Recent years have witnessed a rapidly growing crisis in antimicrobial resistance, especially among microorganisms that cause nosocomial infection. To better understand common risk factors among multiresistant organisms, this review explores risk factors for nosocomial infection with methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococcus, Clostridium difficile, extended-spectrum beta-lactamase-producing gram-negative bacilli, and Candida. This review comprises data from 74 published studies; 53 (71%) were retrospective studies and addressed few risk factors or did not quantify risk. The analysis shows impressive commonality of risk factors across these diverse multiresistant organisms: advanced age; underlying diseases and severity of illness; inter-institutional transfer of the patient, especially from a nursing home; prolonged hospitalization; gastrointestinal surgery or transplantation; exposure to invasive devices of all types, especially central venous catheters; and exposure to antimicrobial drugs, especially cephalosporins. More restricted use of antibiotics, especially cephalosporins, and strategies to prevent medical device-related infection and cross-infection in the hospital would yield benefit with all types of resistant organisms. Preemptive isolation of all patients with risk factors for infection by resistant organisms would very likely reduce secondary spread within the hospital. Conversely, programs that focus on only one organism or one antimicrobial drug are unlikely to succeed. Prospective studies of sufficient size that address all potential risk factors, especially individual anti-infective agents, and that use matched controls who are shown by surveillance cultures to be free of colonization by resistant organisms would enhance understanding of the epidemiology of antimicrobial resistance in institutions and guide efforts to develop more effective strategies for prevention.

In alternative medicine, the main question regarding placebo has been whether a given therapy has more than a placebo effect. Just as mainstream medicine ignores the clinical significance of its own placebo effect, the placebo effect of unconventional medicine is disregarded except for polemics. This essay looks at the placebo effect of alternative medicine as a distinct entity. This is done by reviewing current knowledge about the placebo effect and how it may pertain to alternative medicine. The term placebo effect is taken to mean not only the narrow effect of a dummy intervention but also the broad array of nonspecific effects in the patient-physician relationship, including attention; compassionate care; and the modulation of expectations, anxiety, and self-awareness. Five components of the placebo effect--patient, practitioner, patient-practitioner interaction, nature of the illness, and treatment and setting--are examined. Therapeutic patterns that heighten placebo effects are especially prominent in unconventional healing, and it seems possible that the unique drama of this realm may have "enhanced" placebo effects in particular conditions. Ultimately, only prospective trials directly comparing the placebo effects of unconventional and mainstream medicine can provide reliable evidence to support such claims. Nonetheless, the possibility of enhanced placebo effects raises complex conundrums. Can an alternative ritual with only nonspecific psychosocial effects have more positive health outcomes than a proven, specific conventional treatment? What makes therapy legitimate, positive clinical outcomes or culturally acceptable methods of attainment? Who decides?

Bloodstream infections related to use of catheters, particularly central-line catheters, are an important cause of patient morbidity, mortality, and increased health care costs. This study evaluated the efficacy of skin disinfection with chlorhexidine gluconate compared with povidone-iodine solution in preventing catheter-related bloodstream infection.

To clarify whether screening adults for depression in primary care settings improves recognition, treatment, and clinical outcomes.

This statement summarizes the current U.S. Preventive Services Task Force (USPSTF) recommendations for screening for depression and the supporting scientific evidence and updates the 1996 USPSTF recommendations on this topic. At that time, the USPSTF concluded that there was insufficient evidence to recommend for or against routine use of standardized questionnaires to screen for depression in primary care patients. The complete information on which the current statement is based, including evidence tables and references, is available in the accompanying article in this issue and in the systematic evidence review on this topic, which can be obtained through the USPSTF Web site (http://www.ahrq.gov/clinic/uspstfix.htm) and in print through the Agency for Healthcare Research and Quality Publications Clearinghouse (800-358-9295).

