - domestic abuse/violence - Occurs in relationships - One partner has power and control over the other through abuse. - Male on female - Female on male - Both parties may be involved - Female partners - Male partners - Abuse may be physical, sexual, verbal, economic, or social. - Usually more than one type of abuse is present. - Patients and residents can suffer from domestic abuse. - State laws vary about reporting domestic abuse. - If you suspect domestic abuse, share your concerns with the nurse. What is self-neglect? when a person's behavior puts him or her at risk for harm Who is at risk for being wounded, attacked or damaged? all patients and residents CH 12: Preventing Falls - who are at risk for falls? - Fall risk increases with age. - A history of falls increases the risk of falling again. What are the most common nursing center accidents? What are the causes of falls? - Most falls occur in patient and resident rooms and in bathrooms. - Causes include: - Poor lighting - Cluttered floors - Throw rugs - Out-of-place furniture - Wet and slippery floors, bathtubs, and showers - Urge to urinate is a major cause of falling. - Most falls occur between 1800 and 2100. - They also are more likely to occur during shift changes. Are there fall prevention programs? - Agencies have fall prevention programs - Common sense and simple safety measures can prevent many falls. - Identifies people at high risk for falls - The health team works with the person and family to reduce the risk of falls. - The goal is to prevent falls without decreasing the person�s quality of life. What is the role of bed rails? - Bed rails are raised and lowered. - Bed rails lock in place with levers, latches, or buttons. - They are half, three quarters, or the full length of the bed. - The nurse and care plan tell you when to raise bed rails. When are Bed rails needed? - Persons who are unconscious or sedated with drugs - Some confused or disoriented people What are the hazards of bed rails? - Entrapment is a risk. - May increase risk for falls - May increase injury from falls When are bed rails considered restraints? - The person cannot get out of bed. - The person cannot lower them without help. What standards affect bed rail use? Accrediting agency standards and federal and state laws What should a CNA do if a person uses bed rails? - Check the person often. - Report to the nurse that you checked the person. - If you are allowed to chart, record when you checked the person and your observations. What are some assistive devices? - Hand rails and grab bars - Bed wheels are locked at all times except when moving the bed. - Wheelchair and stretcher wheels also are locked during transfers. What are hand rails? - Hand rails are in hallways and stairways. - They give support to persons who are weak or unsteady when walking. What are grab bars? - Grab bars are in bathrooms and in shower/tub rooms. - They provide support for sitting down or getting up from a toilet. - They are used for getting in and out of the shower or tub. What is the function of transfer/gait belts? - A device used to support a person who is unsteady or disabled. - It helps prevent falls and injuries. - A transfer belt is always applied over clothing. - The belt buckle is never positioned over the person�s spine. What causes a person to fall? - Weakness, light-headedness, or dizziness - Slipping or sliding on spills, waxed floors, throw rugs, or improper shoes If someone falls, what should you never do? - Do not try to prevent the fall. - Helps to prevent injury to care giver - If a person starts to fall, ease him or her to the floor. - Do not let the person move or get up before the nurse checks for injuries - May get a set of vital signs Ch 39: Nervous System Disorders - What is a reflex arc? The reflex arc is the body's rapid response to painful / dangerous stimuli. This also looks at sensory and motor pathways helping you to understand why paralyzed people or stroke patients with a hemiplegia may still be able to feel pain. IT happens in the spinal cord with brain processing occurring after the reflex What affect does nervous system disorders have on a person? - Can affect mental and physical function - Some Mental effects are... - Dementia and cognition - Some Physical effects are.. - Hemiplegia (total paralysis on one half of body) - Paresthesia (numbness of tingling on the skin) - Dysphagia (difficulty swallowing) - (aka: brain attack or cerebrovascular accident: CVA) - Disease affecting arteries that supply blood to the brain. - Stroke occurs when one of the following happens: - A blood vessel in the brain bursts. - Bleeding occurs in the brain (cerebral hemorrhage). - A blood clot blocks blood flow to an area of the brain. - Stroke is the 3rd leading cause of death in the United States. - It is a leading cause of disability in adults. - Emergency care needed promptly - Brain function can be saved. Time is Brain! - 3 hour window for help Define a heomorrhagic stroke? when blood leaks into brain tissue Define Ischemic Stroke? clot prevents perfusion to an area of the brain so brain cells die (large holes in brain) Define Transient ischemic attack? - Symptoms last less than 24 hour - No residual - No lasting affect with full recovery - Predictive of stroke within a 5 year period - Many �mini strokes� over time may lead to dementia - Sometimes warning signs last a few minutes to a few hours. What are some stroke symptoms? - Sudden numbness or weakness - Often unilateral (one side of the body) - hemiplegia - Face: May affect one side of tongue and May affect ability to swallowing - dysphagia - Sudden confusion - Trouble speaking (expressive aphasia) - Trouble understanding speech (receptive aphasia) - -or- both (global aphasia) - Sudden trouble seeing in one or both eyes - Sudden trouble walking - Loss of balance or coordination - Sudden severe headache with no known cause - urge to throw up What are some controllable risk factors for stroke? - Heart disease - High blood cholesterol - Previous stroke or TIA (mini-strokes: transient ischemic attack) What are uncontrollable risk factors for stroke? - Age: Older people are at greater risk than younger people - Family history: risk increases if a parent or sibling had a stroke - Gender: Men and women are affected equally - Race: Blacks are at greater risk than other groups What are the disabilities that arise from stroke? - brain damage - Functional loss dependent on the area of brain damage What is the goal of rehab for a stroke victim? - Goal is to help person regain the highest possible level of function - CNAs and all members of health care team involved Describe Parkinson's disease? - Disorder of dopamine in brain - Slow, progressive disorder with no cure. - Dopamine affects smooth & skeletal muscle - which affects Voluntary movement, B/P and Peristalsis (intestinal contractions) Who is at risk for parkinsons? Persons over the age of 50 What are the signs and symptoms of parkinsons? - Rigid, stiff muscles in the arms, legs, neck, and trunk - Slow movements - Stooped posture and impaired balance - Mask-like expression - fixed stare cannot blink or smile What are some characteristics of dopamine deficit? - Mask like facial expression - Forward tilt - Reduced arm swing - Rigid, trembling extremities - Shuffling gait with short steps - Pill rolling tremor of hands - Difficulty swallowing - Chronic constipation What is the treatment of parkinsons? - Drugs to treat and control the disease - Carbidopa / levodopa - Exercise and physical therapy to improve strength, posture, balance, and mobility - Therapy for speech and swallowing problems What are ways CNA's can help parkinson patients? - The person may need help with eating and self-care. - Normal elimination is a goal. - Safety measures are needed to prevent falls and injury. - Help with communication - Safety is high priority! Describe Multiple SClerosis? - Chronic disease of myelin sheath - The myelin, which covers nerve fibers in the brain and spinal cord, is destroyed. - Nerve impulses are not sent to and from the brain in a normal manner. - There is no cure. - Symptoms usually start between the ages of 20 and 40. - More women are affected than men. - Whites are at greater risk than other groups. - A person�s risk increases if a family member has MS - affects both voluntary and involuntary muscles. What causes MS? - Demyelinating disease of nervous system - Likely autoimmune - Immune system erodes hole in myelin sheath of nerves - Affects only nerves coated with myelin - Any body system may be affected - �Hole� in myelin may slow nerve conduction �or- - Short circuit nerve conduction (analogous to hole in insulating cover on an electrical cord) How does MS progress? - May present as on of the following - Relapsing-remitting: Periods of remission and relapses - Primary progressive: No periods of remission - Secondary progressive: Periods of remission cease and disease progresses - Progressive-relapsing: Periods of remission decrease in onset and length of time Other signs and symptoms of MS? - Vision problems- May be first symptom of MS, Feature in majority of MS patients - Peripheral (arms & legs) muscle weakness - Balance problems that affect standing and walking - Tingling, prickling, or numb sensations - Partial or complete paralysis - Bowel & bladder - Problems with sexual function - Hearing loss - Coordination problems and clumsiness What is the treatment of MS? - Medication - Steroids - MS drugs targeting neuron pumps - Physical therapy, speech therapy - Persons with MS are kept active as long as possible with as much independence as possible. - The care plan reflects the person�s changing needs. Describe ALS (Lou Gherig's Disease)? - Attacks the nerve cells that control voluntary (skeletal) muscles. - Rapidly progressive and fatal - Death within 3 � 5 years of symptom onset - Muscles weaken, atrophy & twitch (fasciculation) - Affects more men than women. - It usually strikes between 40 and 60 years of age. - Motor nerve cells in the brain, brainstem, and spinal cord are affected. What does ALS stand for? Amyotrophic Lateral Sclerosis What causes ALS? - Motor nerve deterioration - Brain cannot start or control voluntary movements as disease progresses - Chest muscles (respiratory pumps) ultimately affected - Ventilator support needed at end stage - Mind, intelligence & memory usually not affected. - Sight, smell, taste, hearing, and touch not affected. - Some drugs can slow disease progression. - Persons with ALS are kept active as long as possible and as independent as possible. A person has ALS, which should you questions if it was on the care plan? measures to prevent confusion. ALS keeps the mind intact. What is a head injury? Trauma to the scalp, skull, or brain. What is a traumatic brain injury? - occurs when a sudden trauma damages the brain. - Brain tissue is bruised or torn. - Bleeding can be in the brain or in nearby tissues. - Spinal cord injuries are likely. What causes brain injuries? - Motor vehicle crashes - Whip lash causes coup contra coup injury - Brain is injured in front and then at back as brain recoils from sudden stop - Shaken baby similar to whiplash injury - Devastating injury or death to infants and small children - Sports and recreation injuries - Permanent damage likely if the person survives like persistent vegetative state - in a vegetative state for more than a month What is coup contra coup? - a coup injury occurs at site of impact with object - a countercoup injury occurs on the side opposite the area that was impacted - can occur as a result of whiplash or shaken baby syndrome What disabilities arise from traumatic brain injury? - Disabilities depend on the severity and location of the injury: - Cognitive problems - Sensory problems - Communication problems - Behavior or mental health problems - Stupor: This is an unresponsive state, Person can be briefly aroused - Coma:Person is unconscious, unresponsive, unaware, cannot be aroused - Vegetative state: Person is unconscious, unaware of surroundings,Person has sleep-wake cycles and periods of alertness - Persistent vegetative state (PVS): Vegetative state lasting more than 1 month,Rehabilitation is required. Describe Spinal Cord Injury? - May cause permanent damage to nervous system. - Nervous system deficits depend on: - Degree of damage to the spinal cord - Level of injury at the spine - The higher the level of injury, the more functions lost. Who is at highest risk? young adult men What are some common causes of spinal cord injuries? - Stab or gunshot wounds - Motor vehicle crashes - Sports injuries What would lumbar injuries cause? Paraplegia: muscle and sensory function in the legs is lost What would thoracic injuries cause? - Paraplegia: Muscle and sensory function below the chest is lost - At risk for Autonomic Dysreflexia if T4 � T6 injury�blood pressure sky rockets! What would cervical injuries cause? - Quadriplegia (both arms and legs paralyzed) /tetraplegia (same) - Muscle and sensory function of the arms, legs, and trunk are lost. - May lose ability to breath if C1 � C2 affected Treatment of spinal cord injuries? - Some survivors require rehabilitation - Learns to function at the highest possible level. - Person learns to use self-help, assistive, and other devices. - Some people return home and live independently. When is autonomic dysreflexia associated with spinal cord injuries? with spinal cord injuries above the mid-thoracic level. What is The most common causes of autonomic dysreflexia? - A full bladder - Constipation or fecal impaction - Skin disorders What arises from autonomic dysreflexia? - Results in uncontrolled stimulation of the sympathetic nervous system. - Hypertensive crisis ensues - Sign is rubor (redness above nipple line) - May results in stroke, heart attack, and death if untreated. How do you treat autonomic dysreflexia? - Raising the head of the bed 45 degrees �or- - Having the person sit upright if allowed - Determining and removing the cause Describe Alzheimer's Disease? - Brain disease caused by accumulation of amylase plaques - Nerve cells that control intellectual and social function are damaged. What functions are affected by Alzheimers? What is the classic sign of Alzheimers? - gradual short term memory loss - Onset of functional and cognitive loss gradual What causes Alzheimers? - Family history of AD increases a person�s risk of developing the disease. - Risk increases with age. - Usually occurs after the age of 60 What are the stages of AD, alzheimers disease? - Signs and symptoms become more severe as the disease progresses. - The disease ends in death. - AD is often described in terms of 3 stages. - The Alzheimer�s Association describes 7 stages: - No impairment - Very mild cognitive decline - Mild cognitive decline - Moderate cognitive decline - Moderately severe decline - Severe cognitive decline - Very severe decline What are some common AD behaviors? - Signs, symptoms, and behaviors of AD increase during hours of darkness - Hallucinations: Seeing, hearing, smelling, or feeling something that is not real - Delusions: false beliefs - Catastrophic reactions: Extreme responses - Agitation and restlessness - Aggression and combativeness CH 6: The nursing process - What is the nursing process? the methods used by nurses to plan and deliver nursing care What are the steps of the nursing process? - 1.Assessment: Collecting information about a person - Nurse must make meaning of information. - Information sources are Medical record, Test results, Patient health history and Family history - 2.Diagnosis:Description of a health problem, using assessment data, that can be treated by nursing measures. - 3. Planning: Setting priorities and goals - 4.Implementation: To carry out or perform the nursing measures contained in the nursing plan of care - 5. Evaluation of plan to make sure it is achieving what it was meant to achieve What is observation? - using all senses to collect information - Sight-Movement / alignment, General appearance / specific appearance - Hearing: Body sounds-Heart sounds,Blood pressure,Abdominal sounds - Touch-Temperature, Texture, Moisture - Smell: Odor- Body, wounds, breath, urine, bowel movements What are the different types of objective data? - �Signs� - Easily measured or quantified - What you hear - Apical pulse is 120 bpm and irregular - What you see-The skin ulcer is 1 mm in depth x 4 cm in diameter & erythematous - What you smell-The stool has an odor of blood - What you feel-The lump feels hard with a nodular texture What are the different types of subjective data? - �Symptoms� - Difficult to measure or quantify - Things the patient (or patient�s family) tells you that cannot be observed - Nausea, Pain, Fear, Fatigue, Sadness What are some basic observations? - Ability to respond - Pain / discomfort - Eyes, Ears, Nose & Mouth - Bowels & Bladder - Activities of daily living (ADLs) - Other: Bleeding / discharge and Anything out of the ordinary for an individual Can CNA's asses a patient? No, only a nurse can do that. CNAs can only observe and report. When should a CNA report and observation at once? - Altered mental status (AMS) / Change in level of consciousness (LOC) - Responsive person no longer responding - Unresponsive person now responding - Abnormal response in formerly normal person - A change in mobility - Loss of function in a body part - Ability to move a non-functional body part - Onset of sudden severe pain anywhere - A sore or reddened area on skin - Sudden change in vision - Complaints of pain or difficulty breathing - Abnormal respirations - Complaints of or signs of difficulty swallowing - Vital signs outside of normal range What does a nursing diagnosis deal with? - a health problem that can be treated by nursing measures - whole person & expressed as �needs� - Change as assessment changes What is a medical diagnosis? - Identification of disease or condition - Physician orders drugs, therapies, surgery for cure or healing Describe the nursing planning process? - Nursing interventions chosen to help meet goals in conjunction with others - Patient, Family and Interdisciplinary team - Priorities :What is most important? To whom? - Maslow�s Hierarchy of Needs - Goals: What is desired in or by a person as a result of nursing care - Interventions: An action or measure Chosen to meet specific goals - Nursing intervention: Provider�s order not required and May originate in the provider�s order What is the nursing care plan? - Written plan that guides care - Consists of: Nursing Diagnosis, Goals and measures and actions for each goal - Communication tool - Consistency of care - What cares needed - Individualized to each patient - Will change as nursing diagnosis changes How is a care plan implemented? - Nurse delegates cares - Simple cares: Cares within nurse assistant scope of practice - Complex care: Assist licensed nurse with cares - Report & record:Always after care has been given - Assignment sheet:Used to record patient assignment, observed data, patient�s care, unit tasks Describe the evaluation process? - Were goals met: Met, Partially met or Not met - Assessment information used May result in changes to: - Nursing diagnosis, Goals and Care plan What is the CNA role in the evaluation process? - Nursing diagnosis - Planning: Observation - Implementation: Nursing actions and Measurements - Evaluation: Observation Details of recording observations? - Must record pertinent data - Observations:May be directed by facility policy - Indelible black ink must be used - Corrections must be made appropriately - Cannot scribble out - Cannot white out - Cannot erase - An error is corrected with a single line through the error, initial and date - Do not leave blank spaces when you are through with an entry - Always sign your appropriate title Details of charting? - Charting must be dated and timed for the time that you are doing the charting. Not when action took place! - If charting is forgotten do the following, make the date, the date that charting is taking place. in the progress notes, say "charting for 1/12/11 at 1015. Mr. Gordon transported via wheelchair. Maria Buagas CNA --------- CH 13: Restraints: Who issued new rules in regards to restraints for medicaid and medicare funds? CMS - centers for medicare and medicaid services What are the rules instituted from CMS in regard to restraints? all patients have the right to be free from restraints or seclusion. They can only be used for immediate physical safety of the person, staff members or others and only as a last resort. They should be discontinued at the earliest possible moment. What other agencies have rules for restraints? FDA, state agencies and joint commissions don't forbid their use but all other alternatives must be tried first. What is an alternative to restraint? diversions like tv provided, extra visitor time, knob guards used on doors, exercise program provided if person is restless. What is a restraint? any manual method either equipment or drugs that restricts freedom of movement What is seclusion? involuntary confinement of a person Are bed rails considered restraints? - yes, in long term care - and if The person cannot get out of bed because of the rails or The person cannot lower them without help - Bed rails must be ordered on care plan before use - Bed rails may be needed by:Persons who are unconscious or sedated with drugs and Some confused or disoriented people - Bed rails are kept up at all times when ordered, except when giving bedside - nursing care What are some hazards of bed rails? - Person can fall when trying to climb over them - Person may become stuck in rails if a person uses bed rails, you need to? - Check the person every 15 minutes - Must provide toileting and exercise every 2 hours - Report to the nurse that you checked the person - Record when you checked the person, what cares were done and your observations How many entrapment zones do hospital beds have? What is zone 1 entrapment? within bed rail What is zone 2 entrapment? Between the top of the compressed mattress and the bottom of the bed rail and between the rail supports What is zone 3 entrapment? Between the bed rail and the mattress What is zone 4 entrapment? Between the top of the compressed mattress and the bottom of the bed rail and at the end of the bed rail What is zone 5 entrapment? between the split bed rails What is zone 6 entrapment? Between the end of the bed rail and the side edge of the headboard or footboard What is zone 7 entrapment? Between the headboard or footboard and the end of the mattress Define freedom of movement? - Any change in place or position of body or any part of the body - Person is physically able to control movement. What is the history of restraint use? Restraints thought to prevent falls What is the reality of restrain use? - Late 1980s nursing research show that: - Restraints cause falls - Injuries are more serious from falls involving restrained persons - Restraints can cause serious harm, even death. When can a restraint be used? - A doctor�s order is required. - Reason for the restraint must be for protection of resident or others - What body part to restrain - What restraint to use - How long to use it: Must be least restrictive method - Restraints are used only after other measures fail - Attempts must be documented - Unnecessary restraint is false imprisonment - Informed consent is required - Person or legal representative must be counseled about restraint - Person or legal representative must give consent before a restraint can be used What are the legal aspects of restraints? - Laws applying to restraint use must be followed. - Restraints must protect the person. - Not for staff convenience - A restraint is used only when necessary to treat a person's medical symptom. - Not to discipline a person. - Restraints are not used to punish or penalize uncooperative persons. - The person must give consent for restraint use How to apply restraints? - Leather restraints are applied to the wrists and ankles - Wrist restraints (limb holders) - Limit arm movement. - Hands are placed in mitt restraints: Prevent finger use if patient is taking out IV or picking at sutures in a wound - The belt restraint is used When there is risk of injury from falls or For positioning during medical treatment How are vest and jacket restraints used? - Vest and jacket restraints are applied to the chest. - A jacket restraint is applied with the opening in the back. - The straps of vest and jacket restraints always cross in the front. - Vest and jacket restraints are never worn backward. - The restraint is always applied over a garment. - Vest and jacket restraints have life-threatening risks. - You are advised to only assist the nurse in applying them. - The nurse should assume full responsibility for applying a vest or jacket restraint. - Never use force to apply a restraint. What are the safety guidelines for restraints? - Observe the person at least every 15 minutes - May be more often as required by the care plan. - Observe for increased confusion and agitation. - Must protect person�s quality of life. - Restraints are used for shortest time needed. - Follow the manufacturer�s instructions for restraint application - Apply restraints with enough help to protect the person and staff from injury. - Remove or release the restraint for at least 10 min, reposition the person, and meet basic needs at least every 2 hours. - Follow the care plan. What are the main pressure areas when using restraints for wheelchair? back, lumbar region, butt, back of knees, heels To minimize the skin breakdown as a result of restraints, you should? - Must release restraint every 2 hours & prn - Must exercise person every 2 hours & prn - Must toilet person every 2 hours & prn - Must offer nourishment every 2 hours & prn When using restraints what should be documented? - The type of restraint applied - The body part or parts restrained - The reason for the application - Safety measures taken - The time you applied the restraint - The time you removed or released the restraint and for how long - The person�s vital signs - The care given when the restraint was removed or released - Skin color and condition - Condition of the limbs - The pulse felt in the restrained part - Changes in the person�s behavior - Complaints of discomfort - A tight restraint - Difficulty breathing - Pain, numbness, or tingling in the restrained part - Report these at once What are the behaviors that result in restraint use? - Behaviors often a result of unmet needs - Knowing and treating the cause can prevent restraint use. - Restraint alternatives for the person are identified - They become part of the care plan. - If restraint alternatives do not protect the person, the doctor may need to order restraints. What are some restraint complications? - injury occurs when Person tries to get free of the restraint. - The wrong restraint is used - The restraint is applied incorrectly - The restraint is kept on too long - -death from strangulation - -can affect dignity and self-esteem causing depression, anger, agitation, embarrassment, humiliation and mistrust When a death occurs of someone who was restrained, when should it be reported to the CMS? - while a person was in a restraint - within 24 hours after restraint was removed - within 1 week after a restraint was removed Restraint alternatives fail to protect a person. You can apply a restraint. T/F - FALSE A device is a restraint only if it is attached to the person's body. T/F FALSE -it can be a tv tray or pushing a wheelchair up against a wall A belt restraint is applied to a person in bed. Where should you tie the straps? to the movable part of the bed frame CH 11: Safety - Is it a human need? What can prevent most accidents? common sense and simple safety measures What does a safe setting offer? - Little risk of illness or injury. - Offers physical & mental safety/security - Low risk of infection, falls, burns, poisoning, and other injuries - Comfortable temperature and noise levels are - Pleasant smells - Enough room and light to move about safely - Safety from are safe from fire and intruders- Both person and property are safe What are some oxygen safety concerns? o2 is a medication that is also a fire hazard, so one must Avoid open flame / smoking around O2 and Avoid petroleum based skin creams on patients using O2 What can CNAs do in regards to giving oxygen? - may turn oxygen on and off at pre-established flow rates set by the nurse - Only the physician or RN can make changes to the amount of oxygen to be given Who is most at risk for accidents? - Age: Very young or Very old - Chronic disease: Heart disease, Neurologic disease, Musculoskeletal disease with Impaired mobility - Sensory impairment: Vision and hearing loss and Impaired smell and touch - Multiple medications: Medications affecting heart or nervous system When giving care, what are some ways to ID the patient? - Carefully compare identifying information on the assignment sheet with that on the ID bracelet. - Use at least two identifiers - Follow agency policy. - Call the person by name when checking the ID bracelet - May ask name & BD in some settings When is equipment unsafe? - Not used correctly - Not working properly What if equipment isn't in good repair? - Remove all malfunctioning items from circulation - Do not use or give damaged items to patients or residents. Describe Wheelchair safety? - Position the person�s feet on the footplates. - Make sure the person�s feet are on the footplates before moving the chair. - Wheel the chair correctly - Push the chair forward when transporting the person - You may pull the chair backward when going through a doorway which requires opening the door -or- when going into an elevator - Make sure removable parts are locked in place - Keep the wheels locked when not moving - Lock both wheels before: Transferring a person to or from the chair - Do not stand on the footplates - Swing footplates out of the way when transferring a person to or from the chair - Do not let the footplates fall back onto the person�s legs - Always support dependent limbs What part should you remove in the wheelchair when transferring patients? remove armrest, swing front rigging out of the way or detach. once patient is in the chair, make sure movable parts are locked in place and that patients fingers, toes, skin not pinched by parts Describe stretcher transfers? - Never transfer a person to or from stretcher by yourself - Always ask for help - Use a transfer sheet or slip �n� slide - Lock the stretcher wheels before the transfer - Fasten the safety straps when the person is properly positioned on the stretcher. - Ask a co-worker to help with the transport. - Always raise the side rails when transporting a person - Keep them up during the transport. - Properly position person - Make sure the person�s arms, hands, legs, and feet do not dangle through the side rail bars - Stand at the head of the stretcher - Your co-worker stands at the foot of the stretcher - Move the stretcher feet first. - Never, ever leave a person alone on a stretcher What are the OSHA requirements for Hazardous substances? - Understand the risks of hazardous substances - Understand safe handling - OSHA requires employers to provide hazardous substance training - container labeling, and MSDS material safety data sheets (contains info about the chemical) What are physical hazards? can cause fires or explosions What are health hazards? chemicals that can cause health problems When can exposure to hazardous substances occur? - Under normal working conditions - During certain emergencies What needs to be on hazardous substances? - Warning labels identify: - Physical and health hazards - Precaution measures - What personal protective equipment to wear - How to use the substance safely - Storage and disposal information What If a warning label is removed or damaged? - Do not use the substance. - Take the container to the nurse and explain the problem. - Do not leave the container unattended. What are MSDSs? Material Safety Data Sheets. Describe MSDS uses? - Every hazardous substance has an MSDS - Employees must have ready access to MSDSs. When do you check for MSDS? - Using a hazardous substance - Cleaning up a leak or spill - Disposing of the substance What if you see a leak or spill? Do not leave it unattended and tell the nurse about it immediately. Define Bloodborne pathogens? - Infectious materials in blood that can cause disease in humans - Hepatitis B and C - Human immunodeficiency virus or HIV - Workers exposed to these pathogens risk serious illness What is the OSHA requirements for bloodborne pathogens? - OSHA requires employers to provide bloodborne pathogen training to their employees yearly - Facilities must have policies & procedures to prevent employee exposure What are the standard precautions for bloodborne pathogens? - PPE must be provided - Use it only once - Never reuse equipment that has been exposed to pathogens - Red biohazard bags are used to contain contaminated material. - it needs to be double bagged What are the fire prevention responsibilities? - The entire health team must: - Prevent fires - Act quickly and responsibly during a fire What are the 3 things needed for a fire? - A spark or flame - A material that will burn - Oxygen:Safety measures are needed where oxygen is used and stored and Turn oxygen off in a fire When was the Smoke Free Workplace Law passed? - Agencies have no-smoking policies and smoke-free areas Good fire safety knowledge? - know where Fire alarms, Fire extinguishers and Emergency exits are - Keep emergency exits clear of barriers - Do not use elevators if there is a fire What is the word RACE for fire safety? - R is for rescue - A is for alarm - C is for confine - E is for extinguish How to use a fire extinguisher? - P-pull safety pin - A-aim low - S-squeeze the lever - S-sweep back and forth - A sudden catastrophic event. - May be human made or natural - Many people are injured and killed. - Property and infrastructure is destroyed. What do you do if there is a disaster in your area? follow agency procedures What about for bomb threats? - follow agency procedures - look for items that look or sound strange Define Workplace Violence? - Any violent act directed toward persons at work or while on duty. - Workplace violence can occur in any place where an employee performs a work-related duty. - It can be a permanent or temporary place. Where does workplace violence most often occur? It occurs most often in mental health units, emergency departments, waiting rooms, and geriatric units. What is risk management? Identifying and controlling risks and safety hazards affecting an agency. What is the intent of risk management? - Protect everyone in the agency - Protect agency property from harm or danger - Protect the person�s valuables - Prevent accidents and injuries Who are risk managers? - People who look for patterns and trends in - Incident reports - Patient and resident complaints - Staff complaints - Accident and injury investigations What should you do if there is an accident? report it at once for any accidents involving patients or residents, visitors or staff Define Errors in care? - Giving the wrong care - Giving care to the wrong person - Not giving care What about a person's belongings? - Belongings must be kept safe - A personal belongings list is completed - A valuables envelope is used for jewelry and money - Personal items kept at the bedside are listed in the person�s record What if a person's property goes missing? - report theft or property damage promptly - Broken or missing items owned by the person - Missing money or clothing What need to be done if workplace violence occurs? an incident report needs to be completed as soon as possible Before shaving a resident with an electric shaver? the maintenance staff must do a safety check Resident brings a radio from home, what prevents property loss? putting the residents name on the radio How to clean eyeglasses? wash hands, take them off patient by grasping the stems, rinse under warm water, lather with liquid soap, rinse, dry with soft cloth, replace on face of patient or put in eyeglass case What should you not do when cleaning glasses? - Use only the stems when handling eyeglasses. - Never use hot water to clean lenses; they may warp. - Use liquid soaps without conditioners. - Never use a paper product to clean or dry lenses. - Glasses are not on the face, should be in a case. CH 37: hearing, speech, vision - what do these senses allow? - Allows communication, learning, and navigation - Important for self-care, work, and most activities - Critical for safety and security needs What are some common causes of hearing or vision loss? - Birth defects - Hereditary factors What is Otitis media? - an infection of the middle ear - Viruses, fungi and bacteria are causes. - Otitis media is acute or chronic. What are some signs or symptoms of otitis media? - Pain (earache) and hearing loss - Tinnitus: a ringing, roaring, hissing, or buzzing sound in the ears or head What is treatment of otitis media? - Drugs for pain relief - Drugs to relieve congestion What is meniere's disease? - Common cause of low frequency hearing loss - Idiopathic disease of inner ear - Endolymphatic hydrops creates increased fluid in middle ear - Usually one ear is affected - Symptoms occur suddenly - Attack can last several hour What are symptoms of meniere's disease? - Vertigo (dizziness) - Hearing loss - Pain or pressure in the affected ear What is the treatment of meniere's disease? - Drugs: Antihistamines - Fluid restriction - A low-salt diet - No alcohol or caffeine What are some safety measures that are needed for people with meniere's disease? - Bed rest during attack - Falls are prevented. - The person�s head is kept still. - Sudden movements are avoided. - Bright or glaring lights are avoided. - The person should not walk alone. Define hearing loss? - Inability to hear the normal range of sounds associated with normal hearing - Hearing loss occurs in all age-groups - Losses are mild to severe Hearing loss in which speech is not comprehensible What are some common causes for hearing loss? - Damage to the outer, middle, or inner ear - Damage to the auditory nerve What are some risk factors that can damage the ear structures? - High decibel sound exposure - Drugs- Antibiotics - Neomycin: Inner ear damage - Too much aspirin- Tinnitus - Reduced blood flow to the ear: High blood pressure, Heart and vascular diseases and Diabetes - Head injuries - Birth defects What are some causes of temporary hearing loss? - Cerumen impaction (earwax) - Cerumen removal restores hearing What are signs of hearing loss? - Hearing loss may result in slurred speech. - Words may be pronounced wrong. - Some have monotone speech or drop word endings. - It may be hard to understand what the person says. - Others notice it before the person does Treatment for hearing loss? - Wear hearing aids or lip-read (speech-read) - Watch facial expressions, gestures, and body language - Learn American Sign Language (ASL) - Some people have hearing assistance dogs (hearing dogs). What are hearing aids? - Electronic devices that fit inside or behind the ear. - They make sounds louder - Background noise and speech are louder. - They do not correct, restore, or cure hearing problems. What are the measure to fix a nonfunctioning hearing aid? - Check if the hearing aid is on - It has an on and off switch. - Check the battery position. - Insert a new battery if needed. - Clean the hearing aid. Define speech disorders? Impaired or ineffective oral communication What are some common causes of speech disorders? - Hearing loss - Developmental disabilities - Brain injury Inability to use the speech muscles to produce understandable speech. What causes Apraxia? - caused by damage to the motor speech area in the brain. - The person understands speech and knows what to say. - The brain cannot coordinate the speech muscles to make the words. What is Dysarthria? difficult or poor speech What causes Dysarthria? - caused by damage to the nervous system. - Mouth and face muscles are affected. What is Aphasia? Partial or total loss of the ability to use or understand language. What is Expressive Aphasia? - (motor aphasia, Broca�s aphasia) - Relates to difficulty expressing or sending out thoughts. What is receptive aphasia? - (Wernicke�s aphasia) - Relates to difficulty understanding language What is expressive-receptive aphasia? when you have both types aka global aphasia or mixed aphasia What are the causes of aphasia? - Head injury - Brain infections What is the goal of speech rehabilitation? - Improve communication ability - The amount of improvement possible depends on many factors. - Cause, amount, and area of brain damage - Age and health - Willingness and ability to learn What do speech language pathologists and health team members help? - Improve affected language skills - Use remaining abilities - Restore language abilities to the extent possible - Learn other methods of communicating - Strengthen the muscles of speech What are eye disorders? - Vision loss occurs at all ages. - Problems range from mild vision loss to complete blindness. - Vision loss may be sudden or gradual in onset. - One or both eyes are affected. What is blindness? Blind is the absence of sight. What is glaucoma? - Damage to the optic nerve. - Problem or aqueous humor build up, trabecular network or both - Pressure from build up of optic fluid - Vision loss with eventual blindness occurs. - can be in one or both eyes - Onset may be sudden or gradual. - Peripheral vision (side vision) is lost. Who is high risk for glaucoma? - African-Americans over 40 years of age - Everyone over 60 years of age - Those with a family history of the disease - Those who have diabetes, high blood pressure, or heart disease - Those who have eye diseases or eye injuries - Those who have had eye surgery How is glaucoma treated? - Glaucoma has no cure. - Prior damage cannot be reversed. - Drugs and surgery can control glaucoma and prevent further damage to the optic nerve. - Pilocarpine drops - Timoptic drops What is cataract? - Clouding of the lens in the eye. - A cataract can occur in one or both eyes What are the signs of cataract? - Cloudy, blurry, or dimmed vision - Colors seem faded - Blues and purples are hard to see - Sensitivity to light and glares - Poor vision at night - Halos around lights - Double vision in one eye What are risk factors for cataracts? - Aging (Most cataracts are caused by aging.) - Alcohol use - Prolonged exposure to sunlight - Everybody should be wearing sunglasses with UVA/UVB protection - Family history of cataracts What is the treatment of cataract? - Surgery is the only treatment - Diseased lens removed and replaced with plastic or cadaver lens What is AMD? - age-related macular degeneration - Disease that blurs central vision. - Damage to the macula located in the center of the retina. - The disease is usually gradual in onset. - Leading cause of blindness in persons 60 years of age and older. What are the two types of AMD? - Wet: More severe and rapidly progressive - Dry: More common, May convert to wet AMD What are the risk factors for AMD? - Race (Whites are at greater risk than any other group.) - Family history - Gender (Women are at greater risk than men.) - Light-colored eyes - Exposure to sunlight - Cardiovascular disease What can reduce the risk of AMD? - Eating a healthy diet high in green leafy vegetables and fish - Not smoking - Maintaining a normal blood pressure - Managing cardiovascular diseases - Maintaining a normal weight - Wearing sunglasses - Regular eye exams What is diabetic retinopathy? - Tiny blood vessels in the retina are damaged - Floaters common sign - Leading cause of blindness in U.S. - Usually both eyes are affected - Everyone with diabetes is at risk What is the treatment of diabetic retinopathy? - Tight control or diabetes, hypertension, hypercholesterolemia - Advanced retinopathy is treated with laser surgery. - Another surgery involves removing blood from the center of the eye. - The person with diabetic retinopathy may need low vision services. What is low version? - Eyesight that cannot be corrected with: - Corrective lenses, Drugs and Surgery What person is at risk for low vision? - Eye diseases - Age-related macular degeneration - Eye injuries What diseases affect vision? What is the treatment for low vision? - May need one or more visual and adaptive devices. - Devices used depend on the person�s needs. How many americans are legally blind? How many older persons are blind or visually impaired? What are the causes of impaired vision or blindness? - Birth defects - Eye diseases - Complications of some diseases How far can the legally blind person see? The legally blind person sees at 20 feet what a person with normal vision sees at 200 feet How can rehab help vision loss? - Adjust to the vision loss - Learn to be independent. What is braille? - A touch reading and writing system - Raised dots for each letter of the alphabet. - The first 10 letters also represent the numbers 0 through 9. What can help a visually impaired person get around? - A long cane with a red tip - A dog guide - Universal mobility aids for the visually impaired What can help correct many vision problems? eyeglasses and contact lenses for near sightedness, Far sightedness and Presbyopia (aka: �old eye�) When would an eyeball be removed? - if injured or diseased - The person is fitted with an ocular prosthesis. - Some prostheses are permanent implants. - If removable, the person may be taught to remove, clean, and insert it. - You need to protect the person�s prosthesis from loss or damage. CH 15: Body Mechanics - What is good body mechanics? - Using the body in an efficient and careful way - Low center of gravity - Broad base of support - Using strongest and largest muscles for work. - Good posture What are the principals of body mechanics? - body alignment - posture - base of support is the area on which an object rests - use your strongest and largest muscles What is good body alignment? - Head, trunk, arms, legs align. - Allows body to move and function with strength and efficiency. What is good base of support? - Feet are base of support when standing - A good base of support is needed for balance. What are your strongest and largest muscles? - Hips and thighs - Shoulders and upper arms Describe good body mechanics? - Bend your knees and squat - Do not bend from your waist, Keep back flat and Tighten abdominal muscles - Hold items close to your body and base of support -This involves upper arm and shoulder muscles.10 lbs held away from body translates to 100lbs Science of designing a job to fit the worker. WHat is the goal of ergonomics? - Eliminate serious and disabling work-related musculoskeletal disorder (WMSD) - WMSDs are injuries and disorders of the muscles, tendons, ligaments, joints, and cartilage. - May involve the nervous system. What are some risk factors for WMSD identified by OSHA? - Force: Amount of physical effort needed to perform a task. - Repeating action: Performing the same motion or series of motions continually or frequently. - Awkward postures: Positions that place stress on the body. - Heaving lifting: Manually lifting patients and residents who cannot move themselves. What are the OSHA requirements for safe work setting? - The setting must be free of recognized hazards that are causing or likely to cause death or serious physical harm to employees. - The employer must make reasonable attempts to prevent or reduce the hazard. What is the most common injury for nurses? What are some signs for back injuries? - Pain when trying to assume a normal posture - Decreased mobility - Pain when standing or rising from a seated position What are the advantages for proper positioning of the patient? - Promote comfort and well-being - Promote breathing - Promote circulation - Help prevent pressure ulcers and contractures All levels of ability for patients in regards to positioning? - Move and turn when in bed or a chair without assistance - Need reminding to adjust their positions - Need help with position changes - Depend entirely on the nursing team for position changes When does repositioning need to occur in bed or chair? - every 2 hours or PRN - follow the nurses instructions and the care plan What are the guidelines to safely position a person? - Use good body mechanics. - Ask a co-worker to help you if needed. - Explain the procedure to the person. - Be gentle when moving the person. - Provide for privacy. - Use pillows as directed by the nurse for support and alignment. - Provide for comfort after positioning. - Place the signal light within reach after positioning. - Complete a safety check before leaving the room What is fowlers positioning? - Semi-sitting position. - Head of the bed is raised 45 to 60 degrees. - Knees may be slightly elevated. What is supine position? What is prone position? Lying on abdomen with the head turned to one side. What is lateral position? The person lies on left or right side. What is Sims' position? This is a left side-lying position. When can a patient sit in a chair? must be able to hold their upper bodies and heads erect What is the best way to have a patient in a chair? - Feet are flat on the floor or wheelchair footplates. - Backs of the knees and calves are slightly away from the edge of the seat. - A pillow can be put between the person's lower back and chair but not if restraints are used - postural supports sometimes required if they can't keep upper bodies erect. Which action is easier? Pushing, pulling, sliding or lifting? Ch 16: safe patient handling - When is safe body mechanics required? - Turning and repositioning persons - Moving persons in bed - Transferring persons to and from Beds, Chairs, Wheelchairs, Stretchers, Toilets moving the person from one place to another. What does OSHA recommend for safe movement? manual lifting be minimized or eliminated when possible Who determines a patient's level of assistance? the nurse and health team determines the amount of assistance needed, what procedure to use and what equipment is needed and this is based on the person's dependence level, amount of assistance needed (1 -4 people) and what procedure or equipment to use What is OSHA's dependence level of code 4? total dependence, use mechanical lift or friction reducing device. at least 2 staff members needed What is OSHA's dependence level of code 3 extensive assistance, use mechanical lift or friction reducing device, at least 2 staff needed. if less than 200 lbs, 2-3 staff needed and friction reducing device. if more than 200 lbs, 3 staff + friction reducing device What is dependence level Code 2? limited assistance, stand assist devises may be mended like walkers or gait belts or slide boards What is dependence level Code 1? staff just needs to supervise and cue the person. some assist devices may be needed What is a Code 0? independent, very limited assistance needed What do you need to do when moving someone in bed? protect the skin, reduce friction and shearing What is friction? rubbing of one surface against another What is shearing? skin sticks to a surface while muscles slide in the direction the body is moving How to reduce friction and shearing? rolling the person, using friction reducing devices How to raise the person's head and shoulders? safely lock arms with person, Do not pull on the person's arm or shoulder When to get help with lifting a person? with older people, those who are heavy or hard to move alone When do you move a person up in bed? for good alignment and comfort When can you move a person in bed by yourself? for children, and lightweight adults with the use of a trapeze When do you need two or more members to move someone? if they are heavy, weak or very old What are some assistive devices for moving? - turn sheets - "geri" pads - slip n slide When are the assistive moving devices used? for most patients, following OSHA recommendations, for people recovering from spinal cord surgery or injuries and for older persons How do you move a person to the side of the bed? 3 segment move Why do you move a person to the side of the bed? - for repositioning and care - before turning - to limit the need to reach over the person When using a mechanical lift or asset device always? - follow OSHA recommendations - for older persons - for people with arthritis - for persons recovering from spinal cord surgery or injuries What are the advantages of right or left side lying position? - prevents complications of bed rest - used to relieve pressure - used for comfort What is the combination of movement? left, back, right, and back What is logrolling? turning a person as a unit in alignment so spine is kept straight Who needs to be logrolled? older people with arthritis, people with hip fractures, spinal cord injuries or recovering from spinal surgery For a safe transfer to/from bed what is needed? room but be arranged so there is enough space and equipment be placed correctly. When are gait belts useD? - to support patients and residents during transfers - to reposition persons in chairs and wheelchairs When can stand and pivot transfers be used? when persons leg strong enough to bear weight, can follow directions, and can help you When are mechanical lifts used? when a person cant help themselves, are too heavy for the staff to transfer When are slings used? - depends on the person's size, condition and other needs - follow agency policy and manufacturers instructions Before using a mechanical lift? - you must be trained on its use - it must be in working order and good repair - weight of patients must not exceed the lifts capacity - need 2 staff members What is a bathing sling? used to transfer a person using a lift from bed into bathtub What is a toileting sling? open on the bottom so they can use toilet, each resident should have their own to avoid infection When can a slide board be used in transfers to toilet? - if they wheelchair armrests are removable - the person has upper body strength - has good sitting balance - and when there is enough room to position the wheelchair next to the toilet When is a stretcher used? - when person cant sit up - must stay in lying position - are seriously ill What is placed on a stretcher? - folded flat sheet or bath blanket - a draw sheet - large incontinence under pad - slide sheet - slide board if 2-3 people needed for safe transfer What safety precautions are used for stretcher transfers? - safety straps used - side rails kept up during transfer - moved feet first - 2 staff members used for transport - person at heard watches breathing and color of patient - never leave person alone on stretcher What are the OSHA recommendations for moving a person? - If the person weighs less than 100 pounds, use a - lateral slide aid and 2 staff members. - 2.If the person weighs 100 to 200 pounds, use a lateral sliding aid or a friction-reducing device and 2 staff members. - 3.If the person weighs more than 200 pounds, use one of the following: - a)A lateral sliding aid and 3 staff members b) A friction-reducing device or lateral transfer device and 2 staff members - c)A mechanical lateral transfer device with a built-in slide board What is good wheelchair positioning? - persons back and buttocks against back of chair - positioning devices used for dependent limbs - don't pull up person under arms from behind the wheelchair You are using a drawsheet as an assist device. It is placed so that� it is nude the person from the head to above the knees. CH 8 and 39 - Skeleton: how many bones do we have? What is tensile strength? - Bends but resists breaking - Proteins provide flexibility - Ca++ & PO4 provide rigidity - Constant building & breaking down - Osteoclasts and osteoblasts - Form in proportion to task required - Heals with little scarring What are the 4 bone types? - long bones: weight bearing like legs and bones - short bones: bones of fingers and toes for skill and ease of move - flat bones: protective like bones of chest, skull and pelvis - irregular bones: vertebrae for mov't and flexibility What are bones covered by? periosteum which have vessels that supply bone with o2 and food What are the sections of the spine? cervical (7), thoracic (12), lumbar (5), sacrum and coccyx What is the function of the skeleton? support, movement, protection, storage of minerals and fat soluble vitamins, hematopoesis What are the 2 major divisions of the skeleton? - axial skeleton of central core: skull, spine, rib cage - appendicular skeleton: arms, legs, shoulder girdles and pelvic What is a joint? where bone meets bone What lines joints? synovial membrane which secretes synovial fluid that lubricates the joint for smooth movement What is cartilage? the connective tissue at the end of long bones, cushions so bones don't rub together What is a ligament? attach bone to bone at joint What is a tendon? attach muscle at bone What are the types of joints? - sutures - fused by 8 months - pivot-rotation atlas/axis - ellipsoidal-limited move carpal and tarsals - hinge- elbow - saddle- thumb - ball and socket-shoulder How many muscles do we have? more than 500 What are the muscle types? skeletal (voluntary/striated), cardiac (involuntary/striated) and smooth (involuntary) Function of muscles? mov't of body parts, maintenance of posture, production of heat what are the 2 parts of the nervous system? - the cns - brain and spinal cord - and pns - contains 12 cranial nerves and 31 spinal nerves What does the myelin sheath do? conducts faster impulses and insulates nerve fiber What are the 3 main parts of the brain? cerebrum contains cerebral cortex (highest brain functions) cerebellum (body move) and brainstem (midbrain, pons and medulla which controls heart rate, breathing, blood vessel size) What covers the spinal cord? - 3 layers of meninges. - dura mater (outer), arachnoid and the pia mater (inner) What are the structures of the eye? sclera-whites, choroid (black), cornea (focuses light into eye), iris (color) pupil (opening), lens (bends light onto retina), retina (photoreceptors), optic nerve Structure of ear? - external ear- sound waves go thru auditory canal, cerumen (wax) secreted, eardrum - middle ear-eustachian tubes from ear to throat and ossicles amplify sound - inner ear-semicircular canals for balance and cochlea containing fluid which carries sound waves to auditory nerve What are the structures and functions of the circulatory system? - blood, heart and vessels - carries nutrients and oxygen to cells - removes waste products from cells - regulate body temp - carry cells that function in immunity What are the 3 layers of the heart? pericardium (outer), myocardium (2nd muscular layer) and endocardium (inner) What is respiration? process of supplying the cells with oxygen and removal of CO2 What is a fracture? a broken bone What is a closed fracture? bone is broken but skin intact What is an open fracture? bone has come through the skin What are causes of bone fracture? - Falls and accidents - Bone tumors - Metastatic cancer What is a closed reduction? - bones ends brought into alignment to fix fracture - held in place with traction, cast or external fixator What is open reduction Internal fixation? - a surgical procedure where bone is exposed and moved into alignment - held in place with screw, plates, cast or external fixator Signs and symptoms of fractures? - Loss of function - Limited or no movement of the part - Movement where motion should not occur - Bruising and skin color changes at the fracture site - Bleeding internal or external What is a cast? Plaster of paris, plastic, or fiberglass What is traction? - Reduces & immobilizes joints & fractures - System of weights, ropes, and pulleys - Used to treat muscle spasms and to correct deformities or contractures - Traction is applied to the neck, arms, legs, or pelvis - Skin traction is applied to the skin - Skeletal traction is applied directly to the bone - For cervical traction, tongs are applied to the skull. When are hip fractures common? - in older persons, specifically older women - very poor outcome for people over 65 with hip fracture How are hip fractures treated? - The fracture requires internal fixation or joint replacement - Post-op avoid the following - Internal rotation - External rotation - Severe hip flexion - Rehabilitation is usually needed after a hip fracture What are some postoperative problems? - immobility can cause - Thrombi (blood clots) in the leg veins - Pulmonary embolus - Pressure ulcers - Confusion, depression, anxiety, delirium - Atelectasis (collapse of a part of a lung) - Pneumonia - Dehydration - Urinary tract infections What is arthritis? joint inflammation - most common joint disease What causes arthritis? - Being overweight - Joint injury - Muscle weakness what are the 3 types of arthritis? osteoarthritis, gout and rheumatoid What is Osteoarthritis? - Degenerative disease - Wear & tear injury - More common in women What is Gout? - Excess uric acid in blood - More common in men - Generally affects large toe joint - Can affect any joint or organ What is Rheumatoid - Inflammatory connective tissue disease - May affect children What are the signs and symptoms of Arthritis? - Joint stiffness occurs with rest and lack of motion. - Pain occurs with weight-bearing and joint motion. - Swelling is common after using the joint. Is there a cure for arthritis? When does rheumatoid arthritis develop? - Develops between the ages of 20 and 50 - RA is more common in women than in men - RA occurs on both sides of the body. What are the symptoms of rheumatoid? - Symptomatic for years prior to diagnosis - Varies from person to person - Fatigue and fever are common. - Joint pain - Tender, swollen and warm - Loss of function - Other body parts may be affected. What is the treatment of arthritis? - Drugs to decrease swelling and inflammation and relieve pain - Heat - Sometimes cold applications - Exercise -Physical therapy and Massage - Rest and joint care - Weight control - Healthy life-style - Joint replacement surgery - arthroplasty What are the goals of arthritic treatment? - Relieve pain - Reduce inflammation - Slow down or stop joint damage and Preserve function - Improve the person�s quality of life What is osteoporosis? - brittle porous bones that are fragile and easily broken - older men and women are at risk, for women increase after menopause - all ethnic gropes are at risk What are other risk factors for osteoporosis? - A family history of the disease - Being thin or having a small frame - Eating disorders - Tobacco use - Lack of exercise What are these signs of osteoporosis? - Back pain - Gradual loss of height - Stooped posture What are some preventive measure of osteoporosis? - Calcium and vitamin supplements - Estrogen for some women - Exercising weight-bearing joints - Not smoking - Limiting alcohol and caffeine - Back supports or corsets if needed for good posture - Walking aids if needed - Safety measures to prevent falls and accidents - Good body mechanics - Safe handling, moving, transfer, and turning and positioning procedures CH 1: Health Care Agency - What is the purpose of an agency? health promotion (diet/exercise), disease prevention (immunizations), detection and treatment of disease and rehab and restorative care. the person is the focus of care What is primary care? - Goal to reduce the risk of illnesses - Teaching and counseling about healthy living What is secondary care? - Early warning signs of disease - Diagnostic tests, exams, surgery, emergency care, medications What is tertiary care? rehab and restorative care - return patients to highest possible level of functioning When does rehab start? when person first seeks health care What are the different types of agencies? - Other agencies free standing or in hospital - Rehabilitation and sub-acute care agencies - Long-term care centers: Skilled nursing facilities (SNFs), Assisted living and Residential care - Mental health centers - Home care agencies - Health care systems What is actor illness? sudden and expected to recover What is chronic illness? ongoing, slow onset, no cure What is terminal illness? no reasonable expectation of recovery. death. What is the chain of command in an agency? - Board of trustees or board of directors. They make policies. - Administrator manages the agency - Directors or department heads manage certain areas - The interdisciplinary health care team can include PT/OT/ST, nursing, dietary, lab, radiology What is a health team? all the health care workers that focus on the person's total care What is the goal of an agency? to provide quality care What is the responsibility for the Director of Nursing - RN? for the entire nursing staff, and nursing/staff education Who assists that DON? nurse managers where each nursing area is headed up by a charge nurse Who do staff RNs report to? charge nurse, LPNs/LVNs Who can provide direct nursing care? - registered nurses: phd, msn, ban, asn - LPN or LVNs - Nursing Assistants What is patient-focused care? when services are moved from departments to the bedside. nurses do jobs usually done by other members of health care team. reduces cost. What determines a nursing care pattern? - How many patients / residents need care - Health care needs of patients / residents - The staff available - Care costs What is functional nursing? focus on tasks and jobs. one nurse is the drug nurse, another is showers What is team nursing? team of nursing staff lead by an RN What is primary nursing? total care provided by registered nurse What is case management? similar to primary nursing except a case manager RN coordinates a person's care. communicates with whole care team even insurance. good for cancer or heart disease patients What is private insurance? bought by individuals and families What is group insurance? bought by groups and organizations for individuals Who ends up paying for the uninsured? the insured do, about an extra $1000 per year What is medicare? - Federal health insurance program for persons 65 years of age or older. - Part A: Automatic - Part B: Voluntary with monthly premium - Some younger people with certain disabilities are covered. What is medicaid? - Health care payment program - Operated by the states - Sponsored by the federal government What is the prospective payment systems? they limit the amount paid by insurers, medicare or medicaid. if treatment coos are less than the amount paid, the agency keeps the extra money. What are DRGs? Diagnosis-related groups are for hospital costs What are RUGs? resource utilization groups are for SNF (skilled nursing facilities) payments What are case mix groups? they are used for rehab centers What are HHRGs? home health resource groups are for home health care What are HMOs? - Managed care deals with health care delivery and payment. - Approval for health care must be approved by many insurers - Insurer pays for the services if need is approved - Person pays if the need is not approved What are managed care limits? - Choice of where to go for health care - Choice of provider - Care provided - insurers contact docs and hospitals to get reduced rates. if you don't go to their preferred docs or hospitals, then they don't cover it, so the insured will have to cover more out of pocket costs. Who sets the standards of care? - Set by Federal and state governments - Accrediting agencies - JCAHO and OSBN What standards must an agency meet? - State issued licensure - License for operation and care provision - Certification - Medicare / Medicaid requirement - Accreditation - Voluntary survey signals quality & excellence What are state surveys? - Agency receives a license, certification, or accreditation if standards are met. - Agency can lose its license, certification, or accreditation if deficiencies are found. - The agency is given time to correct deficiencies. - The agency can be fined for uncorrected or serious deficiencies. - The agency may not admit new residents until state survey is passed. - Students may not practice clinical in a setting which has been found deficient. What is a CNAs role in the survey process? - Following agency policies and procedures - Meeting cleanliness and safety standards - Conducting yourself in a professional manner - Providing quality care - Protecting the person�s rights - Providing for the person�s safety - Providing for your own safety - Having good work ethics - Answering questions honestly and completely CH 4: work ethic - What does professionalism involve? - Following laws - Being ethical - Having good work ethics - Having the skills to do your work What do work ethics involve? - How you look - What you say - How you behave - How you treat others - How you work with others What parts of health, hygiene and appearance is involved in professionalism? diet, 7 hours of sleep, exercise, wear corrective lenses, bathe daily, brush teeth, foot and nail care, body mechanics, don't smoke or drink or do drugs What are employers looking for? dependable, well groomed, have needed skill/training and have values and attitudes that fit with agency For a job interview, what should you do? - greet interviews in polite manner - stand until asked to take a seat - keep your mind on the interview - avoid overly short or long answers What questions should yo ask in an interview? - Pay rate - Work hours - Tuition reimbursement and scholarship programs - Uniform requirements - The new employee orientation program What happens during new employee orientation? agency's policy and procedure manual is reviewed and skills are checked What is a preceptor? a staff member that helps new staff learn the agency's layout, introduce to patients, answers questions about policy How to avoid gossiping? - remove yourself from a gossiping group - don't repeat anything that can hurt a person - don't repeat anything that you know isn't true - don't talk about anything from work at home or in social settings What is a courtesy? polite, considerate or helpful comment or act What is harassment? - Trouble, torment, offend, or worry a person by one�s behavior or comments. - Harassment can be sexual. - Harassment can involve: Age, Race, Ethnic background, Religion and Disability. What is sexual harassment? involved unwanted sexual behaviors by another How to resign from a job? - Give a written notice. - Giving 2-weeks notice is a good practice. - Do not leave a job without notice. - An exit interview is common practice Can you lose your job for not wearing the dress code? Ch 26: Describe nursing process and activity? Used to promote exercise and activity in all persons to the extent possible. Care plan will include person�s activity level and needed exercises Why is bed rest ordered? - Reduce physical activity - Reduce pain - Encourage rest - Regain strength - Promote healing What is strict bed rest? everything is done for the person - no activities are allowed What is bed rest? some activities of daily living (ADL) are allowed What are other types of bed rest? - bed rest with bedside commode privileges - bed rest with bathroom privileges What can bed rest promote? - Pressure ulcers - Constipation and fecal impaction - Urinary tract infections and renal calculi (kidney stones) - Blood clots (thrombi) - Pneumonia (inflammation and infection of the lung) - Muscle atrophy - Orthostatic hypotension (postural hypotension) - Syncope (fainting) What is a contractor? - lack of joint mobility caused by abnormal shortening of a muscle. - person becomes permanently deformed or disabled. How can nursing care prevent complications from bed rest? - Good alignment - Range-of-motion exercises - Frequent position changes - These are part of the care plan. What supportive devices are used? - Bed boards prevent the mattress from sagging. - Foot boards prevent plantar flexion (footdrop �foot falls down at ankle) and serve as bed cradles. - Trochanter rolls prevent the hips and legs from external rotation/turning inward. - Hip abduction wedges keep the hips abducted. - Handrolls or handgrips prevent contractures of the thumb, fingers, and wrist. - Splints keep the elbows, wrists, thumbs, fingers, ankles, and knees in normal position. - Bed cradles keep the weight of top linens off the feet and toes. What does exercise prevent? - Muscle atrophy - Other complications of bedrest When is a trapeze used? - For exercises to strengthen arm muscles - To move up and turn in bed What is range of motion exercises? movement of joint through complete range to the extent possible without pain or to point of resistance What is active range of motion? exercises are done by the person What is passive range of motion? exercises done by someone else moving the limbs What is active-assistive range of motion? exercise is done by the person with some help After prolonged bed rest, activity increases in what steps? - Sit at side of bed with pedaling of feet and ankles - Stand at side of bed and march - Walk across room to chair - Walk in hallway What should you look for when getting people up after bed rest? - Profuse sweating - Nausea and salivation - Increased heart rate In order to achieve the goal of walking, you nee to make sure that? - Contractures and muscle atrophy must be prevented. - Proper positioning and exercises are needed during bed rest. - Walking regularly helps prevent de-conditioning. What is the purpose of walking aids? - Walking aids support the body. - The type ordered depends on: - The person�s condition - The amount of support needed - The type of disability - May be temporary or permanent - PT or RN teaches the person to use the device and fits patient When are crutches are used? - The person cannot use one leg - When one or both legs need to gain strength. What are the safety measures for crutches? - Check the crutch tips. - Check crutches for flaws. - Tighten all bolts. - Make sure the person wears street shoes with flat, non-skid soles. - Make sure clothes fit well. - Practice safety rules to prevent falls - Path is clear of obstacles or spills - Keep crutches within the person�s reach. - Know which crutch gait the person uses. What is a four point gait? both legs used. right crutch moves forward and then left foot moves. the left crutch moves forward followed by the right foot. What is a three point gait? only one leg is used. both crutches move forward and then the good foot is moved forward What is a two point gait? left crutch and right foot moved forward at same time followed by the right crutch and left foot moving forward together What is a swing to gait? both crutches moved forward and then the person swings both legs to the crutches What is a swing through gait. both crutches move forward and then both legs are swung through the crutches at once. When are canes used? - for weakness on one side of the body - provide balance and support - held on strong side of body What is a walker? a four point walking aid, gives more support, sometime come with attachments of trays What is a brace? support weak body parts, prevent or correct deformities, prevent joint movement What is an AFO? ankle foot orthosis is a brace placed in the shoe over ankle and food When using braces what do you need to do? - Keep skin / bony points under braces clean / dry. - Report redness & signs of skin breakdown at once. - Report complaints of pain & discomfort. - Follow the care plan for brace use What activities are required by OBRA? activity programs required for residents so as to improve quality of loofa What do recreational activities promote? - Important for physical and mental well-being - Exercises joints and muscles - Stimulates circulation - Provide social outlet - Provide mental stimulation CH 27: Comfort rest sleep - what can arise from deficits of comfort rest and sleep? injury, illness, pain may be physical or emotional which disrupts sleep and if left untreated can decrease function and quality of life What is comfort? - a state of well-being - The person has no physical or emotional pain. - Person is calm and at peace. What is comfort affected by? - Age, illness, stress and activity - Environmental factors like Temperature, Ventilation, Noise, Odors and Lighting What is pain? - Subjective, personal and individual experience - You must rely on what the person says: Ache, Hurt, Sore - Pain is a warning from the body. - It signals tissue damage. - Pain often causes the person to seek health care. What are the types of pain? acute, chronic, radiating, phantom What is acute pain? felt suddenly from injury, disease, trauma, or surgery. What is chronic pain? - pain lasts longer than 6 months. - Chronic pain may result from inadequate pain control during the acute phase. What is radiating pain? felt at the site of tissue damage and in nearby areas. What is phantom pain? Phantom pain is felt in a body part that is no longer there. What factors affect pain? - Past experience: Knowing what to expect can help or hinder how the person handles pain. - Anxiety: Pain can cause anxiety. Anxiety increases pain. - Anxiety reduction may be needed to adequately control pain. - Rest and sleep:Rest and sleep restore energy and increase healing. May seem worse when tired or restless. - Attention: Pain is reported more frequently at night with greater pain levels. Fewer distractors at night. Night time pain control is paramount for promoting sleep and rest - Personal and family duties: deal with pain in order to take care of kids. - The value or meaning of pain: Culture, experience, religion, societal expectations Give value or meaning to how a person experiences & responds to pain. showing pain is a sign of weakness. - Support from others: Comfort and support from family & friends increases coping. - Illness: May increase or decrease pain sensation What needs to be reported about pain? - OLDCARTS need to be reported immediately. anytime pain level gets to 2. - plus vital signs and any other signs or symptoms What are the nursing measures to deal with pain control? - The nurse uses the nursing process to promote comfort and relieve pain. - Other measures - Distraction: To change the person�s center of attention - Relaxation: Free from mental and physical stress - Guided imagery: Creating and focusing on an image - Medications are ordered to control or relieve pain. - May cause orthostatic hypotension, drowsiness, dizziness, and coordination problems. - Be alert to needed safety measures. What does rest mean? to be calm at ease and relaxed How can rest be promoted? - Meet basic needs - quiet setting, neat room How to Help relieve pain or discomfort so as to promote rest? - Providing a comfortable position and good alignment - Providing a quiet setting - Providing a clean, dry, and wrinkle-free bed - Providing a clean, neat, and uncluttered room - Release tight clothing and remove shoes How to meet higher needs in order to promote rest? - Meeting safety and security needs: Keeping the signal light within reach - Explaining the reasons for care, Explaining how care is given - Following routines and rituals whenever possible - Meeting love and belonging needs: Promoting visits or calls from caring family and friends, Reading cards and letters - Meeting self-esteem needs: Promoting personal choice in sleepwear and Assisting with hygiene and grooming measures as needed Why is sleep necessary? - it is a basic need. A state of unconsciousness, reduced muscle activity & lowered metabolism - It lets the mind and body rest. - The body saves energy. - Body functions slow. - Vital signs are lower than when awake. - Tissue healing and repair occur. - Sleep lowers stress, tension, and anxiety. - The person regains energy and mental alertness. What is a circadian rhythm? - a daily rhythm based on a 24-hour cycle. - It affects functioning. - Circadian rhythm includes a sleep-wake cycle. How many phases of sleep are there? - Two phases of sleep with 4 stages. - NREM sleep (non-REM sleep) is the phase of sleep where there is no rapid eye movement. has 4 stages that go from light to deep sleep. - The rapid eye movement phase is called REM sleep. Important for mental restoration. - Sleep needs vary for each age-group. What are the average sleep needs for an adult? Average adult needs 7 � 9 hours of sleep daily. this requirement changes as a person ages, need less sleep. What factors affect sleep quality? - illness and nutrition (sleep needs increase with weight gain) - exercise, environment, drugs, life style changes, emotional problems. Details about illness affecting sleep? - Signs and symptoms of illness interfere with sleep. - Treatments and therapies interfere with sleep. - Care devices can cause uncomfortable positions. - The emotional effects of illness can affect sleep. Details about nutrition affecting sleep? - Sleep needs increase with weight gain and decrease with weight loss. - Foods with caffeine prevent sleep. - The protein tryptophan tends to help sleep. What can disrupt sleep in daily life? - Exercise improves health and fitness but Exercise before bedtime interferes with sleep. - Environment: People adjust to their usual sleep settings. - Medication and other substances - Caffeine, amphetamines interfere with sleep - Hypnotics, narcotics, muscle relaxers, antidepressants & anxiolytics promote sleep but shorten REM sleep - Alcohol interferes with REM sleep. - Life-style changes can affect sleep. - Emotional problems What are sleep disorders? repeated sleep problems - amount and quality are affected What is insomnia? a chronic condition in which the person: Cannot fall asleep, Cannot stay asleep and Awakens early and cannot fall back asleep What is sleep deprivation? Amount and quality of sleep are decreased. Sleep is interrupted. What is sleepwalking? - Person leaves the bed and walks about. - Usually does not remember episode, High risk for injury What needs to be reported or done about sleep? - Report signs and symptoms of sleep disorders. - Follow the care plan for measures to promote sleep. - Report your observations about how the person slept. CH 30: sputum specimens: define sputum? mucus from the respiratory system when expelled through the month. it is coughed up from the bronchi and teaches. When is the best time to collect it? in the morning What should the patient do before collecting it? rinse mouth with water to decrease saliva and remove food particles What would you like to do? Home > Flashcards > Print Preview	2	29	0	0	1	0.593721	1	24,996
