Although most mechanisms remain to be characterized in detail, they can be broadly grouped into direct and indirect mechanisms. Bacterial pathogens have further evolved a range of mechanisms that divert host signalling processes to promote cell survival and proliferation. Bacteria are also capable of producing pro-inflammatory metabolites, such as secondary bile acids, which can act systemically when reaching the circulation. Finally, some bacteria can also elicit immunosuppressive responses, thereby indirectly contributing to tumour survival through evasion of immune surveillance. Another process by which intestinal bacteria promote hepatocellular carcinoma involves bile acids. Primary bile acids are secreted from the liver into the gut, where they can be converted into secondary bile acids, such as deoxycholic acid, by intestinal Clostridium spp. After re-uptake, deoxycholic acid circulates back to the liver, where it exerts its carcinogenic effects. In sum, several clinical studies have revealed profound changes in the gut microbiota associated with chronic liver diseases, and preclinical 224 Chapter 3. There is also emerging evidence for a bacterial contribution to pancreatic cancer development [13]. In mouse models, germ-free conditions or administration of antibiotics were shown to slow down progression of pancreatic ductal adenocarcinoma. Moreover, the microbiota colonizing the pancreas was found to play an important role in regulating the inflammatory tone in the pancreatic tumour microenvironment in mice via pattern recognition receptor signalling [17]. However, larger clinical studies are needed to validate individual microbial taxa enriched in pancreatic tissue [18] or in the mouth and the gut of patients with pancreatic ductal adenocarcinoma. Role of the gut microbiome in cancer therapy the gut microbiota is increasingly appreciated as a versatile "microbial pharmacist within us" [22], because evidence is accumulating that it can also affect the pharmacokinetics, efficacy, and toxicity of various anticancer therapies. Chemotherapy As one of the first examples, irinotecan was reported to be metabolized by intestinal bacteria. Another example is the chemotherapeutic drug gemcitabine, which can be rendered inactive by bacterial enzymes, as has been demonstrated in mouse models. Bacteria capable of this biotransformation were found in tissue samples from patients with pancreatic ductal adenocarcinoma, suggesting that this bacterial resistance mechanism is clinically relevant [6,16,23,24]. There is also recent evidence that the gut microbiota modulates the anti-tumour efficacy of platin-based and cyclophosphamide chemotherapies. The efficacy of cisplatin and oxaliplatin is greatly decreased in mice under germ-free conditions or when their gut microbiome has been perturbed with broad-spectrum antibiotics. The immunogenic cell death that these drugs induce is dependent on inflammatory responses (partially mediated by signalling through pattern recognition receptors), which in mouse models were enhanced by the administration of specific bacterial species [6,7]. Cancers in organs outside the gastrointestinal tract Breast cancer Among tumour types outside the digestive tract, breast cancer has been most extensively examined for potential associations with microbiota at various body sites [7,21]. As in the liver, tumorigenesis in the breast may potentially be influenced by the gut microbiota through proinflammatory metabolites (microbeassociated molecular patterns). Intestinal bacteria may affect estrogen exposure, a major risk factor for breast cancer (see Chapter 2. Clinical studies have found estrogen-dependent and estrogen-independent microbiome associations with breast cancer, but a mechanistic understanding of hormonal co-metabolism between the host and its gut microbiome has yet to be elucidated, and its clinical significance remains to be established [21]. Other studies have examined microbiota residing in breast tissue of women with and without breast cancer. Whereas structural alterations were not detected in association with breast cancer, some studies found rare taxa to differ in abundance in tumour tissue. However, among the published microbiome-wide association studies there is little agreement on the precise breast cancer-associated bacterial taxa [21]. Lung cancer An involvement of the respiratory tract microbiota in lung cancer development is conceivable, based on epidemiological studies showing bacterial lung infections (including pneumonia) to be associated with lung cancer risk [13]. However, only few studies of relatively small scale have directly investigated this question; hence, the evidence on the role of the airway microbiota in lung cancer is currently still inconclusive.