Echocardiography is not recommended as a routine imaging test to diagnose suspected pulmonary embolism. However, it is useful for identifying patients with pulmonary embolism who may have a poor prognosis. It can be used for rapid and accurate risk assessment. Moderate or severe right ventricular hypokinesis, persistent pulmonary hypertension, a patent foramen ovale, and free-floating right-heart thrombus are echocardiographic markers that identify patients at risk for death or recurrent thromboembolism. Such patients warrant consideration for thrombolysis or embolectomy. Serial imaging of right ventricular function can help physicians monitor the effect of treatment and judge whether the selected management strategy is successful. Further research will clarify and define more precisely the utility and limitations of echocardiography in the management of pulmonary embolism.

Postmenopausal estrogen replacement is widely used in the United States but poses important health risks.

The relative effectiveness of the diverse approaches used to promote preventive care activities, such as cancer screening and adult immunization, is unknown. Despite many high-quality published studies, practices and policymakers attempting to improve preventive care have little definitive information on which to base decisions. Thus, we quantitatively assessed the relative effectiveness of previously studied approaches for improving adherence to adult immunization and cancer screening guidelines.

The Hematology Disease Site Group of the Cancer Care Ontario Practice Guidelines Initiative has systematically reviewed the published literature and, through a consensus process, developed an evidence-based practice guideline assessing the role of stem-cell transplantation in patients with multiple myeloma. The conclusions were validated by solicited feedback from 221 practitioners across Ontario, Canada. The guideline comprises six recommendations: 1) Autologous transplantation is recommended for patients with stage II or III myeloma and good performance status. Evidence of benefit is strongest for patients who are younger than 55 years of age and have a serum creatinine level less than 150 micromol/L (<1.7 mg/dL). Physicians must use clinical judgment in recommending transplantation to other patients. 2) Allogeneic transplantation is not recommended as routine therapy. 3) Patients potentially eligible for transplantation should be referred for assessment early after diagnosis and should not be extensively exposed to alkylating agents before collection of stem cells. 4) Autologous peripheral blood stem cells should be harvested early in the patient's treatment course. The best available data suggest that transplantation is most advantageous when performed as part of initial therapy. 5) The comparative data addressing the specifics of the transplantation process are insufficient to allow definitive recommendations. In the absence of such data, a single transplant with high-dose melphalan, with or without total-body irradiation, is suggested for patients undergoing transplantation outside a clinical trial. 6) At this time, no conclusions can be reached about the role of interferon therapy after transplantation.

Progression to renal parenchymal damage and end-stage renal disease, which seems to be largely independent of the initial insult, is the final common pathway for chronic, proteinuric nephropathies in animals and humans. The key event is enhanced glomerular capillary pressure; this impairs glomerular permeability to proteins and permits excessive amounts of proteins to reach the lumen of the proximal tubule. The secondary process of reabsorption of filtered proteins can contribute to renal interstitial injury by activating intracellular events, including upregulation of the genes encoding vasoactive and inflammatory mediators. Both interstitial inflammation and progression of disease can be controlled by such drugs as angiotensin-converting enzyme inhibitors, which strengthen the glomerular permeability barrier to proteins and thereby limit proteinuria and filtered protein-dependent inflammatory signals. Clinical data strongly suggest that remission can now be achieved in some patients with chronic renal disease. Because of the current lag time between starting treatment and remission, however, a substantial proportion of patients still progress to end-stage renal disease before renal function begins to stabilize. A multimodal approach that centers on reducing or removing all risk factors associated with the progression of renal disease may decrease the time to remission of the disease for most patients with proteinuric nephropathies.

Physicians are increasingly grappling with medical liability issues as complementary and integrative health care practices are made available in conventional medical settings. This article proposes a framework in which physicians can assess potential malpractice liability issues in counseling patients about complementary and integrative therapies. The framework classifies complementary and integrative therapies according to whether the evidence reported in the medical and scientific literature supports both safety and efficacy; supports safety, but evidence regarding efficacy is inconclusive; supports efficacy, but evidence regarding safety is inconclusive; or indicates either serious risk or inefficacy. Clinical examples in each category help guide the clinician on how to counsel patients regarding use of complementary and alternative medical therapies in a given clinical situation. Specific strategies to reduce the risk for potential malpractice liability include the following: 1) determine the clinical risk level; 2) document the literature supporting the therapeutic choice; 3) provide adequate informed consent; 4) continue to monitor the patient conventionally; and 5) for referrals, inquire about the competence of the complementary and alternative medicine provider. This framework provides a basis for clinical decisions involving complementary and integrative care.

