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Two readings should be taken discount 25 mg coreg free shipping; if the average is 140/90 mmHg or more order 6.25mg coreg with mastercard, an additional reading should be taken at the end of the consultation for confirmation. Blood pressure should be measured in both arms initially, and the arm with the higher reading used for future measurements. If the difference between the two arms is more than 20 mmHg for systolic pressure or 10 mmHg for diastolic pressure, the patient should be referred to the next level of care for examination for vascular stenosis. Patients with accelerated (malignant) hyperten- sion (blood pressure ≥ 180/110 mmHg with papilloedema or retinal haemorrhages) or suspected secondary hypertension should be referred to the next level immediately. Risk stratification is not necessary for making treatment decisions for these individuals as they belong to the high risk category; all of them need intensive lifestyle interventions and appropriate drug therapy (5). Each chart has been calculated from the mean of risk factors and the average ten-year event rates from countries of the specific subregion. They are useful as tools to help iden- tify those at high total cardiovascular risk, and to motivate patients, particularly to change behav- iour and, when appropriate, to take antihypertensive and lipid-lowering drugs and aspirin. An individual’s risk of experiencing a cardiovascular event in the next 10 years is estimated as follows: ● Select the appropriate chart (see Annex 3), depending on whether the person has diabetes or not. The mean of two non-fasting measurements of serum cholesterol by dry chemistry, or one non- fasting laboratory measurement, is sufficient for assessing risk. The strength of the various recommendations, and the level of evidence supporting them, are indicated as follows (13) in Table 5. High quality risk of confounding, bias or chance and a case control or cohort studies with a very significant risk that the relationship is not low risk of confounding or bias and a high causal probability that the relationship is causal 2+ Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal 2− Case control or cohort studies with a high risk of confounding or bias and a signifi- cant risk that the relationship is not causal 3 Non-analytical studies e. A body of evidence, including studies rated as 2++, is directly applicable to the target population and demonstrating overall consistency of results; or extrapolated evidence from studies rated as 1++ or 1+. A body of evidence, including studies rated as 2+, directly applicable to the target popu- lation and demonstrating overall consistency of results; or extrapolated evidence from studies rated as 2++. Low risk does nonfatal vascular nonfatal vascular fatal or nonfatal not mean “no” risk. Conservative Monitor risk profile Monitor risk profile Monitor risk profile management every 3–6 months every 3–6 months every 6–12 months focusing on lifestyle interventions is suggestedb. When resources are limited, individual counselling and provision of care may have to be prioritized according to cardiovascular risk. All smokers should be strongly encouraged to quit smoking by a health professional and supported in their efforts to do so. For individuals in low risk categories, they can have a health impact at lower cost, compared to individual counselling and therapeutic approaches. Total fat intake should be reduced to about 30% of calories, saturated fat intake should be limited to less than 10% of calories and trans-fatty acids eliminated. Most dietary fat should be polyunsaturated (up to 10% of calories) or monounsaturated (10–15% of calories). However, applying this recommendation will lead to a large proportion of the adult population receiving antihypertensive drugs. Even in some high-resource settings, current practice is to recommend drugs for this group only if the blood pressure is at or above 160/100 mmHg. Individuals in this Adults over the age Should be advised risk category should of 40 years with to follow a lipid be advised to follow persistently high lowering dietg a lipid-lowering diet serum cholesterol and given a statin. Even in some high-resource settings, current practice is to recommend drugs for this group only if serum cholesterol is above 8mmol/l (320 mg/dl). Modification of behaviour There is little controversy over the benefits to cardiovascular health of not smoking, eating a well balanced diet, maintaining mental well-being, taking regular exercise and keeping active, as demonstrated in large cohort studies. These health behaviours also play an etiological role in other noncommunicable diseases, such as cancer, respiratory disease, diabetes, osteoporosis and liver disease (86), which makes interventions to promote them potentially very cost-effective. Reducing cigarette smoking, body weight, blood pressure, blood cholesterol, and blood glucose all have a beneficial impact on major biological cardiovascular risk factors (83–88). Behaviours such as stopping smoking, taking regular physical activity and eating a healthy diet promote health and have no known harmful effects. They also improve the sense of well-being and are usually less expensive to the health care system than drug treatments, which may also have adverse effects. Further, while effects of drug therapy cease within a short period of discontinuation of treatment the impact of life style modification if it is maintained are longer standing. A variety of lifestyle modifications have been shown, in clinical trials, to lower blood pressure (89, 90). These include weight loss in the overweight (91, 92), physical activity (93, 94), modera- tion of alcohol intake (95), increased fresh fruit and vegetables and reduced saturated fat in the diet (96), reduction of dietary sodium intake (96–98), and increased potassium intake (99). It is important to recognize, however, that most of the trials of lifestyle modification have been of short duration and have tested intensive interventions, which are unlikely to be feasible in routine primary care in many countries. Still, the evidence supports the notion that it is possible to modify health behaviours and reduce blood pressure. More encouragingly, randomized trials, involving a programme of weight reduction, dietary manipulation and physical activity, reduced the incidence of type 2 diabetes among people at high risk of developing it (100–102).