It is marked by intermittent acute psychotic episodes and impaired psychosocial functioning between acute episodes, with most of the deterioration in psychosocial functioning occurring within 5 years after the first psychotic episode. In a subpopulation of patients, probably 5% to 15%, psychotic symptoms are nearly continuous, and response to antipsychotics is poor. After their first episode, patients with schizophrenia rarely have a level of adaptive functioning as high as before the onset of the disorder. Positive symptoms have traditionally attracted the most attention and are the ones most improved by antipsychotics. It has been suggested that symptom complexes can correlate with prognosis, cognitive functioning, structural abnormalities in the brain, and response to antipsychotic drugs. Negative symptoms and cognitive impairment can be more closely associated with prefrontal lobe dysfunction and positive symptoms with temporolimbic abnormalities. Patients with negative symptoms frequently have more antecedent cognitive dysfunction, poor premorbid adjustment, low level of educational achievement, and a poorer overall prognosis. Most deterioration in psychosocial functioning occurs during the first 5 years after the initial psychotic episode, and treatment should be particularly assertive during this period. These programs can include case management, psychoeducation, targeted cognitive therapy, basic living skills, social skills training, basic education, work programs, supported housing, and financial support. In particular, programs aimed at employment and housing have been the more effective interventions and are considered "best practices. People with schizophrenia need comprehensive care, with coordination of services across psychiatric, addiction, medical, social, and rehabilitative services. Social/occupational dysfunction: For a significant portion of the time since onset of the disorder, one or more major areas of functioning such as work, interpersonal relations, or self-care are significantly below the level prior to onset. This must include at least 1 month of symptoms fulfilling criterion A (unless successfully treated). If a history of a pervasive developmental disorder is present, there must be symptoms of hallucinations or delusions present for at least 1 month. A thorough mental status examination, physical and neurologic examination, complete family and social history, and laboratory workup must be performed to confirm the diagnosis and exclude general medical or substance-induced causes of psychosis. Laboratory tests, biologic markers, and commonly available brain imaging techniques do not assist in diagnosis or selection of medication. A pretreatment patient workup is important in not only excluding other pathology, but in serving as a baseline for monitoring potential medication-related side effects, and should include: vital signs, complete blood count, electrolytes, hepatic function, renal function, electrocardiogram, fasting serum glucose, serum lipids, thyroid function, and urine drug screen. This can include gradual dose titration downward if patients do not respond initially, rather than upward titration as has been the traditional approach to dosing antipsychotics. Olanzapine has a very low incidence of extrapyramidal side effects when used within the approved dose range of 10 to 20 mg daily. Side-effect profiles differ among atypical antipsychotics, and this information in combination with individual patient characteristics should be used in deciding which drug to use in an individual patient. Previous patient or family history of response to an antipsychotic is helpful in the selection of an agent. Common to all definitions is the ability of the drug to produce antipsychotic response with few or no acutely occurring extrapyramidal side effects. The major advantage of atypical antipsychotics can be their lower risk of neurologic side-effects, particularly effects on movement. First-episode patients usually require lower antipsychotic dosing and should be closely monitored due to greater sensitivity to medication side effects. In addition, patients on a stable, active medication regimen with persistent, disabling symptoms over a 2-year period should be tried on clozapine. Patient entry into the algorithm is determined by individual patient history and clinical presentation.
Total absence of symptoms is an uncommon outcome, and residual symptoms predispose the patient to relapse. The actual definition of recovery varies, as once-a-month binge/purge episodes are considered by some to be recovery if their episodes were previously more frequent, whereas others consider a patient recovered only when complete absence of these behaviors occurs. Psychiatrists, physician assistants, nurses, nutrition specialists, psychologists, and pharmacists play a role in the care of these complex patients. The absence of an adequate support system of family and friends can be cause for failed treatment. A critical first step is to determine the severity of illness, as that drives both the intensity and the setting for delivery of care. Initial treatment is directed toward restoring a healthy weight (greater than 90% of normal weight for age-matched controls) and treating food phobias. In severe cases, nasogastric refeeding is preferred over intravenous bolus dosing. The decision to administer total parenteral nutrition must be made carefully, because of the potentially devastating psychologic effect on patients who do not wish to gain weight. Most clinicians initiate at low doses, for example 20 mg/day, and increase to a maximum of 60 mg/day based on response and tolerability. Evidence from a 52-week, randomized, placebo controlled clinical trial of 93 patients with the treatment arm receiving doses from 20 mg/day to 80 mg/day showed no difference between fluoxetine and placebo for time-to-relapse. All