Genome-wide search for sarcoidosis susceptibility genes in African Americans.

Sarcoidosis, a systemic granulomatous disease of unknown etiology, likely results from an environmental insult in a genetically susceptible host. In the US, African Americans are more commonly affected with sarcoidosis and suffer greater morbidity than Caucasians. We searched for sarcoidosis susceptibility loci by conducting a genome-wide, sib pair multipoint linkage analysis in 229 African-American families ascertained through two or more sibs with a history of sarcoidosis. Using the Haseman-Elston regression technique, linkage peaks with P-values less than 0.05 were identified on chromosomes 1p22, 2p25, 5p15-13, 5q11, 5q35, 9q34, 11p15 and 20q13 with the most prominent peak at D5S2500 on chromosome 5q11 (P=0.0005). We found agreement for linkage with the previously reported genome scan of a German population at chromosomes 1p and 9q. Based on the multiple suggestive regions for linkage found in our study population, it is likely that more than one gene influences sarcoidosis susceptibility in African Americans. Fine mapping of the linked regions, particularly on chromosome 5q, should help to refine linkage signals and guide further sarcoidosis candidate gene investigation.

Sarcoidosis: social predictors of severity at presentation.

To determine relationships among social predictors and sarcoidosis severity at presentation, demographic characteristics, socioeconomic status, and barriers to care, A Case-Control Etiologic Study of Sarcoidosis (ACCESS) was set up. Patients self-reported themselves to be Black or White and were tissue-confirmed incident cases aged > or =l8-yrs-old (n=696) who had received uniform assessment procedures within one of 10 medical centres and were studied using standardised questionnaires and physical, radiographical, and pulmonary function tests. Severity was measured by objective disease indicators, subjective measures of dyspnoea and short form-36 subindices. The results of the study showed that lower income, the absence of private or Medicare health insurance, and other barriers to care were associated with sarcoidosis severity at presentation, as were race, sex, and age. Blacks were more likely to have severe disease by objective measures, while women were more likely than males to report subjective measures of severity. Older individuals were more likely to have severe disease by both measures. In conclusion, it was found that low income and other financial barriers to care are significantly associated with sarcoidosis severity at presentation even after adjusting for demographic characteristics of race, sex, and age.

Clinical characteristics of patients in a case control study of sarcoidosis.

Sarcoidosis may be affected by sex, race, and age. A Case Control Etiologic Study of Sarcoidosis (ACCESS) enrolled 736 patients with sarcoidosis within 6 mo of diagnosis from 10 clinical centers in the United States. Using the ACCESS sarcoidosis assessment system, we determined organ involvement for the whole group and for subgroups differentiated by sex, race, and age (less than 40 yr or 40 yr and older). The study population was heterogeneous in terms of race (53% white, 44% black), sex (64% female, 36% male), and age (46% < 40 yr old, 54% > or = 40 yr old). Women were more likely to have eye and neurologic involvement (chi(2) = 4.74, p < 0.05 and chi(2) = 4.60, p < 0.05 respectively), have erythema nodosum (chi(2) = 7.28, p < 0.01), and to be age 40 yr or over (chi(2) = 6.07, p < 0.02) whereas men were more likely to be hypercalcemic (chi(2) = 7.38, p < 0.01). Black subjects were more likely to have skin involvement other than erythema nodosum (chi(2) = 5.47, p < 0.05), and eye (chi(2) = 13.8, p < 0.0001), liver (chi(2) = 23.3, p < 0.0001), bone marrow (chi(2) = 18.8, p < 0.001), and extrathoracic lymph node involvement (chi(2) = 7.21, p < 0.01). We conclude that the initial presentation of sarcoidosis is related to sex, race, and age.

Familial aggregation of sarcoidosis. A case-control etiologic study of sarcoidosis (ACCESS).

Despite reports of familial clustering of sarcoidosis, little empirical evidence exists that disease risk in family members of sarcoidosis cases is greater than that in the general population. To address this question, we estimated sarcoidosis familial relative risk using data on disease occurrence in 10,862 first- and 17,047 second-degree relatives of 706 age, sex, race, and geographically matched cases and controls who participated in the multicenter ACCESS (A Case-Control Etiology Study of Sarcoidosis) study from 1996 to 1999. Familial relative risk estimates were calculated using a logistic regression technique that accounted for the dependence between relatives. Sibs had the highest relative risk (odds ratio [OR] = 5.8; 95% confidence interval [CI] = 2.1-15.9), followed by avuncular relationships (OR = 5.7; 95% CI = 1.6-20.7), grandparents (OR = 5.2; 95% CI = 1.5-18.0), and then parents (OR = 3.8; 95% CI = 1.2-11.3). In a multivariate model fit to the parents and sibs data, the familial relative risk adjusted for age, sex, relative class, and shared environment was 4.7 (95% CI = 2.3-9.7). White cases had a markedly higher familial relative risk compared with African-American cases (18.0 versus 2.8; p = 0.098). In summary, a significant elevated risk of sarcoidosis was observed among first- and second-degree relatives of sarcoidosis cases compared with relatives of matched control subjects.

