To review the available information on prevalence, complications, and mortality of non-insulin-dependent diabetes mellitus and primary and secondary prevention activities in black persons, Hispanic persons, Native Americans, and Asians and Pacific Islanders in the United States.

To review important topics related to prostate cancer that have arisen since this subject was last covered in Annals in 1993. The review consists of two parts. Part II describes neoadjuvant hormonal therapy, new local treatment options (including three-dimensional conformal radiation therapy, brachytherapy, and cryosurgery), antiandrogen therapy management of erectile dysfunction, funding and legislation for research, and areas for future research, especially in genetics investigations.

Cytomegalovirus (CMV) retinitis, a common complication of the acquired immunodeficiency syndrome (AIDS), is increasing in frequency as patients infected with the human immunodeficiency virus (HIV) live longer. In recent years, the lifetime risk for CMV disease in HIV-infected persons has increased from 24.9% to 44.9%. Cytomegalovirus retinitis is usually diagnosed clinically: Almost all patients are CMV seropositive and have CD4+ counts less than 50 cells/mm3. Specific diagnostic tests that use antigen detection or quantitation of circulating nucleic acid to detect CMV are being developed, but they have not been validated for routine clinical use. Such tests would help predict disease, diagnose acute retinitis, and monitor therapy. Therapy with systemic agents, including intravenous ganciclovir, intravenous foscarnet, and intravenous cidofovir, is effective. However, it is cumbersome, costly, and associated with considerable toxicity, therapy encouraging investigation of other therapeutic approaches. Intravitreous injections with antiviral agents are effective, but the short half-life of available agents makes these injections inconvenient. Intraocular implants that slowly release ganciclovir have been effective for both acute therapy and long-term maintenance, but they need to be directly compared with intravenous and oral regimens to determine which regimen will optimally maximize convenience, preserve vision, and improve survival. Cytomegalovirus retinitis could be prevented by improved antiretroviral therapies or by immune-based therapies that would prolong the time during which patients remain immunocompetent. Once patients become immunologically susceptible to CMV end-organ disease (when their CD4+ counts decrease to < 50 cells/ mm3), specific chemotherapy with oral ganciclovir is promising, but the cost, inconvenience, toxicity, and conflicting reports of efficacy associated with this strategy mean that it needs careful assessment before it can be considered standard treatment. Management of CMV retinitis is on the verge of major changes. In the next few years, improvements in diagnostic, therapeutic, and preventive tools should reduce morbidity and mortality from this disease.

To review important topics related to prostate cancer that have arisen since this subject was last covered in Annals in 1993. The review consists of two parts, Part I describes advances in prostate-specific antigen (PSA) interpretation (including PSA density and velocity, age-specific reference ranges, "free" and "bound" PSA ratios, the utility of PSA in defining the pathologic extent of prostate cancer, and the use of these concepts in helping define appropriate treatment strategies), the management of patients with organ-confined prostate cancer, and pathologic interpretation of prostatectomy specimens.

Evidence that families requested to permit organ donation refuse half the time has led to proposals for mandated choice. Under mandated choice, a person's donation wishes would be collected and retrieved at death, and requests to families would be avoided. There are both ethical and logistic problems with mandated choice. The view of the family should be respected in organ requests, even when patient wishes are known. Public sentiment against overriding family wishes could cause low rates of pro-donation registration. Caregivers have usually refused to take organs when families oppose donation. Logistic issues with mandated choice include the cost and complexity of maintaining a national database on donors and the enforcement of registration. No such database of adults currently exists, even for tax purposes. Two states that have mandated choice programs through departments of motor vehicles report relatively low number of pro-donation registrants compared with nondonors or undecided persons. Public education and voluntary donor identification hold more potential to increase donation.

A severe shortage of organs greatly limits the ability to deliver the miracle of transplantation to people suffering from end-stage organ disease. Contributing to this shortage is a high rate of refusal among families who are asked for permission to remove organs from a recently deceased relative. Mandated choice offers an alternative to obtaining consent from the family by returning control to the individual. This plan would require all adults to record their wishes about posthumous organ donation and would consider those wishes binding. By moving the decision-making process to a relaxed setting and ensuring that a person's wishes would be honored, mandated choice would hopefully take advantage of favorable public attitudes toward donation and thereby facilitate organ procurement. Preliminary research suggests that public commitment to organ donation would increase under mandated choice. A pilot study of this promising proposal should be undertaken.