antidepressants can cause seizures; thus a careful risk-benefit assessment is warranted if the patient has predisposing factors such as a personal or family history of seizures, cerebrovascular disease, or alcohol or sedative-hypnotic withdrawal. For fluoxetine, the higher end of the dosing range, 60 mg/day, can be necessary for response. In the absence of data, the definition of a therapeutic trial from the depression literature (4 to 8 weeks at a therapeutic dose) should be used. As the majority of subjects will not experience a complete remission, and there are few data on predictors of response or whether switching to another class will improve response, a clear and specific target should be stated initially. The evidence is mixed as to whether any early benefit is sustained, hence the decision to continue treatment should be made based on both initial response and the maintenance of that benefit. If the symptoms return within a few months after antidepressant discontinuation, then the treatment might need to be reinitiated. Recent findings from a 52-week study comparing fluoxetine to placebo in patients with anorexia nervosa after successful weight restoration found that fluoxetine did not provide any benefit in preventing relapse. Second generation antipsychotics are being used by some clinicians in acutely ill patients with severe obsessions and paranoia about eating, although the data supporting this approach are limited. Additionally, several reviews analyzing this body of literature have been published, although there continues to be limited placebo controlled randomized, doubleblind clinical studies. The presence of comorbid mood disorders is not necessary for an antidepressant response. One trial evaluating the impact of fluoxetine versus placebo in the maintenance phase showed a better outcome in patients receiving fluoxetine 60 mg/day, although high dropout rates in both groups blurred the overall benefit. Determine baseline frequency of binge and vomiting episodes, laxative abuse, obsessive thoughts, and compulsive behavior. Determine baseline physical status (especially nutritional status, electrocardiogram, and fluid status [dehydration and electrolytes]). Consider whether an antidepressant should be part of a comprehensive treatment plan that includes nonpharmacologic measures, especially cognitive behavioral therapy. If antidepressant is indicated, start at a low dose, and use a selective serotonin reuptake inhibitor unless there is a medical reason not to do so. Response is determined by change from baseline frequency and severity of target symptoms. If patient responds and response is sustained, continue treatment for 6 to 12 months, then reassess. If response is poor, evaluate compliance and whether patient is vomiting medication. Lithium must be used cautiously, as fluid shifts related to purging and laxative abuse increase the risk of toxicity. The adverse effect of weight gain often makes mood stabilizers and anticonvulsants unacceptable to patients in the long term. Miscellaneous Agents Low-dose benzodiazepines before meals can help reduce anxiety associated with refeeding, although longterm use is not warranted because of the risk of abuse and dependence.
Because of observations of increased suicidality among adolescents (and adults, for that matter), experts are questioning whether these medications merely bring out an increased suicide risk that the patient has suppressed or has been too depressed to act on, or these medications actually increase the risk per se through some pharmacologic effect. This dissimilarity in the incidence of nephrotoxicity implies that newborn infants have less inherent tissue sensitivity for toxicity than do adults. The differences in efficacy, toxicity, and protein binding of drugs in pediatric versus adult patients raise an important question about the acceptable therapeutic range in children. Therapeutic ranges for drugs are first established in adults and often are applied directly to pediatric patients, but specific studies should be conducted in pediatric patients to define optimal therapeutic ranges of drugs. For instance, patients with cystic fibrosis require larger doses of certain drugs to achieve therapeutic concentrations. The manufacturer states that ciprofloxacin can be used in pediatric patients only for inhalation anthrax (postexposure) or for treatment of complicated urinary tract infections and pyelonephritis caused by susceptible Escherichia coli. The American Academy of Pediatrics and Infectious Disease Society of America suggest that their use may be justified for certain other conditions. Reversible arthralgia, sometimes accompanied by synovial effusion, was associated with ciprofloxacin therapy in 1. Hepatic Disease Because the liver is the main organ for drug metabolism, drug clearance usually is decreased in patients with hepatic disease. However, most studies on the influence of hepatic disease on dosage requirements have been performed in adults, and these data may not be extrapolated uniformly to pediatric patients. Drug metabolism by the liver depends on complex interactions among hepatic blood flow, ability of the liver to extract the drug from the blood, drug binding in the blood, and both type and severity of hepatic disease. Routine hepatic function tests, such as determinations of serum aspartate aminotransferase, serum alanine aminotransferase, alkaline phosphatase, and bilirubin levels, have not correlated consistently with drug pharmacokinetics. Furthermore, because of different pathologic changes in various types of hepatic diseases, patients with acute viral hepatitis may have different abilities to metabolize drugs than patients with alcoholic cirrhosis. A decreased hepatic blood flow in the presence of disease states such as cirrhosis and congestive heart failure is expected to decrease the clearance of drugs with high extraction