I. Evaluation and Management of Syncope: What every physician needs to know. Syncope is a symptom not a diagnosis. Syncope is characterized by transient loss of consciousness (TLOC) due to a spontaneously self-limited (usually at most a minute or two) period of cerebral hypoperfusion. The term “presyncope” is best used to depict a period of time just prior to syncope in which the patient may report any of a variety of warning or prodromal symptoms or signs (e.g., light-headedness, visual “gray-out,” palpitations, and nausea.). “Near-syncope” is a term that reflects symptoms that seem to be leading to a full syncope event, but the latter does not materialize. Thus, “near syncope” is best used when the symptomatic episode is limited to the occurrence of only prodromal symptoms without actually subsequent loss of consciousness. Research suggests that the basis for near-syncope in a given individual may not be the same as the cause of true syncope in the same person. Consequently, near-syncope should not be used as a surrogate for syncope when diagnostic testing is undertaken. The term “syncope” is often used by physicians both in casual conversation, as well as during documentation of the patient’s history when an individual presents after having recovered from an apparent temporary loss of consciousness. However, such usage is both incorrect and the source of much wasted diagnostic effort and expense. TLOC is a more precise initial descriptor and should be employed. In essence, even though a patient might ultimately be considered to have suffered a true syncopal episode, the initial presentation should not be automatically considered to have been ‘syncope’. The patient usually has come with complaints such as having experienced a ‘blackout’ or ‘collapse’. It is the physician’s responsibility to determine whether the episode was indeed a ‘syncope spell’ or some other cause of real or apparent TLOC. Thus, in every case, the evaluation begins with TLOC, and only later (usually after a careful history has been obtained), if warranted, is it appropriate to shift the focus to syncope. Once it is concluded that the presenting symptom was syncope, the next steps are: 1. Assessing the likely cause 2. Advising the patient regarding prognosis both in terms of recurrence risk, and mortality, and 3. Initiating a treatment strategy The last two of these steps is critically dependent on the first being correct, and on whether the patient has any evidence of underlying cardiovascular disease. Syncope has many causes. However, in the vast majority of cases the basis for cerebral hypoperfusion is a self-limited period of systemic hypotension (acute severe transient hypoxemia, as in airliner decompression, is certainly an alternative possibility but is very rare). Consequently, subsequent investigation of syncope focuses on those etiologies that could trigger a transient drop in blood pressure. The principal considerations are summarized below. However, in many cases, “syncope-mimics” also enter the diagnostic equation (e.g., psychogenic pseudo-syncope [conversion reactions], narcolepsy, malingering), and these can prove to be challenging for physicians to deal with. The principal conditions that cause syncope due to transient global cerebral hypoperfusion may be classified as follows: A. Reflex (Neurally-mediated reflex) syncope Vasovagal (or “common”) faint in which the triggering of an as yet inadequately understood neural-reflex leads to inappropriate vaso/veno dilation with either severe bradycardia or at least insufficient heart rate compensation (Figure 1); the result is cerebral hypoperfusion and loss of consciousness, often accompanied by premonitory symptoms such as feeling hot or cold, palpitations, and nausea. The triggers for the initial sympathetic activation, which in turn is responsible for reflex parasympathetic activation, may be emotional distress, medical instrumentation, fear, and in some cases prolonged orthostatic stress. Situational faints are similar in nature to vasovagal syncope, but the triggers are more readily identifiable. Typical triggers in susceptible individuals include severe cough, defecation, micturition, visceral pain, and postexercise or postprandial situations. Carotid sinus syncope is usually associated with demonstrable carotid sinus hypersensitivity (i.e., abnormal response to carotid sinus massage). This condition tends to be restricted to older patients and often those with atherosclerotic vascular disease. It is now considered an important cause of otherwise unexplained falls in older individuals. The diagnosis is best made if the history suggests that the collapse was associated with neck movement, although such an association is uncommon. The finding of loss of consciousness during carotid sinus massage (CSM) due to marked bradycardia and/or as a result of vasodepressor hypotension (best demonstrated during CSM with the patient studied on a tilt-table in the head-up position) may also be considered diagnostic if no other causes can be identified. B. Orthostatic hypotension (OH) Immediate (initial) OH refers to the abrupt drop in blood pressure that may be observed almost immediately after change of posture from supine or seated to standing. The phenomenon is almost universal, and occasionally causes transient ‘gray-out’ in even healthy individuals. However, fainting may occur in some cases. The drop in blood pressure occurs as gravity displaces almost a liter of blood from the upper parts of the body to the splanchnic bed and legs. Generally, vasoconstriction and modest tachycardia promptly respond to compensate. However, in some patients (e.g., older, dehydrated, certain neurologic conditions) may not compensate quickly or sufficiently, and syncope occurs. In older patients (who are often amnestic for any prodrome), the collapse may be mistaken for an accidental fall and the real cause is missed. Delayed (classical) OH tends to occur some minutes after movement to upright posture . When the blood pressure is recorded in such cases, it tends to dwindle over time and the faint occurs when systemic pressure is low enough that cerebrovascular autoregulation is no longer able to compensate. In some instances, the collapse may not occur for 10 to 15 minutes after the change in posture. Unlike Immediate OH, the delayed form is more troublesome and is more often associated with important predisposing medical conditions, including: volume depletion, primary or secondary autonomic failure, drug effects, and deconditioning. Primary autonomic failure may be indicative of Parkinson’s disease, Lewy body dementia, and multisystem atrophy. Secondary autonomic failure is observed in patients with diabetes mellitus, alcohol abuse, amyloidosis, uremia, and spinal cord injuries. Drug-induced hypotension is particularly important, and can be the result of treatment with any of a variety of agents including diuretics, antihypertensives, adrenergic blockers, and antidepressants. C. Cardiovascular causes The recent European Society of Cardiology syncope practice guidelines now combine cardiac causes of syncope, along with other cardiovascular disorders that may trigger syncope. In many of these cases, hypotension is triggered directly as a consequence of a drop in cardiac output such as may be expected with abrupt onset of either a bradyarrhythmia or tachycardia. Similarly, acute obstruction to blood flow occurring as a result off an atrial myxoma or severe cardiac tamponade may be expected to trigger symptomatic hypotension. On the other hand, the hypotensive event may be secondary to the triggering of a neural reflex rather than as a direct accompaniment of the structural disturbance; thus the triggering of syncope due to reflex bradycardia and/or vasodepressor responses have been associated with acute myocardial infarction, acute aortic dissection or pulmonary embolism. 1. Arrhythmic causes of syncope Bradyarrhythmias and tachyarrhythmias (both supraventricular and ventricular) are the most frequent causes of syncope in the cardiovascular category. This latter group also includes the growing list of “channelopathies” (long Q–T syndrome, Brugada syndrome, catecholaminergic ventricular tachycardia, idiopathic progressive conduction system disease, etc.). In patients with sinus node dysfunction (SND), syncope may be caused by abrupt slowing of the heart rate (e.g., sinus pauses, sinus arrest) or due to a long pause after termination of an atrial tachyarrhythmia in the so-called bradycardia-tachycardia syndrome (BTS). Similarly, transient symptomatic hypotension may occur if an atrial tachycardia (most often atrial fibrillation) starts and the resulting heart rate is too fast to maintain the cardiac output, while at the same time vasoconstrictive compensation is too slow or inadequate or both. Atrioventricular (AV) conduction disease may also cause syncope, if abrupt conduction block, even if short-lived, slows the heart rate excessively and for a long enough period of time (generally estimated to be approximately 10 seconds or more). Generally, these patients have some evidence on an electrocardiogram (ECG) of conduction system involvement (e.g., bundle-branch block, abnormal frontal axis). They may then progress to complete or high grade AV block (Figure 2) in which multiple atrial impulses (P waves) are blocked and the ventricular rate is unable to sustain an adequate blood pressure. Other less severe forms of AV block, including Mobitz 1 block (i.e., Wenckebach block) in older patients or Mobitz 2 block in any patient, may be a clue indicating that AV block is the cause of the patient’s problems. As a rule, paroxysmal supraventricular tachycardia in young to middle-aged individuals rarely cause syncope. However, syncopal symptoms may occur in older patients or those with left ventricular dysfunction. Conversely, ventricular tachycardias (VTs) are an important cause of syncope. However, the reason is not so much the site of origin of the tachycardia, or even the rate (which is often similar to the paroxysmal supraventricular tachycardias), but the fact that VTs tend to occur in the setting of heart disease. It is the patient’s ability to maintain an adequate stroke volume at fast rates and also invoke compensatory mechanisms to maintain blood pressure that determine whether syncope occurs. Thus, even slow VT in patients with severe left ventricular dysfunction may cause hypotension. On the other hand, torsades de pointes VT (Figure 3), which tends to be very fast, can result in syncope in a young or middle-aged patient with long Q–T syndrome, the heart being structurally normal from a contractile perspective. In some patients with an established diagnosis of arrhythmogenic cause of syncope and have a pacemaker placed for the same may present with syncope due to pacemaker malfunction (Figure 4). (Table 4) 2. Structural cardiovascular causes of syncope Among the more important structural conditions that may be associated with syncope are: acute myocardial infarction, valvular aortic stenosis, acute pulmonary embolism cardiac tamponade, and hypertrophic cardiomyopathy. Less frequently encountered conditions that may also cause syncope include acute aortic dissection, intracardiac tumors (e.g., atrial myxoma), and arrhythmogenic dysplasia. As noted earlier, the cause of syncope in these settings may be due to direct impact of the lesion (e.g., atrial myxoma), or a reflex effect (e.g., acute aortic dissection) or a combination of both (e.g., acute pulmonary embolism, acute myocardial infarction). Additionally, since these structural abnormalities may coexist with left ventricular disease, conduction system abnormalities, or sinoatrial disturbances, the potential exists for the explanation being multifactorial and complex. D. Syncope mimics A number of conditions may present with what appears to be TLOC and might be mistaken to be syncope. While these conditions are not “true syncope” and are not considered further in the remainder of the text, they are noted here for completeness sake. The most important of these conditions is “pseudosyncope” (neurologists call this “pseudoseizures”). The hallmark is the very high frequency of attacks, usually but not always, unassociated with major injury. It is suspected that these patients may have had some true syncope events at some time in the past, and may have been the subject of abuse. In any case the clinical picture evolves into a severe psychiatric disturbance (possibly a conversion reaction) that needs intensive psychiatric and psychological assistance. Functional autonomic disturbances may include real or pseudosyncope in the clinical picture. Thus, while syncope is not a major feature of postural orthostatic tachycardia syndrome (POTS) in most cases, it is a subset of the panoply of symptoms that these patients may complain of. Narcolepsy and cataplexy may also masquerade as syncope, and require experienced neurologic consultation to assess. II. Diagnostic Confirmation: Are you sure your patient has Syncope? Syncope by definition incorporates a self-limited period of loss of consciousness (usually associated with loss of postural tone as would be expected). A careful medical history obtained by an experienced individual is the key to confirming whether a true syncope has occurred (see below). The development of detailed standardized questionnaires may prove to be a useful diagnostic aid, but as yet there is no single well-proven instrument available. The one other condition that most physicians concern themselves with in this setting is an epileptic seizure. Seizures are far less common than are syncopal events. In any case, careful history taking and eye-witness accounts may help distinguish the two problems. In seizures, abnormal movements of the face, tongue, and extremities may be observed before collapse. In syncope, any abnormal jerky movements that occur (and they are common) do so after the loss of consciousness. The quality of the motor activity is also different, but this may not be readily appreciated by nonexperts. Rhythmic tonic clonic activity(which may be absent some times in temporal lobe seizures) are indicative of seizure, while the jerky motions of syncope due to cerebral hypoperfusion are more erratic. The postictal state also differs. In seizures the patient may experience postictal confusion or headache. The syncope patient tends to regain alertness promptly but may be fatigued. Incontinence can occur with both conditions, but tongue-biting is very rare with syncope. In general, more patients are mislabeled as “seizure patients” when they are suffering syncope than vice-versa. Most neurologists would agree that it is important to establish the correct diagnosis, even at risk of recurrence, before labeling the patient and embarking on a futile course of action. If necessary, video-EEG monitoring should be used. Placement of an insertable loop recorder (ILR) has proven valuable and cost-effective when longer term monitoring is needed. Other conditions that occasionally appear similar to syncope are generally readily identified by experienced clinicians. Thus, for example, intoxications (e.g., alcohol, other agents) are usually accompanied by clear evidence of substance abuse; any suspicion can be confirmed with blood and urine tests for the intoxicating agents. Psychogenic pseudosyncope is a far more difficult problem (see earlier discussion) and may only become apparent after considerable diagnostic energy and expense has been expended fruitlessly. A. History Part I: Pattern Recognition The initial evaluation of a patient presenting with TLOC in whom syncope is suspected consists of a careful and detailed medical history, physical examination (including orthostatic blood pressure measurements), and 12-lead ECG. The initial evaluation often also includes echocardiography. Other tests may be selected as appropriate. Usually the most important of these is long-term ECG monitoring. Selection of these latter devices is discussed in more detail later. Neurologic evaluation is rarely needed, and in the absence of any concern regarding an acute head injury from a fall, the use of head imaging and EEG is discouraged. The importance of the initial evaluation goes well beyond its capability to make a diagnosis as it determines the most appropriate subsequent diagnostic pathways and risk assessment. The history is the most important element in the initial evaluation of a patient with suspected syncope. The goal is to establish a diagnosis with sufficient confidence that the patient can be advised of both his or her prognosis and a proper treatment strategy. A carefully obtained comprehensive history (incorporating eyewitness accounts) alone may be diagnostic of the cause of syncope or may suggest the strategy of evaluation (Table 1). The clinical features of the presentation are most important, especially the factors that might have predisposed to syncope. In this regard it is important to inquire in-depth into as many episodes as the patient and eyewitnesses can recall. It is helpful to start with the most recent event as that may be best recollected. Thereafter work backward. If a pattern is defined, then it may be possible to establish a diagnosis. (Table 1) B. History Part 2: Prevalence Syncope is a symptom that is common in the general population, but clinical epidemiologic terms, such as incidence and prevalence, are not readily applicable in understanding the epidemiology of syncope. For instance, as has been pointed out by Sheldon and colleagues, syncope prevalence must approach zero at any given point in time as very few people are unconscious. Further, syncope is a transient symptom and therefore its true incidence is difficult to assess. Cumulative proportion and cumulative incidence are more meaningful indices that can be used to explain the epidemiology of syncope. Studies of the approximate frequency of individuals reporting onset of syncope suggest that first episodes tend to occur between the ages of 10 and 30 years. The peak age for syncope susceptibility seems to be around 15 years where the occurrence is a high as 47% in females and 31% in males. In a cohort study, only 5% had their first syncope above the age of 40 years. Nevertheless, there appears to be a second peak in both men and women above the age of 65 years. Several studies have reported what can be considered as syncope burden and suggest that 40% of people faint at least once in their lives. Gazenboom et al in Netherlands found that the cumulative incidence of syncope is: General population: 18.1 to 39.7 per 1,000 patient-years General practice: 9.3 per 1,000 patient-years, and Emergency departments: 0.7 per 1,000 patient-years The recurrence rate of syncope is estimated at approximately 20% to 30% per year in some population studies, with important predictors of recurrent syncopal episodes including: Age <45 years A long prior history of multiple syncopal episodes Multiple recent syncope events The “prevalence” of the causes of syncope depends strongly on the clinical setting. Thus reflex syncope is the most frequent cause of syncope in any setting (about 40% to 60% in most reports). Orthostatic syncope is likely second in frequency if older patients are included in the population, with cardiovascular causes being third. The mortality rate depends on the underlying cause of syncope. The 1-year mortality is high in patients with cardiac causes of syncope (18% to 33%), as opposed to patients with noncardiac causes of syncope (0 to 12%). However, in most studies, the cardiac basis of syncope did not seem to confer a higher mortality when compared to matched controls having similar degree of heart disease. On the other hand, Olshansky et al found that in the SCD-Heft cohort (predominantly class 2 and class3 heart disease, with patients of both ischemic and nonischemic origin), the presence of syncope was associated with higher mortality. Additional studies examining mortality risk in selected syncope patient subsets are needed. In this regard, it is recognized that in certain disease states, syncope does raise the mortality risk substantially. For instance, syncope at diagnosis is a predictor of increased risk of sudden death in patients with severe aortic stenosis, hypertrophic cardiomyopathy and also to an important extent in patients with channelopathies, such as Brugada syndrome and long Q–T syndrome, and arrhythmogenic right ventricular dysplasia (ARVD). Patients with syncope due to noncardiac causes in general have an excellent prognosis. This is especially true in healthy young individuals with a normal ECG and without any evidence of structural heart disease. C. History Part 3: Competing diagnoses that can mimic Syncope. The competing diagnoses that may cause real or apparent TLOC and need to be considered as part of the overall clinical assessment of the patient with suspected syncope have been discussed in detail earlier. Table 2 lists the key contenders. D. Physical Examination Findings. Certain basic physical findings may be useful in diagnosing the cause of syncope and assessing prognosis. Perhaps the most important is determining whether there is evidence of the presence of underlying structural heart disease (in this case also incorporating ECG and often echocardiographic data). The absence of any abnormality reduces mortality risk as a cardiac cause is diminished. The presence of an abnormality raises concern regarding cardiac syncope, and its associated increased mortality risk. In either case, however, the possibility of recurrence remains an important consideration and patients need to be advised of this possibility. Recognition of susceptibility to orthostatic hypotension (OH, see earlier) and carotid sinus syndrome (CSS, see earlier) are possible during a careful initial evaluation. However, clinicians must become knowledgeable about how to do the proper maneuvers and interpret the findings. The European Society of Cardiology (ESC) guidelines offer excellent guidance. Physical examination can suggest the presence of important underlying structural cardiac disease. For example, the presence of an irregular, rapid or slow heartbeat, cardiac murmur, or severe dyspnea may suggest the presence of structural cardiac disease and lead one to seriously consider a cardiac cause of syncope. On the other hand, while the presence of carotid vascular bruits may necessitate further assessment on their own merit, they do not provide a basis for syncope. As a rule, carotid Doppler assessment is of little value in the evaluation of the syncope patient. E. What diagnostic tests should be performed? In terms of deciding upon a diagnostic testing strategy, it is mandatory that careful consideration be first given to the likely contending etiologic diagnoses. A shotgun approach is costly and often ineffective. The choice of tests is best determined after the medical history is carefully obtained and the risk of underlying structural heart disease (including familial conditions) has been assessed. The latter is termed the “initial evaluation,” and it is the cornerstone upon which a diagnostic strategy is established. Before ordering any diagnostic tests, the clinician should be reasonably certain that the presenting symptom is indeed syncope and not other TLOC conditions, such as a seizure, intoxication, or head trauma. In essence, the initial evaluation should answer three important questions: Has the patient indeed experienced syncope? Are there any apparent clues from the history, ECG, and physical examination regarding what could have caused the syncope episode(s)? Is there any indication that the patient has underlying cardiac disease and suggesting that syncope could be related to a high-risk cardiovascular condition? The initial evaluation is able to define the most likely cause of syncope in 23% to 50% of cases. In this regard, a 12-lead ECG is generally considered to be part of the initial evaluation, although it may not be absolutely essential in all cases (e.g., a young otherwise healthy patient with classic symptoms indicating vasovagal syncope). If the initial evaluation suggests a likely cause of syncope, then any subsequent testing may not be needed. However, should the physician wish to confirm the suspected diagnosis, the choice of testing should be focused on the specific condition under consideration. Thus a tilt-table test or active standing test may be used to support a diagnosis of vasovagal syncope or orthostatic syncope. An electrophysiologic study (EPS) may help to confirm the presence of severe conduction system disease, inducible tachyarrhythmias, or (with less certainty) sinus node dysfunction (Table 3). If the initial evaluation does not define the cause, then the next step is to risk-stratify patients and make the determination whether to admit the patient for evaluation or to discharge the patient and recommend out-patient work up. The latter is best conducted promptly (i.e., within 3 to 4 days) in a setting that specializes in the care of such patients (i.e., so-called “syncope clinic”). In either case, the choice of diagnostic tests should be based on probable causes derived from the history. In many cases, if there is no clear direction evident, specialty consultation from a syncope clinic practitioner may be helpful. (Table 3) There are many tests that can be employed in defining the cause of syncope. However, the specific indications, utility, and limitations for each test must be understood to ensure that they are selected in a cost-effective manner. The most important of these tests and their primary utility are outlined here: Carotid sinus massage (CSM) Indications: In patients >40 years of age presenting with syncope of unclear etiology. When is the test diagnostic? Ideally, this test should be with the patient in a head-up position on a tilt table. If CSM reproduces syncope under these conditions with documentation of hypotension due to asystole or a ventricular pause of >3 seconds and /or fall in systolic blood pressure >50 mm Hg then the diagnosis is supported. Similar findings without reproduction of syncope are less convincing but often are relied upon if no competitive explanation is apparent. CSM should be avoided in patients with a history of cerebrovascular accident (CVA) or stroke within 3 months of the test, or patients with carotid bruits unless significant carotid stenosis is excluded with a Doppler ultrasound. Older patients in whom there is a clinical suspicion of orthostatic hypotension of any etiology. When is this test diagnostic? The test may be done in two ways, but in either case it is best to use beat-to-beat noninvasive blood pressure monitoring (e.g., Finometer). Active standing is likely the better of the two methods. The patient is seated or supine and then physically moves to the standing position. The second method employs passive movement to head-up posture on a tilt-table. OH is defined as a decrease in systolic blood pressure (SBP) >20 mm of Hg and >10 mm of Hg, usually within 3 to 5 minutes of changing position from supine to an upright position. Delayed responses may also be observed as discussed earlier. For patients who are initially hypertensive, the recent consensus document calls for >30 mm Hg drop of systolic pressure for a positive test. In any case, the medical history must be consistent with the laboratory findings before a reliable clinical diagnosis can be established. Tilt-table testing was derived from early physiological studies examining human responses to extended upright posture. The test was introduced in the mid-1980s as a means of assessing susceptibility to vasovagal syncope. It is usually done in a quiet room with continuous ECG and beat-to-beat blood pressure recording. The protocol calls for a 70- degree head-up tilt in a drug free state. Thereafter, if the test is not diagnostic, provocative pharmacologic agents (isoproterenol, nitroglycerin) may be used. These agents improve test sensitivity, but degrade specificity. Main indication—Assess susceptibility to vasovagal syncope in patients in whom reflex syncope is suspected clinically but could not be confirmed by history and physical findings. It should be noted that the test should not be used to assess efficacy of therapeutic interventions. -If patient had associated jerking movements but the episode is not definitive for seizure. Tilt-table testing can be helpful in distinguishing syncope from seizure. -In elderly patients with dementia where good clinical history is difficult to obtain and a fall due to loss of balance needs to be distinguished from a true syncope. -Distinguish syncope due to pure orthostatic hypotension from other causes of symptomatic hypotension (reflex syncope, some cases of postural orthostatic tachycardia syndrome [POTS]). When is the test diagnostic? The diagnosis of reflex syncope can be established when there is reproduction of symptoms with upright tilt and the recordings document sufficient hypotension (either due to marked bradycardia or due to a vasodepressor response with or without bradycardia). Contraindications: Usually safe. The contraindications are mainly relative and restricted to those conditions in which the practitioner wishes to avoid use of isoproterenol (ischemic heart disease, uncontrolled hypertension [HTN], left ventricular [LV] outflow obstruction). Nitroglycerin is a potential alternative provocative agent and has proved to be very safe. ECG monitoring is indicated for diagnosing intermittent bradyarrhythmias and tachyarrhythmias that could cause a syncopal or a near syncopal episode. It is very important to remember that ECG monitoring is indicated only when there is a high pretest probability of identifying an arrhythmia associated with syncope. ECG monitoring is done in two settings: 1. Inpatient: Inpatient monitoring is rarely useful unless the patient is having very frequent events. Given the cost of in-hospital monitoring, it is indicated only when the patient is deemed to have a high risk of life threatening arrhythmias. Such patients include those with: Acute congestive heart failure or acute myocardial infarction (present or very recent) Syncope episode associated with exertion or palpitations Family history of sudden cardiac death (SCD) Nonsustained VT on presentation Prolonged or shortened QT interval Brugada pattern on admission EKG New bifascicular block on ECG Severe sinus bradycardia on admission (HR <40 bpm) 2. Outpatient: Outpatient ECG monitoring as a rule should still be considered for patients with a high probable risk of arrhythmogenic syncope. The following types of monitoring may be considered: Holter monitoring usually for 24- to 48-hour period and sometimes for a 7-day period. This of more valuable in patients with very frequent (e.g., daily or more than once daily episodes) loss of consciousness, where there is higher chance of symptom ECG correlation. External loop recorders: These devices have loop memory and typically store 5 to 15 minutes of pre-activation ECG. The most effective of these are the mobile cardiac outpatient telemetry (MCOT) systems such as Cardionet. Patient compliance is a limitation, as some patients may not like wearing them for more than a few weeks. Implantable loop recorders: These are the ideal devices for detecting infrequent symptomatic events. They are implanted under the skin using local anesthetic in much the same way that a pacemaker is implanted, but there are no intravascular wires and the incision is only about 1.5 cm in length. The initial cost is higher than a wearable recorder, but several studies have shown that the cost per correct diagnosis is substantially less. Early use of ILRs in the evaluation of syncope is justified. Cardiac electrophysiologic study (EPS) For the evaluation of syncope, EPS has proven useful mainly in patients with underlying structural heart disease or suspected paroxysmal supraventricular tachycardia (PSVT). EPS should be considered in the following settings: In syncope in a patient with known structural heart disease in whom ventricular tachyarrhythmias are thought to be a probable cause. EPS is useful in identifying susceptibility to these arrhythmias. In syncope in patients with premonitory symptoms of palpitations (PSVT or VT are possibilities), but in whom monitoring has been ineffective. In syncope with bundle branch block to assess risk of high degree AV block playing a role. In Brugada syndrome to assess arrhythmia inducibility (a controversial indication). In asymptomatic bradyarrhythmias of sinus node origin. EPS may be useful in establishing the severity of the condition and the likelihood of sinus node disease being a contributor to symptoms (a controversial indication). Adenosine triphosphate (ATP) testing This test is controversial. It may have value in identifying a subgroup of syncope patients in whom pacing therapy might be helpful. These are usually middle-aged to older women without substantial cardiac disease. The test remains under evaluation. 1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted? Routine biochemical or hematologic laboratory studies are rarely of value in the syncope evaluation of a syncopal episode. However, in certain cases, when the initial evaluation is appropriately supportive, certain tests may have utility; these tests should be used judiciously, and their results must be consistent with the patient’s history and presentation before they can be considered to be of diagnostic utility. A basic metabolic panel can be useful in identifying prerenal azotemia, hypernatremia or hyponatremia, or hyperkalemia or hypokalemia. The first of these findings may help the clinician support a syncope diagnosis based on orthostatic hypotension due to hypovolemia/dehydration. The remaining findings could favor a conduction disturbance (i.e., inexcitable tissues in hyperkalemia) or tachyarrhythmias (e.g., torsade de pointes in hypokalemia). A complete blood count (CBC) may be helpful if the medical history supports a concern that blood loss or anemia may be provoking syncope, or increasing susceptibility to syncope, in a previously stable patient. In patients with syncope due to severe bradycardia or asystole, a thyroid function testing may be used to rule out any underlying thyroid disease. If the patient has prominent respiratory symptoms, then checking oxygen saturations and/or arterial blood gases may be useful. Although uncommon, chronic hypoxia or acute upon chronic hypoxia may predispose to symptomatic bradycardia or tachycardia. Serial cardiac enzymes can be helpful if acute myocardial ischemia is suspected to have triggered the syncope. Specific drug levels have a role to play in assessment of those infrequent syncope cases in which drug toxicity is suspected. In the past, digitalis toxicity was a relatively frequent concern, but that is far less common today. On the other hand, many drugs may be associated with syncope (Table 4) and physicians may at times need to ascertain whether one or the other agent is a contender in the differential diagnosis. 2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted? Echocardiography is often of value in the syncope evaluation when there is suspicion of structural heart disease being present. The goal is to ascertain both the nature and severity of underlying structural heart disease. The presence of cardiac disease increases the risk of a cardiac cause of syncope, and impacts prognosis as syncope of cardiac cause is associated with a worrisome mortality risk. Thus the echocardiogram has utility for both diagnosis and risk stratification. Certain conditions that may present as syncope are particularly amenable to assessment by echo; these include: valvular aortic stenosis, obstructive cardiac tumors, hypertrophic cardiomyopathy, cardiac tamponade, acute aortic dissection, and congenital anomalies of coronary arteries. CT scan of the chest is appropriate when acute pulmonary embolism is suspected as a basis for syncope. Nuclear cardiac imaging or computed tomography (CT) angiography are rarely of value in syncope patients. If acute coronary syndrome enters the differential diagnosis of a syncope patient, then coronary arteriography is a better choice. CT or magnetic resonance (MR) scans of the head have no utility in the diagnostic evaluation of syncope. In some cases they may be warranted if the patient’s collapse resulted in head injury. However, in such cases the imaging is to exclude a possible consequence of syncope, not its cause. For the most part, physicians only see syncope patients after the victim has recovered from the acute event. Consequently, it is rare that the practitioner actually witnesses the episode. However, should that occur, basic assessment of the patient entails determining if a pulse and respirations are present. If so, the victim should be maintained on his or her side in a gravitationally neutral position until full recovery of consciousness has occurred. Thereafter, documentation of the observed events is wise, as eyewitness accounts can substantially facilitate subsequent diagnostic evaluation. A. Immediate management. Inasmuch as the physician is rarely involved with care of the patient during an acute event, immediate management when the patient comes for evaluation depends primarily on the practitioner’s initial assessment as described earlier. During this step, the need for in-patient assessment versus out-patient evaluation is made. The patients who need to be considered for inpatient monitoring are mainly those with cardiac causes of syncope, in particular: Patients with suspected acute myocardial ischemia Severe ischemic or nonischemic cardiomyopathy Suspected to be high risk for life-threatening arrhythmias (e.g., long Q–T syndrome, Brugada syndrome, etc.) Other structural heart disease (e.g., hypertrophic cardiomyopathy, severe valvular disease) In patients with noncardiac causes of syncope, the need for admission may depend on the suspected cause of the fainting or social issues. Thus, while orthostatic syncope does not typically warrant admission, hospitalization may be needed if the faint was triggered by severe dehydration or acute blood loss anemia. Similarly, in-patient care may be warranted in elderly and/or frail patients who are deemed to be at high risk of physical injuries if syncope should recur. B. Physical Examination Tips to Guide Management. In most cases, the fainter is fully recovered when seen by the clinician for diagnostic evaluation. Consequently, there is rarely any opportunity to record physical findings during spontaneous events. However, eyewitness accounts can be of value, even when derived from individuals who have no specific medical training. Eyewitness reports of physical findings at the time of collapse may help distinguish true syncope from other forms of TLOC and may even help to determine the specific cause of syncope. Often, especially in older fainters, these details are not reported by the patient as they became amnestic or were unconscious. Consequently, eyewitness accounts should be sought out during the initial evaluation of the patient. Pertinent, potentially useful physical findings at the time of the collapse might include one or more of the following: The presence of seemingly inexplicable facial, tongue, or limb movements beginning before collapse favors the diagnosis of a seizure disorder, whereas jerky muscular movements that start after onset of the loss of consciousness favors a syncope diagnosis. It should be noted that “jerking” movements occur commonly in syncope patients, but the movements differ from those seen in epilepsy. In syncope, the movements tend to be smaller, of briefer duration, and not synchronous over the body. The difference from the much more massive and synchronous clonic movements can be helpful in diagnosis, but making such a distinction is beyond the experience of most bystanders including medically trained individuals. Details of the nature of the collapse may be valuable. Most syncope patients fall limply, whereas epilepsy patients tend to collapse rather more stiffly. An apparent faint in the midst of vigorous exercise suggests a cardiac cause, while faints early after completion of such exercise is more likely neural-reflex in origin (possibly triggered by relative volume depletion). Collapse associated with a rapid pulse may provide a clue to a tachyarrhythmia cause. Conversely, recognition of a slow weak pulse may lead to a greater likelihood of a bradycardia cause or neural-reflex mediated etiology. Unfortunately, not many eyewitnesses have the skill or presence of mind to make such observations. Marked pallor in conjunction with cold clammy skin favors neural-reflex syncope (vasovagal or situational syncope). Syncope associated with abrupt neck movement in older individuals (usually >50 years) suggests the possibility of carotid sinus syndrome. Collapse shortly after changing posture (e.g., arising from seated position) favors orthostatic syncope, but may not be remembered by fainters (especially older fainters). Multiple “faints” in a brief period of time, or faints with eye lids tightly closed, or faints that favor pseudosyncope rather than a true faint. Collapse associated with seeming difficulty breathing suggests a cardiac origin or pulmonary embolism. On the other hand, faints in younger individuals associated with apparent emotional upset and/or tachypnea favor reflex syncope or possibly an acute anxiety spell (pseudosyncope). Observations by the clinician in the emergency department or clinic Most often the physician is restricted to recording physical findings that remain to be observed after the victim has fully recovered. Nevertheless, certain findings may be helpful in defining potential causes for the collapse and providing a strategic direction for subsequent evaluation (i.e., specific direction for selecting imaging or other tests). Evidence of trauma resulting from the collapse should be documented. In this regard, tongue biting is more typical of seizure than of syncope. Postevent confusion is more typical of seizure, but fatigue is common after vasovagal faints. Susceptibility to orthostatic hypotension (see earlier discussion diagnostic criteria) should be obtained in all TLOC patients if circumstances permit. A positive finding, if consistent with the medical history of the event (and eyewitness accounts when available), may clinch the diagnosis without need for further testing. Physical findings during carotid sinus massage (CSM) may be considered to be part of the physical examination as it is a generally recommended diagnostic step in all older (>55 years) syncope patients. However, the results of CSM should be interpreted with care. For many years, a CSM-induced ventricular pause >3 seconds duration was been considered a positive response. However, such a finding only suggests the presence of a hypersensitive carotid sinus, but is insufficient to support a diagnosis of carotid sinus syndrome (CSS). The ESC syncope guidelines recommend that CSS be diagnosed only if there is CSM-induced reproduction of symptoms (usually only achieved if CSM is done with the patient in an upright posture), or if the clinical history supports the diagnosis (e.g., syncope associated with neck movement). In the absence of either of these findings, a CSM-induced pause >5 seconds in duration may be accepted as diagnostic if other contending diagnoses have been excluded. Pathologic cardiac and vascular murmurs, and peripheral pulse findings may be suggestive of severe aortic stenosis or idiopathic hypertrophic cardiomyopathy; if present, the significance of such murmurs may reasonably evaluated by echocardiographic study. Differences in blood pressure/pulse in each arm, when identified, may indicate subclavian steal or aortic dissection. Confirmatory imaging is then the next step. Signs of focal neurologic lesions, such as hemiparesis, dysarthria, or diplopia and vertigo, or signs of parkinsonism suggest but are not diagnostic of a neurologic cause. Thus evidence of a stroke may suggest that the collapse was not syncope, but due to loss of stability. A patient with signs of parkinsonism may raise concerns of orthostatic syncope or an accidental fall. Such patients warrant a neurologic evaluation. C. Laboratory Tests to Monitor Response To, and Adjustments in, Management. The majority of faints are neural-reflex in nature, particularly vasovagal syncope. To date, there is no evidence that tilt-table testing has any value in regard to assessing therapy of vasovagal syncope or related situational faints. Therefore, while of value as an initial diagnostic tool in selected cases of vasovagal syncope, its use in assessment of subsequent treatment is not recommended. In patients with orthostatic syncope, many current therapies have the potential to aggravate supine hypertension. This problem requires clinical monitoring and treatment adjustments. However, such monitoring is usually readily achieved in the clinic without special tests. Orthostatic testing (i.e., active standing, tilt-table testing) during follow-up might have merit in orthostatic syncope in those cases in which the medical history alone is not reliable (e.g., forgetful and/or demented patients). Similarly, periodic ECG monitoring and/or ILR use may have a role in similar cases in whom paroxysmal arrhythmias were found to be the cause of fainting. However, in most cases, a careful history is likely to be just as helpful if the patient is a reliable reporter. Follow-up hematologic or biochemical laboratory testing are rarely needed. Perhaps they can be justified if syncope was deemed due to acute blood loss, anemia, or major electrolyte disturbances (e.g., conduction system disturbances associated with severe hyperkalemia or hypokalemia, or hypovolemia). Similarly, in elderly or demented patients with syncope due to repeated but subtle infections (e.g., urinary tract infections), such testing may be warranted. Echocardiographic reassessment is also reasonable in the case of suspected outflow tract obstruction being treated medically. D. Long-term management. The principal goals of treatment in syncope patients is to avert recurrences and diminish the adverse impact of syncope recurrences on quality-of-life, including risks of injury from falls. Preventing premature mortality is also an important priority, but for the most part the risk of death is primarily determined by the severity of underlying cardiac and vascular disease rather than the syncope itself. Thus, aggressive management of structural cardiovascular disease is mandatory, but alone may not be sufficient to prevent syncope recurrences. Recommended long-term treatment strategies for the various causes of syncope may be summarized as follows: For the most part, reflex fainting has a low immediate mortality risk, and therefore the goals of long-term treatment are to prevent recurrence and limit injuries. In the case of vasovagal and situational syncope, the first step is education and assurance regarding the benign (from a mortality perspective) nature of the condition. Education consists of recognition of warning symptoms, and appropriate physical counter-maneuvers (PCMs) (e.g., sitting, squatting, leg crossing) when appropriate. The patient must also be made aware of circumstances that increase risk of an event (overcrowded places, fearful situations, prolonged cough, micturition), early recognition of prodrome symptoms. In the case of situational faints (e.g., cough syncope, post-micturition syncope, etc.) avoidance of the trigger may be difficult but can be addressed (e.g., cough suppression, sitting while voiding, etc.) In the case of CSS, education is similarly recommended. However, most CSS patients are best treated by cardiac pacemakers. PCM should be probably the first line of management for vasovagal syncope. PCMs include maneuvers that will increase the blood pressure (e.g., crossing legs, hand grip, and arm tensing) that can abort or delay attacks if performed on recognizing prodromal symptoms. In the longer-term, physical exercise (lower body isometrics, rowing), and standing training may diminish susceptibility. The pharmacologic management of reflex syncope (and especially vasovagal syncope) is at best restricted to those patients in whom hydration and physical maneuvers have not been completely successful. Only two agents appear to be helpful; specifically, midodrine and the salt retaining mineralocorticoid, fludrocortisone. Some pharmacologic treatments for vasovagal syncope are still used in clinical practice despite the fact that there is little evidence of benefit, and some have been shown to be ineffective in clinical trials. These include: Beta-adrenergic blockers (except possibly in “older” fainters (>40 years of age) The alpha-adrenergic agonist midodrine (actually a pro-drug with an active metabolite) may be effective in some patients, but is only rarely the complete answer. Attention to increased hydration, enhanced salt intake, and physical exercise remain crucial treatment components. Fludrocortisone is currently the subject of a multicenter randomized trial in vasovagal syncope where it has shown some benefit (Prevention of Syncope Trial [POST 2]). The complete article should be reported in 2012. Based on findings from several randomized clinical trials, it is clear that cardiac pacing has only a small role to play in prevention of vasovagal syncope recurrences. However, the International Study on Syncope of Uncertain Etiology (ISSUE 2) study suggests potential value in patients in whom severe spontaneous bradycardia has been demonstrated by ECG monitoring during spontaneous faints. Pacing is also useful in carotid sinus syndrome. 2. Orthostatic syncope Orthostatic syncope is an extremely common problem, especially in the elderly or frail. However, it can occur in even very fit persons who become deconditioned (e.g., astronauts returning from a low gravity environment, patients hospitalized for an extended time). The basic problem is either volume depletion or failure of the appropriate compensatory cardiac and vascular mechanisms with change from a gravitationally neutral position (i.e., seated, supine) to a standing position. In many instances, prescribed drugs undermine these compensatory responses while in others there is evidence of autonomic failure. As in the case of reflex syncope, treatment should start with education regarding the underlying condition. In many cases, removal or reduction of dosage of certain drugs that the patient is currently being treated with (e.g., diuretics, vasodilators) may be the first appropriate step. As with reflex syncope, PCMs may prove helpful acutely. Longer-term, physical exercise (lower body isometrics, rowing), and standing training may offer benefit. Unfortunately, there is a paucity of evidence favoring any of these modalities. As noted above, many prescribed drugs are in fact the cause of the problem. This aspect of “pharmacologic” therapy should be addressed first. Thereafter, drug therapy is very similar to that employed for the reflex faints. However, treatment in these often older patients is complicated by the tendency for drugs to aggravate supine hypertension. Typically, it is necessary to accept higher baseline blood pressure in this population than is normally recommended. Frequently, sustained systolic pressure in the 150 to 260 mm Hg range must be tolerated; the balance (which must be carefully discussed with patients and family members) is stroke/myocardial infarction risk versus falls and physical injury risk. With the above caveats in mind, increased salt and volume in the diet and judicious use of drugs such as midodrine and fludrocortisone may be useful. However, aggravation of supine hypertension must be monitored as noted earlier, and excessive hypertension should be dealt with in the context of the patient’s overall picture. Table 5 summarizes certain therapeutic approaches to orthostatic syncope. 3. Syncope due to cardiac arrhythmia The goals of treatment are to prolong survival, prevent recurrence, and improve quality-of-life. The specific treatment approach depends on the type of arrhythmia, and whether the problem is due to a primary conduction system disease (i.e., intrinsic abnormality) secondary to extrinsic agents (e.g., drugs, autonomic disturbances). The following provides key points to consider in treatment: In patients with syncope due to bradyarrhythmias of any cause, the first step is elimination of any drugs that may be causing or aggravating bradycardia. In symptomatic patients (i.e., syncope, near-syncope) with sinus node dysfunction (SND) and demonstrable bradyarrhythmias (i.e., sinus pauses, sinus arrest, asystole after termination of paroxysmal atrial tachyarrhythmias), cardiac pacemaker therapy is indicated and is highly effective. However, in SND patients, permanent pacing relieves symptoms but may not prolong survival. In syncope patients in whom AV conduction system disease is documented and sufficiently severe to account for symptoms, cardiac pacing should be considered. The ESC syncope guidelines provide specific pacing indications. In patients with syncope due to supraventricular tachycardias or atrial flutter, transcatheter ablation should be considered. This procedure has a very high success rate (>95%) and very few complications. In patients with acquired prolonged Q–T and syncope due to torsades de pointes, elimination of drugs that prolong Q–T interval is the essential step. In the case of congenital long Q–T syndrome, Brugada syndrome, and other channelopathies, management may entail beta-blockers in some cases and ICD therapy in others, or both. The management of these patients is in evolution and readers are advised to monitor the latest guidelines and expert consensus statements. Symptomatic ventricular tachycardias (VT) that occur in the absence of structural heart disease may in some cases be amenable to ablation (e.g., outflow tract VTs, idiopathic fascicular VTs), but often require ICD treatment (e.g., channelopathies). In patients with ischemic or nonischemic cardiomyopathies, symptomatic VT generally is treated with an ICD, although ablation may also be recommended in select cases. In these patients it is important to explain carefully to the patient and family that ICD therapy may not prevent recurrence of syncope (since it takes time to recognize and treat the arrhythmia), but does reduce risk of sudden cardiac death. Finally, while antiarrhythmic drugs no longer are the most prominent treatment strategy for VT, drugs such as beta-adrenergic blockers, amiodarone, sotalol and dofetilide often have an important ancillary role for arrhythmia prevention. 4. Syncope due to structural heart disease The goal of treatment is to prevent recurrence and reduce risk of sudden cardiac death by correcting/ameliorating the underlying structural problem. In this setting the appropriate treatment depends on establishing a correct diagnosis. For the most part, the presence of a severe structural abnormality defines the course of treatment. However, these patients also have increased risk of arrhythmic syncope, and this additional complexity must be considered in the diagnostic assessment. Severe aortic or mitral valvular stenosis, intracardiac tumors atrial myxoma, and congenital coronary artery anomalies are best treated surgically. On the other hand, conditions such as hypertrophic cardiomyopathy (HCM) are more complex. The role of drug therapy versus surgical myectomy needs individualized consideration. Nevertheless, ICD therapy is often also recommended in HCM patients presenting with syncope. E. Common Pitfalls and Side-Effects of Management Syncope is a symptom and the underlying cause needs to be correctly identified as effective treatment strategies are very specific to the underlying etiology (e.g., orthostatic syncope could be due to drug effects, autonomic failure, volume depletion, or a combination of factors. The appropriate treatment strategies differ depending on these specifics). Syncope should be clearly distinguished from other causes of TLOC, such as seizure disorders, concussion, intoxication, and syncope mimics. Failure to distinguish true syncope from other forms of TLOC may lead to incorrect therapy and inappropriate “labeling” of patients (e.g., many syncope patients have been mistakenly labeled as having drug-resistant epilepsy until the correct diagnosis was established, often years later). IV. Management with Co-Morbidities The cornerstone of syncope treatment is to identify the underlying cause and adopt a cause-specific treatment strategy. Not infrequently, comorbidities contribute to syncope susceptibility (Table 6). V. Patient Safety and Quality Measures A. Appropriate Prophylaxis and Other Measures to Prevent Readmission. The principal safety concern in patients with syncope is the risk of physical injuries due to loss of consciousness. Less frequent, but of public health importance are the risks associated with driving, flying, and operating heavy machinery. Treatment should also focus on educating the patient regarding the importance of avoiding potentially hazardous situations, and being alert for and promptly responding to warning symptoms to reduce injury risks, which include: Home and work place safety assessment may be important in some patients, particularly for elderly individuals or persons with high-risk occupations or avocations. Identification of underlying cause and distinguishing syncope from other causes of transient loss of consciousness again is the key. Accurate “risk stratification” when undergoing initial evaluation to ascertain whether a patient is suitable for outpatient assessment. Education and reassurance in patients with reflex syncope so that they do not come to the emergency room every time there is a syncopal episode. Education regarding safety precautions can help prevent dangerous injuries that trigger preventable hospital admission. B. What's the Evidence for specific management and treatment recommendations? The European Society of Cardiology Practice Guidelines (2009) provide recommendations and evidence grades in detail. Moya, A, Sutton, R, Ammirati, F. “Task Force for the Diagnosis and Management of Syncope; European Society of Cardiology (ESC); European Heart Rhythm Association (EHRA); Heart Failure Association (HFA); Heart Rhythm Society (HRS). Guidelines for the diagnosis and management of syncope (version 2009)”. Eur Heart J. vol. 30. 2009. pp. 2631-71. Strickberger, SA, Benson, DW, Biaggioni, I. “American Heart Association Councils on Clinical Cardiology; Cardiovascular Nursing, Cardiovascular Disease in the Young; Stroke; Quality of Care and Outcomes Research Interdisciplinary Working Group; American College of Cardiology Foundation; Heart Rhythm Society; American Autonomic Society. AHA/ACCF scientific statement on the evaluation of syncope”. Circulation. vol. 113. 2006. pp. 316-27. C. DRG Codes and Expected Length of Stay. ICD 10 Code—R55 Syncope is a symptom code. Do not list symptom codes as principal diagnosis when a related definitive diagnosis has been determined. Expected length of stay is variable as it depends on the underlying cause. If diagnosed as reflex syncope on initial evaluation, the patient may not need inpatient admission. There are exceptions, however, such as the older or frail individual who may not have an appropriately protective home environment. Copyright © 2017, 2013 Decision Support in Medicine, LLC. All rights reserved. No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC. The Licensed Content is the property of and copyrighted by DSM. - I. Evaluation and Management of Syncope: What every physician needs to know. - II. Diagnostic Confirmation: Are you sure your patient has Syncope? - A. History Part I: Pattern Recognition - B. History Part 2: Prevalence - C. History Part 3: Competing diagnoses that can mimic Syncope. - D. Physical Examination Findings. - E. What diagnostic tests should be performed? - 1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted? - 2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted? - III. Management. - A. Immediate management. - B. Physical Examination Tips to Guide Management. - C. Laboratory Tests to Monitor Response To, and Adjustments in, Management. - D. Long-term management. - E. Common Pitfalls and Side-Effects of Management - IV. Management with Co-Morbidities - V. Patient Safety and Quality Measures - A. Appropriate Prophylaxis and Other Measures to Prevent Readmission. - B. What's the Evidence for specific management and treatment recommendations? - C. DRG Codes and Expected Length of Stay.	2	13	0	0	2	0.917957	2	13,108
International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) provided by the Centers for Medicare and Medicaid Services (CMS) and the National Center for Health Statistics (NCHS), for medical coding and reporting in the United States. The ICD-10-CM is a morbidity classification for classifying diagnoses and reason for visits in all American health care settings. The ICD-10-CM is based on the ICD-10, the statistical classification of disease published by the World Health Organization (WHO) which replaces ICD-9. - CHAPTER I – Certain infectious and parasitic diseases (A00-B99) - CHAPTER II – Neoplasms (C00-D49) - CHAPTER III – Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism (D50-D89) - CHAPTER IV – Endocrine, nutritional and metabolic diseases (E00-E90) - CHAPTER V – Mental and behavioral disorders (F01-F99) - CHAPTER VI – Diseases of the nervous system (G00-G99) - CHAPTER VII – Diseases of the eye and adnexa (H00-H59) - CHAPTER VIII – Diseases of the ear and mastoid process (H60-H95) - CHAPTER IX – Diseases of the circulatory system (I00-I99) - CHAPTER X – Diseases of the respiratory system (J00-J99) - CHAPTER XI – Diseases of the digestive system (K00-K93) - CHAPTER XII – Diseases of the skin and subcutaneous tissue (L00-L99) - CHAPTER XIII – Diseases of the musculoskeletal system and connective tissue (M00-M99) - CHAPTER XIV – Diseases of the genitourinary system (N00-N99) - CHAPTER XV – Pregnancy, childbirth and the puerperium (O00-O99) - CHAPTER XVI – Certain conditions originating in the perinatal period (P00-P96) - CHAPTER XVII – Congenital malformations, deformations and chromosomal abnormalities (Q00-Q99) - CHAPTER XVIII – Symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified (R00-R99) - CHAPTER XIX – Injury, poisoning and certain other consequences of external causes (S00-T98) - CHAPTER XX – External causes of morbidity (V01-Y99) - CHAPTER XXI – Factors influencing health status and contact with health services (Z00-Z99) ICD 10 PCS— The ICD-10 Procedure Coding System (ICD-10-PCS) is an international system of medical classification used for procedural coding. The Centers for Medicare and Medicaid Services, the agency responsible for maintaining the inpatient procedure code set in the U.S., contracted with 3M Health Information Systems in 1995 to design and then develop a procedure classification system to replace Volume 3 of ICD-9-CM. ICD-9-CM contains a procedure classification; ICD-10-CM does not. ICD-10-PCS is the result. ICD-10-PCS was initially released in 1998. It has been updated annually since that time. HCPCS Level II codes are alphanumeric medical procedure codes, primarily for non-physician services such as ambulance services and prosthetic devices,. They represent items, supplies and non-physician services not covered by CPT-4 codes (Level I). Level II codes are composed of a single letter in the range A to V, followed by 4 digits. Level II codes are maintained by the US Centers for Medicare and Medicaid Services (CMS). There is some overlap between HCPCS codes and National Drug Code (NDC) codes, with a subset of NDC codes also in HCPCS, and vice versa. The CMS maintains a crosswalk from NDC to HCPCS in the form of an Excel file. The crosswalk is updated quarterly. Types of Level II codes The letters at the beginning of HCPCS Level II codes have the following meanings: - A-codes (example:A0021): Transportation, Medical & Surgical Supplies, Miscellaneous & Experimental - B-codes (example:B4034): Enteral and Parenteral Therapy - C-codes (example:C1300): Temporary Hospital Outpatient Prospective Payment System - D-codes: Dental Procedures - E-codes (example:E0100): Durable Medical Equipment - G-codes (example:G0008): Temporary Procedures & Professional Services - H-codes (example:H0001): Rehabilitative Services - J-codes (example:J0120): Drugs Administered Other Than Oral Method, Chemotherapy Drugs - K-codes (example:K0001): Temporary Codes for Durable Medical Equipment Regional Carriers - L-codes (example:L0112): Orthotic/Prosthetic Procedures - M-codes (example:M0064): Medical Services - P-codes (example:P2028): Pathology and Laboratory - Q-codes (example:Q0035): Temporary Codes - R-codes (example:R0070): Diagnostic Radiology Services - S-codes (example:S0012): Private Payer Codes - T-codes (example:T1000): State Medicaid Agency Codes - V-codes (example:V2020): Vision/Hearing Services The Current Procedural Terminology (CPT) code set is a medical code set maintained by the American Medical Association through the CPT Editorial Panel. The CPT code set (copyright protected by the AMA) describes medical, surgical, and diagnostic services and is designed to communicate uniform information about medical services and procedures among physicians, coders, patients, accreditation organizations, and payers for administrative, financial, and analytical purposes. New editions are released each October. The current version is the CPT 2015. It is available in both a standard edition and a professional edition. CPT coding is similar to ICD-9 and ICD-10 coding, except that it identifies the services rendered, rather than the diagnosis on the claim (ICD-10-CM was created for diagnostic coding- it took the place of Volume 3 of the ICD-9). The ICD code sets also contain procedure codes (ICD-10-PCS codes), but these are only used in the inpatient setting. CPT is currently identified by the Centers for Medicare and Medicaid Services (CMS) as Level 1 of the Healthcare Common Procedure Coding System. The Current Procedural Terminology (CPT) was developed by the American Medical Association (AMA). - 1Types of code - 1Category I - 2Category II - 3Category III	4	5	0	2	2	0.820697	4	1,465
Motion sickness occurs in connection with travel or movement when an incongruity comes about between visually perceived movement and the vestibular system's sense of bodily movement. Most kinds are considered terrestrial motion sickness, such as being carsick, airsick, seasick, or sick from reality simulation. Symptoms include dizziness, fatigue, vertigo, depressed appetite, nonspecific malaise, gastrointestinal discomfort, (most commonly) nausea, and nausea-caused vomiting (see Sopite syndrome). If the cause of the nausea is not resolved, the sufferer will usually vomit, but vomiting may not relieve the feeling of weakness and nausea, which means the person might continue to vomit until the underlying cause of the nausea is resolved. \|Other names\|\|Kinetosis, travel sickness, seasickness, airsickness, carsickness, simulation sickness, space motion sickness, space adaptation syndrome\| A specific type of motion sickness with similar symptoms but a possibly different etiology is space adaptation syndrome (sometimes referred to as space motion sickness). There are various theories that attempt to explain the cause of the condition. Sensory conflict theoryEdit At present a "fully adequate theory of motion sickness is not presently available" but contemporary sensory conflict theory, referring to "a discontinuity between either visual, proprioceptive, and somatosensory input, or semicircular canal and otolith input", is probably the most thoroughly studied. According to this theory, when the brain presents the mind with two incongruous states of motion; the result is often nausea and other symptoms of disorientation known as motion sickness. Such conditions happen when the vestibular system and the visual system do not present a synchronized and unified representation of one's body and surroundings. According to sensory conflict theory, the cause of terrestrial motion sickness is the opposite of the cause of space motion sickness. The former occurs when one perceives visually that one's surroundings are relatively immobile while the vestibular system reports that one's body is in motion relative to its surroundings. The latter can occur when the visual system perceives that one's surroundings are in motion while the vestibular system reports relative bodily immobility (as in zero gravity.) A variation of the sensory conflict theory is known as neural mismatch, implying a mismatch occurring between ongoing sensory experience and long-term memory rather than between components of the vestibular and visual systems. This theory emphasizes "the limbic system in the integration of sensory information and long-term memory, in the expression of the symptoms of motion sickness, and the impact of anti-motion-sickness drugs and stress hormones on limbic system function. The limbic system may be the neural mismatch center of the brain." Defense against perception of poisoningEdit A very different alternate is the defense mechanism theory holding that motion sickness functions as a defense mechanism against neurotoxins. The area postrema in the brain is responsible for inducing vomiting when poisons are detected, and for resolving conflicts between vision and balance. When feeling motion but not seeing it (for example, in the cabin of a ship with no portholes), the inner ear transmits to the brain that it senses motion, but the eyes tell the brain that everything is still. As a result of the incongruity, the brain concludes that the individual is hallucinating and further concludes that the hallucination is due to poison ingestion. The brain responds by inducing vomiting, to clear the supposed toxin. Treisman's indirect argument has recently been questioned via an alternative direct evolutionary hypothesis, as well as modified and extended via a direct poison hypothesis. The direct evolutionary hypothesis essentially argues that there are plausible means by which ancient real or apparent motion could have contributed directly to the evolution of aversive reactions, without the need for the co-opting of a poison response as posited by Treisman. Nevertheless, the direct poison hypothesis argues that there still are plausible ways in which the body's poison response system may have played a role in shaping the evolution of some of the signature symptoms that characterize motion sickness. Yet another theory, known as the nystagmus hypothesis, has been proposed based on stimulation of the vagus nerve resulting from the stretching or traction of extra-ocular muscles co-occurring with eye movements caused by vestibular stimulation. There are three critical aspects to the theory: first is the close linkage between activity in the vestibular system, i.e., semicircular canals and otolith organs, and a change in tonus among various of each eye's six extra-ocular muscles. Thus, with the exception of voluntary eye movements, the vestibular and oculomotor systems are thoroughly linked. Second is the operation of Sherrington's Law describing reciprocal inhibition between agonist-antagonist muscle pairs, and by implication the stretching of extraocular muscle that must occur whenever Sherrington's Law is made to fail, thereby causing an unrelaxed (contracted) muscle to be stretched. Finally, there is the critical presence of afferent output to the Vagus nerves as a direct result of eye muscle stretch or traction. Thus, 10th nerve stimulation resulting from eye muscle stretch is proposed as the cause of motion sickness. The theory explains why labyrinthine-defective individuals are immune to motion sickness; why symptoms emerge when undergoing various body-head accelerations; why combinations of voluntary and reflexive eye movements may challenge the proper operation of Sherrington's Law, and why many drugs that suppress eye movements also serve to suppress motion sickness symptoms. A recent theory argues that the main reason motion sickness occurs is due to an imbalance in vestibular outputs favoring the semicircular canals (nauseogenic) vs. otolith organs (anti-nauseogenic). This theory attempts to integrate previous theories of motion sickness. For example, there are many sensory conflicts that are associated with motion sickness and many that are not, but those in which canal stimulation occurs in the absence of normal otolith function (e.g., 0-g) are the most provocative. The vestibular imbalance theory is also tied to the different roles of the otoliths and canals in autonomic arousal (otolith output more sympathetic). Roughly one-third of the population is highly susceptible to motion sickness, and most of the rest may get motion sickness under extreme conditions. The incidence of space motion sickness has been estimated over the years at between forty and eighty percent of those who have entered weightless orbit. Several factors influence susceptibility to motion sickness, including sleep deprivation and the cubic footage allocated to each space traveler. Studies indicate that women are more likely to be affected than men, and that the risk decreases with advancing age. There is some evidence that people with Asian ancestry may suffer motion sickness more frequently compared with people of European ancestry, and there are situational and behavioral factors, such as whether a passenger has a view of the road ahead, and diet and eating behaviors. Motion sickness can be divided into three categories: - Motion sickness caused by motion that is felt but not seen, as in terrestrial motion sickness; - Motion sickness caused by motion that is seen but not felt, as in space motion sickness; - Motion sickness caused when both systems detect motion but they do not correspond, as in either terrestrial or space motion sickness. Motion is felt but not seenEdit This section does not cite any sources. (February 2018) (Learn how and when to remove this template message) A specific form of terrestrial motion sickness, being carsick is quite common and evidenced by disorientation while reading a map, a book, or a small screen during travel. Carsickness results from the sensory conflict arising in the brain from differing sensory inputs. Motion sickness is caused by a conflict between signals arriving in the brain from the inner ear, which forms the base of the vestibular system, the sensory apparatus that deals with movement and balance, and which detects motion mechanically. If someone is looking at a stationary object within a vehicle, such as a magazine, their eyes will inform their brain that what they are viewing is not moving. Their inner ears, however, will contradict this by sensing the motion of the vehicle. Varying theories exist as to cause. The sensory conflict theory notes that the eyes view motion while riding in the moving vehicle while other body sensors sense stillness, creating conflict between the eyes and inner ear. Another suggests the eyes mostly see the interior of the car which is motionless while the vestibular system of the inner ear senses motion as the vehicle goes around corners or over hills and even small bumps. Therefore, the effect is worse when looking down but may be lessened by looking outside of the vehicle. In the early 20th century, Austro-Hungarian scientist Robert Barany observed the back and forth movement of the eyes of railroad passengers as they looked out the side windows at the scenery whipping by. He called it "railway nystagmus". Also called "optokinetic nystagmus". It causes nausea and vomiting. His findings were published in the journal Laeger, 83:1516, Nov.17, 1921. Air sickness is a kind of terrestrial motion sickness induced by certain sensations of air travel. It is a specific form of motion sickness and is considered a normal response in healthy individuals. It is essentially the same as carsickness but occurs in an airplane. An airplane may bank and tilt sharply, and unless passengers are sitting by a window, they are likely to see only the stationary interior of the plane due to the small window sizes and during flights at night. Another factor is that while in flight, the view out of windows may be blocked by clouds, preventing passengers from seeing the moving ground or passing clouds. Seasickness is a form of terrestrial motion sickness characterized by a feeling of nausea and, in extreme cases, vertigo experienced after spending time on a watercraft such as a boat or ship. It is essentially the same as carsickness, though the motion of a watercraft tends to be more regular. It is typically brought on by the rocking motion of the craft or movement while the craft is immersed in water. As with airsickness, it can be difficult to visually detect motion even if one looks outside the boat since water does not offer fixed points with which to visually judge motion. Poor visibility conditions, such as fog, may worsen seasickness. The greatest contributor to seasickness is the tendency for people being affected by the rolling or surging motions of the craft to seek refuge below decks, where they are unable to relate themselves to the boat's surroundings and consequent motion. Some sufferers of carsickness are resistant to seasickness and vice versa. Adjusting to the craft's motion at sea is called "gaining one's sea legs"; it can take a significant portion of the time spent at sea after disembarking to regain a sense of stability "post-sea legs". Centrifuge motion sicknessEdit Rotating devices such as centrifuges used in astronaut training and amusement park rides such as the Rotor, Mission: Space and the Gravitron can cause motion sickness in many people. While the interior of the centrifuge does not appear to move, one will experience a sense of motion.[dubious ] In addition, centrifugal force can cause the vestibular system to give one the sense that downward is in the direction away from the center of the centrifuge rather than the true downward direction. Dizziness due to spinningEdit When one spins and stops suddenly, fluid in the inner ear continues to rotate causing a sense of continued spinning while one's visual system no longer detects motion. Virtual reality disorientationEdit Usually, VR programs would detect the motion of the user's head and abject the rotation of vision to avoid dizziness. However, some cases such as system lagging or software crashing could cause lags in the screen updates. In such cases, even some small head motions could trigger the motion sickness by the defense mechanism that mentioned above:The inner ear transmits to the brain that it senses motion, but the eyes tell the brain that everything is still.As a result of the incongruity, the brain concludes that the individual is hallucinating and further concludes that the hallucination is due to poison ingestion. The brain responds by inducing vomiting, to clear the supposed toxin. Motion seen but not feltEdit In these cases, motion is detected by the visual system and hence the motion is seen, but no motion or little motion is sensed by the vestibular system. Motion sickness arising from such situations has been referred to as "visually induced motion sickness" (VIMS). Zero gravity interferes with the vestibular system's gravity-dependent operations, so that the two systems, vestibular and visual, no longer provide a unified and coherent sensory representation. This causes unpleasant disorientation sensations often quite distinct from terrestrial motion sickness, but with similar symptoms. The symptoms may be more intense because a condition caused by prolonged weightlessness is usually quite unfamiliar. Space motion sickness was effectively unknown during the earliest spaceflights because the very cramped conditions of the spacecraft allowed for only minimal bodily motion, especially head motion. Space motion sickness seems to be aggravated by being able to freely move around, and so is more common in larger spacecraft. Around 60% of Space Shuttle astronauts currently experience it on their first flight; the first case of space motion sickness is now thought to be the Soviet cosmonaut Gherman Titov, in August 1961 onboard Vostok 2, who reported dizziness, nausea, and vomiting. The first severe cases were in early Apollo flights; Frank Borman on Apollo 8 and Rusty Schweickart on Apollo 9. Both experienced identifiable and quite unpleasant symptoms-—in the latter case causing the mission plan to be modified. Disorientation from films, video games, and other screen imagesEdit This type of terrestrial motion sickness is particularly prevalent when susceptible people are watching films presented on very large screens such as IMAX, but may also occur in regular format theaters or even when watching TV or playing games. For the sake of novelty, IMAX and other panoramic type theaters often show dramatic motions such as flying over a landscape or riding a roller coaster. This type of motion sickness can be prevented by closing one's eyes during such scenes. In regular-format theaters, an example of a movie that caused motion sickness in many people is The Blair Witch Project. Theaters warned patrons of its possible nauseating effects, cautioning pregnant women in particular. Blair Witch was filmed with a handheld camcorder, which was subjected to considerably more motion than the average movie camera, and lacks the stabilization mechanisms of steadicams. Home movies, often filmed with a cell phone camera, also tend to cause motion sickness in those who view them. The person holding the cell phone or other camera usually is unaware of this as the recording is being made since the sense of motion seems to match the motion seen through the camera's viewfinder. Those who view the film afterward only see the movement, which may be considerable, without any sense of motion. Using the zoom function seems to contribute to motion sickness as well since zooming is not a normal function of the eye. The use of a tripod or a camera or cell phone with image stabilization while filming can reduce this effect. Virtual reality disorientationEdit Terrestrial motion sickness due to virtual reality is very similar to simulation sickness and motion sickness due to films. In virtual reality the effect is made more acute as all external reference points are blocked from vision, the simulated images are three-dimensional and in some cases stereo sound that may also give a sense of motion. The NADS-1, a simulator located at the National Advanced Driving Simulator, is capable of accurately stimulating the vestibular system with a 360-degree horizontal field of view and 13 degrees of freedom motion base. Studies have shown that exposure to rotational motions in a virtual environment can cause significant increases in nausea and other symptoms of motion sickness. In a study conducted by the U.S. Army Research Institute for the Behavioral and Social Sciences in a report published May 1995 titled "Technical Report 1027 - Simulator Sickness in Virtual Environments", out of 742 pilot exposures from 11 military flight simulators, "approximately half of the pilots (334) reported post-effects of some kind: 250 (34%) reported that symptoms dissipated in less than one hour, 44 (6%) reported that symptoms lasted longer than four hours, and 28 (4%) reported that symptoms lasted longer than six hours. There were also four (1%) reported cases of spontaneously occurring flashbacks." Motion that is seen and felt but whose visual and bodily perception is incongruousEdit When moving within a rotating reference frame such as in a centrifuge or environment where gravity is simulated with centrifugal force, the coriolis effect causes a sense of motion in the vestibular system that does not match the motion that is seen. Many cures and preventatives for motion sickness have been proposed. A motion blocking eyewear device was patented (US patent 6,275,998) to prevent carsickness-related terrestrial motion sickness. Visual cues are an important contributor to land-based vehicular travel in addition to vestibular (inner ear) input. The eyewear device limits what the wearer sees outside the moving vehicle by use of an opaque shield. By removing visual cues outside the vehicle, the device normalizes the visual input dimension involved in sensory conflict, a leading theory behind motion sickness. No evidence exists that motion blocking eyewear alters or eliminates vestibular input or that of other bodily receptors. Carsickness is the most common type of motion sickness given the number of travelers traveling over land versus those traveling by air or sea. A head-worn, computer device with a transparent display can be used to mitigate the effects of motion sickness (and spatial disorientation) if visual indicators of the wearer’s head position are shown. Such a device functions by providing the wearer with digital reference lines in their field of vision that indicate the horizon’s position relative to the user’s head. This is accomplished by combining readings from accelerometers and gyroscopes mounted in the device (US Patent 5,966,680). This technology has been implemented in both standalone devices and Google Glass. In two NIH-backed studies, greater than 90% of patients experienced a reduction in the symptoms of motion sickness while using this technology. Experiments with adaptation to reversion or inversion of the field of view showed the possibility of preliminary adaptation to the conflicts of the visual analyzer with other signals entering from vestibular system. Thus, NASA experts confirmed the recommendations of Hubert Dolizal, who studied the adaptation to optical transformations of the visual field. The recommendations consisted in the preliminary training of astronauts, pilots and people of other specialties, whose activity is connected with vestibular conflicts, with the help of an upside down goggles, a device for inverting the visual field. The vestibular-ocular stage of adaptation to the inversion of the visual field is likely to act as seasickness preventive procedure This article needs additional citations for verification. (May 2017) (Learn how and when to remove this template message) One common suggestion is to simply look out the window of the moving vehicle and to gaze towards the horizon in the direction of travel. This helps to re-orient the inner sense of balance by providing a visual reaffirmation of motion. In the night, or in a ship without windows, it is helpful to simply close one's eyes, or if possible, take a nap. This resolves the sensory conflict between the eyes and the inner ear. Napping also helps prevent psychogenic effects (i.e. the effect of sickness being magnified by thinking about it). Fresh, cool air can also relieve motion sickness slightly, although it is likely this is related to avoiding foul odors which can worsen nausea. While playing computer games, and mainly in first-person shooter games, some cases of simulation sickness can be resolved by changing the field of view in the game. Some games have a default setting which places a player's vision a small distance ahead of the actual object controlled, which will most likely trigger simulation sickness. Over-the-counter and prescription medications are readily available, such as dimenhydrinate commonly known as dramamine, scopolamine, meclizine, promethazine, cyclizine, and cinnarizine. Several of these are antihistamines, with mild sedation being a common side effect. Cinnarizine is not available in the United States, as it is not approved by the FDA. As these medications often have side effects, anyone involved in high-risk activities while at sea (such as SCUBA divers) must evaluate the risks versus the benefits. Promethazine is especially known to cause drowsiness, which is often counteracted by ephedrine in a combination known as "the Coast Guard cocktail". There are special considerations to be aware of when the common anti-motion sickness medications are used in the military setting where performance must be maintained at a high level. Scopolamine is effective and is sometimes used in the form of transdermal patches (1.5 mg) or as a newer tablet form (0.4 mg). The selection of a transdermal patch or scopolamine tablet is determined by a doctor after consideration of the patient's age, weight, and length of treatment time required. Many pharmacological treatments which are effective for nausea and vomiting in some medical conditions may not be effective for motion sickness. For example, metoclopramide and prochlorperazine, although widely used for nausea, are ineffective for motion-sickness prevention and treatment. This is due to the physiology of the CNS vomiting centre and its inputs from the chemoreceptor trigger zone versus the inner ear. Sedating anti-histamine medications such as promethazine work quite well for motion sickness, although they can cause significant drowsiness. As astronauts frequently have motion sickness, NASA has done extensive research on the causes of and treatments for motion sickness. One very promising looking treatment is for the person suffering from motion sickness to wear LCD shutter glasses that create a stroboscopic vision of 4 Hz with a dwell of 10 milliseconds. - Woodhouse's English-Greek Dictionary Page 745 - Woodhouse's English-Greek Dictionary Page 766 - Kohl, R. L. 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What is the ICD-10 code for hypotonia? P94. 2 is a billable/specific ICD-10-CM code that can be used to indicate a diagnosis for reimbursement purposes. What does hypotonia mean? Definition. Hypotonia is a medical term used to describe decreased muscle tone. Normally, even when relaxed, muscles have a very small amount of contraction that gives them a springy feel and provides some resistance to passive movement. What is the ICD-9 code for malnutrition? Table 5ICD-9-CM diagnosis codes for malnutrition \|263.2\|\|Arrested development following protein-calorie malnutrition\| \|263.8\|\|Other protein-calorie malnutrition\| \|263.9\|\|Unspecified protein-calorie malnutrition\| What is the ICD-10 code for developmental delay? 2021 ICD-10-CM Diagnosis Code R62. 50: Unspecified lack of expected normal physiological development in childhood. What are the symptoms of hypotonia? An adult with hypotonia may have the following problems: - clumsiness and falling frequently. - difficulty getting up from a lying or sitting position. - an unusually high degree of flexibility in the hips, elbows and knees. - difficulty reaching for or lifting objects (in cases where there’s also muscle weakness) What is congenital hypotonia? Hypotonia means decreased muscle tone. It can be a condition on its own, called benign congenital hypotonia, or it can be indicative of another problem where there is progressive loss of muscle tone, such as muscular dystrophy or cerebral palsy. It is usually detected during infancy. Can a child outgrow hypotonia? Kids With Hypotonia Will Outgrow It Kids with hypotonia become adults with hypotonia. Along the way, they’ve simply learned how to compensate for their limitations. But without proper hypotonia treatment, poor alignment and other long-term problems can develop. Can babies with hypotonia walk? A child with hypotonia often takes longer to reach motor developmental milestones, such as sitting up, crawling, walking, talking, and feeding themselves. Which code is used for the diagnosis of infantile autism? F84. 0 is a billable/specific ICD-10-CM code that can be used to indicate a diagnosis for reimbursement purposes. What is the ICD 10 code for severe protein-calorie malnutrition? Coding professionals would use ICD-10-CM code E43 to report severe malnutrition, also known as starvation edema. They would use ICD-10-CM code E42 to report severe protein-calorie malnutrition with signs of both kwashiorkor and marasmus. What are the four types of developmental disabilities? There are four main types of developmental disorders: nervous system disabilities, sensory related disabilities, metabolic disabilities and degenerative disorders. Many different subsets of disabilities nest under these four main groups. What is mixed developmental disorder? A specific category of LD, called Mixed Specific Developmental Disorders is characterized by the co-presence of specific developmental disorders of speech and language, of scholastic skills, and of motor function, without a clear predominance of one disorder over the others.	4	3	0	0	10	0.87741	10	681
