To 1) consider the problem of sudden death from heart disease and the role of beta-blockers and other agents in preventing sudden death and 2) review perceived problems with beta-blocker therapy, such as effects on blood lipids, complications in diabetes, and adverse effects on heart failure and quality of life.

Diseases characterized by airway inflammation, excessive airway secretion, and airway obstruction affect a substantial proportion of the population. These diseases include asthma, chronic bronchitis, bronchiectasis, and cystic fibrosis. Asthma and chronic bronchitis may affect 25 million persons in the United States. Much progress has been made in the last decade toward an understanding of the mechanisms underlying chronic airway inflammation; recent work has resulted in several new concepts of the initiation and maintenance of airway inflammation. Airway production of chemokines, cytokines, and growth factors in response to irritants, infectious agents, and inflammatory mediators may play an important role in the modulation of acute and chronic airway inflammation. Lipid mediators may be produced by resident airway cells and by inflammatory cells; production of these mediators may also be altered by inflammatory cytokines. Increased airway obstruction may be related to intercurrent viral respiratory infection and to the induction of airway inflammation and airway hyperreactivity that results from such infection. Furthermore, several models exist to explain the processes by which airway inflammation is perpetuated in diseases such as asthma and chronic bronchitis. These include neurogenic inflammation, the perpetuation of the acute inflammatory response, and cycles of airway epithelial cell-mediated and inflammatory cell-mediated recruitment and activation of inflammatory cells. An understanding of these mechanisms of airway inflammation may provide the clinician with new therapeutic approaches to the treatment of these common and chronic diseases.

To compare the effect of endoscopic ligation with that of sclerotherapy in the treatment of patients with bleeding esophageal varices.

The cloning of the defective gene in cystic fibrosis (CFTR) is the most important step to date toward understanding the pathogenesis of the disease and developing novel therapeutic strategies. Although many studies have provided insights into the molecular defects and knowledge of the expression and role of the gene, the basic defect and its pathogenesis are still unclear. We hypothesize that organ damage in cystic fibrosis is the result of a combination of at least three main factors: the genotype (the type of mutation that alters the function of the cystic fibrosis transmembrane regulator [CFTR]), the rate of CFTR-mediated chloride secretion in the epithelium of each organ (inferred from the level of expression of the gene), and the anatomical and physiologic characteristics of the affected organs (the size and contents of the ducts). Confirmation of this hypothesis should allow a better understanding of the pathogenesis of the disease and help prevent organ damage.

Interferon-gamma has pleiotropic adjuvant effects on host defenses. These effects have made interferon-gamma particularly useful for enhancing host defenses in patients with chronic granulomatous disease of childhood and thus for reducing the incidence of life-threatening infections in these patients. Increasingly, data suggest that interferon-gamma will be useful for treating infections characterized by intracellular persistence in macrophages, such as toxoplasmosis, leishmaniasis, and mycobacteriosis. Interferon-gamma is emerging as an important cytokine for use in the treatment of infectious diseases.

To review the efficacy of antimicrobial prophylaxis in bone marrow transplantation.

Some of the most intensive pharmacotherapy today occurs in nursing homes in very complex and vulnerable patients. The nursing home provides an opportunity for highly effective drug use, but it also presents risks for polypharmacy and adverse events. Nursing homes are complex social institutions, in which physicians, nurses, consultant pharmacists, other health care professionals, aides, and administrators must interact to make decisions about drug use for patients who generally are frail and have numerous comorbid conditions. Federal regulations have recently been implemented to direct the ways in which specific drugs are to be used in this setting. The nursing home environment can present an ideal opportunity for comprehensive drug regimen review, an exercise too often neglected in the care of elderly patients in all clinical settings. Psychoactive medications, analgesics, and laxatives are examples of drugs that should receive such review. The possible underuse of drug therapies that may be beneficial to nursing home residents, including antidepressant, antihypertensive, and antithrombotic agents; calcium supplements; and vaccines, must be further quantified and must receive increased attention. Morbidity and functional incapacity can be substantially reduced by applying currently established principles of geriatric pharmacology in the nursing home setting, but enormous gaps still exist in the knowledge base necessary to guide this aspect of geriatric medical practice. Data on the efficacy, toxicity, and cost-effectiveness of pharmacotherapeutic choices in nursing home patients are in short supply; considerably more clinical and epidemiologic research is needed to define the relations between the benefits and risks of drugs for this unique population.

To assess the effectiveness of azathioprine and 6-mercaptopurine in inducing remission of active Crohn disease and the effectiveness of azathioprine in maintaining remission of quiescent disease.

To review the available information on the diagnostic, prognostic, and therapeutic aspects of cardiac complications in women with the Marfan syndrome during the peripartum period and to develop guidelines for the approach to these patients on the basis of this information.

To review 1) advances in the pathogenesis, diagnosis, and management of dermatologic and joint disease and the antiphospholipid antibody syndrome in patients with systemic lupus erythematosus; 2) controversies related to pregnancy and hormonal therapy and to morbidity and mortality in these patients; and 3) current views on the pathogenesis of systemic lupus erythematosus.