ratios. One report suggested that theophylline clearance may decrease by 45% in a child with acute viral hepatitis. Studies have reported higher clearance of drugs such as gentamicin, tobramycin, netilmicin, amikacin, dicloxacillin, cloxacillin, azlocillin, piperacillin, and theophylline in patients with cystic fibrosis compared with patients without the disease. The apparent volume of distribution of certain drugs also may be altered in cystic fibrosis. Once again, because of limited studies, dosage adjustments in pediatric patients are based largely on data obtained in adults. During the last years of the 20th century, however, many research and clinical studies have been performed in the areas of pain management and assessment of neonates, infants, children, and adolescents. Today, results of these discoveries have been incorporated into clinical practice, making effective pain therapy a standard of care and pain assessment the fifth vital sign in modern pediatric practice. In addition, pain signal transmission in the spinal cord is less precise, and descending inhibitory neurotransmitters are lacking. As a result, neonates and young infants may perceive pain more intensely and be more sensitive to pain than are older children or adults. An inadequately treated initial painful procedure may decrease the effect of adequate analgesia in subsequent procedures as a result of altered pain response patterns. Pharmacologic pain management for medical conditions and surgical and postoperative events has progressed considerably over the past decade with the use of continuous opioid infusions, epidural anesthesia, peripheral nerve blockade, local anesthetics, nonsteroidal antiinflammatory drugs, different routes for traditional agents. New pain management techniques, education, research, and increasing awareness of pain management options have helped to improve the quality of life in children. Age <1 year of age, low-birth-weight infant <1 year of age, full-term infant 2- to 12-year-old child 13- to 21-year-old female 13- to 21-year-old male K 0. Serum drug concentrations should be monitored for drugs with narrow therapeutic indices and eliminated largely by the kidney. Cystic Fibrosis Drug therapy in pediatric patients with cystic fibrosis has been reviewed. Disadvantage: Tingling, itching, or burning sensation from the electric current used to transport drug to the tissues.
Identification of nonadherence should be followed up with appropriate patient education, counseling, and intervention. Patients on antihypertensive therapy should be questioned periodically about changes in their general health perception, energy level, physical functioning, and overall satisfaction with treatment. Persistence with lifestyle modifications should be continually encouraged in patients engaging in such endeavors. A careful history for chest pain (or pressure), palpitations, dizziness, dyspnea, orthopnea, headache, sudden change in vision, one-sided weakness, slurred speech, and loss of balance should be taken to assess for the presence of hypertensive complications. Other clinical monitoring parameters that may be used to assess target-organ disease include funduscopic changes on eye examination, left ventricular hypertrophy on electrocardiogram, proteinuria, and changes in kidney function. These parameters should be monitored periodically because any sign of deterioration requires immediate assessment and followup. Treatment of patients with hypertension should include both lifestyle modifications and pharmacotherapy. If patients with hypertension have a comorbid condition that is considered a compelling indication, a different set of drugs may be recommended for first-line therapy. Therefore, -blockers are not first-line therapy options unless an appropriate compelling indication is present. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Treatment of hypertension in the prevention and management of ischemic heart disease: A scientific statement from the American Heart Association Council for 21. High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention. Heart disease and stroke statistics-2006 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Part 1: Prolonged differences in blood pressure: Prospective observational studies corrected for the regression dilution bias. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Medical Research Council trial of treatment of hypertension in older adults: Principal results. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Recommendations for blood pressure measurement in humans and experimental animals: Part 1: Blood pressure measurement in humans: A statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Cardiovascular prognosis of "masked hypertension" detected by blood pressure self-measurement in elderly treated hypertensive patients. Detection of chronic kidney disease in patients with or at increased risk of cardiovascular disease: A science advisory from the American Heart Association Kidney and Cardiovascular Disease Council; the Councils on High Blood Pressure Research, Cardiovascular Disease in the Young, and Epidemiology and Prevention; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: Developed in collaboration with the National Kidney Foundation. Dietary approaches to prevent and treat hypertension: A scientific statement from the American Heart Association. Diet and lifestyle recommendations revision 2006: A scientific statement from the American Heart Association Nutrition Committee. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. Effects of different blood-pressure-lowering regimens on major cardiovascular events: Results of prospectively-designed overviews of randomised trials. Heart disease and stroke statistics-2007 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Hypertension: Management of Hypertension in Adults in Primary Care: Partial Update.