Health services framework and competent authoritiesHealthcare bodies Describe the bodies and their responsibilities (public and private sector) concerned with the delivery of healthcare and appropriate products for treatment. The responsibility for healthcare in Sweden is divided between the government, the Swedish county councils and local municipalities. On a governmental level, the Ministry of Health and Social Affairs is responsible for all policies related to social welfare in Sweden, including policies regarding the delivery of healthcare. The Ministry of Health and Social Affairs works in concert with various national government agencies, such as the National Board of Health and Welfare, which is responsible for all social services, health and medical services, patient safety and epidemiology, and the Health and Social Care Inspectorate, which is responsible for supervising healthcare and social care, as well as healthcare care staff. On a regional level, the Swedish county councils are responsible for the financing and delivering of healthcare services to citizens. The healthcare is then, by agreement with the county councils, provided by private and public healthcare providers. Care of elderly and disabled persons is, however, provided locally by the Swedish municipalities. When it comes to appropriate products for treatment, the Medical Products Agency (MPA) is responsible for regulation and surveillance of the development, manufacturing and sale of medicinal drugs, medical devices and cosmetics. The Social Care Inspectorate is responsible for the supervision of self-made medical devices as well as the way in which medical devices and medicinal products are prescribed, put into use, used and handled.Competent authorities for authorisation Identify the competent authorities for approval of the marketing of medicinal products and medical devices. What rules apply to deciding whether a product falls into either category or other regulated categories? The MPA is the competent authority for approval of the marketing of new medicinal products and market entry for medical devices in Sweden. The main regulatory frameworks for medicinal products are the Medicinal Products Act (2015:315) and the Medicinal Products Ordinance (2015:458), which are based on EU Directives 2001/83/EC and 2001/82/EC (the Medicinal Products Directives). The definition of ‘medicinal product’ corresponds with the definition in the Medicinal Products Directives. For more details regarding the framework for medicinal products, see the EU chapter. The main regulatory frameworks for medical devices are the Medical Devices Act (1993:584) and Medical Devices Ordinance (1993:876), which are based on EU Directives 90/385/EEC, 93/42/EEC and 98/79/EC (the Medical Device Directives). For more details regarding the framework for medical devices in the Medical Device Directives, and the new EU Regulations 2017/745 and 2017/746 coming into force in May 2020, see the EU chapter. In short, the intended use and the mechanisms of action of the device control whether a device constitutes a medical device or not. The difference between a medicinal product and medical device is that, whereas the mode of action of a medicinal product is pharmacological, immunological or metabolic, medical devices work by other means; for example, by a physical or mechanical mode of action. As for cosmetics, EU Regulation (EC) No. 1223/2009 on cosmetic products is implemented in Swedish law by the Ordinance on cosmetic products (2013:413). The Regulation (and the Ordinance) defines cosmetic products as any substance or mixture intended to be placed in contact with the external parts of the human body exclusively or mainly to clean it, perfume it, change its appearance, protect it, keep it in good condition or to correct body odours. The main distinction between medicinal products and cosmetic products is thus that cosmetic products are applied externally without any intended internal effects; if a product is applied externally but has an intended internal effect it is no longer a cosmetic product. All cosmetic products must comply with the Swedish Environmental Code (1998:808) and the Swedish Environmental Inspection Regulation (2011:13). Food supplements are regulated by food laws and regulations in Sweden. However, if the purpose of a food supplement is to prevent or treat disease, or to adjust or modify physiological functions by pharmacological, immunological or metabolic mode of action (ie, in accordance with the definition of ‘medicinal product’ mentioned above), it shall be classified as a medicinal product.Approval framework Describe the general legislative and regulatory framework for approval of marketing of medicinal products and medical devices. All medicinal products in Sweden must be approved by the MPA, sometimes in concert with other medicinal products agencies in other EU member states, or the EU Commission. The requirements for the approval of new medicinal products included in the Medicinal Products Act are based on and correspond with the requirements set forth in the Medicinal Products Directives. For more details regarding the requirements for approval of new medicinal products in the Medicinal Products Directives, see the EU chapter. All medicinal products need to be of good quality and be appropriate as well as effective in order to obtain a marketing authorisation. The application procedure for clearance by the MPA is included in MPA Regulation LVFS 2011:19. Medical devices do not need approval by the MPA. Instead, market access is conditional upon CE marking. According to MPA Regulation LVFS 2003:11, some medical devices must, however, be registered by the MPA; for example, in vitro diagnostic products and some categories of medical devices as set out in the Regulation. This registration does not mean, however, that the MPA has approved the medical device. All medical devices must, however, comply with the requirements in the Medical Devices Act, which is based on and corresponds with the Medical Device Directives. For more details regarding the requirements for medical devices, see the EU chapter. A medical device needs to be safe and fit for its designated purpose. A medical device that meets the requirements shall be provided with a CE marking. All labelling and instructions for use of medical devices must be written in Swedish according to MPA Regulations LVFS 2001:5, LVFS 2003:11 and LVFS 2001:7. As for medicinal products, there are detailed provisions regarding labelling in LVFS 2005:11, which prescribes that the labelling on the outer package and the container shall be in Swedish. Clinical practiceApplicable rules What legislation controls and which rules apply to ethics committee approval and performance of clinical trials in your territory for medicinal products and medical devices? Primarily, the Medicinal Products Act, the Medicinal Products Ordinance, the Ethical Review Act (2003:460) and MPA Regulation LVFS 2011:19 on clinical trials, which refers to Directives 2001/20/EC and 2005/28/EC regarding good clinical practice, apply to ethics committee approval and performance of clinical trials. The Swedish Association of the Pharmaceutical Industry (LIF) has also issued a framework for ethical rules for the pharmaceutical industry in Sweden (the LER Rules), which contain specific rules on conducting clinical trials. All clinical trials of medicinal products must follow the European Medicines Agency (EMA) Guideline on Strategies to Identify and Mitigate Risks for First-in-Human Clinical Trials with Investigational Medicinal Products. Applications are filed with the Swedish Ethical Review Authority. New EU Regulation No. 536/2014 on clinical trials, replacing EU Directive 2001/20/EC, entered into force on 16 June 2014. However, its application is awaiting the development of a fully functional EU clinical trials portal and database. For the purpose of implementing the new Regulation, the Swedish government has prepared the Additional Provisions on Ethical Review for the EU Regulation on Clinical Trials Act 2018:1091, which is ready to come into force. As for medical devices, clinical trials for the purpose of creating documentation for CE marking are primarily regulated by the Medical Devices Act, the Medical Devices Ordinance, MPA Regulations LVFS 2003:11 on active implants and LVFS 2001:5 on medical devices. All clinical trials for medical devices should be in line with the Swedish standards SS-EN 12155:2011 (for clinical trials) and SS-EN ISO 14971:2012 (for risk management). Furthermore, all clinical trials for medicinal products and medical devices must be conducted in accordance with the latest version of the World Medical Association’s Declaration of Helsinki and be registered with the European Clinical Trials Register.Reporting requirements What requirements exist for reporting the commencement of a trial and its results to the competent authorities or the public? Clinical trials for medicinal products and medical devices require prior approval from both the MPA and an ethics committee (the Swedish Ethical Review Authority). For medicinal products, the reporting of the commencement of a trial to the MPA shall be made through an application document accompanied with a clinical investigation plan and other required information in accordance with the Medicinal Products Act and MPA Regulation LVFS 2011:9. For medical devices, the reporting of the commencement of a trial to the MPA shall be made through an application document accompanied with a clinical investigation plan and other required information in accordance with the Medical Devices Act and MPA Regulations LVFS 2003:11 on medical devices and LVFS 2001:5 on active implants. The results of clinical trials for medicinal products shall be reported to the European Clinical Trials Database (EudraCT); for more information, see the EU chapter. The results of clinical trials of medical devices shall be concluded in a complete report to be provided to the MPA upon request.Consent and insurance Are there mandatory rules for obtaining trial subjects’ consent to participate? Must sponsors arrange personal injury insurance to a particular limit? For clinical trials on medicinal products, consent must be obtained from all trial subjects according to the Medicinal Products Act. Furthermore, the sponsor of the clinical trial for medicinal products must guarantee financial protection for potential damages or reimbursements, through insurance or otherwise. For medical devices, MPA Regulations LVFS 2003:11 on medical devices and LVFS 2001:5 on active implants require that clinical trials are conducted in accordance with the Declaration of Helsinki, which requires consent from all trial subjects. Marketing authorisationTime frame How long does it take, in general, to obtain an authorisation from application to grant, what fees are payable and what is the normal period of validity of the authorisation? In Sweden, being a part of the EU, an application to obtain market authorisation for medicinal products can be made by four different procedures; - a centralised procedure; - a mutual recognition procedure; - a decentralised procedure; and - a national procedure. In the centralised procedure, the assessment is made by the two national competent authorities appointed by the Committee for Veterinary Medicinal Products or the Committee for Medicinal Products for Human Use. The assessment shall be completed within 210 days. The final opinion is forwarded to the EU Commission for decision. Authorisation of medicinal products via the centralised procedure will entitle the companies in question to sell these products throughout the European Economic Area (EEA). By the mutual recognition procedure, a company may request that an existing national authorisation shall be recognised in other EEA countries. The application is assessed by the competent authority where authorisation has already been granted (reference member state (RMS)) and the competent authority in the country where the authorisation shall be extended (concerned member state (CMS)). The total processing time may not exceed 90 days. The general application fee for a complete application is 120,000 Swedish kronor when Sweden is the CMS and 200,000 Swedish kroner when Sweden is the RMS. An extension of an existing authorisation is 200,000 Swedish kronor if Sweden is the RMS or 65,000 Swedish kronor if Sweden is the CMS. There is also a yearly fee, in general, amounting to 51,000 Swedish kronor for authorised medicinal products. The decentralised procedure is applicable in cases where a company wishes to obtain marketing authorisations in a number of EEA countries for a medicinal product that has no previous authorisation. The application is assessed and approved by an RMS selected by the company and approved concurrently by the selected countries (CMS). The assessment shall be completed within 210 days. The application fees are the same as for the mutual recognition procedure. Through the national procedure, a right to marketing in one single country only can be obtained. The assessment by the MPA shall be completed within 210 days after the MPA has validated the application as complete (the validation period is 14 days). The general application fee is 500,000 Swedish kronor, an extension of an existing authorisation amounts to 200,000 Swedish kronor, and the yearly fee amounts to 51,000 Swedish kronor. There is no requirement for marketing authorisation for medical devices. For some categories of medical devices, both the company and the product must, however, be registered with the MPA. The review period is approximately two months from the time a complete application is received. According to the Ordinance on Medical Devices, the company registration fee is 2,150 Swedish kronor per year. Annual registration fees for products are as follows: - for 10 products: 1,000 Swedish kronor; - for 100 products: 2,000 Swedish kronor; - for 500 products: 5,000 Swedish kronor; and - for more than 500 products: 10,000 Swedish kronor. What protection or exclusivities apply to the data submitted by originators to gain initial approval and, on variation or new application, to add indications or pharmaceutical forms? Data exclusivity is regulated by EU Regulation (EC) No. 726/2004; see the EU chapter.Freedom of information To what extent and when can third parties make freedom of information applications for copies of research data submitted by applicants for authorisation to market medicinal products or medical devices? This is regulated by EU Regulation (EC) No. 726/2004; see the EU chapter.Regulation of specific medicinal products Are there specific rules for approval, and rewards or incentives for approval, of particular types of medicinal products, such as traditional herbal and homeopathic products, biologicals and biosimilars, controlled drugs, orphan drugs and those for paediatric use? MPA Regulation HSLF-FS 2017:75 shall be complied with when registering homeopathic medicinal products. The Regulation is based on articles 14 and 15 of the Medicinal Products Directives. As for herbal medicinal products (ie, medicinal products in which the active ingredient consists exclusively of herbal materials or herbal preparations), these also fall within the scope of the Medicinal Products Directives. Furthermore, MPA Regulation LVFS 2006:3 applies. When it comes to biologicals and biosimilars, the criteria for approval is specified in various guidance papers issued by the EMA. As regards orphan drugs and products for paediatric use, see the EU chapter.Post-marketing surveillance of safety What pharmacovigilance or device vigilance obligations apply to the holder of a relevant authorisation once the product is placed on the market? For medical devices, authorisation holders are required to continuously monitor how their products work in practical use and are obliged to report accidents and incidents when there is a suspicion that the medical device may be involved in the event, according to the Medical Devices Directives, which are implemented by MPA Regulations LVFS 2003:11, 2001:5 and 2001:7. Authorisation holders must also report any corrective safety measures on products that have been placed on the market. For medicinal products, there is a requirement to update product information in relation to new knowledge. In cases of non-compliance, the MPA may send a request regarding post-authorisation control of a medicinal product with demands for updates. Avoiding answering such a request might result in an injunction and other consequences, such as deregistration of the product. Furthermore, there is a requirement for periodic safety update recording in accordance with EU Regulation No. 1235/2010, Directive 2010/84/EU and Commission Implementing Regulation (EU) No. 520/2012, implemented by MPA Regulation LVFS 2012:14. See the EU chapter for more details regarding periodic safety update recording.Other authorisations What authorisations are required to manufacture, import, export or conduct wholesale distribution and storage of medicinal products and medical devices? What type of information needs to be provided to the authorities with an application, what are the fees, and what is the normal period of validity? For medicinal products, a licence from the MPA is required for the manufacturing, import from and export to a country outside the EEA of medicinal products according to the Medicinal Products Act. The requirements for such authorisation are included in MPA Regulation LVFS 2004:7. For example, the application needs to include: - general information regarding the applicant (such as name, registration certificate and billing address); - whether the application concerns a certain medicinal product or medicinal products in general; - the form of medicinal product or products; - the location of the premises; - details regarding the premises and equipment; - a description of potential contract manufacturing or contractual analysis; and - a proposal for an expert or adviser and his or her curriculum vitae. A decision on an application shall in general be made by the MPA within 30 days of the submission of a complete application (this period can be prolonged to 90 days). The general application fee for manufacturing is 65,000 Swedish kronor and the yearly fee is, in general, 60,000 to 80,000 Swedish kronor. The licence is valid for as long as the yearly fees are paid; however, not for a period longer than that indicated in the decision. For medical devices, manufacturers are obliged to register certain forms of medical devices with the MPA in accordance with that outlined under section 3 (the term ‘manufacturer’ also includes import of products outside the EEA). There is, however, no licence required for manufacturing or importing medical devices. Naturally, and in accordance with the Medical Devices Directives, medical devices with the appropriate CE marking may be exported freely within the EEA. Countries outside the EEA may, however, request a ‘free sales certificate’, which ensures that the product may be exported without any legal restrictions. The MPA can issue such certificates. The application fee is 950 Swedish kronor. The period of validity is commonly three years or the time period of the CE marking.Sanctions What civil, administrative or criminal sanctions can authorities impose on entities or their directors and officers for breach of the requirements concerning controlled activities? The MPA has the authority to issue injunctions and prohibitions necessary to ensure compliance with the Medicinal Products Act and Medical Devices Act, and may combine such injunctions with a penalty fine. As for criminal sanctions, violations of the Medicinal Products Act and the Medical Devices Act are penalised with a fine or imprisonment for a maximum of one year.Exemptions What, if any, manufacture and supply of medicinal products is exempt from the requirement to obtain an approval to market? There is an exemption from the marketing authorisation requirement for advanced therapy medicinal products defined in article 2 of EU Regulation (EC) No. 1394/2007, which are produced in Sweden in accordance with a non-routine procedure, for a certain patient in accordance with a prescription, and which are used in Swedish hospitals. A licence is required in accordance with the Medicinal Products Act and MPA Regulation LVFS 2011:3. For unlicensed medicinal products, see question 27.Parallel trade Are imports allowed into your jurisdiction of finished products already authorised in another jurisdiction, without the importer having to provide the full particulars normally required to obtain an authorisation to market? What are the requirements? Parallel import of medicinal products from other EEA countries to Sweden (which have been approved in the other EEA country through the national procedure, the mutual recognition procedure or the decentralised procedure) is allowed but requires authorisation from the MPA in accordance with Regulation LVFS 2012:19, and must comply with the labelling requirements in the Regulation. Medicinal products that have been approved through the central procedure may instead be parallel distributed, which is authorised by the EMA; see the EU chapter for more details. Parallel import of medical devices does not require authorisation from the MPA. However, all labelling and instructions for use of medical devices must be written in Swedish (MPA Regulations LVFS 2001:5, LVFS 2003:11 and LVFS 2001:7). What are the main requirements relating to variation of authorisations for medicinal products and medical devices? EU Regulation (EC) No. 1234/2008 regulates variations to a marketing authorisation for approved medicinal products; see the EU chapter. This is not applicable to medical devices.Renewal What are the main requirements relating to renewal of authorisations for medicinal products and medical devices? A marketing authorisation for medicinal products is valid for five years and may be renewed after this period. One renewal after five years is usually sufficient for continued validity until further notice; however, the authority may, for safety reasons, decide that a further renewal is required. The application for a renewal must be received by the MPA no later than nine months before the renewal date for medicinal products for human use, and six months before the renewal date for veterinary medicinal products. The application must include documentation regarding the efficacy, safety and quality (including detailed pharmacovigilance data) as well as a list of all changes made since the first authorisation or last renewal. This is not applicable to medical devices.Transfer How easy is it to transfer the existing approvals or rights to market medicines and medical devices? How long does this take in general? Application for transfer requires submission of an application form (available on the MPA’s website), which shall be accompanied by a wholesale licence for the new marketing authorisation holder, proof of establishment of the new marketing authorisation holder, summary of product characteristics and patient information leaflet and labelling text with tracked changes (if applicable), the latest approved version of the mock-ups and the new final version (if applicable). The time period of assessment by the MPA is three months. This is not applicable to medical devices. RecallDefective and unsafe products What are the normal requirements for handling cases of defective or possibly unsafe products, including approvals required for recall and communication with health professionals? Manufacturers of medical devices are obliged to report serious incidents with CE-marked devices in Sweden to the MPA, according to MPA Regulations LVFS 2001:5, LVFS 2003:11 and LVFS 2001:7 (and the corresponding Medical Device Directives). The manufacturer shall also be informed of corrective safety measures that are taken by the manufacturer, including recalls (field safety corrective actions). Requirements on the vigilance reporting system are to be found in the EU Commission Guide MEDDEV 2.12/1. For medicinal products, according to the Medicinal Products Act, the MPA is authorised to make decisions regarding their recall. The provisions regarding recall in the Medicinal Products Act are based on the Medicinal Products Directives. Summarise the rules relating to advertising and promotion of medicinal products and medical devices, explaining when the provision of information will be treated as promotional. Do special rules apply to online advertising? The Medicinal Products Act contains specific provisions on marketing of medicinal products, while the Marketing Practices Act relates to marketing in general (thus, including marketing of medicinal products and medical devices). The new EU Regulations 2017/745 and 2017/746 on medical devices prescribe a prohibition on misleading marketing of medical devices. In short, the definition ‘advertising of medicinal products’ described in the Medical Products Directives corresponds to the interpretation of when the provision of information will be treated as promotional according to the Medicinal Products Act. In addition, MPA Regulation LVFS 2009:6 lists several measures that specifically should be included in the definition of marketing of medicinal products. MPA Regulation LVFS 2009:6 also lists several measures that are not to be deemed as marketing of medicinal products. These measures also correspond to the measures mentioned in the Directives; see the EU chapter. The Marketing Practices Act applies to any kind of marketing, including online marketing. Under the Marketing Practices Act, the term ‘advertising’ is seen as part of the broader term ‘marketing’. Even the sale itself, even though entirely passive, is considered to be a marketing measure. In addition, measures that aim to promote the supply of products are included in the definition. The LER Rules by LIF also include rules regarding information of medicinal products. Further, if a company is subject to the LER Rules, it will be able to apply for a prior permission from the Swedish Pharmaceutical Industry’s Information Examiner Committee (IGN) to provide information regarding the medicinal product on a special website. The information provided on the website has to be reviewed by the IGN before it is published and before any changes can be made. Due to the prohibition of advertising of medicinal products directly towards consumers, companies are not allowed to refer to, or in any way promote, their informational website. This means that consumers will have to find the website on their own.Inducement What regulations exist to discourage the provision of inducements to healthcare professionals to prescribe, sell, supply or recommend use of a particular medicinal product or medical device? In addition to general criminal rules on bribes that follow from the Swedish Penal Code (1962:700), the LER Rules provide for specific regulations relating to inducements to healthcare professionals in regard to medicinal products. Any form of cooperation between healthcare professionals and pharmaceutical companies where there has been some kind of remuneration shall be documented. Donations made by the company are only permitted if they are supporting research and development. The only gifts that are permitted are informational and educational material, under the condition that the material is of low value, directly relevant to the practice of the recipient and directly beneficial to the care of patients. Items of medical utility may be provided for purposes of educating employees and for the care of patients under the condition that the item is of low value and not such that it is routinely used in the recipient’s business. Furthermore, it is not permitted to provide healthcare professionals with an inexpensive gift unrelated to the practice of medicine on an infrequent basis in acknowledgement of significant national, cultural or religious holidays. For medical device companies, according to the cooperation agreement entered into with, inter alia, LIF, it is not permitted to offer benefits, gifts or other compensation to healthcare professionals. Gifts offered to medical entities (such as hospitals) that could be considered as indirect gifts to the healthcare professionals working within the medical entity are, accordingly, also prohibited. Donations may never be offered or requested to fund healthcare’s internal or regular activities. Donations to healthcare are allowed only if they are made to support research and development and under the condition that the donation is transparent, well-documented and in accordance with the cooperation agreement and its intentions. There is a specific rule in the industry code stating that ‘donations and grants to healthcare shall not be connected to past, present or potential future use, recommendation, sale or prescription of the donor’s products or services, and may not constitute an inducement to recommend, prescribe, purchase, supply, sell or administer specific medicinal products’.Reporting transfers of value What requirements apply to recording and publishing details of transfers of value to healthcare professionals and organisations by companies marketing medicinal products or medical devices? LIF’s ethical rules correspond to the European Federation of Pharmaceutical Industries and Associations’ Discloser Code in this matter. Direct or indirect transfers of value, whether in cash, in kind or otherwise, made for promotional purposes or otherwise, in connection with the development and sale of prescription-only medicinal products exclusively for human use, to a healthcare professional or organisation shall be recorded and published by the pharmaceutical company. In accordance with the cooperation agreement between, inter alia, LIF and the trade association, Swedish Medtech, the principle of documentation applies to (connected) medical device companies in regard to value transfers. These companies are, therefore, obliged to document information about value transfers, but they do not have to publish this information. Enforcement of advertising rulesEnforcers Describe the bodies involved in monitoring and ensuring compliance with advertising controls for medicinal products and medical devices, distinguishing between any self-regulatory framework and control by the authorities. As regards law enforcement, the Swedish Medical Products Agency is responsible for the supervision of compliance with the Medicinal Products Act and the Medical Devices Act. The Swedish Marketing Practices Act is enforced by the Swedish Consumer Agency. For the self-regulatory LIF, the IGN and the Information Practices Committee have a duty to ensure LIF members’ compliance with the LER Rules.Sanctions What are the possible financial or other sanctions for breach of advertising and promotional controls for medicinal products or medical devices? The MPA is entitled to demand information and issue orders and prohibitions necessary to ensure the compliance with the Medicinal Products Act, the Medical Devices Act and any regulations issued based on the acts in question. Such demands, orders and prohibitions can be coupled with a fine. Sanctions available under the Marketing Practices Act consist of prohibitions or orders coupled with a penalty fine, fines for disruptive marketing practices and damages. Pricing and reimbursementPricing What are the controls imposed on pricing of medicines and medical devices and reimbursement by national social security systems that are applicable to manufacturers, distributors and pharmacists? The Dental and Pharmaceutical Benefits Agency (TLV) is responsible for deciding whether a pharmaceutical product or medical device should be eligible for reimbursement and included in the Swedish benefits scheme. The TLV is responsible for setting the purchase and selling price of such products. These decisions are made in accordance with the Act on Pharmaceutical Benefits (2002:160). Prices are based on an ethical platform with three basic principles: - the human value principle; - the need and solidarity principle; and - the cost-effectiveness principle. The Swedish medical benefit scheme consists of two parts: subsidising of medicinal products and medical devices, and a ‘high-cost threshold’. Sweden applies a high-cost threshold for prescription medicinal products and medical devices, which means that patients only have to pay for such products up to a certain threshold; all prescription medicinal products and medical devices are free thereafter. The high-cost threshold starts to apply after purchases amounting to 1,150 Swedish kronor for prescription medicinal products and medical devices during a 12-month period. However, not all products are included in the high-cost threshold scheme, although the scheme includes numerous types of medicinal products and medical devices. Off-label use and unlicensed productsOff-label use May health professionals prescribe or use products for ‘off-label’ indications? May pharmaceutical companies draw health professionals’ attention to potential off-label uses? The MPA recommends that products that have been authorised for a specific indication are used if available. However, as a general rule, doctors have the right to freely prescribe or use products they deem fit for a particular purpose, including for ‘off-label’ indications, if such use can be motivated based on scientific findings and proven experience. Certain limitations apply to, inter alia, narcotic pharmaceutical products authorised for the treatment of ADHD. Pharmaceutical companies have to be careful in drawing health professionals’ attention to potential off-label uses, as the provision of such information would likely be considered as marketing. For the restrictions on marketing of medicinal products and medical devices, see questions 20 and 21.Unlicensed products What rules apply to the manufacture and importation and supply to healthcare providers of unlicensed medicines or medical devices? Unlicensed medicinal products (ie, medicinal products that have not been granted marketing authorisation by the MPA), may, under certain circumstances, be dispensed after obtaining a special licence from the MPA if there is a need that cannot be satisfied with approved medicinal products on the market. The licence may apply to a certain patient (individual licence) or to one or more healthcare entities (general licence). Furthermore, there is a separate licence to be obtained for the manufacturing of extempore medicinal products (ie, non-standardised medicinal products to be produced by a pharmacy for a certain patient or animal, which is regulated by MPA Regulation LVFS 2010:12 (for extempore pharmacies) or LVFS 2009:8 (for standard pharmacies)). Hospitals may manufacture extempore medicinal products without a licence from the MPA, but must notify the MPA of their supply of medicinal products to the public. The manufacturing of extempore medicinal products that are produced for a certain patient but not for a certain occasion (ie, stock preparations of extempore medicinal products) also requires a licence from the MPA according to Regulation LVFS 2004:7.Compassionate use What rules apply to the establishment of compassionate use programmes for unlicensed products? Compassionate use programmes (CUPs) for unlicensed products can be established in Sweden in accordance with EU Regulation (EC) No. 726/2004 for a group of patients with a life-threatening, chronically or seriously debilitating disease, which cannot be treated satisfactorily by currently authorised medicinal products. The medicinal product concerned must either be the subject of an application for a marketing authorisation or be undergoing clinical trials. The manufacturer or the applicant for market authorisation must apply to the MPA before establishing a CUP. The application is free of charge and can be made through a standard form, which can be obtained from the MPA’s website. Patients participating in the CUP must be provided the product free of charge. Sale and supplyRegulation Are there special rules governing the dispensing or sale of particular types of medicinal products or medical devices? To dispense or sale prescription-free medicinal products or medical devices, the Trade with Prescription Free Medicinal Products Act (2009:730) applies. For dispensing or sale of prescription medicinal products and medical devices, the Trade with Prescription Medicinal Products Act (2009:366) applies as well as MPA Regulation LVFS 2009:8. Each respective act specifies which medicinal products and medical devices can be sold under the Act. Both the dispensing or sale of prescription-free medicinal products or medical devices, and the dispensing or sale of prescription medicinal products and medical devices, requires authorisation from the MPA.Online supply What laws and guidelines govern online dispensing, sale and supply of medicinal products and medical devices? There are no additional laws or guidelines relating to e-pharmacies. Update and trendsForthcoming legislation and regulation Is there any current or foreseeable draft legislation or other rules that will affect the regulation of pharmaceuticals and medical devices? What is likely to change, and what steps need to be taken in preparation?Forthcoming legislation and regulation31 Is there any current or foreseeable draft legislation or other rules that will affect the regulation of pharmaceuticals and medical devices? What is likely to change, and what steps need to be taken in preparation? The MPA has recently been tasked by the government with establishing a structure for cooperation between national players within the healthcare sector regarding medicine shortages and with further developing the MPA’s supply of information during a period when a medicine is not accessible on the Swedish market. The MPA has also been tasked with conducting a pilot study in which a risk-benefit assessment of a pharmaceutical product of the MPA’s choosing, that is commonly prescribed or used for ‘off-label’ indication, will be carried out. The purpose of the pilot study is to assess whether the MPA should start to continuously conduct risk-benefit assessments of common off-label products and to suggest a process for such assessments. In September 2019, Sweden’s plan to join the impending International Horizon Scanning Initiative (IHSI) was announced. IHSI is an international cooperation seeking to identify unauthorised innovative medicinal products. The cooperation, expected to start in late October 2019, will inform decision-making on treatment and budgets in the participating countries. IHSI is a good example of a broader trend of expanding international cooperation on medicinal products.	2	12	1	0	0	0.477842	1	7,474
A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase. The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE. A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY. The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION. C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C5 is cleaved by C5 CONVERTASE into COMPLEMENT C5A and COMPLEMENT C5B. The smaller fragment C5a is an ANAPHYLATOXIN and mediator of inflammatory process. The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX. The larger fragment generated from the cleavage of COMPLEMENT C3 by C3 CONVERTASE. It is a constituent of the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb), and COMPLEMENT C5 CONVERTASES in both the classical (C4b2a3b) and the alternative (C3bBb3b) pathway. C3b participates in IMMUNE ADHERENCE REACTION and enhances PHAGOCYTOSIS. It can be inactivated (iC3b) or cleaved by various proteases to yield fragments such as COMPLEMENT C3C; COMPLEMENT C3D; C3e; C3f; and C3g. Complement System Proteins Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY). A 105-kDa serum glycoprotein with significant homology to the other late complement components, C7-C9. It is a polypeptide chain cross-linked by 32 disulfide bonds. C6 is the next complement component to bind to the membrane-bound COMPLEMENT C5B in the assembly of MEMBRANE ATTACK COMPLEX. It is encoded by gene C6. Phosphatidylethanolamine Binding Protein A ubiquitously found basic protein that binds to phosphatidylethanolamine and NUCLEOTIDES. It is an endogenous inhibitor of RAF KINASES and may play a role in regulating SIGNAL TRANSDUCTION. Phosphatidylethanolamine-binding protein is the precursor of hippocampal cholinergic neurostimulating peptide, which is cleaved from the N-terminal region of the protein. A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001). A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE). A 63-kDa serum glycoprotein encoded by gene C9. Monomeric C9 (mC9) binds the C5b-8 complex to form C5b-9 which catalyzes the polymerization of C9 forming C5b-p9 (MEMBRANE ATTACK COMPLEX) and transmembrane channels leading to lysis of the target cell. Patients with C9 deficiency suffer from recurrent bacterial infections. A 77-kDa subcomponent of complement C1, encoded by gene C1S, is a SERINE PROTEASE existing as a proenzyme (homodimer) in the intact complement C1 complex. Upon the binding of COMPLEMENT C1Q to antibodies, the activated COMPLEMENT C1R cleaves C1s into two chains, A (heavy) and B (light, the serine protease), linked by disulfide bonds yielding the active C1s. The activated C1s, in turn, cleaves COMPLEMENT C2 and COMPLEMENT C4 to form C4b2a (CLASSICAL C3 CONVERTASE). Complement Membrane Attack Complex A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC. A 80-kDa subcomponent of complement C1, existing as a SERINE PROTEASE proenzyme in the intact complement C1 complex. When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. No fragment is released when either C1r or C1s is cleaved. Complement Inactivator Proteins Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors. A 93-kDa serum glycoprotein encoded by C7 gene. It is a polypeptide chain with 28 disulfide bridges. In the formation of MEMBRANE ATTACK COMPLEX; C7 is the next component to bind the C5b-6 complex forming a trimolecular complex C5b-7 which is lipophilic, resembles an integral membrane protein, and serves as an anchor for the late complement components, C8 and C9. Complement C3-C5 Convertases Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue. Complement Factor B Complement Pathway, Alternative Complement activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX. Complement Pathway, Classical Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX. Complement C1 Inactivator Proteins A 150-kDa serum glycoprotein composed of three subunits with each encoded by a different gene (C8A; C8B; and C8G). This heterotrimer contains a disulfide-linked C8alpha-C8gamma heterodimer and a noncovalently associated C8beta chain. C8 is the next component to bind the C5-7 complex forming C5b-8 that binds COMPLEMENT C9 and acts as a catalyst in the polymerization of C9. The first complement component to act in the activation of CLASSICAL COMPLEMENT PATHWAY. It is a calcium-dependent trimolecular complex made up of three subcomponents: COMPLEMENT C1Q; COMPLEMENT C1R; and COMPLEMENT C1S at 1:2:2 ratios. When the intact C1 binds to at least two antibodies (involving C1q), C1r and C1s are sequentially activated, leading to subsequent steps in the cascade of COMPLEMENT ACTIVATION. Receptors, Complement 3b Molecular sites on or in some B-lymphocytes and macrophages that recognize and combine with COMPLEMENT C3B. The primary structure of these receptors reveal that they contain transmembrane and cytoplasmic domains, with their extracellular portion composed entirely of thirty short consensus repeats each having 60 to 70 amino acids. Complement Factor H An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY). The larger fragment generated from the cleavage of C5 by C5 CONVERTASE that yields COMPLEMENT C5A and C5b (beta chain + alpha' chain, the residual alpha chain, bound by disulfide bond). C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly-C9, the MEMBRANE ATTACK COMPLEX. Receptor, Anaphylatoxin C5a Complement Activating Enzymes Complement Inactivating Agents Complement Hemolytic Activity Assay A screening assay for circulating COMPLEMENT PROTEINS. Diluted SERUM samples are added to antibody-coated ERYTHROCYTES and the percentage of cell lysis is measured. The values are expressed by the so called CH50, in HEMOLYTIC COMPLEMENT units per milliliter, which is the dilution of serum required to lyse 50 percent of the erythrocytes in the assay. 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. Receptors, Complement 3d Molecular sites on or in B-lymphocytes, follicular dendritic cells, lymphoid cells, and epithelial cells that recognize and combine with COMPLEMENT C3D. Human complement receptor 2 (CR2) serves as a receptor for both C3dg and the gp350/220 glycoprotein of HERPESVIRUS 4, HUMAN, and binds the monoclonal antibody OKB7, which blocks binding of both ligands to the receptor. Serum peptides derived from certain cleaved COMPLEMENT PROTEINS during COMPLEMENT ACTIVATION. They induce smooth MUSCLE CONTRACTION; mast cell HISTAMINE RELEASE; PLATELET AGGREGATION; and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from the strongest to the weakest is C5a, C3a, C4a, and C5a des-arginine. Amino Acid Sequence Complement Fixation Tests Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1. Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Complement Factor D Complement C1 Inhibitor Protein An endogenous 105-kDa plasma glycoprotein produced primarily by the LIVER and MONOCYTES. It inhibits a broad spectrum of proteases, including the COMPLEMENT C1R and the COMPLEMENT C1S proteases of the CLASSICAL COMPLEMENT PATHWAY, and the MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. C1-INH-deficient individuals suffer from HEREDITARY ANGIOEDEMA TYPES I AND II. Complement Factor I A plasma serine proteinase that cleaves the alpha-chains of C3b and C4b in the presence of the cofactors COMPLEMENT FACTOR H and C4-binding protein, respectively. It is a 66-kDa glycoprotein that converts C3b to inactivated C3b (iC3b) followed by the release of two fragments, C3c (150-kDa) and C3dg (41-kDa). It was formerly called KAF, C3bINF, or enzyme 3b inactivator. Complement C4b-Binding Protein Complement C3b Inactivator Proteins Endogenous proteins that inhibit or inactivate COMPLEMENT C3B. They include COMPLEMENT FACTOR H and COMPLEMENT FACTOR I (C3b/C4b inactivator). They cleave or promote the cleavage of C3b into inactive fragments, and thus are important in the down-regulation of COMPLEMENT ACTIVATION and its cytolytic sequence. Complement C3-C5 Convertases, Classical Pathway Carrier proteins produced in the Sertoli cells of the testis, secreted into the seminiferous tubules, and transported via the efferent ducts to the epididymis. They participate in the transport of androgens. Androgen-binding protein has the same amino acid sequence as SEX HORMONE-BINDING GLOBULIN. They differ by their sites of synthesis and post-translational oligosaccharide modifications. Electrophoresis, Polyacrylamide Gel An adrenal microsomal cytochrome P450 enzyme that catalyzes the 21-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP21 gene, converts progesterones to precursors of adrenal steroid hormones (CORTICOSTERONE; HYDROCORTISONE). Defects in CYP21 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL). Complement C3-C5 Convertases, Alternative Pathway Complement C3 Convertase, Alternative Pathway Complement C5 Convertase, Classical Pathway Sequence Homology, Amino Acid Complement C3 Convertase, Classical Pathway I-kappa B Proteins Lupus Erythematosus, Systemic A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Complement C5 Convertase, Alternative Pathway The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). 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. Protein Structure, Tertiary The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure. Complement Pathway, Mannose-Binding Lectin Complement activation triggered by the interaction of microbial POLYSACCHARIDES with serum MANNOSE-BINDING LECTIN resulting in the activation of MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. As in the classical pathway, MASPs cleave COMPLEMENT C4 and COMPLEMENT C2 to form C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX. 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. A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections. Mitochondrial Proton-Translocating ATPases Complement C5a, des-Arginine Intracellular Signaling Peptides and Proteins Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors. Cholesterol Ester Transfer Proteins 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. 5'-Adenylic acid, monoanhydride with imidodiphosphoric acid. An analog of ATP, in which the oxygen atom bridging the beta to the gamma phosphate is replaced by a nitrogen atom. It is a potent competitive inhibitor of soluble and membrane-bound mitochondrial ATPase and also inhibits ATP-dependent reactions of oxidative phosphorylation. Gene Expression Regulation A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). Protein Phosphatase 1 A eukayrotic protein serine-threonine phosphatase subtype that dephosphorylates a wide variety of cellular proteins. The enzyme is comprised of a catalytic subunit and regulatory subunit. Several isoforms of the protein phosphatase catalytic subunit exist due to the presence of multiple genes and the alternative splicing of their mRNAs. A large number of proteins have been shown to act as regulatory subunits for this enzyme. Many of the regulatory subunits have additional cellular functions. Protein components on the surface of LIPOPROTEINS. They form a layer surrounding the hydrophobic lipid core. There are several classes of apolipoproteins with each playing a different role in lipid transport and LIPID METABOLISM. These proteins are synthesized mainly in the LIVER and the INTESTINES. Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN. Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC 18.104.22.168. A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Genetic Complementation Test Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY. Cyclin-Dependent Kinase Inhibitor p21 Polymerase Chain Reaction In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. Major Histocompatibility Complex The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms. Proto-Oncogene Proteins c-raf A family of DNA repair enzymes that recognize damaged nucleotide bases and remove them by hydrolyzing the N-glycosidic bond that attaches them to the sugar backbone of the DNA molecule. The process called BASE EXCISION REPAIR can be completed by a DNA-(APURINIC OR APYRIMIDINIC SITE) LYASE which excises the remaining RIBOSE sugar from the DNA. Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone Inhibitor of Apoptosis Proteins A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat. The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Reverse Transcriptase Polymerase Chain Reaction Recombinant Fusion Proteins Disease Models, Animal Blood Bactericidal Activity The natural bactericidal property of BLOOD due to normally occurring antibacterial substances such as beta lysin, leukin, etc. This activity needs to be distinguished from the bactericidal activity contained in a patient's serum as a result of antimicrobial therapy, which is measured by a SERUM BACTERICIDAL TEST. Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation. 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) Complement C3 Nephritic Factor An IgG autoantibody against the ALTERNATIVE PATHWAY C3 CONVERTASE, found in serum of patients with MESANGIOCAPILLARY GLOMERULONEPHRITIS. The binding of this autoantibody to C3bBb stabilizes the enzyme thus reduces the actions of C3b inactivators (COMPLEMENT FACTOR H; COMPLEMENT FACTOR I). This abnormally stabilized enzyme induces a continuous COMPLEMENT ACTIVATION and generation of C3b thereby promoting the assembly of MEMBRANE ATTACK COMPLEX and cytolysis. Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses. Cyclin-Dependent Kinase Inhibitor p27 A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2. Dose-Response Relationship, Drug The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). C1-Esterase inhibitor: an anti-inflammatory agent and its potential use in the treatment of diseases other than hereditary angioedema. (1/83)C1-esterase inhibitor (C1-Inh) therapy was introduced in clinical medicine about 25 years ago as a replacement therapy for patients with hereditary angioedema caused by a deficiency of C1-Inh. There is now accumulating evidence, obtained from studies in animals and observations in patients, that administration of C1-Inh may have a beneficial effect as well in other clinical conditions such as sepsis, cytokine-induced vascular leak syndrome, acute myocardial infarction, or other diseases. Activation of the complement system, the contact activation system, and the coagulation system has been observed in these diseases. A typical feature of the contact and complement system is that on activation they give rise to vasoactive peptides such as bradykinin or the anaphylatoxins, which in part explains the proinflammatory effects of either system. C1-Inh, belonging to the superfamily of serine proteinase inhibitors (serpins), is a major inhibitor of the classical complement pathway, the contact activation system, and the intrinsic pathway of coagulation, respectively. It is, therefore, endowed with anti-inflammatory properties. However, inactivation of C1-Inh occurs locally in inflamed tissues by proteolytic enzymes (e.g., elastase) released from activated neutrophils or bacteria thereby leading to increased local activation of the various host defense systems. Here we will give an overview on the biochemistry and biology of C1-Inh. We will discuss studies addressing therapeutic administration of C1-Inh in experimental and clinical conditions. Finally, we will provide an explanation for the therapeutic benefit of C1-Inh in so many different diseases. (+info) C1 inhibitor cross-linking by tissue transglutaminase. (2/83)C1 inhibitor, a plasma proteinase inhibitor of the serpin superfamily involved in the regulation of complement classical pathway and intrinsic blood coagulation, has been shown to bind to several components of the extracellular matrix. These reactions may be responsible for C1 inhibitor localization in the perivascular space. In the study reported here, we have examined whether C1 inhibitor could function as a substrate for plasma (factor XIIIa) or tissue transglutaminase. We made the following observations: 1) SDS-polyacrylamide gel electrophoresis and autoradiography showed that C1 inhibitor exposed to tissue transglutaminase (but not to factor XIIIa) incorporated the radioactive amine donor substrate [(3)H]putrescine in a calcium-dependent manner; 2) the maximum stoichiometry for the uptake of [(3)H]putrescine by C1 inhibitor was 1:1; 3) proteolytic cleavage and peptide sequencing of reduced and carboxymethylated [(3)H]putrescine-C1 inhibitor identified Gln(453) (P'9) as the single amine acceptor residue; 4) studies with (125)I-labeled C1 inhibitor showed that tissue transglutaminase was also able to cross-link C1 inhibitor to immobilized fibrin; and 5) C1 inhibitor cross-linked by tissue transglutaminase to immobilized fibrin had inhibitory activity against its target enzymes. Thus, tissue transglutaminase-mediated cross-linking of C1 inhibitor to fibrin or other extracellular matrix components may serve as a mechanism for covalent serpin binding and influence local regulation of the proteolytic pathways inhibited by C1 inhibitor. (+info) SERPIN regulation of factor XIa. The novel observation that protease nexin 1 in the presence of heparin is a more potent inhibitor of factor XIa than C1 inhibitor. (3/83)In the present studies we have made the novel observation that protease nexin 1 (PN1), a member of the serine protease inhibitor (SERPIN) superfamily, is a potent inhibitor of the blood coagulation Factor XIa (FXIa). The inhibitory complexes formed between PN1 and FXIa are stable when subjected to reducing agents, SDS, and boiling, a characteristic of the acyl linkage formed between SERPINs and their cognate proteases. Using a sensitive fluorescence-quenched peptide substrate, the K(assoc) of PN1 for FXIa was determined to be 7.9 x 10(4) m(-)(1) s(-)(1) in the absence of heparin. In the presence of heparin, this rate was accelerated to 1.7 x 10(6), M(-)(1) s(-)(1), making PN1 a far better inhibitor of FXIa than C1 inhibitor, which is the only other SERPIN known to significantly inhibit FXIa. FXIa-PN1 complexes are shown to be internalized and degraded by human fibroblasts, most likely via the low density lipoprotein receptor-related protein (LRP), since degradation was strongly inhibited by the LRP agonist, receptor-associated protein. Since FXIa proteolytically modifies the amyloid precursor protein, this observation may suggest an accessory role for PN1 in the pathobiogenesis of Alzheimer's disease. (+info) The native metastable fold of C1-inhibitor is stabilized by disulfide bonds. (4/83)C1-inhibitor is a member of the serpin family of proteinase inhibitors and is an important inhibitor of complement and contact system proteinases. The native protein has the characteristic serpin feature of being in a kinetically trapped metastable state rather than in the most stable state it could adopt. A consequence of this is that it readily forms loop-sheet dimers and polymers, by a mechanism believed to be the same as observed with other serpins. An unusual feature of C1-inhibitor is that it has a unique amino-terminal domain, of unknown function, held to the serpin domain by two disulfide bonds not found in other serpins. We report here that reduction of these bonds by DTT, causes a conformational change such that the reactive center loop inserts into beta-sheet A. This form of C1-inhibitor is less stable to heat and urea than the native protein, and is more susceptible to extensive degradation by trypsin. These data show that the disulfide bonds in C1-inhibitor are required for the protein to be stabilized in the metastable state with the reactive center loop expelled from beta-sheet A. (+info) Hereditary angioedema with a de novo mutation of exon 8 in the C1 inhibitor gene showing recurrent edema of the hands around the peripheral joints: importance for the differential diagnosis of joint swelling. (5/83)We describe a patient with hereditary angioedema (HAE), showing recurrent edema around the peripheral joints. Her symptoms began at the age of 18 with hand swelling distal to the wrist joints. Until she was referred to our hospital 3 years after her initial symptoms, she was still undiagnosed, although she was suspected of having rheumatoid arthritis. Laboratory examination showed reduced levels of CH50 and C4 with normal C3 levels. The C1 inhibitor (C1-INH) was decreased to 5 mg/ml, with remarkably reduced activity. Although these findings were compatible with a diagnosis of HAE, there were no episodes of skin edema in her family. To establish the diagnosis, we carried out DNA analysis of the C1-INH gene, which revealed a newly identified de novo mutation of G to A at nucleotide 16869 in exon 8. As described in this patient, localized edema around the peripheral joints may be the only manifestation of HAE. HAE should therefore be taken into consideration for the differential diagnosis of joint swelling. (+info) Complement components, but not complement inhibitors, are upregulated in atherosclerotic plaques. (6/83)Complement activation occurs in atherosclerotic plaques. The capacity of arterial tissue to inhibit this activation through generation of the complement regulators C1 inhibitor, decay accelerating factor, membrane cofactor protein (CD46), C4 binding protein (C4BP), and protectin (CD59) was evaluated in pairs of aortic atherosclerotic plaques and nearby normal artery from 11 human postmortem specimens. All 22 samples produced mRNAs for each of these proteins. The ratios of plaque versus normal artery pairs was not significantly different from unity for any of these inhibitors. However, in plaques, the mRNAs for C1r and C1s, the substrates for the C1 inhibitor, were increased 2.35- and 4.96-fold, respectively, compared with normal artery; mRNA for C4, the target for C4BP, was elevated l.34-fold; and mRNAs for C7 and C8, the targets for CD59, were elevated 2.61- and 3.25-fold, respectively. By Western blotting and immunohistochemistry, fraction Bb of factor B, a marker of alternative pathway activation, was barely detectable in plaque and normal arterial tissue. These data indicate that it is primarily the classical, not the alternative pathway, that is activated in plaques and that key inhibitors are not upregulated to defend against this activation. (+info) A new type of acquired C1 inhibitor deficiency associated with systemic lupus erythematosus. (7/83)Acquired C1 inhibitor (C1-INH) deficiency with consequent angioedema is a rare condition that may indicate an underlying lymphoproliferative disorder. The defect is caused by increased catabolism, which is often associated with the presence of serum autoantibodies to C1-INH. The present report describes 3 patients with systemic lupus erythematosus who developed typical symptoms of acquired angioedema, characterized by recurrent swelling of subcutaneous and mucous tissues. The 3 patients demonstrated a major classical pathway-mediated complement consumption, with very low levels of C3 antigen and decreased levels of C1-INH antigen. Neither antibodies to C1-INH nor associated lymphoproliferative disease was found. No patient had clinical and biologic signs of lupus activity at the time the angioedema occurred. All patients were treated with steroids and exhibited a good response, without relapse of angioedema and with normalization of plasma levels of C1-INH. In lupus patients who present with an angioedema syndrome, acquired or hereditary angioedema must be sought by examining parameters of the classical pathway and levels of C1-INH. Our observations suggest the existence of a new form of acquired C1-INH deficiency associated with a major classical pathway-mediated complement consumption and systemic autoimmunity. (+info) In vivo biosynthesis of endogenous and of human C1 inhibitor in transgenic mice: tissue distribution and colocalization of their expression. (8/83)We have produced transgenic mice expressing human C1 inhibitor mRNA and protein under the control of the human promoter and regulatory elements. The transgene was generated using a minigene construct in which most of the human C1 inhibitor gene (C1NH) was replaced by C1 inhibitor cDNA. The construct retained the promoter region extending 1.18 kb upstream of the transcription start site, introns 1 and 2 as well as a stretch of 2.5 kb downstream of the polyadenylation site, and therefore carried all known elements involved in transcriptional regulation of the C1NH gene. Mice with high serum levels of human C1 inhibitor, resulting from multiple tandem integrations of the C1 inhibitor transgene, were selected. Immunohistochemistry in combination with in situ hybridization was applied to localize the sites of C1 inhibitor biosynthesis and to demonstrate its local production in brain, spleen, liver, heart, kidney, and lung. The distribution of human C1 inhibitor-expressing cells was qualitatively indistinguishable from that of its mouse counterpart, but expression levels of the transgene were significantly higher. In the spleen, production of C1 inhibitor was colocalized with that of a specific marker for white pulp follicular dendritic cells. This study demonstrates a stringently regulated expression of both the endogenous and the transgenic human C1 inhibitor gene and reveals local biosynthesis of C1 inhibitor at multiple sites in which the components of the macromolecular C1 complex are also produced. (+info) Gentaur Molecular :Molecular Innovations \ HUMAN PLASMA PROTEINS C-1 Esterase Inhibitor, Human Plasma \ HC1EIN Gentaur molecular products has all kinds of products like :search , Molecular Innovations \ HUMAN PLASMA PROTEINS C-1 Esterase Inhibitor, Human Plasma \ HC1EIN for more molecular products just contact us Ultrasonic Solution Long Term Rust Inhibitor Chem-Crest 77-C Chem-Crest 77-C is a long-term rust inhibitor concentrate designed as a rinse injection into an overflowing ultrasonic rinse tank. Order now. Car Diagnostics Pro VAG OBD2 - Slunečnice.cz Car Diagnostics Pro VAG OBD2 0.9.2.2 download - PRO Diagnostics, Programming and Monitoring for all Audi, Volkswagen, Seat and Škoda vehicles. BASIC… Angioedema as the first presentation of B-cell non-Hodgkin lymphoma--an unusual case with normal C1 esterase inhibitor level: a... Gunatilake, S.Sihindi.Chapa.; Wimalaratna, H., 2015: Angioedema as the first presentation of B-cell non-Hodgkin lymphoma--an unusual case with normal C1 esterase inhibitor level: a case report Administration of C1-esterase inhibitor during emergency coronary artery bypass surgery in acute ST-elevation myocardial... OBJECTIVE Myocardial inflammatory response including complement activation was demonstrated as an important mechanism of ischemia-reperfusion injury and complement inhibition by C1-esterase inhibitor (C1-INH) has recently shown to have cardioprotective effects in experimental and clinical settings. METHODS The effects of C1-INH on complement activation, myocardial cell injury, and clinical outcome were studied in patients undergoing emergency CABG due to acute ST-elevation myocardial infarction (STEMI) with (group 1, CABG+STEMI+C1-INH, n=28) and without (group 2, CABG+STEMI, n=29) bolus administration of C1-INH (40 IU kg(-1)) during reperfusion and 6 h postoperatively (20 IU kg(-1)) besides the same study protocol. C1-INH activity, C3c and C4 complement activation fragments, and cardiac troponin I (cTnI) were measured preoperatively and up to 48 h postoperatively and compared to another elective set of CABG patients without STEMI as controls (group 3, CABG-STEMI, n=10). Clinical data, adverse events, Recombinant Human C1 Esterase Inhibitor in the Prevention of Contrast-induced Nephropathy in High-risk Subjects \| Clinical... New life-saving treatments for Acute kidney injury in clinical trial on Recombinant Human C1 Esterase Inhibitor in the Prevention of Contrast-induced Nephropathy in High-risk Subjects Berinert P Study of Subcutaneous Versus Intravenous Administration - Full Text View - ClinicalTrials.gov Patients with hereditary angioedema (HAE), suffer from recurring and mostly unforeseeable attacks of acute oedema of subcutaneous tissues of various organs. The pathophysiological correlate of this disease is a deficiency in functionally active C1-Esterase Inhibitor (C1-INH). Today, two main types of HAE are described. In HAE type I, an impaired synthesis and an elevated turnover of a normal and functional active C1-INH molecule takes place, causing reduced amounts in functionally active C1-INH. In HAE type II, normal levels of a functionally impaired C1-INH molecule are synthesized. Both defects are inherited as an autosomal dominant trait. HAE type III is limited to females and not associated with C1-INH deficiency; the pathophysiology of this type remains to be determined. Corticosteroids, antihistamines or epinephrine usually do not exert any positive effect in acute attacks caused by HAE. This is of particular importance as these types of medication are often used in case of oedema in ... vag 81 Manufacturer - vag 81 Manufacturers and vag 81 Supplier vag 81 directory - It includes sources from vag 81 manufacturers and vag 81 suppliers, and those qualified vag 81 manufacturer are extensively from china, Taiwan, Hong Kong. Angioedema: An Overview HAE is an autosomal-dominant disorder characterized by recurrent nonpruritic edema of the skin and submucosal tissues.1,2,4-6 The prevalence of HAE ranges from 1 in 10,000 to 1 in 50,000 persons in the United States.4,7 Prevalence is not affected by sex or ethnicity; however, women may have more severe disease.1,4,7 A family history is present in approximately 75% of cases, indicating genetic inheritance; however, 25% of cases are thought to be due to a spontaneous mutation (i.e, a family history is absent).7 Patients often experience disease onset and a swelling episode during childhood, with an increase in severity during puberty.4,5,7,8 The frequency of attacks, which varies between patients, may be weekly or yearly.8. HAE is a congenital quantitative or functional deficiency of C1 esterase inhibitor (C1-INH); it is not associated with a hypersensitivity to foods or other allergens.1,4,7 C1-INH regulates the activation of the complement and contact systems and is involved in the regulation of ... Henley-In-Arden Medical Practice - Library - Health A-Z Rarely, angioedema occurs because of a genetic fault that you inherit from your parents.. The fault affects the gene responsible for the production of a substance called C1 esterase inhibitor. If you dont have enough of this, the immune system can occasionally misfire and cause angioedema.. The swelling may happen randomly, or it may be triggered by:. ... Addington Road Surgery - Library - Health A-Z Rarely, angioedema occurs because of a genetic fault that you inherit from your parents.. The fault affects the gene responsible for the production of a substance called C1 esterase inhibitor. If you dont have enough of this, the immune system can occasionally misfire and cause angioedema.. The swelling may happen randomly, or it may be triggered by:. ... Patients getting on sipuleucel-t and the cause is medrogestone To submit our knowledge, this is the first study that shows steps that a combination of benzodiazepines diazepam and human c1 - esterase inhibitor causes lower levels downstream of spo2 in opioid - tolerant patients who were treated with high doses of pharmaceutical grade medrogestone. Last high grammar school final half last year the jhp pharmaceuticals llc has dealt entirely won a joint development contract for efficient amphotropic packa FUNZONE VULCAN Ripe Vagina Masturbátory, vagíny, zadočky Masturbačná vagína so silikónovým vnútrom, ktoré je vrúbkované pre lepšiu stimuláciu.Materiál- silikónParametre- dĺžka: 15cm 11 Reasons why SEX is painful for some women \| georgeasamani However, S3x is very painful for some women, for a number of reasons including size of the pen!s/vag!na, health challenges and mental readiness. Pain during or after S3x, medically termed dyspareunia, can happen during or after S3x and could be felt in the vag!na or the inner pelv!c region. However, all women should know that… How Can I Tighten My Vagina Naturally Here are the top 3 vaginal tightening methods that actually work! Weve tested dozens of methods and found that the fastest way to tighten your vag is to... PRKAB1 ELISA & Assay Kits 多种适用的PRKAB1ELISA试剂盒，如Cow, 人, 小鼠等。在antibodies-online.cn对比PRKAB1ELISA试剂盒，以便找到您需要的产品。 Lack of treatment adherence in hereditary angioedema: Case report of a female adolescent requiring tracheostomy<... TY - JOUR. T1 - Lack of treatment adherence in hereditary angioedema. T2 - Case report of a female adolescent requiring tracheostomy. AU - Aguilar, Jorge. AU - Silverman, Bernard. AU - Murali, Mandakolathur. AU - Mills, Regina. AU - Schneider, Arlene. PY - 2000/1/1. Y1 - 2000/1/1. N2 - Hereditary angioedema (HAE) is an autosomal dominant disorder characterized by deficient or dysfunctional C1 esterase inhibitor. Clinically, it is characterized by paroxysmal attacks of swelling of subcutaneous tissues and mucous membranes that may be life threatening. Current long-term treatment is achieved with the attenuated androgens danazol and stanozolol, drugs that are known to have minimal virilizing side effects. We report a teenager with hereditary angioedema whose nonadherence with the prescribed medications and clinic visits, as-well as her incomplete understanding of the life-threatening severity of the disease, led to acute airway obstruction requiring tracheostomy. Following appropriate patient ... Ongoing Contact Activation in Patients with Hereditary Angioedema<... TY - JOUR. T1 - Ongoing Contact Activation in Patients with Hereditary Angioedema. AU - Konings, Joke. AU - Cugno, Massimo. AU - Suffritti, Chiara. AU - ten Cate, Hugo. AU - Cicardi, Marco. AU - Govers-Riemslag, José W P. PY - 2013/8/27. Y1 - 2013/8/27. N2 - Hereditary angioedema (HAE) is predominantly caused by a deficiency in C1 esterase inhibitor (C1INH) (HAE-C1INH). C1INH inhibits activated factor XII (FXIIa), activated factor XI (FXIa), and kallikrein. In HAE-C1INH patients the thrombotic risk is not increased even though activation of the contact system is poorly regulated. Therefore, we hypothesized that contact activation preferentially leads to kallikrein formation and less to activation of the coagulation cascade in HAE-C1INH patients. We measured the levels of C1INH in complex with activated contact factors in plasma samples of HAE-C1INH patients (N=30, 17 during remission and 13 during acute attack) and healthy controls (N=10). We did not detect differences in enzyme-inhibitor ... The impact of hereditary angioedema on quality of life and family planning decisions \| AVESİS Objective Hereditary angioedema is a serious disease with unpredictable attacks. It has an impact on patients health-related quality of life. This study aimed to assess the quality of life of the hereditary angioedema patients and to investigate the relationship between quality of life and demographic, clinical, laboratory, and psychiatric parameters. Method A semistructured face-to-face interview, Hamilton depression rating scale, and Hamilton anxiety rating scale were performed by a psychiatrist. Participants completed Medical Outcomes Study Short Form-36, Revised Form of the Multidimensional Scale of Perceived Social Support, Anxiety Sensitivity Index-3, and Adult Separation Anxiety Questionnaire. Patients complement results were recorded, and clinical data obtained by interview were cross-checked from patients files. Results In 33 hereditary angioedema patients, subscales of the Study Short Form-36, except for physical functioning, vitality, and mental health were significantly lower ... Hereditary Angioedema - Andy Long Bass Player A Personal Case History As a sufferer of Hereditary Angioedema (HAE) I am posting this page, detailing my own case history, as a resource for other sufferers. I hope you find it helpful. What is Hereditary Angioedema? (taken from www.hereditaryangioedema.com) Hereditary Angioedema (HAE) is a rare and serious genetic condition occurring in about 1/10,000 to 1/50,000… Safety of C1-Esterase Inhibitor in Acute and Prophylactic Therapy of Hereditary Angioedema - Danish National Research Database... BACKGROUND: The plasma-derived, pasteurized C1-inhibitor (C1-INH) concentrate, Berinert has a 4-decade history of use in hereditary angioedema (HAE), with a substantial literature base that demonstrates safety and efficacy. Thromboembolic events have rarely been reported with C1-INH products, typically with off-label use or at supratherapeutic doses. OBJECTIVES: Active surveillance of safety and clinical usage patterns of pasteurized C1-inhibitor concentrate and the more recent pasteurized, nanofiltered C1-INH, with a particular interest in thromboembolic events. METHODS: A registry was initiated in April 2010 at 27 US and 4 EU sites to obtain both prospective and retrospective safety and usage data on subjects who were administered C1-INH (Berinert). RESULTS: As of May 10, 2013, data were available for 135 subjects and 3196 infusions. By subject, 67.4% were using C1-INH as on-demand therapy and 23.0% as both on-demand therapy and prophylactic administration. Approximately half of the infusions ... Assessment of inhibitory antibodies in patients with hereditary angioedema treated with plasma-derived C1 inhibitor<... TY - JOUR. T1 - Assessment of inhibitory antibodies in patients with hereditary angioedema treated with plasma-derived C1 inhibitor. AU - Farkas, Henriette. AU - Varga, Lilian. AU - Moldovan, Dumitru. AU - Obtulowicz, Krystyna. AU - Shirov, Todor. AU - Machnig, Thomas. AU - Feuersenger, Henrike. AU - Edelman, Jonathan. AU - Williams-Herman, Debora. AU - Rojavin, Mikhail. PY - 2016/11/1. Y1 - 2016/11/1. N2 - Background Limited data are available regarding C1 inhibitor (C1-INH) administration and anti-C1-INH antibodies. Objective To assess the incidence of antibody formation during treatment with pasteurized, nanofiltered plasma-derived C1-INH (pnfC1-INH) in patients with hereditary angioedema with C1-INH deficiency (C1-INH-HAE) and the comparative efficacy of pnfC1-INH in patients with and without antibodies. Methods In this multicenter, open-label study, patients with C1-INH-HAE (≥12 years of age) were given 20 IU/kg of pnfC1-INH per HAE attack that required treatment and followed up for 9 ... the complement systems part, a protein group involved in some allergic and immune reactions. C1 inhibitors abnormal activity or deficiency results in swelling in skins local area and the tissues beneath it, or in the mucous membrane that is the lining body opening including gastrointestinal tract, throat, and the mouth.. Viral infections or injury frequently precipitates the attack, that may be caused by emotional distress. Attacks usually produce swelling areas, that are achy rather than itchy and are not accompanied by hives. Many individuals with Hereditary Angioedema have cramps, vomiting and nausea. The most severe complications include the upper airways swelling, which may affect breathing. Blood tests that measure activity or levels of C1 inhibitor, confirm diagnosis.. The treatment consists of medication called Aminocaprotic acid, which sometimes ends hereditary angioedema attacks. Corticosteroids, antihistamines, and epinephrine are frequently prescribed; although there is no proof ... Hereditary Angioedema Risk Factors, Symptoms and Ways to Live Better - Sharecare \|p\|Hereditary angioedema is a rare genetic condition characterized by recurrent episodes of severe swelling in the limbs, face, intestines and airways. If you’ve been diagnosed with hereditary angioedema, it’s important to be prepared for an attack. Check out this expert-backed advice on risk factors, symptoms, treatment options and more.\|/p\| Hereditary Angioedema (HAE) Treatment, Symptoms & Diagnosis Read about hereditary angioedema (HAE), a genetic disease that causes symptoms of headache, fatigue, abdominal pain, hoarseness, and shortness of breath. There are three types or forms of hereditary angioedema. Causes, triggers, diagnosis, treatment, and prognosis information are provided. Hereditary Angioedema: Hereditary Angioedema is a rare genetic condition that causes episodes of edema (swelling) in various parts of the body intermittently. Hereditary Angioedema (HAE) Center by MedicineNet.com Consumer information about hereditary angioedema (HAE), a genetic disease that causes symptoms of headache, fatigue, abdominal pain, hoarseness, and shortness of breath. There are three types or forms of hereditary angioedema. Causes, triggers, diagnosis, treatment, and prognosis information are provided. What is Hereditary Angioedema? - Hereditary Angioedema Definition - GoodRx Compare prices and find information about prescription drugs used to treat Hereditary Angioedema. Treatment for hereditary angiodema includes... Hereditary Angioedema Market - Global Industry Analysis, Size, Share, Growth, Trends, and Forecast 2017 - 2025 \| virginia news... This report on the Global Hereditary Angioedema Market analyzes the current and future prospects of the market. The report comprises an elaborate executive summary, including a market snapshot that provides overall information of various segments and sub-segments.. Request for Sample Report: http://www.mrrse.com/sample/3380. The research is a combination of primary and secondary research. Primary research formed the bulk of our research efforts along with information collected from telephonic interviews and interactions via e-mails. Secondary research involved study of company websites, annual reports, press releases, stock analysis presentations, and various international and national databases. The report provides market size in terms of US$ Mn for each segment and sub-segment for the period from 2017 to 2025, considering the macro and micro environmental factors. Growth rates for each segment within the global hereditary angioedema market have been determined after a thorough analysis of past ... Most recent papers in the shared collection Hereditary angioedema \| Read by QxMD Hereditary angioedema (HAE) due to C1 esterase inhibitor (C1-INH) deficiency (HAE-C1-INH) is a rare but medically significant disease that can be associated with considerable morbidity and mortality. Research into the pathogenesis of HAE-C1-INH has expanded greatly in the last six decades and has led to new clinical trials with novel therapeutic agents and treatment strategies. Mechanisms of pharmacotherapy include (a) supplementing C1-INH, the missing serine-protease inhibitor in HAE; (b) inhibiting the activation of the contact system and the uncontrolled release of proteases in the kallikrein-kinin system, by blocking the production/function of its components; (c) inhibiting the fibrinolytic system by blocking the production/function of its components; and (d) inhibiting the function of bradykinin at the endothelial level ... Current management of hereditary angio-oedema (C1 esterase inhibitor deficiency) \| CHAEN-RCAH Hereditary angio-oedema is characterised by recurrent swellings in any part of the body and also by recurrent attacks of severe abdominal pain. The disease is inherited in an autosomal dominant manner but up to 25% of cases can occur as a spontaneous mutation. Attacks of swelling can be precipitated by trauma, certain drugs, and emotional stress. Treatment usually involves a combination of prophylaxis, using androgens or antifibrolytic drugs, and replacement with C1 esterase inhibitor concentrate for acute attacks and before surgery or other traumatic procedures. [References: 106].. Apr;55(4):266-270. Available online at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769636/. ... Assessment of inhibitory antibodies in patients with hereditary angioedema treated with plasma-derived C1 inhibitor Background Limited data are available regarding C1 inhibitor (C1-INH) administration and anti-C1-INH antibodies. Objective To assess the incidence of antibody formation during treatment with pasteurized, nanofiltered plasma-derived C1-INH (pnfC1-INH) in patients with hereditary angioedema with C1-INH deficiency (C1-INH-HAE) and the comparative efficacy of pnfC1-INH in patients with and without antibodies. Methods In this multicenter, open-label study, patients with C1-INH-HAE (≥12 years of age) were given 20 IU/kg of pnfC1-INH per HAE attack that required treatment and followed up for 9 months. Blood samples were taken at baseline (day of first attack) and months 3, 6, and 9 and analyzed for inhibitory anti-C1-INH antibody (iC1-INH-Ab) and noninhibitory anti-C1-INH antibodies (niC1-INH-Abs). Results The study included 46 patients (69.6% female; mean age, 38.9 years; all white) who received 221 on-site pnfC1-INH infusions; most patients received 6 or fewer infusions. No patient tested positive ... Experimental protocol of dental procedures In patients with hereditary angioedema: the role of anxiety and the use of nitrogen... Hereditary angioedema (HAE) is a rare disease, little known to the medical and dental community, but with a growing rate of hospitalization over the years. HAE is due to a deficit/dysfunction of C1 esterase inhibitor which leads to an increase in vascular permeability and the appearance of edemas widespread in all body areas. The airways are the most affected and laryngeal swelling, which can occur, it is dangerous for the patients life, is also a sensitive spot in our daily practice, therefore, it is also important to be aware of all the signs of this disease. Episodes of HAE have no obvious cause, but it can be triggered by anxiety, invasive procedures and trauma. So this disease is a major problem in oral and maxillofacial surgery, ENT, endoscopy, emergency medicine and anesthesia because even simple procedures can cause laryngeal edema. The recommendations on the management of HAE include long- and short-term prophylaxis and treatment for acute attacks, however, the importance of anxiety control Clinical review of hereditary angioedema: diagnosis and management. Hereditary angioedema (HAE) is caused by a deficiency in C1 esterase inhibitor and is characterized by sudden attacks of edema associated with discomfort and pain. The disease places patients at risk for disability and death if left untreated. Sympto Recombinant and Plasma-Purified Human C1 Inhibitor for the Treatment of Hereditary Angioedema \| World Allergy Organization... Agents for prophylaxis of hereditary angioedema (HAE) have been available in the United States for several decades, but their usefulness is limited by side effects and they cannot be used at all in some patients. No agents have been available in the United States to specifically treat acute attacks. HAE types I and II are associated with low functional levels of C1 inhibitor, and evidence accumulated over decades suggests that intravenous infusion of C1 inhibitor is useful for terminating angioedema attacks and for prophylaxis. C1 inhibitor derived from pooled human plasma has been available for decades in Europe, and 2 preparations have been recently introduced into the United States. Both have been efficacious in carefully controlled double-blind studies. One preparation, Cinryze, was approved by the U.S. Food & Drug Administration (FDA) for prophylaxis of HAE attacks in October 2008, and the second, Berinert, was approved by the FDA for treatment of acute attacks in October 2009. A third preparation, Hereditary Angioedema Clinical Presentation: History, Physical Examination Although rare, hereditary angioedema (HAE) is associated with episodic attacks of edema formation that can have catastrophic consequences. Laryngeal edema can result in asphyxiation; abdominal angioedema attacks can lead to unnecessary surgery and delay in diagnosis, as well as to narcotic dependence due to severe pain; and cutaneous attacks ... Hereditary angioedema: Epidemiology, clinical manifestations, exacerbating factors, and prognosis Hereditary angioedema (HAE) is a disease characterized by recurrent episodes of angioedema,withouturticaria or pruritus, which most often affect the skin or mucosal tissues of the upper respiratory and gastrointestinal tracts. Although the swelling i Hereditary angioedema - Wikipedia Hereditary angioedema (HAE) is disorder that results in recurrent attacks of severe swelling. This most commonly affects the arms, legs, face, intestinal tract, and airway. Itchiness does not typically occur. If the intestinal tract is affected abdominal pain and vomiting may occur. Swelling of the airway can result in its obstruction. Attacks, without treatment, typically occur every couple of weeks and last for a few days. There are three main types of HAE. Type I and II are caused by a mutation in the SERPING1 gene that makes the C1 inhibitor protein while type III is often due to a mutation of the factor XII gene. This results in increased amounts of bradykinin which promotes swelling. The condition may be inherited from a persons parents in an autosomal dominant manner or occur as a new mutation. Triggers of an attack may include minor trauma or stress, but often occurs without any obvious preceding event. Diagnosis of type I and II is based upon measuring C4 and C1-inhibitor levels. ... Canadian hereditary angioedema guideline \| Allergy, Asthma & Clinical Immunology \| Full Text Hereditary angioedema (HAE) is a disease which is associated with random and often unpredictable attacks of painful swelling typically affecting the extremities, bowel mucosa, genitals, face and upper airway. Attacks are associated with significant functional impairment, decreased Health Related Quality of Life, and mortality in the case of laryngeal attacks. Caring for patients with HAE can be challenging due to the complexity of this disease. The care of patients with HAE in Canada is neither optimal nor uniform across the country. It lags behind other countries where there are more organized models for HAE management, and where additional therapeutic options are licensed and available for use. The objective of this guideline is to provide graded recommendations for the management of patients in Canada with HAE. This includes the treatment of attacks, short-term prophylaxis, long-term prophylaxis, and recommendations for self-administration, individualized therapy, quality of life, and comprehensive Shires Investigational Treatment Lanadelumab Reduces Hereditary Angioedema Monthly Attack Rate by 87% Versus Placebo in Phase... Shires Investigational Treatment Lanadelumab Reduces Hereditary Angioedema Monthly Attack Rate by 87% Versus Placebo in Phase 3 26-week Pivotal Trial Monitoring Your Hereditary Angioedema Triggers Hereditary angioedema (HAE) can be a life-threatening condition, but knowing your triggers can help prepare you for attacks. Learn about common triggers. Survey on hereditary angioedema in a German cohort \| Abstract Background and objectives: Hereditary angioedema (HAE) is a rare disease characterized by recurrent swelling attacks affecting almost every part of th.. Hereditary angioedema with normal C1 inhibitor Hereditary angioedema (HAE) is characterized by recurrent, self-limited episodes of swelling primarily involving the skin and the mucosa of the gastrointestinal tract and upper airway. There are several subtypes. The clinical manifestations, pathogen Hereditary Angioedema Treatment Market: Global Market Estimation, Dynamics, Regional Share, Trends, Competitor Analysis 2012... Hereditary angioedema is an inherited condition characterized by re-occurant severe swelling. It affects arms, face, legs, airway and intestinal... Henrik Balle Boysen, Author at HAE International (HAEi) From Executive Director Peter Waite, Canadian Hereditary Angioedema Network: The Canadian Hereditary Angioedema Network has updated its 2014 Canadian Hereditary Angioedema Guideline with an expanded scope to include the management of HAE patients worldwide. It is a collaboration of Canadian and international HAE experts and patient groups led by the Canadian Hereditary Angioedema Network. The objective of this guideline is to provide evidence-based recommendations, [...]. ... US Hereditary Angioedema Association - HAEA We are dedicated to provide support and information on Hereditary Angioedema (HAE) to both patients and physicians, including information on recently FDA Hey HAE: Hereditary Angioedema Blog Engage with the hereditary angioedema (HAE) community and find resources through our blog, created for those who have HAE and family of people who have HAE. Hey HAE Blog - Day-by-Day with Hereditary Angioedema Read blog posts describing how it is to have hereditary angioedema (HAE) day-by-day and offering stories and advice to help you on your journey. Hereditary Angioedema Market to be Worth US$3.81 Billion by 2025: Initiatives to Generate Awareness ALBANY, New York, August 23, 2017 /PRNewswire/ -- Hereditary Angioedema Market to be Worth US$3.81 Billion by 2025: Initiatives to Generate Awareness by... Inflammation and Fever- Online Textbook Chapters - Alyvea.com Given her fathers premature death, Angelas doctor suspects that she has hereditary angioedema, a genetic disorder that compromises the function of C1 inhibitor protein. Patients with this genetic abnormality may have occasional episodes of swelling in various parts of the body. In Angelas case, the swelling has occurred in the respiratory tract, leading to difficulty breathing. Swelling may also occur in the gastrointestinal tract, causing abdominal cramping, diarrhea, and vomiting, or in the muscles of the face or limbs. This swelling may be nonresponsive to steroid treatment and is often misdiagnosed as an allergy.. Because there are three types of hereditary angioedema, the doctor orders a more specific blood test to look for levels of C1-INH, as well as a functional assay of Angelas C1 inhibitors. The results suggest that Angela has type I hereditary angioedema, which accounts for 80%-85% of all cases. This form of the disorder is caused by a deficiency in C1 esterase inhibitors, the ... Airway Management in a Patient with Angioedema \| Hungs Difficult and Failed Airway Management, 3e \| AccessAnesthesiology \|... Angioedema can be divided into hereditary angioedema (HAE) and acquired angioedema. HAE is extremely rare, affecting in the range of 1:30,000 to 1 in 80,000 people.4,5 It develops due to a C1 esterase inhibitor deﬁciency, which is inherited in an autosomal dominant pattern with almost complete penetrance.5 This deﬁciency results in an abnormal increase in the activation of C1 and subsequent excessive formation of the enzyme kallikrein. The excess kallikrein transforms kininogen into kinins, including bradykinin. Bradykinin, the primary biologic mediator of angioedema,5 is highly vasoactive and produces the characteristic tissue swelling seen in angioedema.4 HAE is commonly precipitated by trauma and emotional stress. Frequently, the trauma is considered to be minor and can be as innocuous as prolonged sitting on a hard surface or clapping of the hands. Dental and surgical trauma are well-recognized precipitators of an acute attack.5 ... Open-Label C1 Esterase Inhibitor (C1INH-nf) for the Treatment of Acute Hereditary Angioedema (HAE) Attacks - Tabular View -... Subjects were to assess their symptoms every 15 minutes up to 4 hours after the initial dose or until substantial relief of the defining symptom was achieved. The conservative analysis defined substantial relief as 3 consecutive assessments of improvement of the defining symptom; any attack that did not have 3 consecutive documented reports of improvement was considered a treatment failure. In the less conservative analysis, attacks also were considered to have responded if clinical improvement of the defining symptom occurred but data were incomplete due to cessation of symptom assessments ... TWEETS from #ACEP17 LLSA readings reviews. 2017 LLSA review with Lovata at #ACEP17 https://t.co/dOTCNOLga5. ACEP clincial policy on aortic dissection for 1st #LLSA #ACEP17. Are there clincial decision rules for low risk pts for aortic dissection? NO #LLSA #ACEP17. Is D Dimer adequate to ID low risk aortic dissection? NO #LLSA #ACEP17. Is CTA equivalent to MRI or TEE for dx of aortic dissection? YES. #LLSA #ACEP17 level B. Can transthoracic echo rule out aortic dissection? NO #LLSA #ACEP17. When we decrease SBP and HR for aortic dissection is morbidity and mortality reduced? Not great evidence level C #LLSA #ACEP17. Angioedema up next #LLSA #ACEP17 rapid firing. Types are Histamine with and without anaphylaxis, ACE inhib and hereditary angioedema #LLSA #ACEP17. Most widely available agent for hereditary angioedema is FFP (not beat but most available) #LLSA #ACEP17. Upper airway angioedema; lower too? Direct visualization to assess. #LLSA #ACEP17. CCB overdose with literature review article. ... Cinryze® (C1 Esterase Inhibitor [Human]) Data Presented at 2010 International Scientific Conference of the World Allergy... ...DUBAI United Arab Emirates Dec. 6 2010 /- ViroPharma I...This is the first international presentation of these data which were...Cinryze is the first and only U.S. FDA-approved C1 esterase inhibitor ... These scientific posters mark the first international presentation of...,Cinryze®,(C1,Esterase,Inhibitor,[Human]),Data,Presented,at,2010,International,Scientific,Conference,of,the,World,Allergy,Organization,(WAO),medicine,advanced medical technology,medical laboratory technology,medical device technology,latest medical technology,Health Lev Pharma Seeks Solutions for HAE Sufferors LEV PHARMACEUTICALS Hereditary Angioedema Background Hereditary angioedema (HAE) is a genetic disorder characterized by episodes of edema (swelling) in the extremeties (hands and feet), face, gastrointestinal tract and airway passages. The majority of patients experience periods of severe abdominal pain, nausea and vomiting caused by swelling in the intestinal wall. Attacks that involve the face… hereditary angioedema Archives \| Asthma & Allergy Associates, P.C. At Asthma and Allergy Associates, PC in Colorado Springs we have taken care of patients with swelling concerns for many years. The medical term for ... ViroPharma Launches Ryze Above(TM), A Personalized Patient Resources Program For Patients With Hereditary Angioedema (HAE) ViroPharma Incorporated (Nasdaq: VPHM) today announced the launch of Ryze Above (www.ryzeabove.com), an exclusive patient resources program within the companys patient support ICER to Use Aetion Observational RWE to Update Value Assessment of Treatments for Hereditary Angioedema /PRNewswire/ -- The Institute for Clinical and Economic Review (ICER) today announced it is using observational real-world evidence (RWE) to update its 2018... Takeda Announces Approval of TAKHZYRO® (lanadelumab) subcutaneous injection in China for the Treatment of Hereditary Angioedema... The latest company information, including net asset values, performance, holding & sectors weighting, changes in voting rights, and directors and dealings. Feasibility of home infusion and self-administration of nanofi... Feasibility of home infusion and self-administration of nanofiltered C1 esterase inhibitor for routine prophylaxis in patients with hereditary angioedema and ch Bowman-Birk Inhibitor Concentrate - AdisInsight Bowman-Birk Inhibitor Concentrate is an anticarcinogenic derived from soybeans which inhibits the protease chymotrypsin. The inhibitor was being developed at Hereditary angioedema (HAE) is an inherited disorder caused by a specific mutation in the affected persons genetic code. The gene in question is located on chromosome 11 and is responsible for the production of an enzyme known as C1-esterase inhibitor (C1-INH). C1-INH is an important protein that regulates a variety of metabolic processes in the body. As a result of the underlying genetic mutation, persons suffering from HAE either produce too little C1-INH or a type of C1-INH that does not function properly. One of the effects of C1-INH is to prevent an excessive production of bradykinin in response to inflammation, coagulation reactions and other processes in the body. Bradykinin acts to increase the permeability of the blood vessel walls ... Most Popular \| Managed Care magazine A phase 3 trial has demonstrated that, at the approved dose of 60 IU/kg, Haegarda (C1 esterase inhibitor subcutaneous [human]) reduced the median number of hereditary angioedema (HAE) attacks per month by 98% in patients who had frequent attacks, from a 16-week placebo period to a 16-week treatment ... ... named C1-inhibitor. The inhibition of C1-inhibitor leads to over-activation of the complement pathway and one protein that ... Also, there has been some speculation as to an additional autoantibody against an inhibitor protein (in the complement pathway ... Consequently, levels of all complement proteins become low. The complement pathway is composed of several subset pathways: the ... C1q is an integral component within the complement pathway - a complicated cascade of protein interactions, culminating in an ... List of proteins Serum albumin Complement proteins C1-inhibitor C3-convertase Factor VIII Factor XIII Protein C Protein S Protein Z Protein Z- ... A list of proteins (and protein complexes). This list aims to organize information on the protein universe. All proteins can be ... G-protein-coupled receptor Rhodopsin Estrogen receptor Histones Protamines CI protein % Transcription regulatory proteins that ... For more information about categorizing protein types, see List of types of proteins. Arp2/3 Coronin Dystrophin FtsZ Gloverin ... ... the first component of the classical complement pathway C1 domain, an important secondary messenger protein domain C1-inhibitor ... C1, C01, C.I or C-1 may refer to: C1, a note-octave in music C1 Television, a Mongolian television channel Schecter C-1 ... a precursor protein to Cytochrome C Proanthocyanidin C1, a type of polyphenolic compound Prostaglandin C1, a form of ... C-1), a Spanish submarine Cluster 1, also known as Rumba, an ESA satellite C1, a solo sprint canoe C1 (classification), a para- ... Proteins produced and secreted by the liver Breakdown of fibrin clots Plasminogen Inhibitors of fibrinolysis α2-antiplasmin Complement components C1-9, complement ... The liver plays the major role in producing proteins that are secreted into the blood, including major plasma proteins, factors ... Vitamin D-binding protein, carries vitamin D FGF21, a protein hormone that induces mitochondrial oxidation of fatty acids, ... forming a blood clot that stops bleeding C-reactive protein, opsonin on microbes, acute phase protein Various other globulins ... Disorders of the proteins that act to inhibit the complement system (such as C1-inhibitor) can lead to an overactive response, ... C1-inhibitor deficiency or hereditary angioedema will have low C4 with normal C1 levels. Acquired hypocomplementemia may occur ... Complement deficiency is an immunodeficiency of absent or suboptimal functioning of one of the complement system proteins. ... "Complement Deficiencies. What are complement deficiencies?". patient.info. Retrieved 31 December 2017. "Complement Deficiencies ... C1 inhibitor (C1-INH) antigenic protein, C1 inhibitor (C1-INH) functional level if available. Analysis of complement C1 ... Other treatment modalities can stimulate the synthesis of C1 inhibitor, or reduce C1 inhibitor consumption. Purified C1 ... In this type, atypical C1-inhibitor proteins are produced which are less capable of suppressing activation of the complement ... There are three types of C1 inhibitor deficiency: HAE type I is primarily caused by a deficiency in blood proteins (C1 esterase ... The classical pathway is inhibited by C1-inhibitor, which binds to C1 to prevent its activation. C3-convertase can be inhibited ... Over 30 proteins and protein fragments make up the complement system, including serum proteins, and cell membrane receptors. ... Polymorphisms of complement component 3, complement factor B, and complement factor I, as well as deletion of complement factor ... The complement system is regulated by complement control proteins, which are present at a higher concentration in the blood ... ... is not essential for C1-inhibitor to inhibit proteases. This domain has no similarity to other proteins. C1-inhibitor is highly ... This way, C1-inhibitor prevents the proteolytic cleavage of later complement components C4 and C2 by C1 and MBL. Although named ... C1-inhibitor (C1-inh, C1 esterase inhibitor) is a protease inhibitor belonging to the serpin superfamily. Its main function is ... Note that C1-inhibitor is the most important physiological inhibitor of plasma kallikrein, fXIa, and fXIIa. C1-inhibitor is the ... The classical pathway is inhibited by C1-inhibitor, which binds to C1 to prevent its activation. ... Over 30 proteins and protein fragments make up the complement system, including serum proteins, and cell membrane receptors. ... complement factor B, and complement factor I, as well as deletion of complement factor H-related 3 and complement factor H- ... Deficiencies in complement regulatorsEdit. Mutations in the complement regulators factor H and membrane cofactor protein have ... Complement deficiencies are the result of a lack of any of these proteins. They may predispose to infections but also to ... C1-inhibitor deficiency (hereditary angioedema) Factor I deficiency (pyogenic infections) Factor H deficiency (haemolytic- ... The complement system is part of the innate as well as the adaptive immune system; it is a group of circulating proteins that ... MASP2 deficiency Complement receptor 3 (CR3) deficiency Membrane cofactor protein (CD46) deficiency Membrane attack complex ... Among soluble inhibitors there are factor H, C1 inhibitor, C4b-binding protein, factor I, S protein or clusterin, the membrane- ... Non-apoptotic cells also express complement inhibitors, preventing the assembly of C3 convertase or the lytic pore. ... bound inhibitors are CR1, membrane cofactor protein (MCF), decay accelerating factor (DAF) or protectin (CD59). Phagocytes are ... Besides complement particles C1q and C3b which help to opsonize the apoptotic cells, also thrombospondin, pentraxins (C- ... ... which result in either diminished levels of the C1-inhibitor protein (type I HAE) or dysfunctional forms of the same protein ( ... especially depletion of complement factors 2 and 4, may indicate deficiency of C1-inhibitor. HAE type III is a diagnosis of ... Ruconest (C1-inhibitor). References. ^ a b c d e f g h i j k l m n o p q r s t Bernstein, JA; Cremonesi, P; Hoffmann, TK ... Acute treatment consists of C1-INH (C1-esterase inhibitor) concentrate from donor blood, which must be administered ... Complement component 1s ... (EC 22.214.171.124, C1 esterase, activated complement C1s, complement C overbar 1r, C1s) is a protein ... Katz Y, Strunk RC (March 1989). "Synthesis and regulation of C1 inhibitor in human skin fibroblasts". Journal of Immunology. ... complement activation, lectin pathway. • complement activation. • regulation of complement activation. Sources:Amigo / QuickGO ... protein binding. • hydrolase activity. • metal ion binding. • identical protein binding. • serine-type endopeptidase activity. ... List of primary immunodeficiencies MASP2 deficiency Complement receptor 3 deficiency Membrane cofactor protein (CD46) deficiency Membrane attack complex inhibitor ... C1-inhibitor deficiency (hereditary angioedema) Factor I deficiency (pyogenic infections) Factor H deficiency (haemolytic- ... Complement deficiencies are the result of a lack of any of these proteins. They may predispose to infections but also to ... These proteins, generated by plasma cells, normally bind to pathogens, targeting them for destruction. Absent B cells with a ... C1-inhibitor (which protects the body from excessive protease-triggered activation of its own complement system), antithrombin ... Natural protease inhibitors include the family of lipocalin proteins, which play a role in cell regulation and differentiation ... Other natural protease inhibitors are used as defense mechanisms. Common examples are the trypsin inhibitors found in the seeds ... The natural protease inhibitors are not to be confused with the protease inhibitors used in antiretroviral therapy. Some ... 