This statement summarizes the U.S. Preventive Services Task Force (USPSTF) recommendations on routine vitamin supplementation to prevent cancer and cardiovascular disease and the supporting scientific evidence. Part of the information on which this statement is based, including evidence tables and references, is available in the accompanying article on vitamins to prevent cardiovascular disease in this issue. More complete information can be found in the summaries of the evidence on vitamins to prevent cancer and vitamins to prevent cardiovascular disease, available on the USPSTF Web site (http://www.preventiveservices.ahrq.gov) and through the National Guideline Clearinghouse (http://www.guideline.gov). The summaries of the evidence on these topics and the recommendation statement are also available in print through subscription to the Guide to Clinical Preventive Services, Third Edition: Periodic Updates. A subscription costs $60 U.S. and can be ordered through the Agency for Healthcare Research and Quality Publications Clearinghouse (call 800-358-9295 or e-mail mailto:ahrqpubs@ahrq.gov).

Patients with hepatitis C virus (HCV) are at increased risk for hepatocellular carcinoma. Although serum alpha-fetoprotein (AFP) is often used to detect hepatocellular carcinoma in HCV-infected individuals, its utility is unclear.

There is no consensus on the effectiveness of inhaled corticosteroids for the treatment of chronic obstructive pulmonary disease (COPD).

Pulmonary embolism is a common clinical disorder that is associated with high morbidity and mortality if untreated. It is important to confirm or rule out the diagnosis in patients with clinical suspicion of the disease.

Dementia is a large and growing problem but is often not diagnosed in its earlier stages. Screening and earlier treatment could reduce the burden of suffering of this syndrome.

Clinical trials have demonstrated that angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and spironolactone improve survival in patients with heart failure. Because patients with heart failure and renal insufficiency have been underrepresented in these trials, little evidence is available to guide clinicians in the optimal management of patients with both conditions. Approximately one third to one half of patients with heart failure have renal insufficiency (estimated glomerular filtration rate [GFR] <60 mL/min per 1.73 m2), and renal insufficiency is among the strongest predictors of mortality in patients with heart failure. Evidence supports the use of ACE inhibitors to improve survival in patients with moderate renal insufficiency (GFR, 30 to 60 mL/min per 1.73 m2), but there is little evidence with which to weigh the risks and benefits in patients with more advanced renal dysfunction. beta-Blockers improve survival in patients with heart failure, and their beneficial effect is unlikely to differ according to renal function. Spironolactone improves outcomes in patients with advanced heart failure, but renal insufficiency appears to increase risk for hyperkalemia and limits the use of the drug in patients with severe renal insufficiency. Future clinical trials in heart failure should include a representative number of patients with renal insufficiency to improve the evidence base and outcomes in this vulnerable population.

Congestive heart failure is a progressive disorder that is frequently preceded by asymptomatic left ventricular systolic dysfunction. We reviewed the epidemiology, diagnosis, and natural history of asymptomatic left ventricular systolic dysfunction and evaluated community-wide screening for this condition as a potential strategy to reduce the incidence of heart failure. Asymptomatic left ventricular systolic dysfunction has an estimated prevalence of 3% to 6%, and is at least as common in the community as systolic heart failure. Because it often occurs in the absence of known cardiovascular disease, this condition may go unrecognized and undertreated. In randomized trials, individuals with asymptomatic left ventricular systolic dysfunction have high rates of incident heart failure and death. However, little is known about the prognosis of individuals with this condition in the community, who have a substantially lower prevalence of myocardial infarction, have milder degrees of systolic dysfunction, and are older than patients enrolled in clinical trials. Current evidence is inadequate to support community-wide screening for asymptomatic left ventricular systolic dysfunction, either with echocardiography or with assays for natriuretic peptides. Given the increasing prevalence of heart failure, additional studies are needed to develop effective strategies to detect and optimally manage individuals with asymptomatic left ventricular dysfunction in the community.

Few treatments for back pain are supported by strong scientific evidence. Conventional treatments, although widely used, have had limited success. Dissatisfied patients have, therefore, turned to complementary and alternative medical therapies and providers for care for back pain.

Low back pain is a costly illness for which spinal manipulative therapy is commonly recommended. Previous systematic reviews and practice guidelines have reached discordant results on the effectiveness of this therapy for low back pain.

Over the past decade, noninvasive positive-pressure ventilation (NPPV) in the setting of acute exacerbations of chronic obstructive pulmonary disease (COPD) has increased in popularity. Although several trials have been published on the relative effectiveness of this treatment, apparent inconsistencies in study results remain.

