Competitive insulin autoantibody assay. Prospective evaluation of subjects at high risk for development of type I diabetes mellitus.

A quantitative fluid-phase radioassay for autoantibodies reacting with insulin (competitive insulin autoantibody assay, CIAA) was developed. The assay's features include 1) use of a physiologic amount of 125I-labeled insulin, 2) parallel incubations with supraphysiologic cold insulin (competitive), and 3) an incubation time of 7 days and a single-step multiple-wash polyethylene glycol separation. Mean +/- SE CIAA levels in 50 controls were 8 +/- 1.4 nU/ml (range -16-33.3). In 36 cytoplasmic islet cell antibody (ICA)-positive nondiabetic first-degree relatives of type I (insulin-dependent) patients less than 30 yr of age, CIAA levels exceeded the normal range in 20 (55.6%) of 36 (mean 86.8 +/- 17.1 nU/ml). In 26 ICA-positive relatives greater than 30 yr of age, only 5 (19.2%) of 26 exceeded the normal range (mean 26.1 +/- 9.4 nU/ml); P less than .001 compared with younger ICA-positive relatives). Six ICA-negative HLA-identical siblings of type I diabetic patients had normal CIAA levels (mean 3.6 +/- 5.8 nU/ml), and only 2 of 13 ICA-negative identical twins discordant for diabetes (mean 15.4 +/- 6.6 nU/ml) exceeded the normal range. Nine (50%) of 18 ICA-positive schoolchildren exceeded the normal range (mean 105.3 +/- 36.7 nU/ml). Genetically susceptible subjects negative for CIAA (with only 3 exceptions) remained negative for CIAA on multiple determinations (3 conversions observed), and CIAA levels of positive subjects were relatively stable. Linear regression of the first CIAA level versus last (interval between sampling 1 mo to 10 yr) in genetically susceptible individuals showed a highly significant correlation (r = .95, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Patients who refuse treatment in medical offices.

Five hundred sixty-two consecutive patient visits to a medical office were prospectively evaluated for the presence of ethical problems. During 23 (4.0%) visits, patients refused recommended medical intervention. Refusal was defined as the rejection of preventive health measures, diagnostic evaluation, hospitalization, and other office procedures. Preventive health measures, vaccinations, and cancer screening were the most common types of intervention refused (n = 10). Diagnostic studies, such as roentgenograms, biopsies, and cardiac stress testing were also commonly refused (n = 9). The reasons for the refusal included psychologic factors, such as fear and anxiety, previous "bad" experiences with the recommended intervention, distrust of physicians, and problems of communication. Fourteen patients suffered no major consequences from their refusal, five of whom were seen twice during the study. Five patients had a delayed diagnosis and one patient died of a myocardial infarction after refusing hospitalization for unstable angina.

Clinical outcomes in statin treatment trials: a meta-analysis.

OBJECTIVE: To determine the risk of cardiovascular events and death in patients receiving statin treatment for cholesterol regulation. METHODS: Systematic review and meta-analysis of all randomized controlled trials that were published as of April 15, 1997. Primary or secondary prevention trials or regression trials were eligible. MAIN OUTCOME MEASURES: All-cause mortality, fatal myocardial infarction (MI) or stroke, nonfatal MI or stroke, angina, and withdrawal from the studies. Both random- and fixed-effects models were run for the outcomes of interests, and results are expressed as odds ratios (ORs). Sensitivity analyses tested the impact of the study type and duration, statin treatment type, and control arm event rates. Intent-to-treat denominators were used whenever they were available, and the number needed to treat was calculated when appropriate. RESULTS: Seventeen studies (21 303 patients) were included (2 secondary prevention studies, 5 mixed primary-secondary prevention population studies, and 10 regression trials). Treatment groups included lovastatin (t = 5), pravastatin (t = 10), and simvastatin (t = 3). For all-cause mortality, the OR was 0.76 (95% confidence interval [CI], 0.67-0.86) in favor of receiving statin treatment; for fatal MI, the OR was 0.61 (95% CI, 0.48-0.78); for nonfatal MI, the OR was 0.69 (0.54-0.88); for fatal stroke, the OR was 0.77 (95% CI, 0.57-1.04); for nonfatal stroke, the OR was 0.69 (95% CI, 0.54-0.88); and for angina, the OR was 0.70 (95% CI, 0.65-0.76). CONCLUSIONS: Patients who received statin treatment demonstrated a 20% to 30% reduction in death and major cardiovascular events compared with patients who received placebo. This advantage was generally present across study types and statin treatment types and for patients with less severe dyslipidemias. The benefit in clinical outcomes was noticeable as early as 1 year.