Caution is warranted not to lower preload excessively, which may reduce stroke volume and cardiac output. Thiazolidinediones should be discontinued in patients with symptoms related to volume overload. As pressure throughout diastole falls, mean diastolic pressure, pulmonary capillary wedge pressure, and pulmonary venous pressure fall. These agents effectively reduce the central blood volume and lower diastolic pressures, thus alleviating the symptoms of the congestive state. Diuretics can provide disease-targeted therapy by decreasing blood pressure and favorably affecting the myocardial oxygen supply-versus-demand ratio. Diuretics alone and especially in combination with other antihypertensive drugs are an effective approach to therapy. Treatment with diuretics should be initiated at low doses in order to avoid hypotension and fatigue. If prompt and sustained diuresis is not achieved, the dosage of a single diuretic should be increased, or a loop and thiazide or thiazide-like diuretic should be used in combination. Excessive diuresis may result in hypotension, low-output syndrome, and worsening renal insufficiency. Electrolyte imbalances, including hypokalemia and hypomagnesemia, are common with diuretics. Carbohydrate intolerance and hyperuricemia are dose-related adverse drug reactions seen with thiazide diuretics. Eplerenone may be used as an alternative to spironolactone in patients who complain of gynecomastia. Like diuretics, therapy should be initiated at low doses in order to avoid hypotension. Isosorbide dinitrate 10 mg three or four times daily, isosorbide mononitrate (Imdur) 30 mg/day, nitroglycerin paste 0. Nitrate tolerance has not been studied in this patient population but probably occurs (for more detail regarding nitrate tolerance, see Chap. Sublingual nitroglycerin tablets or nitroglycerin spray may be used for patients who develop shortness of breath with mild exercise, and they can be used much in the same way as in patients with ischemic symptoms. Prinzmetal vasospastic angina, occlusive peripheral vascular disease, type 1 diabetes mellitus that is prone to hypoglycemia, severe heart block, and excessive bradycardia are contraindications to blockers. The main side effects of -blockers are depression, fatigue, bradycardia, bronchospasm, and impotence. Many of the -blockers are eliminated via hepatic metabolism and may be affected by other drugs that either inhibit. Because the doses are titrated to patient response, these interactions are managed easily. Initial doses are verapamil 120 to 240 mg/day, diltiazem 90 to 120 mg/day, and amlodipine 2. The most common side effects are bradycardia and heart block (for the nondihydropyridines). Nondihydropyridines exacerbate the bradycardic effects of -blockers, and verapamil raises digoxin serum concentrations by 70%. Intravenous calcium salts inhibit the pharmacologic effect of calcium channel blockers. Generic formulations or similar products, but not necessarily generic equivalents to the original brand names, are available for some of the calcium channel blockers. By decreasing heart rate and increasing the duration of diastole, -blockers can help to lower and maintain low pulmonary venous pressures.
However, many children who are overweight also have parents who are overweight, and the adult world shapes what children see and respond to . Societal actions that have favourable impacts on vulnerable groups of all ages and backgrounds offer the greatest potential for equitable effects. Tackling obesity is more complex than addressing either energy intake or energy expenditure, and there are no simple solutions. Approaches that tackle both environmental factors, which support or undermine the ability of people to participate in healthful behaviours, and individual action are desirable. This situation reinforces preferences and demands for foods of poor nutritional quality, thus maintaining unhealthy food environments. Approaches by governments to address obesity have tended to focus on one or two target areas and lack the comprehensive approach needed for sustainable behaviour change. It is clear that relevant policy actions for addressing obesity need to be identified in a systematic manner. The Food Environment Policy Index [24], which offers a useful tool for developing consensus for action, has been used in Thailand, New Zealand, Australia, and England. For example, in England the toppriority policy actions identified for government were those that affect both children and adults: (i) control the advertising of unhealthy foods to children; (ii) implement the levy on sugary beverages; (iii) reduce the sugar, fat, and salt content in processed foods; (iv) monitor school and nursery food standards; (v) prioritize health and the environment in the 25-year Food and Farming Plan; (vi) adopt a national food action plan; (vii) monitor the food environment; (viii) apply buying standards to all public institutions; (ix) strengthen planning laws to discourage lesshealthy food offers; and (x) evaluate food-related programmes and policies [25]. The combined forces of regulatory actions from governments and increased efforts from industry and civil society will be necessary to address obesity (see Chapter 6. Public advocacy efforts [26] (including those from cancer organizations) are considered to be a key component in creating demand and support for effective obesity policies and in mitigating reaction against their implementation. Important issues for obesity coalitions to address include challenges from the food and beverage industry and ways to avoid stigmatization