Sarcoidosis severity and socioeconomic status.

Several chronic diseases are more severe in persons who are Black, of low socioeconomic status (SES), and underinsured. The authors ask if this is true for sarcoidosis. Associations among sarcoidosis disease severity, SES, insurance coverage, and functional limitations were analysed. Back and White sarcoidosis patients (n=110) of a municipal and university hospital sarcoidosis registry were interviewed by telephone. Data on disease severity were abstracted from patient charts. Most patients reported good or excellent health by demographic characteristics. Low SES and no or public insurance were associated with worse health status and more severe dyspnoea. More advanced radiographic stage was associated with lower income, and forced vital capacity impairment with less education. Physical and social activity limitations due to physical and emotional disability were related to no or public insurance and lower income, but not education. Sarcoidosis severity is associated with socioeconomic status and insurance indicators; no or public insurance and low income are associated with functional limitations. Sarcoidosis-associated limitations are substantial, emphasizing the social significance of sarcoidosis. Lack of private insurance may inhibit the use of medical care, contributing to disease severity and impairment.

Pulmonary sarcoidosis: comparison of patients at a university and a municipal hospital.

Charts and radiographs of sarcoidosis patients seen at a private university hospital and at a municipal hospital were reviewed to determine whether there was a difference in the severity of disease retrospectively. A standardized abstract form was used to identify and abstract information on new and continuing sarcoidosis patients seen at either Georgetown University Medical Center (GUMC) or District of Columbia General Hospital (DCGH) during a 2-year period. Because there were too few white sarcoidosis patients for comparison, analysis was done for African-American patients only. African-American patients at GUMC were slightly older, with a higher percentage of women. For GUMC patients, 76% had private insurance and 21% had public insurance, and for DCGH patients, one-half had public insurance and 29% had no insurance. Significantly fewer GUMC patients (7% versus 36%) reported moderate to severe dyspnea. Chest radiographs showed a larger percentage of patients with stage 1 disease at GUMC and more patients with stage 4 disease at DCGH. Spirometry showed more impairment of forced expired volume in one second (FEV1) in GUMC patients, but diffusing capacity of the lung for carbon monoxide (DLCO) values were significantly lower among DCGH patients. Less than 8% of GUMC patients showed disease progression compared with almost one-third of DCGH patients. These results demonstrate that substantially less severe pulmonary sarcoidosis was seen in African-American patients treated at a private, nonprofit university hospital compared with a municipal hospital. Factors that determine the use of municipal hospitals, such as limited financial access to care and sources of patients, may have played a major role in the differences seen.

Adapting an effective primary care provider STD/HIV prevention training programme.

Sexually acquired human immunodeficiency virus (HIV) infection continues to be the major source of HIV infection in the USA. Preventing sexual transmission of HIV can be accomplished through patient behaviour change. Such behaviour change can also decrease risk of other sexually transmitted diseases (STDs) and unwanted pregnancies, both far more common problems than HIV infection. Primary care physicians and other providers can increase patients' safe sex practices by conducting effective sexual risk assessment (RA) and risk reduction (RR) counselling, but physicians both infrequently and incompletely do sexual RA and RR. A programme was developed to improve primary care physicians' prevention practice using Simulated Patient Instructors (SPIs) and mailed educational materials. Programme evaluations showed improved sexual RA and RR practice both by self-report as well as by observation by Simulated Patient Evaluators (SPEs). This paper briefly reviews these findings and then presents adaptations made to improve the programme's content, decrease its cost and increase its availability for training many other care providers. Evaluation of the adapted programme indicates that content and training methods are highly regarded by a diverse array of trainees. To disseminate the modified programme beyond the local area, a Train-the-Trainer programme and manual have been developed, including discussion of recruiting, training and using SPIs for sexual risk reduction. Wider use of this training, as well as more effective and more readily available STD/HIV prevention training, are needed to attain national goals of provider clinical prevention practice.