Systematic review and meta-analysis of the literature regarding the diagnosis of sleep apnea.

To establish the evidence base for the diagnosis of sleep apnea (SA) in adult patients, a systematic review of the literature from 1980 through November 1, 1997 was performed. Diagnostic studies were included if they reported results of any test to establish or support a diagnosis of SA, in comparison to a diagnosis from a full polysomnogram (PSG). Test results were meta-analyzed using fixed effects models and summary receiver operating characteristic curves (ROCs) to examine consistency of tests within and between diagnostics vs. the "gold standard" of PSG. From a total of 937 studies, 249 fit the broad eligibility criteria for inclusion in the clinical trial database and its data were extracted from these reports; useable data for statistical analyses were reported in 71 studies (7,572 patients). The sensitivity and specificity of partial channel and partial time PSGs appeared most promising as replacements for full PSG in patients suspected of obstructive SA. Clinical prediction rules (multivariate models) were also promising. Studies of portable sleep monitors, radiologic or morphologic features, and focused questionnaires were too heterogeneous to be meta-analyzed. In general, the diversity of study designs and objectives were very high and the methodological rigor of these studies as assessments of diagnostic tests was very low. Thus, we are still not in a position to recommend standardization of diagnostic methodology for sleep apnea. Instead, our recommendations for future research include standardization of terms and diagnostic criteria, and consistently reported statistics to enhance the utility of this literature.

Safety of GM-CSF in patients with AIDS: a review of the literature.

We performed a literature search for all clinical studies reporting outcomes in patients with the acquired immunodeficiency syndrome (AIDS) receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) for any indication. Safety outcomes included human immunodeficiency virus replication, immune status, and frequency of opportunistic infections and neoplasms. Data were synthesized qualitatively. We identified 22 studies (274 patients): 12 addressed AIDS neutropenia, 8 AIDS cancer therapy, and 2 opportunistic infections. Viral burden was assessed by serum p24Ag in 15 studies. Nine reported no change in levels, three net decreases, and three net increases. All studies showing net increases involved patients receiving GM-CSF without a concurrent antiretroviral. The CD4 counts were unchanged in 5 studies, increased in 3, and not reported in 14. The incidence of neoplasms or new opportunistic infections was low. The literature suggests no increased risk of viral replication or clinical deterioration in patients with AIDS who take GM-CSF concurrently with zidovudine.

A systematic review and meta-analysis of the incidence of cancer in randomized, controlled trials of verapamil.

We conducted a systematic review of all published randomized, controlled trials to assess the risk of cancer or death in patients receiving verapamil for hypertension, angina pectoris, or cardiac arrhythmias. Meta-analysis comparing the risk of new cancers, cancer deaths, and all deaths was performed. Thirty-nine trials comprising 11,201 patients were eligible. Study durations ranged from 8 days-6 years (mean 29.5 wks). Nine trials (6507 patients) were 24 weeks in duration or longer. For cancer and cancer death, OR was 1.20 (95% CI = 0.60-2.42) for verapamil versus active controls and 0.73 (95% CI = 0.39-1.39) for verapamil versus placebo. For all deaths, OR was 1.13 (95% CI = 0.70-1.82) for verapamil versus active controls and 0.85 (95% CI = 0.71-1.00) for verapamil versus placebo. Sensitivity analysis for the 9 trials 24 weeks' duration or longer gave similar results. There is no statistically significant increased risk of cancer or deaths with verapamil compared with active controls or placebo.