by insensitive programmes and campaigns, and thus lose support for obesity programmes by civil society. Driving action to prevent cancer and other non-communicable diseases: a new policy framework for promoting healthy diets, physical activity, breastfeeding and reducing alcohol consumption. Promoting changes in diet and physical activity in breast and colorectal cancer screening settings: an unexplored opportunity for endorsing healthy behaviors. Background, principles, implementation, and general experiences of the North Karelia Project. A systematic review of real-world diabetes prevention programs: learnings from the last 15 years. Strengthening of accountability systems to create healthy food environments and reduce global obesity. Public awareness of the link between alcohol and cancer in England in 2015: a population-based survey. Effectiveness of brief interventions in primary health care settings to decrease alcohol consumption by adult non-dependent drinkers: a systematic review of systematic reviews. Are physical activity interventions for healthy inactive adults effective in promoting behavior change and maintenance, and which behavior change techniques are effective Nonworksite interventions to reduce sedentary behavior among adults: a systematic review. Patchy progress on obesity prevention: emerging examples, entrenched barriers, and new thinking. A notable fraction of cancer cases in humans (~15%) are caused by infections [1], and these are largely amenable to effective preventive interventions. Because of the long latency between the occurrence of infection and the diagnosis of cancer, data on efficacy against invasive cancers remain limited, but findings on precancerous lesions and viral end-points are extremely favourable and robust. In 2018, there were an estimated 841 000 new cases of liver cancer and 781 000 deaths from liver cancer worldwide [3]. However, most girls in low- and middle-income countries, who are at highest risk of cervical cancer, are not yet immunized [6]. The vaccine can safely and effectively be administered simultaneously with many other routine childhood immunizations.
Are beta-blockers effective in patients who develop heart failure soon after myocardial infarction A report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina). The long-term impact of the angiotensin-converting enzyme inhibitor trandolapril on mortality and hospital admissions in patients with left ventricular dysfunction after a myocardial infarction: Follow-up to 12 years. Effects of an angiotensin-converting enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. Effects of long-term treatment with angiotensin-converting enzyme inhibitors in the presence or absence of aspirin: A systematic review. Eplerenone, a selective aldosterone blocker in patients with left ventricular dysfunction after myocardial infarction. Coordinating Committee of the National Cholesterol Education Program, Endorsed by the National Heart, Lung, and Blood Institute, American College of Cardiology Foundation, and American Heart Association. The effect of early, intensive statin therapy on acute coronary syndrome: A meta-analysis of randomized controlled trials. Pravastatin or Atorvastatin Evaluation and Infection Therapy: Thrombolysis in Myocardial Infarction 22 Investigators. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. Canadian Cardiovascular Society position statement-Recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease. Mortality risk reduction associated with smoking cessation in patients with coronary heart disease: A systematic review. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: A statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity). Guidelines on diabetes, prediabetes, and cardiovascular disease: Executive summary. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Routine vitamin supplementation to prevent cancer and cardiovascular disease: Recommendations and rationale. Homocysteine lowering and cardiovascular events after acute myocardial infarction. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: A randomized controlled trial. Impact of medication therapy discontinuation on mortality after myocardial infarction. A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease. Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. Usefulness of in-hospital prescription of statin agents after angiographic diagnosis of coronary artery disease in improving continued compliance and reduced mortality. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. Pharmacist intervention to improve medication adherence in heart failure: A randomized trial. Effect of a pharmacy care program on medication adherence and persistence, blood pressure, and low-density lipoprotein cholesterol: A randomized controlled trial. Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as compared with streptokinase for acute myocardial infarction. North of England evidence based guideline development project: Guideline on the use of aspirin as secondary prophylaxis for vascular disease in primary care. Health and economic benefits of increased beta-blocker use following myocardial infarction. Cost-effectiveness of eplerenone compared with placebo in patients with myocardial infarction complicated by left ventricular dysfunction and heart failure. Cost-effectiveness of 3hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors in the secondary prevention of cardiovascular disease: Forecasting the incremental benefits of preventing coronary and cerebrovascular events.
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