Commentary on the federal role in clinical prevention research.

Effective clinical prevention practice is the objective of the long journey from laboratory and epidemiologic studies to clinical understanding, interventions, and prevention practice with individual patients. The ability to ask ever more fundamental questions about the molecular basis of disease, as is rapidly being developed by NIH's Human Genome Project, promises to make this journey even longer and more complicated, but eventually to make screening and intervention for preventable disease even more amenable to clinical intervention. As we expect in the future, much of what we currently do in clinical prevention practice had its genesis in earlier federal support for basic and clinical research. We comment on the content and major points of the papers on the federal role in prevention research. These papers, in addition to describing the past accomplishment, current state, and future opportunities for prevention research, raise questions about the ultimate application of the enormous and successful national investment in prevention research. A fault line exists among the increasing knowledge of prevention practice, the rapid changes in the way services are delivered, and demonstration of the effectiveness of prevention procedures applied for the good of the whole population. The federal agencies most concerned with the application of prevention knowledge are those most limited in their research budgets: the Agency for Health Care Policy and Research (AHCPR) and the Centers for Disease Control and Prevention (CDC). The National Institutes of Health (NIH), with the greatest research dollars for investment, also has the broadest mandate for investment in research. Meeting all the demands to fund high-quality research is challenging; however, NIH may have review procedures that disadvantage clinical researchers and, among these, applied prevention researchers. The restructuring of the health care system by managed care promises opportunity for more effectiveness research. However, the same competition that fosters the development of managed care may limit the extent of prevention experimentation and the dissemination of results. Current national concerns for the weakening of support for clinical research are in part due to the reduced availability of patient care revenue to support clinical research brought about by managed care. The academic and practice communities that share concern for prevention research should recognize the increasing gap between basic and applied prevention knowledge. Those committed to the clinical application of this knowledge should encourage increased federal research support to assure that what we think we know is indeed so, that what is efficacious is available to all in the society that so generously supports research.

Association of ventricular ectopy with nuclear scintigraphic perfusion defects during dipyridamole stress testing.

BACKGROUND AND HYPOTHESIS: No information is available regarding the significance of ventricular ectopic activity induced during dipyridamole nuclear scintigraphic stress testing. This study tested the hypothesis that dipyridamole-induced ventricular ectopy predicts a thallium-201 or technetium-99m sestamibi perfusion defect. METHODS: A group of 186 consecutive patients with premature ventricular contractions and/or couplets occurring during dipyridamole stress testing (ventricular tachycardia did not occur) was compared with a control group of 194 patients without ventricular ectopy during dipyridamole stress testing. RESULTS: The results indicated that ventricular ectopy induced during dipyridamole infusion occurred more frequently in patients demonstrating either a fixed or reversible perfusion defect on scintigraphic imaging (p < 0.01). The higher frequency of perfusion defects in this group of patients was attributable to a higher frequency of "fixed" compared with "reversible" defects (p < 0.05). This finding is consistent with the additional observation that ventricular ectopy induced by dipyridamole was associated with the presence of Q waves on the resting ECG (p < 0.05). The positive and negative predictive values of the presence of ventricular ectopy in predicting a fixed myocardial perfusion defect were 59 and 54%, respectively. CONCLUSIONS: Ventricular ectopy induced during dipyridamole infusion suggests the presence of a fixed myocardial perfusion defect.

Improving office-based physician's prevention practices for sexually transmitted diseases.

OBJECTIVE: To determine whether office-based interventions increase primary care physicians' risk assessment of and counseling practices for patients regarding sexually transmitted diseases and the human immunodeficiency virus (HIV). DESIGN: Randomized controlled clinical trial. SETTING: Washington, D.C., Metropolitan Statistical Area. STUDY PARTICIPANTS: Office-based primary care physicians (family or general practice, internal medicine, and obstetrics-gynecology). INTERVENTION: Mailed educational materials alone or coupled with a simulated patient instructor office visit. MEASUREMENTS: Self-reported and observed frequency of assessing and counseling patients regarding their risk factors for sexually transmitted diseases and HIV infection. Participants were interviewed by telephone before and after the intervention (n = 757). A subset of participants (n = 194) was also observed after the intervention by simulated patient evaluators in blinded office visits. RESULTS: 89% of physicians who received both educational materials and a simulated patient instructor visit reported that they reviewed the educational materials compared with 53% of those who only received the educational materials (P < or = 0.001). Physicians in the combined intervention group had higher self-reported and observed rates for several risk assessment questions and counseling recommendations than did physicians in the control group or the group that only received educational materials. Seventy-three percent of physicians of the combined intervention group reported an increase in counseling patients about reducing risky sexual behavior compared with 53% of the group receiving only educational materials and 42% of the control group (P < or = 0.001). CONCLUSIONS: Mailed educational materials combined with an office visit by a simulated patient instructor for role-play and feedback on clinical performance increased the frequency of office-based physicians' risk assessment and risk reduction counseling of patients for sexually transmitted diseases and HIV infection.