1994). "Regulation of the synthesis of C1 subcomponents and C1-inhibitor". Behring Inst. Mitt. (93): 196-203. PMID 8172568. ... Complement C1q subcomponent subunit A is a protein that in humans is encoded by the C1QA gene. This gene encodes a major ... 1994). "The envelope glycoprotein of HIV-1 gp120 and human complement protein C1q bind to the same peptides derived from three ... 1994). "Expression of the components and regulatory proteins of the classical pathway of complement in normal and diseased ... ... which result in either diminished levels of the C1-inhibitor protein (type I HAE) or dysfunctional forms of the same protein ( ... especially depletion of complement factors 2 and 4, may indicate deficiency of C1-inhibitor. HAE type III is a diagnosis of ... Acute treatment consists of C1-INH (C1-esterase inhibitor) concentrate from donor blood, which must be administered ... C1-esterase (aka: C1-inhibitor or C1INH), and continuous production of kallikrein, another process inhibited by C1INH. This ... List of MeSH codes (D12.776.124) ... complement c1 inactivator proteins MeSH D12.776.124.486.274.920.250.500 - complement c1 inhibitor protein MeSH D12.776.124.486. ... complement c1 MeSH D12.776.124.486.274.050.270 - complement c1q MeSH D12.776.124.486.274.050.280 - complement c1r MeSH D12.776. ... complement factor i MeSH D12.776.124.486.274.920.662 - complement c4b-binding protein MeSH D12.776.124.486.274.930 - complement ... complement c3b inactivator proteins MeSH D12.776.124.486.274.920.325.200 - complement factor h MeSH D12.776.124.486.274.920. ... Six mutations of the gene SERPING1 (Serpin Peptidase Inhibitor, Clade G (C1 Inhibitor), Member 1) are associated with AMD. ... on chromosome 6 at 6p21.3 Polymorphisms in genes for complement system proteins: Variation in the genes for the complement ... Complement factor H (CFH) is an important inhibitor of this inflammatory cascade, and a disease-associated polymorphism in the ... While there is increasing academic and pharmaceutical interest in developing complement inhibitors to treat ophthalmic ... Checkpoint inhibitors (CTLA-4, PD-1, and PD-L1) operate by this mechanism. Briefly, checkpoint inhibitors are proteins that ... Complement-dependent cytotoxicity occurs when antibodies bind to the cancer cell surface, the C1 complex binds to these ... The complement system includes blood proteins that can cause cell death after an antibody binds to the cell surface (the ... Checkpoint inhibitors bind these proteins and prevent them from functioning normally, which increases the activity of the ... ... that are not involved in coagulation such as trypsin and the C1s subunit of the enzyme C1 involved in the classical complement ... Antithrombin is a serpin (serine protease inhibitor) and is thus similar in structure to most other plasma protease inhibitors ... As deduced from protein and cDNA sequencing, cow, sheep, rabbit and mouse antithrombins are all 433 amino acids in length, ... Unexpectedly the protein crystallized as a heterodimer composed of one molecule of native antithrombin and one molecule of ... C1-inhibitor (which protects the body from excessive protease-triggered activation of its own complement system), antithrombin ... Natural protease inhibitors include the family of lipocalin proteins, which play a role in cell regulation and differentiation ... Inhibitors. Main articles: Protease inhibitor (biology) and Protease inhibitor (pharmacology). The activity of proteases ... Thus, protease inhibitors are developed as antiviral means. Other natural protease inhibitors are used as defense mechanisms. ... APOE qualifies as a checkpoint inhibitor of the classical complement pathway by complex formation with activated C1q. ... Proteins similar in function have been found in choanoflagellates, suggesting that they are a very old class of proteins ... The gene, APOE, is mapped to chromosome 19 in a cluster with apolipoprotein C1 (APOC1) and the apolipoprotein C2 (APOC2). The ... Apolipoprotein E (APOE) is a protein involved in the metabolism of fats in the body of mammals. A subtype is implicated in ... ... soluble complement receptor type 1, anti-C5 antibodies, or C1 inhibitor (C1-INH). Disadvantages of this approach include the ... hormone and protein differences - some proteins will be molecularly incompatible, which could cause malfunction of important ... The binding of XNAs initiate complement activation through the classical complement pathway. Complement activation causes a ... Interruption of the complement cascade The recipient's complement cascade can be inhibited through the use of cobra venom ... Hyperimmunoglobulin E syndrome Complement. deficiency. C1-inhibitor (Angioedema/Hereditary angioedema). Complement 2 deficiency/Complement 4 deficiency ... Genetic disorder, protein biosynthesis: Transcription factor/coregulator deficiencies. (1) Basic domains. 1.2. Feingold ... ... s are classed as irreversible inhibitors and as suicide inhibitors since each serpin protein permanently inactivates a ... Beinrohr L, Harmat V, Dobó J, Lörincz Z, Gál P, Závodszky P (July 2007). "C1 inhibitor serpin domain structure reveals the ... Mollnes TE, Jokiranta TS, Truedsson L, Nilsson B, Rodriguez de Cordoba S, Kirschfink M (September 2007). "Complement analysis ... it became clear that these inhibitors were part of superfamily of related proteins that included both protease inhibitors (e.g ... Complement component 1r "Fluid-phase interaction of C1 inhibitor (C1 Inh) and the subcomponents C1r and C1s of the first component of complement, C1". ... Complement C1r subcomponent (EC 126.96.36.199, activated complement C1r, C overbar 1r esterase, C1r) is a protein involved in the ... C1r along with C1q and C1s form the C1 complex, which is the first component of the serum complement system. C1r is an enzyme ... Arlaud GJ, Gagnon J (April 1983). "Complete amino acid sequence of the catalytic chain of human complement subcomponent C1-r". ... Outline of immunology C6 C7 C8 C9 Complement pathway inhibitors C1-inhibitor - Classical, Lectin, Alternate Decay-accelerating factor (CD59) - ... see complement proteins section) Collectins Mannan-binding lectin (MBL) Surfactant protein A (SP-A) Surfactant protein D (SP-D ... system Complement system Classical complement pathway Mannan-binding lectin pathway Alternate complement pathway Complement ... CL-L1 CL-P1 CL-K1 Peptidoglycan recognition proteins (PGRPs) PGLYRP1 PGLYRP2 PGLYRP3 PGLYRP4 Ficolins FCN1 FCN2 FCN3 Complement ... Complement membrane attack complex Inhibitors. CLA: C1-inhibitor. Decay-accelerating factor/CD59. Factor I. CL: C4BP ... MAC is composed of a complex of four complement proteins (C5b, C6, C7, and C8) that bind to the outer surface of the plasma ... The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5 into C5a and C5b. All three ... Stanley KK, Marazziti D, Eggertsen G, Fey GH (1988). "Relationships between the gene and protein structure in human complement ... Antibody-dependent cellular cytotoxicity Complement. deficiency. C1-inhibitor (Angioedema/Hereditary angioedema). Complement 2 deficiency/Complement 4 deficiency ... Next, the NK cells which have Fc Receptors will bind to that antibody, inducing the NK cell to release proteins such as ... ADCC is independent of the immune complement system that also lyses targets but does not require any other cell. ADCC requires ... During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell. ... ... acts (as a CETP inhibitor) by inhibiting cholesterylester transfer protein (CETP), which normally transfers ... FC(F)(F)c1cc(cc(c1)C(F)(F)F)CN(C(=O)OC)[[email protected]@H]3c2c(ccc(c2)C(F)(F)F)N(C(=O)OCC)[[email protected]@H](C3)CC ... Drugs that interfere with the action of these peptides would aid in lowering cholesterol levels by complementing the action of ... Anacetrapib, CETP inhibitor undergoing development by Merck. Dalcetrapib, CETP inhibitor which also failed in clinical trials ... It was the third TNF inhibitor, after infliximab and etanercept, to be approved in the United States. It was constructed ... CC(C)(C)C(=O)OC1=CC=C(C=C1)S(=O)(=O)NC1=CC=CC=C1C(=O)NCC(O)=O ... antibody and etanercept is a TNF receptor-IgG fusion protein.[ ... Like other TNF inhibitors, it is an immunosuppressive medication, used to treat autoimmune diseases such as rheumatoid ... Chen, Yuehong; Friedman, Marcia; Liu, Gang; Deodhar, Atul; Chu, Cong-Qiu (2018). "Do tumor necrosis factor inhibitors increase ... ... soluble complement receptor type 1, anti-C5 antibodies, or C1 inhibitor (C1-INH). Disadvantages of this approach include the ... hormone and protein differences - some proteins will be molecularly incompatible, which could cause malfunction of important ... The binding of XNAs initiate complement activation through the classical complement pathway. Complement activation causes a ... Interruption of the complement cascade The recipient's complement cascade can be inhibited through the use of cobra venom ... Complement. deficiency. C1-inhibitor (Angioedema/Hereditary angioedema). Complement 2 deficiency/Complement 4 deficiency ... Autoimmune disease, immune response to self-proteins. Allergy, immune response to harmless non-self proteins Histamine ... Complement deficiency is where the function of the complement system is deficient ... OPM protein. 1cwa. Ciclosporin, also spelled cyclosporine and cyclosporin, is an immunosuppressant medication and natural ... Lawen A (October 2015). "Biosynthesis of cyclosporins and other natural peptidyl prolyl cis/trans isomerase inhibitors". ... InChI=1S/C62H111N11O12/c1-25-27-28-40(15)52(75)51-56(79)65-43(26-2)58(81)67(18)33-48(74)68(19)44(29-34(3)4)55(78)66-49(38(11)12 ... CsA binds to cyclophilin D to block the opening of MPTP, and thus decreases the release of protein cytochrome C, which can ... When a single gene deficiency does cause lupus, it is usually attributed to the complement protein genes C1, C2, or C4. The ... Acquired C1 esterase inhibitor deficiency. Adrenergic urticaria. Exercise urticaria. Galvanic urticaria. Schnitzler ... CLA: C1-inhibitor - Faktor ubrzanja raspada/CD59 - Faktor I CL: C4BP. A: Faktor H ... C5a receptor (receptor 1 komplementne komponente 5a, C5AR1, CD88, klaster diferencijacije 88) je G protein spregnuti receptor ... Sengeløv H (1996). "Complement receptors in neutrophils.". Crit. Rev. Immunol. 15 (2): 107-31. PMID 8573284. ... Moždano specifični angiogenezni inhibitor (1, 2, 3) • Cadherin (1, 2, 3) • Kalcitonin • CALCRL • CD97 • Kortikotropin- ... Alternative complement pathway Inhibitors. CLA: C1-inhibitor. Decay-accelerating factor/CD59. Factor I. CL: C4BP ... there are several different kinds of regulatory proteins that disrupt the complement activation process: Complement Receptor 1 ... CFHR5 (Complement Factor H-Related protein 5) is able to bind to act as a cofactor for factor I, has decay accelerating ... Factor I requires a C3b-binding protein cofactor such as complement factor H, CR1, or Membrane Cofactor of Proteolysis (MCP or ... Inhibitors. CLA: C1-inhibitor. Decay-accelerating factor/CD59. Factor I. CL: C4BP ... is a protein that in humans is encoded by the BSG gene. This protein is a determinant for the Ok blood group system. ... protein binding involved in cell-cell adhesion. Cellular component. • integral component of membrane. • membrane. • focal ... protein localization to plasma membrane. • homophilic cell adhesion via plasma membrane adhesion molecules. • axon guidance. • ... ... killer activated and killer inhibitor receptors (KARs and KIRs), complement receptors, Fc receptors, B cell receptors and T ... and can be a protein or peptide (short protein), or another small molecule such as a neurotransmitter, hormone, pharmaceutical ... In biochemistry and pharmacology, a receptor is a protein molecule that receives chemical signals from outside a cell. When ... The proton pump inhibitor omeprazole is an example of an irreversible antagonist. The effects of irreversible antagonism can ... Small-molecule inhibitors of protein kinases generally prevent either phosphorylation of proteins substrates or ... This domain consists of molecular regions that make hydrophobic interactions with the FKB domain and triene region from C-1-C-6 ... PI3K inhibitor. References. ^ a b c d e f g h i j k l Pópulo, Helena; Lopes, José Manuel; Soares, Paula (2012). "The ... The second generation of mTOR inhibitors is known as ATP-competitive mTOR kinase inhibitors. mTORC1/mTORC2 dual inhibitors ... List of skin conditions Acquired C1 esterase inhibitor deficiency Acute urticaria Adrenergic urticaria Anaphylaxis Aquagenic urticaria Cholinergic ... Complement deficiency DiGeorge syndrome (DiGeorge anomaly, thymic hypoplasia) Graft-versus-host disease Griscelli syndrome ... cutaneous neoplasms associated with systemic syndromes List of cutaneous conditions caused by problems with junctional proteins ... Childhood dermatomyositis Childhood discoid lupus erythematosus Childhood systemic lupus erythematosus Complement deficiency ... List of OMIM disorder codes PSAP Complement component 4, partial deficiency of; 120790; C1NH Complement factor H deficiency; 609814; HF1 Complement factor ... HRG Thrombophilia due to protein C deficiency, autosomal dominant; 176860; PROC Thrombophilia due to protein C deficiency, ... type C1; 257220; NPC1 Niemann-Pick disease, type C2; 607625; NPC2 Niemann-Pick disease type D; 257220; NPC1 Night blindness, ... Lutheran inhibitor; 111150; KLF1 Bloom syndrome; 210900; RECQL3 Blue cone monochromacy; 303700; OPN1MW Blue cone monochromacy; ... List of MeSH codes (D12.776) ... wnt1 protein MeSH D12.776.624.664.700.978 - wnt2 protein MeSH D12.776.624.776.355.100 - cyclin-dependent kinase inhibitor p15 ... lupus coagulation inhibitor MeSH D12.776.377.715.548.114.323.300 - complement c3 nephritic factor MeSH D12.776.377.715.548.114. ... cytochromes c1 MeSH D12.776.422.220.286.300 - cytochromes c2 MeSH D12.776.422.220.286.600 - cytochromes c6 MeSH D12.776.422.220 ... groel protein MeSH D12.776.602.500.500.100 - fusion proteins, bcr-abl MeSH D12.776.602.500.500.320 - fusion proteins, gag-onc ... Effector functions also require the use of complement proteins in serum or Fc-receptor on cell membranes. Ansuvimab has been ... August 2011). "Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection". Nature. 477 (7364): ... would interact with virus's cell receptor protein, Niemann-Pick C1 (NPC1). This "competition" by ansuvimab prevents Ebola virus ... Ansuvimab is a neutralizing antibody, meaning it binds to a protein on the surface of Ebola virus that is required to infect ... The Factor H-related protein 1 (FHR1) has been identified as a novel inhibitor of the complement pathway. FHR1 blocks C5 ... C2a produced by cleavage mediated by C1 complex, and C3b produced by cleavage mediated by the classical pathway C3 convertase ( ... The target of C5 convertase is complement protein C5. C5 is a two-chain (α, β) plasma glycoprotein (Mr = 196,000). C5 and C3 ... 2009). "Factor H-related protein 1 (FHR-1) inhibits complement C5 convertase activity and terminal complex formation". Blood. ... Complement C1 Inhibitor Protein \| Harvard Catalyst Profiles \| Harvard Catalyst "Complement C1 Inhibitor Protein" by people in Harvard Catalyst Profiles by year, and whether "Complement C1 Inhibitor Protein" ... Complement C1 Inactivator Proteins [D12.776.124.486.274.920.250]. Complement C1 Inhibitor Protein [D12.776.124.486.274.920. ... "Complement C1 Inhibitor Protein" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH ( ... Below are the most recent publications written about "Complement C1 Inhibitor Protein" by people in Profiles. ... complement C1 inhibitor protein \| American Society of Nephrology JoVE Search Results: Complement C1 Inhibitor Protein Complement, Immunity, Disease, Morbidity, Risk, Mortality, and Treatment ... Human complement regulators C4b-binding protein and C1 esterase inhibitor interact with a novel outer surface protein of ... Human pasteurized C1-inhibitor concentrate for the treatment of hereditary angioedema due to C1-inhibitor deficiency. Abstract ... Treatment with C1-inhibitor concentrate does not induce IgM type anti-C1 inhibitor antibodies in patients with hereditary ... C1 Protein Inhibitor) Determination Reagents" , "Reagents, Immunoassay, Protein, Complement Component, C1 Inhibitor" ... an esterase inhibitor of the C1 protein found in the classic pathway of the complement components proteins. The absence of this ... IVD Test Reagent/Kits, Immunoassay, Protein, Complement Component, C1 Inhibitor. Definition : Immunoassay reagents intended to ... Home > Specialties > IVD Test Reagent/Kits, Immunoassay, Protein, Complement Component, C1 Inhibitor ... RUCONEST® as a Therapeutic Strategy to Reduce the Incidence of Delayed Graft Function - Full Text View - ClinicalTrials.gov Complement C1 Inhibitor Protein. Complement Inactivating Agents. Immunosuppressive Agents. Immunologic Factors. Physiological ... Blom AM, Villoutreix BO, Dahlbäck B. Complement inhibitor C4b-binding protein-friend or foe in the innate immune system? Mol ... Davis AE 3rd, Lu F, Mejia P. C1 inhibitor, a multi-functional serine protease inhibitor. Thromb Haemost. 2010 Nov;104(5):886-93 ... The specific aim of this study is to evaluate the effect of recombinant human C1-inhibitor (rhC1INH), as a kidney recipient ... Safety of Ruconest in 2-13 Year Old Hereditary Angioedema (HAE) Patients - Full Text View - ClinicalTrials.gov Complement C1 Inhibitor Protein. Complement Inactivating Agents. Immunosuppressive Agents. Immunologic Factors. Physiological ... Experimental: Recombinant Human C1 Inhibitor Drug: rhC1INH Patients up to 84 kg will receive one i.v. injection of Ruconest at ... Pharmacokinetics and Efficacy of Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks in Pediatric Patients With ... A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous CINRYZE Administration - Full Text View ... Complement C1 Inhibitor Protein. Complement Inactivating Agents. Immunosuppressive Agents. Immunologic Factors. Physiological ... C1 Inhibitor (C1INH) and C4 Levels [ Time Frame: 18 days in each treatment period ]. Number of Subjects With C1INH Antibodies ... Drug Information available for: SERPING1 protein, human Genetic and Rare Diseases Information Center resources: Hereditary ... C1 esterase inhibitor (human). Experimental: IV CINRYZE First, Then SC CINRYZE Dose 2 Biological: CINRYZE C1 esterase inhibitor ... Kinetics, Efficacy and Safety of C1-Esteraseremmer-N - Full Text View - ClinicalTrials.gov Complement C1 Inhibitor Protein. Complement Inactivating Agents. Immunosuppressive Agents. Immunologic Factors. Physiological ... markedly decreased C1 inhibitor activity, decreased level of C1 inhibitor antigen and a decreased level of C4. ... The changes in the manufacturing process of C1-esteraseremmer-N, compared to Cetor® (the currently marketed C1-inhibitor ... The changes in the manufacturing process of C1-esteraseremmer-N, compared to Cetor® (the currently marketed C1-inhibitor ... Serum concentrations of C reactive protein, alpha(1) antitrypsin, and complement (C3, C4, C1 esterase inhibitor) before and... ... complement C3 and C4) and anti-inflammatory (α1 antitrypsin, C1 esterase inhibitor (C1-INH)) acute phase proteins in elite ... complement C3 and C4) and anti-inflammatory (α1 antitrypsin, C1 esterase inhibitor (C1-INH)) acute phase proteins in elite ... complement C3 and C4) and anti-inflammatory (α1 antitrypsin, C1 esterase inhibitor (C1-INH)) acute phase proteins in elite ... complement C3 and C4) and anti-inflammatory (α1 antitrypsin, C1 esterase inhibitor (C1-INH)) acute phase proteins in elite ... Endothelial cells cultured from human brain microvessels produce complement proteins factor H, factor B, C1 inhibitor, and C4<... Endothelial cells cultured from human brain microvessels produce complement proteins factor H, factor B, C1 inhibitor, and C4. ... Endothelial cells cultured from human brain microvessels produce complement proteins factor H, factor B, C1 inhibitor, and C4. ... Endothelial cells cultured from human brain microvessels produce complement proteins factor H, factor B, C1 inhibitor, and C4. ... In the present study, expression of complement proteins (C1 inhibitor, factor H, factor B, C4) by cultured endothelial cells ... The Correlation between Inflammatory Biomarkers and Polygenic Risk Score in Alzheimer's Disease C1 inhibitor (C1inh), terminal complement complex (TCC)] and the benchmark inflammatory marker C-reactive protein (CRP). Plasma ... We measured five complement biomarkers [complement receptor 1 (CR1), clusterin, complement component 9 (C9), ... The results suggest that elevated plasma levels of inflammatory biomarkers, including complement proteins, associate with ... Hereditary angioedema in Costa Rica] Keywords: Angioedema; Bradykinin; Complement C1 esterase inhibitor protein; Kallikrein; SERPING1. Publication types * English ... as a primary immunodeficiency of the complement system because it is characterized by the absence of C1 esterase inhibitor (C1- ... debido a que se caracteriza por la ausencia de C1 inhibidor esterasa y por edema periódico de cualquier región del cuerpo que ... SciELO - Brazil - Icatibant, an inhibitor of bradykinin receptor 2, for hereditary angioedema attacks: prospective... Angioedemas, hereditary; Complement C1 inhibitor protein; Therapy [subheading]; Receptors, bradykinin; Bradykinin. CONTEXTO E ... Hereditary angioedema (HAE) with C1 inhibitor (C1-INH) deficiency is a rare disease that manifests as recurrent episodes of ... Two forms of HAE have been described: type I HAE with low C1-INH antigenic protein and functional activity (85% of the cases); ... Zanichelli A, Vacchini R, Badini M, Penna V, Cicardi M. Standard care impact on angioedema because of hereditary C1 inhibitor ... Clinical review of hereditary angioedema: diagnosis and management. ... is caused by a deficiency in C1 esterase inhibitor and is characterized by sudden attacks of edema associated with discomfort ... 0/Complement C1 Inactivator Proteins; 0/Complement C1 Inhibitor Protein; 0/Estrogen Antagonists; 0/SERPING1 protein, human; ... Complement C1 Inactivator Proteins / adverse effects, therapeutic use. Complement C1 Inhibitor Protein / metabolism. Danazol / ... Hereditary angioedema (HAE) is caused by a deficiency in C1 esterase inhibitor and is characterized by sudden attacks of edema ... Genomic blueprint of a relapsing fever pathogen in 15th century Scandinavia \| PNAS 2010) Human complement regulators C4b-binding protein and C1 esterase inhibitor interact with a novel outer surface protein of ... these proteins are the surface lipoproteins vlp and vsp, which are also known to be its main proinflammatory proteins (30). The ... 2002) Characterisation of silent and active genes for a variable large protein of Borrelia recurrentis. BMC Infect Dis 2:25. ... 3). Strikingly, these genes mark the end of mapping for plasmid pl33 and pl37, while pl53 retains a hypothetical protein at its ... Systems-Level Analysis of Proteolytic Events in Increased Vascular Permeability and Complement Activation in Skin Inflammation ... ... only one per protein). (F) Assignment of N termini to C1 inhibitor (C1 Inh) and ApoC1. C1 inhibitor was identified by its ... C1 inhibitor also controls the complement system whereby intact C1 inhibitor reduces the extent of complement activation (9). ... We found that the complement 1 (C1) inhibitor attenuated the increase in serum protein accumulation in inflamed skin. Cleavage ... D) Inhibition of complement activity by C1 inhibitor (C1 Inh) as assessed in a hemolytic assay with sheep red blood cells. ... Current Topics in Complement II \| SpringerLink Complement has long been regarded as a pivotal effector arm of the innate immune response, eliciting important immunoregulatory ... Human Astrovirus Coat Protein: A Novel C1 Inhibitor Neel K. Krishna, Kenji M. Cunnion ... protein structures, design of complement inhibitors, and complement assays discussed during the conference. ... Role of Complement in Motor Neuron Disease: Animal Models and Therapeutic Potential of Complement Inhibitors ... EP2756302A1 - Methods of predicting and decreasing the risk of pre-term birth - Google Patents ... zinc finger protein 23 (ZNF23), collagen type XXVII al (COL27AI), Kazrin isoform-1, keratin-associated protein 10-9 (KRTAPIO-9 ... Huntingtin (HTT), microtubule associated protein 9 (MAP9), coiled-coil domain-containing protein 13 (CCDC13), inositol ... ALLI-fused gene from chromosome 4 protein (AR4)/Fragile X Mental Retardation 2 (FMR2) family member 3 (AFF3), transthyretin ( ... methods include providing a sample from the subject and detecting the level of one or more of growth arrest-specific protein 1 ... complement C1 esterase inhibitor - WellSpan Health Library People with a condition called hereditary angioedema do not have enough of this protein. Hereditary angioedema can cause ... Complement C1 esterase inhibitor is a man-made form of a protein in blood that helps control swelling in the body. ... What is complement C1 esterase inhibitor?. Complement C1 esterase inhibitor is a man-made form of a protein in blood that helps ... Complement C1 esterase inhibitor is used in people with hereditary angioedema. Berinert is used to treat attacks of angioedema ... Plasma Derived Proteins and Enzymes \| China-Mainland \| Sigma-Aldrich Complement C1 Esterase inhibitor. 15-35. Complement C1r Component. -. Complement C4 Binding Protein. -. ... Many of these proteins are produced on a large-scale custom basis under GMP for our manufacturing customers. For more extensive ... It is estimated that plasma may contain as many as 40,000 different proteins from about 500 gene products. Sigma-Aldrich has ... From "The Plasma Proteins", Volume IV, 2nd Edition, 1984, Frank W. Putnam. ... MEDLINE - Results of the search \|page 1\| Complement C1 Inactivator Proteins/genetics. Complement C1 Inhibitor Protein/chemistry. Complement C1 Inhibitor Protein/ ... 0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Complement C1 Inactivator Proteins); 0 (Complement C1 Inhibitor Protein); 0 ( ... 0 (Antifibrinolytic Agents); 0 (Complement C1 Inactivator Proteins); 0 (Complement C1 Inhibitor Protein); 0 (Complement ... Complement C1 Inactivator Proteins); 0 (Complement C1 Inhibitor Protein); 0 (Peptides); 0 (Recombinant Proteins); 0 (SERPING1 ... Department of Medicine - Research Output - Penn State Current Topics in Complement II \| John D. Lambris \| Springer Complement has long been regarded as a pivotal effector arm of the innate immune response, eliciting important immunoregulatory ... Human Astrovirus Coat Protein: A Novel C1 Inhibitor. Pages 228-242. Krishna, Neel K. (et al.) ... protein structures, design of complement inhibitors, and complement assays discussed during the conference. ... Role of Complement in Motor Neuron Disease: Animal Models and Therapeutic Potential of Complement Inhibitors ... Frontiers \| Proteomic Markers of Non-functional Overreaching During the Race Across America (RAAM): A Case Study \| Physiology ... complement C4-B (231%), serum amyloid A-4 protein (210%), inter-alpha-trypsin inhibitor heavy chain H4 (191%), and alpha-1- ... complement C4-B (231%), serum amyloid A-4 protein (210%), inter-alpha-trypsin inhibitor heavy chain H4 (191%), and alpha-1- ... Proteomic analysis indicated large increases for immune-related proteins involved with complement activation and the acute ... The blood proteins with the largest increase were complement component C7 (359%), ... Angioedema - Immune Disorders - Merck Manuals Consumer Version C1 inhibitor is one of the proteins in the complement system, which is part of the immune system. Symptoms usually start during ... acquired C1 inhibitor deficiency) are caused by a deficiency or malfunction of C1 inhibitor, which is part of the immune system ... Acquired C1 Inhibitor Deficiency). By Peter J. Delves, PhD, Professor of Immunology, Division of Infection & Immunity, Faculty ... These drugs, taken by mouth, can stimulate the body to produce more C1 inhibitor, but they may be less effective for acquired ... BestBets: In patients with acute hereditary angioedema is treatment with C1 esterase inhibitor better than fresh frozen plasma? ... exp Complement C1 Inactivator Proteins/ OR exp Complement C1 Inhibitor Protein/ OR exp Complement C1/ OR c1 esterase inhibitor. ... OR c1 inhibitor.mp.) LIMIT to English Language and Humans CINAHL - (Angioedema) AND (Fresh Frozen Plasma) and (C1 inhibitor) ... In the UK C1 inhibitor is licensed for use in acute hereditary angioedema attacks and despite a lack of clinical trials it is ... Despite little evidence C1 inhibitor seems to be the treatment of choice for acute hereditary angioedema attacks rather than ... Urticarial vasculitis - Wikipedia ... named C1-inhibitor. The inhibition of C1-inhibitor leads to over-activation of the complement pathway and one protein that ... Also, there has been some speculation as to an additional autoantibody against an inhibitor protein (in the complement pathway ... Consequently, levels of all complement proteins become low. The complement pathway is composed of several subset pathways: the ... C1q is an integral component within the complement pathway - a complicated cascade of protein interactions, culminating in an ... Acute Transverse Myelitis disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials Complement C1 Inactivator Proteins. Phase 1. 41. Complement C1 Inhibitor Protein. Phase 1. ... C1-esterase Inhibitor (Cinryze) for Acute Treatment of Neuromyelitis Optica Exacerbation. Completed. NCT01759602 Phase 1. C1- ... esterase inhibitor (Cinryze). 7. Ublituximab for Acute Neuromyelitis Optica (NMO) Relapses. Active, not recruiting. NCT02276963 ... Nanofiltered C1 esterase inhibitor for treatment of laryngeal attacks in patients with hereditary angioedema<... C1 INH) deficiency. The preparation of nanofiltered C1 INH (C1 INH-nf) used in this study is indicated for routine prophylaxis ... C1 INH) deficiency. The preparation of nanofiltered C1 INH (C1 INH-nf) used in this study is indicated for routine prophylaxis ... C1 INH) deficiency. The preparation of nanofiltered C1 INH (C1 INH-nf) used in this study is indicated for routine prophylaxis ... C1 INH) deficiency. The preparation of nanofiltered C1 INH (C1 INH-nf) used in this study is indicated for routine prophylaxis ... Complement 1 Inhibitor Is a Regulator of the Alternative Complement Pathway \| JEM Complement 1 inhibitor (C1-INH)* is a critically important protein that controls activation of multiple plasma mediator ... We studied complement 1 inhibitor (C1-INH) as an inhibitor of the alternative complement pathway. C1-INH prevented lysis, ... C1-INH and alternative-complement activities in C1-INH depleted serum. C1-INH functional activity (white bars) and alternative- ... All the above attempts failed to detect interaction between labeled proteins and C1-INH or control proteins. However, C1-INH ... Inactivator ProteinsAngioedemaSerumActivationC1INHDeficiency of C1 inhibitorSERPING1Recombinant humanPathwayEfficacyInflammationAcquired C1 Inhibitor DeficiencyGeneInhibitory ProteinsBradykininAttacksInhibitionFunctional C1 inhibitorAntibodiesLysisCytokinesCoagulationReceptorsKallikreinEsterase InhibitorsRegulateComponentSerpin familyCascadeRole of ComplementPathwaysInflammatoryAutosomal-dominantLevelsRegulatesMetabolismDysfunctionSerine proteaseTherapyPathogensPatientsInnateRegulatoryGroup of proteinsMembrane proteinRegulator - AND (exp Complement C1 Inactivator Proteins/ OR exp Complement C1 Inhibitor Protein/ OR exp Complement C1/ OR c1 esterase inhibitor.mp. (bestbets.org) - The Effectiveness and Value of Lanadelumab and C1 Esterase Inhibitors for Prophylaxis of Hereditary Angioedema Attacks. (harvard.edu) - The absence of this inhibitor is associated with an inherited disease (i.e., angioedema) that causes localized subcutaneous and visceral edema. (optometricmanagement.com) - A multicentre study to investigate pharmacokinetics, clinical efficacy and safety of nanofiltered Cetor® (called C1-esteraseremmer-N during the development phase) for the treatment of hereditary angioedema (HAE) will be performed. (clinicaltrials.gov) - This study KB2003.01 consists of three parts, part A pharmacokinetics (phase II), part B treatment of attacks of angioedema (phase III) and part C prophylactic use of C1 inhibitor (phase III). (clinicaltrials.gov) - In part A, the pharmacokinetics of C1-esteraseremmer-N in patients with hereditary angioedema will be compared with the current registered product, Cetor®, in a randomised, blinded cross-over design. (clinicaltrials.gov) - Hereditary angioedema is classified as a primary immunodeficiency of the complement system because it is characterized by the absence of C1 esterase inhibitor (C1-INH) and by the periodic edema of any region of the body that involves soft tissue. (nih.gov) - Antecedentes: El angioedema hereditario se encuentra clasificado como una inmunodeficiencia primaria del sistema de complemento, debido a que se caracteriza por la ausencia de C1 inhibidor esterasa y por edema periódico de cualquier región del cuerpo que involucre tejido blando. (nih.gov) - Objetivo: Caracterizar a los pacientes adultos con diagnóstico de angioedema hereditario atendidos en el Servicio de Alergología Clínica del Hospital México de la Caja Costarricense del Seguro Social. (nih.gov) - Los datos fueron obtenidos de los expedientes clínicos de los pacientes con diagnóstico confirmado de angioedema hereditario que estaban en seguimiento en el Servicio de Alergología del Hospital México, Caja Costarricense del Seguro Social. (nih.gov) - Hereditary angioedema (HAE) with C1 inhibitor deficiency manifests as recurrent episodes of edema involving the skin, upper respiratory tract and gastrointestinal tract. (scielo.br) - O angioedema hereditário (AEH) com deficiência de inibidor de C1 manifesta-se por episódios recorrentes de edema envolvendo pele, trato respiratório superior e gastrointestinal. (scielo.br) - Hereditary angioedema (HAE) is caused by a deficiency in C1 esterase inhibitor and is characterized by sudden attacks of edema associated with discomfort and pain. (biomedsearch.com) - People with a condition called hereditary angioedema do not have enough of this protein. (wellspan.org) - Complement C1 esterase inhibitor is used in people with hereditary angioedema. (wellspan.org) - BestBets: In patients with acute hereditary angioedema is treatment with C1 esterase inhibitor better than fresh frozen plasma? (bestbets.org) - In the UK C1 inhibitor is licensed for use in acute hereditary angioedema attacks and despite a lack of clinical trials it is recommended for use over fresh frozen plasma. (bestbets.org) - Despite little evidence C1 inhibitor seems to be the treatment of choice for acute hereditary angioedema attacks rather than fresh frozen plasma but more trials need to be carried out. (bestbets.org) - Background: Laryngeal edema is a life-threatening manifestation of hereditary angioedema (HAE), an autosomal-dominant disorder caused by quantitative or functional C1 esterase inhibitor (C1 INH) deficiency. (elsevier.com) - The preparation of nanofiltered C1 INH (C1 INH-nf) used in this study is indicated for routine prophylaxis against angioedema attacks in the United States and for treatment, preprocedure prevention, and routine prevention of HAE in Europe. (elsevier.com) - Conclusion: This analysis supports that C1 INH-nf is an effective and well-tolerated therapy for laryngeal angioedema attacks. (elsevier.com) - They had a familial history of angioedema and normal C1 inhibitor (C1-INH) levels, leading to the diagnosis of HAE with normal C1-INH (HAEnC1-INH) or HAE type III. (bireme.br) - The inhibition of C1-inhibitor leads to over-activation of the complement pathway and one protein that builds up controls angioedema (vessel - swelling), resulting in excess water building up under the skin (the weal appearance). (wikipedia.org) - The literature search was performed using Pubmed, and the terms Africa and African and Zulu in combination with each of C1 esterase inhibitor, hereditary angio-oedema and hereditary angioedema . (scielo.org.za) - Hereditary angioedema (a genetic disorder) and acquired angioedema (acquired C1 inhibitor deficiency) are caused by a deficiency or malfunction of C1 inhibitor, which is part of the immune system. (merckmanuals.com) - Hereditary angioedema is a genetic disorder that causes a deficiency or malfunction of C1 inhibitor. (merckmanuals.com) - Doctors diagnose hereditary or acquired angioedema by measuring C1 inhibitor levels or activity in a sample of blood. (merckmanuals.com) - While functional anti-FceRIa and anti-lgE have the potential to play a role in histamine-mediated angioedema, C1 inhibitor (INH) deficiency or dysfunction, sometimes due to anti-C1 INH, plays a role in bradykinin (BK)-mediated angioedema. (thefreedictionary.com) - Hereditary angioedema due to C1 inhibitor deficiency: Patient registry and approach to the prevalence in Spain. (thefreedictionary.com) - 15 Feb 2018 According to a Shire media release, based on the data of LEVP 2006-1, LEVP 2006-4, 0624-203 and 0624-301 studies, U.S. FDA has accepted the CINRYZE (C1 esterase inhibitor [human]) sBLA to expand the currently approved indication to include children aged 6 years and older with hereditary angioedema (HAE). (springer.com) - Hereditary angioedema (HAE) is an autosomal dominant disorder characterized by deficient or dysfunctional C1 esterase inhibitor. (elsevier.com) - Introduction:Hereditary angioedema (HAE) is a rare disorder characterized by C1 esterase inhibitor (C1-INH) deficiency, resulting in periodic attacks of acute edema that can be life-threatening if they occur in the laryngeal region. (elsevier.com) - Kiessling, Peter C. / Prospective study of rapid relief provided by C1 esterase inhibitor in emergency treatment of acute laryngeal attacks in hereditary angioedema . (elsevier.com) - The prevalence of non-hereditary angioedema was investigated in a general population sample (n = 7,931) and in a sample of Danish patients (n = 7,433) tested for deficiency of functional complement C1 esterase inhibitor protein (functional C1 INH). (medicaljournals.se) - Hereditary angioedema (HAE) is a rare, life-threatening, autosomal dominant disease characterized by recurrent episodes of angioedema, and caused by a deficiency of the plasma protein C1-esterase inhibitor (C1-INH). (bvsalud.org) - They were diagnosed as having hereditary angioedema with C1-INH deficiency (C1-INH hereditary angioedema) for the first time. (bvsalud.org) - Conclusion: Patients with C1-INH hereditary angioedema may be misdiagnosed as having familial Mediterranean fever in regions where the disorder is endemic. (bvsalud.org) - Danazol and C1 replacement treatments provide significant reduction in hereditary angioedema attacks. (bvsalud.org) - We report on an angioedema patient with a genetic defect in complement 1 inhibitor, manifesting migraine-like episodes of headache, effective prophylaxis with Danazol, and triptan for a treatment of acute clinical episode. (bvsalud.org) - Although hereditary angioedema accounts for only a small fraction of all cases of angioedema, it is the most common genetically linked clinical disorder caused by the deficiency of a protein associated with complement activation. (utmb.edu) - Hereditary angioedema (HAE) is predominantly caused by a deficiency in C1 esterase inhibitor (C1INH) (HAE-C1INH). (elsevier.com) - Conestat alfa is a recombinant human C1 esterase inhibitor, which inhibits activation of the complement system and is licensed in Europe and USA for the treatment of a hereditary condition (hereditary angioedema). (centerwatch.com) - Patients with recurrent angioedema without wheals, who are not on ACE-inhibitors, should be asked for a detailed family history. (epgonline.org) - They should be checked for hereditary bradykinin-mediated angioedema (HAE I-III) and angioedema due to acquired C1-inhibitor (C1-INH) deﬁciency (AAE). (epgonline.org) - 2 Normal C4 complement levels, C1-inhibitor protein and function levels, the absence of C1-INH antibodies, or mutations in the C1-INH or factor XII gene rules out bradykinin-related angioedema. (epgonline.org) - For example, C1 esterase inhibitor deficiency is the underlying defect in hereditary angioedema, discussed in a separate chapter. (psychiatryadvisor.com) - If the level of C1 inhibitors is not normal and is lower or higher in the blood, it leads to hereditary or acquired angioedema. (marketresearchreports.biz) - The global C1 inhibitors market is projected to grow at a rapid pace due to usage in hereditary angioedema (HAE) treatment and more preferred use as prophylactic treatment. (marketresearchreports.biz) - Common symptoms of C1 deficiency leading to hereditary or acquired angioedema are painful swelling on face, lips, tongue, hands, feet, and others. (marketresearchreports.biz) - C1 inhibitors are the most effective and feasible treatment for HAE and acquired angioedema. (marketresearchreports.biz) - Deficiencies in C1inhibitor are the primary cause of hereditary angioedema (HAE, hereditary angioneurotic edema), a disease characterized by edema in the respiratory and gastrointestinal tracts. (reliatech.de) - Acquired angioedema (AAE) patients have deficiency of C1 esterase inhibitor (C1INH) that is not due to genetic defect. (mastattack.org) - Treatment for HAE follows the guidelines set out by the World Allergy Organization (WAO) by using C1-INH or other drugs to treat hereditary angioedema. (medicinenet.com) - A deficiência do inibidor de C1 leva a uma patologia conhecida como angioedema hereditário. (usp.br) - The deficiency of C1 inhibitor leads to a condition known as hereditary angioedema. (usp.br) - Hereditary Angioedema is caused by a missing C1 esterase inhibitor protein (C1-INH), which helps regulate inflammation. (pptaglobal.org) - Deficiency of or defect in the protein causes hereditary angioedema . (thefreedictionary.com) - Objectives: To determine serum concentrations of proinflammatory (C reactive protein, complement C3 and C4) and anti-inflammatory (α1 antitrypsin, C1 esterase inhibitor (C1-INH)) acute phase proteins in elite cyclists before and during a three week cycle tour. (edu.au) - abstract = "Objectives: To determine serum concentrations of proinflammatory (C reactive protein, complement C3 and C4) and anti-inflammatory (α1 antitrypsin, C1 esterase inhibitor (C1-INH)) acute phase proteins in elite cyclists before and during a three week cycle tour.Methods: Seventeen professional cyclists participating in the Vuelta a Espańa volunteered for the study. (edu.au) - During inflammation, vascular permeability is increased by various proteolytic events, such as the generation of bradykinin, that augment local tissue responses by enabling tissue penetration of serum proteins, including complement and acute-phase proteins. (sciencemag.org) - In response to phorbol ester-induced inflammation, mice deficient in matrix metalloproteinase 2 (MMP2) showed reduced accumulation of serum proteins in the skin and exhibited different proteolytic networks from those of wild-type mice. (sciencemag.org) - C1-INH prevented lysis, induced by the alternative complement pathway, of paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes in human serum. (rupress.org) - Removal of C1-INH from serum, in the presence of Mg-EGTA with an anti-C1-INH immunoabsorbant, markedly increased alternative-pathway lysis. (rupress.org) - Arp2/3 Coronin Dystrophin FtsZ Gloverin Keratin Myosin Tubulin Collagen Elastin F-spondin Pikachurin Fibronectin Serum Amyloid P Component Serum albumin Complement proteins C1-inhibitor C3-convertase Factor VIII Factor XIII Protein C Protein S Protein Z Protein Z-related protease inhibitor Thrombin Von Willebrand Factor C-reactive protein Hemoglobin (oxyhemoglobin and deoxyhemoglobin) Cadherin Ependymin Integrin NCAM Selectin Ion pumping enzymes are in the enzymes section. (wikipedia.org) - Although often overlooked as a defense of the respiratory tract, complement levels in this location are normally 10 to 20% of that found in serum and increase during inflammation ( 21 ). (asm.org) - Resistance to complement mediated killing, or serum resistance, is a common trait of pathogenic bacteria. (semanticscholar.org) - Marr N, Shah N, Lee R, Kim E, Fernandez R. Bordetella pertussis autotransporter Vag8 binds human C1 esterase inhibitor and confers serum resistance. (labome.org) - The C1-INH antigen serum level and functional assay of the index patient and ten other family members were studied. (bvsalud.org) - Surrogate markers of kidney injury including serum creatinine and cystatin C and urinary Neutrophil gelatinase-associated lipocalin and TIMP2 * Insulin-like growth factor-binding protein 7 (IGFBP7) will be assessed over a 48 hours time period. (centerwatch.com) - Serum C1 esterase inhibitor levels immediately before and 10 minutes after administration of Conestat alfa or placebo will be assessed. (centerwatch.com) - The role of thyroxine (T4)-binding serum proteins in oleic acid-induced increase in free T4 in nonthyroidal illnesses. (harvard.edu) - Seasonal changes in serum thyroid hormone binding proteins in the woodchuck (Marmota monax). (harvard.edu) - HAE is diagnosed by the patient's appearance, family history, blood testing for serum C4 levels, and other complement levels such as C1, C2 and C4. (medicinenet.com) - The transfer of the major egg yolk proteins such as Very Low Density Lipoproteins (VLDL) containing essentially apovitellenin and apolipoprotein-B, but also vitellogenins and some other plasma proteins from the blood such as serum albumin to the interstitial fluid of the thecae is possible due to the presence of broad discontinuities in the capillary endothelium. (biomedcentral.com) - Several surfaces that have the capacity for initiating FXII contact activation have been identified, including misfolded protein aggregates, collagen, nucleic acids, and platelet and microbial polyphosphate. (bireme.br) - Complement 1 inhibitor (C1-INH) * is a critically important protein that controls activation of multiple plasma mediator pathways ( 1 ). (rupress.org) - C1-INH is a known inhibitor of kinin generating (kallikrein), fibrinolytic (plasmin), and contact activation (intrinsic) pathway of the coagulation cascade (factor XIIa, XIIf, and factor XIa) ( 1 , 6 - 9 ). (rupress.org) - Recently, it has been shown to be an inhibitor of the mannan-binding lectin pathway of complement activation, inhibiting mannan-binding lectin-associated serine proteases (MASPs) in that pathway ( 10 ). (rupress.org) - Proteomic analysis indicated large increases for immune-related proteins involved with complement activation and the acute phase response, which could be useful biomarkers for non-functional overreaching. (frontiersin.org) - The anti-C1q antibodies found in patients with hypocomplementemic urticarial vasculitis activate C1q, which instigates activation of the entire complement pathway. (wikipedia.org) - The study shows that post-transplant treatment with C1-INH results in significant increases in the levels of complement components 3 and 4, suggesting that C1-INH inhibits activation of the complement system following transplantation. (bio-medicine.org) - Antibody-mediated rejection is a major cause of kidney transplant failure and is often associated with activation of complement, a set of proteins that work with antibodies and play a role in the development of inflammation and tissue damage. (bio-medicine.org) - Our findings provide additional insight into how C1-INH affects complement activation and represent an important advance in the study of complement-targeting therapeutics. (bio-medicine.org) - It is a consequence of either a deficiency (type 1 - 85% of affected families) or a dysfunction (type 2) of C1 inhibitor (C1-INH) - a protein that prevents complement activation by both the classic route and the mannan-binding pathway. (scielo.org.za) - Complement activation was monitored by enzyme-linked immunosorbent assay (ELISA) or Western blotting. (asm.org) - These studies show that BrkA inhibits the classical pathway of complement activation and prevents accumulation of deposited C4. (asm.org) - Both the classical and alternative pathways of complement activation are represented, although details are given only for the classical pathway. (asm.org) - The nonactivated complement proteins are indicated above and to the right of the wide arrows, and the arrows pointing from them show the product that is released during activation. (asm.org) - Its protein inhibits activated C1r and C1s of the first complement component and thus regulates complement activation. (genetex.com) - Regulation of complement activation by C-reactive protein: targeting of the inhibitory activity of C4b-binding protein. (semanticscholar.org) - Previous work has defined an immune evasion role of flavivirus NS1 in limiting complement activation by forming a complex with C1s and C4 to promote cleavage of C4 to C4b. (jimmunol.org) - In this study, we demonstrate a second mechanism, also involving C4 and its active fragment C4b, by which NS1 antagonizes complement activation. (jimmunol.org) - Together, these studies further define the immune evasion potential of NS1 in reducing the functional capacity of C4 in complement activation and control of flavivirus infection. (jimmunol.org) - Each complement activation pathway is initiated by a distinct set of recognition molecules and converges at the cleavage of C3 to C3a and C3b. (jimmunol.org) - CD59) to prevent host tissue bystander damage after complement activation. (arvojournals.org) - CD46 and CD55 act early in complement activation to disable the central amplification enzymes C3 and C5 convertases. (arvojournals.org) - In regard to complement resistance, Borrelia utilize a plethora of immune evasion strategies involves capturing of host-derived complement regulators, terminating complement activation as well as shedding of cell-destroying complement complexes to manipulate and to expeditiously inhibit human complement. (frontiersin.org) - This prolonged neuroprotection may depend, at least in part, on increased expression of neuroplasticity-related genes driven by reduced complement activation. (springer.com) - 2003. Complement activation contributes to hypoxic-ischemic brain injury in neonatal rats. (springer.com) - The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate immunity. (hindawi.com) - Uncontrolled activation of the complement system during sepsis and SIRS with in excessive generation of complement activation products contributes to an ensuing dysfunction of various organ systems. (hindawi.com) - In humans, the plasma levels of complement activation products rise early, are persistently elevated in patients after thermal injury, trauma, and sepsis, and correlate with the severity of injury and inversely with the outcome [ 16 - 22 ]. (hindawi.com) - It is well established that activation of the complement cascade alters functional responses of neutrophils (PMN) in the course of systemic inflammation and contributes to the development of organ failure [ 15 , 23 ]. (hindawi.com) - Following renal ischemia activation of the lectin pathway of complement in particular has been associated with local tissue damage in the kidney. (centerwatch.com) - This damage, called "reperfusion injury", is associated with an inflammatory reaction, characterised by an invasion of white blood cell in the transplanted organ, and activation of a group of proteins called the complement system. (europa.eu) - complement activation is thought to play a critical role in the reperfusion injury. (europa.eu) - Blocking complement activation is known to improve the function of transplanted kidneys in experimental models. (europa.eu) - Enzyme-linked immunosorbent assay (ELISA) for complement components, cytokine IL-12 and western blot for C3 activation were performed on CSF and plasma samples. (biomedcentral.com) - The activity of the complement system in CSF was increased in non-HIV patients with CM. C1q, MBL and FB are the important participants in the complement activation in CM. The relative contribution of each of the specific complement pathways and complement cascades in protection and inflammation resolution against CM warrant further investigation. (biomedcentral.com) - Activation of the complement system in response to invading pathogens is initiated through the classical (CP), alternative (AP) and lectin (LP) pathways. (biomedcentral.com) - The complement system has the inhibitory proteins to regulate the location and efficacy of complement activation. (biomedcentral.com) - Complement has many functions, including promoting phagocytosis of pathogens by acting as an opsonin, inducing lysis of bacteria or susceptible cells and generatinginflammation by products formed during complement activation. (psychiatryadvisor.com) - Complement is often associated with unregulated inflammation, and many mechanisms exist for downregulation of complement activation. (psychiatryadvisor.com) - C1 inhibitors are protease inhibitors whose main function is inhibition of the complement system to prevent spontaneous activation. (marketresearchreports.biz) - Activation was prevented in the presence of protease inhibitors iodoacetamide and 1,10-phenanthroline but was not abolished upon substitution of Ala for the active site Ser(645) of MASP-3, indicating extrinsic proteolysis. (au.dk) - C1Inhibitor is a protease inhibitor that functions to inhibit the complement system in order to prevent over-activation or spontaneous activation. (reliatech.de) - Inhibition is achieved by binding to and irreversibly inhibiting the C1r and C1s proteases of the C1 complex, which has the effect of shutting down all subsequent downstream events in the complement activation cascade. (reliatech.de) - The inflammation in turn, is an important body's response to the aggression and involves several biological mechanisms related and highly regulated, such as coagulation, fibrinolysis, activation of the complement system (CS), oxidation and hormonal regulation. (usp.br) - Activation of coagulation factor XII is controlled by the same regulatory protein activation of the complement inhibitor C1. (usp.br) - We measured five complement biomarkers [complement receptor 1 (CR1), clusterin, complement component 9 (C9), C1 inhibitor (C1inh), terminal complement complex (TCC)] and the benchmark inflammatory marker C-reactive protein (CRP). (nih.gov) - Key fluid phase complement regulators include Factor H (FH), Factor I (FI), C4-binding protein (C4BP) and C1 inhibitor (C1INH). (biomedcentral.com) - C1 inhibitor (C1INH) regulates the C1 protein, which activates the complement system (for fighting infections), controls formation of blood clots and generation of bradykinin. (mastattack.org) - AAE often presents with low CH50, C2, C4 and sometimes C1q, poorly functioning or low C1 esterase inhibitor (C1INH). (mastattack.org) - C1 inhibitor (C1INH) inactivates C1r and C1s to stop the complement pathway. (mastattack.org) Deficiency of C1 inhibitor2 - It develops when certain cancers (such as lymphoma) or autoimmune disorders (such as systemic lupus erythematosus [lupus] or dermatomyositis) cause a deficiency of C1 inhibitor. (merckmanuals.com) - Hereditary angioneurotic edema is a rare disorder caused by the congenital deficiency of C1 inhibitor. (nih.gov) - Additionally, there are three autosomal dominant inherited forms known, due to mutations in the genes that control the clotting cascade , including the SERPING1 gene, which results in deficiency of the blood protein C1-inhibitor (type I HAE) and the F12 gene, which controls Factor XII (type III HAE). (bionity.com) - The specific aim of this study is to evaluate the effect of recombinant human C1-inhibitor (rhC1INH), as a kidney recipient intra- and post operative treatment strategy to decrease systemic inflammation and decrease the incidence of DGF from donation after cardiac death donors (DCD). (clinicaltrials.gov) - Conestat alfa (recombinant human C1 esterase inhibitor) has been shown to decrease renal ischemic damage in experimental models of renal ischemia. (centerwatch.com) - The Recombinant Human C1 Esterase Inhibitor in the Prevention of Contrast-induced Nephropathy in High-risk Subjects (PROTECT) Study is a randomized, placebo-controlled, double-blind single-center trial that will assess the effect of prophylactic administration of Conestat alfa on the degree of acute kidney injury subjects undergoing elective coronary angiography. (centerwatch.com) - On 20 February 2007, orphan designation (EU/3/07/435) was granted by the European Commission to Pharming Group N.V., Netherlands, for recombinant human C1-inhibitor for the prevention of delayed graft function in organ transplant. (europa.eu) - Recombinant human C1-inhibitor is analogous to a natural human protein, C1-inhibitor, which circulates in low levels in the blood. (europa.eu) - At the time of submission of the application for orphan designation, no clinical trials with recombinant human C1-inhibitor in patients with delayed graft function in organ transplant were initiated. (europa.eu) - Recombinant human C1-inhibitor was not authorised anywhere worldwide for prevention of delayed graft function in organ transplant, at the time of submission. (europa.eu) - Orphan designation of recombinant human C1-inhibitor was granted in the United States for the condition in June 2006. (europa.eu) - Measured by its ability to inhibit recombinant human complement component C1a cleavage of a colorimetric peptide substrate, N Carbobenzyloxy-Lys-ThioBenzyl ester (Z-K-SBzl). (reliatech.de) - Recombinant Human C1 Inhibitor is a highly glycosylated glycoprotein containing 445 amino acid residues (49.4kDa), corresponding to amino acids 56 - 500 of the C1 inhibitor precursor, and is fully functional in its ability to inhibit the C1 complex. (reliatech.de) - plasma is possible) to detect and/or measure levels of alpha-2-globulin, an esterase inhibitor of the C1 protein found in the classic pathway of the complement components proteins. (optometricmanagement.com) - We studied complement 1 inhibitor (C1-INH) as an inhibitor of the alternative complement pathway. (rupress.org) - Because the alternative complement pathway has many features in common with the classical complement pathway, and because many proteins of that pathway function in a manner analogous to proteins of the classical pathway, we studied the role of the C1-INH in inhibition of the alternative complement pathway. (rupress.org) - and factor D serves a function analogous to that of C1 of the classical pathway. (rupress.org) - C1q is an integral component within the complement pathway - a complicated cascade of protein interactions, culminating in an immune response against a broad variety of pathogens. (wikipedia.org) - The complement pathway is composed of several subset pathways: the lectin/mannose pathway, alternative pathway and the classical pathway. (wikipedia.org) - All pathways culminate in the production of a C3 convertase, which catalyses C3 into its constitutive parts (better detailed here - classical complement pathway). (wikipedia.org) - Also, there has been some speculation as to an additional autoantibody against an inhibitor protein (in the complement pathway) named C1-inhibitor. (wikipedia.org) - This unit describes several assay methods that can be used to determine the functional status of the classical pathway of complement and to quantitate its component proteins. (currentprotocols.com) - Antigen-antibody complexes on the surface of a microorganism can activate the classical pathway of complement, a part of the acquired immune system (Fig. 1 ), by providing a binding site for C1. (asm.org) - Mannose binding protein activates the classical pathway by binding to mannose residues on microbial surfaces and activating C4 in a manner similar to that for C1. (asm.org) - Interestingly, B. pertussis does not activate the alternative pathway of complement ( 7 ). (asm.org) - The Bordetella resistance to killing (BrkA) protein has been shown to inhibit killing by this pathway ( 7 ). (asm.org) - Our data demonstrated that the CSF levels of complement components of C1q, FB, MBL as well as complement pathway factors sC5b-9 and complement regulator FH were all elevated in patients with CM as compared to the controls, CSF C3 breakdown products iC3b were found in both CSF and plasma samples of the CM patients. (biomedcentral.com) - The complement system is composed of three pathways: the classical pathway, the alternative pathway, and the lectin pathway (Figure 1). (psychiatryadvisor.com) - A second set of initiating proteins, the ficolins, interact with acetylated sugars and proceed as in the mannose-binding lectin (MBL) pathway. (psychiatryadvisor.com) - The classical pathway is activated by C1 protein when microbes are present. (mastattack.org) - The alternative pathway is activated by the C3 protein changing into C3b. (mastattack.org) - The lectin pathway is activated by two proteins called MBL and ficolin binding to the surfaces of microbes. (mastattack.org) - C1q is the target recognition protein of the classical complement pathway and a major connecting link between innate and acquired immunity. (naver.com) - C1 inhibitor (C1 INH) a member of the serpin group, an inhibitor of C1, the initial component activated in the classical complement pathway . (thefreedictionary.com) - Part B + C will provide data on the efficacy of C1-esteraseremmer-N. (clinicaltrials.gov) - SAN FRANCISCO , July 30, 2014 /PRNewswire/ -- A study presented at the 2014 World Transplant Congress evaluated the safety and efficacy of CSL Behring's C1 Inhibitor (C1-INH) concentrate in preventing antibody-mediated rejection following kidney transplants in highly sensitized patients. (bio-medicine.org) - We assessed the efficacy of C1-INH concentrate in the emergency treatment of rarely occurring acute laryngeal HAE attacks in a prospective, open-label clinical study. (elsevier.com) - Complement has long been regarded as a pivotal effector arm of the innate immune response, eliciting important immunoregulatory functions in the context of inflammation and also serving as a vital link between the innate and adaptive immune response. (springer.com) - We quantified changes in the proteome and the nature of protein amino termini (the N-terminome) and the altered abundance of murine proteases and inhibitors during skin inflammation. (sciencemag.org) - Through analysis of the N-terminome by iTRAQ-TAILS, we identified cotranslational and posttranslational αN-acetylation motifs, quantitative increases in protein abundance, and qualitative changes in the proteolytic signature during inflammation. (sciencemag.org) - Of the proteins identified in normal skin, about half were cleaved, and phorbol ester-induced inflammation increased the proportion of cleaved proteins, including chemokines and complement proteins, that were processed at previously uncharacterized sites. (sciencemag.org) - Nonetheless, it is unclear whether TSPO, a mitochondrial protein, can be interpreted as a general marker for inflammation in diseases involving psychosis. (medworm.com) - McQuibban G, Gong J, Tam E, McCulloch C, Clark Lewis I, Overall C. Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3. (labome.org) - Complement, inflammation, and oxidant injury contribute to age-related macular degeneration (AMD). (arvojournals.org) - This article is sought to provide insights into the pathogenesis of multiorgan failure associated with systemic inflammation with particular focus on the role of the complement system. (hindawi.com) - The inhibitors nearly double due to increase in inflammation, but its normal level in blood is around 0.25g/L. These are known as the most essential physiological inhibitors of plasma kallikrein, fXIa, and fXIIa. (marketresearchreports.biz) - NMO pathogenesis involves AQP4-IgG antibody binding to astrocytic AQP4, which causes complement-dependent cytotoxicity and secondary inflammation with granulocyte and macrophage infiltration, blood-brain barrier disruption and oligodendrocyte injury. (nih.gov) - Antibody-dependent astrocyte damage involving complement-dependent cytotoxicity, CDCC and ADCC mechanisms lead to inflammation, oligodendrocyte injury, demyelination and neuronal loss. (nih.gov) Acquired C1 Inhibitor Deficiency1 - Increase in level of bradykinin caused by C1 deficiency leads to HAE and acquired C1 inhibitor deficiency. (marketresearchreports.biz) - Complement research is now faced with the challenge of trying to integrate isolated biochemical pathways into complex gene and protein regulatory circuits. (springer.com) - It is estimated that plasma may contain as many as 40,000 different proteins from about 500 gene products. (sigmaaldrich.com) - Genetic studies have made advancements in establishing the molecular cause of this disease, identifying mutations in the complement factor H (CFH) gene and a locus on chromosome 10 encompassing the HTRA1/LOC387715/ARMS2 genes. (cdc.gov) - This gene encodes a highly glycosylated plasma protein involved in the regulation of the complement cascade. (genetex.com) - 11 12 In addition, a unique rodent transmembrane protein known as Crry (complement-receptor 1-related gene/protein y) has both CD46 and CD55 activities and is considered a functional homologue of human CD46. (arvojournals.org) - Methods: The medical history, clinical features and C1-INH gene mutation of a Turkish family were investigated and outcomes of long-term treatments were described. (bvsalud.org) - A) in C1-INH gene was detected. (bvsalud.org) - C1 inhibitors are heavy glycosylated proteins and the human C1-inhibitor gene is found on the eleventh chromosome. (marketresearchreports.biz) - This powerful surveillance system comprises a network of precursors, regulatory and inhibitory proteins that can be immediately activated upon recognition of invading microorganisms ( 9 , 10 ). (frontiersin.org) - The aim here was to evaluate the response to therapy for these attacks using icatibant, an inhibitor of the bradykinin receptor, which was recently introduced into Brazil. (scielo.br) - The objective of this analysis was to evaluate the effectiveness and tolerability of C1 INH-nf when used for the treatment of laryngeal attacks. (elsevier.com) - Methods: A post hoc analysis of an open-label treatment study evaluated the effectiveness of C1 INH-nf in the treatment of laryngeal attacks in patients with HAE. (elsevier.com) - When C1 INH-nf was administered within 4 hours of symptom onset, clinical relief was achieved in 94% (45/48) of attacks within 4 hours after treatment. (elsevier.com) - Of 265 attacks from the four studies, 62% received two 1000-U doses of C1 INH-nf. (elsevier.com) - If approved for this new indication, RUCONEST is to become the first C1 inhibitor therapy to be approved for both acute treatment and prophylaxis of HAE attacks. (thefreedictionary.com) - Methods Acute laryngeal attacks were each treated with C1-INH concentrate (Berinert) at a single dose of 20 U/kg body weight. (elsevier.com) - Conclusion C1-INH concentrate is an effective and safe emergency treatment for providing reliable and rapid relief from the potentially life-threatening symptoms of laryngeal HAE attacks. (elsevier.com) - C1 inhibitors are used to treat acute attacks and as routine prophylaxis against HAE. (marketresearchreports.biz) Functional C1 inhibitor1 - Both antigenic and functional C1 inhibitor levels will be determined. (clinicaltrials.gov) - Complement Components and Antibodies. (rupress.org) - Antibodies are usually raised against foreign proteins, such as those made by a replicating virus or invading bacterium. (wikipedia.org) - Antibodies against self proteins are known as autoantibodies, and are not found in healthy individuals. (wikipedia.org) - CD59 on hematologic cells is required to prevent unregulated complement lysis. (psychiatryadvisor.com) - The inflammatory mediators, cytokines and complement proteins are believed to regulate the sequential events during the development. (elsevier.com) - Association of vitamin K-dependent coagulation proteins and C4b binding protein with triglyceride-rich lipoproteins of human plasma. (semanticscholar.org) - Previous studies strongly suggest a mutual crosstalk between the complement and the coagulation system [ 27 - 30 ]. (hindawi.com) - Physiologically, the complement and coagulation systems share components. (usp.br) - it is a glycoprotein of the serpin family of proteinase inhibitors and also inhibits several other proteins involved in coagulation (thrombin, kallikrein, and coagulation factors X and XI) and urokinase. (thefreedictionary.com) - G-protein-coupled receptor Rhodopsin Estrogen receptor Histones Protamines CI protein % Transcription regulatory proteins that are receptors are in the receptors section. (wikipedia.org) - Whereas much attention has been focused on the properties and activities of the TLRs in this process ( 13 ), many other innate immune molecules expressed by glia and neurons have been described (e.g., complement, lectins, scavenger receptors) ( 14 ). (jimmunol.org) - C1 inhibitors are also known as C1 esterase inhibitors and unlike other serpin family members, it has two domains: C-terminal and N-terminal. (marketresearchreports.biz) - Although deficiencies in complement components are rare, defects in the proteins that regulate complement are far more common. (psychiatryadvisor.com) - The complement system is a key component of the early innate immune response to pathogens. (jimmunol.org) - We observed early increases in the deposition of immunoglobulin M, mannose-binding lectin 2, and annexin IV on cerebral endothelial cells, induction of the complement components C3 and C3a, by 24 h after IRI, and a later significant increase in the complement component C1q by 48 h. (springer.com) - 2006. Complement component C3 mediates inflammatory injury following focal cerebral ischemia. (springer.com) - The purpose of this study was to evaluate the baseline complement component profiles in human cerebrospinal fluid (CSF) and plasma from non-HIV patients with CM, and therefore to provide insights of possible roles of the complement system in CM. (biomedcentral.com) - The complement system is well known as a major component of the host innate immune defense system against infection. (biomedcentral.com) - A complete deficiency of a complement component is rare, and partial deficiencies are rarely of any clinical significance. (psychiatryadvisor.com) - C1 Inhibitor is a member of the serpin family of structurally related proteins, and is the primary regulator of the immune complement system. (reliatech.de) - In this study we characterized the step in the complement cascade where BrkA acts, using three strains: a wild-type strain, a strain containing an insertional disruption of brkA , and a strain containing two copies of the brkA locus. (asm.org) - The complement cascade. (asm.org) - To elucidate the molecular basis for complement resistance by BrkA, in this study we have attempted to determine which step in the complement cascade is affected by BrkA by monitoring the deposition of complement proteins on the surface of strains either expressing or not expressing BrkA. (asm.org) - The complement cascade plays a central role in the modulation of inflammatory responses. (arvojournals.org) - Furthermore, potential therapeutic strategies targeting the complement cascade to prevent the development of MOF as well as possible future research directions are addressed. (hindawi.com) Role of Complement3 - In analogy to the newly described neuroimmune regulatory proteins also known as "don't eat me" signals (CD200, CD47, CD22, fractalkine, semaphorins), we herein identify the key role of complement regulator factor H (fH) in controlling neuroinflammation initiated in an acute mouse model of Ab-dependent experimental autoimmune encephalomyelitis. (jimmunol.org) - This review focuses on the current knowledge of immune evasion mechanisms exhibited by Lyme disease spirochetes and highlights the role of complement-interfering, infection-associated molecules playing an important part in these processes. (frontiersin.org) - Here, we investigated the role of complement in mediating effects of salidroside after cerebral IRI in rats. (springer.com) - For example, the mannose binding protein is a pattern recognition molecule with structural similarity to C1 that bridges the classical and alternative pathways ( 18 ). (asm.org) - Dengue, West Nile, or yellow fever virus NS1 directly associated with C4b binding protein (C4BP), a complement regulatory plasma protein that attenuates the classical and lectin pathways. (jimmunol.org) - C4b binding protein (C4BP) is the primary fluid-phase regulator of the CP and lectin pathways. (jimmunol.org) - C3 is the central protein of all three complement pathways and plays a critical role in the opsonization of pathogens. (psychiatryadvisor.com) - In addition, all three complement pathways result in the formation of the membrane attack complex, which is vital to bactericidal activity. (psychiatryadvisor.com) - Conclusions: Although not as pronounced as those reported in marathon/ultramarathon runners, elite cyclists participating in a three week cycle tour experienced increases in selected proinflammatory and anti-inflammatory acute phase proteins, indicating an acute phase/inflammatory response. (edu.au) - It is tenable that the increase in α1 antitrypsin and C1-INH (anti-inflammatory mediators) at T2 served to attenuate the acute phase/inflammatory response. (edu.au) - The lower than normal resting concentrations of the acute phase proteins supports the notion that chronic aerobic exercise induces an anti-inflammatory state. (edu.au) - Serine proteases, plasmin and miniplasmin induce the expression of C4, decrease the level of ELISA detectable C1 inhibitor, and do not affect the production of factors H and B. These data indicate that complement proteins are expressed locally by the brain microvessels, and may modulate the inflammatory responses of brain tissue. (elsevier.com) - The results suggest that elevated plasma levels of inflammatory biomarkers, including complement proteins, associate with polygenic risk scores in AD, further strengthening the link between genetic and biomarker disease predictors and indicating a potential role for these markers in disease prediction and patient stratification in AD. (nih.gov) - Proteases also govern inflammatory responses by processing extracellular matrix proteins and soluble bioactive mediators. (sciencemag.org) - The complement system is a series of proteins that act in a defined sequence (Fig. 1 ) to promote immune clearance by opsonizing or killing microorganisms and augmenting the inflammatory response. (asm.org) - In the present review, mechanisms of the inflammatory response in the development of MOF in sepsis and SIRS with particular focus on the complement system are discussed. (hindawi.com) - The marked elevation of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and a neutrophilic leukocytosis are characteristic for auto-inflammatory disorders. (epgonline.org) - Complement, a part of the innate immune system, is composed of more than 30 plasma- and cell membrane-bound proteins that function cooperatively in antimicrobial and inflammatory reactions. (psychiatryadvisor.com) - Most of the genetically determined deficiencies of the complement system are inherited as autosomal recessive traits, with the exception of C1 esterase inhibitor, which is inherited as an autosomal dominant trait, and properdin deficiency, which is inherited as an X-linked recessive trait. (psychiatryadvisor.com) - Consequently, levels of all complement proteins become low. (wikipedia.org) - Patients treated with C1-INH experienced increased C3 levels on day 30 (p=0.005), while C4 levels were significantly higher at all time points. (bio-medicine.org) - Mouse neurons expressed other complement regulators crry and low levels of CD55. (jimmunol.org) - Flavivirus nonstructural protein 1 (NS1) is a secreted nonstructural glycoprotein that accumulates in plasma to high levels and is displayed on the surface of infected cells but absent from viral particles. (jimmunol.org) - CD59 protein levels in cultured hRPE cells were higher than in native hRPE cells. (arvojournals.org) - Normal levels during symptomatic periods rule out the diagnosis, whereas decreased levels warrant determination of C1 esterase inhibitor titer by immunoassay or functional assay. (utmb.edu) - Levels of proteins in ischemic brain were measured by immunofluorescence and western blotting. (springer.com) - There is an additional type in which C1 levels are normal but C1 function is decreased (type II HAE). (bionity.com) - Pearson's correlation coefficients were calculated on variables between complement components and the levels of total protein in the CSF samples. (biomedcentral.com) - A positive correlation was found between the levels of CSF protein and MBL, C1q or FB. (biomedcentral.com) - Membrane proteins, CD46 and CD55, also control C3 levels, and defects in CD46 have also been associated with atypical hemolytic uremic syndrome and macular degeneration. (psychiatryadvisor.com) - Type I HAE is caused by low levels of C1 inhibitor protein (C1-INH). (medicinenet.com) - Type II HAE is characterized by normal or elevated levels of dysfunctional C1 inhibitor protein. (medicinenet.com) - We began these experiments with the hypothesis that C1-INH regulates factor D activity. (rupress.org) - These include 37 proteases and antiproteases, which are likely to play a role in the formation of the yolk (vitellogenesis), as regulators of protein metabolism. (biomedcentral.com) - This protein, a member of the serine protease inhibitor (serpin) group, originally was described as an inhibitor of C1 ( 2 ). (rupress.org) - What is a plasma protein therapy? (pptaglobal.org) - Complement is also part of the innate immune defenses and provides a defense against pathogens that have not previously infected the host by recognizing repeating structures such as lipopolysaccharide (LPS) found on the surface of bacteria. (asm.org) - Complement resistance is common among respiratory pathogens. (asm.org) - Many pathogens are equipped with factors providing resistance against the bactericidal action of complement. (semanticscholar.org) - The complement system plays a pivotal protective role in the innate immune response to many pathogens including flaviviruses. (jimmunol.org) - To survive and establish a persistent infection in the human host, pathogens must evade the first line of host defense by counteracting complement as an essential part of innate immunity. (frontiersin.org) - As a central entity of innate immunity, the complement system is immediately activated after trauma or infection in order to control the replication of intruding pathogens. (hindawi.com) - The complement system consists of several circulating proteins that are implicated in the first-line defence against pathogens and in the removal of dying cells. (centerwatch.com) - In addition, this study provides data on safety of C1-esteraseremmer-N. Twelve HAE patients without signs of an attack will receive an administration of 1,000 U, 1,500 U or 2,000 U of C1-esteraseremmer-N or Cetor® and later on the same dose of the other product. (clinicaltrials.gov) - According to study findings, fewer patients who were administered C1-INH developed serious adverse events compared to those administered placebo (20 percent versus 30 percent). (bio-medicine.org) - 3 4 5 Complement components found in drusen from eyes with AMD and genetic variation in several complement factor genes in patients with AMD indicate the complement system may be an important factor in AMD pathogenesis. (arvojournals.org) - We did not detect differences in enzyme-inhibitor complexes between samples of controls, patients during remission and patients during an acute attack. (elsevier.com) - Investigations from animal model and human patients have shown the importance of the complement system against cryptococcal infections [ 10 ]. (biomedcentral.com) - Several studies indicate that complement proteins exert functions that are either more complex than previously thought, or go well beyond the innate immune character of the system. (springer.com) - For instance, there is new emphasis on the role of neuroimmune regulatory proteins (NIRegs) 3 that are involved in silencing or reshaping an adverse innate immune response and polarizing phagocytes such as macrophages and microglia toward a protective phenotype (for review, see Ref. 23 ). (jimmunol.org) - Surfactant proteins A (SP-A) and D (SP-D) have been implicated in pulmonary innate immunity. (naver.com) - Membrane complement regulatory proteins (mCRPs) such as CD46, CD55, and CD59, protect host cells from complement attack. (arvojournals.org) Group of proteins2 - Analysis of blood cells showed the absence of the phosphatidylinositol-linked membrane protein CD59. (rupress.org) - The latter group of genetically and structurally unrelated proteins has been collectively referred to as "complement regulator-acquiring surface proteins" and consists of CspA, CspZ, ErpA, ErpC, ErpP, and the as yet unidentified protein p43. (frontiersin.org)	2	49	1	0	9	0.532216	10	41,652