While this ra¬ targeting critical appraisal exercises to may find that the structure of medical tionale appears compelling to us buy coreg 6.25mg with amex, com¬ areasin which there is likely to be high- practice must be shifted in basic ways to pelling rationale has often proved mis¬ quality evidence that will affect clinical facilitate the practice of evidence-based leading purchase 12.5mg coreg amex. Increasingly, scientific over¬ is adduced, adoption of evidence-based bers can be reduced by the availability views will be systematically integrated medicine should appropriately be re¬ of "quick and dirty" (as well as more with information regarding toxicity and stricted to two groups. One group com¬ sophisticated) coursesoncritical apprais¬ side effects, cost, and the consequences prises those who find the rationale com¬ al of evidence and by the teaching part¬ of alternative courses of action to de¬ pelling, and thus believe that use of the nerships and teaching workshops de¬ velop clinical policy guidelines. A medical residency is full of The proof of the pudding of evidence- that the practice of medicine in the new competing demands, and the appropri¬ based medicine lies in whether patients paradigm is more exciting and fun. What we do have are a number of medicine deals directly with the uncer¬ Barriers to Practicing short-term studies which confirm that tainties of clinical medicine and has the Evidence-Based Medicine the skills ofevidence-based medicine can for the educa¬ potential transforming Even ifourresidency program is suc¬ be taught to medical students35 and med¬ tion and practice of the next generation cessful in producing graduates who en¬ ical residents. These physicians will con¬ ter the world of clinical practice enthu¬ pared the graduates of a medical school tinue to face an exploding volume of siastic to apply what they have learned that operates under the newparadigm literature, rapid introduction of new about evidence-based medicine, they will (McMaster) with the graduates of a tra¬ technologies, deepening concern about face difficult challenges. A random sample of burgeoning medical costs, and increas¬ straints and counterproductive incen¬ McMaster graduates who had chosen ing attention tothe quality and outcomes tives may compete with the dictates of careers in family medicine were more of medical care. The likelihood that ev¬ evidence as determinants of clinical de¬ knowledgeable with respect to current idence-based medicine can help amelio¬ cisions; the relevant literature may not therapeutic guidelines in the treatment rate these problems should encourage be readily accessible; and the time avail¬ of hypertension than were the gradu¬ its dissemination. While strategies for inculcat¬ Some solutions to these problems are tion of the evidence-based medicine ap¬ ing the principles ofevidence-based med¬ already available. Reference to literature over- dence ofits superiority in improving pa- practices into postgraduate medical ed- Downloaded from www. AnnIn- ical journals, V: to distinguish useful from useless interim results for symptomatic patients with se- tern Med. A a diagnostic market test: lessons from the rise and Outcome-based doctor-patient interaction analysis. Rapid advances in genomics, as demonstrated by the tangible use of gene diagnosis and targeted thera- pies indicate that the impact of genomics in healthcare is only going to increase. The debate is not “if genomic medicine will impact healthcare” as much as how rapidly it will impact healthcare. However, caution needs to be exercised with respect to three key enablers whose success is critical in order to fully harvest the potential of genomics and successfully integrate genomics in healthcare. Health service organizations and healthcare leaders will play a pivotal role in this regard, by beginning to strategize and plan for how they will incorporate genomics into healthcare delivery. IntroductIon The impact of genomic medicine on healthcare continues to generate healthy debate in the literature (Epstein 2004). The availability of over 1,500 genetic tests and several targeted therapies and the use of pharmacogenomic data for drug and dosage selec-1 2 tion suggest that genomics is already integrated into healthcare and that it will be a game changer. On the other hand, there is scepticism regarding the current and future impact of genomics in healthcare because of the lack of everyday use of such technolo- gies in clinical practice, the questionable clinical utility and validity of some genetic tests