Teachers' perceptions of difficulties in teaching ethics in residencies.

In 1989 the authors surveyed faculty who were teaching medical ethics in residencies in order to obtain information concerning the goals, formats, topics, and settings of such teaching, as well as the difficulties encountered. Of 163 teachers contacted, 94 (58%) responded and 63 (39%), representing 50 institutions, reported participation in formal ethics teaching programs for residents. The 63 teachers reported using a variety of formats, including ethics rounds, lectures, and incorporating ethics teaching into weekly case-management conferences. Frequently mentioned goals of ethics teaching included improving the residents' skills in reasoning about ethical decisions and improving the residents' understanding of the language and concepts of ethics. Thirty-four of the 63 teachers (54%) taught ethics in hospital settings exclusively and 21 (33%) taught both in hospitals and in outpatient clinics or offices. The teachers identified a number of barriers encountered in carrying out such teaching, most of which can be grouped in six categories: (1) time constraints due to residents' heavy schedules; (2) attitudes of residents that pose obstacles; (3) logistical problems associated with teaching in the clinical setting; (4) time demands placed on teachers; (5) lack of reinforcement for teaching ethics from other faculty; and (6) shortcomings in the background and training of faculty for teaching ethics in the clinical setting. The authors conclude that difficulties are commonly encountered and discuss ways to overcome the principal barriers to effective teaching of ethics in the residency years.

Healthy patients who perceive poor health: why are they worried sick?

OBJECTIVE: To explore characteristics of patients who are physically healthy but who perceive poor health by investigating the hypothesis that mental health problems, financial strain, and deficiencies in social support underlie why these patients are "worried sick." METHODS: Three hundred forty-eight continuity patients in 2 rural primary care practices were administered the PRIME-MD, the MOS SF-36, a health-related worry (1-item, 5-point) scale, the MOS social support survey, and perceived economic strain instruments. The patient's physician rated physical health on a 10-point scale. Health care utilization was defined as the number of office visits and total office and laboratory charges for 6 months before and after the interview date. RESULTS: Two hundred thirty-seven patients (group A) scored in the upper and middle terciles on the MOS health perceptions scale. One hundred eleven patients scored in the lower tercile on health perceptions: 59 (group B) were rated as having good physical health (physical health rating > 6) and 52 (group C) as having poor health (rating < or = 6). The "worried sick" patients (group B) resembled Group A with regard to physical health, but resembled the sick (group C) with regard to all MOS functional scales, prevalence of mental health diagnoses, and worry. Social support was similar across groups. Only 1 of 3 measures of economic strain was less in group A than B and C. CONCLUSIONS: Our measures of mental health problems, financial strain, and deficiencies in social support accounted only in part for the differences among the three groups. Other explanations of why some are "worried sick" require study, such as other life stressors and personality traits.

Restoring balance to internal medicine training: the case for the teaching office practice.

Medical residents require an experience beyond the tertiary care hospital to understand many aspects of contemporary medical practice and to make informed career choices. To provide this balanced training, the University of Virginia has operated for 10 years an internal medicine teaching office practice to provide an outpatient experience similar to private practice. It allows residents to work closely with general internal medicine faculty and introduces them to the knowledge and skills necessary to establish and manage a successful practice. The curriculum of the 10 week rotation includes patient care in the office and by telephone, nursing home and home visits, tutorials and seminars on primary care and office management topics, and training in the use of microcomputers. A survey of 46 (92%) of the first 50 residents completing the rotation revealed that the content of the rotation was valuable, the rotation substantially influenced career choices, and the rotation helped provide a balanced view of internal medicine practice.

Emotions and the process of ethical decision-making.

Emotions play a central role in our daily lives. They influence our behavior as well as the development and direction of our relationships. Clinically, emotions may signal the presence of ethical conflicts between patients, physicians, and others involved in the patients' care. Emotions need to be recognized as physicians work toward empathic interactions, while both reason and emotion need to be integrated into the process of ethical decision making to ensure balanced outcomes.