Atrial fibrillation predisposes to left atrial thrombus formation and carries a sixfold increased risk for stroke. Antithrombotic therapies are the mainstay for stroke prevention. The National Institute of Neurological Disorders and Stroke-sponsored Stroke Prevention in Atrial Fibrillation (SPAF) studies assessed the value of warfarin, aspirin, and their combination for preventing stroke in six multicenter trials involving 3950 participants. This review presents the major results and implications, which offer unique perspectives on antithrombotic therapies for stroke prevention in atrial fibrillation. Warfarin and aspirin reduce stroke. Anticoagulation substantially benefits high-risk patients with atrial fibrillation, while many younger patients with atrial fibrillation have a low stroke rate when given aspirin. Pathogenetic and transesophageal echocardiographic correlations shed light on mechanisms by which antithrombotic agents prevent stroke. Warfarin inhibits formation of atrial appendage thrombi and markedly reduces cardioembolic strokes, while aspirin primarily prevents smaller, noncardioembolic strokes. The SPAF III stroke risk stratification scheme has been validated for identifying patients with high versus moderate versus low risk for stroke. Women with atrial fibrillation benefit from anticoagulation significantly more than men do. Many elderly patients with recurrent paroxysmal atrial fibrillation have high rates of stroke. Antithrombotic prophylaxis should be individualized on the basis of the estimated risk for stroke during aspirin therapy and the risk for bleeding during anticoagulation. Overall, nearly one third of patients with atrial fibrillation are low risk and should be treated with aspirin, and about one third are high risk and should receive warfarin if it can be given safely. For patients at moderate risk for stroke, patient preferences and access to reliable anticoagulation monitoring are particularly relevant.

The Philadelphia chromosome translocation (t(9;22)) results in the molecular juxtaposition of two genes, BCR and ABL, to form an aberrant BCR-ABL gene on chromosome 22. BCR-ABL is critical to the pathogenesis of chronic myelogenous leukemia and a subset of acute leukemias. The chimeric Bcr-Abl protein has constitutively elevated tyrosine phosphokinase activity. This abnormal enzymatic activation is critical to the oncogenic potential of Bcr-Abl. Initially, protein kinases were thought to be poor therapeutic targets because of their ubiquitous nature and crucial role in many normal physiologic processes. However, the advent of imatinib mesylate (Gleevec, Novartis Pharmaceuticals, Basel, Switzerland), formerly known as STI571 and CGP57148B, demonstrated that designer kinase inhibitors could be specific. This agent has shown striking activity in chronic myelogenous leukemia. It also inhibits phosphorylation of Kit (stem-cell factor receptor) and platelet-derived growth factor receptor. In addition, it has shown similar impressive responses, with little host toxicity, in gastrointestinal stromal tumors, which harbor activating Kit mutations, and in tumors with activated platelet-derived growth factor receptor. The studies of imatinib mesylate provide proof-of-principle for using aberrant kinases as a therapeutic target and are a model for the promise of molecular therapeutics. This paper reviews the current knowledge on the function of Bcr-Abl and its normal counterparts (Bcr and Abl), as well as the impact of this knowledge on the development of a remarkably successful targeted therapy approach.

Etanercept and infliximab are U.S. Food and Drug Administration-approved tumor necrosis factor (TNF) antagonists.

Rofecoxib and celecoxib (coxibs) effectively treat chronic arthritis pain and reduce ulcer complications by 50% compared with nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). However, their absolute risk reduction is small and the cost-effectiveness of treatment is uncertain.

Coronary stents are widely used in interventional cardiology, but a current quantitative systematic overview comparing routine coronary stenting with standard percutaneous transluminal coronary angioplasty (PTCA) and restricted stenting (provisional stenting) has not been published.

There have been many proposals for objective standards designed to optimize training, testing, and maintaining competency in interpretation of electrocardiograms (ECGs). However, most of these recommendations are consensus based and are not derived from clinical trials that include patient outcomes.

This paper is part 1 of a 2-part series on interpretation of 12-lead resting electrocardiograms (ECGs). Part 1 is a position paper that presents recommendations for initial competency, competency assessment, and maintenance of competency on ECG interpretation, as well as recommendations for the role of computer-assisted ECG interpretation. Part 2 is a systematic review of detailed supporting evidence for the recommendations. Despite several earlier consensus-based recommendations on ECG interpretation, substantive evidence on the training needed to obtain and maintain ECG interpretation skills is not available. Some studies show that noncardiologist physicians have more ECG interpretation errors than do cardiologists, but the rate of adverse patient outcomes from ECG interpretation errors is low. Computers may decrease the time needed to interpret ECGs and can reduce ECG interpretation errors. However, they have shown less accuracy than physician interpreters and must be relied on only as an adjunct interpretation tool for a trained provider. Interpretation of ECGs varies greatly, even among expert electrocardiographers. Noncardiologists seem to be more influenced by patient history in interpreting ECGs than are cardiologists. Cardiologists also perform better than other specialists on standardized ECG examinations when minimal patient history is provided. Pending more definitive research, residency training in internal medicine with Advanced Cardiac Life Support instruction should continue to be sufficient for bedside interpretation of resting 12-lead ECGs in routine and emergency situations. Additional experience or training in ECG interpretation when the patient's clinical condition is unknown may be useful but requires further study.

Chronic aortic regurgitation can lead to significant morbidity and mortality. For more than a century, numerous eponymous signs of aortic regurgitation have been described in textbooks and the literature.