and the availability of only a handful of targeted therapies amidst others that have failed clinical trials. Regardless of which position one chooses to take, recent accomplishments in genomics demonstrate that healthcare stakeholders have a remarkable opportunity – an oppor- 1 A type of treatment that uses drugs or other substances, such as monoclonal antibodies, to identify and attack specific cancer cells. Targeted therapy may have fewer side effects than other types of cancer treat- ments (National Cancer Institute N. Data from a number of recent publications and websites affirm that the current use of genomics in everyday clinical practice represents only the tip of the iceberg. In the case of chronic diseases in particular, such data will lead to significant pre-emptive measures to prevent the onset of disease years in advance of symptoms appearing. This paper examines these enablers and outlines opportunities for health service organizations and health professionals to plan for the integration of genomics in healthcare. The genetic alphabet contains four nucleotides bases – adenine, guanine, cytosine and thymine – which chemically combine in pairs: adenine with cytosine and guanine with thymine. It is estimated that there are three billion base pairs in the human genome and approximately 20,000–25,000 protein-coding genes. Clearly, the billion-plus data elements needed to define even one person’s genetic signature are several orders of magnitude more complex than the few hundred to few thousand data points in a traditional medical record. Rather than dealing with diseases after they have manifested themselves, genomics allows clinicians to look into a person’s future and determine what diseases that person is susceptible to and which drugs and interventions hold the highest likelihood for success. It changes healthcare from retrospective, interventional care to prospective, preventative care that is highly personalized and pre-emptive. The true value of genomic medicine rests in understanding and incorporating genomic information, both from clinical and research outcomes, into a person’s health record. Genomics will become an integral part of a person’s medical record for the following reasons: • The cost of sequencing an individual complete genome will decrease from hundreds of thousands of dollars to under $1,000. Genomic medicine will also have a significant impact on healthcare delivery due to its intensely personal, predictive, ethical, legal and social dimensions and impacts. She would then face emotional upheaval on learning her risk for breast and ovarian cancer and a very personal choice regarding what to do with this information (e.

The role of the newer insulin secretagogues order 6.25mg coreg with visa, the thiazolidinediones generic 25mg coreg amex, is still being evaluated in clinical trials. In most circumstances, metformin is the drug of choice for initial therapy of obese patients with type 2 diabetes and mild to moderate hyperglycaemia (370). For each patient the risk of hypoglycaemia must be considered when determining the target HbA1c level, especially in people treated with insulin and those with type 1 diabetes. Health care practitioners should be aware that more intensive glycaemic control increases the risk of hypo- glycaemia. However, it is important to set targets appropriate to the individual and in consultation with him or her. It is also important to recognize that adherence to medicines is much lower in real-life settings than in clinical trials. The results of controlled trials are unlikely to be achieved in clinical practice unless specific measures are taken to improve compliance with treatment. In summary, good glycaemic control should be a key goal of treatment of diabetes, to delay the onset and progression of microvascular and macrovascular disease. Treatment should aim to achieve: ● a fasting blood glucose level of 4–7 mmol/l (72–126 mg/dl); ● an HbA1c level of 6. The first approach to controlling glycaemia should be through diet alone; if this is not sufficient, oral medication should be given, followed by insulin if necessary. Aspirin therapy Issue Does long-term treatment with aspirin reduce cardiovascular risk? The numbers of women enrolled in most of these trials were too small to allow robust con- clusions to be drawn about the role of aspirin in primary prevention for women. In the Women’s Health study (376), women aged 45 years or older (n = 39 876) were randomly assigned to receive low-dose aspirin therapy or placebo, and followed up