Self-reports of HIV risk factors by patients at a sexually transmitted disease clinic: audio vs written questionnaires.

OBJECTIVES: The purpose of this study was to determine how the method of assessment affects patient report of human immunodeficiency virus (HIV) risks. METHODS: Patients at a sexually transmitted disease clinic randomly received either a written self-administered questionnaire or an audio self-administered questionnaire delivered by cassette player and headset. These questionnaires were followed by face-to-face interviews. RESULTS: Audio questionnaires had fewer missing responses than written questionnaires. Audio questionnaires also identified more unprotected vaginal intercourse and sexual partners suspected or known to have HIV infection or acquired immunodeficiency syndrome than did written questionnaires. Although both the audio and written questionnaires identified more risks than the face-to-face interviews, the difference in the mean number of reported risks between the audio questionnaires and the face-to-face interviews was greater than that between the written questionnaires and the face-to-face interviews. CONCLUSIONS: Audio questionnaires may obtain more complete data and identify more HIV risk than written questionnaires. Research is warranted about whether audio questionnaires overcome barriers to the completion and accuracy of HIV risk surveys. This study emphasizes the need to elucidate the relative strengths and weaknesses of written questionnaires, audio questionnaires, and face-to-face interviews for HIV risk assessment.

Knowledge, attitudes, and practices of obstetricians-gynecologists regarding the prevention of human immunodeficiency virus infection.

OBJECTIVE: To determine the knowledge, beliefs, attitudes, and practices of obstetricians-gynecologists regarding human immunodeficiency virus (HIV) prevention. METHODS: Office-based obstetricians-gynecologists in the Washington, DC metropolitan area who reported providing primary care were interviewed by telephone. The survey response rate was 62% (N = 268). RESULTS: The percentages of obstetricians-gynecologists who reported regularly assessing the HIV risk of new adolescent and adult patients were 67 and 40%, respectively. Seventy-two percent reported regularly counseling patients at risk to use condoms for vaginal intercourse, and 60% regularly counseled patients at risk to limit their number of sexual partners. The level of general risk-factor assessment and confidence in the ability to reduce patients' HIV risk were the strongest correlates of the frequency and thoroughness of HIV risk assessment and counseling. CONCLUSIONS: The percentage of obstetricians-gynecologists who assess and counsel patients about HIV risks is below the 75% goal for the year 2000 established by the United States Department of Health and Human Services. Continuing medical education for obstetricians-gynecologists is needed to improve their knowledge and skills in HIV prevention.

Functional limitations among home health care users in the National Health Interview Survey Supplement on Aging.

A case-control study compared home health care (HHC) users from the 1984 Supplement on Aging to users of other community services and of no community service, matched on age and gender. Examination of specific activities of daily living (ADLs), instrumental activities of daily living (IADLs), and sociodemographic variables showed that HHC users were significantly more limited than controls in every ADL and IADL. In multivariate analyses, HHC use was significantly associated with three ADLs (dressing, going outside, bathing), two IADLs (shopping, heavy housework), and poor health status.

The effect of educational preparation on physician performance with a sexually transmitted disease-simulated patient.

BACKGROUND: Simulated patients are used with increased frequency for medical students and residents, but have not been used very often with practicing physicians. We hypothesized that educational materials could improve primary care physicians sexual practices history taking and counseling as assessed by a simulated patient in the physician's office. METHODS: Simulated patient (SP) visits were made to 232 (75% of eligible) primary care physicians. The patient simulated was a sexually active young woman with vaginitis and sexually transmitted disease/human immunodeficiency virus risk behaviors. In advance of the visit, physicians were provided educational materials (monograph, pamphlet, and audiotape) developed for the study, including a risk assessment questionnaire that could be used with patients. RESULTS: Most physicians randomly allocated to the intervention participated. Twenty-one percent of physicians refused to schedule an SP visit. Physicians who received an SP rated the experience highly. Physicians who prepared for the visit with the educational materials performed significantly better than those who did not. About two thirds of physicians reviewed the materials, many for the second time, after the SP visit. Physicians who used the study risk assessment questionnaire performed better. Many physicians (24.9% to 39.8%) did not meet each of the four goals for the visit, as assessed subjectively by the SP. Physician performance was better for measures of general patient interaction than for measures of sexual practices history taking and counseling techniques. CONCLUSION: The SP visit was acceptable to most physicians practicing in a community and was evaluated by them as an appealing and an effective educational experience. The SP, however, has limited feasibility because of cost. The SP led to review of materials by nearly all physicians either before or after the visit. Physicians who prepared before the visit performed better on every dimension, eliciting more information, displaying better patient interaction skills, and meeting more of the educational goals. Even with educational preparation, however, many physicians were not perceived as being effective counselors.