An in-depth report on the causes, diagnosis, treatment, and prevention of heart failure. Cardiomyopathy; Congestive heart failure Heart failure is a condition in which the heart does not pump enough blood to meet the needs of the body’s tissues. Heart failure can develop slowly over time as the result of other conditions (such as high blood pressure and coronary artery disease) that weaken the heart. It can also occur suddenly as the result of damage to the heart muscle. Common signs and symptoms of heart failure include: - Shortness of breath - Wheezing or cough - Fluid retention and weight gain - Loss of appetite - Abnormally fast or slow heart rate Treatment for heart failure depends on its severity. All patients need dietary salt restriction and other lifestyle adjustments, medication, and monitoring. Patients with very weakened hearts may need implanted devices (such as pacemakers, implantable cardiac defibrillators, or devices that help the heart pump blood) or surgery, including heart transplantation. Doctors usually treat heart failure, and the underlying conditions that cause it, with a combination of medications. These medications include: - Angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) - Beta blockers - Aldosterone blockers - Hydralazine or nitrates Other medications that may be helpful include: - Aspirin and warfarin Decision Making in Advanced Heart Failure For patients with advanced heart failure, symptom relief, quality of life, and personal values are as important to consider as survival, according to a 2012 scientific statement from the American Heart Association (AHA). The AHA notes that while technology has increased the treatment options for advanced heart failure, “doing everything is not always the right thing.” The guidelines emphasize a patient-centered approach to treatment and the importance of patients discussing with their doctors their preferences, expectations, and goals. Heart failure is a condition in which the heart does not pump enough blood to meet the needs of the body’s tissues. To understand what occurs in heart failure, it helps to be familiar with the anatomy of the heart and how it works. The heart is composed of two independent pumping systems, one on the right side, and the other on the left. Each has two chambers, an atrium and a ventricle. The ventricles are the major pumps in the heart. The Right Side of the Heart. The right system receives blood from the veins of the whole body. This is "used" blood, which is poor in oxygen and rich in carbon dioxide. - The right atrium is the first chamber that receives blood. - The chamber expands as its muscles relax to fill with blood that has returned from the body. - The blood enters a second muscular chamber called the right ventricle. - The right ventricle is one of the heart's two major pumps. Its function is to pump the blood into the lungs. - The lungs restore oxygen to the blood and exchange it with carbon dioxide, which is exhaled. The Left Side of the Heart. The left system receives blood from the lungs. This blood is now rich in oxygen. - The oxygen-rich blood returns through veins coming from the lungs (pulmonary veins) to the heart. - The heart receives the oxygen-rich blood from the lungs in the left atrium, the first chamber on the left side. - Here, it moves to the left ventricle, a powerful muscular chamber that pumps the blood back out to the body. - The left ventricle is the strongest of the heart's pumps. Its thicker muscles need to perform contractions powerful enough to force the blood to all parts of the body. - This strong contraction produces systolic blood pressure (the first and higher number in blood pressure measurement). The lower number (diastolic blood pressure) is measured when the left ventricle relaxes to refill with blood between beats. - Blood leaves the heart through the aorta, the major artery that feeds blood to the entire body. The Valves. Valves are muscular flaps that open and close so blood will flow in the right direction. There are four valves in the heart: - The tricuspid regulates blood flow between the right atrium and the right ventricle. - The pulmonary valve opens to allow blood to flow from the right ventricle to the lungs. - The mitral valve regulates blood flow between the left atrium and the left ventricle. - The aortic valve allows blood to flow from the left ventricle to the aorta. The Heart's Electrical System. The heartbeats are triggered and regulated by the conducting system, a network of specialized muscle cells that form an independent electrical system in the heart muscles. These cells are connected by channels that pass chemically-triggered electrical impulses. Description of Heart Failure Heart failure is a process, not a disease. The heart doesn't "fail" in the sense of ceasing to beat (as occurs during cardiac arrest). Rather, it weakens, usually over the course of months or years, so that it is unable to pump out all the blood that enters its chambers. As a result, fluids tend to build up in the lungs and tissues, causing congestion. This is why heart failure is also sometimes referred to as "congestive heart failure." Ways the Heart Can Fail. Heart failure can occur in several ways: - The muscles of the heart pumps (ventricles) become thin and weakened. They stretch (dilate) and cannot pump the blood with enough force to reach all the body's tissues. - The heart muscles stiffen or thicken. They lose elasticity and cannot relax. Insufficient blood enters the chamber, so not enough blood is pumped out into the body to serve its needs. - Sometimes the valves of the heart are abnormal. (Valves open or close to control the flow of blood entering or leaving the heart). They may narrow, such as in aortic stenosis, causing a back up of blood, or they may close improperly so that blood leaks back into the heart. The mitral valve (which regulates blood flow between the two chambers on the left side of the heart) often becomes leaky in severe heart failure -- a condition called mitral regurgitation. - The very mechanisms that the body uses to compensate for inefficient heart pumping can, over time, change the architecture of the heart (called remodeling) and finally lead to irreversible problems. The specific effects of heart failure on the body depend on whether it occurs on the left or right sides of the heart. Over time, however, in either form of heart failure, the organs in the body do not receive enough oxygen and nutrients, and the body's wastes are removed slowly. Eventually, vital systems break down. Failure on the Left Side (Left-Ventricular Heart Failure). Failure on the left side of the heart is more common than failure on the right side. The failure can be a result of abnormal systolic (contraction) or diastolic (relaxation) action: - Systolic. Systolic heart failure is a pumping problem. In systolic failure, the heart muscles weaken and cannot pump enough blood throughout the body. The left ventricle is usually stretched (dilated). Fluid backs up and accumulates in the lungs (pulmonary edema). Systolic heart failure typically occurs in men between the ages of 50 - 70 years who have had a heart attack. - Diastolic. Diastolic heart failure is a filling problem. When the left ventricle muscle becomes stiff and cannot relax properly between heartbeats, the heart cannot fill fully with blood. When this happens, fluid entering the heart backs up. This causes the veins in the body and tissues surrounding the heart to swell and become congested. Patients with diastolic failure are typically women, overweight, and elderly, and have high blood pressure and diabetes. Failure on the Right Side (Right-Ventricular Heart Failure). Failure on the right side of the heart is most often a result of failure on the left. Because the right ventricle receives blood from the veins, failure here causes the blood to back up. As a result, the veins in the body and tissues surrounding the heart to swell. This causes swelling in the feet, ankles, legs, and abdomen. Pulmonary hypertension (increase in pressure in the lung's pulmonary artery) and lung disease may also cause right-sided heart failure. Ejection Fraction. To help determine the severity of left-sided heart failure, doctors use an ejection fraction (EF) calculation, also called a left-ventricular ejection fraction (LVEF). This is the percentage of the blood pumped out from the left ventricle during each heartbeat. An ejection fraction of 50 - 75% is considered normal. Patients with left-ventricular heart failure are classified as either having a preserved ejection fraction (greater than 50%) or a reduced ejection fraction (less than 50%). Patients with preserved LVEF heart failure are more likely to be female and older, and have a history of high blood pressure and atrial fibrillation (a disturbance in heart rhythm). Heart failure has many causes and can evolve in different ways. - It can be a direct, latest-stage result of heart damage from one or more of several heart or circulation diseases. - It can occur over time as the heart tries to compensate for abnormalities caused by these conditions, a condition called remodeling. In all cases, the weaker pumping action of the heart means that less blood is sent to the kidneys. The kidneys respond by retaining salt and water. This in turn increases edema (fluid buildup) in the body, which causes widespread damage. High Blood Pressure Uncontrolled high blood pressure (hypertension) is a major cause of heart failure even in the absence of a heart attack. In fact, about 75% of cases of heart failure start with hypertension. It generally develops as follows: - The heart muscles thicken to make up for increased blood pressure. - The force of the heart muscle contractions weaken over time, and the muscles have difficulty relaxing. This prevents the normal filling of the heart with blood. Hypertension is a disorder characterized by consistently high blood pressure. In adults, high blood pressure is diagnosed when the systolic blood pressure (the "top" number, which represents the pressure generated when the heart beats) is 140 or higher or the diastolic blood pressure (the "bottom" number, which represents the pressure in the vessels when the heart is at rest) is 90 or higher. Coronary Artery Disease and Heart Attack Coronary artery disease is the end result of a process called atherosclerosis (commonly called "hardening of the arteries"). It is the most common cause of heart attack and involves the build-up of unhealthy cholesterol in the arteries, with inflammation and injury in the cells of the blood vessels. The arteries narrow and become brittle. Heart failure in such cases most often results from a pumping defect in the left side of the heart. People often survive heart attacks, but many eventually develop heart failure from the damage the attack does to the heart muscles. Valvular Heart Disease The valves of the heart control the flow of blood leaving and entering the heart. Abnormalities can cause blood to back up or leak back into the heart. In the past, rheumatic fever, which scars the heart valves and prevents them from functioning properly, was a major cause of death from heart failure. Fortunately, antibiotics and other advances have now made this disease a minor cause of heart failure in industrialized nations. Birth defects may also cause abnormal valvular development. Although more children born with heart defects are now living to adulthood, they still face a higher than average risk for heart failure as they age. Cardiomyopathy is a disorder that damages the heart muscles and leads to heart failure. There are several different types. Injury to the heart muscles may cause the heart muscles to thin out (dilate) or become too thick (become hypertrophic). In either case, the heart doesn't pump correctly. Viral myocarditis is a rare viral infection that involves the heart muscle and can produce either temporary or permanent heart muscle damage. Dilated Cardiomyopathy. Dilated cardiomyopathy involves an enlarged heart ventricle. The muscles thin out, reducing the pumping action, usually on the left side. Although this condition is associated with genetic factors, the direct cause is often not known. (This is called idiopathic dilated cardiomyopathy.) In other cases, viral infections, alcoholism, and high blood pressure may increase the risk for this condition. Hypertrophic Cardiomyopathy. In hypertrophic cardiomyopathy, the heart muscles become thick and contract with difficulty. Some research indicates that this occurs because of a genetic defect that causes a loss of power in heart muscle cells and, subsequently, lower pumping strength. To compensate for this power loss, the heart muscle cells grow. This condition, rare in the general population, is often the cause of sudden death in young athletes. Restrictive Cardiomyopathy. Restrictive cardiomyopathy refers to a group of disorders in which the heart chambers are unable to properly fill with blood because of stiffness in the heart. The heart is of normal size or only slightly enlarged. However, it cannot relax normally during the time between heartbeats when the blood returns from the body to the heart (diastole). The most common causes of restrictive cardiomyopathy are amyloidosis and scarring of the heart from an unknown cause (idiopathic myocardial fibrosis). It frequently occurs after a heart transplant. Severe Lung Diseases Chronic obstructive pulmonary disease (severe emphysema) and other major lung diseases are risk factors for right-side heart failure. Pulmonary hypertension is increased pressure in the pulmonary arteries that carry blood from the heart to the lungs. The increased pressure makes the heart work harder to pump blood, which can cause heart failure. The development of right-sided heart failure in patients with pulmonary hypertension is a strong predictor of death within 6 - 12 months. An overactive thyroid (hyperthyroidism) or underactive thyroid (hypothyroidism) can have severe effects on the heart and increase the risk for heart failure. Nearly 6 million Americans are living with heart failure. About 670,000 new cases of heart failure are diagnosed each year. Although there has been a dramatic increase over the last several decades in the number of people who suffer from heart failure, survival rates have greatly improved. Coronary artery disease, heart attack, and high blood pressure are the main causes and risk factors of heart failure. Other diseases that damage or weaken the heart muscle or heart valves can also cause heart failure. Heart failure is most common in people over age 65, African-Americans, and women. Heart failure risk increases with advancing age. Heart failure is the most common reason for hospitalization in people age 65 years and older. Men are at higher risk for heart failure than women. However, women are more likely than men to develop diastolic heart failure (a failure of the heart muscle to relax normally), which is often a precursor to systolic heart failure (impaired ability to pump blood). African-Americans are more likely than Caucasians to develop heart failure before age 50 and die from the condition. Family History and Genetics People with a family history of cardiomyopathies (diseases that damage the heart muscle) are at increased risk of developing heart failure. Researchers are investigating specific genetic variants that increase heart failure risk. People with diabetes are at high risk for heart failure, particularly if they also have coronary artery disease and high blood pressure. Some types of diabetes medications, such as rosiglitazone (Avandia) and pioglitazone (Actos), have been associated with heart failure. Chronic kidney disease caused by diabetes also increases heart failure risk. Obesity is associated with both high blood pressure and type 2 diabetes, conditions that place people at risk for heart failure. Evidence strongly suggests that obesity itself is a major risk factor for heart failure, particularly in women. Smoking, sedentary lifestyle, and alcohol and drug abuse can increase the risk for developing heart failure. Medications Associated with Heart Failure Long-term use of high-dose anabolic steroids (male hormones used to build muscle mass) increases the risk for heart failure. The drug itraconazole (Sporanox), used to treat skin, nail, or other fungal infections, has occasionally been linked to heart failure. The cancer drug imatinib (Gleevec) has been associated with heart failure. Other chemotherapy drugs, such as doxorubicin, can increase the risk for developing heart failure years after cancer treatment. (Cancer radiation therapy to the chest can also damage the heart muscle.) Nearly 290,000 people die from heart failure each year. Nevertheless, although heart failure produces very high mortality rates, treatment advances are improving survival rates. Cardiac Cachexia. If patients with heart failure are overweight to begin with, their condition tends to be more severe. Once heart failure develops, however, an important indicator of a worsening condition is the occurrence of cardiac cachexia, which is unintentional rapid weight loss (a loss of at least 7.5% of normal weight within 6 months). Impaired Kidney Function. Heart failure weakens the heart’s ability to pump blood. This can affect other parts of the body including the kidneys (which in turn can lead to fluid build-up). Decreased kidney function is common in patients with heart failure, both as a complication of heart failure and other diseases associated with heart failure (such as diabetes). Studies suggest that, in patients with heart failure, impaired kidney function increases the risks for heart complications, including hospitalization and death. Congestion (Fluid Buildup). In left-sided heart failure, fluid builds up first in the lungs, a condition called pulmonary edema. Later, as right-sided heart failure develops, fluid builds up in the legs, feet, and abdomen. Fluid buildup is treated with lifestyle measures, such as reducing salt in the diet, as well as drugs, such as diuretics. Arrhythmias (Irregular Beatings of the Heart) Atrial fibrillation is a rapid quivering beat in the upper chambers of the heart. It is a major cause of stroke and very dangerous in people with heart failure. Left bundle-branch block is an abnormality in electrical conduction in the heart. It develops in about 30% of patients with heart failure. Ventricular tachycardia and ventricular fibrillation are life-threatening arrhythmias that can occur in patients when heart function is significantly impaired. Angina and Heart Attacks. While coronary artery disease is a major cause of heart failure, patients with heart failure are at continued risk for angina and heart attacks. Special care should be taken with sudden and strenuous exertion, particularly snow shoveling, during colder months. Many symptoms of heart failure result from the congestion that develops as fluid backs up into the lungs and leaks into the tissues. Other symptoms result from inadequate delivery of oxygen-rich blood to the body's tissues. Since heart failure can progress rapidly, it is essential to consult a doctor immediately if any of the following symptoms are detected: Fatigue. Patients may feel unusually tired. Shortness of Breath (Dyspnea). Patients typically report that they feel out of breath after exertion. While this may begin only when climbing stairs or taking longer walks, it can eventually be present even when walking around the home. (Those who have chest pain or feel like a heavy weight is pressing on the chest should also be evaluated for possible angina.) Orthopnea refers to the shortness of breath patients may have when they lie flat at night. Patients may report that they need to use one or two pillows underneath their head and shoulders in order to be able to sleep. Sitting up with legs hanging over the side of the bed often relieves symptoms. Paroxysmal nocturnal dyspnea (PND) refers to sudden episodes that awaken a patient at night. Symptoms include severe shortness of breath and coughing or wheezing, which generally occur 1 - 3 hours after going to sleep. Unlike orthopnea, symptoms are not relieved by sitting up. Fluid Retention (Edema) and Weight Gain. Patients may complain of foot, ankle, leg or abdominal swelling. In rare cases, swelling can occur in the veins of the neck. Fluid retention can cause sudden weight gain and frequent urination. Wheezing or Cough. Patients may have asthma-like wheezing, or a dry hacking cough that occurs a few hours after lying down but then stops after sitting up. Loss of Muscle Mass. Over time, patients may lose muscle weight due to low cardiac output and a significant reduction in physical activity. Gastrointestinal Symptoms. Patients experience loss of appetite or a sense of feeling full after eating small amounts. They may also have abdominal pain. Pulmonary Edema. When fluid in the lungs builds up, it is called pulmonary edema. When this happens, symptoms become more severe. These episodes may happen suddenly, or gradually build up over a matter of days: - In addition to shortness of breath, patients sometimes have a cough that produces a pinkish froth. - Patients may experience a bubbling sensation in the lungs and feel as if they are drowning. - Typically, the skin is clammy and pale, sometimes nearly blue. This is a life-threatening situation, and the patient must go immediately to an emergency room. Abnormal Heart Rhythms. Patients may have episodes of abnormally fast or slow heart rate. Central Sleep Apnea. This sleep disorder results when the brain fails to signal the muscles to breathe during sleep. It occurs in up to half of people with heart failure. Sleep apnea causes disordered breathing at night. If heart failure progresses, the apnea may be so acute that a person, unable to breathe, may awaken from sleep in panic. Doctors can often make a preliminary diagnosis of heart failure by medical history and careful physical examination. A thorough medical history may identify risks for heart failure that include: High blood pressure Abnormal cholesterol levels Heart disease or history of heart attack Lifestyle factors (such as smoking, alcohol use, and drug use) The following physical signs, along with medical history, strongly suggest heart failure: - Enlarged heart - Abnormal heart sounds - Abnormal sounds in the lungs - Swelling or tenderness of the liver - Fluid retention in legs and abdomen - Elevation of pressure in the veins of the neck Both blood and urine tests are used to check for problems with the liver and kidneys and to detect signs of diabetes. Lab tests can measure: Complete blood counts to check for anemia Kidney function blood and urine tests Sodium, potassium, and other electrolytes Cholesterol and lipid levels Blood sugar (glucose) - Thyroid function - Brain natriuretic peptide (BNP), a hormone that increases during heart failure. BNP testing can be very helpful in correctly diagnosing heart failure in patients who come to the emergency room complaining of shortness of breath (dyspnea). An electrocardiogram (ECG) is a test that measures and records the electrical activity of the heart. It is also called an EKG. An electrocardiogram cannot diagnose heart failure, but it may indicate underlying heart problems. The test is simple and painless to perform. It may be used to diagnose: - Previous heart attack - Abnormal cardiac rhythms - Enlargement of the heart muscle, which may help to determine long-term outlook - A finding called a prolonged QT interval may indicate people with heart failure who are at risk for severe complications and therefore need more aggressive therapies. A completely normal ECG means that heart failure is unlikely. The best diagnostic test for heart failure is echocardiography. Echocardiography is a noninvasive test that uses ultrasound to image the heart as it is beating. Cardiac ultrasounds provide the following information: - Evaluations of valve function - Information about how well the heart is pumping, especially a measurement called left ventricle ejection fraction (LVEF) - Type of heart failure - Changes in the structure of the heart that may be a result of heart failure Doctors use information from the echocardiogram for calculating the ejection fraction (how much blood is pumped out during each heartbeat), which is important for determining the severity of heart failure. Stress echocardiography may be needed if coronary artery disease is suspected. Doctors may recommend angiography if they suspect that blockage of the coronary arteries is contributing to heart failure. This procedure is invasive. - A thin tube called a catheter is inserted into one of the large arteries in the arm or leg. - It is gently guided through the artery until it reaches the heart. - The catheter measures internal blood pressure at various locations, giving the doctor a comprehensive picture of the extent and nature of the heart failure. - Dye is then injected through the tube into the heart. - X-rays called angiograms are taken as the dye moves through the heart and arteries. - These images help locate problems in the heart's pumping action or blockage in the arteries. Radionuclide Ventriculography. Radionuclide ventriculography is an imaging technique that uses a tiny amount of radioactive material (called a trace element). It is very sensitive in revealing heart enlargement or evidence of fluid accumulation around the heart and lungs. It may be done at the same time as coronary artery angiography. It can help diagnose or exclude the presence of coronary artery disease and helps demonstrate how the heart works during exercise. Other Imaging Tests Chest x-rays can show whether the heart is enlarged. Computed tomography (CT) and magnetic resonance imaging (MRI) may also be used to evaluate the heart valves and arteries. Exercise Stress Test The exercise stress test measures heart rate, blood pressure, electrocardiographic changes, and oxygen consumption while a patient is performing physically, usually walking on a treadmill. It can help determine heart failure symptoms. Doctors also use exercise tests to evaluate long-term outlook and the effects of particular treatments. A stress test may be done using echocardiography or may be done as a nuclear stress test (myocardial perfusion imaging). Heart failure is classified into four stages (Stage A through Stage D) that reflect the development and progression of the condition. Treatment depends on the stage of heart failure. Stage A is not technically heart failure, but indicates that a patient is at high risk for developing it. In Stage B, the patient has had damage to the heart (for example, from a heart attack) but does not yet have symptoms of heart failure. In Stage C, heart failure symptoms manifest. Stage D is advanced heart failure accompanied by symptoms that may be difficult to manage with standard drug treatments and may require more technologically complex care (defibrillators, mechanical pumps, heart transplantation). The American Heart Association emphasizes the importance of a patient-centered approach to treatment decisions. Patients with advanced heart failure should have ongoing honest discussions with their health care providers concerning their personal preferences and quality of life goals. Management of Risk Factors and Causes Stage A. In Stage A, patients are at high risk for heart failure but do not show any symptoms or have structural damage of the heart. The first step in managing or preventing heart failure is to treat the primary conditions that cause or complicate heart failure. Risk factors include high blood pressure, heart diseases, diabetes, obesity, metabolic syndrome, and previous use of medications that damage the heart (such as some chemotherapy). Important risk factors to manage include: - Coronary artery disease. Treatment includes a healthy diet, exercise, smoking cessation, medications, and, possibly, bypass or angioplasty. - Cholesterol and lipid problems. Treatments include lifestyle management and medications, especially statin drugs. - High blood pressure. A normal systolic blood pressure is considered below 120 mm Hg, and a normal diastolic blood pressure is below 80 mm Hg. Patients with diabetes, atherosclerosis, or chronic kidney disease should maintain blood pressure readings of 130/80 or less, while other patients with high blood pressure should aim for readings no higher than 140/90. Effective reduction of blood pressure reduces the risk of heart failure by 30 - 50%. - Diabetes. Treating type 1 diabetes and type 2 diabetes is extremely important for reducing the risk for heart disease. ACE inhibitors are especially beneficial, particularly for people with diabetes. Research suggests that metformin, a drug used to treat diabetes, may also help prevent heart failure. - Valvular abnormalities, such as aortic stenosis and mitral regurgitation. Surgery may be required. - Abnormal health rhythms (arrhythmias). Ventricular assisted devices, notably biventricular pacers (BVPs), can help prevent hospitalizations for patients with these conditions. - Anemia. Patients with heart failure and underlying anemia should have their anemia corrected. On occasion, this may require erythropoiesis-stimulating drugs. - Thyroid function. Various medications are used to treat overactive thyroid (hyperthyroidism) or underactive thyroid (hypothyroidism). - Drugs. Avoid drugs that can worsen heart failure symptoms. Talk with your doctor about your heart failure before taking nonsteroidal anti-inflammatory drugs (NSAIDs), calcium channel blockers (verapamil and diltiazem), thiazolidinediones (drugs used for diabetes), antitumor necrosis factor medications, and most drugs used to treat irregular heart rhythms (arrhythmia). - Diet and Exercise. It is particularly important to reduce sodium (salt) intake to less than 1,500 mg a day. Patients should engage in medically supervised exercise programs. Dietary changes and exercise are important for treating all stages of heart failure. Treatment Based on Heart Failure Stage Stage B. Patients have a structural heart abnormality seen on echocardiogram or other imaging tests but no symptoms of heart failure. Abnormalities include left ventricular hypertrophy and low ejection fraction, asymptomatic valvular heart disease, and a previous heart attack. In addition to the treatment guidelines for Stage A, the following types of drugs and devices may be recommended for some patients: Angiotensin-converting enzyme (ACE) inhibitors, or angiotensin-receptor blockers (ARBs) for patients who cannot tolerate ACE inhibitors. Beta blockers for patients with a recent or past history of heart attack. Also for patients who have not had a heart attack but who do have reduced LVEF identified in diagnostic tests. Stage C. Patients have a structural abnormality and current or previous symptoms of heart failure, including shortness of breath, fatigue, and difficulty exercising. Treatment includes those for Stage A and B plus: Restrict dietary sodium (salt). Lowering sodium in the diet can help diuretics work better. ACE inhibitors or angiotensin-receptor blockers (ARBs). Beta blockers (bisoprolol, carvedilol, and sustained release metoprolol). Diuretics are recommended for most patients, with loop diuretics such as furosemide generally being the first-line choice. Aldosterone inhibitors are recommended for many patients. Digitalis may be prescribed for some patients. A hydralazine and nitrate combination (BiDil) should be used for African-American patients who are taking an ACE inhibitor, beta blocker, and diuretic and who still have heart failure symptoms. Exercise training for appropriate patients. - Implantable cardiac defibrillators (ICDs) may be considered for patients with very low ejection fraction or those who have had dangerous arrhythmias. Cardiac resynchronization therapy (pacemaker), with or without ICD, for some patients. Stage D. Patients have end-stage symptoms that do not respond to standard treatments. Treatment focuses not only on survival but on symptom relief and quality of life issues. Treatment includes appropriate measures used for Stages A, B, and C plus: Strict control of fluid retention. Heart transplantation referral for appropriate patients. Left-ventricular assist devices (LVADs) as permanent therapy for patients who are not candidates for heart transplants. LVADs are surgically implanted to help pump blood through the body. Hospice and end-of-life care information for patients and families. Patients have the right to choose or decline treatments based on their personal preferences, values, and goals. Quality of life is as important a consideration as survival. Managing Triggers of Heart Failure Symptoms Whenever heart failure worsens, whether quickly or chronically over time, various factors must be considered as the cause: Dietary indiscretion. Sometimes as little as eating a sausage or some sauerkraut with a high sodium content is enough to precipitate an acute episode. Failure to comply with fluid and salt restrictions must be considered whenever heart failure worsens. Alcohol. Depending on the severity of a patient's heart failure, one or more drinks may suddenly worsen symptoms. Medication compliance. Patients may forget or purposely skip a medication, or they may not be able to afford or have access to medications. Angina or heart attack. Worsening of coronary artery disease may make the heart muscle less able to pump enough blood. Arrhythmias. Increases in the heart rate, or a slowing of the heart rate below normal, may also affect the ability of the heart to function. Likewise, an irregular heart rhythm such as atrial fibrillation may cause a flareup. Anemia. It is unclear whether anemia causes heart failure or is a symptom of heart failure. Some anemias may be treated with iron replacement therapy. A more significant anemia can cause a worsening of heart failure and should be treated promptly. Many different medications are used in the treatment of heart failure. They include: - Angiotensin-converting enzyme (ACE) inhibitors - Angiotensin-receptor blockers (ARBs) - Beta blockers - Aldosterone blockers - Hydralazine and nitrates - Aspirin and warfarin Angiotensin-converting enzyme (ACE) inhibitors are among the most important drugs for treating patients with heart failure. ACE inhibitors open blood vessels and decrease the workload of the heart. They are used to treat high blood pressure but can also help improve heart and lung muscle function. ACE inhibitors are particularly important for patients with diabetes, because they also help slow progression of kidney disease. Brands and Indications. ACE inhibitors are used to treat Stage A high-risk conditions such as high blood pressure, heart disease, and diabetic nerve disorders (neuropathy). They are also used to treat Stage B patients who have had a heart attack or who have left ventricular systolic disorder, and Stage C patients with heart failure. Specific brands of ACE inhibitors include: Benazepril (Lotensin, generic) Captopril (Capoten, generic) Enalapril (Vasotec, generic) Fosinopril (Monopril, generic) Lisinopril (Prinivil, Zestril, generic) Moexipril (Univasc, generic) Perindopril (Aceon, generic) Quinapril (Accupril, generic) Ramipril (Altace, generic) Trandolapril (Mavik, generic) Side Effects of ACE Inhibitors: Low blood pressure is the main side effect of ACE inhibitors. This can be severe in some patients, especially at the start of therapy. Irritating cough is a common side effect, which some people find intolerable. All ACE inhibitors can have this side effect, but angiotensin-receptor blockers do not. Although ACE inhibitors can protect against kidney disease, they also increase potassium retention by the kidneys. This increases the risk for cardiac arrest (when the heart stops beating) if potassium levels become too high. Because of this action, they are not generally given with potassium-sparing diuretics or potassium supplements. - Patients who have difficulty tolerating ACE inhibitor side effects are usually switched to an angiotensin-receptor blocker (ARB). Angiotensin-Receptor Blockers (ARBs) ARBs, also known as angiotensin II receptor antagonists, are similar to ACE inhibitors in their ability to open blood vessels and lower blood pressure. They may have fewer or less-severe side effects than ACE inhibitors, especially coughing, and are sometimes prescribed as an alternative to ACE inhibitors. Some patients with heart failure take an ACE inhibitor along with an ARB. Brands and Indications. ARBs are used to treat Stage A high-risk conditions such as high blood pressure and diabetic nerve disorders (neuropathy). They are also used to treat Stage B patients who have had a heart attack or who have left ventricular systolic disorder, and Stage C patients with heart failure. Specific brands include: Common Side Effects Beta blockers are almost always used in combination with other drugs, such as ACE inhibitors and diuretics. They help slow heart rate and lower blood pressure. When used properly, beta blockers can reduce the risk of death or rehospitalization. Brands and Indications. Beta blockers treat Stage A high blood pressure. They also treat Stage B patients (both those who have had a heart attack and those who have not had a heart attack but who have heart damage). A specialist should monitor patients with heart failure who take beta blockers. The three beta blockers that are best for treating Stage C patients with heart failure are: - Carvedilol (Coreg, generic) - Bisoprolol (Zebeta) - Metoprolol succinate (Toprol XL, generic) Beta Blocker Concerns Do not abruptly stop taking these drugs. The sudden withdrawal of beta blockers can increase the risk of angina and even a heart attack. If you need to stop your beta-blocker, your doctor may want you to slowly decrease the dose before stopping completely. Beta blockers are categorized as non-selective or selective. Non-selective beta blockers, such as carvedilol, can narrow bronchial airways. Patients with asthma, emphysema, or chronic bronchitis should not use non-selective beta blockers. Beta blockers can lower HDL (“good”) cholesterol, although the benefits they provide for coronary artery disease and heart failure outweigh any bad effects on cholesterol. These drugs can hide warning signs of low blood sugar (hypoglycemia) in patients with diabetes, especially those who take insulin. Common Side Effects Fatigue and lethargy Vivid dreams and nightmares Dizziness and lightheadedness Reduced ability to exercise Coldness in extremities (legs, toes, arms, hands) Check with your doctor about any side effects. Do not stop taking these drugs on your own. Diuretics cause the kidneys to rid the body of excess salt and water. Fluid retention is a major symptom of heart failure. Aggressive use of diuretics can help eliminate excess body fluids, while reducing hospitalizations and improving exercise capacity. These drugs are also important to help prevent heart failure in patients with high blood pressure. In addition, certain diuretics, notably spironolactone (Aldactone, generic), block aldosterone, a hormone involved in heart failure. This drug class is beneficial for patients with more severe heart failure (Stages C and D). Patients taking diuretics usually take a daily dose. Under the directions and care of a doctor or nurse, some patients may be taught to adjust the amount and timing of the diuretic when they notice swelling or weight gain. Diuretics come in many brands and are generally inexpensive. Some need to be taken once a day, some twice a day. Treatment is usually started at a low dose and gradually increased. Diuretics are virtually always used in combination with other drugs, especially ACE inhibitors and beta blockers. There are three main types of diuretics: These include amiloride (Midamor, generic) and triamterene (Dyrenium, generic). Potassium-sparing diuretics have their own risks, which include dangerously high levels of potassium in people with existing elevated levels of potassium or in those with damaged kidneys. However, all diuretics are generally more beneficial than harmful. Patients should not take potassium supplements at the same time as this type of diuretic without their doctor's knowledge, and may need to avoid foods with high potassium content. Thiazide diuretics. These include chlorothiazide (Diuril, generic), chlorthalidone (Clorpres, generic), indapamide (Lozol, generic), hydrochlorothiazide (Esidrix, generic), and metolazone (Zaroxolyn, generic). Loop diuretics. These are considered the preferred diuretic type for most patients with heart failure. Loop diuretics include bumentanide (Bumex, generic), furosemide (Lasix, generic), and torsemide (Demadex, generic). Loop and thiazide diuretics deplete the body's supply of potassium, which, if left untreated, increases the risk for arrhythmias. (Arrhythmias are heart rhythm disturbances that can, in rare instances, lead to cardiac arrest). In such cases, doctors will prescribe lower doses of the current diuretic, recommend potassium supplements, or use potassium-sparing diuretics either alone or in combination with a thiazide. Dehydration (loss of too much fluid) is also another concern. Common Side Effects Aldosterone is a hormone that is critical in controlling the body's balance of salt and water. Excessive levels may play important roles in hypertension and heart failure. Drugs that block aldosterone are prescribed for some patients with symptomatic heart failure. They have been found to reduce death rates for patients with heart failure and coronary artery disease, especially after a heart attack. These blockers pose some risk for high potassium levels. Brands include: Spironolactone (Aldactone, generic) Eplerenone (Inspra, generic) Elevated levels of potassium in the blood are also a concern with these drugs. Patients should not take potassium supplements at the same time as this drug without their doctor's knowledge and may need to avoid foods with high potassium content. Digitalis is derived from the foxglove plant. It has been used to treat heart disease since the 1700s. Digoxin (Lanoxin, generic) is the most commonly prescribed digitalis preparation. Digoxin decreases heart size and reduces certain heart rhythm disturbances (arrhythmias). Unfortunately, digitalis does not reduce mortality rates, although it does reduce hospitalizations and worsening of heart failure. Controversy has been ongoing for more than 100 years over whether the benefits of digitalis outweigh its risks and adverse effects. Digitalis may be useful for select patients with left-ventricular systolic dysfunction who do not respond to other drugs (diuretics, ACE inhibitors). It may also be used for patients who have atrial fibrillation. Side Effects and Problems. While digitalis is generally a safe drug, it can have toxic side effects due to overdose or other accompanying conditions. The most serious side effects are arrhythmias (abnormal heart rhythms that can be life threatening). Early signs of toxicity may be irregular heartbeat, nausea and vomiting, stomach pain, fatigue, visual disturbances (such as yellow vision, seeing halos around lights, flickering or flashing of lights), and emotional and mental disturbances. Many factors increase the chance for side effects. - Low blood potassium levels (which may be caused by diuretics) - Valvular heart disease - Impaired kidney function Digitalis also interacts with many other drugs, including quinidine, amiodarone, verapamil, flecainide, amiloride, and propafenone. For most patients with mild-to-moderate heart failure, low-dose digoxin may be as effective as higher doses. If side effects are mild, patients should still consider continuing with digitalis if they experience other benefits. Hydralazine and Nitrates Hydralazine and nitrates are two older drugs that help relax arteries and veins, thereby reducing the heart's workload and allowing more blood to reach the tissues. They are used primarily for patients who are unable to tolerate ACE inhibitors and angiotensin receptor blockers. In 2005, the FDA approved BiDil, a drug that combines isosorbide dinitrate and hydralazine. BiDil is approved to specifically treat heart failure in African-American patients. Statins are important drugs used to lower cholesterol and to prevent heart disease leading to heart failure. These drugs include lovastatin (Mevacor, generic), pravastatin (Pravachol, generic), simvastatin (Zocor, generic), fluvastatin (Lescol), atorvastatin (Lipitor, generic), rosuvastatin (Crestor), and pitavastatin (Livalo). Atorvastatin is specifically approved to reduce the risks for hospitalization for heart failure in patients with heart disease. Anti-Platelet and Anticoagulant Drugs Aspirin. Aspirin is a type of non-steroid anti-inflammatory (NSAID). Aspirin is recommended for protecting patients with heart disease, and can safely be used with ACE inhibitors, particularly when it is taken in lower dosages (75 - 81 mg). Warfarin (Coumadin, generic). Warfarin is recommended only for patients with heart failure who also have: A history of blood clots to the lungs, stroke, or transient ischemic attack A blood clot in one of their heart chambers Nesiritide (Natrecor). Nesiritide is an intravenous drug that has been used for hospitalized patients with decompensated heart failure. Decompensated heart failure is a life-threatening condition in which heart failure progresses over the course of minutes or a few days, often as the result of a heart attack or sudden and severe heart valve problems. Because nesiritide may cause serious kidney damage and has been linked to an increased risk of death from heart failure, the drug is of limited value. Erythropoietin. Many patients with chronic heart failure are also anemic. Treatment of these patients with erythropoietin has been shown to provide some benefit for heart failure control and hospitalization risk. However, erythropoietin therapy can also increase the risk of blood clots. The exact role of this drug for the treatment of anemia in patients with heart failure is not yet decided. Tolvaptan. Tolvaptan (Samsca) is a drug approved for treating hyponatremia (low sodium levels) associated with heart failure and other conditions. Levosimendan. Levosimendan is an experimental drug that is being investigated as a treatment for severely ill patients with heart failure. It belongs to a new class of drugs called calcium sensitizers that may help improve heart contractions and blood flow. The drug appears to reduce levels of BNP (brain natriuretic peptide), a chemical marker for heart failure severity. Surgery and Devices Revascularization surgery helps to restore blood flow to heart affected by coronary artery disease. It can treat blocked arteries in patients with coronary artery disease and may help select patients with heart failure. Surgery types include coronary artery bypass graft (CABG) and angioplasty (also called percutaneous coronary intervention [PCI]). CABG is a traditional type of open heart surgery. Angioplasty uses a catheter to inflate a balloon inside the artery. A metal stent may also be inserted during an angioplasty procedure. Pacemakers, also called pacers, help regulate the heart’s beating action, especially when the heart beats too slowly. Biventricular pacers (BVPs) are a special type of pacemaker used for patients with heart failure. Because BVPs help the heart’s left and right chambers beat together, this treatment is called cardiac resynchronization therapy (CST). BVPs are recommended for patients with moderate-to-severe heart failure that is not controlled with medication therapy and who have evidence of left-bundle branch block on their EKG. Left-bundle branch block is a condition in which the electrical impulses in the heart do not follow their normal pattern, causing the heart to pump inefficiently. Implantable Cardioverter Defibrillators (ICDs) Patients with enlarged hearts are at risk for having serious cardiac arrhythmias (abnormal heartbeats) that are associated with sudden death. Implantable cardioverter defibrillators (ICDs) can quickly detect life-threatening arrhythmias. The ICD is designed to convert any abnormal heart rhythm back to normal by sending an electrical shock to your heart. This action is called defibrillation. This device can also work as a pacemaker. In recent years, certain ICD models and biventricular pacemaker-defibrillators have been recalled by the manufacturers because of circuitry flaws. However, doctors stress that the chance of an ICD or pacemaker saving a person’s life far outweigh the possible risks of these devices failing. Ventricular Assist Devices Ventricular assist devices are mechanical devices that help improve pumping actions. They are used as a bridge to transplant for patients who are on medications but still have severe symptoms and are awaiting a donor heart. In some cases, they may delay the need for a transplant. Therefore they may be used as short-term (less than 1 week) or longer term support. Ventricular assist devices include: Left ventricular assist devices (LVADs) are used for patients whose heart beat has slowed dangerously to help take over the pumping action of the failing heart. Until recently, these machines required remaining in the hospital. Smaller battery-powered implanted LVAD units are now allowing many patients to leave the hospital while they wait for a transplant. Intra-aortic balloon pumps are helpful for temporarily maintaining heart function in patients with left-side failure who are waiting for transplants and for those who develop a sudden and severe deterioration of heart function. The IABP is an implanted thin balloon that is usually inserted into the artery in the leg and threaded up to the aorta leading from the heart. Its pumping action is generating by inflating and deflating the balloon at certain rates. Fully implanted miniature artificial pumps that assist the heart are also being tested. The risks and complications involved with many of these devices include bleeding, blood clots, and right-side heart failure. Infections are a particular hazard. Patients who suffer from severe heart failure and whose symptoms do not improve with drug therapy or mechanical assistance may be candidates for heart transplantation. About 2,000 heart transplant operations are performed in the United States each year, but thousands more patients wait on a list for a donor heart. The most important factor for heart transplant eligibility is overall health. Chronological age is less important. Most heart transplant candidates are between the ages of 50 - 64 years. While the risks of this procedure are high, the 1-year survival rate is about 88% for men and 77% for women. Five years after a heart transplant, about 73% of men and 67% of women remain alive. In general, the highest risk factors for death three or more years after a transplant operation are coronary artery disease and the adverse effects (infection and certain cancers) of immunosuppressive drugs used in the procedure. The rejection rates in older people appear to be similar to those of younger patients. Implantable Artificial Heart Abiocor is a permanent implantable artificial heart. It is available only for patients who are not eligible for a heart transplant and who are not expected to live more than a month without medical treatment. The device requires a large chest cavity, which means that most women are not eligible for it. Up to half of patients hospitalized for heart failure are back in the hospital within 6 months. Many people return because of lifestyle factors, such as poor diet, failure to comply with medications, and social isolation. Programs that offer intensive follow-up to ensure that the patient complies with lifestyle changes and medication regimens at home can reduce rehospitalization and improve survival. Patients without available rehabilitation programs should seek support from local and national heart associations and groups. A strong emotional support network is also important. Monitoring Weight Changes Patients should weigh themselves each morning and keep a record. Any changes are important: - A sudden increase in weight of more than 2 - 3 pounds may indicate fluid accumulation and should prompt an immediate call to the doctor. - Rapid wasting weight loss over a few months is a very serious sign and may indicate the need for surgical intervention. Sodium (Salt) Restriction. All patients with heart failure should limit their sodium (salt) intake to less than 1,500 mg a day, and in severe cases, very stringent salt restriction may be necessary. Patients should not add salt to their cooking and their meals. They should also avoid foods high in sodium. These salty foods include ham, bacon, hot dogs, lunch meats, prepared snack foods, dry cereal, cheese, canned soups, soy sauce, and condiments. Some patients may need to reduce the amount of water they consume. People with high cholesterol levels or diabetes require additional dietary precautions. Here are some tips to lower your salt and sodium intake: Look for foods that are labeled “low-sodium,” “sodium-free,” “no salt added,” or “unsalted.” Check the total sodium content on food labels. Be especially careful of canned, packaged, and frozen foods. A nutritionist can teach you how to understand these labels. Don’t cook with salt or add salt to what you are eating. Try pepper, garlic, lemon, or other spices for flavor instead. Be careful of packaged spice blends as these often contain salt or salt products (like monosodium glutamate, MSG). Avoid processed meats (particularly cured meats, bacon, hot dogs, sausage, bologna, ham, and salami). Avoid foods that are naturally high in sodium, like anchovies, nuts, olives, pickles, sauerkraut, soy and Worcestershire sauces, tomato and other vegetable juices, and cheese. Take care when eating out. Stick to steamed, grilled, baked, boiled, and broiled foods with no added salt, sauce, or cheese. Use oil and vinegar, rather than bottled dressings, on salads. Eat fresh fruit or sorbet when having dessert. People with heart failure used to be discouraged from exercising. Now, doctors think that exercise, when performed under medical supervision, is extremely important for stable patients with stable conditions. Studies have reported that patients with stable conditions who engage in regular moderate exercise (three times a week) have a better quality of life and lower mortality rates than those who do not exercise. However: - Exercise is not appropriate for all patients with heart failure. If you have heart failure, always consult your doctor before starting an exercise program. - People who are approved for, but not used to, exercise should start with 5 - 15 minutes of easy exercise with frequent breaks. Although the goal is to build up to 30 - 45 minutes of walking, swimming, or low-impact aerobic exercises three to five times every week, even shorter times spent exercising are useful. Studies report benefits from specific exercises: - Progressive strength training may be particularly useful for patients with heart failure since it strengthens muscles, which commonly deteriorate in this disorder. Strength training typically uses light weights, weight machines, or even the body's weight (leg raises or sit-ups, for example). Even performing daily handgrip exercises can improve blood flow through the arteries. - Patients who exercise regularly using supervised treadmill and stationary-bicycle exercises can increase their exercise capacity. Exercising the legs may help correct problems in heart muscles. Exercise has also been associated with reduced inflammation in blood vessels. Some people with severe heart failure may need bed rest. To reduce congestion in the lungs, the patient's upper body should be elevated. For most patients, resting in an armchair is better than lying in bed. Relaxing and contracting leg muscles is important to prevent clots. As the patient improves, a doctor will progressively recommend more activity. Stress reduction techniques, such as meditation and relaxation response methods, may have direct physical benefits. Anxiety can cause the heart to work harder and beat faster. Herbs and Supplements Patients with heart failure may resort to alternative remedies. Such remedies are often ineffective and may have severe or toxic effects. Of particular note for patients with heart failure is an interaction between St. John's wort (an herbal medicine used for depression) and digoxin (a heart drug). St. John's wort can significantly interfere with this drug. Fish Oil Supplements. Some research shows that a daily capsule of fish oil may help improve survival in patients with heart failure. Fish oil contains omega-3 polyunsaturated fatty acids, a healthy kind of fat. However, while evidence is not conclusive, some studies have suggested that fish oil supplements may not be safe for patients with implanted cardiac defibrillators. Coenzyme Q10 and Vitamin E. Small studies suggested that coenzyme Q10 (CoQ10) may help patients with heart failure, particularly when combined with vitamin E. CoQ10 is a vitamin-like substance found in organ meats and soybean oil. More recent studies, however, have found that CoQ10 and vitamin E do not help the heart or prevent heart disease. In fact, vitamin E supplements may actually increase the risk of heart failure, especially for patients with diabetes or vascular diseases. Other Vitamins and Supplements. A wide variety of other vitamins (thiamin, B6, and C), minerals (calcium, magnesium, zinc, manganese, copper, selenium), nutritional supplements (carnitine, creatine), and herbal remedies (hawthorn) have been proposed as treatments for heart failure. None have been adequately tested. There is no evidence that a particular vitamin or supplement can cure heart failure. In any case, vitamins are best consumed through the food sources contained in a healthy diet. Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements. Adabag S, Roukoz H, Anand IS, Moss AJ. Cardiac resynchronization therapy in patients with minimal heart failure: a systematic review and meta-analysis. J Am Coll Cardiol. 2011 Aug 23;58(9):935-41. Allen LA, Stevenson LW, Grady KL, Goldstein NE, Matlock DD, Arnold RM, et al. Decision Making in Advanced Heart Failure: A Scientific Statement From the American Heart Association. Circulation. 2012 Apr 17;125(15):1928-1952. Epub 2012 Mar 5. Al-Majed NS, McAlister FA, Bakal JA, Ezekowitz JA. Meta-analysis: cardiac resynchronization therapy for patients with less symptomatic heart failure. Ann Intern Med. 2011 Mar 15;154(6):401-12. Epub 2011 Feb 14. Bibbins-Domingo K, Pletcher MJ, Lin F, Vittinghoff E, Gardin JM, et al. Racial differences in incident heart failure among young adults. N Engl J Med. 2009 Mar 19;360(12):1179-90. Carlson MD, Wilkoff BL, Maisel WH, Carlson MD, Ellenbogen KA, Saxon LA, et al. Recommendations from the Heart Rhythm Society Task Force on Device Performance Policies and Guidelines Endorsed by the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) and the International Coalition of Pacing and Electrophysiology Organizations (COPE). Heart Rhythm. 2006 Oct;3(10):1250-73. Epstein AE, Dimarco JP, Ellenbogen KA, Estes NA 3rd, Freedman RA, Gettes LS, et al. ACC/AHA/HRS 2008 Guidelines for device-based therapy of cardiac rhythm abnormalities. Heart Rhythm. 2008 Jun;5(6):e1-62. Epub 2008 May 21. Ghanbari H, Dalloul G, Hasan R, Daccarett M, Saba S, David S, et al. Effectiveness of implantable cardioverter-defibrillators for the primary prevention of sudden cardiac death in women with advanced heart failure: a meta-analysis of randomized controlled trials. Arch Intern Med. 2009 Sep 14;169(16):1500-6. Gissi-HF Investigators, Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, et al. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Oct 4;372(9645):1223-30. Epub 2008 Aug 29. Greenberg B and Kahn AM. Clinical assessment of heart failure. In: Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. Saunders; 2012:chap 26. Haykowsky MJ, Liang Y, Pechter D, Jones LW, McAlister FA, Clark AM. A meta-analysis of the effect of exercise training on left ventricular remodeling in heart failure patients: the benefit depends on the type of training performed. J Am Coll Cardiol. 2007 Jun 19;49(24):2329-36. Epub 2007 Jun 4. Heart Failure Society of America, Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA, et al. HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail. 2010 Jun;16(6):e1-194. Hildebrandt P. Systolic and nonsystolic heart failure: equally serious threats. JAMA. 2006 Nov 8;296(18):2259-60. Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG, et al. 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009 Apr 14;119(14):1977-2016. Epub 2009 Mar 26 Khush KK, Waters DD, Bittner V, Deedwania PC, Kastelein JJ, Lewis SJ, et al. Effect of high-dose atorvastatin on hospitalizations for heart failure: subgroup analysis of the Treating to New Targets (TNT) study. Circulation. 2007 Feb 6;115(5):576-83. Epub 2007 Jan 29. Mann DL. Pathophysiology of heart failure. In: Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. Saunders; 2012:chap 25. Mant J, Al-Mohammad A, Swain S, Laramée P; Guideline Development Group. Management of chronic heart failure in adults: synopsis of the National Institute For Health and Clinical Excellence guideline. Ann Intern Med. 2011 Aug 16;155(4):252-9. McAlister FA, Ezekowitz J, Dryden DM, Hooton N, Vandermeer B, Friesen C, et al. Cardiac Resynchronization Therapy and Implantable Cardiac Defibrillators in Left Ventricular Systolic Dysfunction. Evidence Report/Technology Assessment No. 152 (Prepared by the University of Alberta Evidence-based Practice Center under Contract No. 290-02-0023). AHRQ Publication No. 07-E009. Rockville, MD: Agency for Healthcare Research and Quality. June 2007. Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP, et al. N Engl J Med. 2009 Oct 1;361(14):1329-38. Epub 2009 Sep 1. Cardiac-resynchronization therapy for the prevention of heart-failure events. O'Connor CM, Starling RC, Hernandez AF, Armstrong PW, Dickstein K, Hasselblad V, et al. Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med. 2011 Jul 7;365(1):32-43. Schocken DD, Benjamin EJ, Fonarow GC, Krumholz HM, Levy D, Mensah GA, et al. 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. Circulation. 2008 May 13;117(19):2544-65. Epub 2008 Apr 7. - Last Reviewed on 05/28/2012 - Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997- 2013 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.	2	26	0	0	1	0.987894	1	14,176
Pneumonia ranks sixth in frequency of diagnoses processed by the McKesson Emergency Medicine Services division. Patients who visit the emergency department for medical symptoms such as coughing, shortness of breath or difficulty breathing, low or mild fever, enlarged lymph nodes, sore throat, sharp chest pain, or dark or bluish fingernails or toenails may be evaluated for a respiratory/lung problem. Emergency medicine providers may consider pneumonia one of the differential diagnoses, which would be considered a working diagnosis. If the provider’s cognitive thought process leads them to the path of pneumonia, they will also consider the type of pneumonia which may be present – viral, bacterial, infectious or a mycoplasma type of pneumonia. If pneumonia is suspected, specific measures may be taken. A chest X-ray may be ordered, CBC blood tests may be drawn to check the white blood count, arterial blood gasses may be used to check if enough oxygen is getting into the blood from the lungs, and other specific tests may be performed. A CAT scan will be used to determine how the lungs are functioning; sputum tests will used to look for the organism (that can be detected by studying the saliva); and other tests may identify potential fluid in the space around the lungs. Additionally, a pulse Oximetry will be used to measure the oxygen moving through the bloodstream and possibly a bronchoscopy if the condition continues to worsen. To date, many emergency department charts have shown final diagnosis documentation that states “typically after study, pneumonia,” without any elaboration of the type of pneumonia. In ICD-9 the code is “486 – Pneumonia, organism unspecified” and it approximately converts to ICD-10 code “J18.9 – Pneumonia, unspecified organism”. This type of medical condition, with the varied number of pneumonia types, requires the provider to include more detail to the final diagnosis based on the findings after study. As stated above there are many types of pneumonia. There is a one-to-one crosswalk for pneumonia, organism unspecified. Treatment for pneumonia depends on the type of pneumonia and how severe it is. The goals of treatment are to cure the infection and prevent complications. The entire work-up and treatment plan prepared for the patient is the provider’s responsibility. However, for that provider to get the greatest level of specificity in the final diagnosis under the ICD-10 world, more detailed documentation is required in that final statement of diagnosis for proper billing. This requirement also applies to the coding – in order for the coding staff to assign the appropriate ICD-10 code to its greatest level of specificity, it is important for the provider to document the detailed findings of study in the final impression or diagnosis. When a provider documents a final diagnosis that is not to its greatest level of detail, an unspecified code is typically assigned. Pneumonia codes in ICD-9 are in the code range 480 – 488 under “Pneumonia and Influenza.” The ICD-10 section for Pneumonia is J09 – J18 under Influenza and Pneumonia. Note that this is not a typo but the way it is listed in the code books. The description has been reversed – as was similar to the description for the ICD-9 and ICD-10 codes for pneumonia unspecified. The beginning of the ICD-9 and ICD-10 pneumonia sections has a note which shows codes that are excluded from this family of codes. Some of the excluded codes are other types of pneumonia (i.e., allergic, aspiration and rheumatic – all pneumonia). These are good examples of why the greater level of detail is so important in order to assign the most appropriate ICD-10 code. Some examples of crosswalks from ICD-9 to ICD-10 for pneumonia are outlined below. As shown in the table above, there are a number of ICD-10 codes for pneumonia. This is only a small example of those codes in both ICD-9 and ICD-10 books. It is imperative that the provider document exactly what the diagnostic study’s findings are, if any, to determine the exact course of action for the condition presented or defined after study in order to establish the appropriate code. This commentary is a summary prepared by McKesson’s Business Performance Services division and highlights certain changes, not all changes, in 2014 CPT® codes relating to the specialty of emergency medicine and emergency medical services. This commentary does not supplant the American Medical Association’s current listing of CPT® codes, its documentation in the annual CPT Changes publications, and other related publications from American Medical Association, which are the authoritative source for information about CPT® codes. Please refer to your 2014 CPT® Code Book, annual CPT® Changes publication, HCPCS Book and Payer Bulletins for additional information, including additions, deletions, changes and interpretations that may not be reflected in this document. CPT is a registered trademark of the American Medical Association (“AMA”). The AMA is the owner of all copyright, trademark and other rights to CPT® and its updates.	4	3	0	0	4	0.868762	4	1,076
National Organization for Rare Disorders, Inc. It is possible that the main title of the report Andersen-Tawil Syndrome is not the name you expected. 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 T-U wave pattern 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 been able to establish 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 that is 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 degenerate to 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 crowed 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. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child. 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. Symptoms of the following disorders can be similar to those of Andersen-Tawil syndrome. Comparisons may be useful for a differential diagnosis. Andersen-Tawil syndrome needs to be distinguished from other forms of periodic paralysis including hypokalemic periodic paralysis, hyperkalemic period paralysis, and thyrotoxic periodic paralysis. Other conditions that cause a prolonged QT interval or syncope should be ruled out as well including vasovagal syncope, orthostatic hypotension, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and catecholamingergic polymorphic ventricular tachycardia (CPVT). (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.) 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. Genetic counseling may be of benefit for affected individuals and their families. 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, have been used successfully to treat periodic paralysis in individuals with Andersen-Tawil syndrome. These drugs have also been shown to be effective in other forms of periodic paralysis. Despite a high rate of ventricular arrhythmias, the prognosis regarding arrhythmias is generally very good. Many arrhythmias do not cause symptoms and go away on their own with 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 only be used in individuals with Andersen-Tawil syndrome with caution. Treatment with an implantable automatic cardioverter-defibrillator or ICD has been used 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. Information on current clinical trials is posted on the Internet at //www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site. For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office: Toll-free: (800) 411-1222 TTY: (866) 411-1010 For information about clinical trials sponsored by private sources, in the main, contact: For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu Tristani-Firouzi M, Tawil R. Andersen-Tawil Syndrome. In: Cardiac Electrophysiology: From Cell to Bedside, 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. //www.ncbi.nlm.nih.gov/pubmed/24861851 Almuqbil M, Srour M. Child neurology: Andersen-Tawil syndrome. Neurology. 2015;84:e78-80. //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. //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. //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. //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. //www.ncbi.nlm.nih.gov/pubmed/24383070 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. //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. //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. //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. //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. //www.ncbi.nlm.nih.gov/pubmed/17272325 Sansone V, Tawil R. Management and treatment of Andersen-Tawil syndrome (ATS). Neurotherapeutics. 2007;4:233-237. //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. //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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC151085/ Statland JM, Tawil R, Venance SL. Andersen-Tawil Syndrome. 2004 Nov 22 [Updated 2013 Jan 3]. In: Pagon RA, Bird TD, Dolan CR, et al., GeneReviews. Internet. Seattle, WA: University of Washington, Seattle; 1993-. Available at: //www.ncbi.nlm.nih.gov/books/NBK1264; Accessed on: July 16, 2015. Sripathi N. Periodic Paralyses. Emedicine Journal, December 16, 2014. Available at: //emedicine.medscape.com/article/1171678-overview; Accessed on: July 16, 2015. 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: //omim.org/entry/170390; Accessed on: July 16, 2015. International Long QT Syndrome Registry - Heart Research Follow-up Program - Box 653 - Rochester, NY 14642-8653 - Tel: (585)276-0016 - Fax: (585)273-5283 - Email: [email protected] Muscular Dystrophy Association - 3300 East Sunrise Drive - Tucson, AZ 85718-3208 - Tel: (520)529-2000 - Fax: (520)529-5300 - Tel: (800)572-1717 - Email: [email protected] - Website: //www.mda.org/ NIH/National Heart, Lung and Blood Institute - P.O. Box 30105 - Bethesda, MD 20892-0105 - Tel: (301)592-8573 - Fax: (301)251-1223 - Email: [email protected] - Website: //www.nhlbi.nih.gov/ NIH/National Institute of Neurological Disorders and Stroke - P.O. Box 5801 - Bethesda, MD 20824 - Tel: (301)496-5751 - Fax: (301)402-2186 - Tel: (800)352-9424 - Website: //www.ninds.nih.gov/ Periodic Paralysis Association - 155 West 68th Street - Apt. 1732 - New York, NY 10023 - Tel: (407)339-9499 - Fax: (407)339-9499 - Email: [email protected] - Website: //www.periodicparalysis.org Periodic Paralysis News Desk - 2235 B 36th St. SW - Calgary, Alberta, T3E 2Z3 - Tel: 4032447213 - Email: [email protected] - Website: //www.hkpp.org - Ronnerweg 2 - Nidau, 2560 - Tel: 41794741535 - Email: [email protected] - Website: //www.qtsyndrome.ch/index.html SADS UK (Sudden Arrhythmic Death Syndrome) - Suite 6 - Churchill House - West Horndon, CM13 3XD - United Kingdom - Tel: 1277811215 - Email: [email protected] - Website: //www.sadsuk.org Sudden Arrhythmia Death Syndromes Foundation - 508 E. South Temple - Suite 202 - Salt Lake City, UT 84102 - Tel: (801)531-0937 - Fax: (801)531-0945 - Tel: (800)786-7723 - Email: [email protected] - Website: //www.sads.org For a Complete Report This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html. For additional information and assistance about rare disorders, please visit the National Organization for Rare Disorders web site at www.rarediseases.org The information provided in this report is not intended for diagnostic purposes. It is provided for informational purposes only. It is possible that the title of this topic is not the name you selected. Please check the Synonyms listing to find the alternate name(s) and Disorder Subdivision(s) covered by this report. This disease entry is based upon medical information available through the date at the end of the topic. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Last Updated: 8/4/2015 Copyright 2015 National Organization for Rare Disorders, Inc. Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.	2	20	2	0	0	0.759065	2	5,549
In Course 12, you learned about Current Procedural Terminology (CPT) codes. CPT codes describe medical, surgical, and diagnostic procedures and services in five-digit numerical sequences. These codes are published and copyrighted by the American Medical Association (AMA). They allow for standardized documentation and communication between medical facilities and organizations, as well as between patients, healthcare providers, and insurance companies. In order to describe the myriad number of different medical services, procedures, and factors accurately, CPT codes are divided into three Categories. Category I CPT codes describe medical, surgical, and diagnostic procedures (for instance, a routine checkup of low complexity is CPT code 99213). Category II CPT codes provide supplemental information to Category I CPT codes. The example used in Course 12 is the code for low-density lipoprotein cholesterol (CPT I code 80061) with a result of less than 100 mg of cholesterol per deciliter (CPT II code 3048F). This test and its result would be coded as 80061-3048F. Category II CPT codes supply information that streamlines administrative work and tracks the performance of certain tests or procedures. These Category II codes, however, do not always provide important information about the specifics of a procedure, like on which side of the body a surgery took place, or whether a surgery was discontinued due to concern for patient safety. See Examples of CPT Modifiers In order to communicate this extremely detailed information in an efficient, standardized way, the AMA created CPT modifiers. CPT modifiers are two-character suffixes that healthcare providers or coders attach to a CPT code to give additional information about the procedure documented. CPT modifiers are always two characters in length. They may consist of two numbers from 21 to 99, two letters, or a mix (alphanumeric). These modifiers are appended to the initial CPT code by a hyphen. Some examples of common CPT modifiers include: - -53 (discontinued procedure) - -59 (distinct procedural service) - -79 (unrelated procedure or service performed by the same physician during the postoperative procedure). Some common letter-based modifiers include: - -LT (denotes a procedure on the left side of the body) - -RT (denotes the right side of the body), - -GC (identifies that a service has been performed by residents or students under the guidance of a teaching physician). If you had to code a partial mastectomy of the left breast, you would use the CPT code 19302 for the procedure, with the modifier –LT to describe on which side of the body the procedure took place. Our code would read 19302-LT. If, however, the procedure had to be stopped because of a concern for the well-being of the patient, you would add another modifier: -53. The new code would read 19302-LT-53. Note that this is a simplified example, and that a procedure as complex as a mastectomy often has numerous additional codes). Certain CPT modifiers are only used with a particular type of procedure or service. For instance, the modifier –LT used above is only valid when describing a procedure on an appendage or organ paired in the body, such as the lung, kidney, leg, or breast. The modifiers, -21, -24, -25, and -27 are only used for evaluation and management. Also, note that unlike CPT codes and ICD codes, CPT modifiers are not necessarily grouped into related procedures. Functional vs. informational modifiers There are a number of additional rules that govern the use of CPT modifiers. Coders must constantly look out for certain restrictions, formats, and guidelines, as a miscoded CPT modifier can result in a denied claim. Medical coders typically only use two CPT modifiers. While there is room for up to four modifiers on the CMS 1500 and UB-04 claim forms, the Center for Medicare and Medicaid Services (CMS) or other payers may not recognize modifiers after the first two. For this reason, coders should list first the modifiers that will affect reimbursement. These are often called functional or pricing modifiers, while modifiers that provide information about the procedure are known as informational. There are certain CPT modifiers, such as -22 (for unusual procedural services) and -52 (for reduced services), that affect reimbursement if documentation supports the use of this modifier. Take, for example, the partial mastectomy of the left breast (code 19302-LT-53). If you were to swap out the -53 (discontinued procedure) with the functional modifier -52 (for reduced services), you would then code the whole procedure 19302-52-LT. Note that the functional modifier (-52) now comes before the informational modifier (-LT). If the informational modifier is listed first in a claim, an insurance company will deny that claim and return it to the healthcare provider. Certain modifiers also have guidelines specific to them. The modifier -51, for multiple procedures, is one of the more commonly used CPT modifiers. In the instance of multiple procedures provided by the same specialist or healthcare provider, a coder would list the initial procedure’s CPT code, then append the modifier -51 to the end of the code for the additional procedure or procedures. Certain procedures, however, are listed in the CPT book as “-51 exempt,” and coders must be aware of this distinction. Note that some modifiers can be used in conjunction with each other (like -23, unusual anesthesia, and -47, for anesthesia by surgeon). Others contradict one another and cannot be included in the same code For example, the modifier –LT (procedure on the left of two paired appendages or organs) cannot be coded with the modifier -50, which describes a bilateral procedure. Wrapping Up Course 13 Medical coders should familiarize themselves with the CPT modifiers as much as possible. While there are not as many modifiers as there are ICD-9-CM or CPT codes, they are very specific. A misused modifier can often be the difference between an accepted and denied claim.	4	6	14	0	0	0.506727	14	1,283
The Obstructive Sleep Apnea ICD 10 case definition was developed by the Armed Forces Health Monitoring Branch (AFHSB) for the needs of epidemiological supervision of a condition that is important for the military-related population. In 2004, there is a research of the Veterans Health Administration. He concluded three percent million US military veterans had diagnoses of sleep apnea. That is the shocking fact that American people especially health care professional to overcome this problem. Obstructive sleep apnea (OSA) is characterized by total or almost complete obstruction of the upper airway, usually at the oropharyngeal level. The patient then returns to sleep, and the sequence of events is repeated often up to 400-500 times per night or called as Obstructive Sleep Apnea ICD 700 when repeated until 700 times per night, resulting in real sleep fragmentation. This condition is more common in men, and some symptoms of sleep apnea such as snoring, insomnia, daytime sleepiness, headaches after wake up usually in the morning, choking and gasping during sleep. Treatment depends on OSA severity and may include weight loss, alcohol avoidance, intraoral equipment, surgery, and continuous positive airway pressure (CPAP) during sleep. What is Incident Case to know Sleep Apnea? Incident Case Definitions and Rules for screening for obstructive sleep apnea icd 10, obstructive sleep apnea cases are defined as: One hospital with a definition of obstructive sleep apnea diagnosis in any diagnostic position; or two outpatient medical meetings, within 90 days of each other, with the definition of obstructive sleep apnea diagnosis in any diagnostic position. Rule of incident: For individuals who meet the case definition: Incidence is considered as the date of the first hospitalization or medical meeting which includes a definite diagnosis of obstructive sleep apnea. Cases of incidents are only once in a lifetime. Definition and Rules of Incident Cases for monitoring purposes, obstructive sleep apnea cases are defined as: One hospital with a definition of obstructive sleep apnea diagnosis in any diagnostic position; or two obstructive sleep apnea can be caused by another prespective. Kinds of Diagnostic Codes of Sleep Apnea The following code is ICD-10-CM G47.30 Obstructive ICD-9-CM code (sleep apnea, non-specific) sleep apnea 780.51 (insomnia with sleep apnea, not specific) 780.57 (non-specific sleep apnea) G47.33 (obstructive sleep apnea) 327.23 (obstructive, adult, pediatric sleep apnea) G47.39 (other sleep apnea) 780.53 (hypersomnia with sleep apnea, not specific) Development and Revision In January 2016 Case definitions were updated to include screening for obstructive sleep apnea ICD10 codes. This case definition was developed based on reviews of ICD9 and ICD10 codes, scientific literature, and previous AFHSC analysis. The case definition was developed by MSMR AFHSC staff for the might 2010 MSMR about Sleep Apnea. 4 Case Definition and Rational Events The 90-day interval between visits is needed to make an accurate OSA diagnosis. Diagnostic protocols for OSA often require various studies in intensive home polysomnographic sleep overnight at the sleep center. Collection of Determination Codes and Rationale The aim of this case is to capture obstructive sleep apnea cases. Some cases of central sleep apnea can be captured by the code ICD10 G47.39 (other sleep apnea) because individuals are mixed with symptoms of sleep apnea (both obstructive and central). G47.3 is a diagnosis of the main code for sleep apnea, but by itself is not a billable code. The obstructive sleep apnea ICD-10 requires further details and specifications. There are 9 codes in the G47.3 category that explain this diagnosis in more detail. G47.30 (unspecified), G47.31 Central apnea sleep, G47.32 High-altitude periodic breathing, G47.33 possible Obstructive sleep apnea (adults) (children), G47.34 Alveolar hypoventilation associated with hypoventilation associated idiopathic sleep , nonobstructive, G47.35 Congenital central alveolar hypoventilation syndrome, G47.36 Hypoventilation is associated with sleep under conditions elsewhere, G47.37 Central sleep apnea in conditions classified elsewhere, G47.39 Other sleep apnea Diagnostic criteria for apnea sleep, International Sleep Disorder Classification, 3rd Edition. Out patient medical findings, within 90 days of each other, with the definition of obstructive sleep apnea diagnosis in each diagnostic position. Rule of incident: For individuals who meet the case definition: Incidence is considered as the date of the first hospitalization or medical meeting which includes a definite diagnosis of obstructive sleep apnea. Cases of incidents are only once in a lifetime. Thats short description about obstructive sleep apnea ICD-10.	4	7	0	0	9	0.84964	9	1,052
It is done during cardiac catheterization. Cardiac Catheterization and Coronary Angiography - Explore from the MSD Manuals - Medical Consumer Version. . Left heart catheterization Defined as left heart hemodynamics Systolic and end-diastolic pressures, etc. Ventriculography is a type of angiography in which x-rays are taken as a radiopaque contrast agent is injected into the left or right ventricle of the heart through a catheter. During a cardiac catheterization, your healthcare provider puts a long, narrow tube (catheter) into a blood vessel in your leg or arm and moves it to your coronary arteries. Magnetic resonance imaging (MRI) of the heart. Cardiac catheterization is used to: Evaluate or confirm the presence of coronary artery disease, valve disease or disease of the aorta Evaluate heart muscle function During the procedure, the pressure and blood flow in your heart can be measured. - Ventriculography.-Coronarography. What sets each apart is the following: 93454: no heart catheterization performed. Cardiac catheterization involves passing a catheter into the right or left side of the heart. Other procedures can also be done at this time, such as: Ventriculography to check the heart's pumping function. It is also known as transradial cardiac cath or angiography. The images show how well your heart is pumping. Cardiac catheterization (also called cardiac cath, heart cath, or coronary angiogram) is a procedure that allows your doctor to see how well your blood vessels supply your heart. When an endomyocardial biopsy (CPT code 93505) is performed during cardiac catheterization, bill only one unit of service regardless of the number of biopsies taken. Other procedures, can also be done at this time, such as: Ventriculography to check the heart's pumping function. And, if you're accessing/injecting the ventricles, you've done a heart cath (see page 393 of the Professional Edition of CPT-4 2007 for further specifics on 93508). . In addition, cardiac catheterization might be performed when there is lack of consistency between the clinical findings and the results of the non-invasive testing in order to rule out cardiac etiologies or . Unexpected drainage, pus, redness or swelling of your incision. When left ventriculography is performed, proper technique must be used to generate high-quality data to direct patient management. Cardiac catheterization is useful to evaluate mitral regurgitation when the results of the non-invasive testing are insufficient. Right and Left Heart Cath with Coronaries and Bypass work RVU 8.10. AU - Shoshani, Oren. Catheterization can determineblood pressure and blood flow in the chambers of the heart, permits blood sample collection, and record films of the heart's ventricles (contrast ventriculography) or arteries (coronary arteriography or . This documentation includes, but is not limited to, relevant medical history, physical examination and results of pertinent diagnostic tests or procedures. Exclusion of coronary . The radial artery is a blood vessel in the arm. An x-ray will be used to carefully guide the catheter to your heart. This statement aims to demonstrate the role of left ventriculography at the time of coronary angiography or left heart catheterization. 1 The procedure may increase reimbursement, although the amount is small compared with the . AU - Goldenberg, Iian. However, entry into the left ventricle with hemodynamic measurement and visualization of the left ventricle using contrast ventriculography remains an important aspect . Pain in or change in color of your toes or foot. The catheterization data is presented at our weekly cardiology conference (attended by cardiologists and surgeons) held Thursday mornings. . Coronary angiography to examines the coronary arteries. A 64-year-old man is admitted for a left heart catheterization, coronary angiography of multiple coronary arteries and left ventriculography, using low osmolar contrast. It is sometimes combined with coronary angiography. And search more of iStock's library of royalty-free stock images that features Catheter photos available for quick and easy download. Right heart ventricular angiography is a study that images the right chambers (atrium and ventricle) of the heart. Judkins left 4 (JL4) catheter in place. . Definition. Ventriculography is a type of angiography in which x-rays are taken as a radiopaque contrast agent is injected into the left or right ventricle of the heart through a catheter. Introduction. In general, cardiac catheterization is not necessary to determine the severity of aortic stenosis. Code 93453 is another procedure code that will be utilized less . Left heart ventricular angiography is a procedure to look at the left-sided heart chambers and the function of the left-sided valves. Cardiac catheterization is a procedure that allows the doctor to see how well your blood vessels supply your heart. The left anterior descending coronary artery had total occlusion in the proximal and mid portion. Therapeutic applications of cardiac catheterization. Diagnostic Combined Heart Catheterization includes: a single procedure which includes the evaluation of both the left and right as above. 93458: left heart catheterization (LHC) performed. Transradial cardiac catheterization is a procedure used to treat and diagnose certain heart conditions. Ventriculography is a type of angiography in which x-rays are taken as a radiopaque contrast agent is injected into the left or right ventricle of the heart through a catheter. The decision to perform a left heart catheterization and left ventriculography is left to the discretion of the operator and the patient's primary physician. The clinicians frequently disagreed as to the presence of physical signs of heart failure in individuals. This paper attempts to show the role of left ventriculography at the time of coronary angiography or left heart catheterization. Right heart catheterization 93451 Left heart catheterization, inc. left ventriculography 93452 Combined left and right heart catheterization, inc. left ventriculography 93453 Coronary angiography 93454 Coronary angiography w/o left or right heart cath, with angiography of bypass graft(s) 93455 Coronary angiography w/ right heart cath 93456 Appointments 800.659.7822 The catheter is then moved through the aortic valve into the left side of your heart. CPT codes 93454 and 93455 (catheter placement, angiography) should be billed, as appropriate, when coronary or bypass angiography without left heart catheterization is performed. 3. T1 - Left ventriculography complicated by cerebral air embolism. During the procedure, a healthcare provider inserts a long thin tube (catheter) through the radial artery. Look to code 93459 when coronary and bypass graft angiography are performed. cardiac ventriculography is used to define the anatomy and function of the ventricles and related structures in patients with congenital, valvular, coronary, or myopathic heart disease. The pictures let your doctor check the health of the lower chambers of your heart, called ventricles. Coronary angiography procedures, however, are classified to the Imaging . Cardiac catheterization (heart cath) is the insertion of a catheter into a chamber or vessel of the heart.This is done both for diagnostic and interventional purposes. Findings from these procedures resulted in the decision to perform a percutaneous transluminal coronary angioplasty (PTCA) of two separate lesions in the left anterior . Ventriculography to examines the heart's pumping activity. This allows the physician to . 93545 Injection for selective coronary angiography. Fever. Live x-ray pictures are used to help guide the catheters up into your heart and arteries. but neither finding was detected on echocardiography or angiographic ventriculography. Whether you're an experienced practitioner, resident or cardiology fellow, you'll find this an irreplaceable cardiac reference. X-ray test: During cardiac catheterization, x-ray dye is injected into the heart while x-ray movies are taken during the injection. The price for heart catheterization depends on the clinic and country where it is performed, whether it is done for the entire heart or only part of it and the other procedures which are needed (X-ray, etc). First cardiac catheterization on human was introduced by Werner Forssmann in 1929 who inserted a catheter through his own antecubital vein to the right heart. Chapter 28 Coding Practice 1. Right heart catheterization may be combined with this procedure. Right and Left Heart Cath with Coronaries and Bypass CPT code 93461. When coronary angiography is performed during left heart catheterization, use 93458. This test can be done as a noninvasive test or as part of an invasive procedure. I have found that the left sided heart cath with selective coronary angiography cpt code is 93452 this also includes the ventriculography Wiki User 2013-02-09 19:08:22 All catheterization laboratory personnel should recognize the importance of preprocedure assessment and be aware of the indications why the patient is having the procedure performed. If that is the case, that ventriculography requires accessing the ventricle(s), then 93508 cannot be correct and we need to educate them on this issue. The pressure is measured in the heart in this position. View 1 more answer. Report 93452 when coronary angiography is not performed during the left heart cath. This helps show blockages in the blood vessels that lead to your heart. . Introduction. iStock Cardiac Ventriculography Catheterization Stock Photo - Download Image Now Download this Cardiac Ventriculography Catheterization photo now. "Until recently, there have been no specific guidelines to help clinicians recognize when it's appropriate to perform left ventriculography at the time of coronary angiography or left heart catheterization," explains Osvaldo S. Gigliotti, MD, FSCAI. . These changes were due to the work done by a committee that was doing a 5-year review on How the Test is Performed Before the test, you will be given medicine to help you relax. The patient's medical record should contain documentation that fully supports the medical necessity for cardiac catheterization and coronary angiography as it is covered by Medicare. How the Test is Performed You will get a mild sedative 30 minutes before the procedure. A contrast dye visible in X-rays is injected through the catheter. The Cardiac Cath Report provides the overall clinical results of the catheterization procedure and interventions. A 41-year-old member asked: . Coronary angiography (PDF) is done during cardiac catheterization. In the other set of Pediatric codes, five new codes, 93593-93597, were developed for Cardiac Catheterization for Congenital Defects to replace codes 93530-93533, which have now been deleted. Cardiac catheterization involves the insertion of fine-bore tubes (catheters) into the heart through cannulae inserted into a peripheral artery or vein. Transcatheter left ventricular restoration device implantation including right and left heart catheterization and left ventriculography when performed . radiation injury due to X-ray exposure during a long catheterization . . What will happen: Your healthcare provider will insert a catheter into an artery in your arm or leg. In many cases, more detailed information is optionally available in other reports (Hemodynamic Measurements, Procedure Log, etc.). Dye (sometimes called "contrast") will be injected into your body. Cardiac cath is performed to find out if you have disease of the heart muscle, valves or coronary (heart) arteries. A ventriculogram is a test that shows images of your heart. Fletcher further details what sets these procedures apart so you can feel confident knowing which code to use. During the test . damage to your blood vessels, heart tissue, or heart valves. - Cardio-angiographic examination.-Aortography. - Coronary heart disease: clinical manifestations with coronary artery correlations e Less urine output than normal. It is sometimes combined with coronary angiography. It is done during cardiac catheterization. . The definition of Measurement is "determining the level of a physiological or physical function at a point in time.". He will inject a dye so he can see the blood vessels, muscle, or valves of your heart more clearly. During this procedure, a catheter (long thin tube) is inserted in an artery or vein in your groin, neck, or arm and threaded through your blood vessels . Left ventriculography, imaging of the left ventricle with a contrast injection, was one of the first methods of measuring left ventricular function and wall motion and is usually performed at the discretion of the cardiologist during cardiac catheterization (eg, coronary angiography). - Oxford, England Travel - Alcohol In Checked Baggage - Singapore Airlines - Mortal Kombat 11 Trade In Value - How To Connect Bose Sport Earbuds To Android - British Heraldry Ranks - Usa Sled Hockey Team Roster 2022 - Fema Automated Map Production - Crunches During First Trimester - Websocket Sniffer Chrome - New Ford Maverick For Sale Near Me - Electric Built-in Fireplace - W203 Rear Bumper Removal - Uterine Contractions Normal Range - Steam Achievement Not Unlocking - Ashley Furniture Marsilona Chairs - Best Follow Through In Nba 2k20 Mobile - Tactical Drone Training - Types Of Datum In Engineering - Cornell Campus-to-campus Bus	4	17	25	0	0	0.815894	25	2,957