Ethical problems in the medical office.

The majority of health care in this country is provided to patients in the office setting. This study, conducted in an internal medicine office practice, describes the ethical problems encountered in medical offices. Two hundred eighty consecutive patients, a total of 562 office visits, were prospectively evaluated. Ethical problems were defined as being present when specific ethical issues came into conflict with the physician's moral obligation to benefit the patient. The majority of the patients studied were white (214) and were women (212). The mean age of the patients was 49 years, with a range from 17 to 98 years. Ethical problems were present in 84 (30%) of the patients and in 119 (21%) of the office visits. The most common ethical problems for the patients were costs of care (11.1%), psychological factors that influence preferences (9.6%), competence and capacity to choose (7.1%), refusal of treatment (6.4%), informed consent (5.7%), and confidentiality (3.2%). Ethical problems were more common in patients over 60 years of age. This study establishes an educational as well as a research base for a broad study of biomedical ethics that looks beyond the problems encountered in the hospital.

KIE: In an effort to broaden the traditional focus of biomedical research and education on problems that occur in the hospital, the authors describe the prevalence and range of ethical problems encountered by 280 outpatients during 562 office visits to a community-based general internal medicine practice. Their study, which compiles statistics about the frequency of ethical problems during office visits according to sex, race, age, and classification of ethical issues, indicates that almost one third of the patients seen in office visits present ethical problems that influence their health care. Failure to teach students skills in this area may leave young physicians unable to cope with ethical problems, which may compromise good quality health care and diminish both the physicians' and the patients' satisfaction with medicine in general.

The medical school's mission and the population's health.

A conference organized by the Royal Society of Medicine Foundation was attended by 37 participants from Canada, the United Kingdom, the United States, and Australia. The discussants reviewed eight precirculated papers and concluded that society's concerns about the provision, availability, and costs of health care warranted re-examination of the assumptions and priorities of medical education. To reorient medical education to the actual and perceived health care needs of the population, specific recommendations were developed in five areas that integrate the patient, physician, and population perspectives on medical education: the medical school's goals and objectives, faculty development, undergraduate and postgraduate education, educational resources, and health intelligence. The participants also devised implementation strategies.

The reasons patients request "checkups": implications for office practice.

When patients request checkups, physicians may assume it is for detection of asymptomatic disease. However, such patients may have other, covert reasons for seeking medical care which might not be addressed by a periodic health examination. The authors interviewed 38 consecutive patients who requested a new appointment at an academic, hospital-based general medical practice, and said the appointment was for a checkup and not an acute problem. Health screening was the principal reason for requesting evaluation of only 24% of patients. Fifty-two per cent had two or more reasons: psychosocial problems, health concerns, or symptoms. Psychosocial problems, with and without other problems, were the reason 45% of patients requested checkups. Physicians should be alert to the various reasons why patients request checkups, and not assume that a periodic health examination alone is an appropriate response.

The prevalence of mental disorders in rural office practice.

OBJECTIVE: To determine the prevalence of mental disorders in rural primary care office practice. DESIGN: Patient interview; chart review. SETTING: Two rural primary care office practices. PATIENTS: Three hundred-fifty scheduled or walk-in patients age 18 years or older. MEASUREMENTS: Medical Outcomes Study 36-Item Short-Form Health Survey (MOS SF-36), the Primary Care Evaluation of Mental Disorders (PRIME-MD), physical health using Greenfield's index of coexistent disease (ICED), and health care utilization using the number of office visits and total office and laboratory charges six months before until six months after the interview. RESULTS: Of these patients 34% met criteria for one or more of the 18 mental disorders evaluated by the PRIME-MD; 19% met criteria for specific disorders according to criteria from the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R). Mood disorders were most common (21.7%), followed by anxiety disorders (12.3%), somatoform disorders (11.1%), probable alcohol abuse or dependence (6.0%), and eating disorders (2.0%). By logistic regression, there was an association of age, sex, race (black), and education with lower prevalence of various mental disorder categories. Even after adjustment for demographic variables and physical health (ICED score), those with PRIME-MD diagnoses had significantly lower function as measured by the eight MOS SF-36 scales and higher utilization of office services (p < .001). CONCLUSIONS: The prevalence of mental disorders in rural primary care office practice is as high as in urban office practice.