As the health care system changes and large managed care entities gain greater control in some markets, proponents of antitrust reform have expressed concern that physicians could lose their autonomy. To respond to this concern, the American College of Physicians has consistently argued that physicians should be allowed to establish their own health plans and networks to provide high-quality and cost-effective care. Moreover, the College has advocated utilization review reform and due process protections to empower physicians in their dealings with insurers. Under current antitrust law, as interpreted by the federal enforcement agencies, physicians already have the legal authority to form their own health plans and networks, and many state medical societies are sponsoring such plans. The law also allows physicians to operate the clinical components of a health plan, regardless of who owns it. Moreover, physicians can share information about quality, utilization, and, in some circumstances, fees. An examination of federal enforcement agency actions since the mid-1970s shows that physician networks have rarely been challenged. In light of market developments, however, the College has urged the federal antitrust agencies to analyze the effect of their current enforcement policies on physician activities and adopt a more flexible approach. Further monitoring and analysis of the changing health care marketplace are necessary to ensure that physicians are being treated fairly and to determine which factors spur or inhibit the development of physician-run health plans and networks.

To review the current understanding of the clinical significance, detection, pathogenesis, and prevention of anthracycline-induced cardiotoxicity.

The term "failure to thrive" is frequently used to describe older adults whose independence is declining. The term was exported from pediatrics in the 1970s and is used to describe older adults with various concurrent chronic diseases, functional impairments, or both. Despite this heterogeneity, failure to thrive has had its own international Classification of Diseases, Ninth Revision (ICD-9) code since 1979 and has been approached as a clinically meaningful diagnosis in many review articles. This conceptual framework, however, can create barriers to proper evaluation and management. The most worrisome of these barriers is the reinforcement of both fatalism and intellectual laziness, which need to be balanced with a deconstructionist approach, wherein the major areas of impairment are identified and quantified and have their interactions considered. Four syndromes known to be individually predictive of adverse outcomes in older adults are repeatedly cited as prevalent in patients with failure to thrive: impaired physical functioning, malnutrition, depression, and cognitive impairment. The differential diagnosis of contributors to each of these syndromes includes the other three syndromes, and multiple contributors often exist concurrently. Some of these contributors are unmodifiable, some are easily modifiable, and some are potentially modifiable but only with the use of resource-intensive strategies, initial interventions should be directed at easily remediable contributors in the hope of improving overall functional status, because a single contributor may simultaneously influence several other syndromes that conspire to create the phenotype of failure to thrive. How aggressively should more resource-intensive strategies for less easily modifiable contributors be pursued? This is a central clinical, ethical, and policy issue in geriatric medicine that cannot be settled without better process and outcome data. This paper examines the medical etymology of failure to thrive and proposes a rational approach to evaluation and management that is based on the limited medical literature.

Human herpesvirus-6 can be an opportunistic pathogen in transplant recipients.

Unlike patients in a randomized, clinical trial, patients in an observational study choose if and when to begin treatment. Patients who live longer have more opportunities to select treatment; those who die earlier may be untreated by default. These facts are the essence of an often overlooked bias, termed "survivor treatment selection bias," which can erroneously lead to the conclusion that an ineffective treatment prolongs survival. Unfortunately, misanalysis of survivor treatment selection bias has been prevalent in the recent literature on the acquired immunodeficiency syndrome. Approaches to mitigating this bias involve complex statistical models. At a minimum, initiation of therapy should be treated as a time-dependent covariate in a proportional hazards model. Investigators and readers should be on the alert for survivor treatment selection bias and should be cautious when interpreting the results of observational treatment studies.

Despite the increased intensity and sophistication of research on pain mechanisms in the past three decades, serious uncertainties remain about the neuronal origin of pain, especially in painful clinical conditions. Although a positive correlation between nociceptive afferent activity and the subjective perception of pain has been seen under controlled experimental conditions, important mismatches point to the critical importance of central nervous system processes as determinants of pain. Multiple peripheral, segmental, and supraspinal neuronal activities control nociceptive processing at all levels of the neuraxis. Three studies in this issue highlight the problem of identifying the neuronal determinants of pain by addressing contrasting mismatches: angina-like chest pain without an obvious cause and a potential source of angina (myocardial ischemia) without pain. The results of these studies suggest that selective visceral hyperalgesia and hypoalgesia of peripheral or central origin may be present without other clinical evidence for neurologic abnormality. Complex mechanisms interacting at several levels of the nervous system appear to be involved.