- 1 What is Lennox Gastaut Syndrome? - 2 Lennox Gastaut Syndrome Symptoms - 3 Complications - 4 What Causes Lennox Gastaut Syndrome - 5 Lennox Gastaut Syndrome Tests and Diagnosis - 6 Treatment and Management What is Lennox Gastaut Syndrome? Lennox Gastaut Syndrome (LGS), also called childhood epileptic encephalopathy, is a rare severe form of progressive epilepsy, characterized by multiple types of seizures that are most prominent during infancy or early childhood (age 3-8 years), but may persist through adolescence to adult years. Affected children may also have intellectual functioning impaired as well as face behavioral problems and delayed development. The disorder, first discovered by Tissot in 1770, can be classified into two types on the basis of the cause of the symptoms: - Symptomatic LGS - Cryptogenic or Idiopathic LGS Lennox Gastaut Syndrome Symptoms Symptoms consist of different types of seizures and neurological malfunctions. Amidst the seizures, the more common are the tonic and atonic or “drop” seizures. Tonic Seizures, affecting about 74-90% of children with LGS are brief, occur mostly at night and can be triggered by noise, contact or movement. They may cause: - A slight bending of the body inward due to muscle contractions - Brief holding of breath - The opening of mouth and rolling of eyes - Abnormal rise of upper arms and legs much like a ballet dancer - Sudden collapse of the affected individual due to short loss of consciousness Atonic Seizures, also lasting for a minute time are characterized by: - Dropping of eyelids and nodding of head - Sudden falls - A tendency to collapse forward or backward particularly at the waist - Brief consciousness loss - Jerking muscle movements Atypical Absence Seizures, which are abrupt, are characterized by: - A span of unconsciousness - Unresponsive staring - Twitching around eyes or mouth - Stiffening of neck - Drooping of head and body Less common forms of seizures occurring in the condition include myoclonic, tonic-clonic, status epilepticus and nonconvulsive status epilepticus seizures. The less frequent neurological symptoms that generally develop with time involve: - Difficulty in sitting, crawling or walking suggesting delayed motor development - Loss of previously learned skills - Hyperactivity, aggressiveness and a tendency to seek attention suggesting behavioral problems - A slowing down of thought with reduced physical movement indicating psychomotor regression - Drop seizures replaced by partial seizures and secondarily generalized convulsions - Acute psychotic episodes - Chronic psychosis - Mental retardation - Cognitive incapability involving slowness in response and information processing - Head injuries and even death from fall or seizure - Renal, cardiac or metabolic complications - Cerebral palsy - Hearing loss What Causes Lennox Gastaut Syndrome The reasons behind Symptomatic Lennox-Gastaut syndrome, which accounts for nearly 70-80% of cases, are: - Internal injuries of brain resulted from problems before, at or during birth such as prematurity, insufficient supply of oxygen called perinatal hypoxia and low birth weight - Abnormal brain cortex development suggesting cortical dysplasia - Severe brain infections such as encephalitis or meningitis - A rare genetic disorder known as tuberous sclerosis - Degenerative or metabolic nervous system disorders Cryptogenic LGS which does not have an identifiable cause may have a later onset. ** Although in most cases, the causes are identifiable, yet the exact mechanisms that bring about the seizures are not known, and more researches need to be done to derive a genetic basis of the syndrome. - Family history of epilepsy - West syndrome Lennox Gastaut Syndrome Tests and Diagnosis The diagnosis of LGS is based on the identification of the clinical triad that comprises of multiple seizures, an abnormal EEG with a significant spike-wave pattern of the brain and some degree of cognitive and behavioral dysfunction. An advanced imaging technique such as MRI is also done to get three-dimensional images of the brain anatomy. - Early onset childhood absence epilepsy - Dravet syndrome - Atypical benign partial epilepsy - Myoclonic astatic epilepsy Treatment and Management Administration of Anti-Epileptic Drugs (AEDs) Treatment may start with medications, which often include: - Valproate, which may be given alone or in combination with other drugs like lamotrigine, topiramate or clobazam. Though valproate is beneficial for all types of seizures, yet it has side effects such as tremors or reduction in platelet counts. - Another drug of choice, topiramate may help lessen both drop attacks and multiple seizures but an increased dose can have side effects like sleepiness and ataxia. - Clonazepam, the most commonly used representative of the benzodiazepine class of drugs may have partial effect in myoclonic seizures. - Lamotrigine seems to be efficient in multiple seizures as well as a mood stabilizer. - Felbamate may help promote alertness, but it too can induce aplastic anemia. - FDA has approved Levetiracetam for partial seizures, but it may prove efficient in other seizures too. - Rufinamide (Benzel) is used as an adjunctive therapy for adults and children aged one or above having seizures. Occupational therapy, speech and physical therapy are the rehabilitation procedures that may help children suffering from the syndrome in reducing the levels of disability. The Ketogenic Diet However, since the above mentioned drugs may lose their effect with the passage of time, the condition may be treated with the help of another approach called the ketogenic diet. This strict high fat, low carbohydrate diet is initiated after a 24-hour fasting, intending to raise the ketone level in the brain. By restricting an intake of carbohydrates, this diet forces the body to burn fat to get energy instead of sugar. Followed under the strict supervision of a doctor and dietician, it does not prevent the use of medications. Vitamins and minerals may be supplemented to avoid a deficiency. Though proving effective in a minority of patients, it may have side effects like dehydration, constipation, kidney stones and vomiting. Surgical Therapies – Lennox Gastaut Syndrome Patients not responding to either medications or dietary therapy undergo a surgical procedure called corpus callosotomy. This surgery, accomplished by cutting the large bundle of nerve fibers called the corpus callosum that connects the two hemispheres is done to reduce the severity of drop attacks, tonic, and tonic-clonic seizures. According to several studies, in 50- 70% of cases, partial callosotomy is beneficial whereas complete callosotomy may result in the decrease of drop attacks in about 80-90% of cases. Vagus Nerve Stimulator This surgery lasting for about an hour and usually conducted under anesthesia, involves the insertion of a device called a pulse generator into the chest to transmit mild, electrical impulses to the brain through the vagus nerve. This process, intending to reduce the frequency of the seizures may have side effects such as voice hoarseness, tickling in the throat and coughing. The other surgical procedures are RNS stimulator, deep brain stimulation, and trigeminal nerve stimulation. Treatment Through Nonpharmacological Means Include - Intravenous Immunoglobulin (IVIG): IVIS is a blood product that can be given intravenously in the treatment of LGS. - Medical Marijuana/CBD (Cannabidiol): A compound called cannabidiol found in cannabis might reduce chemical as well as electrical activity that occurs in the brain and thus may be used therapeutically for patients living with LGS. The annual incidence of children having LGS is about 2 per 1000,000 children. Nearly 1-2% of all childhood epilepsies are represented by LGS. Amidst this, 75-90% children suffer from mental retardation which generally begins within a few years of the onset of the syndrome. Prognosis and Life Expectancy The prognosis of this progressive syndrome varies with individuals. Seizures continue in more than 80% of patients. MRIs and other clinical exams may occasionally be repeated to look for any change in the brain. The mortality rate of the syndrome ranges from 3% to 7% with most of the deaths occurring from accidents. The degree of disability may be lessened with early and useful treatment. Recovery also depends on the combined efforts of health care providers such as social workers and neuropsychologists. ICD Code- 9 and ICD Code- 10 The icd-9 code for LGS is 345.0 and the ICD- 10 Code is G40.814.	2	8	0	0	2	0.687876	2	1,872
Published: August 2010 The concept of a state of hypercoagulability dates back to 1854, when German pathologist Rudolph Virchow postulated that thrombosis resulted from, and in turn precipitated, three interrelated factors1: decreased blood flow (venous stasis), inflammation of or near the blood vessels (vascular endothelial injury), and intrinsic alterations in the nature of the blood itself. These “blood changes” alluded to in Virchow's triad have become what are now known as hypercoagulable states, or thrombophilias. Hypercoagulable states can be defined as a group of inherited or acquired conditions associated with a predisposition to venous thrombosis (including upper and lower extremity deep venous thrombosis with or without pulmonary embolism, cerebral venous thrombosis, and intra-abdominal venous thrombosis), arterial thrombosis (including myocardial infarction, stroke, acute limb ischemia, and splanchnic ischemia), or both. Venous thromboembolic disease is the most common clinical manifestation resulting from hypercoagulable states. Although most inherited conditions appear to increase only the risk of venous thromboembolic events (VTEs), some of the acquired conditions have been associated with both VTEs and arterial thrombosis. These include cancer, myeloproliferative syndromes, antiphospholipid antibodies (APAs), hyperhomocysteinemia, and heparin-induced thrombocytopenia. Most hypercoagulable states alter the blood itself, whereas others affect the vasculature directly. Although patients with hypercoagulable states are at greater risk for developing a thrombotic event than those without such disorders, not all persons with a well-defined hypercoagulable state will develop an overt thrombosis and not all persons with thrombosis have an identifiable hypercoagulable state. In fact, in 2003, testing for an inherited hypercoagulable state was likely to uncover an abnormality in more than 60% of patients presenting with idiopathic (i.e., spontaneous or unprovoked) VTEs (Fig. 1).2 Although the remaining 30% to 40% would have unremarkable test results, this does not imply a true absence of a hypercoagulable state. Some of these individuals may have an acquired condition such as cancer or APA, and others may have a disorder or defect that has not yet been discovered or characterized. This can be illustrated by the fact that before 1993—before the discoveries of factor V Leiden and the prothrombin G20210A mutation—an inherited predisposition to hypercoagulability was identified in only 15% to 20% of patients presenting with idiopathic VTEs.2 This chapter will focus on the most common hypercoagulable states and their association with VTEs. Readers are referred to reports on the association between hypercoagulable states and arterial thrombosis.3,4 Specific derangements that will be reviewed in this chapter include activated protein C resistance, factor V Leiden, prothrombin G20210A mutation, deficiencies of natural anticoagulants (antithrombin, protein C, and protein S), APAs, and hyperhomocysteinemia. Although it is beyond the scope of this chapter to review the association between cancer and thrombosis or to discuss issues pertaining to cancer screening following VTEs, malignant diseases are likely the most common acquired hypercoagulable state. At a minimum, appropriate age- and gender-specific cancer screening must be considered after VTEs, particularly in older individuals and in young patients with idiopathic VTEs but without laboratory evidence for a hypercoagulable state. Guidelines for the early detection of cancer have been updated by the American Cancer Society.5 Hypercoagulable states can be inherited, acquired, or both. Activated protein C (APC) resistance secondary to factor V Leiden, prothrombin G20210A mutation, and deficiencies of natural anticoagulants are examples of inherited conditions, whereas APAs are an acquired set of disorders. Hyperhomocysteinemia can be precipitated by both genetic defects and acquired medical conditions, including vitamin deficiency states. Factor V Leiden, or factor V G1691A, is a single-point mutation in the gene that codes for coagulation factor V.2 It involves a G (guanine)-to-A (adenine) substitution at nucleotide 1691 (G1691A) in exon 10, which predicts the replacement of arginine at amino acid residue 506 by glutamine (Arg506Gln).6 The mutation, transmitted through autosomal dominant inheritance, renders factor V resistant to inactivation by APC (a natural anticoagulant protein). Factor V Leiden accounts for 92% of cases of APC resistance (APC-R), with the remaining 8% of cases resulting from pregnancy, oral contraceptive use, cancer, select APA, and other factor V point mutations. Therefore, the terms factor V Leiden and APC-R should not be considered synonymous; in fact, APC-R is an independent risk factor for VTEs, even in the absence of factor V Leiden. It is estimated that the mutation arose in a single white ancestor some 21,000 to 34,000 years ago, well after the evolutionary separation of non-Africans from Africans (approximately 100,000 years ago) and of Caucasoid (white non-Africans) from Mongoloid (Asians) subpopulations (approximately 60,000 years ago).7 Prothrombin G20210A is a single-point mutation (G-to-A substitution at nucleotide 20210) in the 3′ untranslated region of the prothrombin (coagulation factor II) gene.2 This autosomal dominant mutation appears to result in elevated concentrations of plasma prothrombin. Like factor V Leiden, the prothrombin G20210A mutation arose in a single common white founder, and probably also occurred after the evolutionary divergences of subpopulations.8 Over 100 different mutations have been detected in the genes that code for each of the natural anticoagulant proteins (protein C, protein S, and antithrombin), resulting in quantitative (type I) or qualitative (type II) deficiencies.9 Both antithrombin and protein S deficiencies have an autosomal dominant pattern of inheritance.10,11 Protein C deficiency was believed to be inherited in an autosomal dominant pattern, with incomplete penetrance. Studies have suggested that protein C deficiency is an autosomal recessive disorder and that coinheritance of another defect, particularly factor V Leiden, results in a high degree of penetrance that appears as dominant inheritance in double-heterozygous carriers.12,13 APAs consist of two major subgroups, the lupus anticoagulants and the anticardiolipin antibodies. Lupus anticoagulants are detected by their ability to prolong phospholipid-dependent coagulation tests in vitro (e.g., activated partial thromboplastin time and dilute Russell viper venom time). Anticardiolipin antibodies are detected by the enzyme-linked immunosorbent assay (ELISA).14 APAs that occur in association with autoimmune disorders, such as systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, and mixed connective tissue disease, as well as in the setting of cancer, are considered secondary;15 APAs detected in those without any obvious underlying autoimmune or malignant diseases are called primary. APAs have also been reported in conjunction with idiopathic autoimmune hemolytic anemia, malaria, syphilis, Q fever, infections by mycobacteria, Pneumocystis jiroveci, cytomegalovirus, and after exposure to drugs such as neuroleptics, quinidine, and procainamide.14,16 The metabolism of the amino acid homocysteine consists of a vitamin B6-dependent trans-sulfuration pathway involving the enzyme cystathionine β-synthase (CBS) and a folate- and vitamin B12–dependent remethylation pathway involving the enzymes methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (Fig. 2).17,18 Inherited severe hyperhomocysteinemia (plasma level >100 µmol/L), as seen in classic homocystinuria, may result from homozygous MTHFR or CBS deficiencies and, more rarely, from inherited errors of cobalamin (vitamin B12) metabolism.19 Inherited mild to moderate hyperhomocysteinemia (plasma level 15-100 µmol/L) may result from heterozygous MTHFR and CBS deficiencies, but most commonly results from the C677T gene polymorphism, which is the most common mutation in the gene that codes for the MTHFR enzyme.18,19 This single-point mutation (C677T) in the coding region for the MTHFR binding site (exon 4) is autosomal recessive, leads to the substitution of a valine for an alanine, and results in a thermolabile variant of the MTHFR (tlMTHFR).18 Acquired hyperhomocysteinemia in the absence of any mutation or polymorphism may be caused by folate deficiency, vitamins B6 and B12 deficiencies, renal failure, diabetes mellitus, hypothyroidism, carcinoma, pernicious anemia, inflammatory bowel disease, and methotrexate, theophylline, or phenytoin therapy.17,18 Individuals who are heterozygous for the tlMTHFR variant have normal plasma homocysteine levels, whereas homozygous carriers may have mild to moderate fasting hyperhomocysteinemia in the setting of concomitant folate deficiency.17,19 However, homozygosity for the tlMTHFR in the absence of hyperhomocysteinemia does not appear to be associated with an increased risk of VTEs, and most patients with hyperhomocysteinemia do not have the tlMTHFR polymorphism.19 Excess homocysteine in the plasma is the risk factor and is the target of therapeutic intervention, not the C677T mutation. The prevalence of hypercoagulable states depends on the ethnicity and clinical history of the studied population. Prevalence is lowest in the general population, greater in individuals with a single VTE, and highest in those with recurrent VTEs or who are from known thrombophilic families (Table 1).20 \|Hypercoagulable State\|\|General Population (%)\|\|Patients with Single VTE (%)\|\|Thrombophilic Families (%)\| \|Factor V Leiden\|\|3-7\|\|20\|\|50\| \|Protein C deficiency\|\|0.2-0.4\|\|3\|\|6-8\| \|Protein S deficiency\|\|N/A\|\|1-2\|\|3-13\| N/A, not readily available or unknown; VTE, venous thromboembolic event. Data from Rosendaal FR: Risk factors for venous thrombosis: prevalence, risk, and interaction. Semin Hematol 1997;34:171-187. APC-R caused by factor V Leiden is the most common inherited predisposition to hypercoagulability in white populations of northern European background.2 Factor V Leiden follows a geographic and ethnic distribution; it occurs most frequently in northern and western Europe (the highest prevalence of 15% has been reported in Sweden), but high prevalences are also found in Cyprus (13%), Turkey (9%), and the Middle East (5.4%).21 The mutation is also found in whites from eastern Europe and South America (prevalences of 2%-4%), but is rare in the Asian and African continents as well as in ethnic groups of Asian descent, such as the Inuit Eskimos, Native Americans, Australian aboriginals, and Polynesians.21 In the United States, factor V Leiden is most commonly seen in whites (6%), with lower prevalences in Latin Americans (2.2%), African Americans and Native Americans (1.2%), and Asian Americans (0.45%).22 The prothrombin G20210A mutation is the second most common inherited predisposition to hypercoagulability, occurring more frequently in whites of southern European background. In fact, the 3% prevalence in southern Europe is almost twice the prevalence observed in northern Europe.23 Similar to factor V Leiden, the prothrombin G20210A mutation is also found in the Middle East and Indian regions, but is virtually absent in individuals of African and eastern Asian backgrounds.23 These distributions provide support to the estimate that both mutations (factor V Leiden and prothrombin G20210A) originated relatively recently in the European founding population, after the evolutionary divergences of subpopulations. The deficiencies of natural anticoagulants are rare in the general population and, combined, are found in less than 15% of all individuals with a single VTE (see Table 1 and Fig. 1). The prevalence of APA (an acquired set of disorders) is significantly higher in patients with autoimmune disorders than in healthy individuals from the general population. In patients with systemic lupus erythematosus, the reported average prevalences for lupus anticoagulants and anticardiolipin antibodies are 34% and 44%, respectively.15 Appreciation of the mechanisms whereby hypercoagulable states lead to pathologic thrombosis requires an understanding of normal hemostasis, which comprises two equally important processes, primary hemostasis and secondary hemostasis. Although described as separate events, both primary and secondary hemostases occur concurrently at a site of vascular injury. Primary hemostasis consists of three events that lead to the formation of a platelet plug—namely, platelet adhesion, platelet activation, and platelet aggregation. Platelets adhere to the vascular subendothelium by attaching to subendothelial von Willebrand factor molecules exposed at a site of vascular injury. Once adherent, platelets are activated by a number of agonists, including thrombin, collagen, epinephrine, and thromboxane A2, and are stimulated to release their alpha and dense granule contents, which further promote platelet recruitment, activation, and aggregation. After additional platelets are recruited, they are linked by fibrinogen through the surface glycoprotein IIb/IIIa receptors to form the platelet plug. Secondary hemostasis consists of a series of sequential reactions, a coagulation cascade, in which inactive protease zymogens are converted to active serine proteases, ultimately resulting in the production of thrombin and covalently cross-linked fibrin (Fig. 3). In response to vascular injury, the in vivo coagulation cascade is triggered by the exposure of tissue factor. Tissue factor not only complexes with trace amounts of activated factor VII, present in the circulation of normal individuals, but also activates factor VII to factor VIIa. The complex formed by factor VIIa and tissue factor then activates factors IX and X, leading to the formation of small amounts of thrombin. However, this pathway is rapidly downregulated by tissue factor pathway inhibitor. Nevertheless, potent positive feedback by thrombin itself results in the activation of factor XI to factor XIa, which can activate factor IX, hence perpetuating the production of thrombin and, subsequently, of a fibrin clot. Thrombin also promotes ongoing thrombosis by activation of factors VIII, V, and XIII. Factor VIIIa functions as a cofactor during the activation of factor X to Xa, catalyzed by factor IXa. Factor Va functions as a cofactor during the activation of prothrombin to thrombin, catalyzed by factor Xa. The end result of these sequential reactions is the conversion of fibrinogen to fibrin monomers. Factor XIIIa cross-links fibrin to promote the development of a stabilized platelet plug (see Fig. 3). The natural anticoagulants function to confine thrombus formation to the site of vascular injury and to limit thrombus size. Whereas it promotes ongoing coagulation by a number of positive feedbacks, thrombin also provides an important negative feedback to limit thrombus formation by binding to thrombomodulin on endothelial cells. The thrombin-thrombomodulin complex then converts protein C to APC. Antithrombin and protein C are the major natural anticoagulants, and protein S serves as a vital cofactor for APC-mediated inactivation of factors Va and VIIIa (see Fig. 3). Vascular endothelial disruption triggers not only coagulation reactions but also the fibrinolytic pathways (Fig. 4). Physiologic fibrinolysis is initiated by endothelial cell-derived tissue plasminogen activator (tPA)-mediated conversion of plasminogen to plasmin. Plasmin can degrade fibrinogen and fibrin, thus limiting the size of a thrombus and helping to clear a thrombus once the vascular injury has been repaired. The fibrinolytic pathways are regulated by the inhibitory proteins α2-antiplasmin and plasminogen activator inhibitor-1. Therefore, the human hemostatic system can be defined as consisting of multiple independent yet integrally related cellular and protein components; these function to maintain blood fluidity under normal conditions and to promote localized, temporary thrombus formation at sites of vascular injury (Fig. 5). The six major components of this hemostatic system are vascular endothelium, platelets, plasma coagulation proteins or “factors,” natural anticoagulant proteins, fibrinolytic proteins, and antifibrinolytic proteins. In the presence of an intact endothelium, there is no clot formation taking place inside the blood vessels, even though a low, basal, physiologic level of coagulation factor activation is occurring continuously. This highly regulated hemostatic system maintains a delicate balance between a prohemorrhagic and prothrombotic state, which is maintained by the concomitant actions of platelets, coagulation factors, and fibrinolytic inhibitors (on one side of the hemostatic scale), and of natural anticoagulants and fibrinolytic proteins (on the other side of the scale), as shown in Figure 6. Marked thrombocytosis, accentuated platelet aggregation, increased activity levels of coagulation factors, and excess plasma levels of fibrinolytic inhibitors may lead to pathologic thrombosis. Similarly, quantitative or qualitative deficiencies of a natural anticoagulant coagulation factor resistance to inactivation by a natural anticoagulant (in the specific case of factor V Leiden), and a deficiency of a fibrinolytic protein, may all be associated with a state of hypercoagulability. Thus, it is not surprising that a multitude of potential hypercoagulable states have been described (Box 1). \|Box 1: Established or Potential Hypercoagulable States \|Activated protein C resistance\| \|Factor V Leiden\| \|Factor V deficiency, excess\| \|Factor VII excess\| \|Factor VIII excess\| \|Factor XI excess\| \|Heparin cofactor II deficiency\| \|Protein C deficiency\| \|Protein S deficiency\| PAI-1, plasminogen activator inhibitor-1; TFPI, tissue factor pathway inhibitor; tPA, tissue plasminogen activator. © 2003 The Cleveland Clinic Foundation. The factor V Leiden mutation renders factors V and Va partially but not completely resistant to inactivation by APC.2,6 APC inactivates factor Va in an orderly and sequential series of cleavages, first at Arg506 and then at Arg306 and Arg679.6 This partial resistance is explained by the fact that cleavage of factor Va by APC at Arg306 continues to occur, although at a slower rate. In fact, factor V Arg506Gln (factor V Leiden) is inactivated 10 times slower than normal factor Va.24 This provides a pathophysiologic explanation for why factor V Leiden, although common, is a relatively weak risk factor for VTEs. Because factor Va functions as a cofactor in the conversion of prothrombin to thrombin, the mutation results in greater amounts of factor Va available for coagulation reactions, shifting the hemostatic balance toward more thrombin generation.2,9 By unknown mechanisms, the prothrombin G20210A mutation results in elevated concentrations of plasma prothrombin, which is the immediate precursor of thrombin. The tendency to hypercoagulability is believed to be derived from the greater availability of prothrombin for conversion to thrombin.2 Antithrombin is the primary inhibitor of thrombin and the other serine proteases, factors XIIa, XIa, Xa, and IXa. Deficiency of antithrombin leads to enhanced thrombin formation. Complete deficiency of antithrombin likely leads to unfettered thrombin formation and hypercoagulability to degrees that are fatal in utero. Protein C, in its activated form (APC), controls the formation of thrombin in the presence of its cofactor, free protein S. Thus, in the setting of protein C or protein S deficiency, thrombin formation is also enhanced, leading to hypercoagulability.9 Type I deficiencies of natural anticoagulants are characterized by low antigen and activity (functional) levels of the deficient natural anticoagulant, whereas type II defects are characterized by normal (total) antigen levels but low activity, dysfunctional molecules.6,10,11 Under normal conditions, protein S exists in plasma in two forms, bound to C4b-binding protein (60% of total) and free (40% of total). Because only free protein S has cofactor activity, a type III protein S has been described, consisting of low activity and free antigen levels but with a normal total antigen level.6,11 This type III protein S deficiency may result from excess C4b-binding protein or free protein S inhibitory and clearing antibodies.25 The exact mechanisms whereby APAs cause thrombosis are unknown. Some proposed mechanisms include the following: acquired APC-R: stimulation of platelet adhesion, activation, and aggregation; upregulation of the tissue factor pathway; enhanced expression of cell adhesion molecules; and reduction of the free protein S level by inducing protein S binding to C4b-binding protein.14,16 One mechanism described for APA-associated fetal loss involves the presence of trophoblast-reactive antibodies that disrupt the annexin V shield on trophoblast cell membranes, thus enhancing thromboxane A2 production and leading to placental insufficiency.14 The pathophysiology of thrombosis in hyperhomocysteinemia is also unclear. Proposed mechanisms include direct endothelial injury, increased tissue factor activity, inhibition of protein C activation, increased platelet activation and aggregation, suppression of thrombomodulin expression, and impaired fibrinolysis by inhibition of tPA binding to its endothelial cell receptor.17,18 There are no specific signs or symptoms associated with hypercoagulable states. The finding of livedo reticularis on examination of the skin has been frequently associated with the presence of APA, but a true causality has not been established. The most common clinical manifestation of an underlying hypercoagulable state is lower extremity deep venous thrombosis, with or without pulmonary embolism. Because the clinical signs and symptoms associated with deep venous thrombosis and pulmonary embolism are insensitive and nonspecific, objective diagnostic confirmation by the use of an imaging method, such as contrast venography and duplex ultrasound, is mandatory. Other less common or unusual clinical presentations of venous thrombosis appear to occur more commonly, but not exclusively, in certain hypercoagulable states, as depicted in Table 2. \|VTE Presentation\|\|Hypercoagulable Condition\| \|Cerebral venous thrombosis\|\|Prothrombin G20210A, antiphospholipid antibodies, antithrombin deficiency, essential thrombocythemia, paroxysmal nocturnal hemoglobinuria\| \|Cerebral venous thrombosis in women using oral contrac eptive pills\|\|Prothrombin G20210A\| \|Inferior vena cava, renal venous, mesenteric venous, portal and hepatic venous thromboses\|\|Antiphospholipid antibodies, cancer, antithrombin deficiency, myeloproliferative syndromes, paroxysmal nocturnal hemoglobinuria\| \|Migratory superficial thrombophlebitis (Trousseau's syndrome)\|\|Cancer (particularly adenocarcinoma of the gastrointestinal tract)\| \|Recurrent superficial thrombophlebitis\|\|Factor V Leiden, polycythemia vera, deficiencies of natural anticoagulants\| \|Warfarin skin necrosis\|\|Protein C and protein S deficiencies\| \|Neonatal purpura fulminans\|\|Homozygous protein C and protein S deficiencies\| \|Unexplained fetal loss (three or more first-trimester miscarriages or one second- or third-trimester unexplained death of a morphologically normal fetus)\|\|Antiphospholipid antibodies\| VTE, venous thromboembolic event. © 2003 The Cleveland Clinic Foundation. The risk of a first VTE varies, depending on the hypercoagulable state being considered (Table 3).2,14,19,20 This risk is usually expressed as relative risk. Although the relative risk is useful in comparing the VTE rates between a patient population with a given disorder and normal controls, the absolute risk is the best measure to assess the importance of a given risk factor for an individual patient.2 This is particularly important, considering the fact that the baseline risk of thrombosis for women and men increases exponentially with age.20 \|Hypercoagulable State\|\|Relative Risk of Lifetime Single VTE\| \|Factor V Leiden\|\|2-10\| \|Factor V Leiden and prothrombin G20210A (“double heterozygous”)\|\|20.0\| \|Protein C deficiency\|\|6.5-31\| \|Protein S deficiency\|\|2-36\| * Relative risks are highly variable, depending on whether they were derived from population- or family-based studies. Differences in risk can be explained in part by greater difficulty in obtaining reliable population-based estimates because of the overall low prevalence of these disorders. It is also possible that event rates were overestimated in early familial studies. VTE, venous thromboembolic event. Data from Deitcher SR, Caiola E, Jaffer A: Demystifying two common genetic predispositions to venous thrombosis. Cleve Clin J Med 2000;67:825-826, 829, 833-836; Levine JS, Branch DW, Rauch J: The antiphospholipid syndrome. N Engl J Med 2002;346:752-763; De Stefano V, Casorelli I, Rossi E, et al: Interaction between hyperhomocysteinemia and inherited thrombophilic factors in venous thromboembolism. Semin Thromb Hemost 2000;26:305-311; Rosendaal FR: Risk factors for venous thrombosis: prevalence, risk, and interaction. Semin Hematol 1997;34:171-187. Laboratory testing for hypercoagulable states can uncover an inherited abnormality in more than 60% of patients presenting with a first VTE (see Fig. 1). However, testing is costly, it rarely influences acute VTE management, and its results are frequently misinterpreted, which may lead to a non–evidence-based use of antithrombotic drugs and inappropriate justification of lifelong therapy. More important, a focus exclusively on hypercoagulable state testing may undermine the performance of age- and gender-specific cancer screening in patients with idiopathic VTEs. In the absence of validated guidelines, testing for hypercoagulable states should be performed only in select patients, and only if the results will significantly affect management. Select testing should be considered mainly in the following circumstances: Testing should be strongly considered for patients who present with two or more of these criteria. It may also be considered for select asymptomatic individuals, particularly female relatives of patients with known inherited hypercoagulability, provided that the results will affect their decision to begin oral contraceptive pill (OCP) use or hormone replacement therapy (HRT). Testing should be performed if the results will affect management by guiding the following: The issue of OCP use and HRT in the setting of an inherited hypercoagulable state remains a matter of intense debate. Both groups of medications are associated with a two- to sixfold increased relative risk of a VTE in women without hypercoagulable states.26 Based on data from the Leiden Thrombophilia Study,27 the risk of a VTE is increased sevenfold in heterozygous carriers of factor V Leiden. The relative risk of VTEs is increased exponentially in women taking an OCP who are carriers of factor V Leiden (35-fold) and prothrombin G 20210A (16-fold).28,29 The VTE risk appears even higher in women homozygous for factor V Leiden, and an absolute risk of VTEs of 4% per year has been reported in women who are taking an OCP and carry a natural anticoagulant deficiency.30,31 OCP users who carry the prothrombin G20210A mutation also have a 150-fold increased risk of cerebral venous thrombosis.32 It is not currently recommended that all asymptomatic women be screened before initiation of such therapies, mainly because it is not cost effective.33 It is clear, however, that the combination of factor V Leiden with OCP use leads to an exponential increase in the relative risk of VTEs, even though the absolute risk still remains fairly low (Table 4). Thus, in asymptomatic women with a family history of VTEs, select testing may be considered if the results of testing will affect a woman's decision to proceed with OCP use. It is generally recommended that OCP use be avoided in the setting of objectively and properly confirmed antithrombin, protein C, and protein S deficiency states because of the high annual rates of VTEs reported in this group of women.31,33 However, current evidence does not allow that such a firm recommendation be made regarding OCP use in a woman with factor V Leiden or even prothrombin G20210A mutation heterozygosity. This is because OCPs remain the most effective form of prescribed contraception, and the increased risk of VTEs associated with the presence of factor V Leiden or prothrombin G20210A heterozygosity needs to be balanced against the possibility of unwanted pregnancy, with its attendant 9- to 15-fold increased risk of VTEs in this same population.34 \|Parameter\|\|Relative Risk\|\|Absolute Risk\| \|Noncarrier women on OCP\|\|4\|\|3.2/10,000\| \|Factor V Leiden heterozygosity\|\|7\|\|5.7/10,000\| \|Factor V Leiden heterozygous woman on OCP\|\|35\|\|28.5/10,000\| Estimated number of cases of VTE/10,000 persons/year.28 VTE, venous thromboembolic event. © 2003 The Cleveland Clinic Foundation. The relative risk of VTEs is also further increased (by 15-fold) in women on HRT who are heterozygous for factor V Leiden. The epidemiologic importance of this increased risk lies in the fact that women on HRT belong to an older group than those on OCP, with a baseline risk of VTEs between 1 in 100 to 1000 persons (instead of 1/10,000 persons)/year.26 Thus, it is likely that the impact of a 15-fold increased risk of VTEs is more significant in women within this age group, and it is possible that the benefits of HRT may not outweigh the risk of VTEs. Testing for hypercoagulable states is best performed in stages. Highest yielding assays (screening tests) should be performed first and, if positive, should be followed by appropriate confirmatory tests (Table 5). If screening test results are negative and sufficient suspicion exists, less common disorders can be tested for. Specific testing for factor V Leiden is not necessary if the test result for APC-R is negative. Prothrombin G20210A mutation detection by the polymerase chain reaction assay is preferred over prothrombin activity level quantification because the latter does not sufficiently differentiate carriers from noncarriers of the mutation.2 Activity assays for antithrombin, protein C, and protein S are initially preferred, because they will be abnormal in both type I (quantitative) and type II (qualitative) deficiencies.35 If activity assay results are normal, there is no benefit to pursuing antigenic testing. Factor VIII activity testing should also be considered, especially in patients suspected of having protein S deficiency. Both factor VIII activity higher than 250% and APC-R can interfere with some available protein S activity assays.36 \|Screening Test\|\|Confirmatory Test\| \|Activated protein C resistance\|\|Factor V Leiden PCR\| \|Prothrombin G20210A mutation testing by PCR\|\|Antigenic assays for antithrombin, protein C, and/or protein S levels\| \|Antithrombin, protein C, and protein S activity (functional) levels\|\|Confirmatory tests for lupus anticoagulants\| \|Factor VIII activity level\| \|Screening tests for lupus anticoagulants (sensitive aPTT, aPTT mixing studies, dilute Russell viper venom time)\| \|Anticardiolipin antibody testing by ELISA\| \|Fasting total plasma homocysteine level\| Include at least one of the following: platelet neutralization procedure, hexagonal phase phospholipids, Textarin/Ecarin ratio, platelet vesicles, DVV Confirm assay.37 aPTT, activated partial thromboplastin time; ELISA, enzyme-linked immunosorbent assay; PCR, polymerase chain reaction; VTE, venous thromboembolic event. © 2003 The Cleveland Clinic Foundation. The International Society on Thrombosis and Haemostasis Guidelines for APA testing have suggested that two distinct lupus anticoagulant assays be carried out, in addition to anticardiolipin antibody testing by ELISA.37 If either the clot end point lupus anticoagulant assay result (either the activated partial thromboplastin time [aPTT] or the dilute Russell viper venom time [dRVVT]) is abnormal, the assay should be repeated with a phospholipid or platelet neutralization step to increase its specificity. I do not recommend genotyping for the tlMTHFR polymorphism because hyperhomocysteinemia from any cause is the risk factor for thrombosis, not the presence of the tlMTHFR polymorphism.19 Total plasma homocysteine should be determined in a fasting state.17,19 Ideally, testing should be performed in the outpatient setting at least 4 to 6 weeks after any acute thrombotic event. This is because acute illness states, including VTEs, can cause elevations of a number of acute phase reactants, including factor VIII, C4b-binding protein, fibrinogen, and IgM anticardiolipin antibodies, all of which may interfere with testing and often lead to false-positive diagnoses. Unfractionated and low-molecular-weight heparins can interfere with antithrombin activity and with lupus anticoagulant assays, and warfarin predictably lowers proteins C and S activity levels.35 Low activity levels of natural anticoagulants also occur as a result of liver disease, because protein C, protein S, and antithrombin are all synthesized in the liver.10,11,35 Antithrombin activity level may be reduced in nephrotic syndrome and active colitis, and protein S activity may also be reduced in the setting of HIV infection. There are no specific therapies to reverse most hypercoagulable states. Recombinant factor concentrates of antithrombin and APC exist and may be useful in select situations beyond the scope of this review. Gene transfer to correct a particular genetic defect is theoretically feasible but likely cost prohibitive at this time. Attempts to eliminate APA by plasmapheresis or immunosuppressive therapy have not been very successful. Hyperhomocysteinemia is treatable, and plasma homocysteine levels can be lowered in many individuals by folic acid or other B-complex vitamin supplementation.3 It is not known whether normalization of plasma homocysteine levels reverses the hypercoagulability completely. Initiation of oral anticoagulation for primary VTE prophylaxis in asymptomatic carriers of any hypercoagulable state has not been advised, mainly because the annual absolute risk of idiopathic VTE is low or not high enough to be favorably balanced against the annual risk of oral anticoagulation-related major and fatal hemorrhage.38 However, because most VTEs (50%-70%) in patients with a predisposition to hypercoagulability occur following a situational risk factor, such as major or orthopedic surgery, aggressive VTE prophylaxis should be prescribed to asymptomatic carriers of hypercoagulable states during high-risk situations.2,38 The presence of a hypercoagulable state should not affect acute VTE treatment (i.e., initial anticoagulation with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin followed by oral anticoagulation with warfarin) in most patients, except for those with a lupus anticoagulant. Because these antibodies can prolong the activated partial thromboplastin time, monitoring of unfractionated heparin therapy in this scenario should be performed by heparin assay (protamine titration or anti–factor Xa activity assay). If such assays are not immediately available, the use of weight-based, subcutaneous, low-molecular-weight heparin should be considered instead of unfractionated heparin, because the former compounds do not require monitoring. Moreover, 26.8% to 53% of all patients with a lupus anticoagulant have an abnormal, prolonged, baseline prothrombin time, and in many of these patients the international normalized ratio is not an adequate tool for monitoring warfarin therapy. In this situation, monitoring by chromogenic factor X activity assay is recommended.39 Many physicians justify hypercoagulable state testing because, if an abnormality is found, prescription of long-term oral anticoagulation is believed to be more appropriate than the recommended 3- to 6-month course. However, it must be emphasized that there currently are no data from prospective, randomized, controlled trials specifically designed to address the optimal duration of anticoagulation therapy in patients with specific hypercoagulable states. Thus, any decisions regarding the ideal duration of therapy must take into account the estimates of VTE recurrence for a given disorder, the nature of the index VTE, and the risk of bleeding associated with prolonged oral anticoagulation. The Sixth American College of Chest Physicians (ACCP) Guidelines to Antithrombotic Therapy do not recommend continuation of anticoagulation therapy beyond 3 to 6 months after a situational VTE in patients with heterozygous factor V Leiden or the prothrombin G20210A mutation, and suggest that such therapy should last “1 year to lifetime” only in individuals with active cancer, persistently elevated anticardiolipin antibodies, and antithrombin deficiency.40 Based on available data, it is also reasonable to consider long-term anticoagulation therapy for patients with conditions known to be associated with increased rates of VTE recurrence. These include patients with documented, persistent lupus anticoagulants, homozygous factor V Leiden, and perhaps patients with a deficiency of protein C or protein S, or with double heterozygosity for factor V Leiden and the prothrombin G20210A mutation. However, the simple fact that a condition increases the risk of VTE recurrence should not be viewed as a mandatory indication for long-term or lifelong therapy. This is because most recurrent VTEs tend to occur within the first 1 to 3 years following the index VTE, with the annual rate of recurrence declining thereafter. Conversely, the risk of oral anticoagulation-related major bleeding increases with aging. Therefore, the balance between the benefits of long-term oral anticoagulation in preventing recurrent VTEs and the bleeding risk associated with this therapy, particularly of major and fatal hemorrhage, are likely to evolve over time, with risks outweighing benefits as the patients age. The outcomes of patients with hypercoagulable states are dependent on the rates of VTE recurrence associated with the different disorders. There currently are no data to suggest reduced survival in patients who carry an inherited predisposition to hypercoagulability.	2	11	2	0	2	0.944421	4	9,023
Quetiapine, marketed as Seroquel among other names, is an atypical antipsychotic used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. It is also sometimes used as a sleep aid due to its sedating effect, but this use is. May 07, 2018 · Bipolar disorder, which in the ICD-10 is classified as bipolar affective disorder, or manic-depressive illness (MDI), is a common, severe, and. Major depression with psychotic features, Schizoaffective Vs Psychotic Depression 2018 Find out about brief psychotic disorder symptoms (delusions, Print Serious Vs. Non-Serious Mental Illness. The law defines the following conditions as a serious mental illness: Schizophrenia ; Paranoid and other psychotic disorders The bullish case for Acadia is that the FDA will stand by its approval decision for Nuplazid in treating Parkinson’s disease. What Is Bipolar Disorder? According to http://www.nami.org/Learn-More/Mental-Health-Conditions/Schizoaffective-Disorder, the following symptoms are present in Bipolar Disorder: Bipolar mania, hypomani. Schizoaffective Disorder shares a variety of. is a combination of schizophrenia symptoms with either depression or mania. Here are the major differences. Learn about schizoaffective disorder signs and symptoms and the causes & effects of having schizoaffective disorder. Delta Medical Center. Schizoaffective disorder vs depression with psychotic features – As a symptom of Schizoaffective disorder and depression can it feel like someone is in your body? Yes, schizoaffective. HCPs – Explore Resources on Approaches to Diagnosing Major Depressive Disorder. Psychotic depression is defined as a major depressive episode with features of psychosis. Psychotic depression is sometimes confused with or misdiagnosed as schizoaffective disorder, as the two con. Major depressive disorder (MDD), also known simply as depression, is a mental disorder characterized by at least two weeks of low mood that is. Schizoaffective disorder describes a condition that includes aspects of both schizophrenia and a mood disorder (either major depressive disorder or bipolar disorder). Scientists are not entirely certain whether schizoaffective disorder is a condition related mainly to schizophrenia or a mood. But schizoaffective disorder also involves symptoms of mood disorders like major depression. The schizoaffective disorder vs. depression and any psychotic. In fact, major differences already exist in the way schizoaffective disorder is defined in. and affective symptoms equivalent to those in major depression and/ or mania. This overlap means that patients require treatments for both psychotic and. Schizoaffective disorder is, like schizophrenia, a psychotic disorder. In addition to psychotic features, schizoaffective disorder has significant mood symptoms. This rare mental illness is related to both schizophrenia and bipolar disorder or major depressive disorder and affects approximately one. Early detection and the right treatment are most effective for cure of psychosis," said Dr Anita Shrivastava who provides cou. Seroquel XL 50 mg prolonged-release tablets. Seroquel XL 150 mg prolonged-release tablets. Seroquel XL 200 mg prolonged-release tablets. Seroquel XL 300 mg prolonged-release tablets 2.1. DepressionCBT for depression has been studied in over 75 clinical trials since 1977 (Gloaguen, Cottraux, Cucherat, & Blackburn, 1998).Parker et al. (2003) reviewed meta-analyses and primary studies in this area and concluded that CBT is not as effective as proponents of the therapy suggest. Schizophrenia Symptoms and Diagnosis. There is currently no physical or lab test that can absolutely diagnose schizophrenia – a psychiatrist usually comes to the diagnosis based on clinical symptoms. Read about ICU psychosis, a disorder in which ICU patients experience serious psychiatric symptoms such as anxiety, hearing voices, hallucinations, nightmares, paranoia, disorientation, agitation, delusions and more. REVIEW. Religion, spirituality and psychotic disorders. Harold G. Koenig. Professor of Psychiatry and Behavioral Sciences. Associate Professor of Medicine. Borderline Personality Disorder And Schizoaffective Disorder Show Symptoms Similar To Bipolar Disorder Feb 1, 2014. This paper reviews the definition of schizoaffective disorder which is not. fourth, patients with a third psychosis unrelated to schizophrenia mood. an episode of mania, major depression or combination of both while also. Psychosis is a mental disorder where a person loses the capacity to tell what’s real from what isn’t. They may believe or sense things that aren’t rea. Seroquel official prescribing information for healthcare professionals. Includes: indications, dosage, adverse reactions, pharmacology and more. Hi All, I'm trying to diagnose someone and just want some clarification on the major differences between schizoaffective disorder and MDD with psychosis. disorder" and "major depression or bipolar disorder with mood- congruent or mood-incongruent psychotic features." "Schizoaffective disorder" survives only as a. Major Depression; Bipolar Disorders. Schizoaffective Disorder vs. Also unlike those with psychotic depression or bipolar disorder, the psychotic experiences of. Schizophrenia and schizoaffective disorder are. characterized by episodes of mania and major depression;. In schizoaffective disorder, the psychotic. Note for Health Care Providers: People with bipolar disorder are more likely to seek help when they are depressed than when experiencing mania or hypomania. Therefore, a careful medical history is needed to ensure that bipolar disorder is not mistakenly diagnosed as major depression. How to differentiate between psychotic depression and schizoaffective. Difference Between Schizoaffective Disorder And Major Depression With Psychotic Features. Major depression vs Schizoaffective disorder USMLE Step 2. Major depressive disorder with psychotic features because his delusion only appeared after he developed. This section will focus mainly on Major Depressive Disorder (MDD), commonly referred to as "Major Depression" or simply, "Depression." Other mood-related conditions will be explored, including Bipolar Disorders, Dysthymic Disorder, Anxiety Disorders, Seasonal Affective Disorder, Mood Disorder Due. May 1, 2013. Schizoaffective Disorder; Schizophreniform Disorder; Delusional. Sometimes the definition of psychosis is extended to include “disordered” or. In rare cases of severe major depression, psychotic symptoms may also occur. Schizoaffective Disorder vs. Major Depression or. but the gist seemed to be that the difference is that in schizoaffective disorder, the psychotic features. Oct 11, 2011. People with schizoaffective disorder have more chronic psychotic symptoms than do people with bipolar disorder (or psychotic depression). . an individual can become psychotic during a major depressive or. F25.1 Schizoaffective disorder, depressive. of episodes are schizoaffective, depressive. In a snapshot, the sometimes-confused conditions of Bipolar Disorder and Borderline Personality Disorder can look similar. But it’s really the movie of the symptom presentation over time that can help make the diagnosis distinct. Learn symptoms, prognosis, and treatment of schizoaffective disorder, a mental illness featuring schizophrenia and a mood disorder — depression or bipolar disorder. The benefit was maintained at 4-week follow-up (mean change in score, -25.1 in the VR group vs -1.5 in the. such as psycho. John Read on “Childhood Adversity and Psychosis: From Heresy to Certainty” Yet, the trauma and dissociation field often goes to great lengths in an apparent effort to draw a decisive line in the sand between “real” trauma “disorders” and “schizophrenia.” Learn about common symptoms and warning signs of schizoaffective disorder, along with symptoms of either manic episodes or major depressive episodes. Depression. Depression – Introduction, Depression – What Is Depression – Who Has Depression?, What Does It Feel Like To Be Depressed?, It Can Happen To Anyone, Depression – How Can You Spot Depression – Are You Depressed?, Minor Depression Vs. Informing DSM-5: biological boundaries between bipolar I disorder, schizoaffective disorder, and schizophrenia. Victoria E Cosgrove and; Trisha SuppesEmail. Psychotic depression, also known as depressive psychosis, is a major depressive episode that is. It can be difficult to distinguish from schizoaffective. schizoaffective disorder, bipolar disorder, major depression with psychosis and/or delusional disorder.” The move to exclude. Stress Anxiety And Depression Scale Does stress cause depression? Search for best relief & treatments. Are you stressed, depressed or affected by anxiety? Lovibond and Lovibond developed the Depression Anxiety Stress Scale 42.Answer the following questions in relation to your past week and Psychologist World will compare your answers with the scale to find out how stressed you are: Huge In this particular section, I will describe what Schizoaffective Disorder is. According to psychcentral.com, Schizoaffective Disorder is a combination of a psychotic disorder. including a major dep. Dec 18, 2009. Schizoaffective disorder vs Dysthymia Schizoaffective disorder refers to. of perception in the schizoaffective disorder is medically termed as psychosis. most of the other major depression disorders that patients complain of. (Note: The behavior of individuals between mood and psychotic episodes is normal.) The 5 Major Dimensions of Mental Illness More Depression Articles ... - Depression Connection Fort Worth Texas: Collins Executive Center, and the second workshop will be held on Tuesday, Jan. 25 at Texas Christian University's Brown-Lupton University Union (2901 Stadium Drive, Fort Worth. planted the past se. Discover Company Info on Depression Connection Team... - Depression And Pelvic Pain: Here you can read posts from all over the web from people who wrote about Depression and Pelvic Pain, and check the relations between Depression and Pelvic Pain Mast cells in chronic inflammation, pelvic pain and depression in women. Alessandra Grazi... - Does Hypothyroidism Cause Depression Or Anxiety: WebMD explains how chronic health problems can cause depression and anxiety and how to manage and treat both. Hypothyroidism can cause muscle and joint problems, such as joint pain and stiffness. My doctor(endocrinologist) diagnose me with hypogonadi... - How Depression Meds Work: [embedyt]//www.youtube.com/embed/[/embedyt] WebMD explains the different types of depression medicines and how you can most effectively treat your depression with medications. Some antidepressants work. Read about antidepressants and find out how ant... - Manic Depression Memory Loss: Choline supplement benefit side effects bitartrate 350 mg and 500 mg dosage Eventually, my memory issues were so bad that I was forgetting whole conversations. For instance, the. Gradually, the memory loss was getting less noticeable. However. Topic:... - Humanistic Psychology For Depression: Nov 6, 2007. 3Department of Psychological Medicine, Imperial College London, London, UK. Contact address: Anna. compare the effects of music therapy for people with depression against other psychological or pharmacological therapies. such as behaviou...	2	10	0	0	1	0.956779	1	2,363
Medical Policies - Medicine Peripheral Subcutaneous Field Stimulation CAREFULLY CHECK STATE REGULATIONS AND/OR THE MEMBER CONTRACT Peripheral subcutaneous field stimulation is considered experimental, investigational and/or unproven. Peripheral subcutaneous field stimulation (PSFS; also called peripheral nerve field stimulation or target field stimulation) is a form of neuromodulation intended to treat chronic neuropathic pain. Applications of PSFS being evaluated are craniofacial stimulation for headache/migraine, craniofacial pain, or occipital neuralgia. PSFS is also being investigated for low back pain, neck and shoulder pain, inguinal and pelvic pain, thoracic pain, abdominal pain, fibromyalgia, and post herpetic neuralgia. Chronic, noncancer pain is responsible for a high burden of illness. Common types of chronic pain are lumbar and cervical back pain, chronic headaches, and abdominal pain. All of these conditions can be challenging to treat. Pharmacologic agents are typically the first-line treatment for chronic pain, and several classes of medications are available. They include analgesics (opioid and nonopioid), antidepressants, anticonvulsants, and muscle relaxants. A variety of nonpharmacologic treatments also exist, including physical therapy, exercise, cognitive-behavioral interventions, acupuncture, chiropractic, and therapeutic massage. Neuromodulation, a form of nonpharmacologic therapy, is usually targeted toward patients with chronic pain refractory to other modalities. Some forms of neuromodulation, such as transcutaneous electrical nerve stimulation (TENS) and spinal cord stimulation (SCS), are established methods of chronic pain treatment. Peripheral nerve stimulation, which involves placement of an electrical stimulator on a peripheral nerve, is also used for neuropathic pain originating from peripheral nerves. Peripheral Subcutaneous Field Stimulation PSFS is a modification of peripheral nerve stimulation. In PSFS, leads are placed subcutaneously within the area of maximal pain. The objective of PSFS is to stimulate the region of affected nerves, cutaneous afferents, or the dermatomal distribution of the nerves, which then converge back on the spinal cord. Combination SCS plus PSFS is also being evaluated. Similar to SCS or peripheral nerve stimulation, permanent implantation is preceded by a trial of percutaneous stimulation with at least 50% pain reduction. Currently, there is no consensus on the indications for PSFS. Criteria for a trial of PSFS may include a clearly defined, discrete focal area of pain with a neuropathic or combined somatic/neuropathic pain component with characteristics of burning and increased sensitivity, and failure to respond to other conservative treatments including medications, psychological therapies, physical therapies, surgery, and pain management programs. The mechanism of action in PSFS is unknown. Theories include an increase in endogenous endorphins and other opiate-like substances; modulation of smaller A delta and C nerve fibers by stimulated large diameter A beta fibers; local stimulation of nerve endings in the skin; local anti-inflammatory and membrane-depolarizing effect; or a central action via antegrade activation of A beta nerve fibers. Complications of PSFS include lead migration or breakage and infection of the lead or neurostimulator. No devices have been approved by the U.S. Food and Drug Administration (FDA) specifically for PSFS. PSFS is an off-label use of SCS devices that have been approved by the FDA for the treatment of chronic pain. This medical policy was originally created in October 2013, and has been updated regularly with searches of the MEDLINE database. The most recent literature review covered the period through February 23, 2017. Case series provide limited evidence for the efficacy of pain treatments due to the variable nature of pain and the subjective nature of pain outcome measures. Randomized controlled trials (RCTs) with adequate blinding are needed to control for the variable natural history of pain and for the expected placebo effect in research on pain treatment; therefore, we focused our literature review on RCTs with blinded outcome measures. Chronic Neuropathic Pain No sham- or active pain treatment-controlled RCTs evaluating peripheral subcutaneous field stimulation (PSFS) were identified. One crossover RCT compared levels of PSFS stimulation. McRoberts et al. (2013) reported on a randomized, crossover trial of different types of PSFS in 44 patients with chronic back pain. In the first phase of the trial, patients rotated through 4 levels of trial PSFS: minimal, subthreshold, low frequency, and standard stimulation. (1) Of 30 patients who completed the first phase, 24 reported that pain was significantly reduced by at least 50% in any of the stimulation groups and were considered responders to PSFS. In phase 2, a permanent PSFS system was placed in 23 responders. During the 52 weeks over which these patients were followed, reported mean visual analog scale (VAS) scores, present pain index, and total scores on the Short-Form McGill Pain Questionnaire were significantly improved from baseline at all follow-up visits (p<0.001). Because this trial did not include a control group, the methodologic strength of these results is similar to that of an uncontrolled study. Another comparative study used a 2-part comparative evaluation of combined use of spinal cord stimulation (SCS) and PSFS in patients with low back pain; it was reported by Mironer et al. in 2011. (2) In the first part of the study, 20 patients with failed back surgery syndrome or spinal stenosis underwent a trial with both SCS and PSFS and selected the type of stimulation they found most efficacious (program 1: SCS alone; program 2: PSFS alone; program 3: combined SCS and PSFS). Patients were blinded to the differences among the programs (randomized order of presentation) and were encouraged to try each program for at least 8 hours; 79% percent of patients preferred the simultaneous use of SCS and PSFS. In the second part of the study, 20 patients were implanted with SCS and PSFS electrodes and selected which program they preferred (SCS and PSFS used simultaneously, SCS as anode and PSFS as cathode, SCS as cathode and PSFS as anode). The programs were presented in a random order, and patients were blinded to the differences among the programs offered. Communication between SCS and PSFS was reported to provide wider coverage of axial pain, with an overall success rate (>50% pain relief) of 90%. The most effective program was SCS as cathode and PSFS as anode. In addition to the controlled studies, a number of case series have been published, several of which included 50 or more patients. In 2014, Kloimstein et al. reported on a prospective multicenter study of 118 patients treated with PSFS for chronic low back pain. (3) Before patients were implanted with the permanent PSFS system, trial stimulation was given for at least 7 days. The permanent stimulation system was implanted in 105 patients. Significant improvements occurred at the 1-, 3-, and 6-month follow-ups after implantation in average pain VAS, Oswestry Disability Questionnaire, Beck Depression Inventory, and 12-Item Short-Form Health Survey scores. Significant reductions in use of opioid, nonsteroidal anti-inflammatory, and anticonvulsant medications were also reported. Sator-Katzenschlager et al. (2010) reported on a retrospective multicenter study of PSFS. (4) A total of 111 patients with chronic focal noncancer pain were treated, including 29 patients with low back pain, 37 with failed back surgery syndrome, 15 with cervical neck pain, and 12 patients with postherpetic neuralgia. The median duration of chronic pain was 13 years, and the median number of previous surgeries was 2.7. For permanent implantation of the leads, patients had to have achieved at least 50% reduction in pain on a numeric rating scale during the trial period. After permanent implantation, pain intensity decreased in 102 (92%) patients. Mean pain intensity decreased from 8.2 at baseline to 4.0 at follow-up, with a concomitant reduction in consumption for analgesics and antidepressants. Lead dislocation or fracture occurred in 20 (18%) patients. In 2011, Verrills et al. reported on a series of 100 patients treated with PSFS for chronic neuropathic pain. Indications included chronic pain occurring among varying regions: occipital/craniofacial (n=40), lumbosacral (n=44), thoracic (n=8), groin/pelvis (n=5), or abdominal (n=3). (5) Selection criteria included a clearly defined, discrete focal area of pain with a neuropathic component or combined somatic/neuropathic pain component with characteristics of burning and increased sensitivity, and failure to respond to other conservative treatments, including medications, psychological therapies, physical therapies, surgery, and pain management programs. Outcomes, assessed at a mean of 8.1 months after implantation (range, 1-23 months), included a combination of numeric pain scores, self-report questionnaires, and patient medical histories. For the entire cohort, pain decreased from 7.4 at baseline to 4.2 at follow-up. Pain scores improved by 75% or more in 34% of patients and by 50% or more in 69% of patients. Analgesia use decreased in 40% of patients after PSFS. Adverse events were reported in 14% of patients and included unpleasant sensations, lead erosions, and lead or battery migration. In 2014, Verrills et al. reported on PSFS for chronic headache conditions. (6) After a trial stimulation period, 60 patients underwent permanent implantation of the PSFS system and were followed for an average of 12.9 months (range, 3-42 months). Ten patients required revision of the implant system. Significant reductions in pain from baseline were reported (p≤0.001). Additionally, use of analgesics or prophylactic medications was reduced in 83% of patients, and reductions in degree of disability and depression were noted. Practice Guidelines and Position Statements In 2013 the National Institute for Health and Care Excellence issued guidance on PSFS for chronic low back pain. (7) The guidance stated “Current evidence on the efficacy of peripheral nerve-field stimulation (PNFS) for chronic low back pain is limited in both quantity and quality, and duration of follow-up is limited. Evidence on safety is also limited and there is a risk of complications from any implanted device. Therefore, this procedure should only be used with special arrangements for clinical governance, consent and audit or research.” Ongoing and Unpublished Clinical Trials Some currently unpublished trials that might influence this review are listed in Table 1. Table 1. Summary of Key Trials A randomised, patient-assessor blinded, sham-controlled trial of external non-invasive peripheral nerve stimulation for chronic neuropathic pain following peripheral nerve injury (EN-PENS trial) Multimodal Treatment for Hemiplegic Shoulder Pain Table Key: NCT: national clinical trial: ISRCTN: International Standard RCT Number. Summary of Evidence For individuals who have chronic neuropathic pain who receive peripheral subcutaneous field stimulation (PSFS), the evidence includes 1 randomized controlled trial (RCT), 1 nonrandomized comparative study, and case series. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. The single RCT, which used a crossover design, did not compare PSFS to alternatives. Rather, it compared different methods of PSFS. Among trial participants, 24 (80%) of 30 patients had at least a 50% reduction in pain with any type of PSFS. However, because the RCT did not include a sham group or comparator with a different active intervention, this trial offers little evidence for efficacy beyond that of a prospective, uncontrolled study. Case series are insufficient to evaluate patient outcomes due to the variable nature of pain and the subjective nature of pain outcome measures. Prospective controlled trials comparing PSFS with placebo or alternative treatment modalities are needed to determine the efficacy of PSFS for chronic pain. The evidence is insufficient to determine the effects of the technology on health outcomes Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern. Disclaimer for coding information on Medical Policies Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations. Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. The following codes may be applicable to this Medical policy and may not be all inclusive. 64999, [Deleted 1/2017: 0282T, 0283T, 0284T, 0285T] ICD-9 Diagnosis Codes Refer to the ICD-9-CM manual ICD-9 Procedure Codes Refer to the ICD-9-CM manual ICD-10 Diagnosis Codes Refer to the ICD-10-CM manual ICD-10 Procedure Codes Refer to the ICD-10-CM manual The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans. The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion. A national coverage position for Medicare may have been developed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>. 1. McRoberts WP, Wolkowitz R, Meyer DJ, et al. Peripheral nerve field stimulation for the management of localized chronic intractable back pain: results from a randomized controlled study. Neuromodulation. Nov 2013; 16(6):565- 575. PMID 23577773 2. Mironer YE, Hutcheson JK, Satterthwaite JR, et al. Prospective, two-part study of the interaction between spinal cord stimulation and peripheral nerve field stimulation in patients with low back pain: development of a new spinal-peripheral neurostimulation method. Neuromodulation. Mar-Apr 2011; 14(2):151-154; discussion 155. PMID 21992203 3. Kloimstein H, Likar R, Kern M, et al. Peripheral nerve field stimulation (PNFS) in chronic low back pain: a prospective multicenter study. Neuromodulation. Feb 2014; 17(2):180-187. PMID 24320718 4. Sator-Katzenschlager S, Fiala K, Kress HG, et al. Subcutaneous target stimulation (STS) in chronic noncancer pain: a nationwide retrospective study. Pain Pract. Jul-Aug 2010; 10(4):279-286. PMID 20230450 5. Verrills P, Vivian D, Mitchell B, et al. Peripheral nerve field stimulation for chronic pain: 100 cases and review of the literature. Pain Med. Sep 2011; 12(9):1395-1405. PMID 21812906 6. Verrills P, Rose R, Mitchell B, et al. Peripheral nerve field stimulation for chronic headache: 60 cases and long- term follow-up. Neuromodulation. Jan 2014; 17(1):54-59. PMID 24165152 7. National Institute for Health and Care Excellence (NICE). Peripheral nerve-field stimulation for chronic low back pain: guidance [IPG451]. 2013; Available at <https://www.nice.org.uk> (Accessed June 6, 2017). 8. Peripheral Subcutaneous Field Stimulation. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (March 2015) Surgery 7.01.139. \|6/15/2018\|\|Reviewed no changes.\| \|7/15/2017\|\|Document updated with literature review. Coverage unchanged.\| \|2/1/2017\|\|Reviewed no changes.\| \|8/1/2015\|\|Document updated with literature review. Coverage unchanged.\| \|7/1/2014\|\|Reviewed no changes.\| \|10/15/2013\|\|New medical document. Peripheral subcutaneous field stimulation is considered experimental, investigational and unproven. (Coverage is unchanged. This topic was previously addressed on MED205.032, Percutaneous and Implanted Nerve Stimulation and Neuromodulation).\| \|Title:\|\|Effective Date:\|\|End Date:\| \|Peripheral Subcutaneous Field Stimulation\|\|06-15-2018\|\|07-31-2019\| \|Peripheral Subcutaneous Field Stimulation\|\|07-15-2017\|\|06-14-2018\| \|Peripheral Subcutaneous Field Stimulation\|\|02-01-2017\|\|07-14-2017\| \|Peripheral Subcutaneous Field Stimulation\|\|08-01-2015\|\|01-31-2017\| \|Peripheral Subcutaneous Field Stimulation\|\|07-01-2014\|\|07-31-2015\| \|Peripheral Subcutaneous Field Stimulation\|\|10-15-2013\|\|06-30-2014\|	2	22	2	0	0	0.900161	2	3,869
What is Autism? Autism spectrum disorder (ASD) is a pervasive developmental disorder characterised by a triad of symptoms; impaired social skills, rigid communication style & characteristic repetitive and ritualised behaviours. Although, it is considered a lifelong condition, one’s impairments can significantly improve with appropriate awareness, support and, where required, intervention. ASD could be considered an umbrella term for autistic conditions as seen in the ICD and DSM diagnostic manuals. ICD-10 outlines eight conditions under F84: childhood autism, atypical autism, Rett’s syndrome, other childhood disintegrative disorder, overactive disorder associated with mental retardation and stereotyped movements, Asperger’s syndrome, other pervasive developmental disorders and pervasive developmental disorder, unspecified. DSM-IV set out five conditions within chapter one’s description of pervasive developmental disorders: autistic disorder, Rett’s disorder, childhood disintegrative disorder, Asperger’s syndrome and pervasive developmental disorder - not otherwise specified, including atypical autism. The most recent version of the DSM diagnostic criteria, DSM-5 combined autism, Asperger’s syndrome and pervasive developmental disorder into a single diagnosis and changed the name of this group from ‘pervasive developmental disorders’ to ‘autism spectrum disorder’ (American Psychiatric Association, 2013). Although the category remains broad, DSM-5 no longer provides differing criteria for each condition, instead a single set of criteria can be used to diagnose ASD. The ICD-10 and DSM-5 criteria: Diagnostic Criteria for Subtypes of Autism Spectrum Disorder International Classification of Diseases-10 (World Health Organisation, 1992) ‘A. Abnormal or impaired development is evident before the age of 3 years in at least one of the following areas: 1. receptive or expressive language as used in social communication. 2. the development of selective social attachment or of reciprocal social interaction. 3. functional or symbolic play. B. A total of at least six symptoms from (1), (2) and (3) must be present, with at least two from (1) and at least one from each of (2) and (3) 1. Qualitative Impairment in social Interaction are manifest in at least two of the following areas: a) failure adequately to use eye-to-eye gaze, facial expression, body posture and gestures to regulate social interaction. b) failure to develop (in a manner appropriate for mental age, and despite ample opportunities) peer relationship that involve a mutual sharing of interests, activities and emotions. c) lack of socio-emotional reciprocity as shown by an impairment or deviant response to other people's emotions; or lack of modulation of behaviour according to social context; or a weak integration of social, emotional and communicative behaviours. d) lack of spontaneous seeking to share enjoyment, interests or achievements with other people (e.g. a lack of showing, bringing or pointing out to other people objects of interest to the individual). 2. Qualitative abnormalities in communication as manifest in at least one of the following areas: a) delay in or total lack of development of spoken language that is not accompanied by an attempt to compensate through the use of gestures or mime as an alternative mode of communication (often preceded by a lack of communicative babbling). b) relative failure to initiate or sustain conversational Interchange (at whatever level of language skill is present) in which there is reciprocal responsiveness to the communications of the other person. c) stereotyped and repetitive use of language or idiosyncratic use of words or phrases. d) lack of varied spontaneous make-believe play or (when young) social imitative play. 3. Restricted, repetitive and stereotypes patterns of behaviour, interests and activities are manifested in at least one of the following: a) an encompassing preoccupation with one or more stereotyped and restricted patterns of interest that are abnormal in content of focus, or one or more interests that are abnormal in their intensity and circumscribed nature though not in their content or focus. b) apparently compulsive adherence to specific non-functional routines and rituals stereotyped and repetitive motor mannerisms that involve either hand or finger flapping or twisting or complex whole body movements. d) preoccupations with part-objects of non-functional elements of play materials (such as their order, the feel of their surface or the noise or vibration they generate). The clinical picture is not attributable to the other varieties of pervasive developmental disorders, specific development disorder of receptive language with secondary socio-emotional problems, reactive attachment disorder or disinhibited attachment disorder, mental retardation with some associated emotional or behavioural disorders, schizophrenia of unusually early onset and Rett’s syndrome’. A. Abnormal or impaired development is evident at or after the age of 3 years. B. There is insufficient demonstrable abnormalities in one or two of the three areas of psychopathology required for the diagnosis of childhood autism (namely reciprocal social interactions, communication or restrictive, stereotyped, repetitive behaviours). C. Atypical autism constitutes a meaningfully separate condition from childhood autism. A. Diagnostic criteria 1 - 3 of B are fulfilled for childhood autism. B. No evidence of general delay or retardation in language or cognitive development. C. Generally associated with normal intelligence. Diagnostic and Statistical Manual of Mental Disorders-5 (American Psychiatric Association, 2013) Autism spectrum disorder (ASD) A. Persistent deficits in social communication and social interaction across multiple contexts, as manifested by the following, currently or by history: · Deficits in socio-emotional reciprocity. · Deficits in non-verbal communicative behaviours used for social interaction. · Deficits in developing, maintaining and understanding relationships. B. Restricted, repetitive patterns of behaviour, interests, or activities, as manifested by at least two of the following, currently or by history: · Stereotyped or repetitive motor mannerisms, use of objects or speech. · Insistence on sameness, inflexible adherence to routines or ritualised patterns of verbal or non-verbal behaviour. · Highly restricted, fixated interests that are abnormal in intensity or focus. · Hyper- or hypo- reactivity to sensory input or unusual interest in sensory aspects of the environment. C. Symptoms must be present in early developmental period. D. Symptoms cause clinically significant impairment in social, occupational or other important areas of current functioning. E. These disturbances are not better explained by intellectual or global developmental delay. Autism and Physical Illness Erroneously early researchers thought that individuals with autism spectrum disorder did not perceive pain and did not communicate their distress; perhaps lacking the ‘social inclination’ to do so (Lainhart 1999). In the mid 2000’s, researchers hypothesised that those with ASD actually have difficulty reporting physical ailments and instead express pain and physical distress as agitation and / or behavioural disturbance (Russell 2005). Although current literature on physical illness in adults with ASD is sparse, a 2016 study by O’Rourke revealed a prevalence rate of 84% for at least one physical health condition among adults with ASD. Atopy was the most commonly diagnosed condition and epilepsy was also notably more common in those with ASD. Although historically considered almost diagnostic for ASD, eating disturbance is now known to occur in approximately 25% of adults with ASD. Restricted dietary repertoire was most commonly reported, followed by reduced appetite, picky eating, eating only a single meal per day, only eating when alone, unhealthy dietary choices, binge-eating and overeating (O’Rourke 2016). Available research in relation to gastrointestinal disease in ASD is varied and controversial. However, available literature would suggest that previously reported higher rates of gastrointestinal disease in individuals with ASDs were greatly exaggerated. Sleep is a relatively well-researched topic in ASD. In fact, it has been referred to as the second most researched area of ASD comorbidity, only surpassed by epilepsy (Mannion 2014). Sleep studies in normal IQ infants with ASD have shown that 90% of sleep difficulties start at an early age including difficulty falling asleep, more frequent night waking and early morning waking (Øyane 2005). Studies of school-age children with ASD have noted difficulties with bedtime resistance, increased sleep latency, poor sleep maintenance, early morning waking, reduced sleep time and quality, increased night waking and irregular sleep patterns in 50% - 80% of subjects (Øyane 2005, Limoges 2005, Canitano 2007, Reynolds 2011). Insomnia rates of 36% have been reported in the child population, most commonly middle insomnia, followed by initial insomnia (Mattila 2010). Adolescent and young adult studies also identify a high prevalence of sleep disorders (80%) including low sleep efficiency, short total sleep time, long sleep latency, more frequent shifts into REM sleep from waking and increased REM sleep disruption (Ghaziuddin 2002a, Øyane 2005). In general, it is acknowledged that motor skill deficits are frequently observed in patients with ASD with a prevalence of 21% - 100% (Gowen 2012). Asperger described awkwardness as typical in autistic psychopathy (Wing 2002a, Barnhill 2007, Raja 2009) while Kanner (1943) noted that several children under his care were somewhat clumsy in gait with gross motor deficits but all were skilled in fine motor movements. Although not included in the DSM-5 diagnostic criteria, clumsiness is commented upon in the ICD-10’s description of Asperger’s syndrome (World Health Organisation 1992). Wing (1981) observed poorly co-ordinated movements, odd posture and abnormal gait while more recently Vannucchi (2014) described clumsiness and illegible handwriting as atypical features of Asperger’s syndrome and Van Wijngaarden-Cremers (2014) noted clumsiness in the case of a 14 year old girl with Asperger’s syndrome and comorbid drug addiction. Autism and Mental Illness Increasingly autism spectrum disorder is associated with a higher prevalence of mental illness than seen in the general population (Stewart 2006, Nylander 2008, Raja 2008). Roy (2015) noted a lifetime prevalence of one or more comorbid psychiatric illness in 70% of adults with High-functioning ASD. Rates of anxiety spectrum disorders are higher in the ASD population compared to the general population, including obsessive compulsive disorder, generalised anxiety disorder, social phobia and agoraphobia (O’Rourke 2016). Rates for mood disorders range from 24% - 53% (Ketelaars 2008, Hofvander 2009, Stunz 2014). Lifetime prevalence of major depressive disorder is 70% - 77%, recurrent depression 50%, current depressive episode 30% and dysthymia 8% (Cath 2008, Lugnegård 2011, Joshi 2013). O’Rourke (2016) identified a prevalence rate of 25% for deliberate self-harm and a rate of 16% for self-injurious behaviour in autistic adults. Schizoid, schizotypal, paranoid, obsessive-compulsive, anxious-avoidant and dependent personality styles are more common in autistic adults than in the general population (Anckarsäter 2006). Schizophrenia has a lifetime prevalence of 0.30% - 0.87% in the general population (Perälä 2007, Van Os 2009). Rates among those with ASD are less clearly defined. As early as the 1940’s, Asperger noted that only one of the 200 cases he studied developed schizophrenia (Wing 1981). Volkmar and Cohen (1991) restarted the debate on comorbidity between ASD and schizophrenia when they identified only a single patient with schizophrenia from 163 cases assessed. Volkmar and Cohen (1991) described schizophrenia as rare in those with ASD, ‘no more commonly observed together than would be expected by chance’. While research on eating disorder in autistic adults is scarce, it is agreed that ASD is over-represented in the anorexia nervosa population (Oldershaw 2011). A single study was identified which showed a prevalence rate of 5% for comorbid ASD and eating disorder. The comparable occurrence rate in the general population is anorexia nervosa 0.9% and bulimia nervosa 1.5% for women and anorexia nervosa 0.3% and bulimia nervosa 0.5% for men (Hudson 2007).s	2	6	0	0	2	0.638647	2	2,628
Cardiovascular disease (CVD) makes a substantial contribution to the burden of disease in New Zealand. Rates of CVD are declining over time however there are disparities in the rate of new CVD diagnoses (CVD incidence) by ethnicity and socioeconomic position. There is extensive literature on the risk factors for CVD and the impact of CVD on social outcomes. This post summarises some of the methods used to identify cardiovascular disease (CVD, Part B) and the ischaemic heart disease (IHD, Part A) subset in administrative health datasets, such as the Integrated Data Infrastructure (IDI). There are several ways of identifying new cases of CVD and each method has different strengths and limitations. Two main health datasets underpin these methods; hospital admissions data and pharmaceutical data. The research question and study design will have an influence on the choice of methods selected. An understanding of the hospital admission datasets and diagnostic codes is crucial. There are two relevant tables; the hospital admissions table (publically funded hospital discharges event information) and the diagnostic codes table (publically funded hospital discharges – diagnosis/ procedure information). Hospital admissions have an event id for each admission (moh_evt_event_id_nbr) that can be used to link to the table with the corresponding diagnostic codes. Diagnosis codes use a system of coding called ICD codes (including diagnosis codes, procedural codes etc.). There are primary and secondary diagnostic codes for each hospital admission, and the primary code is the main reason for hospital admission. The version of ICD codes used in health data has changed over time. The Health Data Dictionary is an excellent source of information about these changes and the meaning of variables in the admissions and diagnosis datasets (See the IDI Wiki, and Statistics NZ website). ICD diagnosis and procedural codes can be obtained online from the World Health Organization (WHO). The Australian Modification (ACM) ICD codes are used in New Zealand and some of the end digits in the ACM ICD codes differ from those on the WHO website. This is important for identifying diagnoses that use the full ICD code length rather than just the higher level groupings. It is also important to define what is meant by new cases of disease (incidence rate). Will the analysis include all cases after a particular date? Or will the analysis eliminate cases where a previous diagnosis with the same disease has been recorded previously, and within what time range? Or is the study question about the number of people who have ever had a diagnosis (prevalence)? Chronic conditions table The Ministry of Health produces a variable in the long-term conditions table for coronary heart disease (CHD; aka IHD), stroke and for myocardial infarction. This is an excellent source of data with minimal manipulation required however an understanding of how these tables are produced is important in interpreting an analysis. These codes are based on specific definitions summarised here, but do not include a broader category of CVD. Data sources used included publically and privately funded hospital discharge information. For the detailed information please see the data dictionary; Statistics New Zealand (2015). IDI Data Dictionary: Chronic condition/significant health event cohort (November 2015 edition). Available from http://www.stats.govt.nz/browse_for_stats/snapshots-of-nz/integrated-data-infrastructure/idi-data/chron-condn-sig-health-evt-data.aspx The definition of CHD is a healthcare user who meets any one of the following conditions: - National Minimum Dataset (NMDS) diagnosis codes: ICD-9-CMA: 410-414, V4581, V4582 ICD-10-AM: I20-I25, Z951, Z955 (MI, angina, stent) - NMDS procedure codes: ICD-9-CMA: 3601, 3602, 3603, 3604, 3605, 3606, 3607, 3610, 3611, 3612, 3613, 3614, 3615, 3616 ICD-10-AM: 3530400, 3530500, 3531000, 3531001, 3531002, 3849700, 3849701, 3849702, 3849703, 3849704, 3849705, 3849706, 3849707, 3850000, 3850001, 3850002, 3850003, 3850004, 3850300, 3850301, 3850302, 3850303, 3850304, 3863700, 9020100, 9020101, 9020102, 9020103 - Two or more dispensings of any of the following drugs, in the most recent 12 month period: 1577 – Glyceryl trinitrate, 2377 – Isosorbide dinitrate, 2836 – Isosorbide mononitrate, 1272 – Nicorandil, 1949 – Perhexiline maleate The ‘first incident date’ field represents the first date the person received a ‘CHD diagnosis’ (listed above) in NMDS. This may not necessarily be the first incident date as a person may have been dispensed a ‘CHD pharmaceutical’ (listed above) before this date. The CHD data is complete between 01/01/2007 and 30/06/2013. It has been provided from 1985 onwards (the record from 1955 is likely an error), but the Ministry of Health recommend that records with an incident date before 2007 should be used with caution. Definition: where the healthcare user had a publicly funded discharge in NMDS between 1 Jan 1988 and 30 Jun 2001 with a primary diagnosis of 430-432, 433.01, 433.11, 433.21, 433.31, 433.81, 433.91, 434.01, 434.11, 434.91, 436 (ICD 9) or a hospital discharge in NMDS between 1 Jul 2001 and 31 Dec 2013 with a primary diagnosis of I60- 164 (ICD-10-AM-II). Acute myocardial infarction Definition: where the healthcare user had a publicly funded discharge in NMDS between 1 Jan 1988 and 30 Jun 2001 with a primary diagnosis of 410 (ICD 9) or a discharge between 1 Jul 2001 and 31 Dec 2013 with a primary diagnosis of I21 (ICD-10-AM-II). Slight modification to define Ischaemic Heart disease IHD has also been identified, using similar methods as above, by Thornley et al (2011). The Thornley definition includes some procedure codes that are not used in the chronic conditions IHD definition, and uses one or more dispensing episode of any of the 5 drugs, rather than two dispensing episodes in the chronic conditions definition. The figure below shoes the overlap between the two datasets in their population (Figure 2). People were classified as IHD if they had either: - Hospital discharge diagnosis of coronary artery disease, or one of the following procedures: coronary angioplasty, stent, percutaneous coronary intervention, or coronary artery bypass graft surgery) - ICD9: 410x to 414x, 36.0x, 36.1x to 36.2x - ICD10: I20x to I25x, 3530400 to 3530501, 3531000 to 3531005, 3849700 to 3850304, 9020100 to 9020103, 3863700, 3845619, 3865308, 3850500 - One or more dispensing episodes for any of the following drugs used to treat CHD between 2007 and 2008: glyceryl trinitrate, isosorbide dinitrate, isosorbide mononitrate, nicorandil, perhexiline The above codes do not provide a definition for the broader category of CVD which includes coronary heart disease and other diagnoses as well such as strokes, heart disease and other cardiovascular disease (Figure 1). Definitions of CVD differ by what datasets they use, and by how broad or specific is the list of conditions that they comprise. 1. Hospital diagnosis codes only, a broad CVD definition The ICD codes used by BODE3 and in the VHIN CVD earthquake research project in the IDI required broad definitions of CVD and are listed here below. This categorisation includes all the diagnoses in Figure 1 such as valvular disease, arrhythmias, strokes and other cerebrovascular events but excluding transient ischaemic attacks (TIAs). These ICD10 codes originate from CVD studies in Christchurch and were derived by cardiologists for the classification of clinical events (Ellis et al., 2011). This categorisation uses primary diagnosis codes and not procedural codes or angina medications. ICD10 codes for this CVD definition; I00-I00XX, I010-I012X, I018-I020X, I029-I029X, I050-I052X, I058-I062X, I068-I072X, I078-I083X, I088-I092X, I098-I099X, I10-I10XX, I110-I110X, I119-I120X, I129-I132X, I139-I139X, I150-I152X, I158-I159X, I200-I201X, I208-I214X, I219-I221X, I228-I236X, I238-I238X, I240-I241X, I248-I250X, I2510-I2513,I252-I256X, I258-I260X, I268-I272X, I278-I281X, I288-I289X, I300-I301X, I308-I313X, I318-I321X, I328-I328X, I330-I330X, I339-I342X, I348-I352X, I358-I362X, I368-I372X, I378-I379X, I38-I38XX, I390-I394X, I398-I398X, I400-I401X, I408-I412X, I418-I418X, I420-I432X, I438-I438X, I440-I447X, I450-I456X, I458-I461X, I469-I472X, I479-I479X, I48-I48XX, I490-I495X, I498-I501X, I509-I521X, I528-I528X, I600-I616X, I618-I621X, I629-I636X, I638-I639X, I64-I64XX, I650-I653X, I658-I664X, I668-I682X, I688-I688X, I690-I694X,I698-I698X, I700-I701X, I7020-I7024,I708-I709X,I7100-I7103,I711-I716X, I718-I724X, I728-I729X,I738-I739X, I790-I790X, I980-I981X Subset of ICD10 codes for myocardial infarction, which includes STEMI and NSTEMI events. 2. Diagnosis codes and angina drug codes In some cases the above code was adjusted to include angina medications. Statistical code is available that uses this CVD definition. This was developed in the VHIN Catalyst project examining the costs of cardiovascular disease; VHIN costs of cardiovascular disease project. 3. Diagnosis codes and procedural codes, more specific CVD definition In another paper on CVD medication dispensing by Kerr et al (2014) CVD was defined using diagnostic and procedural ICD codes. The definition of CVD was generally more specific with a narrower set of ICD codes (excludes strokes and valve disease), however it also included a handful of ICD codes that were not in the broad CVD definition described above. (Kerr et al., 2014) We have broadly outlined some of the challenges in defining cardiovascular disease and coronary heart disease in the IDI, and some examples of how this has been done. The Ministry of Health Chronic Conditions table provides an important starting point, and should be used with a full understanding of the Health Data Dictionary. The final choice of IHD or CVD definition will depend on the research question and study design. For any queries or feedback please contact [email protected]. - ELLIS, K. L., FRAMPTON, C. M., PILBROW, A. P., TROUGHTON, R. W., DOUGHTY, R. N., WHALLEY, G. A., ELLIS, C. J., SKELTON, L., THOMSON, J., YANDLE, T. G., RICHARDS, A. M. & CAMERON, V. A. 2011. Genomic risk variants at 1p13.3, 1q41, and 3q22.3 are associated with subsequent cardiovascular outcomes in healthy controls and in established coronary artery disease. Circ Cardiovasc Genet, 4, 636-46. - KERR, A., EXETER, D., HANHAM, G., GREY, C., ZHAO, J., RIDDELL, T., LEE, M., JACKSON, R. & WELLS, S. 2014. Effect of age, gender, ethnicity, socioeconomic status and region on dispensing of CVD secondary prevention medication in New Zealand: The Atlas of Health Care Variation CVD cohort (VIEW-1). - THORNLEY, S., CHAN, W. C., CRENGLE, S., RIDDELL, T., AMERATUNGA, S., MEHTA, S., GENTLES, D., WELLS, S., MARSHALL, R. & JACKSON, R. 2011. Sociodemographic differences in prevalence of diagnosed coronary heart disease in New Zealand estimated from linked national health records. New Zealand Medical Journal, 124, 21-34. PDF available here (for a printable version) By Andrea Teng, Amanda Eng, Hayley Denison Version: Original 30 June 2017	4	14	0	4	8	0.759419	12	3,092