Warfarin skin necrosis: recurrence in the absence of anticoagulant therapy.

Skin necrosis is a well-known yet rare complication of oral anticoagulant therapy. We report the unusual recurrence of lesions typical of warfarin skin necrosis in the absence of anticoagulant therapy. A 59-year-old woman developed skin necrosis while receiving prophylactic warfarin following the detection of a large left ventricular thrombus. The warfarin was discontinued and the lesions improved. One month later new areas of skin necrosis developed although the patient had received no further warfarin. Progressive congestive heart failure, poor nutrition, and prolonged oral antibiotic therapy preceded the recurrence. Vitamin K deficiency was present on admission. The potential role of vitamin K-dependent coagulation factors in the pathogenesis of anticoagulant-associated skin necrosis is discussed.

Home visits in a rural office practice: clinical spectrum and effect on utilization of health care services.

OBJECTIVE: To describe the clinical features of home visits and their role in continuity of care, costs, and benefits in a rural office practice. DESIGN: Prospective study of all home visits performed during a 26-month period. SETTING: A general medicine teaching office practice located in rural Virginia. PATIENTS: All persons to whom home visits were made during the study period. MAIN RESULTS: 138 home visits were made to 47 patients who had a mean age of 73.2 years. Home visits accounted for 1.4% of patient encounters in the practice, required a mean of 7.1 miles of one-way travel and a mean of 48 minutes, including travel time, to complete, and generated $36 in income per visit. Most patients (27 of 47) were not permanently homebound. Reasons for patients' being homebound were grouped into six categories (acute illness, frail elderly, terminal illness, advanced chronic disease, neurologic problem, and miscellaneous reasons). The reasons for visits were grouped into four categories (acute self-limited illness, exacerbation of chronic disease, routine follow-up of chronic disease, and psychosocial problem). Physicians judged that 80% of home visits represented appropriate use of their services. In addition, 46% of home visits made an emergency room visit unnecessary, and 9% made a hospital admission unnecessary. At the time of 75% of home visits, physicians reported personal benefits of making the visit. CONCLUSIONS: Home visits have an important role in the care of ambulatory as well as permanently homebound patients. While physicians judged most home visits to be appropriate and personally beneficial, these visits required more time and generated less revenue than did office visits for comparable problems. Because home visits generated as well as prevented the use of medical services, their impact on the overall cost of medical care in this setting is unclear.

Healthy patients who perceive poor health and their use of primary care services.

OBJECTIVE: To determine what proportion of patients who have poor health perceptions are physically healthy and to explore why some patients perceive a healthy state while others perceive illness. DESIGN: A prospective consecutive series of office patients completed the Rand Corporation's General Health Perceptions Questionnaire, and their physicians rated their physical health. Their use of health care services was determined for the following 12 months. SETTING: A rural teaching office practice. PATIENTS: Of 243 adult patients asked to complete the questionnaire, 32 were excluded, for dementia (8), illiteracy (4), illness (8), incomplete questionnaires (6), and other reasons (6). 208 patients (86%) formed the final study group. MEASUREMENTS AND MAIN RESULTS: 62 of 208 patients had poor health perception scores. 39 of the 62 were rated by physicians as physically healthy and were not statistically different in physical health ratings or numbers of prescribed medications from the 146 patients who had higher health perception scores. However, these 39 patients had significantly more health-related worry, acute pain, and depression than did the other 146 patients. They also made more office visits and telephone calls and had higher total primary care charges. CONCLUSIONS: This study suggests that 21% of adult primary care patients (39 of 208) have health perceptions lower than expected for their levels of physical health. These low health perceptions are correlated with increased emotional distress and higher utilization of health care resources. Strategies to identify these patients and interventions to improve their views of their health could reduce utilization.