To evaluate the use of thyroid function tests to monitor therapy in patients taking levothyroxine.

Considerable indirect evidence, based on the natural history of colorectal cancer and the ability of tests to detect adenomas and invasive cancers, suggests that screening for colorectal cancer reduces mortality. Without screening, a 50-year-old person at average risk has approximately a 530-in-10,000 chance of developing invasive colorectal cancer in the rest of his or her life and approximately a 250-in-10,000 chance of dying from it. Analysis of indirect evidence with a mathematic model indicates that screening persons for 25 years, from the age of 50 to the age of 75 years should reduce the chance of developing or dying from colorectal cancer by 10% to 75%, depending on which screening tests are used and how often screening is done. Screening for colorectal cancer is optional. A possible recommendation is that annual fecal occult blood tests and 65-cm flexible sigmoidoscopy every 3 to 5 years be done for average-risk men and women who are between 50 and 75 years of age. In addition to having annual fecal occult blood tests, persons with first-degree relatives with colorectal cancer can be offered barium enemas instead of sigmoidoscopies every 3 to 5 years.

To determine whether corticosteroids affect short-term mortality from alcoholic hepatitis.

Septic shock is the commonest cause of death in intensive care units. Although sepsis usually produces a low systemic vascular resistance and elevated cardiac output, strong evidence (decreased ejection fraction and reduced response to fluid administration) suggests that the ventricular myocardium is depressed and the ventricle dilated. In survivors, these abnormalities are reversible. Failure to develop ventricular dilatation in nonsurvivors suggests that dilatation is a compensatory mechanism needed to maintain adequate cardiac output. With a canine model of septic shock that is very similar to human sepsis, myocardial depression was confirmed using load-independent measures of ventricular performance. Endotoxin administration to humans simulates the qualitative, cardiovascular abnormalities of sepsis. The pathogenesis of septic shock is extraordinarily complex. Diverse microorganisms can generate toxins, stimulating release of potent mediators that act on vasculature and myocardium. A circulating myocardial depressant substance has been closely associated with the myocardial depression of human septic shock. Therapy has emphasized early use of antibiotics, critical care monitoring, aggressive volume resuscitation, and, if shock continues, use of inotropic agents and vasopressors. Pharmacologic or immunologic antagonism of endotoxin or other mediators may prove to enhance survival in this highly lethal syndrome.

Indirect evidence indicates that cervical cancer screening should reduce the incidence and mortality of invasive cervical cancer by about 90%. In the absence of screening, a 20-year-old average-risk woman has about a 250 in 10,000 chance of developing invasive cervical cancer during the rest of her life, and about a 118 in 10,000 chance of dying from it. Screening at least every 3 years from 20 to 75 years of age will decrease these probabilities by about 215 in 10,000 and 107 in 10,000, respectively, and will increase a 20-year-old woman's life expectancy by about 96 days. The particular age at which screening is begun (for example, 17 or 20 years), the requirement of several initial annual examinations before reducing the frequency, and screening every 1 or 2 years compared with every 3 years improves the effectiveness by less than 5%. Screening is recommended at least every 3 years from about age 20 to about age 65 years.

In studies in experimental animals and in edematous patients, the nonosmotic release of vasopressin has been found to be consistently associated with activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. Moreover, the sympathetic nervous system is known to modulate the nonosmotic release of vasopressin and activation of the renin-angiotensin-aldosterone system. These findings led to our proposal that body fluid volume regulation involves dynamic interaction between cardiac output and peripheral arterial resistance. In this context, neither total extracellular fluid volume nor total blood volume are determinants of renal sodium and water excretion. With a decrease in effective arterial blood volume (EABV) initiated by either decreased cardiac output or peripheral arterial vasodilation, the acute response involves vasoconstriction mediated by angiotensin, sympathetic mediators, and vasopressin. The renal vasoconstriction, which accompanies either decreased cardiac output or peripheral arterial vasodilation, causes a decreased distal tubular delivery of sodium and water, thus maximizing the water-retaining effect of vasopressin and impairing normal escape from the sodium-retaining effect of aldosterone. The elevated glomerular filtration rate and filtered sodium load seen in pregnant women allow increased distal sodium and water delivery despite a decrease in EABV, thus limiting edema formation during gestation.

To review the evidence for efficacy of three contemporary treatments for intermittent claudication: pentoxifylline, exercise programs, and smoking cessation.

