When cytotoxic agents were initially introduced, their ability to disrupt nucleic acid and protein synthesis led to their effective use for the treatment of neoplastic disease. During the course of this use, however, it became apparent that these agents also suppress the immune system. This usually unwelcome effect was subsequently studied and beneficially directed toward the treatment of non-neoplastic diseases in which autoimmune mechanisms were considered important to pathogenesis. As a result of these investigations, cytotoxic agents and, more recently, cyclosporine have emerged to become an important part of the therapeutic regimen for many autoimmune diseases. Nonetheless, these medications may still cause treatment-induced illness or even death. It is therefore particularly important to weigh the benefits and risks of cytotoxic therapy when treating a non-neoplastic disease. This two-part Clinical Staff Conference reviews data on the efficacy and toxicity of cytotoxic drugs and cyclosporine in selected autoimmune diseases. Part 1 examines the manner in which these agents have been used to treat rheumatologic and renal diseases.

Hip fractures are an important cause of death and functional dependence in the United States.

In recent years, it has become apparent that overproduction of the Th1 cytokines interleukin-12 and interferon-gamma is the probable driving force behind murine models of intestinal inflammation resembling Crohn disease and intestinal inflammation in humans with Crohn disease. In addition, studies of murine models strongly suggest that this overproduction is associated with inadequate secretion of the counter-regulatory and anti-inflammatory cytokine transforming growth factor-beta. Thus, mucosal inflammation in models (and possibly in humans) may result from an imbalance between normally occurring positive (immunogenic or inflammatory) responses and negative (tolerogenic or anti-inflammatory) mucosal immune responses. These new findings and the hypotheses that arise from them are being used to construct new approaches to the treatment of Crohn disease that are based on the administration of anti-inflammatory cytokines and anti-cytokine antibodies.

To briefly review the role of calcium in the pathophysiology of atherosclerosis and to comprehensively review and analyze studies of coronary artery calcium detected by electron-beam computed tomography (CT).

Randomized, controlled trials have not shown that the perioperative use of antilymphocyte antibodies (induction therapy) improves survival of cadaveric kidney allografts. This study combined individual patient-level data from published trials to examine the effect of induction therapy on allograft survival.

To determine whether the seeming relation between low or lowered cholesterol levels and violence is consistent with causality according to Hill's criteria and whether construct validity is supported by convergence of findings across different types of studies.

To review the association between combined oral contraceptives and cardiovascular disease, with emphasis on oral contraceptives containing low doses of estrogen (low-dose oral contraceptives).

This article examines the ethics of medical practice under managed care from a pragmatic perspective that gives physicians more useful guidance than do existing ethical statements. The article begins with a framework for constructing a realistic set of ethical principles, namely, that medical ethics derives from physicians' role as healers; that ethical statements are primarily aspirational, not regulatory; and that preserving patient trust is the primary objective. The following concrete ethical guidelines are presented: Financial incentives should influence physicians to maximize the health of the group of patients under their care; physicians should not enter into incentive arrangements that they are embarrassed to describe accurately to their patients; physicians should treat each patient impartially without regard to source of payment, consistent with the physician's own treatment style; if physicians depart from this ideal, they should inform their patients honestly; and it is desirable, although not mandatory, to differentiate medical treatment recommendations from insurance coverage decisions by clearly assigning authority over these different roles and by physicians advocating for recommended treatment that is not covered.

To review evidence about thyroxine suppressive therapy in patients with thyroid nodules, including the clinical importance and natural history of nodules and the effects and potential side effects of thyroxine therapy.

Indiscriminate use of the terms dehydration and volume depletion, so carefully crafted by our predecessors, risks confusion and therapeutic errors. These two conditions should be distinguished at the bedside and in how we speak to one another. Dehydration largely refers to intracellular water deficits stemming from hypertonicity and a disturbance in water metabolism. The diagnosis of dehydration cannot be established without laboratory analysis of p[Na +] or calculation of serum tonicity. In contrast, volume depletion describes the net loss of total body sodium and a reduction in intravascular volume and is best termed extracellular fluid volume depletion. The diagnosis of this condition relies principally on history, careful physical examination, and adjunctive data from laboratory studies. The pathophysiology of both dehydration and extracellular fluid volume depletion must be understood if these conditions are to be recognized and appropriately treated when they occur separately or together. There is no inclusive therapy for all situations. For example, indiscriminate treatment with 0.45% saline cannot be recommended when these conditions coexist because extracellular fluid volume depletion is often treated rapidly with 0.9% saline and dehydration is often treated more slowly with 5% dextrose.