Unannounced simulated patients' observations of physician STD/HIV prevention practices.

Studies describing sexually transmitted disease (STD) and human immunodeficiency virus (HIV) prevention practices of primary care physicians have relied on physician or patient reports. This study describes physician STD/HIV prevention practices as observed by unannounced simulated patient evaluators (SPEs). SPEs visited sixty-five primary care physicians. Each SPE portrayed a sexually active female, new to the area, requesting a consultation on STD prevention. One-third of the physicians in the study asked no risk questions, and over 80% failed to ask the SPE specifically about her sexual practices. Most physicians discussed the risks of STDs and HIV and covered basic recommendations (use condoms and know partners better); however, few physicians provided any individualized information or advice about safer sexual practices and the specifics of condom use, such as how to use them or what kind to use. These observations support the low rates of STD/HIV prevention indicated in physicians' self-report and further identify specific deficiencies in the thoroughness of their risk assessment and preventive counseling practices.

An acquired hemorrhagic disorder from long-acting rodenticide ingestion.

A 62-year-old man who presented with gross hematuria was found to have a severe and prolonged coagulopathy. The workup involved mixing studies, which suggested an acquired factor deficiency, and specific factor assays, which demonstrated isolated defects in vitamin K-dependent factors. With vitamin K deficiency excluded, and serum warfarin levels undetectable, so-called superwarfarin ingestion was suspected. This diagnosis was subsequently proved by biochemical evidence (an increase in the serum vitamin K epoxide-vitamin K ratio) and compatible history. This case illustrates how a logical workup can lead to a diagnosis of superwarfarin ingestion, even without a history of such an ingestion. New serum assays for specific superwarfarins are also mentioned. This case report should increase clinicians' awareness of long-acting rodenticide ingestions.

Frequency and thoroughness of STD/HIV risk assessment by physicians in a high-risk metropolitan area.

The US Preventive Services Task Force recommends that all primary care physicians assess the sexually transmitted disease/human immunodeficiency virus (STD/HIV) risk of all adolescent and adult patients. To determine whether factors amenable to change through continuing medical education are associated with frequent and thorough STD/HIV risk assessment, a telephone survey of primary care physicians in the Washington, DC metropolitan area was conducted (n = 961). Thirty-seven percent of physicians reported regularly asking new adult patients about their sexual practices; 60% asked new adolescent patients. STD/HIV risk questioning was associated with physicians' confidence in their ability to help prevent HIV, comfort with discussing patients' sexual practices, and perception of a large STD/HIV problem in their practice. These findings suggest that continuing medical education should target improvement in physicians' sexual practice questioning skills.

Implementing the Association of Teachers of Preventive Medicine's recommendations into the undergraduate medical school curriculum.

In 1989, an expert panel appointed by the Association of Teachers of Preventive Medicine proposed minimum curricular content requirements for health promotion-disease prevention, including recommendations for timing, duration, and course sequencing during medical school. Making clinical preventive medicine an integral part of a primary care rotation is a central feature of the proposal. The panel presents recommendations for using the Guide to Clinical Preventive Services, which assesses the effectiveness of 169 types of prevention interventions, in both undergraduate and postgraduate medical education. Recommendations for incorporating the guide into the undergraduate medical school curriculum are outlined. The recommendations include options for using the guide as part of a curriculum in quantitative skills, in clinical preventive medicine, in a primary care rotation, as a health services and community dimension curriculum, and as part of continuing self-education. Recognizing that teaching methods and curriculum structures are varied in preventive medicine, the panel designed the recommendations to be adaptable to all medical schools' programs. The recommendations are aimed at achieving the goal of making preventive medicine an integral part of the education, training, and practice of physicians.