In aplastic anemia, hematopoiesis fails: Blood cell counts are extremely low, and the bone marrow appears empty. The pathophysiology of aplastic anemia is now believed to be immune-mediated, with active destruction of blood-forming cells by lymphocytes. The aberrant immune response may be triggered by environmental exposures, such as to chemicals and drugs or viral infections and, perhaps, endogenous antigens generated by genetically altered bone marrow cells. In patients with post-hepatitis aplastic anemia, antibodies to the known hepatitis viruses are absent; the unknown infectious agent may be more common in developing countries, where aplastic anemia occurs more frequently than it does in the West. The syndrome paroxysmal nocturnal hemoglobinuria (PNH) is intimately related to aplastic anemia because many patients with bone marrow failure have an increased population of abnormal cells. In PNH, an entire class of proteins is not displayed on the cell surface because of an acquired X-chromosome gene mutation. The PNH cells may have a selective advantage in resisting immune attack. In contrast, the disease myelodysplasia can be confused with aplasia and can also evolve from aplastic anemia. The occurrence of cytogenetic abnormalities in patients years after presentation implies that genomic instability is a feature of this immune-mediated disease. Aplastic anemia can be effectively treated by stem-cell transplantation or immunosuppressive therapy. Transplantation is curative but is best used for younger patients who have histocompatible sibling donors. Antithymocyte globulin and cyclosporine restore hematopoiesis in approximately two thirds of patients. However, recovery of blood cell count is often incomplete, recurrent pancytopenia requires retreatment, and some patients develop late complications (especially myelodysplasia).

Physical activity has been associated with reduced blood pressure in observational epidemiologic studies and individual clinical trials. This meta-analysis of randomized, controlled trials was conducted to determine the effect of aerobic exercise on blood pressure.

Testicular cancer is the most common solid tumor diagnosed in men 20 to 35 years of age. Because of highly effective treatments that may include surgery, chemotherapy, and radiation therapy, most patients become long-term survivors. Health-related issues that confront testicular cancer survivors include the late medical effects of chemotherapy, the late relapse of disease, the development of second cancers, the effect of the disease and treatment on fertility, and the psychosocial consequences. This case-based discussion focuses on the primary care physician's evaluation and management of a long-term survivor of testicular cancer who was previously treated with surgery and chemotherapy.

Population-based longitudinal studies of hypertension have usually shown a continuous and positive relationship between blood pressure and mortality. However, several studies in hypertensive patients receiving treatment have described this relationship as J-shaped, with an increased risk for events in patients with low blood pressure.

Traditionally, acupuncture is embedded in naturalistic theories that are compatible with Confucianism and Taoism. Such ideas as yin-yang, qi, dampness, and wind represent East Asian conceptual frameworks that emphasize the reliability of ordinary, human sensory awareness. Many physicians who practice acupuncture reject such prescientific notions. Numerous randomized, controlled trials and more than 25 systematic reviews and meta-analyses have evaluated the clinical efficacy of acupuncture. Evidence from these trials indicates that acupuncture is effective for emesis developing after surgery or chemotherapy in adults and for nausea associated with pregnancy. Good evidence exists that acupuncture is also effective for relieving dental pain. For such conditions as chronic pain, back pain, and headache, the data are equivocal or contradictory. Clinical research on acupuncture poses unique methodologic challenges. Properly performed acupuncture seems to be a safe procedure. Basic-science research provides evidence that begins to offer plausible mechanisms for the presumed physiologic effects of acupuncture. Multiple research approaches have shown that acupuncture activates endogenous opioid mechanisms. Recent data, obtained by using functional magnetic resonance imaging, suggest that acupuncture has regionally specific, quantifiable effects on relevant brain structures. Acupuncture may stimulate gene expression of neuropeptides. The training and provision of acupuncture care in the United States are rapidly expanding.