The treatment of tuberculosis requires at least two drugs to retard the development of drug resistance. Unfortunately, patients may take only one drug (monotherapy) when more than one is prescribed. Fixed-dose combinations with two or more antituberculous drugs in one capsule or tablet are available to prevent this. In the United States, these drugs are Rifamate (Marion Merrell Dow), which contains isoniazid plus rifampin, and Rifater (Marion Merrell Dow), which contains isoniazid plus rifampin and pyrazinamide. Because these preparations make monotherapy impossible, they are clearly preferable to individual drugs. In the United States in 1993, however, only 15% to 18% of rifampin was sold in the form of fixed-dose combinations. To correct this deficiency, fixed-dose combinations should be widely promoted and accepted as a primary way to prevent drug-resistant tuberculosis. There are two caveats regarding these preparations. First, many fixed-dose combinations, especially those in developing countries, achieve inadequate blood levels of one or more of the component drugs, especially rifampin. Our recommendations apply only to preparations with proven bioavailability. Second, because the name Rifamate is similar to the name rifampin, mistakes in prescribing and dispensing can result in the patient receiving rifampin alone when Rifamate is intended. A name change from Rifamate to a highly distinctive name such as Rif-Isoniazid is needed to prevent such occurrences.

To review advances and controversies in the diagnosis and management of systemic lupus erythematosus with visceral involvement (renal, neuropsychiatric, cardiopulmonary, and hematologic disease).

In 1993, the Clinical Efficacy Assessment Subcommittee began evaluation of new topics and reevaluation of previous guidelines on common screening tests, which were published in Annals of Internal Medicine between 1988 and 1990 and republished as a collection in 1991 (Eddy DM, ed. Common Screening Tests. Philadelphia: American College of Physicians; 1991). Of the 11 guidelines contained in Common Screening Tests, only 3 (for breast, colon, and cholesterol screening) will be published with new data supporting new recommendations. Dr. Littenberg's analysis of the evidence that has appeared since the publication of the original paper on screening for hypertension (Littenberg B, Garber AM, Sox HC. Screening for Hypertension. Ann Intern Med. 1990;112:192-202) presents a new format for updating Clinical Efficacy Assessment Project (CEAP) guidelines that have not been altered by new evidence. This "updated guideline" reports on new published studies and its analysis affirms the approved American College of Physicians recommendations of 1990. The Clinical Efficacy Assessment Subcommittee carried out the Internal and external review procedures that are used for all CEAP guidelines. The plan is to keep all American College of Physicians guidelines updated in this way on a regular basis. Direct any comments or suggestions to Director, Scientific Policy, American College of Physicians, 6th Street at Race, Philadelphia, PA 19106.

To quantify the protection of previously infected persons from developing tuberculosis after intense exposure.

To do a meta-analysis on the efficacy of early or deferred zidovudine monotherapy in patients with human immunodeficiency virus (HIV) infection but not the acquired immunodeficiency syndrome (AIDS).

Cost-effectiveness analysis and other forms of decision analysis are becoming more common in the medical literature and are increasingly influential in the development of health policy. Nevertheless, many clinicians find it difficult to apply policies developed from these analyses to individual encounters with patients. We examine the assumptions behind these analyses and argue that the perspective they embody can make clinical strategies appear to be less risky in theory than they are at the bedside. We believe that this problem underlies the intuitive concern many physicians have about policy analyses and calls into question the value of these analyses in shaping clinical practice. These analyses aggregate the benefits and burdens of alternative interventions across different individual persons. Thus, overall population risk appears blunted, as it would in a diversified portfolio of stocks that react differently to financial forces or in a herd of cattle that react differently to veterinary interventions. The assumptions behind these analyses make sense if aggregate outcome is what matters, but not if one cares about each individual investment or animal. Because such aggregation tends to understate individual risk, when applied to human health policy, it may misrepresent the interests of patients and cannot be assumed to provide useful guidelines for decision making at the bedside.

To review the literature on the long-term health effects of exposure to diethylstilbestrol (DES) among women prescribed DES during pregnancy (DES mothers), among their children exposed inutero to the drug (DES sons and daughters) and among the progeny of these exposed sons and daughters (DES grandchildren).

To review clinical scenarios in which nonelectrophysiologist physicians may interact with patients who have implantable defibrillators.

The myositis syndromes, the most common forms of which are polymyositis and dermatomyositis, are defined by idiopathic chronic inflammation in skeletal muscle. Although initially described more than a century ago, these diseases are so rare and heterogeneous that we have only a limited understanding of their causes and treatment. Recently, autoimmune responses to nuclear and cytoplasmic autoantigens that are unique to patients with myositis, the myositis-specific autoantibodies, have proved clinically useful in helping predict signs and symptoms of myositis, immunogenetics, responses to therapy, and prognosis. We summarize this new information on the variety and nature of these autoantibodies, their target epitopes, and their possible use in identifying causes, pathogenetic mechanisms, and better therapies for these increasingly recognized disorders.