Myopia of Prematurity Myopia of prematurity (MOP) is a form of refractive error related to alterations in the development of the anterior segment, rather than axial length, that occur in individuals born prematurely. It is a distinct entity from pathologic or school-age myopia. MOP is closely linked to retinopathy of prematurity (ROP) and its treatment, although there is evidence that premature individuals are at risk for myopic refractive error even in the absence of ROP. Efforts to describe the role ROP has in MOP have led to a number of proposed names to distinguish whether myopia developed solely from prematurity (i.e. true “myopia of prematurity”) or as a sequela of ROP with treatment (myopia of retinopathy of prematurity) or without treatment (“myopia of spontaneously regressed ROP”). These terms are not universally accepted, however, and many publications do not differentiate between them. There is no specific ICD code for myopia of prematurity. Depending on the context, codes for retinopathy of prematurity (ICD-9: 362.20; and ICD-10: H35.109), progressive high myopia (ICD-9: 360.21), degenerative myopia (ICD-10: H44.20), or simply myopia (ICD 9: 367.1; and ICD-10: H52.13) may be appropriate. Likewise, there is no specific MeSH identifier for MoP. Early studies on infants with ROP led to the observation that premature infants with and without ROP were predisposed to myopic refractive error, but the prevalence of myopia was much higher in infants with ROP. In 1981, Fledelius observed “‘Myopia of prematurity’ is almost obligatory in cases of incomplete cicatricial retrolental fibroplasia” 3. (The term “retrolental fibroplasia” is a historic name for stage 5 ROP.) The Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) trial (study start date:1986) included a natural history subgroup which helped to conclusively demonstrate the reality of MOP. This and subsequent trials, including the Early Treatment of Retinopathy of Prematurity (ET-ROP) trial (study start date: 2001) and the Bevacizumab Eliminates the Angiogenic Threat of Retinopathy of Prematurity (BEAT-ROP) trial (study start date: 2008) provided key information about MOP and the effects of ROP treatment (cryotherapy, laser photocoagulation, and intravitreal bevacizumab) on its development. In the natural history population of the CRYO-ROP trial there was an overall prevalence of myopia (< -0.25 D) of 21% among all subjects at 1 year, but the prevalence of myopia at the same time point among the subgroup with severe ROP was 80%. Likewise, the overall prevalence of high myopia (< -5.0 D) was 3.9% at one year among all participants but was ~43% among those with severe ROP. Each 100g decrease in birth weight correlated with a 10% increase in the prevalence of myopia. In the ET-ROP study, which enrolled participants with pre-threshold ROP, the prevalence of myopia and high myopia was ~65% and ~35% respectively. MOP prevalence appears to vary with treatment. Laser photocoagulation results in lower incidence of MOP than cryotherapy ablation. The BEAT-ROP study compared outcomes following laser photocoagulation or intravitreal bevacizumab (IVB) and demonstrated a lower prevalence of myopia in those treated with IVB. The prevalence of myopia at 2.5 years in individuals with zone 1 ROP was 79% in the laser group and 43% in the IVB group. The prevalence of high myopia was 50% in the laser group and 22% in the IVB group. Prevalence of myopia and high myopia was lower among subjects with zone 2 ROP., The study also found a positive correlation between the degree of myopia (in diopters) and the number of laser shots used: -0.14D/100 laser shots. Longitudinal studies of the development of MOP indicate that the degree of myopia is not static from birth, but in fact develops over time, with the most rapid changes occuring during the first year of life. In one prospective observational study, refractive change over time followed a bi-linear pattern in infants who required panretinal photocoagulation with the most rapid changes in refractive error occurring during the first year of life; conversely, refractive changes followed a steady linear pattern in infants with severe ROP that spontaneously regressed without treatment. The defining pathophysiologic feature of MOP (with and without associated ROP) is abnormal development of the anterior segment. Eyes with MOP exhibit increased corneal curvature, thick lenses, and shallow anterior chambers. In contrast to pathologic myopia, where increased axial length is a hallmark, eyes with MOP characteristically have shorter axial lengths relative to their dioptric value. The exact mechanism whereby prematurity and ROP lead to the characteristic anterior segment aberrations of MOP is not known. Observations about the timing of MOP development and the improved refractive outcomes of laser over cryotherapy and IVB over laser have led some to suggest that MOP development reflects a mechanical restriction of ocular growth. Other theories include bone deficiency, retinal dysfunction, and temperature interactions. Premature infants and especially those with severe ROP should be monitored vigilantly for development of myopia with correction with spectacles as clinically indicated. Such infants may also be at risk for other refractive complications such as astigmatism and anisometropia. Monitoring for amblyopia secondary to high myopia, anisometropia, or strabismus is also prudent. Laser treatment could be more efficacious in treating ROP than anti-VEGF. However, laser treatment seems to increase myopia and cause more eye complications. Anti-VEGF-treated preterm children develop a significantly less myopic and astigmatic refractive error compared with laser-treated children; furthermore, high myopia is less prevalent. Although significantly less myopic than laser-treated children even across age, spherical equivalent development of most anti-VEGF-treated children is still relatively abnormal compared with the normal full-term children. - Fielder AR, Quinn GE. Myopia of prematurity: nature, nurture, or disease? Br J Ophthalmol 1997;81:2–3. - Fledelius HC. Pre-term delivery and the growth of the eye An oculometric study of eye size around term-time. Acta Ophthalmol 1992;70:10–15. - Fledelius HC. Myopia of Prematurity — Changes During Adolescence. Ultrasonography in Ophthalmology 1981:217–223. Available at: http://dx.doi.org/10.1007/978-94-009-8659-6_30. - Nissenkorn I, Yassur Y, Mashkowski D, et al. Myopia in premature babies with and without retinopathy of prematurity. Br J Ophthalmol 1983;67:170–173. - Geloneck MM, Chuang AZ, Clark WL, et al. Refractive outcomes following bevacizumab monotherapy compared with conventional laser treatment: a randomized clinical trial. JAMA Ophthalmol 2014;132:1327–1333. - Scharf J, Zonis S, Zeltzer M. Refraction in premature babies: a prospective study. J Pediatr Ophthalmol Strabismus 1978;15:48–50. - Quinn GE, Dobson V, Repka MX, et al. Development of Myopia in Infants with Birth Weights Less than 1251 Grams. Ophthalmology 1992;99:329–340. - Quinn GE, Dobson V, Davitt BV, et al. Progression of myopia and high myopia in the Early Treatment for Retinopathy of Prematurity Study: Findings at 4 to 6 years of age. Journal of American Association for Pediatric Ophthalmology and Strabismus 2013;17:124–128. Available at: http://dx.doi.org/10.1016/j.jaapos.2012.10.025. - Quinn GE, Dobson V, Kivlin J, et al. Prevalence of myopia between 3 months and 5 12 years in preterm infants with and without retinopathy of prematurity. Ophthalmology 1998;105:1292–1300. - Wang J, Ren X, Shen L, et al. Development of refractive error in individual children with regressed retinopathy of prematurity. Invest Ophthalmol Vis Sci 2013;54:6018–6024. - Garcia-Valenzuela E, Kaufman LM. High myopia associated with retinopathy of prematurity is primarily lenticular. J AAPOS 2005;9:121–128. - Fang Y, Yokoi T, Nagaoka N, et al. Progression of Myopic Maculopathy during 18-Year Follow-up. Ophthalmology 2018;125:863–877. - Pohlandt F. Hypothesis: myopia of prematurity is caused by postnatal bone mineral deficiency. Eur J Pediatr 1994;153:234–236. - Lue CL, Hansen RM, Reisner DS, et al. The course of myopia in children with mild retinopathy of prematurity. Vision Res 1995;35:1329–1335. - Fielder AR, Levene MI, Russell-Eggitt IM, Weale RA. Temperature—a factor in ocular development? Developmental Medicine & Child Neurology 1986;28:279–284. - Yang C-S, Wang A-G, Sung C-S, et al. Long-term visual outcomes of laser-treated threshold retinopathy of prematurity: a study of refractive status at 7 years. Eye 2010;24:14–20. Available at: http://dx.doi.org/10.1038/eye.2009.63. - Li Z, Zhang Y, Liao Y, Zeng R, Zeng P, Lan Y. Comparison of efficacy between anti-vascular endothelial growth factor (VEGF) and laser treatment in Type-1 and threshold retinopathy of prematurity (ROP). BMC Ophthalmol. 2018 Jan 30;18(1):19. doi: 10.1186/s12886-018-0685-6. PMID: 29378530; PMCID: PMC5789737. - : Tan Q-Q, Christiansen SP, Wang J (2019) Development of refractive error in children treated for retinopathy of prematurity with anti-vascular endothelial growth factor (anti-VEGF) agents: A meta-analysis and systematic review. PLoS ONE 14(12): e0225643. https://doi.org/10.1371/journal. pone.0225643	2	8	0	0	2	0.574861	2	2,457
Waves of pain in abdomen: Abdominal pain: MedlinePlus Medical Encyclopedia Abdominal Pain in Appendicitis \| Everyday Health Possible Causes of Abdominal Pain, Including Appendicitis Aside from appendicitis, some of the most common causes of abdominal pain include: The severity of the pain doesn’t always correspond to the seriousness of the condition that’s causing the pain. Life threatening conditions such as colon cancer may cause only mild pain, while a minor bout of gas may cause painful cramping. (1) Looking at the specific type of pain you’re experiencing can help you zero in on the condition you may have. For example, cramping abdominal pain is commonly due to gas and bloating. It’s generally not caused by something serious (such as appendicitis), and may be followed by diarrhea. (1) “Colicky pain,” or abdominal pain that’s severe and comes and goes in waves, is typically the result of kidney stones or gallstones. (1) If your pain isn’t localized to a specific area, and instead you feel it in more than half of your belly, you may have a stomach virus, indigestion, or gas. Sometimes stress or anxiety causes vague, nonlocalized abdominal pain as well. (1) If that pain becomes more severe over time, or your abdomen becomes swollen, it could be the result of something obstructing or blocking your large intestine. On the other hand, if your pain is only found in one area of your belly, it’s possibly due to an issue with one of your organs, such as the gallbladder, pancreas, appendix, or stomach. The way the pain evolves over time can also be useful in determining what’s causing it. Certain conditions tend to cause acute pain over the course of hours or days, while other conditions cause pain that comes and goes but doesn’t necessarily worsen over time. (2) Is It Appendicitis Pain or Something Else? Most often, the pain you feel when you have appendicitis begins as a dull ache around your belly button that shifts to your lower right abdomen, where your appendix is located. Additionally, appendicitis pain: - Begins suddenly; it often wakes people up at night - Becomes significantly sharper in a matter of a few hours - Starts before other co-occurring symptoms, such as fever, nausea, and vomiting - Is associated with loss of interest in eating - Worsens when you move around, breathe deeply, cough, or sneeze - Spikes when you drive over a speed bump or experience other jarring motions (3) To diagnose appendicitis, your doctor will perform a physical exam, which will investigate the finer points of your abdominal symptoms. If you have appendicitis, you will likely: (4) - Hurt when someone applies and then quickly releases pressure in your lower right abdomen, a symptom called “rebound tenderness” - Experience rebound tenderness in your lower right abdomen when someone applies and quickly releases pressure on the lower left side of your abdomen - Unconsciously guard your lower right abdomen when someone tries to touch it - Feel pain when someone applies resistance to your right knee as you try to lift that leg up while lying down on your back - Ache in your abdomen when you move your bent right knee to the left and right while lying down on your back Abdominal Pain – Clinical Methods It is imperative to analyze abdominal pain with particular emphasis on six features: onset, progression, migration, character, intensity, and localization. Abdominal pain may be of sudden, rapid, or gradual onset. Pain of sudden onset occurs within a second. The patient will relate the time of onset at a precise moment, usually stating exactly what activity was going on at the time the pain began. Sudden onset of pain is commonly associated with perforation of the gastrointestinal tract from a gastric or duodenal ulcer, a colonic diverticulum, or a foreign body. Other common causes include a ruptured ectopic pregnancy, mesenteric infarction, ruptured aortic aneurysm, and embolism of an abdominal vessel. Pain of rapid onset begins with a few seconds and steadily increases in severity over the next several minutes. The patient will recall the time of onset in general but without the precision noted in pain of sudden onset. Pain of rapid onset is associated with cholecystitis, pancreatitis, intestinal obstruction, diverticulitis, appendicitis, ureteral stone, and penetrating gastric or duodenal ulcer. Pain of gradual onset is pain that slowly becomes more severe only after a number of hours or even days have elapsed. The patient’s memory as to the time of onset of the pain is vague; he or she can pinpoint only the day or possibly the week of onset. Pain of gradual onset is commonly associated with neoplasms, chronic inflammatory processes, and large bowel obstruction. Many other intra-abdominal conditions are associated with pain of gradual onset, making an accurate diagnosis from the history more difficult with this symptom than in pain of sudden or rapid onset. It is of real diagnostic significance to determine the progression of the pain over the interval from the time of onset until the patient seeks medical attention. Has the pain abated, or has it increased? Have there been intervals of total absence of the pain, or has the pain always been present, changing only in character? From this information the clinician may be able, for example, to identify a perforated ulcer that has produced pain of sudden onset that subsequently abates dramatically if the perforation seals and no further leak occurs. Intermittent attacks of abdominal pain that progress to a steady, constant ache suggest a small bowel obstruction with vascular compromise that will lead to the grave complication of necrosis of the involved incarcerated bowel. Pain that “shifts” from the original site of onset to another location in the abdomen is most often associated with acute appendicitis where periumbilical or epigastric pain (visceral) that is present early in the course of the disease is replaced with right lower quadrant (somatic) pain later in the illness when the parietal peritoneum becomes involved with the inflammatory process. Pain produced by irritation of the parietal peritoneum by duodenal contents leaking from a perforated duodenal ulcer may begin in the epigastrum and may migrate to the lower quadrants of the abdomen or pelvis depending on the pathway that the leaking material takes through the abdominal cavity. Determining the character, or what kind of pain the patient is experiencing, is of prime importance in discovering the pathologic process responsible for it. Since the patient’s description of the pain must be purely subjective, it is essential that the clinician and the patient communicate clearly so that the precise character of the pain can be identified. The patient will usually need help from the doctor in describing the pain by suggesting similarities or comparisons, such as hunger pain, burning pain, sticking pain. It is especially important that the presence or absence of cramping pain be established. The term cramp has many interpretations, so the patient will need to have an example of a cramplike pain that leaves no room for misinterpretation. One such example is to liken the pain to the wringing out of a washcloth with intense pain corresponding to wringing of the washcloth and abating when the washcloth is untwisted. Abdominal pain can be characterized as cramping, dull, or aching and as either constant or intermittent. Cramping abdominal pain is characterized by pain that increases in intensity in short waves to a maximum and then abruptly ceases for a period of complete absence of pain. Repetition of the pain occurs at intervals. This type of pain is associated with mechanical small bowel obstruction, and when clearly present, it is pathognomonic of that condition. The interval between cramping pain helps locate the site of the obstruction with short pain-free intervals in more proximal obstructions and longer pain-free intervals in more distal obstruction. Constant dull or aching abdominal pain is usually caused by distention or edema of the wall of a hollow viscus. Pain from stretch of the capsule of the liver and the spleen may also be perceived as dull or aching pain. When a hollow viscus such as the gall bladder is distended, as is most common, from obstruction of the cystic duct, constant, dull, aching pain is experienced. When the gall bladder contracts against the obstruction, the stretch of the gall bladder wall is suddenly intensified, producing a crescendo of pain in addition to the constant dull ache already present (gall bladder colic). Each individual perceives pain intensity differently. The intensity of pain in an individual patient can often be assessed by the way in which the patient physically responds to it. Patients with peritonitis (somatic pain) invariably lie still, perhaps on one side or the other with the knees and hips flexed, whereas patients with pain arising from the hollow or solid viscera (visceral pain) do not lie still but constantly change position or move about. Take, for example, a patient with the sudden onset of chemical peritonitis secondary to a perforated duodenal ulcer. The patient will immediately stop whatever activity he or she was doing at the moment of perforation, quickly sit or lie down, and remain as still as possible. By contrast, a patient who has the onset of abdominal pain caused by acute distention of the gall bladder will not be able to find comfort by lying down in any position, but will move from chair to bed to the bathroom, where numerous attempts to relieve the pain by enemas, cathartics, self-induced vomiting, antacids, or other home remedies for “gas” pains are characteristic responses to visceral pain. Visceral pain resulting from stretch of smooth muscle is localized in one of the three midline zones of the abdomen: epigastric, midabdominal, and lower abdominal. This midline zone pain, the sum of pain from the right and left splachnic pathways, is poorly localized, covers several body segments and, depending on its cause, varies from dull, aching, constant pain to cramping pain. Nausea, vomiting, pallor, and sweating are commonly associated with visceral pain. Somatic pain is well localized. It is located asymmetrically and is intensified by jarring, deep inspiration or pressure on the abdominal wall. One of the most useful physical examination procedures to identify the presence of abdominal pain of somatic origin is to ask the patient to distend his abdomen alternately by “pushing out” his umbilicus to touch the examiner’s hand (held a few inches above the abdomen) and then to “suck in” his umbilicus to touch his spine. These subjective parietal peritoneum stretching procedures often identify the site of somatic pain by simple observation. It is especially useful in examination of children, as the subjective location of the pain without actual palpation of the abdomen by the physician may obviate misinterpretation from the child’s anxiety. Since the cerebrospinal nerves that supply sensation to the anterior and lateral peritoneal surfaces are unilateral, any stimulation of the parietal peritoneal surfaces are lateralized quite well. Nausea, vomiting, pallor, and sweating are seldom associated with somatic pain. It is well to have the patient indicate the site of the pain while standing and in the prone position to be certain of the true location. Referred Pain and Accompanying Symptoms Three cerebrospinal nerves, the phrenic, obturator and genitofemoral, are of particular importance because of the characteristic referred pain carried over these pathways in certain intra-abdominal conditions. Irritation, stretch, or injury of the dorsal or ventral aspects of the dome of the diaphragm produces referred pain in the supraclavicular fossa (Kehr’s sign) corresponding to the sensory branches of the phrenic nerve (C3 through C5). Irritation of the genitofemoral nerve from such retroperitoneal inflammatory processes as retrocecal appendicitis or retroperitoneal perforation of the duodenum produces pain in the labia, testicle, or shaft of the penis on the involved side. Irritation of the obturator nerve in the obturator fossa, usually from an incarcerated obturator hernia, produces pain along the medial aspect of the thigh to the knee (Howship–Romberg’s sign). Clearly, symptoms that accompany abdominal pain are important in making an accurate diagnosis. Among the most important are nausea, vomiting, abdominal distention, diarrhea, constipation, obstipation, tarry stools, chills, fever, urinary frequency, hematuria, and jaundice. There is no substitute for a careful history of the type, onset, location, and progression of abdominal pain, as these symptoms closely match the pathogenesis of each disease process within the abdomen. This, coupled with understanding of the splanchnic and cerebrospinal innervation of the abdominal viscera, is essential for arriving at an accurate diagnosis in patients presenting with abdominal pain. Differences in the location and rate of progression of lesions within the abdominal cavity may be summarized as outlined by Smith (1961) in terms of five possible components. Visceral pain alone is a symmetric pain located in the midline anteriorly, with or without associated vasomotor phenomena. On occasion, when visceral pain is of rapid onset and of great severity, at the peak intensity of the pain it may “spill over” at the spinal cord level by viscerosensory and visceromotor reflexes into the corresponding cerebrospinal pathways, producing somatic findings without pathologic involvement of somatic receptors. Visceral and somatic pain often become combined as the causative lesion progresses from the viscus to involve adjacent somatic nerves. Visceral pain may continue, but a new and different pain is added. Somatic pain may be so severe that it overshadows the visceral pain of origin in the affected viscus, making an accurate diagnosis difficult. Referred pain due to irritation of the phrenic, obturator, and genitofemoral nerves are unique and diagnostically important findings remote from the abdomen that may provide clues to the source of abdominal pain. The clinical significance of the pathways and stimuli responsible for the production of abdominal pain can perhaps best be appreciated by an analysis of the pathogenesis of acute appendicitis, as that disease process correlates with symptoms and physical findings common to that disorder. The initiating event that starts the pathogenesis of the most common type of appendicitis is obstruction of the lumen of the appendix by a calcified concretion of fecal material called a fecolith. With obstruction of the appendiceal lumen, the continued production of large amounts of mucus from the rich concentration of goblet cells in the crypts of Lieberkuhn distends the appendix. At this stage in the pathogenesis of appendicitis, the pathologic diagnosis is an acute appendiceal mucocoele. Since stretch and distention are the only stimuli appreciated by the splanchnic (visceral) nerves, the characteristic midline, upper abdominal visceral pain of distention of a hollow viscus of embryologic origin from the midline, the classic periumbilical pain of early appendicitis begins. Although the appendix may be located almost anywhere in the abdominal or pelvic cavity due to its variable length as well as to rotation of the midgut, it is important to recognize that the epigastric or periumbilical visceral pain produced by distention will always be in the same midline upper abdominal location. Since peristalsis in the appendix is absent, or at best ineffective, as demonstrated by the presence of a fecolith that otherwise would be extruded from the lumen, the visceral pain of distention of the appendix is characteristically a steady, dull, aching pain without intermittent waves of intensity. It is of great value in the diagnosis of abdominal pain to attempt to establish both a pathologic and an anatomic diagnosis. For example, the pathologic diagnosis of “acute appendicitis” is not nearly as meaningful as a pathologic and anatomic diagnosis such as “acute suppurative right iliac fossa appendicitis.” Understanding of the pain pathways and the types of stimuli responsible for initiating pain responses from the abdomen make precise pathologic and anatomic diagnoses possible. The upper abdominal visceral pain of early appendicitis continues to increase gradually in intensity as the steady mucous production causes further distention of the obstructed appendiceal lumen. Intraluminal pressure progresses until the veins in the submucosa of the appendix become occluded by entrapment between the mucous membrane and the rigid, unyielding lamina propria in the appendiceal wall. At this stage in the pathogenesis, edema of the wall secondary to venous outflow occlusion rapidly ensues. This swelling, in addition to collection of edema fluid, causes a rather rapid, sharp increase in stretch of the appendiceal wall. This results in a marked increase in the intensity of the visceral pain. This point in the progression of the disease often prompts the patient to seek medical aid. The pathologic stage at the time of maximal swelling of the wall changes from an acute mucocoele to what is called acute catarrhal appendicitis. Since there is no inflammatory process in the appendix at this time, it is easily understood why there is no elevation of the white blood cell count or increase in body temperature. As the pressures within the lumen and in the wall of the appendix continue to increase, interference with arteriolar blood flow in the submucosa ensues. At this stage the cells in the wall of the appendix, along with the mucosal lining of the lumen, begin to die. The stage is now set for invasion of the wall of the appendix by organisms from the lumen and the onset of acute suppurative appendicitis begins. Obviously, as the wall of the appendix with the stretch-sensitive pacinian corpuscles dies, the dull, aching, intense upper midabdominal pain transmitted from these nerve endings disappears. Further pain patterns of appendicitis now depend on its anatomic location. It has been said that there is no characteristic symptomatology of acute appendicitis. Not so: The symptoms of appendicitis are characteristic for each stage in the progression of the pathologic process and for each of the anatomic sites in which the appendix may be located. The prodrome, produced by the early pathologic changes in the appendix and characterized by the visceral pain of distention, is the same no matter where the appendix is located, but the symptoms of suppuration and the continuing pathologic progression leading to gangrene, rupture, abscess formation, and local or generalized peritonitis differ markedly depending on the anatomic location of the appendix. The appendix, as part of the midgut that rotates outside the abdominal cavity during embryologic development, may be located in at least nine locations: right iliac fossa, retrocecal, paraileal, retroileal, interloop, pelvic, right upper quadrant, left upper quadrant, and left iliac fossa. The most common location of the appendix is in the right iliac fossa. In this location the inflammatory process in the suppurating appendix involves the contiguous parietal peritoneum. It is then that a new pain, entirely different from the visceral pain of the early stages and mediated over an entirely different neural pathway, begins. It is the sharp, well-localized, somatic pain of irritation of the parietal peritoneum transmitted to the dorsal root via the intercostal nerves. The patient points with one finger to the location of the pain, and jarring or any other stretch (deep breath, production of direct or indirect rebound tenderness) increases the local intensity of the pain. Additional pathognomonic features of acute appendicitis in the right iliac fossa include straightforward motor and sensory reflex arcs that produce involuntary guarding over the involved irritated dermatome, as well as hyperesthesia similarly distributed. Although it is often stated that the periumbilical pain in appendicitis “shifts” to the right lower quadrant, it is instructive to emphasize that the right lower quadrant pain is a new and entirely different pain. It is initiated by irritation of somatic nerve endings, transmitted by different neural pathways, and produces sharply localized symptoms and findings, in marked contrast to diffuse nature of visceral pain. Examination of the symptoms and findings of acute suppurative appendicitis in a retrocecal location, another common position, serves to emphasize further the importance of an understanding of not only the anatomy and innervation of the peritoneal cavity but of the retroperitoneum and pelvis as well. As has been stated, the visceral peritoneum has no somatic innervation. When the appendix is located retrocecally, for example, it is essential to remember that in this location it is retroperitoneal and, accordingly, has no contiguity with either visceral or parietal peritoneal serosa. The early abdominal pain produced by stretch is present in its characteristic upper abdominal location, but as suppuration begins, there is no inflammatory involvement of parietal peritoneal surfaces, as in iliac fossa appendicitis, and consequently there is no localized right lower quadrant pain. The reason for absence of somatic pain when the appendix is retrocecal is obvious. As the inflammatory process of retrocecal appendicitis continues, it may involve the psoas muscle, the obturator muscles, the ureter, and the genitofemoral nerve. Irritation of these structures is responsible for producing a positive psoas or obturator sign, white blood cells in the urine, and referred pain in the distribution of the branches of the genitofemoral nerve. The latter is manifested by pain in the testicle, shaft of the penis, or the labia on the right. When the appendix is located in the pelvis, it must be remembered that the pelvis is not part of the abdominal cavity and that the pelvic parietal peritoneum receives its somatic innervation from the lumbosacral rather than the intercostal nerves. Accordingly, irritation of the pelvic parietal peritoneum is not recognized by the patient in a localized abdominal wall distribution. It is helpful to recall that irritation of the pelvic parietal peritoneum usually produces localized pain in the midline suprapubicly, regardless of the location of the inflammatory process. The preceding detailed discussion of some of the characteristic pain patterns seen in appendicitis and the pathology responsible for them serves to illustrate the diagnostic importance of accurate interpretation of abdominal pain based on anatomy and pathology. Other Structures That Can Cause Pain Upper abdominal organs have anatomic features that make pain patterns emanating from them far more complex than those of the appendix. Painful lesions of the gastroesophageal junction, the fundus and lesser curvature of the stomach, the biliary tract, and proximal portions of the duodenum commonly produce pain in the interscapular zone corresponding to the sixth thoracic segment, since the somatic innervation of the lesser omentum is supplied by that thoracic nerve. Pancreatic pain is often perceived in the same location one segment lower. The stomach is so situated that portions of its surface are in contact with the diaphragm, the gastrohepatic ligament, the lesser sac, the pancreas, the parietal peritoneum, the splenic hilus, the gastrocolic ligament, the transverse mesocolon, and the transverse colon. Inflammatory or neoplastic lesions of the stomach that involve any of these surfaces may irritate somatic nerves from several different spinal segments. Accordingly, pain may be localized by the patient to the supraclavicular fossa from phrenic nerve stimuli, the interscapular region from irritation of T6 through T8, or even the lumbar region from involvement of the T12 through L1 spinal cord segments. Similarly to the stomach, the duodenum is in anatomic relationship to a number of somatic cerebrospinal nerve roots. As a result, perforating ulcer pain can be appreciated in the interscapular zone, the right subcostal region, and the right lower quadrant depending on which somatic nerves are involved in the pathologic process. Retroperitoneal perforation of the duodenum from blunt abdominal trauma may cause irritation of the genitofemoral nerve from leaking duodenal contents resulting in pain in the right testicle or labia. Pain from the gall bladder and biliary tract may have bilateral localization because they arise from outbudding of the midline gut and have bilateral splanchnic innervation. If the inflammatory process of acute suppurative cholecystitis involves the parietal peritoneum of the right upper quadrant, somatic pain with its usual local manifestations and referred pain along the involved cerebrospinal nerve to the tip of the scapula (T8) may be present. Involvement of the parietal peritoneum in the right upper quadrant from suppuration of the gall bladder is not a very common event, as the greater omentum (which has no somatic sensory innervation) often surrounds the inflamed gall bladder as a buffer between the inflammatory process and the parietes. Pathologic conditions that arise from the pancreas are responsible for a broad spectrum of pain-producing syndromes. In addition, extrinsic lesions (e.g., penetrating duodenal ulcer) are frequently involved in the production of pain from the pancreas. Further, disruption of the integrity of the gland by pancreatitis permits the extravasation of enzymes that spread to many different intra-abdominal locations that may involve somatic spinal pathways from the phrenic nerve to the lumbosacral plexus. The small intestine, like the rest of the midgut, produces upper midline, periumbilical visceral pain in response to distention or stretch. The foregut and hindgut are far less sensitive to stretch or distention. Pain from these portions of the intestinal tract, the stomach and duodenum from the former and the descending colon and rectum from the latter, is more often initiated by inflammatory lesions than from distention. Experimental studies of the production of pain from the gastrointestinal tract in humans by inflation of balloons at various locations within the lumen of the gut should be interpreted very cautiously, as they bear little or no resemblance to actual pathologic conditions that produce pain in humans. The most valid observations concerning the origins of abdominal pain come from surgeons who have the advantage of prompt inspection of the site of pathology within the abdomen and the opportunity to compare these findings on the spot with the patient’s perception of the abdominal pain. The skin, subcutaneous tissues, fascia, muscle, and parietal peritoneum of the abdominal wall are richly supplied with somatic nerves from T6 through T12. Pain in the abdominal wall can result from neuromas in scars from previous laparotomies, such medical conditions as acute porphyria, or from herpes zoster. In addition, pain from trauma to the abdominal wall from blunt injury must be carefully identified to rule out abdominal pain originating from an intraperitoneal injury. The ureters are second only to the pancreas as a source of abdominal pain caused by structures in the retroperitoneum. The renal pelvis is sensitive to distention, and the ureters are richly supplied with nerves from T10 through T12. Ureteral pain is ipsilateral, severe, and cramping in nature (renal colic). It is usually of such severity and located in the flank that the diagnosis is difficult to confuse with other abdominal catastrophies. Pain in the testicle or labia (T10) may on occasion confuse the diagnosis of renal colic with retrocecal appendicitis. The presence of red blood cells in the urinalysis may help solve this diagnostic dilemma. Since the lower intercostal nerves also provide the parietal pleura and periphery of the diaphragm with sensory (somatic) innervation, as well as the abdominal wall and anterior peritoneal parietes, it is understandable that inflammatory processes that involve the parietal pleura innervated by these nerves may also be manifested by abdominal pain. Needless to say, an appendectomy is poor therapy for right lower lobar pneumonia that has produced reflex abdominal wall pain in the right lower quadrant. Pericarditis, myocardial infarction, and pulmonary infarction may also cause inflammatory lesions that involve the parietal diaphragmatic or thoracic pleura, producing referred abdominal pain that may be misdiagnosed as a primary intraperitoneal disorder. Abdominal pain \| Health Navigator NZ Pain in your abdomen (stomach or puku) is common. It can be hard to know what’s causing it and many people never find out the exact cause. The important thing is knowing when and how you can take care of your symptoms at home and when you need to see a doctor. Your abdomen is the part of your body between the bottom of your ribs and the top of your hips. It often gets called your stomach, tummy or puku, but there’s a number of other organs in that area too. Most pain in this part of your body will pass quickly and can be treated at home by yourself or with medication from your pharmacist. This includes when you have: \|See your family doctor or call HealthLine (0800 611 116) if:\| \|Call 111 and ask for an ambulance if you:\| What causes abdominal pain? It can be difficult to know what is causing pain in your abdomen, and often the pain settles without knowing what caused it or needing any treatment. Causes of sudden, severe abdominal pain include: Causes of long-term or recurring abdominal pain include: If your child has a sore stomach or abdominal pain, see gastroenteritis in children, constipation in children and vomiting in children. How is abdominal pain diagnosed? As well as asking where the pain is, your doctor will ask you to describe your pain, so notice whether it’s sharp, stabbing, cramping or a dull ache. Also, notice whether the pain is there all the time or if it comes and goes in waves. Your doctor will also ask if the pain came on suddenly (acute), or whether you have had it for a while (chronic). They will also want to know if you have been sick (vomited) or had diarrhoea (watery, runny poo). Depending on what they think is causing your abdominal pain, they may want to do further tests. What is the treatment for abdominal pain? The treatment will depend on the cause of the abdominal pain. Once you know the cause of your pain, you can find out more on the page for that condition. What self-care is there to relieve abdominal pain? If your abdominal pain is mild, and there are no concerning symptoms, you can take care of yourself and reduce pain and discomfort by: - drinking plenty of water - putting a heat pack or hot water bottle where it hurts, or having a warm bath - taking paracetamol to ease pain, but not aspirin or anti-inflammatory drugs, unless advised to do so by a doctor, as these can make abdominal pain worse - avoiding alcohol, tea and coffee - avoiding eating, and then starting again when you feel better on bland foods (such as rice, crackers, bananas or toast) - lying down and resting - asking your pharmacist about medicines to ease wind, spasms or to stop diarrhoea - telling your doctor if your medication causes indigestion, constipation or diarrhoea. If you know the cause of your abdominal pain, you can go to the Health Navigator page for that condition to find out what support is available to you. Call Healthline phone 0800 611 116 for free advice from registered nurses 24 hours a day, seven days a week, if you are unsure about what to do. How can I prevent abdominal pain? - You can keep your gut healthy by eating lots of fruit and vegetables, as well as other foods high in fibre, such as whole grains and legumes. Find out more about healthy eating. - You can reduce the chance of food poisoning and gut infections by following food safety practices and keeping your hands clean. - Find out about preventing specific conditions by linking on the related topics and links in the list of causes above. Abdominal pain Patient Info, UK, 2015 Abdominal pain in adults Better Health, Australia, 2012 Beat the bloat NHS Choices, UK, 2016 Flatulence NHS Choices, Uk, 2015 - Abdominal pain Ministry of Health - Abdominal pain and stomach ache NHS Choices, UK, accessed Nov 2016. - Hunt, R et al. Coping with common gastrointestinal symptoms in the community – a global perspective on heartburn, constipation, bloating, and abdominal pain/discomfort May 2013, WHIO Guideline. Journal of Clinical Gastroenterology, August 2014, 48, 7: 567–578. - Manterola C, Vial M, Moraga J, Astudillo P. Analgesia in patients with acute abdominal pain. Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No. CD005660. Information for healthcare providers on abdominal pain The content on this page will be of most use to clinicians, such as nurses, doctors, pharmacists, specialists and other healthcare providers. Diagnosing and managing abdominal pain Urgent or easily missed causes of acute abdominal pain Patient Info, UK, 2015 Colonoscopy should not be considered as a first line of investigation with isolated abdominal pain NZMA 2013 Managing pain in children aged under 12 years BPAC, NZ, 2014 Abdominal pain in childhood Starship clinical guidelines Also see Health Navigator Clinicians pages for dyspepsia, constipation, diverticular disease and diverticulitis, appendicitis, irritable bowel syndrome, kidney stones, gallstones, urinary tract infection (UTI), pelvic inflammatory disease, dysmenorrhoea, gastroenteritis, Crohn’s disease, ulcerative colitis, coeliac disease, lactose intolerance, peptic ulcer. Regional HealthPathways NZ Access to the following regional pathways is localised for each region and access is limited to health providers. If you do not know the login details, contact your DHB or PHO for more information: Kids Health Information : Abdominal pain Common questions our doctors are asked How can I tell if my child has appendicitis? Appendicitis can be difficult for doctors to diagnose, but a sign that your child may have appendicitis is that they have severe pain starting around their belly button and moving to the right side of their abdomen. Most children with appendicitis will be very reluctant to move. See your GP if you are worried. My child has been diagnosed with mesenteric adenitis. What does this mean? Mesenteric adenitis occurs when the lymph nodes in the abdomen enlarge in response to an infection – most commonly a viral infection. This results in stomach pain. Mesenteric adenitis is diagnosed clinically (without the need for blood tests or imaging). It is important that children who are diagnosed with mesenteric adenitis are reviewed to determine if it is developing into appendicitis. Why is it so difficult to work out the cause of my child’s ongoing stomach aches? Stomach aches are difficult to diagnose in all ages. Children differ in their ability to describe the type, severity and location of their pain, which can make this process even harder. Many problems from the chest down to the groin may be interpreted by children as stomach aches, making it very difficult to find out the true cause. Your child’s doctor will examine and investigate your child in order to rule out anything serious, while trying to find the underlying cause. The doctor says my child has abdominal migraine. What is As the name suggests, abdominal migraine is a migraine experienced in the abdomen instead of the head. A child with abdominal migraine will often have tummy pain along with nausea/vomiting, loss of appetite and pale skin. There is no headache involved and the child is well between episodes. There is still quite a lot that is unknown about abdominal migraine, but the risk factors and triggers are thought to be similar to traditional migraines (e.g. having a family member with migraines, being stressed or overtired, chemicals in food). See our fact sheet Having Abdominal Pains? When You Should Go To The ER Virtually everyone experiences some form of stomach pain from time to time. In many cases, pain in the abdomen can be mild and harmless. However, some stomach pains – particularly when they are severe or accompanied by additional symptoms – may be indicative of a more serious problem that requires immediate diagnosis and treatment. The expert team of board-certified emergency room physicians and professional medical staff at iCare ER & Urgent Care in Frisco and Fort Worth, TX utilize the most advanced diagnostic tools and treatment techniques available to help identify the cause of abdominal pain, provide rapid relief, and avoid further complication. Learn more about stomach pain here, including how to tell if your symptoms warrant a trip to the ER. What could be causing my stomachache? Abdominal pain can occur for a number of reasons and range from mild to severe. It may come on suddenly, but it can also develop gradually and may remain constant, become progressively worse, or wax and wane in intensity. In some cases, the cause of stomach pain is relatively harmless and will resolve on its own. Other times, a potentially life-threatening condition or process may be causing abdominal pain. Because a stomachache is a common symptom for such a wide range of diagnoses, it is important to be evaluated by an experienced ER physician to determine with certainty what may be causing your pain and get appropriate treatment. Possible causes of stomach pain that may still warrant treatment but don’t necessarily require emergent care include: - Constipation or bowel gas - Food poisoning - Heartburn, reflux, or GERD - Stomach virus - Stomach flu More serious causes of abdominal pain that should be diagnosed and treated in the 24/7 emergency room side of our unique dual hybrid facilities in Fort Worth and Frisco, TX include: - Bowel obstruction - Stomach or colon cancer - Kidney stones Additionally, there are a number of potentially fatal conditions that can cause abdominal pain and require immediate diagnosis and treatment as an emergency case, including: - AAA (abdominal aortic aneurysm) - Ectopic pregnancy (ruptured) - Ruptured appendix - Ischemic bowel - Perforated bowel or stomach How do I know when to go to the ER for stomach pain? Because common conditions, like food poisoning or constipation, can cause abdominal pain, it can often be difficult to know when your symptoms require a trip to the ER. If you are having unexplained or severe abdominal pain, or if you are in doubt about the cause of your abdominal pain, it is always best to be examined by a professional. If your stomach pain is severe, chronic, or accompanied by additional symptoms, visit your nearest ER as soon as possible to receive a diagnosis and treatment. Some signs and symptoms that may mean your stomach pain is serious enough to go to the ER include: - New onset of pain - Chronic abdominal pain - Worsening pain - Radiating pain - Nausea or vomiting - Bloating or swelling - Loss of consciousness - Shortness of breath - Blood in stool When you arrive at either of iCare ER & Urgent Care’s state-of-the-art facilities in Fort Worth or Frisco, you will be promptly seen by one of our knowledgeable board-certified ER physicians. Your physician will perform a thorough examination, take a detailed health history, and run any necessary tests – such as lab work or imaging studies – to help elucidate the cause of your stomach pain. From there, effective and appropriate treatment will be administered depending on your diagnosis, severity of symptoms, and other factors. Your doctor may recommend additional therapies or prescribe medications for you to continue at home. Don’t take any chances when it comes to abdominal pain in North Texas Get to the bottom of your stomach pain, get rapid relief from your symptoms, and start feeling more like yourself again with advanced diagnosis and treatment at either of iCare ER & Urgent Care’s convenient locations in Frisco and Fort Worth, TX. Whether your abdominal pain is moderate, severe, chronic, or new, our team of award-winning board-certified emergency room physicians and professional staff is here to help you get the effective treatment and reliable relief you deserve. Abdominal Pain, Age 11 and Younger Does your child have pain or cramping in the belly? This also includes injuries to the belly. How old are you? Less than 3 months Less than 3 months 3 months to 11 years 3 months to 11 years 12 years or older 12 years or older Are you male or female? Why do we ask this question? - If you are transgender or nonbinary, choose the sex that matches the body parts (such as ovaries, testes, prostate, breasts, penis, or vagina) you now have in the area where you are having symptoms. - If your symptoms aren’t related to those organs, you can choose the gender you identify with. - If you have some organs of both sexes, you may need to go through this triage tool twice (once as “male” and once as “female”). This will make sure that the tool asks the right questions for you. Has your child had surgery on the chest or belly in the past 2 weeks? Recent abdominal surgery Recent abdominal surgery Has your child swallowed or inhaled an object? Swallowed or inhaled object Swallowed or inhaled object Does your baby seem sick? A sick baby probably will not be acting normally. For example, the baby may be much fussier than usual or not want to eat. How sick do you think your baby is? Baby is very sick (limp and not responsive) Baby is sick (sleepier than usual, not eating or drinking like usual) Is your child having trouble drinking enough to replace the fluids he or she has lost? Little sips of fluid usually are not enough. The child needs to be able to take in and keep down plenty of fluids. Unable to drink enough fluids Able to drink enough fluids Does your child have pain in the belly? Does the belly feel hard when you touch it? Normally the belly is soft and has some “give.” A hard, rigid belly may be a sign of a more serious problem. Abdomen is hard (rigid) to the touch Abdomen is hard (rigid) to the touch Does pressing on the belly cause severe pain? Pressing on abdomen causes severe pain Pressing on abdomen causes severe pain Has the pain: Pain is increasing Stayed about the same (not better or worse)? Pain is unchanged Pain is improving How long has your child had pain? Less than 4 hours Less than 4 hours 4 hours but less than 1 day (24 hours) 4 hours but less than 1 day (24 hours) More than 3 days More than 3 days Does the belly hurt all over or mostly in one area? Pain that is most intense in just one area is likely to be more serious than a bellyache that hurts all over. Mostly in one area Does your child have pain with a new bulge in the belly button or groin? Pain with new bulge in navel or groin Pain with new bulge in navel or groin Is your child nauseated or vomiting? Nauseated means you feel sick to your stomach, like you are going to vomit. Within the past week, has your child had an injury to the abdomen, like a blow to the belly or a hard fall? Abdominal injury within past week Abdominal injury within past week Since the injury, has there been any bleeding from the rectum, urethra, or vagina? Bleeding from rectum, vaginal or urethra since injury Bleeding from rectum, vaginal or urethra since injury Is there a belly wound that is deeper than a scratch? Do you suspect that the injury may have been caused by abuse? This is a standard question that we ask in certain topics. It may not apply to you. But asking it of everyone helps us to get people the help they need. Injury may have been caused by abuse Injury may have been caused by abuse Has your child vomited since the injury? Is there pain just below the ribs? Pain just below the ribs after an injury can be a symptom of serious damage to the liver or spleen. Do you think your baby has a fever? Did you take a rectal temperature? Taking a rectal temperature is the only way to be sure that a baby this age does not have a fever. If you don’t know the rectal temperature, it’s safest to assume the baby has a fever and needs to be seen by a doctor. Any problem that causes a fever at this age could be serious. Rectal temperature taken Rectal temperature taken Is it 100.4°F (38°C) or higher? Temperature at least 100.4°F (38°C) Temperature at least 100.4°F (38°C) Do you think your child has a fever? Did you take your child’s temperature? How high is the fever? The answer may depend on how you took the temperature. NOTE: Most people have an average body temperature of about 98.6°F (37°C). But it can vary by a degree or more and still be considered normal. If a low body temperature is your only symptom, it’s usually not something to worry about. But be sure to watch for other symptoms. High: 104°F (40°C) or higher, oral High fever: 104°F (40°C) or higher, oral Moderate: 100.4°F (38°C) to 103.9°F (39.9°C), oral Moderate fever: 100.4°F (38°C) to 103.9°F (39.9°C), oral Mild: 100.3°F (37.9°C) or lower, oral Mild fever: 100.3°F (37.9°C) or lower, oral How high do you think the fever is? Feels fever is moderate Mild or low Feels fever is mild How long has your child had a fever? Less than 2 days (48 hours) Fever for less than 2 days From 2 days to less than 1 week Fever for more than 2 days and less than 1 week 1 week or longer Fever for 1 week or more Does your child have a health problem or take medicine that weakens his or her immune system? Disease or medicine that causes immune system problems Disease or medicine that causes immune system problems Does your child have shaking chills or very heavy sweating? Shaking chills are a severe, intense form of shivering. Heavy sweating means that sweat is pouring off the child or soaking through his or her clothes. Shaking chills or heavy sweating Shaking chills or heavy sweating Are your child’s stools black or bloody? Black or bloody stools Black or bloody stools How much blood is there? More than a few drops. Blood is mixed in with the stool, not just on the surface. More than a few drops of blood on stool or diaper A few drops on the stool or diaper A few drops of blood in stool or diaper Does your child have diabetes? Is your child’s diabetes getting out of control because your child is sick? Diabetes is affected by illness Diabetes is affected by illness Is the plan helping get your child’s blood sugar under control? Diabetes illness plan working Diabetes illness plan not working How fast is it getting out of control? Quickly (over several hours) Blood sugar quickly worsening Slowly (over days) Blood sugar slowly worsening Do you think that a medicine could be causing the belly pain? Think about whether the belly pain started after you began using a new medicine or a higher dose of a medicine. Medicine may be causing abdominal pain Medicine may be causing abdominal pain Have your child’s symptoms lasted longer than 1 week? Child’s symptoms have lasted longer than 1 week Child’s symptoms have lasted longer than 1 week Many things can affect how your body responds to a symptom and what kind of care you may need. These include: - Your age. Babies and older adults tend to get sicker quicker. - Your overall health. If you have a condition such as diabetes, HIV, cancer, or heart disease, you may need to pay closer attention to certain symptoms and seek care sooner. - Medicines you take. Certain medicines, such as blood thinners (anticoagulants), medicines that suppress the immune system like steroids or chemotherapy, herbal remedies, or supplements can cause symptoms or make them worse. - Recent health events, such as surgery or injury. These kinds of events can cause symptoms afterwards or make them more serious. - Your health habits and lifestyle, such as eating and exercise habits, smoking, alcohol or drug use, sexual history, and travel. Try Home Treatment You have answered all the questions. Based on your answers, you may be able to take care of this problem at home. - Try home treatment to relieve the symptoms. - Call your doctor if symptoms get worse or you have any concerns (for example, if symptoms are not getting better as you would expect). You may need care sooner. With cramping pain in the belly: - The pain may hurt a little or a lot. - The amount of pain may change from minute to minute. Cramps often get better when you pass gas or have a bowel movement. - The pain may feel like a tightness or pinching in your belly. - The pain may be in one specific area or be over a larger area. It may move around. Babies can quickly get dehydrated when they lose fluids because of problems like vomiting or fever. Symptoms of dehydration can range from mild to severe. For example: - The baby may be fussy or cranky (mild dehydration), or the baby may be very sleepy and hard to wake up (severe dehydration). - The baby may have a little less urine than usual (mild dehydration), or the baby may not be urinating at all (severe dehydration). You can get dehydrated when you lose a lot of fluids because of problems like vomiting or fever. Symptoms of dehydration can range from mild to severe. For example: - You may feel tired and edgy (mild dehydration), or you may feel weak, not alert, and not able to think clearly (severe dehydration). - You may pass less urine than usual (mild dehydration), or you may not be passing urine at all (severe dehydration). Severe dehydration means: - The baby may be very sleepy and hard to wake up. - The baby may have a very dry mouth and very dry eyes (no tears). - The baby may have no wet diapers in 12 or more hours. Moderate dehydration means: - The baby may have no wet diapers in 6 hours. - The baby may have a dry mouth and dry eyes (fewer tears than usual). Mild dehydration means: - The baby may pass a little less urine than usual. Severe dehydration means: - The child’s mouth and eyes may be extremely dry. - The child may pass little or no urine for 12 or more hours. - The child may not seem alert or able to think clearly. - The child may be too weak or dizzy to stand. - The child may pass out. Moderate dehydration means: - The child may be a lot more thirsty than usual. - The child’s mouth and eyes may be drier than usual. - The child may pass little or no urine for 8 or more hours. - The child may feel dizzy when he or she stands or sits up. Mild dehydration means: - The child may be more thirsty than usual. - The child may pass less urine than usual. If you’re not sure if a child’s fever is high, moderate, or mild, think about these issues: With a high fever: - The child feels very hot. - It is likely one of the highest fevers the child has ever had. With a moderate fever: - The child feels warm or hot. - You are sure the child has a fever. With a mild fever: - The child may feel a little warm. - You think the child might have a fever, but you’re not sure. A baby that is extremely sick: - May be limp and floppy like a rag doll. - May not respond at all to being held, touched, or talked to. - May be hard to wake up. A baby that is sick (but not extremely sick): - May be sleepier than usual. - May not eat or drink as much as usual. Pain in children under 3 years It can be hard to tell how much pain a baby or toddler is in. - Severe pain (8 to 10): The pain is so bad that the baby cannot sleep, cannot get comfortable, and cries constantly no matter what you do. The baby may kick, make fists, or grimace. - Moderate pain (5 to 7): The baby is very fussy, clings to you a lot, and may have trouble sleeping but responds when you try to comfort him or her. - Mild pain (1 to 4): The baby is a little fussy and clings to you a little but responds when you try to comfort him or her. Pain in children 3 years and older - Severe pain (8 to 10): The pain is so bad that the child can’t stand it for more than a few hours, can’t sleep, and can’t do anything else except focus on the pain. No one can tolerate severe pain for more than a few hours. - Moderate pain (5 to 7): The pain is bad enough to disrupt the child’s normal activities and sleep, but the child can tolerate it for hours or days. - Mild pain (1 to 4): The child notices and may complain of the pain, but it is not bad enough to disrupt his or her sleep or activities. Shock is a life-threatening condition that may occur quickly after a sudden illness or injury. Babies and young children often have several symptoms of shock. These include: - Passing out (losing consciousness). - Being very sleepy or hard to wake up. - Not responding when being touched or talked to. - Breathing much faster than usual. - Acting confused. The child may not know where he or she is. Blood in the stool can come from anywhere in the digestive tract, such as the stomach or intestines. Depending on where the blood is coming from and how fast it is moving, it may be bright red, reddish brown, or black like tar. A little bit of bright red blood on the stool or on the toilet paper is often caused by mild irritation of the rectum. For example, this can happen if you have to strain hard to pass a stool or if you have a hemorrhoid. A large amount of blood in the stool may mean a more serious problem is present. For example, if there is a lot of blood in the stool, not just on the surface, you may need to call your doctor right away. If there are just a few drops on the stool or in the diaper, you may need to let your doctor know today to discuss your symptoms. Black stools may mean you have blood in the digestive tract that may need treatment right away, or may go away on its own. Certain medicines and foods can affect the color of stool. Diarrhea medicines (such as Pepto-Bismol) and iron tablets can make the stool black. Eating lots of beets may turn the stool red. Eating foods with black or dark blue food coloring can turn the stool black. If you take aspirin or some other medicine (called a blood thinner) that prevents blood clots, it can cause some blood in your stools. If you take a blood thinner and have ongoing blood in your stools, call your doctor to discuss your symptoms. Certain health conditions and medicines weaken the immune system’s ability to fight off infection and illness. Some examples in children are: - Diseases such as diabetes, cystic fibrosis, sickle cell disease, and congenital heart disease. - Steroid medicines, which are used to treat a variety of conditions. - Medicines taken after organ transplant. - Chemotherapy and radiation therapy for cancer. - Not having a spleen. Temperature varies a little depending on how you measure it. For children up to 11 years old, here are the ranges for high, moderate, and mild according to how you took the temperature. Oral (by mouth), ear, or rectal temperature - High: 104° F (40° C) and higher - Moderate: 100.4° F (38° C) to 103.9° F (39.9° C) - Mild: 100.3° F (37.9° C) and lower A forehead (temporal) scanner is usually 0.5° F (0.3° C) to 1° F (0.6° C) lower than an oral temperature. Armpit (axillary) temperature - High: 103° F (39.5° C) and higher - Moderate: 99.4° F (37.4° C) to 102.9° F (39.4° C) - Mild: 99.3° F (37.3° C) and lower Note: For children under 5 years old, rectal temperatures are the most accurate. It is easy for your diabetes to become out of control when you are sick. Because of an illness: - Your blood sugar may be too high or too low. - You may not be able take your diabetes medicine (if you are vomiting or having trouble keeping food or fluids down). - You may not know how to adjust the timing or dose of your diabetes medicine. - You may not be eating enough or drinking enough fluids. An illness plan for people with diabetes usually covers things like: - How often to test blood sugar and what the target range is. - Whether and how to adjust the dose and timing of insulin or other diabetes medicines. - What to do if you have trouble keeping food or fluids down. - When to call your doctor. The plan is designed to help keep your diabetes in control even though you are sick. When you have diabetes, even a minor illness can cause problems. Many prescription and nonprescription medicines can cause belly pain or cramping. A few examples are: - Aspirin, ibuprofen (such as Advil or Motrin), and naproxen (such as Aleve). - Iron supplements. Seek Care Today Based on your answers, you may need care soon. The problem probably will not get better without medical care. - Call your doctor today to discuss the symptoms and arrange for care. - If you cannot reach your doctor or you don’t have one, seek care today. - If it is evening, watch the symptoms and seek care in the morning. - If the symptoms get worse, seek care sooner. Seek Care Now Based on your answers, you may need care right away. The problem is likely to get worse without medical care. - Call your doctor now to discuss the symptoms and arrange for care. - If you cannot reach your doctor or you don’t have one, seek care in the next hour. - You do not need to call an ambulance unless: - You cannot travel safely either by driving yourself or by having someone else drive you. - You are in an area where heavy traffic or other problems may slow you down. Call 911 Now Based on your answers, you need emergency care. Call 911 or other emergency services now. Sometimes people don’t want to call 911. They may think that their symptoms aren’t serious or that they can just get someone else to drive them. Or they might be concerned about the cost. But based on your answers, the safest and quickest way for you to get the care you need is to call 911 for medical transport to the hospital. Make an Appointment Based on your answers, the problem may not improve without medical care. - Make an appointment to see your doctor in the next 1 to 2 weeks. - If appropriate, try home treatment while you are waiting for the appointment. - If symptoms get worse or you have any concerns, call your doctor. You may need care sooner. Swallowed or Inhaled Objects Abdominal Pain, Age 12 and Older Why Does My Stomach Hurt? 17 Possible Causes of Stomach Pain What Is Abdominal Pain? Abdominal pain is discomfort or other uncomfortable sensations that you feel in your belly area. Just about everybody at one time or another will get a bellyache. Most causes of abdominal pain aren’t reasons to worry, and your doctor can easily diagnose and treat the problem. Sometimes, though, it can be a sign of a serious illness that needs medical attention. Types of Abdominal Pain There are several types of abdominal pain, which are based on how quickly your pain starts and how long it lasts: - Acute pain starts over a few hours or days and may come with other symptoms. - Chronic pain lasts longer — from weeks to months or more — and may come and go. - Progressive pain gets worse over time and often comes with other symptoms. Abdominal Pain Causes Whether you’ve got a mild ache or serious cramps, abdominal pain can have many causes. For instance, you might have indigestion, constipation, a stomach virus or, if you’re a woman, menstrual cramps. Other possible causes include: You may also get abdominal pain if you’re lactose intolerant or have ulcers or pelvic inflammatory disease. Other causes include: - Kidney stones - Gastroesophageal reflux disease (GERD) - Abdominal aortic aneurysm (swelling in the belly’s main artery) - Bowel blockage or obstruction - Cancer of the stomach, pancreas, liver, bile duct, gallbladder, or immune cells - Ovarian cancer or cysts - Pancreatitis (inflammation of the pancreas) - Cholecystitis (inflammation of the gallbladder) - Low blood flow to your intestines caused by a blocked blood vessel - Ectopic pregnancy (when a fertilized eggs grows outside the uterus, for example, in a Fallopian tube) When to Call the Doctor About Abdominal Pain If your abdominal pain is serious, doesn’t go away, or keeps coming back, talk to your doctor. Call 911 right away if your belly hurts because you had a recent injury there or if you have any chest pain. You should also contact your doctor as soon as you can if you have symptoms along with the pain, such as: - Can’t keep food down for more than 2 days - Signs you’re getting dehydrated, including not urinating frequently, dark-colored urine, and being very thirsty - Can’t have a bowel movement, especially if you’re also vomiting - Pain when you pee, or you need to urinate often Also call your doctor if: - Your belly is tender to the touch - Pain lasts more than a few hours You may have other symptoms that could be a sign of a problem inside your body that needs treatment as soon as possible. Get medical care right away if you have abdominal pain and you also: - Vomit blood - Notice bloody or black, tarry bowel movements - Have trouble breathing - Vomit constantly - Have swelling in your belly - Have yellow skin - Are pregnant - Have unexplained weight loss Abdominal Pain Diagnosis Since there are so many possible causes, your doctor will do a thorough physical exam. They’ll also ask you some questions about your symptoms and want to know what type of pain you have. For instance, is it a severe stabbing pain or a dull ache? Some other questions your doctor may ask you: - Does it hurt throughout your abdomen, or is it just in one particular area? - When does it hurt? Always? More often in the morning or at night? - If the pain comes and goes, about how long does it last each time? - Does it hurt after you eat certain foods or drink alcohol? - Are you in pain during menstruation? - How long have you been hurting? - Does the pain sometimes move into your lower back, shoulder, groin, or buttocks? - Do you take any medications or herbal supplements? - Are you pregnant? - Does any activity ease the pain, such as eating or lying on one side? - Does an activity or position make the pain worse? - Were you injured recently? After your exam is over and your doctor is done asking you questions, you may need tests to help find the cause of your pain. These tests may include: Abdominal Pain Treatment and Home Remedies The treatment for abdominal pain depends on its cause, and may include: - Medications to lower inflammation, prevent acid reflux, or treat ulcers or infection - Surgery to treat a problem with an organ Over-the-counter pain relievers like aspirin and ibuprofen can irritate your stomach and worsen your pain. Don’t take them unless a doctor has diagnosed the cause of your belly pain and recommends their use. Some diet and lifestyle changes may help belly pain caused by gas and indigestion. Here are some things you can try: - Eat smaller portions at more frequent meals - Eat slowly - Chew your food well - Drink beverages at room temperature - Avoid foods that give you gas or indigestion - Manage your stress - Limit alcohol and caffeine - Sit up straight after you eat - Get regular physical activity and take a short walk after you eat Right abdominal pain, possible diseases Only the most common diseases that cause abdominal pain on the right and left are considered here . This material is for preliminary determination of the cause of the occurrence of abdominal pain , and not for making accurate diagnoses without consulting a doctor. Remember – self-medication leads to complications of diseases. In case of abdominal pain – you need to call an ambulance, or consult a dispatcher by phone, call or visit a surgeon of the clinic.In case of severe pain, prolonged pain, recurring pain in the abdomen (right or left) , be sure to see a doctor – these may be symptoms of very serious diseases. The main groups of diseases and pathological conditions leading to pain in the abdomen on the right First of all, having felt pain in the abdomen, on the right or on the left , determine the place of the greatest localization of pain. Try to understand exactly where hurts: left, right, above, below, in the chest, in the back, in the lower back .Try to define more clearly the nature of the abdominal pain : dull, aching, pressing (as if something is squeezing), sharp, dagger (as if a knife was thrust in with a swing), bursting (as if they had swallowed a ball and opened it). A doctor or ambulance team will ask you to answer questions: - how it appeared and how it developed abdominal pain: pain appeared suddenly, after physical exertion, after stress, after hypothermia; - How long has passed since the onset of the attack pain ; - what were the first abdominal pains : mild, then intensified, immediately sharp, dull.Whether abdominal pain intensified sweat and how – quickly or gradually; - whether pain changed localization: for example, with appendicitis , abdominal pain first appears in the iliac region – where the stomach is, and then goes down to the right ; - whether there is irradiation pain , that is – where pain in the abdomen gives and under what circumstances: movement, cough, tilt, etc. For example, if it hurts in the right hypochondrium and pain is given under the scapula on the right – this is a sign of cholecystitis. Severe cutting abdominal pain may indicate the presence of appendicitis, stomach or duodenal ulcer, strangulated hernia, volvulus. Even if you have very severe pain , do not put a heating pad with hot water or ice on your stomach. Take a spasmolytic like no-shpa or drotaverine. Call an ambulance or see a surgeon the next day. Pain in the upper abdomen on the right The upper right quadrant of your abdomen contains: the liver, the gallbladder, part of the intestine (each quadrant of the abdomen contains a part of the intestine), the pancreas, and the right side of the diaphragm.Disease or injury to these organs brings you pain in the upper abdomen . How strong it is and what kind of pain it is will depend on what is happening and where. Is it liver pain? Anything that causes the liver to swell makes it ache. Some parasites can infect the liver. Whatever the cause of the inflammation or infection, the result is called hepatitis. Usually they get sick with hepatitis A after swallowing food or water contaminated by sewage (shellfish are the first aggressors here).Hepatitis B is especially common among homosexuals, drug addicts and those who have had close contact with them. Hepatitis C is almost always spread through contaminated blood transfusions, medical needles, and blood products. Various chemical agents and medications can damage the liver because they are toxic to it. However, the most dangerous poison for the liver is alcohol (which causes alcoholic hepatitis). Hepatic pain is constant, aching, mild or dagger.You feel it all over the right upper abdomen – deep inside, not on the surface. The discomfort develops constantly and relentlessly, not in spasms or waves. Does the gallbladder hurt? Symptoms of gallbladder disease appear gradually. A violent attack is often preceded by a time when you feel gas and bloating an hour or two after eating fried or greasy, or some vegetables. However, you can only become seriously anxious for the first time with an attack.When this happens, the pain on the right is sharp, in contrast to the aching hepatic pain. When the pain reaches its maximum, sweat and nausea appear, which even vomiting does not relieve. A high fever is unlikely unless the gallbladder is inflamed; in this case, she can jump up to forty, and you will have chills. The pain itself is most severe in the right upper quadrant, but can also spread to the back, under the right shoulder blade. Most of the “bad” gallbladders have stones. If the stones are small, then one or two may exit the bladder into the ducts that carry bile into the intestines.Then you will have biliary colic, the pains of which start quickly and come in waves as the ducts try to squeeze out the stone that is blocking them. When they succeed, you feel better. But if the stone remains in the duct, it must be removed from there in one way or another – by operation, dissolution or extraction without surgery. Blocked bile ducts cause jaundice, which disappears if the stone passes into the intestines. Does the pancreas hurt? An attack of acute pancreatitis can be extremely painful and is accompanied by sweating, nausea and vomiting.Symptoms differ from those in the pathology of the gallbladder in that the pain penetrates directly into the back, it is worse for you when lying down, and it is easier for you to sit with an inclination forward. The diagnosis usually requires confirmation by laboratory tests to determine the content of certain enzymes secreted by the damaged gland. Is it pneumonia in the abdomen? In medical practice, there are patients who, after several days of cough and fever as a result of cooling, suddenly develop pain in the right upper quadrant.A “cold” turns out to be an inflammation of the lungs. The inflamed and infected lung comes into contact with the diaphragm, which in turn becomes irritated and involves the adjacent intestine, causing symptoms. Remember, therefore, that any abdominal pain preceded by a respiratory illness may in fact be due to an infection in the lungs. Always think of shingles whenever you feel unexplained pain anywhere. The first symptoms are superficial tenderness, a burning sensation or itching, which later develop into severe pain.For 4 or 5 days, you just have a lot of pain in a certain place. The skin appears perfectly normal with no rash or other warning signs. Aside from pain, you generally feel healthy. But if the pain is in the right upper quadrant of the abdomen, your doctor may be on the wrong track, thinking about gallbladder disease, pancreatitis, or even kidney stones. He orders analysis after analysis and finds nothing. After a few days, the characteristic reddish pimples appear exactly where it hurt.The rash follows the inflamed nerve, never crosses the midline or passes to the other side of the body. This “one-sided” rash gives you an accurate diagnosis – shingles. Is the pain on the right kidney? Renal pathology can sometimes cause pain in the right upper quadrant. The kidneys are located on the sides, one on each side of your body, so kidney disease usually causes pain in the corresponding side and back rather than the front. If the problem is associated with a small stone that has come out of the kidneys, the pain comes in waves, excruciating and often radiates into the groin and right testis, testicle. Pain in the lower abdomen on the right Let’s start again with what’s in this part of the belly. First of all, here is the appendix, a small, finger-sized piece of tissue that leaves the large intestine. Then the intestine itself, which can be affected by various diseases, including cancer. But we have a whole host of new organs here: the ovaries and fallopian tubes in women, the ureters that drain urine from the kidneys into the bladder in both sexes. Is the pain on the right an appendix? Remember a good rule of thumb: Any pain in the right lower abdomen is appendicitis unless proven otherwise.If you can point the pain with one finger and it lasts 12 hours without relieving, you almost certainly have appendicitis. This is especially true if the pain is also near the navel. In case you suspect that your appendix is inflamed, see your doctor immediately. When confirming the diagnosis, the doctor will almost certainly advise surgery before this organ of unknown function festers and bursts. Right pain – other causes Pain can be caused by irritation, inflammation, or infection of the intestines (ulcerative colitis, ileitis, Crohn’s disease, or diarrhea caused by parasites such as amoeba or worms), shingles, and compression of the nerves that extend from the spine and end in this area.A kidney stone on its way down into the bladder will also cause excruciating pain in that quadrant. If a woman does not have her next period and she suddenly feels severe pain in the left or right lower abdomen, think first – and quickly – about a rupture with an ectopic pregnancy. Pain that worsens during menstruation suggests endometriosis. Doctors said that COVID-19 is becoming a more transient disease The symptoms of coronavirus this fall differ significantly from previous waves – at first, it became even easier to confuse COVID-19 with a cold or flu.Subsequently, new symptoms appear, and the disease itself becomes more fleeting. This was reported on September 30 by Public news service , which interviewed doctors. So, experts called a severe runny nose a new symptom of coronavirus infection, which also develops more rapidly – pneumonia manifests itself on the third day, and not on the seventh, as it was before. From the first days, those infected with the coronavirus have symptoms similar to acute flu: pain and sore throat, high fever.To this may be added deafness with dizziness and loss of smell. Both symptoms indicate a central nervous system (CNS) virus infection, doctors noted. “Discharge from the nose, sore throat, sore throat. A rapidly developing and long-lasting cough with a lot of phlegm. Fever behaves like a flu, but lasts longer. Neurological symptoms are largely expressed: dizziness, headaches, severe weakness. Fainting is possible when you try to stand up suddenly.There is a rapid lesion of the central nervous system. All these symptoms appear immediately, maximum – on the second day and last for weeks, ”explained doctor Alexander Ediger. Of the previous symptoms, digestive disorders remain, but now they are more pronounced – these are abdominal pains, diarrhea. “Food is very poorly tolerated, even cereals and soups. Nausea and vomiting are possible. The analyzes show pronounced liver enzymes, which have not been observed before, ”Ediger added. The main symptoms of coronavirus in previous waves were fever, fatigue, cough with a small amount of sputum.As the disease progressed, some patients (about 15%) developed symptoms such as dyspnea (a feeling of shortness of breath). An increase in body temperature was recorded in more than 90% of patients, a dry cough – in about 80%, chest tightness – in more than 20%. Rise in incidence Deputy Prime Minister of the Russian Federation Tatyana Golikova on September 30 warned of the onset of a difficult period due to the rise in the incidence of COVID-19. “I want to ask you to be careful, observe all restrictive measures, take care of yourself and your loved ones,” she said at a meeting of the Council on Guardianship in the Social Sphere. In turn, the head of Rospotrebnadzor Anna Popova previously noted that the rise in the incidence of coronavirus infection has been going on for three weeks against the backdrop of the next season of growth in the incidence of ARVI and influenza. Since the beginning of the pandemic, about 233.3 million people have become infected with the coronavirus in the world, more than 4.7 million have died. In Russia, according to the federal operational headquarters, 7,511,026 cases of infection were registered, 6,672,767 people recovered, 207,255.9,016 died. On the spread of coronavirus 90,097 The number of confirmed cases of coronavirus infection in Russia has increased by 23,888 over the past day.The country has registered 867 deaths of the disease. Thus, the maximum number of deaths due to COVID-19 is updated for the third day in a row. The conditional mortality rate of the disease remained at the level of 2.76%, it follows from the data of the headquarters. 90,097 62 patients with coronavirus have died in Moscow. The number of people infected in the capital increased by 3,998.9,016 The spread of coronavirus infection in Russia on Thursday dropped to 1.03, it follows from the calculations of TASS .In Moscow, it dropped to 1.01. The indicator shows how many people, on average, have time to infect one infected person before they are isolated. Wandering pains throughout the body: causes and treatment - Causes of wandering pains; - Pain in different parts of the body; Sometimes patients complain of wandering pains throughout the body of varying intensity, they can suddenly appear and disappear regardless of the time of day. In ICD 10, there is no such disease, usually symptoms provoke various pathologies or disorders that occur in a latent or subacute stage.Clients often come to a traumatologist and ask why their arms and legs become numb, and in such cases, a neurologist’s consultation is needed. But migratory muscle pains will be cured by a therapist. Diagnostics will help to determine the provoking factor. Causes of wandering pains When all muscles, bones and joints of the whole body hurt, the search for the causes begins with a visit to the doctor. But in order to know which doctor to go to, you need to take into account the presence of chronic diseases, previous infections or a predisposition to the development of various pathologies. All provoking factors can be general and characteristic for a certain localization of the symptom. The most common causes of wandering pain throughout the body are systemic disorders and pathologies: - physical overload and muscle strain; - transferred ARVI or infectious poisoning; - posture disorders and diseases of the spine; - Inflammation of the muscles due to hypothermia; - constant stress and neuroses; - various chronic diseases (diabetes mellitus, rheumatism, arthritis, etc.)etc.). These are the most common causes of a symptom. To determine what the muscles of the whole body hurt from is possible only by carrying out instrumental diagnostics and examination. Before going to the doctor, you need to assume a provoking factor that can cause pain. To do this, you need to take into account its localization and manifestations. Pain in different parts of the body Usually, migratory pains spread throughout the body in a specific area – the right or left limb along the forearm, hand, thigh, lower leg or foot.Synchronization of the lesion on the right and on the left is often noted; with such a severity, it is possible to assume a specific disease and make a preliminary diagnosis. This will help prescribe a course of treatment that will give the most effective result. It is possible to determine what causes discomfort by localization – usually it is the head, neck, back, abdomen or limbs. Attachment to topography is present in certain diseases, in which the nature of the pain is different. In the head If migratory pains throughout the body are accompanied by the appearance of a symptom in the head region, neurological disorders should be assumed.They are caused by exogenous or internal causes: - Pinched nerves – due to osteochondrosis or muscle spasms, the spinal roots can be compressed, which provoke sharp stabbing or burning pain; - With injuries, infections or the initial stage of osteochondrosis, pressing pain in the frontal lobe may appear. In this condition, it is better to be examined immediately, sometimes the symptom is provoked by oncology; - Headaches often appear when wearing uncomfortable hats, caps, tight motorcycle helmets, glasses, etc.In such cases, after elimination of the provoking factor, the symptoms completely disappear. The therapy is individually tailored. If pinching is observed, massage, physiotherapy exercises, various physiotherapy procedures with skeletal traction are prescribed. If there is an infection, medications are prescribed, which must be taken urgently to prevent meningitis. In the muscles and joints In case of wandering pain in the joints and muscles, you need to visit an orthopedic traumatologist, and if the doctor does not reveal any damage, a neurologist will be appointed.The search for the cause is carried out depending on the clinical picture: - With arthritis, pain can migrate through the joints, affect the knees, ankles, elbows, and shoulder blades. Depending on the form of the disease, there may be synchrony or one-sided localization; - Injuries or overloads of the extremities – in this case, an analogy can be drawn between pain and a provoking factor: if you often work with your hands, discomfort will be in your hands or forearms, and if your knees are bruised, they will periodically hurt; - Infections – often intoxication is accompanied by aching muscles and joints.In this case, pain will be noted not only in the limbs, but also throughout the body; - Diseases of the spine in the cervicothoracic or lumbosacral regions – if nerves of nearby plexuses are pinched during osteochondrosis, hernias or protrusions, the pain will spread to the limbs. In the back and neck Frequently wandering pains in the muscles throughout the body appear in the head and neck, here it is necessary to immediately assume diseases of the spine or nearby muscles: - When nerves are pinched, stabbing pain usually occurs, when squeezed – burning …It can be provoked by osteochondrosis, various curvatures, protrusions or hernias. Less often, oncology is observed; - If myositis is noted, a sharp cutting pain appears and can spread throughout the back. If you are bleeding, your temperature may rise, weakness and loss of strength may occur; - Muscle spasms sometimes develop and cause severe pain. They usually appear in the presence of previous causes, but can greatly complicate the clinical picture of the disease. Back and neck pain is the most common concern for people with a sedentary lifestyle.When the nerves are pinched, the vessels that feed the brain are often squeezed. Particularly dangerous is the defeat of the vertebral artery, which is located in the transverse processes of the cervical vertebrae – then dizziness and headaches appear. In the abdomen Most often, migratory pains in the abdomen are chronic diseases of internal organs: hepatitis, pancreatitis, gastritis and other pathologies. The most dangerous is appendicitis, in this condition an operation is urgently needed. Less commonly, abdominal pain provokes systemic pathologies.As in previous cases, an instrumental examination will help establish the exact cause. Rogue’s Daughter on Apple Podcasts Please do not listen to this podcast if you are under 18 years of age. It contains descriptions of scenes of violence. This is the first of a three-episode spin-off of the Robber’s Daughter podcast called The Price of the Trip. At the beginning of autumn, Nastya learned the story of the girl Yana, who was raped by a taxi driver. Acquaintance with Yana gave rise to a lot of questions and a desire to understand: how often do such crimes happen? How do women experience unwanted attention and harassment from drivers? is it possible to achieve justice – or at least justice? How do aggregators react to what is happening? In this episode, girls from different cities of Russia talk about their experiences, and we are trying to figure out how aggregators work and what is their responsibility for what is happening in a taxi. We found answers to some legal questions about the work of a taxi in these materials: What can you learn about the work of taxi services and their relations with passengers if you read the user agreement Is it true that taxi drivers work for days and earn a penny? Where to complain if the driver is rude? Shameful questions about taxi aggregators * Resolution of the Plenum of the Supreme Court of the Russian Federation of 06/26/2018 N 26 “On some issues of the application of legislation on the contract for the carriage of goods, passengers and luggage by road and on the contract of transport expedition” The Cabinet of Ministers proposed to prohibit drivers with a criminal record from working in a taxi Taxi aggregators will review liability * Meduza is recognized as a foreign media agent in Russia At the beginning of the episode, at the party, Polina Gagarina’s song “The play is over” is played Creator and presenter: Nastya Krasilnikova (instagram) Editor: Anya Shinkaretskaya Composer: Alexey Zelensky Sound engineer: Yuri Shustitsky Cover: Ruslana Mirzalieva Transcripts: Olga Averkieva For communication: unsudden @ gmail.com read I am obsessed with you Chapter 459 Veniamin Rodionovich stood nearby and sobbed mournfully to himself. – How unhappy she is! Dmitry stood in the doorway and still did not enter the room, disheveled hair hid his expression. – I remember how on her twentieth birthday, when my parents died, and they grabbed me, she ran everywhere and tried to pull me out, – Veniamin Rodionovich had a lump in his throat, – I didn’t know everything then, how she was did.Only after some time did I find out that she had made a deal with a woman named Anfisa Nikonovna, so that I would not be sent to prison, she paid her a large sum of money to pay off my debts and I was released. And my stepmother … My sister immediately left with Anfisa to another city. This Anfisa slipped her husband Liza, hoping that they would start a relationship, love each other … After that, Liza became pregnant, Anfisa wanted the child to be their official, so she told everyone that she herself was pregnant … After giving birth, the child passed to Anfisa, and she told everyone that this was her child, whom she gave birth to. Only unfortunately, Fadey noticed Liza, believing that she wanted to take Anfisa’s husband away. Then his father Nikon Kirillovich was still in power and was powerful, Fadey was acting outrageous, and he grabbed Liza, forced her to leave Ilya. She certainly resisted, but he somehow found out about her first love and also grabbed Athanasius to blackmail her. Liza had no choice but to call Ilya Nikitich and inform him that it was time to leave, because she still loves Afanasy. After the call, Fadey imprisoned her and Afanasy for six whole years … Later, Anfisa found out about this, she came to her brother and asked to let them go.Then six years had already passed, Fadey hoped that so much time had passed, and their feelings between Liza and Ilya faded away. And the child of Anfisa and Ilya has already grown up, so he agreed to let her go … For six years! They grabbed her right after giving birth. Because of this, she was injured and could no longer have children. She also had problems with her head, only a year later she recovered. Later, in order to be close to her son, she married Ilya, but Fadey was against it and said that he would only agree on the condition that she would be given “family heirlooms”.And how Anfisa died in the end, I do not know at all. Withstanding a pause, Benjamin raised his reddened eyes, looked at Dmitry and continued in a grieving voice: – This woman who lies under the white sheet is your own mother, – and added with special emphasis, – She carried you for nine months and gave birth in heavy pain. Dmitry did not raise his eyes and vaguely saw the trembling of his body. Ilya got up, all meaning was lost in his eyes, he carefully let go of Elizabeth’s hand, and in complete sorrow and misfortune looked at Benjamin Rodionovich. eSg3Cc0h2TSriuMYGVJ3oQjYUCf40XnTBReNBi8x76HQSgdgXNFHZN + w2h3M2PqzwOvBdyKUUz0TwASRGU / NFZoyncfu3loIgg8iHc6wKc2KLcJF7Tye1J08uiF0yxAAaVgU2LQmtcbdlQJ8gr8ncjyS8WTJFWK / y8EpYhvX6U7enkDyt + E376zwcUBCbUI2ZsbN0GldppTZMVYpIB / itEn5GRhoaJBkIrfP032R8qg6Og5v2HQtAHFUcDwFcXsK4cys1m9m5ib7VaibxrKbJihr1ELYJp3 / h2CFM09RVxrlUcpMYnb + 7WmfEnOROtLZlgRPByx1XHIna8KdEGkTEOw24LwS / 8O92nHe9AJoGlCE1HYiYybKVr2jjG5rP0BheB1WkuzfS9djf / evtJ1KActV0JWXlVIE8FsecGuW4YUblZtZfPFXqWwHjGEOk8PBOf3TBI + w49vMxSDkeJQmj8JSvLixgvLUMbfKSMaQcgwGx0S / wcgsm4FzAXRECjyJyajB8uND / aM4rA7llHBraJFofZ5dicCoQfJf3MgwTG7c2SIxKKRo / zz / UzbaAN4PzNgU8Pud668z5aFh0hM + hbmQmLx24jbqTPPZKfwdf8NKF56Nkkt951ydqwBmJzyzLyK + lFuZLQv8PrjDLKRLUHa8aoH + rGxPvunvTIN12aFCS5 / YOO8LTR9StJp31mWi2GNlhBHfZsq / OiQ08lY0mNz7KqUw1y3r8vPT + 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如果你不知道冬天该怎么去吃，才能对身● 好的话，今天就让我来给你说一说，进入冬季以后，中老年人一定要多吃的 6 种食材。所以进入冬天以后，我们一定要记得多喝乌鸡汤，其所富含的营养价值，有很好的抗衰老，滋阴壮阳、健脾，提高抵抗力等等作用。 Time flies so fast and it’s cold winter again.Every year after the onset of winter, we must replenish our body with nutrients in time.Because The climate is cold in winter, The body’s resistance will decrease, Eating more nutritious food can effectively increase our body’s resistance. When faced with cold winters, especially for middle-aged and older friends, you should pay special attention to the cold winter: if you are not careful, it will take its toll on your body.So this time How to eat properly in winter has become a very important question. If you don’t know how to eat well in winter to maintain your health, let me tell you today. After winter there are 6 types of ingredients that middle-aged and elderly people should eat more. This is all the knowledge that my 90-year-old grandmother shared with me: he eats this way every winter and he has a very good body. After winter enters, middle-aged and older people should eat 6 more ingredients that ensure good nutrition and good health. XNUMX. White radish There is a saying: Eat ginger in summer and radish in winter, The taste of radish in winter is very crunchy and sweet. Rich in vitamins, carbohydrates, vitamins, vegetable protein. Always wait for a variety of nutrients. Has a reputation for “little ginseng”. It can be seen how high its nutritional value is. In addition, there are many ways to eat radishes in winter: they can be eaten with pickles, fried, stewed in soup, or eaten raw.The taste is very good. This is especially important for stewing soup, it can also make the soup taste very fresh and sweet. Second, black chicken soup Three nines make up one winter, in the coming year there will be no pain, Entering winter, you must remember to feed your body in time. So, entering winter, we must Do not forget to drink more chicken soup with black bones, His rich nutritional value is very good. Anti-aging, nourish yin and yang, invigorate the spleen, increase resistance And so on. Especially for middle-aged and elderly people, Good for preventing cardiovascular diseases, May make your body healthier in winter. A small bowl of black bone chicken soup every day can also nourish your skin and make your face glow. Every day is beautiful and beautiful. XNUMX. Fresh lamb. As we enter the cold winter, we need to eat more warm sex foods. Among the many warm sex foods, lamb is one of the best foods to choose from.Because compared to many meat ingredients, Lamb meat is inherently warm, so it effectively drives away the cold in our body. In cold winters, lamb is best used in soup. A hot bowl of lamb soup warms the body and stomach. Especially for those Middle-aged and old friends with cold hands and feet, Remember to drink plenty of lamb soup to keep warm at any time. In the cold winter, due to the dry climate, many people tend to get angry, so you need to eat more fruits during this time. When faced with a lot of fruit, Sydney should be the first choice. Because Sydney is very good The effect of moving fluid in the body to quench thirst, relieve cough and phlegm, remove heat and eliminate fire. It is still effective if you eat Sydney in winter Prevent colds and coughs , Especially older friends who get old, if they cough in winter, the whole person will feel very uncomfortable. So at this time, please remember Boil one Sydney pear every day, Can play a very good coaching role, May he calmly survive the winter. Five black beans Black beans have a reputation as the “king of beans”, They are very high in protein, calcium and trace elements. Compared to the milk we usually drink, the protein content in black beans is ten times higher. So if you drink milk in winter, you can eat black beans as well. In addition to the high nutritional value of black beans, they are also Rich in unsaturated fatty acids and vitamins Looking forward to nutrition.These nutrients are very beneficial for the health of middle-aged and older friends. Can prevent various diseases of hypertension . In addition, there is black beans in winter, there is a good Nourish the liver, moisturize dryness Oh, the role. Six, lotus root There is a saying about the lotus root: “The lotus is a treasure, the root of the autumn lotus is the most tonic.” hence When winter came, it was the season when there were many lotus roots in the market., Because the lotus root harvest season is in the late autumn season, so newly introduced lotus roots have a very high nutritional value and are especially suitable for human consumption. Small lotus root, no need to look at it, but its nutritional value is very high. Rich in micronutrients, dietary fiber, iron, potassium And other nutrients especially suitable for eating friends. Winter If you have a poor appetite, eat more lotus root., Very good for improving appetite. Well, this is what I want to recommend to you today, 6 types of food to eat more in winter. When faced with these 6 foods, which one do you think is the most complementary in winter? You can leave a message in the comments area and give your opinion. In fact, besides these 6 types of food, there are many foods in winter that are very nutritious for the body.If you have a better understanding, you can also recommend it to us, What foods do you eat in winter to nourish your body! Images and materials in this article were taken from the Internet and are used for communication, training and research. If there are errors or inaccuracies in the translation of the text in the data of the article, please contact for removal and correction. Allows you to easily receive tens of millions of coupons for Taobao, Tmall, Pinduoduo and JD products every day. Get Coupons Now: Shopping center platform with discount on big tickets Overwrite Editor TopItInfo: 时间飞逝，一晃又到了严寒的冬天，每一年进到冬天之后，大家一定要立即对身 ble 开展养分上的摄入哦。由于冬天天气严寒，身 ble 抵抗能力便会减少，多吃一些营养成分的食材，才可以合理提高，大家身կ 的抵抗能力。在应对的的冬天时，尤其是中老年人好朋友，一定要需注意寒冷的冬季，稍不留意得话，便会对身 ble 产生危害。因此这个时候，冬天要如何去吃，就变成了一件十分重要的事儿。假如你永远不知道冬季该怎样吃，才可以对身 ble 好得话，今日就要我让你说进到冬天之后，中老年一定要多吃的 6 种食物。这可全是我 90 岁的姥姥，帮我共享的专业知识，每一年冬季他都那样吃，身子尤其棒。进到冬天后，中老年要多吃 6 样食物，养分好身棒一萝卜有一句老话是那样说的，夏吃生姜冬吃萝卜，冬季的箩卜口味是十分甜脆的，其还含有了充足的维他命，糖类与碳水化合物，维他命，大豆蛋白等多种营养，一直都拥有 “小人参的美名，由此可见其营养成分多大。此外，冬季的萝卜吃法还很充足，可以腌着吃炒着吃，还可以用于煲汤吃，或是是可以直接直接生吃，口味全是十分出色的，尤其是用于煲汤，还能让汤的味儿，十分鲜美。二鸽子汤三九补一冬，明年无病苦，进到冬季之后，一定要还记得立即对身文开展滋补养生。因此进到冬季之后，大家一定要还记得多喝鸽子汤，其所含有的营养成分，有有效的延缓衰老，补肾固精健脾胃，提高抵抗力这些功效。尤其是针对中老年而言，还能非常好防止心脑血管疾病，能使你在冬季有一个更健康的身 ble。每日一小碗鸽子汤，还能非常好润养肌肤，使你容貌容光焕发，每天都美若天仙。三新鮮牛肉进到严寒的冬天之后，大家一定要多吃性温的食物，在许多的温性食材中，牛肉是最好的优选食材之之一。由于相较为于诸多肉类食品食物的情况下，牛肉的肉质地温性，这样一来就能合理，对大家身կ 身 ble 内的凉气开展祛除。在严寒的冬天，牛肉的最好使用方法，便是用于熬汤，一碗热呼呼的羊汤，暖身又养胃。尤其是针对这些手脚冰冷中老年人好朋友定一定要还记得多喝羊汤，能使你身 ble 随时随地都温暖的。四梨子寒冷的冬季，因为气侯干躁，因此很多人都非常容易发生容易上火的状况，因此这个时候，大家就需要多吃新鲜水果，在应对诸多新鲜水果的情况下，一定要优选梨子。由于梨子有有效的生津解渴，化痰止咳清热祛火实际效果。在冬季吃梨子得话，还能合理预防流感干咳哦，尤其是上年龄的中老年好朋友，冬季一咳嗽得话，全部人便会很难受。因此此刻，请还记得每日烫一个梨子服用，就能具有不错的基本功效，使你安全过冬季。五黑芝麻黑芝麻拥有 “豆中霸主的美名，其所含有的蛋白，钙成分，营养元素都非常的高。相较为于大家平常喝的牛乳时，黑芝麻中常含的蛋白质含量，但是其十几倍哦。因此冬季喝纯牛奶得话，还比不上吃黑豆。黑芝麻除开营养成分高之外，其还含有了丰富不饱和脂肪酸，维他命等养分。这种营养元素，针对中老年人好朋友而言，全是十分有益于身文身心健康的，能防止各种各样血压高病症。此外，冬天吃黑豆，也有不错的护肝润肺功效哦。六莲藕针对莲藕这类食物，有一句老话是那样说的， “荷莲一身 QL ，秋藕最补人。因而刚进到冬天的情况下，恰好是莲藕很多发售的时节，由于莲藕的采收时节，归属于初秋时节。因此，在应对这种刚推出的莲藕时，其营养成分是十分丰富的，尤其合适服用。小小莲藕，请别看他看起来不咋滴，可是它的营养成分则是十分高的，其內部含有了充足的营养元素，膳食纤维，铁，钾等营养元素，尤其合适女性服用。冬季胃口不太好的好朋友，就可以多吃一些莲藕，有有效的改进胃口功效。好啦，以上是今日我想给大伙儿介绍的， 6 种冬天要多吃的食材。在应对这 6 种食材的情况下，你觉得哪一种食材，才算是冬天最补身 ble 的呢？热烈欢迎各位在评论留言板留言，说一说你的观点。实际上除开这 6 种食材之外，冬天也有许多食材，全是很滋补养生身文的。假如你那边有更强掌握得话大还可以给大家建议一下，你冬天全是吃什么食物，的滋补养生身的！这篇文章照片及文章资料来自互联网技术，用以沟通交流学习培训沟通交流学习和科学研究。 If there is incorrect information in the conversion of the text or an incorrect violation of the data of the article, please contact us for removal and correction.	2	29	0	0	4	0.931202	4	32,457