Cost-effectiveness analysis can be used to help set priorities for funding health care programs. For each intervention, the costs and clinical outcomes associated with that strategy must be compared with an alternate strategy for treating the same patients. If an intervention results in improved outcomes but also costs more, the incremental cost per incremental unit of clinical outcome should be calculated. The incremental cost-effectiveness ratios for various programs can be ranked to set funding priorities. By using this list, the person responsible for allocating resources can maximize the net health benefit for a target population derived from a fixed budget. Clinicians may not share this objective because, individually, they are appropriately concerned solely with the effectiveness of a specific intervention for their patients and are not concerned with the benefit derived from spending those resources on other patients in the target population. In addition, allocation may be driven by distributional and political objectives. Nevertheless, cost-effectiveness analysis demonstrates the consequences of allocation decisions. Because clinicians should participate in policy making, they must understand d the role of this technique in setting funding priorities.

Following proposals in 1987 and 1988, several medical journals have provided more informative abstracts ("structured abstracts") for articles of clinical interest. Structured abstracts for original studies require authors to systematically disclose the objective, basic research design, clinical setting, participants, interventions (if any), main outcome measurements, results, and conclusions; and for literature reviews the objective, data sources, methods of study selection, data extraction and synthesis, and conclusions. More informative abstracts of this kind can facilitate peer review before publication, assist clinical readers to find articles that are both scientifically sound and applicable to their practices, and allow more precise computerized literature searches. We review the feasibility, acceptability, and dissemination of structured abstracts, reassess the underlying strategy, and describe modifications of the approach. This innovation can aid communication from scientists to clinicians, and other clinical journals are invited to join this effort.

To evaluate the clinical efficacy of ambulatory electrocardiographic (ECG) monitoring and to develop guidelines for its use in clinical practice.

The neurofibromatoses comprise at least two autosomal dominant disorders affecting an estimated 100,000 Americans with clinical manifestations that may require care from every type of clinician. Neurofibromatosis 1 and neurofibromatosis 2 have in common the occurrence of many neurofibromas but are distinctly different clinical disorders. The disease genes are on different chromosomes. Magnetic resonance imaging, particularly with gadolinium enhancement, has generally supplanted other techniques for visualizing brain, spinal, and other neural tumors in both disorders. The technique has rekindled the controversy over the nature and frequency of optic pathway tumors in patients with neurofibromatosis 1 and has revealed, throughout the brains of young patients, bright lesions that have uncertain clinical consequences and unknown pathologic bases. In patients with neurofibromatosis 2, small acoustic neuromas can be seen, leading to the possibility of excision with preservation of hearing and facial nerve function. Abnormal hearing may occur to excess in patients with neurofibromatosis 1, but acoustic neuroma has never been documented. In patients with neurofibromatosis 2, a battery of audiologic tests has a high positive predictive power. Lisch nodules or iris hamartomas, probably a universal sign in adults with the neurofibromatosis 1 gene, cause no problem with vision. Posterior capsular lens opacity in patients with neurofibromatosis 2 is a helpful diagnostic sign and a potential source of additional handicap in persons at risk for impaired hearing. Progress in the clinical delineation of the disorders has been matched with considerable research into the still obscure pathogenesis of the disorders. Such rapid advances may necessitate reconsideration of the conclusions of the National Institutes of Health Consensus Development Conference on Neurofibromatosis, especially those on the categories of persons in which a neurofibromatosis should be considered and the need for caution in recommending surgery. Watchful waiting may often be the best management for acoustic neuromas in neurofibromatosis 2.

The notion of medical futility has quantitative and qualitative roots that offer a practical approach to its definition and application. Applying these traditions to contemporary medical practice, we propose that when physicians conclude (either through personal experience, experiences shared with colleagues, or consideration of published empiric data) that in the last 100 cases a medical treatment has been useless, they should regard that treatment as futile. If a treatment merely preserves permanent unconsciousness or cannot end dependence on intensive medical care, the treatment should be considered futile. Unlike decision analysis, which defines the expected gain from a treatment by the joint product of probability of success and utility of outcome, our definition of futility treats probability and utility as independent thresholds. Futility should be distinguished from such concepts as theoretical impossibility, such expressions as "uncommon" or "rare," and emotional terms like "hopelessness." In judging futility, physicians must distinguish between an effect, which is limited to some part of the patient's body, and a benefit, which appreciably improves the person as a whole. Treatment that fails to provide the latter, whether or not it achieves the former, is "futile". Although exceptions and cautions should be borne in mind, we submit that physicians can judge a treatment to be futile and are entitled to withhold a procedure on this basis. In these cases, physicians should act in concert with other health care professionals, but need not obtain consent from patients or family members.

To review the current therapeutic options for patients with the myelodysplastic syndromes.