The ability to quantitate human immunodeficiency virus (HIV) in blood and tissues from patients at all stages of disease has provided new insights into the pathogenesis of HIV disease. There is a dynamic equilibrium between HIV production and clearance even during the period of clinical latency, which may permit resistant virus to emerge with the imposition of drug pressure. Disruption of the equilibrium with effective drugs reduces circulating levels of HIV within 1 week, thus allowing the rapid assessment of new candidate drugs. To maximize the magnitude and durability of HIV RNA suppression, therapeutic strategies must be implemented that are effective against high levels of rapidly replicating virus that consist of many genetic variants.

The National Cholesterol Education Program recommends reducing total and low-density lipoprotein cholesterol levels to decrease the risk for coronary heart disease. The available evidence clearly indicates that higher cholesterol levels increase the risk for coronary heart disease and that cholesterol reduction results in corresponding decreases in risk. In contrast, existing data do not strongly support the idea that cholesterol reduction causes increases in any specific nonvascular cause of death. The outcomes of ongoing, large-scale trials will enable existing guidelines to be refined. However, current recommendations, which encourage nonpharmacologic interventions for about 30% of U.S. adults and cholesterol-reducing drugs for about 7% of U.S. adults, seem both justified and warranted.

Over the last decade, the number of pharmaceutical benefits managers has increased, and their influence has expanded rapidly. These managers now provide prescription drug coverage to more than 100 million Americans. The effect of pharmaceutical benefits managers on health care delivery remains unclear. We review the development of these organizations, their current role in the delivery of pharmaceutical therapies to patients, and their relationship with pharmaceutical manufacturers. We discuss potential advantages and disadvantages of pharmaceutical benefits manager practices and suggest ways in which these organizations can be made more accountable to the employer groups that hire them.

To review the current knowledge about breast cancer in black women--including epidemiology, risk factors, screening practices, pathology, clinical manifestations, treatment, and outcome--with emphasis on issues that might explain why the survival rate in this population of women is lower than that in white women.

To assess the effect of dietary calcium supplementation on blood pressure.

To do a meta-analysis of studies that have evaluated the sensitivity and specificity of polymerase chain reaction (PCR) assay for the diagnosis of human immunodeficiency virus (HIV) infection in adults. Evaluating the performance of PCR is difficult because in certain clinical situations, the sensitivity or specificity of PCR may exceed those of the current reference standard tests (enzyme immunoassay followed by confirmatory Western blot analysis). Therefore, an additional goal was to develop recommendations for 1) the design of future evaluative studies of PCR and 2) the use of PCR in persons with suspected HIV infection.

The preoperative evaluation of the cardiac patient having noncardiac surgery offers an opportunity to identify occult and further define known cardiovascular disease to modify both perioperative and long-term care. The baseline probability of cardiovascular disease should initially be assessed using clinical variables and identifying unstable symptoms, including unstable angina and congestive heart failure. The decision about whether to obtain noninvasive testing to further define cardiovascular status should be made on the basis of the testing's potential to modify perioperative care, the prior probability of advanced coronary disease based on clinical history, and the magnitude of the surgical procedure. Noninvasive testing is best done in selected patients who are at moderate clinical risk. Otherwise, testing loses its predictive value because of a high incidence of false-negative and false-positive results. Quantitative imaging can also be used to identify those patients in whom coronary angiography is indicated. The value of coronary revascularization before noncardiac surgery has not been studied in a randomized, prospective manner, but several cohort studies have suggested that patients who survive coronary artery bypass grafting have decreased risk during subsequent noncardiac surgery. Given the potential short-term increase in morbidity from two surgical procedures, it is prudent to reserve coronary revascularization before noncardiac surgery for those patients in whom it is associated with improved long-term survival. If coronary revascularization is reserved for these patients, then the overall evaluation should prove cost-effective from the perspective of both perioperative and long-term cardiovascular care.