for 10 years. A review of observational studies (380) suggested that the background risk of major gastrointestinal complications is about 1–2 per 1000 per year at age 60 years. The excess risks attributable to aspirin are therefore 1–2 per 1000 per year at age 60. Among unselected people under 60 years, therefore, the expected benefit in terms of myocardial infarction (2 per 1000 per year avoided) does not exceed the expected risk of a major gastrointestinal bleed. Further observational studies strongly suggested that the risk of bleeding associated with aspirin increases substantially in older people, rising to 7 per1000 per year at age 80; the balance of benefit and risk, therefore, needs to be clearly defined before aspirin can recommended for all elderly people. Estimates of the rate of excess haemorrhagic stroke associated with the use of aspirin in three primary prevention trials were 0. The meta-analysis of these studies (378) also found that aspirin was associated with an increased risk of haemorrhagic stroke (summary odds ratio 1. A similar analysis using the same primary prevention studies estimated comparable effects for haemorrhagic stroke, confirming that the absolute excess risk of haemorrhagic stroke attributable to aspirin is small (around 0. Balance of risks and benefits When considering the use of aspirin, the benefits must be weighed against the possible risks associated with its use, particularly the risk of haemorrhagic stroke but also gastrointestinal bleed- ing In people at high risk, the risk–benefit ratio of aspirin therapy is favourable in some European countries and North America, but may be less favourable in populations with a high incidence of gastrointestinal bleeding or haemorrhagic stroke and a low prevalence of coronary heart disease (382). In clinical practice, physicians should consider the individual’s probable risk–benefit profile before using aspirin for primary prevention. Fixed-dose combinations As many high-risk patients would benefit from treatment with several drugs proven to reduce cardiovascular disease, the notion of a combination pill, using fixed-dose formulations of effective drugs, was originally proposed to overcome two problems: the difficulty of adherence to treatment involving multiple pills; and the inadequate dosages often prescribed in routine clinical practice (384). The polypill was conceived as a means of mass treatment for everyone over 55 years of age, regardless of their risk factor profile or estimated total cardiovascular risk. The risk reduc- tion was estimated to be 88% for coronary heart disease and 80% for stroke. While the efficacy of aspirin in men is established, for example (387), the recently completed women’s health study found no difference in all-cause mortality or fatal and non-fatal myocardial infarction between groups of women given 100 mg of aspirin every other day or placebo (388). In reviewing the evidence supporting the use of combination therapy, a recent working group report commented that: (a) the estimates of effect may have been exaggerated; (b) adherence to treatment may be low in healthy populations; (c) new studies of efficacy, effectiveness and cost- effectiveness are needed; and (d) social and behavioural issues related to population coverage, adoption, and long-term maintenance need to be examined (393). In addition, the potentially damaging effect of a mass-medication approach on population-wide public health measures for tobacco control, healthy diets and physical activity need to be considered. Commentators are gen- erally agreed on the need for further research on the combination pill, and for continued strong engagement with public health programmes for cardiovascular disease prevention (394, 395). Marketing a polypill directly to individuals without testing, thus avoiding the costs of clinical consultation, risk factor measurement and scoring, and individualized prescription of treatments, sounds tempting, but runs the risk of overtreating people who are at low cardiovascular risk and undertreating people at substantial risk. Use of the polypill to treat people who have been classi- fied according to their total cardiovascular risk does have attractions, as it would simplify selec- tion of drugs and ensure predefined doses. In summary, while a combination pill has some promise as a means of targeted treatment, it raises major challenges that would have to be addressed if it is to meet the claims made for it. Hormone therapy Issue Does hormone replacement therapy reduce cardiovascular risk?