In health care circles these days, you hear about the social determinants of health (SDOH) almost as often as you hear: “You’re on mute!” SDOH are the conditions in the places where people are born, live, learn, work, play, worship, and age that affect health outcomes. These non-medical factors like income, socioeconomic status and access to health care, safe housing, and reliable transportation drive more than 80 percent of health outcomes. Conversely, medical care accounts for no more than 20 percent of patient outcomes — very sobering. International Classification of Diseases (ICD) codes, published by the World Health Organization, are used to classify diseases and related health problems. ICD, Tenth Revision, Clinical Modification (ICD-10-CM) codes have been used in the U.S. since 2015. ICD-10-CM contains a subset of codes, Z55–Z66, the SDOH-related Z codes, that are used to document SDOH-related data. The coding guidelines initially required documentation by a physician for these Z codes to be reported. So unmet social needs documented by non-physicians, such as social workers and nurses, could not be reported. To promote the utilization of Z codes, the American Hospital Association provided clarification in 2018 that allowed unmet social needs documented by non-physicians to be used by coders to assign SDOH-related Z codes. Although this change was associated with an increase in utilization, SDOH-related Z codes remain underutilized. An analysis of utilization of Z codes for SDOH among Medicare fee-for-service (FFS) beneficiaries found that among the 33.1 million continuously enrolled Medicare beneficiaries in 2019, 1.59 percent had claims with Z codes — an increase from 1.31 percent in 2016. The top five categories of clinicians providing codes were physicians in family medicine, internal medicine and psychiatry, nurse practitioners and licensed social workers. The five most utilized codes were Z59.0 (homelessness), Z63.4 (disappearance and death of family member), Z60.2 (problems related to living alone), Z59.3 (problems related to living in a residential institution), and Z63.0 (problems in a relationship with spouse or partner). Barriers to the documentation of Z codes include lack of clarity on who can document patients’ social needs, lack of systems and processes for documenting and coding social needs, unfamiliarity with SDOH-related Z codes and a low priority placed on the collection of this data previously. Additional barriers have included lack of financial incentive as Z codes have not generally been used for payment purposes, the limited number of Z codes, limited or lack of training regarding Z codes — and clinicians feeling limited in what they can do and/or requiring guidance in assisting patients once non-medical needs have been identified. As of January 1, 2021, evaluation and management (E/M) coding for office and outpatient services changed significantly such that coding is based either on the level of medical decision making (MDM) or the total time spent performing the service on the day of the encounter. The three elements of MDM include the number and complexity of problems addressed during the encounter, the amount and/or complexity of data reviewed and analyzed, and the risk of complications and/or morbidity or mortality of patient management decisions made at the visit. The four levels of MDM are straightforward, low, moderate, and high. To qualify for a level of MDM, two of the three elements for that level must be met or exceeded. Diagnosis or treatment significantly limited by SDOH is an example of moderate risk. Documenting an SDOH-related Z code when relevant to the patient encounter gets risk to moderate. If either of the other two MDM elements is also moderate, the encounter can be coded at the moderate level (Level 4). The ability to incorporate Z codes into E/M coding in 2021 may facilitate increased utilization and could significantly impact disease management, population and public health, and reimbursement. My excitement is dampened by the realization that the increase in the utilization of these Z codes may not be as substantial as one would hope. There are key considerations for effectively incorporating this into my practice: - All members of my patient’s care team must be aware that they can collect SDOH-related data. - Training in the collection and reporting of SDOH-related data is required for all team members. - The process cannot be cumbersome and must not significantly disrupt workflow. A process that is tedious and involves multiple additional mouse clicks or navigation across multiple screens in the electronic medical record (EMR) would not be easily integrated or sustainable in a busy practice. - Systems must be in place to connect my patients with the appropriate services to address their unmet social needs. Otherwise, why put a patient in the position of disclosing vulnerable information simply to collect data? Without a clear, user-friendly process for referral to social services, it would feel like I’m opening a can of worms and taking responsibility for an issue that I am not equipped to address. So, how do I envision this working? Let’s say I’m seeing a new patient with an overactive bladder. She indicates that she is experiencing homelessness on a social needs screening tool, which is available in hard copy and online and can be self-administered or administered by clinic staff. We discuss the impact of homelessness on her ability to implement behavioral/dietary modification and complete a voiding diary. I document ICD-10 codes N32.81 (overactive bladder) and Z59.0 (homelessness). Entering Z59.0 into the EMR triggers an automatic pop-up for a referral to the social worker and automatically populates the patient’s visit instructions with links to resources such as FindHelp.org, where she finds resources for free or reduced-cost services and programs like financial and housing assistance and food pantries. In this ideal scenario, a social worker will be available and have appropriate funding, and documentation of this patient’s unmet social needs does not require 20 mouse clicks and a million pop-ups. Now we come back to reality where documentation of unmet social needs is a daunting task if clinicians must bear the brunt of the work for connecting each patient with the appropriate social services. Provision of the necessary social services will require the investment of time, funding, and human resources. A collaborative systems-based approach involving hospital systems, insurers, community-based organizations, and local and federal government will be needed to ensure that clinicians in large hospital systems and solo practices alike are provided with the tools needed to help address their patients’ unmet social needs. The Congressional SDOH Caucus launched in July 2021 to “explore opportunities to improve the impact of services delivered to address social determinants with the support of federal funding.” This bipartisan caucus will highlight the opportunities to coordinate federal investments in SDOH such as health, food, housing, and transportation. There are currently 163 SDOH and 52 health equity/disparities bills in Congress, an increase from 31 SDOH and 23 health disparities bills in the previous Congress. Clearly, SDOH is getting a lot of attention. I am cautiously optimistic that will translate into meaningful change for affected patients. Gjanje L. Smith is a urologist. Image credit: Shutterstock.com	3	6	0	0	7	0.673592	7	1,534
NORD gratefully acknowledges Andrew G. Engel, MD, Department of Neurology and Muscle Research Laboratory, Mayo Clinic, for the preparation of this report. The congenital myasthenic syndromes (CMS) are a diverse group of disorders that have an underlying defect in the transmission of signals from nerve cells to muscles. These disorders are characterized by muscle weakness, which is worsened upon exertion. The age of onset, severity of presenting symptoms, and distribution of muscle weakness can vary from one patient to another. A variety of additional symptoms affecting other organ systems can be present in specific subtypes. Severity can range from minor symptoms such as mild exercise intolerance to severe, disabling ones. Most CMS are transmitted by autosomal recessive inheritance; a few specific subtypes are transmitted by autosomal dominant inheritance. Genetic diagnosis these disorders is important because therapy that benefits one type CMS can worsen another type. The CMS involve the neuromuscular junction which is a synapse where signals from motor nerves are passed to muscle fibers and tell the muscles fibers when to contract. The normal neuromuscular junction consists of a presynaptic region, a synaptic space, and a postsynaptic region. The presynaptic region contains the end of a motor nerve cell called the motor nerve terminal. The motor nerve terminal overlies a specialized region of the muscle fiber called the postsynaptic region. The space between the motor nerve terminal and the postsynaptic region is called the synaptic space or synaptic cleft. The postsynaptic region displays multiple folds, known as junctional folds. The motor nerve terminal contains small vesicles that are filled by the neurotransmitter, acetylcholine, or ACh for short that acts as a chemical ‘messenger’ with instructions for the muscles to contract. The membrane covering the motor nerve terminal and facing the synaptic space is known as the presynaptic membrane. The membrane covering the postsynaptic region is known as the postsynaptic membrane. The segment of the postsynaptic membrane that covers the tips of junctional folds is lined by molecules of the acetylcholine receptor, or AChR for short. The synaptic space is lined by a membrane known as the synaptic basement membrane. This membrane anchors molecules of acetylcholinesterase, or AChE for short, an enzyme that converts ACh to acetate and choline. The process of how the motor nerve endings communicate with the muscle fibers is a highly specialized process and a genetic defect that impairs that communication can result in a congenital myasthenic syndrome. Understanding this process helps to understand myasthenic disorders. When muscles are in the resting state, there is a randomly occurring release of acetylcholine from single synaptic vesicles in the motor nerve terminal. This release is known as exocytosis. The amount of ACh released from a single synaptic vesicle is referred to as a quantum of ACh. ACh released from a synaptic vesicle travels through the synaptic space and binds to the AChRs that are concentrated on the tips of the junctional folds. When this binding occurs, it causes a channel in the center of AChR to and allows positively charged sodium and lesser amounts of calcium ions to enter the muscle fiber. This process briefly changes the electric charge across the postsynaptic membrane from negative to positive (small postsynaptic depolarization) which is referred to as a miniature endplate potential (MEPP). When a person wants to perform a voluntary action, (e.g. raising one’s hand, dancing, kicking a ball, etc.), a series of successive nerve impulses are sent to the motor nerve terminal where they depolarize the presynaptic membrane, causing structures called voltage-gated calcium channels to open which allows calcium to enter the motor nerve terminal. This calcium influx results in a nearly synchronous release of the contents of several synaptic vesicles which results in a larger depolarization of the postsynaptic membrane, known as the endplate potential (EPP). When the EP reaches a certain threshold, it opens voltage-gated sodium channels found along the entire muscle fiber outside of the motor endplate area and this triggers a propagated muscle fiber action potential which causes the muscle fiber to contract. The difference between the endplate potential and the depolarization required to activate the voltage-gated sodium channels is known as the safety margin of neuromuscular transmission. In healthy individuals, the amplitude of the EPP is quite large. With continued activity the EPP begins to decrease but still remains large enough to trigger a muscle fiber action potential. After the muscle contracts, ACh is released from the AChRs into the synaptic space) where it is broken down (hydrolyzed) by AChE into two molecules, acetate and choline. Choline is transported back into the nerve terminal where it recombines with acetate under the influence of an enzyme known as choline acetyltransferase to be stored once again within the synaptic vesicles. The factors governing the safety margin of neuromuscular transmission fall into four major categories: (1) factors that affect the number of ACh molecules in the synaptic vesicle; (2) factors that affect quantal release mechanisms; (3) the density of AChE in the synaptic space; and (4) factors that affect the efficacy of individual quanta. The efficacy of individual quanta depends on the endplate geometry, the packing density of AChRs on the tips of the junctional folds, the affinity of AChRs for ACh, and the kinetic properties of the AChR ion channel. Congenital myasthenic syndromes are caused when there is an alteration (mutation) in a specific gene. This results in an abnormal protein or even loss of a protein that impairs some part of the process described above. The abnormal protein (disease protein) can reside in the motor nerve terminal, or the synaptic space, or in the postsynaptic region that underlies the nerve terminal, but in some patients the disease protein is also present in others tissues or organs causing not only CMS but also a variety of other symptoms. The cardinal symptom of all myasthenic disorders is muscle weakness that is induced or worsened by exertion. This is referred to as fatigable weakness. In healthy people, physical activity causes a small decrease in the number of ACh quanta released from the nerve terminal that does not impair the safety margin of neuromuscular transmission, but it is incapacitating in myasthenic patients in whom the safety margin is already reduced. In some patients with CMS, the weakness is confined to muscles supplied (innervated) by the cranial nerves causing double vison, droopy eyelids (eyelid ptosis), facial weakness, hypernasal or slurred speech, and swallowing difficulties. In other patients, the above symptoms are combined with weakness of the limb and torso muscles causing generalized myasthenia. In still others, the weakness is limited to the limb and torso muscles causing ‘limb-girdle myasthenia’. The myasthenic disorders caused by defects in enzymes required for protein glycosylation can also be associated with development delay, seizures, intellectual disability, neuropathy, and metabolic abnormalities of different organs. Several different types of CMS have been identified.1 The currently identified types are: Each type can be subdivided into several subtypes that are discussed below. Endplate Choline Acetyltransferase (ChAT) Deficiency After acetylcholine is released from the nerve terminal, it binds to acetylcholine receptor for a brief period; when it is released from the receptor, it is rapidly broken down (hydrolyzed) by the enzyme acetylcholinesterase into choline and acetate. The released choline is transported to the nerve terminal where the enzyme choline acetyltransferase (ChAT) reforms (resynthesizes) acetylcholine. The resynthesized acetylcholine is then transported into the synaptic vesicles, where it becomes available to be released into the synaptic space as needed. Deleterious mutations in the CHAT gene, alone or in combination, alter the expression, catalytic efficiency, or stability of the ChAT protein.2,3 The defect in ChAT causes progressive decrease of the acetylcholine content of the synaptic vesicles during activity and hence reduces the amplitude of the EPP, which reduces the safety margin of neuromuscular transmission. Some patients present with hypotonia (low muscle tone), paralysis of cranial and limb muscles and apnea (failure to breathe) at birth. Others are normal at birth and develop attacks of apnea during infancy or childhood precipitated by infection, excitement, or no apparent cause.3-7 In some children an acute attack is followed by respiratory failure that lasts for weeks.8 A few patients are respirator-dependent and paralyzed since birth3 and some develop brain atrophy caused by lack of oxygen (hypoxia) during episodes of apnea.3,7 Others improve with age, but still have variable eyelid drooping (ptosis), impaired movement of the ocular muscles, fatigable weakness, and recurrent episodes of cyanosis, in which there is bluish discoloration of the skin due to impaired respiration and inadequate oxygenation of the blood. Some patients complain only of mild to moderately severe fatigable weakness. The weakness is worsened by exposure to cold because this further reduces the efficiency of the mutant enzyme.5 Treatment consists of preventive (prophylactic) therapy with pyridostigmine (Mestinon) which is a medication that inhibits the activity of acetylcholinesterase (which breaks down acetylcholine in the synaptic space). This prolongs the life time of acetylcholine in the synaptic space and, consequently, the number of acetylcholine receptors it can activate. Parents of affected infants should be provided an inflatable rescue bag and a fitted mask, and should be instructed in the intramuscular injection of neostigmine methylsulfate (another inhibitor of acetylcholinesterase), and are advised to install an apnea monitor in their home. A single patient reported to date had a severe CMS associated with an unusually exaggerated response to brain stimuli (cerebral cortical hyperexcitability), ataxia (lack of coordination), and intellectual disability.9 Genetic studies revealed a dominant single amino acid change in the gene SNAP25B, which produces an essential protein required by the synaptic vesicles to release acetylcholine (exocytosis). The endplates were structurally normal on examination by the electron microscope. Treatment with 3,4-diaminopyridine (3,4-DAP), which increases the number of quanta released by nerve impulse, improved the patient’s weakness but not her ataxia or intellectual disability. Synaptotagmin 2 Deficiency Synaptotagmin 2 is another presynaptic protein. It senses the calcium concentration in the nerve terminal; when this is increased, it acts on other proteins to initiate the release of acetylcholine into the synaptic space (exocytosis). In two kinships, mutations in this gene caused limb muscle weakness, loss of the tendon reflexes, and a reduced amplitude of the muscle fiber action potential that precedes muscle fiber contraction. This response as well as the weakness was transiently improved by exercise. The treatment of this condition has not been described.10 Paucity of Synaptic Vesicles and Impaired Quantal Release The clinical features resemble that of autoimmune myasthenic gravis, but the onset is at birth or in early infancy and tests for anti-acetylcholine receptor antibodies are negative. A specific diagnosis requires electron microscopy and electrophysiology studies of the motor endplate. A presynaptic defect is revealed by a severe decrease (to approximately 20% of normal) in quantal release of acetylcholine by nerve impulse accompanied by a proportionate decrease in the number of synaptic vesicles in the nerve terminal. This CMS responds to treatment with pyridostigmine.11 SYNAPTIC BASAL LAMINA-ASSOCIATED Endplate Acetylcholinesterase (AChE) Deficiency The endplate species of acetylcholinesterase (AChE) is composed of 12 catalytic subunits, which rapidly breaks down (hydrolyzes) acetylcholine, plus a collagenic subunit, called ColQ, which anchors the entire molecule to the basal lamina of the endplate. Subunits are single protein molecules that combine with other proteins to form a larger protein complex. The ColQ protein is composed of three identical strands each of which binds to 4 catalytic subunits. Histochemical and electron microscopy studies reveal absence of acetylcholinesterase from the endplate and smaller than normal nerve terminals. Severely affected patients present at birth with apnea and generalized weakness that persists throughout life. Less severely affected patients present later in childhood.12 The patients do not respond to, or are worsened by, pyridostigmine which acts by inhibiting acetylcholinesterase. Therapy is still unsatisfactory, but ephedrine13 and albuterol14 have a gradually developing beneficial effect. CMS Associated with β2-Laminin Deficiency β2-laminin is a component of the basal lamina of different tissues and is highly expressed in kidney, eye, and at the endplate where the protein is important for the appropriate alignment of the nerve terminal with the postsynaptic region. β2-laminin also contributes to the development and organization of the two regions. Mutations in β2-laminin result in Pierson syndrome, a rare disorder associated with malformations of the kidneys and eyes. A patient with Pierson syndrome had a myasthenic syndrome. The kidney defect was corrected by renal transplant at age 15 months. Quantal release by nerve impulse and the MEPP amplitude were both reduced. Electron microscopy revealed abnormally small nerve endings accounting for the decreased quantal release. The synaptic space was widened and the junctional folds were simplified, accounting for the decreased MEPP amplitude.15 DEFECTS IN ACETYLCHOLINE RECEPTOR (AChR) Primary AChR Deficiency The acetylcholine receptor is made up 5 subunits. Subunits are single protein molecules that combine with other proteins to form a larger protein complex; in this case, the acetylcholine receptor. Two of these subunits are called alpha (α) and the remaining 3 are called beta (β), delta (δ) and epsilon (ε) in adults. Before birth, the fetal subunit contains a gamma (γ) instead of a ε subunit. In primary AChR deficiency, the amount of AChR expressed at the endplate is reduced and the safety margin of neuromuscular transmission is impaired by the decreased amplitude of the EPP. The clinical deficits vary from mild to severe. Patients with recessive mutations in the ε subunit are generally less severely affected than those with mutations in other subunits because compensatory expression of the fetal γ subunit can partially substitute for the defective ε subunit. The sickest patients have severe ocular, bulbar and respiratory muscle weakness from birth and survive only with respiratory support and gavage feeding. Gavage feeding is the use of a small, narrow tube inserted through an infant’s nostrils and run down the throat to the stomach to directly supply nourishment to an affected infant. Infants may be weaned from a respirator and begin to tolerate oral feedings during the first year of life, but have bouts of aspiration pneumonia and may need intermittent respiratory support during childhood and adult life. Motor development is severely delayed; they seldom learn to take steps and can walk for only for a short distance. Older patients close their mouths by supporting their jaw with their hand and elevate their eyelids with their fingers. Facial deformities, protruding jaw, misalignment teeth (malocclusion), and abnormal curvature of the spine such as scoliosis or kyphoscoliosis become noticeable during the second decade. Muscle bulk is reduced. The tendon reflexes are normal or hypoactive. Less severely affected patients experience moderate physical handicaps from early childhood. Limited eye movements and ptosis of the lids become apparent during the first year of life. They fatigue easily, walk and negotiate stairs with difficulty, cannot keep up with their peers in sports, but can perform most activities of daily living. Mutations in the AChR α, β, and δ subunits that reduce or prevent the expression of AChR are either lethal in embryonic life or cause marked disability and high mortality after birth. In the least affected patients motor development is only slightly delayed; they only have mild eyelid ptosis and limitation of eye movements. They are often clumsy in sports, fatigue easily, and cannot run well, climb rope, or do pushups. In some patients, a myasthenic disorder is suspected only when they develop prolonged respiratory arrest on exposure to a neuromuscular blocking agent drug during a surgical procedure. Treatment consists of pyridostigmine an inhibitor of acetylcholinesterase. This medication increases the lifetime of acetylcholine in the synaptic space which allows each acetylcholine molecule to bind to different acetylcholine receptors repeatedly before it leaves the synaptic space by diffusion. Many patients derive additional benefit from the use of 3,4-diaminopyridine (3,4-DAP)16 which prolongs the depolarization of the presynaptic membrane by nerve impulse. This allows more calcium to enter the nerve terminal which increases the number of acetylcholine quanta released by each nerve impulse. Finally, some patients derive still additional benefit from albuterol. 17 Kinetic Defect in AChR: The Slow-Channel Syndrome This syndrome is caused by dominant mutations in the acetylcholine receptor (AChR) gene that leads to the abnormally slow closure of the AChR ion channel. The prolonged openings of the ion channel cause overloading of the postsynaptic region with positively charged ions, including calcium. The local increase in calcium concentration damages the junctional folds, and can damage the muscle fiber nuclei under the folds. The onset of symptoms ranges from infancy to early adult life. The disease causes selectively severe weakness and loss of bulk (atrophy) of the cervical, scapular, and of the wrist and finger extensor muscles.18 The safety margin of synaptic transmission is compromised by damage to the junctional folds with loss of acetylcholine receptors, and by the receptors becoming desensitized (unresponsive) during physiologic activity due to prolonged exposure to acetylcholine. This syndrome does not respond to, or is worsened by, pyridostigmine but is improved by relatively high doses of fluoxetine (Prozac) which blocks (plugs) the acetylcholine receptor ion channel and thereby reduces the length of channel openings.19 Kinetic Defect in AChR: The Fast-Channel Syndrome This syndrome is transmitted by recessive inheritance and is the physiologic and anatomic opposite of the slow-channel syndrome.18 The length of the AChR channel openings is decreased because the mutations reduce the ability of AChR to bind acetylcholine, or because they hinder the opening of the AChR ion channel, or because they cause the ion channel to become intermittently unstable. The structural integrity of the endplate is unaffected. This syndrome becomes manifest only if the second copy of the AChR subunit gene is not expressed, or if both copies of the gene harbor the same mutation, so that the fast- channel mutation dictates the clinical consequences. The safety margin of neuromuscular transmission is reduced because the mutant gene reduces the probability and length of channel openings, which reduce the amplitude and duration of EPP. The clinical consequences vary from mild to severe. Most patients respond to combined treatment with pyridostigmine and 3,4-DAP. Prenatal CMS Caused by Mutations in AChR Subunits and Other Specific Proteins The first identified prenatal myasthenic syndrome was traced to mutations in the fetal AChR γ subunit. In humans, AChR harboring the fetal subunit appears on developing muscle fibers around the ninth week of gestation and becomes concentrated at early nerve-muscle junctions around the sixteenth week of gestation. Subsequently, the γ subunit is replaced by the adult ε subunit and is no longer present at fetal endplates after the thirty-first week of gestation. Thus harmful mutations of the γ-subunit reduce fetal movements (hypomotility) between the sixteenth and thirty-first week of gestation.20 The clinical consequences at birth are contractures of large joints, small muscle bulk, webbing around the neck, armpits, elbows, fingers, or behind the knees, flexion contractures of the fingers, rocker-bottom feet with prominent heels, and a characteristic facial appearance with mild eyelid ptosis and a small mouth with downturned corners. A contracture is a condition in which a joint becomes permanently fixed in a bent or straightened position, completely or partially restricting the movement of the affected joint. Myasthenic symptoms are absent after birth because by then the normal adult ε subunit is expressed at the endplates.21 Recent studies also identified lethal fetal akinesia syndromes arising from deleterious null mutations in both copies of the AChR α, β, and δ subunits as well as in other CMS disease genes. CMS CAUSED BY DEFECTS IN ENDPLATE DEVELOPMENT OR MAINTENANCE To date, mutations have been detected in genes for proteins that are essential for motor endplate development and maintenance. As with the communication of nerve signals from nerve cells to muscle fibers described above, the health and development of the motor endplate depends upon a sequence of interrelated, chemical reactions involving multiple genes and their protein products. These genes are MuSK, Agrin, LRP4, and DOK-7. Agrin is secreted into the synaptic space by the nerve terminal where it binds to the lipoprotein-related protein LRP4 in the postsynaptic membrane creating an agrin-LRP4 protein complex. The Agrin-LRP4 complex then binds to and activates MuSK. This enhances MuSK phosphorylation and leads to clustering of LRP4 and MuSK. Activated MuSK in concert with postsynaptic DOK-7 and other postsynaptic proteins acts on Rapsyn to concentrate AChR in the postsynaptic membrane, enhances synapse specific gene expression by postsynaptic nuclei, and promotes postsynaptic differentiation. Clustered LRP4, in turn, promotes differentiation of motor axons. The agrin-LRP4-MuSK-Dok-7 signaling system is also essential for maintaining the structure of the adult neuromuscular junction.22 Only a few patients with agrin-related CMS have been reported. The severity of the symptoms varies according to the location of the mutations in the agrin gene and whether or not the mutations affect agrin expression.23,24,25 The consequences are severe when a mutation that hinders attachment of agrin to LRP4 dominates the clinical picture. In such a patient the synaptic contacts were dispersed, the postsynaptic regions were poorly differentiated, the nerve terminals were small, and there were degenerative changes in the muscle fibers under the junctional folds.24 Another report describes three kinships in which the agrin mutations were associated with slowly progressive wasting of the distal leg and later of the upper arm muscles.25 Treatment of the agrin-related CMS is unsatisfactory, but one patient responded partially to ephedrine.24 There are only two reports of LRP4-related CMS. The first report described a 17-year-old girl with moderately severe fatigable limb-girdle weakness, irregularly shaped synaptic contacts, and mild endplate AChR deficiency. In a muscle located between the ribs (intercostal muscle) of this patient the MEPPs and EPPs were of normal amplitude indicating the identified mutations could spare neuromuscular transmission in some muscles.26 Subsequently, two sisters with moderately severe CMS and harboring a homozygous mutation that hinders LRP4 from activating MuSK were shown to have structurally and functionally abnormal endplates and endplate AChR deficiency.27 This disease presents at birth or in early life with eyelid ptosis or respiratory distress. Subsequently, it involves the ocular, facial and proximal limb muscles, and in some kinships the bulbar muscles as well.28,29,30,31,32 Introduction of the mutant gene in mice results in recurrent cycles of focal loss of nerve supply (denervation) and reestablishment of nerve supply (reinnervation) resulting in extensive remodeling of the endplates.33 Pyridostigmine therapy is ineffective or worsens the disease.31 A recent report indicates that therapy with albuterol has been highly effective in two brothers.34 No clear genotype-phenotype correlations (correlation between a given mutation and the clinical features) have been observed. DOK-7 is expressed within developing and mature muscle fibers. In developing muscle fibers it serves as an intrinsic activator of MuSK.35 In mature muscle, it is activated by MuSK to activate rapsyn to concentrate acetylcholine receptors on the junctional folds and to promote the development and maintenance of the endplate. This CMS can be mild or severe. The pathogenic mutations can curtail DOK-7 expression or prevent DOK-7 to activate, or be activated by, other intracellular proteins. There appears to be no consistent correlation between the identified mutations and the clinical features. All affected patients have limb-girdle weakness with lesser facial and neck muscle weakness but a few have severe bulbar weakness and few have significant limitation of the eye movements.36,37 The clinical course is mild to severe. Impaired maintenance of the endplates is evidenced by ongoing destruction and remodeling of the endplates. Neuromuscular transmission is compromised by the decreased quantal release from the nerve terminal by nerve impulse and by a reduced amplitude of the MEPP.37 Importantly, this CMS is rapidly worsened by pyridostigmine but responds well over a period of time to ephedrine38 or albuterol.37 Rapsyn concentrates and anchors acetylcholine receptors on the junctional folds39 and is required for development of the junctional folds.40 Most patients present in the first year of life.41 Joint contractures at birth and other congenital malformations occur in close to one-third.42 Intercurrent infections or fever can trigger respiratory crises that can cause brain damage due to lack of oxygen (anoxia). 43,44 The eye movements are intact in most patients.42 Multiple synaptic contacts appear on single muscle fibers. The endplate acetylcholine receptor deficiency is milder than in primary acetylcholine receptor deficiency42 and the junctional folds are not well differentiated. Most patients respond well to pyridostigmine; some derive additional benefit from ephedrine or albuterol43 and some are further improved by 3,4-DAP. Indo-Europeans harbor a common N88K mutation in the gene that produces rapsyn, which involves replacement of an asparagine molecule (N) by a lysine molecule (K) at codon 8845 (codon: a sequence of 3 adjacent nucleotides that constitutes a genetic code for a specific amino acid). Different mutations hinder self-association of rapsyn molecules, or their binding to acetylcholine receptors, or impede agrin-MuSK-LRP4-mediated clustering of these receptors, or decrease rapsyn expression.40,46 There are no genotype-phenotype correlations (correlation between a given mutation and the clinical features) except that Near-Eastern Jewish patients with a homozygous E-box mutation (E-box: a sequence before the coding region of a gene involved in regulating gene expression) have a milder course with eyelid ptosis, a large protruding jaw, severe weakness of the masticatory and facial muscle, and hypernasal speech.47 MYASTHENIC SYNDROMES ASSOCIATED WITH CONGENITAL DEFECTS OF GLYCOSYLATION Glycosylation is the process by which sugar ‘trees’ or residues (glycans) are created, altered and chemically attached to certain proteins or fats (lipids). When these sugar molecules are attached to proteins, they form glycoproteins; when they are attached to lipids, they form glycolipids. Glycoproteins and glycolipids have numerous important functions in all tissues and organs. Glycosylation involves many different genes, encoding many different proteins such as enzymes. A deficiency or lack of one of these enzymes can lead to a variety of symptoms potentially affecting multiple organ systems. Glycosylation to nascent peptides increases their solubility, folding, stability, assembly, and intracellular transport. Peptides are amino acid compounds and can perform a wide range of functions in the body. O-glycosylation involves addition of sugar residues to the amino acids serine and threonine; N-glycosylation occurs in sequential steps that decorate the amino group of the amino acid asparagine.48,49 To date, defects in four enzymes subserving N-glycosylation have been shown to cause a CMS: GFPT1,50,51 DPAGT1,52,53 ALG2, and ALG14.54 Accumulation of small tubules within the muscle fibers, referred to as tubular aggregates, are a clue to the diagnosis but are not seen in all patients. Because glycosylated proteins are present at all endplate sites, the safety margin of neuromuscular transmission is likely compromised by a combination of pre- and postsynaptic defects. GFPT1 controls the entry of glucose into the glycosylation pathway. A defect in GFPT1 predicts reduced glycosylation, and therefore defective function, of several endplate- associated proteins.50 The synaptic contacts are small and the postsynaptic regions are poorly developed .51 One patient whose mutations abolished expression of the muscle- specific exon of GFPT1 had severe facial, bulbar, and respiratory muscle weakness, and has been paralyzed since birth. She has a vacuolar myopathy, reduced quantal release evoked by nerve impulse, and low MEPP amplitude. A vacuolar myopathy is a muscle disease that is associated with the development of abnormal pockets or spaces called vacuoles within muscle tissue. DPAGT1 catalyzes the first committed step of N-linked protein glycosylation. DPAGT1 deficiency predicts impaired asparagine glycosylation of multiple proteins distributed throughout the organism, but in the first 5 patients harboring DPAGT1 gene mutations only neuromuscular transmission was adversely affected.52 A subsequent study of two siblings and of a third patient showed the DPAGT1 deficiency associated with intellectual disability.9 The siblings respond poorly to pyridostigmine and 3,4-DAP; the third patient was partially improved by pyridostigmine and albuterol. Intercostal muscle studies showed fiber type disproportion, small tubular aggregates in some muscle fibers, and autophagic vacuoles (vacuoles that degrade and digest subcellular structures). Evoked quantal release, the MEPP amplitude, and the endplate acetylcholine receptor content were all reduced to ~50% of normal. ALG2 AND ALG14 Deficiency ALG2 catalyzes the second and third committed steps of N-glycosylation. In one family, four affected siblings had a deleterious homozygous mutation, and a third patient was homozygous for a low-expressor mutation. ALG14 forms an enzyme complex with ALG13 and DPAGT1 and also contributes to the first committed step of N-glycosylation. In one family two affected siblings carried two different recessive mutations. Endplate ultrastructure and parameters of neuromuscular transmission were not investigated.54 OTHER CONGENITAL MYASTHENIC SYNDROMES PREPL Deletion Syndrome The hypotonia-cystinuria syndrome is caused by recessive deletions involving the SLC3A1 and PREPL genes at chromosome 2p21. The major clinical features are cystinuria, growth hormone deficiency, muscle weakness, eyelid ptosis, and feeding problems. Cystinuria is an inherited metabolic disorder characterized by the abnormal movement (transport) in the intestines and kidneys, of certain organic chemical compounds (amino acids). A patient with isolated PREPL deficiency had myasthenic symptoms since birth and growth hormone deficiency but no cystinuria, and responded transiently to pyridostigmine during infancy.55 She harbors a paternally inherited nonsense mutation in the PREPL gene and a maternally inherited deletion involving both PREPL and SLC3A1; therefore the PREPL deficiency determines the phenotype. PREPL expression was absent from the patient’s muscles and endplates. Endplate studies revealed decreased evoked quantal release and small MEPP amplitude despite robust endplate acetylcholine receptor expression.55 Because PREPL is an essential activator of the clathrin associated adaptor protein 1 (AP1),56 and AP1 is required by the vesicular acetylcholine transporter to fill the synaptic vesicles with acetylcholine,57 the small MEPP is attributed to a decreased vesicular content of acetylcholine. Two patients with this syndrome have been identified to date. The first patient had abrupt episodes of respiratory and facial weakness associated with weakness of muscles required for speaking and swallowing since birth lasting from 3 to 30 minutes typical of periodic paralysis as well as a myasthenic disorder. Studies of neuromuscular transmission revealed normal amplitude EPPs that frequently failed generate muscle action potentials pointing to voltage-gated sodium channels (SCN4A gene) as the culprit. The gene for voltage-gated sodium channels (SCN4A) harbored two recessive mutations which caused the sodium channel to become inactive soon after it was activated by the EPP.58 A second patient with similar clinical findings was recently identified. In this patient two different recessive mutations in voltage-gated sodium channel caused abnormal inactivation of the sodium (Na) channel by activity.59 CMS Caused by Plectin Deficiency Plectin, encoded by the PLEC gene, has different tissue-specific and organelle-specific forms (known as isoforms) that serve to link cytoskeletal filaments to target organelles.60-62 Organelles are a general term for any number of organized or specialized structures within a living cell. Plectin is concentrated at sites of mechanical stress. For example, in skeletal muscle it is present under the junctional folds of the endplates, under the surface membrane of the muscle fiber, at the Z-disks (thin protein bands that mark the boundaries of adjoining contractile units), and around nuclei and mitochondria, which are found by the hundreds within virtually every cell of the body and which generate most of the cellular energy. In skin, it is associated with hemidesmosomes (peg-like structures that link epithelial cells to the underlying basement membrane). Alone or in combination, mutations in plectin can result in a blistering skin disease known as epidermolysis bullosa simplex (EBS), in progressive muscular dystrophy, and sometimes in a myasthenic syndrome. The two patients investigated by the author had EBS, a myasthenic syndrome due to low amplitude MEPPs caused by degenerating junctional folds, as well as muscular dystrophy associated with dislocation of the muscle fiber nuclei, mitochondria and myofibrils (basic rod-like units of muscle cells) as well as defects in the muscle fiber surface membrane causing calcium overloading and degeneration of the muscle fibers.63 CMS Associated with Defects in the Mitochondrial Citrate Synthase Carrier SLC25A1 The SLC25A1 gene encodes a transporter protein that is responsible for the movement of citrate across the inner membranes of mitochondria. Mutations in the SLC25A1 gene interfere with brain, eye, and psychomotor development.64 Two siblings born to consanguineous parents had a CMS associated with intellectual disability and whole exome sequencing revealed they carried a homozygous mutation in SLC25A1. Subsequent studies showed that the mutation impairs the transport activity of the enzyme, and that knockdown of the gene equivalent to SLC25A1 in zebra fish hindered motor axons from innervating muscle fibers.65 A third patient who harbored two recessive mutations in SLC25A1 had myasthenic symptoms as well underdeveloped optical nerves, undeveloped corpus callosum (a structure connecting the two cerebral hemispheres), and excessive urinary excretion of 2-hydroxyglutaric acid.64 CMS Associated with Centronuclear Myopathies Eyelid ptosis, weakness of the external ocular and facial muscles, exercise intolerance, a decremental EMG study, and response to pyridostigmine have been documented in patients with centronuclear myopathies (CNM) caused by mutations in amphiphysin (BIN1),66 myotubularin (MTM1),67 and dynamin 2 (DNM2)68 as well as in other CNM patients with no identified mutations.69 Congenital myasthenic syndromes are caused by alterations (mutations) in specific genes. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body. Approximately 30 different genes are known to cause CMS. These genes contain instructions for proteins that are essential for the proper function or health of the neuromuscular junction and the motor endplate. Some of these proteins are found in other areas of the body and, in those subtypes, other areas of the body in addition to the neuromuscular junction can be affected. In some individuals with CMS, no altered gene has been found indicating that additional, as-yet-unidentified genes exist that can cause a congenital myasthenic syndrome. In most subtypes, CMS are inherited as autosomal recessive traits. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females. Specific CMS subtypes, specifically SNAP25, synaptotagmin 2, and the slow-channel-myasthenic syndrome are transmitted by autosomal dominant inheritance. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females. A generic diagnosis of a CMS can be made on clinical grounds from a history of fatigable weakness involving ocular muscles, bulbar muscles (muscles of the face, and muscles used for speaking and swallowing), and limb muscles since infancy or early childhood, a history of similarly affected relatives, and a variety of tests. Such tests include a decremental electromyographic (EMG) response, and negative tests for antibodies against the acetylcholine receptor (AChR) and the muscle specific receptor tyrosine kinase (MuSK). However, in many CMS patients the family history is negative; in others the onset is delayed, the EMG abnormalities are not present in all muscles or are present only intermittently, and the weakness has a restricted distribution. An electromyography or EMG test records electrical activity in skeletal (voluntary) muscles at rest and during muscle contraction. The decremental EMG response is measured by stimulation of a motor nerve to muscle at a rate of 2 to 3 times per second; the evoked electrical responses from muscle, known as compound muscle action potentials, or CMAPs, are recorded by electrodes placed on skin overlying the stimulated muscle. The response is abnormal if the fourth evoked CMAP is more than 10% smaller than the first evoked CMAP. Single fiber EMG is a more sensitive but less specific test for a myasthenic disorder. In this test, single intramuscular nerve fibers are stimulated repetitively and the evoked single fiber action potentials are recorded simultaneously from 2 to 4 muscle fibers at a time. An abnormally increased variability in the time-locked firing of individual action potentials is an early indicator of a defect in neuromuscular transmission.1 A specific diagnosis of a CMS depends on identifying the disease gene and the pathologic mutations in that gene. Commercially available studies can readily detect mutations in previously identified types of CMS. Mutations in previously unrecognized types of CMS can be detected by whole exome sequencing or whole genome sequencing but the bioinformatic analysis of the obtained result remains challenging. Genetic diagnosis of the CMS is important because therapy that benefits one type CMS can worsen another type. There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the CMS overall and that fact that certain subtypes have only been identified in a handful or fewer individuals, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with CMS. As stated above, it is critically important to identify the specific subtype in each individual as medications that prove effective for one type of CMS may be ineffective or even harmful in another. More detailed treatment information for specific subtypes of CMS is discussed in the “Signs and Symptoms” section above under each individual subtype listing. Current therapies for CMS include medications known as cholinergic agonists such as pyridostigmine or amifampridine (3,4-diaminopyridine), long-lived open channel blockers of acetylcholine receptor ion channel fluoxetine and quinidine, and adrenergic agonists such as salbutamol and ephedrine. Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site. For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office: Toll-free: (800) 411-1222 TTY: (866) 411-1010 Some current clinical trials also are posted on the following page on the NORD website: For information about clinical trials sponsored by private sources, in the main, contact: For more information about clinical trials conducted in Europe, contact: Engel AG, Shen,X.M., Sine,S.M. 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Haeuptle MA, Hennet T. Congenital disorders of glycosylation: An update on defects affecting the biosynthesis of dolichol-linked oligosaccharides. Hum Mutat. 2009;30:1628-1641. 49. Freeze HH, Chong JX, Bamshad MJ, Ng BG. Solving glycosylation disorders: Fundamental approaches reveal complicated pathways. Am J Hum Genet. 2014;94:161-165. 50. Senderek J, Muller JS, Dusl M, et al. Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect. Am. J. Hum. Genet. 2011;88:162-172. 51. Selcen D, Shen XM, Milone M, et al. GFPT1-myasthenia: Clinical, structural, and electrophysiologic heterogeneity. Neurology. 2013;23:370-378. 52. Belaya K, Finlayson S, Slater C, et al. Mutations in DPAGT1 cause a limb-girdle congenital myasthenic syndrome with tubular aggregates. Am J Hum Genet. 2012;91:1-9. 53. Selcen D, Shen XM, Li Y, Stans AA, Wieben E, Engel AG. DPAGT1 myasthenia and myopathy. Genetic, phenotypic, and expression studies. Neurology. 2014;82:1822-1830. 54. 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Ann Neurol. 2015;77:840-850. 60. Elliott CE, Becker B, Oehler S, Castanon MJ, Hauptmann R, Wiche G. Plectin transcript diversity: identification and tissue distribution of variants with distinct first coding exons and rodless isoforms. Genomics. 1997;42:115-125. 61. Fuchs P, Zorer M, Rezniczek GA, et al. Unusual 5′ transcript complexity of plectin isoforms: novel tissue- specific exons modulate actin binding activity. Hum Mol Genet. 1999;8:2461-2472. 62. Konieczny P, Wiche G. Muscular integrity – a matter of interlinking distinct structures via plectin. In: Laing NG, ed. The sarcomere and skeletal muscle disease: Springer; 2008:165-175. 63. Selcen D, Juel VC, Hobson-Webb LD, et al. Myasthenic syndrome caused by plectinopathy. Neurology. 2011;76:327-336. 64. Edvardson S, Porcelli V, Jalas C, et al. Agenesis of corpus callosum and optic nerve hypoplasia due to mutation in SLC25A1 encoding the mitochondrial citrate transporter. J Med Genet. 2013;50:240-245. 65. 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What the Anesthesiologist Should Know before the Operative Procedure As a group, patients undergoing ophthalmic surgery have a low risk of developing perioperative cardiac complications, but frequently have associated medical conditions associated with the extremes of age. Nitrous oxide (N2O) can increase intraocular pressure and cause blindness in patients who recently had a medical gas injected into the eye (a treatment for retinal detachment). To avoid this complication, N2O should not be used for patients who have had SF6 injected within the previous 4 weeks or C3F8 injected within the previous 3 months. 1. What is the urgency of the surgery? What is the risk of delay in order to obtain additional preoperative information? Most ophthalmic operations are elective. As a general rule medical conditions should be optimized before ophthalmic surgery. Emergent: Chemical burn, central retinal artery occlusion, and acute glaucoma (unresponsive to medication) are ophthalmic emergencies and require operations as soon as possible to improve the chance of maintaining vision in the affected eye. Urgent: Ruptured globe is considered an urgent case. Surgery should generally be performed within 24 hours of injury to reduce the chance of endophthalmitis from developing. Detached retinas are also considered to require urgent repairs if the macula is attached to the retina. In this situation surgery is usually performed within 24 hours of the diagnosis to reduce the risk of the macula detaching. (Macular detachment is associated with a poorer visual outcome.) However, surgery for a ruptured globe or a detached retina can generally be delayed until acute medical conditions are optimized. Elective: Most other eye operations are elective and can be delayed if necessary until the patient is optimized for surgery. 2. Preoperative evaluation The goals of a focused history and physical (H&P) are to establish a good doctor-patient relationship, assess patient risks, psychologically and physically prepare the patient for surgery, inform the patient about the risks and benefits of anesthesia, document this informed consent, assist in ensuring the correct site is operated upon, and plan for perioperative management. A good H&P will reduce the risk of perioperative delay, cancellation, and optimize perioperative care. Medical conditions should be optimized before elective ophthalmic surgery. Medical problems frequently encountered in adults include hypertension, diabetes, use of antithrombotic agents, coronary artery disease, congestive heart failure, COPD, arrhythmias, and implanted cardiac devices. Infants and children frequently present with complications of prematurity and congenital abnormalities. “Routine” preoperative labwork and electrocardiography (ECG) has not been shown to improve perioperative outcome (at any age) for low-risk surgery. Therefore, preoperative labwork and ECG are only warranted for specific medical conditions. Although there are guidelines, currently there are no nationally agreed upon preoperative lab recommendations. The guidelines we use at our institution (Massachusetts Eye & Ear Infirmary) for low-risk surgery include electrolytes for diuretic use, preoperative blood sugar for diabetics, and repeat blood sugar(s) for insulin-dependent diabetics on the day of surgery, INR for patients who took warfarin within 4 days or less before surgery, BUN/creatinine for renal dysfunction, LFTs, CBC, PT/INR, PTT for severe liver disease, and ECG for patients with cardiac disease. Because most eye operations are elective, most medically unstable conditions should be optimized before surgery. Delaying surgery may be indicated if the patient has acute respiratory illness, hypertension that is unevaluated or unresponsive to medication (systolic BP>180, diastolic BP>110), exacerbation of COPD or CHF, or a new clinically signficant arrhythmia. 3. What are the implications of co-existing disease on perioperative care? b. Cardiovascular system Acute or unstable cardiac conditions should generally be stabilized before eye surgery. Baseline coronary artery disease or cardiac dysfunction Goals of management are to minimize stress responses (e.g., tachycardia, hypertension) and maintain cardiovascular stability. A focused history is the most important method for detecting cardiovascular diseases. A preoperative ECG may be useful (as a baseline) for patients with known or suspected cardiac disease but most patients with stable cardiovascular disease can undergo ophthalmic surgery without other specialized cardiac testing. Delaying surgery or requesting additional preoperative evaluation for cardiac conditions is indicated for unstable cardiac conditions, such as MI within 30 days (7 days if additional myocardium shown not to be at risk), unstable angina, unstable CHF, unstable severe arrhythmias, and, if general anesthesia is required, undiagnosed murmurs. Other unstable cardiovascular conditions such as recent CVA or TIA may also warrant delaying surgery and obtaining additional medical evaluation. Hypertension (HTN) is a common problem in the elderly. The goal is to maintain the patient’s blood pressure (BP) in their therapeutic range such as systolic BP (SBP) <180 and diastolic BP (DBP) <110. Patients undergoing elective eye surgery with undiagnosed and untreated HTN should generally be delayed until their BP is evaluated and treated by an internist. Some patients who are anxious will have SBP> 180 and/or diastolic BP> 110 on the day of surgery despite having well-controlled BP preoperatively and are compliant with antihypertensive medication (“white coat syndrome”). For these (adult) patients, it is appropriate to administer a small dose(s) of a benzodiazine (e.g., midazolam 0.5-1 mg IV) or, if no contraindication, a beta blocker (e.g., lopressor 5 mg IV) or smooth muscle dilator (e.g., hydralazine 5-10 mg IV). Sedatives must be give judiciously so that intraoperatively, patients are aware of their surroundings and can respond to verbal commands. Allow sufficient time for the initial dose of sedative and/or antihypertensive agent to have an effect (e.g., 5-10 minutes midazolam and lopressor, 20 minutes hydralazine) before giving an additional dose. One study demonstrated treating diastolic HTN between 110-130 preoperatively on the day of surgery until BP was controlled vs cancelling surgery and making the patient return at a later date when BP was controlled showed no difference in outcomes. Patients with pacemakers and implanted cardiac defibrillators (ICDs) should be identified far enough in advance of surgery to confirm the device will continue to function appropriately in the perioperative period. Although these devices only occasionally fail unexpectedly, there are recommendations that before any surgical procedure these devices be checked. This check should include identification of the device (e.g., pacemaker? ICD? brand? model?), implanted date, date of last interrogation (our current guidelines; 6 months for pacemakers, 3 months for ICDs), has adequate perioperative battery life, the generator and leads are functioning appropriately, how the generator will respond to a magnet, and in the case of an ICD, if there have been any recent therapies for arrhythmias. (Recent therapy could increase the risk of device discharging during eye surgery, causing the patient to move.) In addition it is prudent to question the patient about any recent episodes of syncope, near syncope, and shortness of breath. (These could be signs of device malfunction or worsening underlying disease.) Patients with ICDs should also be asked about episodes of recent (known) device discharge. If present, and the device is left active intraoperatively, the patient will be at increased risk of the device delivering therapy and possibly causing patient movement. Adults with undiagnosed murmurs, or moderate or greater severity aortic stenosis, not reevaluated within the previous 12 months should have a preoperative echocardiogram evaluation to rule out significant aortic stenosis, mitral stenosis, a VSD, or an ASD before receiving general anesthesia. Children and adults with complex cardiac abnormalities, even if repaired, should receive a cardiology evaluation before undergoing general anesthesia. If general anesthesia is required in individuals with complex cardiac abnormalities or MAC or general anesthesia is required for patients with single chamber physiology, consideration should be given to performing anesthesia and surgery in a center that has experience with caring for individuals with complex congenital cardiac abnormailities. Perioperative risk reduction strategies Continue most cardiac and HTN medications up to and including the day of surgery. (Hold diuretics on the day of surgery unless required for CHF.) It is recommended to continue warfarin and other antithrombotic agents (e.g., clopidogrel [Plavix] and aspirin) for patients prescribed these medications undergoing cataract surgery. For vitrectomies and other eye operations, preoperative consultation between the ophthalmologist and patient’s internist or cardiologist is the best method to asses the perioperative risk of bleeding and develop a perioperative management strategy. Patients who had a drug eluting cardiac stent placed within the previous 12 months, or a bare metal cardiac stent within the previous 4-6 weeks, are at high risk of stent clotting if clopidogrel and/or aspirin is stopped within these periods. Elective surgery requiring stopping these medications should be delayed during these periods. If surgery is urgent and the risk of bleeding is considered to be moderate to high, generally clopidogrel is stopped and aspirin is continued perioperatively. A cardiology consultation should be considered if these drugs need to be stopped before the times outlined above. Do not administer eye drops that can exacerbate HTN (e.g., NeoSynephrine) until BP is well controlled (e.g., SBP <180, DBP <110). Administer a small additional dose of anti-anxiety and antihypertensive agents only as needed. Avoid or treat measures that increase pulse rate and BP (e.g. anxiety, pain, full bladder). If the patient is having eye pain request the surgeon to administer additional local anesthesia. For patients with a history of CHF undergoing MAC, minimize time supine. Consider having the head of the bed slightly elevated, or having the bed in reverse trendelenberg position. Determine by history, physical exam, and information from the patient’s electrophysiology lab, that pacemakers and ICDs are functioning appropriately preoperatively, and has adequate battery life to function into the perioperative period. Patients with appropriately functioning pacemakers can be operated on with no changes in routine management if a monopolar electrosurgical instrument (e.g. Bovie) is not used. (Rare for ophthalmic procedures) ICDs are commonly left active during eye operations if Bovie not used, the ICD has not delivered therapy recently, and the surgeon and anesthesia staff are warned that if an arrythmia is detected, the ICD can delivered electrical therapy with subsequent patient movement within 6-15 seconds. If indicated, most (but not all) ICDs can be temporarily inactivated by placing a magnet over the generator (after have working external defibrillator immediately in room). Preoperatively check with patient’s ICD lab, or manufacturer, how to inactivate and reactivate ICD if this might be necessary. Significant valvular lesions should be ruled out preoperatively for patients requiring general anesthesia. If general anesthesia is required in individuals with complex cardiac abnormalities, or M.A.C. or general anesthesia is required for patients with single chamber physiology, these patients should be evaluated by a cardiologist preoperatively and consideration should be given to performing anesthesia and surgery in a center that has experience with caring for individuals with complex congenital cardiac abnormailities. An acute respiratory condition (e.g., URI), or unstable chonic condition (e.g., asthma or COPD) should be ruled out by history and physical exam. For adults undergoing local anesthesia with MAC, it should be determined if the patient can lie flat for the duration of the procedure without movement or coughing. Be aware that the rare patient with pulmonary artery hypertension, will be at increased isk of morbidity and mortality if GA required. Preoperative consultation wilth a pulmonologist is recommended if GA might be required. Be aware that infants and children born prematurely with bronchopulmonary dysplasia have an increased risk of preoperative respiratory complications that may be compounded by acute pulmonary conditions Perioperative risk reduction strategies After discussion with the ophthalmologist, consider delaying surgery for acute or unstable pulmonary conditions until optimized. This might mean delaying surgery a few days to several weeks. For patients with mild asthma, a preoperative bronchodilator or nebulizer treatment may be useful. Exacerbation of severe or chronic pulmonary problems may require management by the patient’s primary care physician or pulmonologist. Patients with a history of kidney disease should have preoperative electrolytes and renal function tests if general anesthesia may be required. These tests should be repeated preoperatively on the day of surgery if the patient receiving dialysis and general anesthesia may be required. Ensure no unstable GI conditions. Inquire about a history of postoperative nausea or vomiting (PONV). Perioperative risk reduction strategies Patients requiring dialysis should be scheduled for surgery whenever possible the day after dialysis. Patients with significant kidney disease should have IV fluids that do not contain potassium. For patients with fluid restrictions the IV infusion rate should be appropriately maintained. If general anesthesia is required, be aware succinyl choline can increase serum potassium 0.5-1.0 mEq/L. Cis-atracurium may be the intermediate muscle relaxant of choice because of its nonrenal elimination and minimal hemodynamic effect. Confirm that the patient has complied with institution’s NPO guidelines before administering sedation or general anesthesia. Consider administering antiemetic(s) such as odansetron and/or dexamethasone to reduce risk of PONV if general anesthesia is required or patient has a history of PONV with MAC. Consider adding third antiemetic (e.g., scopolamine patch) and/or using TIVA techniques if patient has a significant history of PONV. Inquire about history of seizures, CVA, TIA, weakness, chronic pain, tremor, anxiety, claustrophobia, and dementia. Perioperative risk reduction strategies Request patient to continue antiseizure, chronic pain, and other essential neurologic medications to time of surgery with sip(s) water. Plan with surgeon preoperatively most appropriate anesthesia technique (e.g., MAC? GA?). If MAC, consider restraining head with tape, maintain verbal contact, reassure patient if necessary, and hold patient’s hand if patient desires. If patient is anxious, consider using clear drape, elevate drape allowing air to circulate onto patient’s face. g. Additional systems/conditions which may be of concern in a patient undergoing this procedure and are relevant for the anesthetic plan (eg. 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? As a general rule, most essential medications (e.g., most antihypertensives, cardiac, pulmonary, and antiseizure medications) are continued on their normal schedule with a sip(s) water until the time of surgery. (See more detailed recommendations below.) Some herbal medications (e.g., Ginko, ginseng). and many NSAIDs have some antithrombotic properties. h. Are there medications commonly seen in patients undergoing this procedure and for which should there be greater concern? For patients taking clopidogrel (Plavix) or other thienopyridines, or aspirin, it is important to ascertain the reason these drugs are being taken. If the patient had a cardiac stent placed within the previous year and these drugs are stopped, it may increase the risk of clotting of the stent. (See recommendations in Cardology section above.) Patients who have taken tamsulosin (Flomax) may have a floppy iris syndrome requiring use of iris hooks to perform cataract surgery and increase the length of surgery slightly. i. What should be recommended with regard to continuation of medications taken chronically? Continue most cardiac, antihypertensive, pulmonary, and antiseizure medications on schedule up to and including the day of surgery. Medications may be taken with sips of water. (Hold diuretics on the day of surgery unless required for CHF.) Request the patient to bring inhaler(s) to hospital. See recommendation regarding clopidogrel (Plavix), other thienopyridines, and aspirin above. Recent guidelines recommend continuing warfarin in therapeutic doses for cataract surgery and other procedures on superficial structures. Some studies suggest the risk of significant bleeding is small if warfarin is continued up to the day of surgery for a vitrectomy. However, there is concern by many retinal surgeons about the possibility of a significant bleeding complication in this situation. For patients who do stop warfarin several days preoperatively, and who are at moderate to high risk of developing a thrombotic complication, recent guidelines suggest considering administration of a low molecular weight heparin for several days preoperatively, with the last dose approximately 24 hours before surgery, and resuming warfarin the evening of or morning following surgery. Essential renal, neurologic (e.g., antiseizure medications), and psychiatric medications should also be continued up to the time of surgery. j. How To modify care for patients with known allergies – Ester anesthetics are avoided for patients with allergies to this class of drug (e.g., procaine [Novocain], tetracaine, chloroprocaine) and amide anesthetics (e.g., lidocaine, bupivacaine) are substituted. k. Latex allergy- If the patient has a sensitivity to latex (eg. rash from gloves, underwear, etc.) nonlatex containing gloves are used, and drugs with latex caps are removed (not punctured) when drawing up medications. The operating room staff is informed and only with latex free products are used. l. Does the patient have any antibiotic allergies- [Tier 2- Common antibiotic allergies and alternative antibiotics] Allergic reaction to antibiotics are noted and communicated to the surgeon. If the patient has a reaction to a penicillin derivative, and an antibiotic is required, another class of antibiotic is administered (e.g., clindamycin). m. Does the patient have a history of allergy to anesthesia? For patients with history of, significant risk factor for, or close family member history of malignant hyperthermia (MH) Consider regional anesthesia If general anesthesia required Ensure MH cart is available Avoid succinylcholine and inhalational agents if general anesthesia required History of sensitivity or allergic reaction to local anesthesia Determine if sensitivity likely to be epinephrine, possibly previously mixed with local anesthesia. If so, avoid epinephrine. If allergic to local anesthetic (usually ester based), use different class drug (e.g., amide). Also see above. 5. What laboratory tests should be obtained and has everything been reviewed? Preoperative labwork and ECG are only warranted for specific medical conditions. Guidelines in use (at our institution) for low-risk (eye) surgery include electrolytes for diuretic use, preoperative blood sugar for all diabetics and repeat blood sugar(s) for insulin-dependent diabetics on the day of surgery, INR for patients who took warfarin within 5 days of surgery, BUN/creatinine for renal dysfunction, LFTs, CBC, PT/INR, PTT for severe liver disease, and ECG for patients with history of cardiac disease. Hemoglobin levels: Only indicated if concerned about severe preoperative anemia (rare) Electrolytes: Indicated if taking diuretics and/or has kidney disease and GA possible. Coagulation panel: Indicated for history of bleeding diathesis. Day of surgery INR (fingerstick if possible) for patients who took warfarin 4 days or less before surgery. Imaging: Not routinely indicated. Other tests: Not routinely indicated. Intraoperative Management: What are the options for anesthetic management and how to determine the best technique? Regional anesthesia of the orbit (usually with sedation during block) and general anesthesia are the two options for providing analgesia and eye akinesia during orbital surgery. Commonly used techniques for orbital regional anesthesia include topical eye drops (mostly used for cataract surgery), extraconal block (sometime referred to as peribulbar block), intraconal block (retrobulbar block), and sub-Tenon’s block. Regional anesthesia (with or without sedation) and MAC Regional anesthesia of the orbit (topical or block), usually with sedation for needle blocks, are the most common methods of providing analgesia for adults undergoing procedures on the globe. Regional anesthesia (with MAC) Benefits: Low risk of side effects (e.g., prolonged sedation, PONV, sore throat) Drawbacks: Small risk of injury to eye and surrounding structures, small risk of systemic spread and cardiovascular instability. Increased risk of minor bleeding (e.g. skin hematoma, and conjunctiva bleeding) if taking antithrombotics. Contraindicated if infection at injection site. Issues: Need cooperative motionless patient. Not appropriate for patients who cannot lie flat for duration of procedure (e.g., has orthopnea, severe claustrophobia, severe sleep apnea,, or dementia) Slowing of heart rate from block (oculocardiac reflex) common, usually self-limited. Must be prepared to resuscitate from complications of block. (Self-inflating bag/mask, oxygen, airways, atropine, crash cart must be immediately available.) Limited access to head and neck during procedure if oversedated. Fire risk if Fio2 0.50 or greater administered around face (recommend starting Fio2 0.30 or less during surgery) CO2 can build up under drapes and cause restlessness (can dissipate CO2 by having mouth and nose exposed. If draped, have flows of at least 10 L/min of compressed air or air/oxygen mixture, or use vacuum tubing to remove CO2 buildup) b. General Anesthesia Benefits: Patient immobility and anesthesia. Drawbacks: PONV, longer time until fit for discharge, sore throat, higher risk of postoperative confusion in elderly, higher risk of cardiovascular and respiratory complications. Other issues: Must ensure patient immobility during procedure (movement can result in damage to eye). Airway concerns: Must ensure secure airway during intraorbital surgery. c. Monitored Anesthesia Care (See Regional Anesthesia above) 6. What is the author's preferred method of anesthesia technique and why? Regional anesthesia is preferred over general anesthesia because of reduced risk of PONV, reduced time to be street ready postoperatively, no sore throat, reduced risk of cardiovascular and respiratory complications, and reduced medicolegal liability from patient movement if awake. What antibiotic is given prophylactically? None routinely. Antibiotic administered only if surgeron requests it. What do I need to know about the surgical technique to optimize anesthetic care? Nitrous oxide (N20) can increase intraocular pressure and cause blindness in patients who recently had a medical gas injected into the eye. (A treatment for retinal detachment) To avoid this complication N20 should not be used for patients who have had SF6 injected within the previous 4 weeks, or C3F8 injected within the previous 3 months. Body motion during intraocular surgery can be disastrous. Every effort should be made to prevent movement during introcular surgery. Need to wait until surgeon marks eye before performing orbital block for patients having Toric lens implanted. What can I do intraoperatively to assist the surgeon and optimize patient care? Maintain normotension, prevent patient movement. What is the most common intraoperative complications and how can it be avoided/treated? Oculocardiac reflex (vagally mediated bradycardia). Avoid by minimizing traction on extraoccular muscles, consider prophylactic orbital block. Treat with anticholinergic (e.g., glycopyrrolate or atropine), orbital block. b. If the patient is intubated, are there any special criteria for extubation? To reduce the risk of straining on the endotracheal tube, many patients are extubated “deep” if they meet commonly used criteria for extubation (e.g., no signficant muscle paralysis by nerve stimulator, respiratory rate 10-18, adequate tidal volume, normothermic, no difficulty with airway or respiratory status anticipated). c. Postoperative management What analgesic modalities can I implement? Frequently acetaminophen is all that is needed for analgesia after minor eye operations (e.g., cataracts). Narcotic are usually required after orbital surgery and sometimes required after other types of ophthalmic surgery. Ketorolac should be considered for procedures likely to cause moderate or severe pain after discussion with surgeon about drug’s mild antithrombotic properties. What level bed acuity is appropriate? Most patients are discharged home on the day of surgery. Infants born prematurly (less than 36 weeks) and are less than 60 weeks gestational age are admitted overnight and monitored continuously with oximeter. What are common postoperative complications, and ways to prevent and treat them? Serious postoperative complications related to anesthesia are rare after ophthalmic surgery. Patients undergoing general anesthesia can have PONV, sore throat, and somnolence. PONV can be reduced by prophylactic antiemetics (e.g. odansetron and dexamethasone) and a TIVA techniques. Somnolence can be reduced by short actiong anesthethic agents (e.g., propofol, desflurane, remifentanil infusion). What's the Evidence? Feldman, MA, Patel, A. “Anesthesia for eye, ear, nose and throat surgery. In Miller's Anesthesia”. 2010. pp. 2378-88. (Good general review on the subject of anesthesia for ophthalmologic surgery.) Schein, OD, Katz, J, Bass, EB. “The value of routine preoperative medical testing before cataract surgery. Study of medical testing for cataract surgery”. N Engl J Med. vol. 20. 2000. pp. 168-175. (Important paper giving evidence "routine lab & EKG" do not improve perioperative outcomes for cataract surgery.). “ASA practice advisory for preanesthesia evaluation”. Anesthesiology. vol. 116. 2012. pp. 522-38. (Updated advisory of what preoperative testing is likely to be useful.) Weksler, N, Klein, M, Szendro, G. “The dilemma of immediate preoperative hypertension; to treat and operate, or postpone surgery”. J Clin Anesth. vol. 15. 2003. pp. 179-83. (Provides evidence that treating hypertension preoperatively on the day of surgery for patients with diastolic BP 110-130 had no worse outcome than canceling surgery, admitting patient and treating patient for hypertension, and performing surgery at a later date for surgery.) “ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery”. JACC. vol. 50. 2007. pp. e159-241. (Excellent general advisory on preoperative cardiac evaluation.) Douketis, JD, Berger, PB, Dunn, AS. “The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines”. Chest. vol. 133. 2008. pp. 299S-339S. (Excellent review of the literature. Gives evidence that continuing aspirin and warfarin [in therapeutic levels] perioperatively does not increase the risk of serious perioperative bleeding complications for cataract surgery.) Rozner, MA. “Implantable cardiac pulse generators: Pacemakers and cardioverter-defibrillators. In Miller's Anesthesia”. 2010. pp. 1389-409. (Excellent review on perioperative management of pacemakers, ICDs, and implanted cardiac devices for CHF.) Hart, RH, Vote, BJ, Borthwick, JH. “Loss of vision caused by expansion of intraocular perfluoropropane C3F8 gas during nitrous oxide anesthesia”. J Ophthalmol. vol. 134. 2002. pp. 761-3. (Case reports of nitrous oxide causing blindness in patients who had C3F8 gas bubble for retinal detachment.) Astrom, S, Kjellgren, D, Monestam, E. “Nitrous oxide anesthesia and intravitreal gas tamponade”. Acta Anaesthesiol Scand. vol. 47. 2003. pp. 361-2. (Case report of nitrous oxide causing blindness in patients who had SF6 gas bubble for retinal detachment.) 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: - g. Additional systems/conditions which may be of concern in a patient undergoing this procedure and are relevant for the anesthetic plan (eg. 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 (eg. rash from gloves, underwear, etc.) nonlatex containing gloves are used, and drugs with latex caps are removed (not punctured) when drawing up medications. The operating room staff is informed and only with latex free products are used. - l. Does the patient have any antibiotic allergies- [Tier 2- Common antibiotic allergies and alternative antibiotics] - 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? - a. Neurologic: - b. If the patient is intubated, are there any special criteria for extubation? - c. Postoperative management	2	15	0	0	2	0.463913	2	6,825

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