The aim of many analyses of large databases is to draw causal inferences about the effects of actions, treatments, or interventions. Examples include the effects of various options available to a physician for treating a particular patient, the relative efficacies of various health care providers, and the consequences of implementing a new national health care policy. A complication of using large databases to achieve such aims is that their data are almost always observational rather than experimental. That is, the data in most large data sets are not based on the results of carefully conducted randomized clinical trials, but rather represent data collected through the observation of systems as they operate in normal practice without any interventions implemented by randomized assignment rules. Such data are relatively inexpensive to obtain, however, and often do represent the spectrum of medical practice better than the settings of randomized experiments. Consequently, it is sensible to try to estimate the effects of treatments from such large data sets, even if only to help design a new randomized experiment or shed light on the generalizability of results from existing randomized experiments. However, standard methods of analysis using available statistical software (such as linear or logistic regression) can be deceptive for these objectives because they provide no warnings about their propriety. Propensity score methods are more reliable tools for addressing such objectives because the assumptions needed to make their answers appropriate are more assessable and transparent to the investigator.

Generic health surveys have been proposed for use in increasingly diverse applications and populations. This paper describes the history of generic tools in the past 30 years and suggests a more modern measurement platform for advances in the 21st century. Many generic tools lack the precision required for effective health care decision making. A meaningful goal for the next era of development of generic measures should be the generation of equiprecise measurement for generic health concepts. Equiprecise tests yield measures of equal precision at all levels of the underlying construct. Equiprecise measurement can be achieved through conjoint use of computerized-adaptive testing as the survey platform and item response theory as the measurement theory.

To increase the utility of administrative databases, it has been recommended that they include disease-specific, patient-centered outcome measures. This paper reviews practical and theoretical considerations and the critical evidence to support this recommendation. The strengths and weaknesses of the recommended approach are illustrated by examples of disease-specific measures for arthritis and musculoskeletal diseases. Current experience suggests that routine capture of these measures in administrative databases has formidable practical problems and would be unlikely to affect patient care. They could be used as gross indicators of a population's experience but would be insensitive to clinically meaningful improvement on the level of the individual patient. By themselves, these measures are unlikely to identify actionable strategies to improve outcomes, but they could improve efficiency. Overall, implementing this type of disease management improvement strategy would have little value in direct patient care and would be costly.

The Institute of Medicine defines health care quality as increasing "the likelihood of desired health outcomes" using "services ... consistent with current professional knowledge." This definition implies that quality measures can be based on either achieving health care outcomes or completing processes that experts agree have been shown by scientific evidence to improve outcomes. Process-based measures are especially suitable when the user needs to know how to improve quality, when provider comparisons show equivalent outcomes but all providers should improve processes, when measures are needed to evaluate health care that is intended to improve long-term outcomes, or when the contribution of individual providers (especially providers who have a small number of cases) needs to be defined. However, many different process-based measures are needed to comprehensively assess quality, and many process-based measures require detailed clinical data currently found only in medical records. Therefore, the expense of abstracting records is a barrier to process-based measurement. Fortunately, large-scale process-based measures are becoming more feasible because the required clinical data are being included in large databases. The merging of existing inpatient and outpatient databases with pharmacy and laboratory databases is an important step toward obtaining data that link all patient admissions, appointments, diagnostic procedures, and prescriptions with diagnoses and test results. Other data that are valuable for process-based measures must still be obtained by abstracting data from records, including clinical findings, patient preferences, and medical and family history. In the future, such data may be added to large databases to create computerized medical records.

Performance measurement has become increasingly popular in the health care delivery system of the United States. Until recently, the hospital was the most commonly scrutinized setting. With the expansion of managed care and the resulting compilation of large administrative databases, interest in performance measurement beyond the hospital setting has increased considerably. In particular, the performance of health maintenance organizations is now being assessed and reported publicly. The performance of individual physicians is also garnering considerable attention. This paper summarizes some of the many developments in performance measurement in managed care. The Health Plan Employer Data and Information Set (HEDIS) is described in the context of the national Report Card Pilot Project and with respect to local report card projects emerging around the United States. The lessons learned are identified, particularly with respect to external auditing of HEDIS data. Finally, the new initiatives of physician profiling and outcomes reporting are discussed.