If the level is normal patients venousheparininplaceoflow-molecular-weighthep- are defined as having unstable angina order coreg 6.25mg otc. Artery occluded Pattern of infarction r 24–72 hours: Cellular inflammation visible purchase coreg 25 mg without a prescription. If the atrioventricu- Acute myocardial infarction is caused by the occlusion lar node is involved bradyarrhythmias are common, of a coronary artery, usually as the result of rupture of although any arrhythmia is possible. The myocardium supplied by that artery eas of infarction, which cause contractile dysfunction. Myocardial infarctions due to extensive myocardial damage, rupture of the occur more commonly in the early morning possibly ventricular septum or papillary muscle leading to mi- due to increased coronary artery tone, increased platelet tral regurgitation. The latter present with worsening aggregatability and decreased fibrinolytic activity. The refractory heart failure and a loud pansystolic mur- extent and distribution of the infarct is dependent on the mur. If left untreated this has a very poor prognosis, coronary artery affected, but also on individual variation and early surgical correction should be considered. A haemopericardium develops due to exsanguination into the pericardial cavity resulting in tamponade and rapid death. This Clinical features complication tends to affect older hypertensive pa- Patients typically present with central crushing chest tients, females more than males and the left ventricle pain worse than stable angina, radiating to the jaw and more than the right. It may provoke fear of imminent death over the infarction with resulting risk of embolism. It is often associated with restlessness, breath- r Recurrent ischaemia or myocardial infarction may oc- lessness, sweating, nausea and vomiting. Signs may in- cur due to thrombus formation within the same or clude pallor, sweating, hypotension, tachycardia, raised other coronary arteries. Macroscopy/microscopy r Ventricular aneurysms may form as the collagen scar In the infarct-related artery, there is nearly always evi- that replaces the infarcted tissue formation does not dence of plaque rupture/erosion and thrombotic occlu- contract and is non-elastic. In the infarct zone a sequence of changes occurs: frequently complicated by thrombus formation but r 0–12hours:Notvisiblemacroscopically,thereislossof embolism is rare. The development of tion, hypotension or in patients previously exposed persistent Q waves usually denotes a more substantial in- to streptokinase. It is now available as These should be given to all patients without evidence abedside test. They reduce mortality, reduce the number who de- Myoglobin velop cardiac failure and slow progression of the in- farct, by improving the remodelling of myocardium postinfarct. All di- Days after onset of acute Ml abetic patients should be treated with subcutaneous insulin for 3 months after discharge rather than oral Figure 2. Primary percu- Arrhythmiasmayoccurintheischaemicepisode(usually taneous coronary intervention (i. It is of particular value in patients with contraindica- Investigations tions to thrombolysis. Management Full mobilisation should be achieved after about 3 days r Nitrates and calcium antagonists are useful as pro- and discharge at 5 days, if there are no complications. The patient Prognosis may return to work after 2–3 months, depending on the The prognosis in patients with angina without underly- typeofwork. Rheumatic fever Prognosis Definition 50% 30-day mortality; 25% die before reaching hospital. Recurrent inflammatory disease affecting the heart; it Of those who leave hospital alive, 15–25% die within the occurs following a streptococcal infection. Incidence 1in100,000 United Kingdom/United States population peryear; incidence has declined over the last 100 years. Variant/Prinzmetal’s angina Definition Age Angina of no obvious provocation not as a direct result First attack usually 5–15 years. Sex Aetiology/pathophysiology M = F Causedbyspasmofacoronaryarterymostoftenwithout atheroma or in association with a mild eccentric lesion. Common in Middle and Far East, South America and Central Africa, declining in the West. Clinical features Pain is usually more severe and more prolonged than Aetiology classical angina occurring at rest particularly in the early Cell-mediated autoimmune reaction following a pha- morning. Risk fac- centre over the trunk and limbs, which appear and tors forstreptococcalinfectionincludepovertyandover- disappear over a matter of hours. Non-specific symptoms include It appears that antistreptococcal antibodies crossre- malaise and loss of appetite. Macroscopy r Pericarditis: Nodules are seen within the pericardium Fibrinous vegetations form on the edges of the valve associated with an inflammatory pericardial effusion.