Examining if the relationship between BMI and incident type 2 diabetes among middle-older aged adults varies by race/ethnicity: evidence from the Multi-Ethnic Study of Atherosclerosis (MESA).

AIMS: Disparities persist on the prevalence of undiagnosed type 2 diabetes in racial/ethnic minorities in the USA. This study evaluated the association between BMI and incident type 2 diabetes risk by racial/ethnic group, to determine whether BMI and presence of type 2 diabetes risk factors may help clinicians better target type 2 diabetes screening. METHODS: This prospective cohort analysis included 5659 adults free of type 2 diabetes at baseline from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort (2000-2011). BMI was measured at baseline and time-updated at subsequent visits. Incident type 2 diabetes was defined as fasting glucose ≥ 7.0 mmol/l, or use of any diabetes medications. RESULTS: The mean (sd) age was 62 (10) years and 42% of participants were white, 26% African American, 20% Hispanic and 12% Chinese American. During follow-up, 696 (12%) new type 2 diabetes cases were observed. In age- and sex-adjusted models, in the presence of one or more type 2 diabetes risk factors (the most common scenario), a 10% risk of incident type 2 diabetes was observed at a BMI of 21.7 kg/m2 [95% confidence interval (CI) 20.1 to 22.8] in Chinese Americans, 23.8 kg/m2 (22.7 to 24.9) in Hispanics, 24.7 kg/m2 (23.7 to 25.6) in African Americans and 26.2 kg/m2 (25.1 to 26.9) in white participants. CONCLUSIONS: This study supports including BMI and presence of type 2 diabetes risk factors as action points for clinicians to prioritize which adults aged ≥ 45 years should be screened. The application of race/ethnicity-specific BMI thresholds may reduce the disparity of undiagnosed type 2 diabetes observed in minority groups.

American College of Rheumatology classification criteria for Sjögren's syndrome: a data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance cohort.

OBJECTIVE: We propose new classification criteria for Sjögren's syndrome (SS), which are needed considering the emergence of biologic agents as potential treatments and their associated comorbidity. These criteria target individuals with signs/symptoms suggestive of SS. METHODS: Criteria are based on expert opinion elicited using the nominal group technique and analyses of data from the Sjögren's International Collaborative Clinical Alliance. Preliminary criteria validation included comparisons with classifications based on the American­European Consensus Group (AECG) criteria, a model-based "gold standard"obtained from latent class analysis (LCA) of data from a range of diagnostic tests, and a comparison with cases and controls collected from sources external to the population used for criteria development. RESULTS: Validation results indicate high levels of sensitivity and specificity for the criteria. Case definition requires at least 2 of the following 3: 1) positive serum anti-SSA and/or anti-SSB or (positive rheumatoid factor and antinuclear antibody titer >1:320), 2) ocular staining score >3, or 3) presence of focal lymphocytic sialadenitis with a focus score >1 focus/4 mm2 in labial salivary gland biopsy samples. Observed agreement with the AECG criteria is high when these are applied using all objective tests. However, AECG classification based on allowable substitutions of symptoms for objective tests results in poor agreement with the proposed and LCA-derived classifications. CONCLUSION: These classification criteria developed from registry data collected using standardized measures are based on objective tests. Validation indicates improved classification performance relative to existing alternatives, making them more suitable for application in situations where misclassification may present health risks.

Utilization of TCD screening for primary stroke prevention in children with sickle cell disease.

BACKGROUND: In 1998, the Stroke Prevention Trial in Sickle Cell Anemia showed a >90% reduction in stroke rates after blood transfusion therapy in children with sickle cell disease (SCD) identified as high risk with transcranial Doppler ultrasonography (TCD) screening. METHODS: We studied the utilization of TCD screening in a retrospective cohort of all children with SCD within a large managed care plan from January 1993 to December 2005. Rates of first TCD screening were estimated using life table methods; predictors of TCD were evaluated using Cox proportional hazards regression. Stroke incidence rates were estimated in person-time before (pre-TCD) and after (post-TCD) first TCD. RESULTS: The average annual rate of TCD screening in 157 children with SCD was 1.8 per 100 person-years pre-1998, 5.0 from January 1, 1998, to December 31, 1999, and 11.4 after 1999. The only independent predictor of TCD screening was proximity to the vascular laboratory. The annualized stroke rate pre-TCD was 0.44 per 100 person-years, compared to 0.19 post-TCD. CONCLUSIONS: Since the Stroke Prevention Trial in Sickle Cell Anemia, the rate of transcranial Doppler ultrasonography (TCD) screening in sickle cell disease (SCD) has increased sixfold within a large health care plan. Children living farther from a vascular laboratory are less likely to be screened. Increased availability of TCD screening could improve the utilization of this effective primary stroke prevention strategy.

Sociodemographic, behavioral, and clinical correlates of inconsistent condom use in HIV-serodiscordant heterosexual couples.

We examined sociodemographic, behavioral, and clinical characteristics associated with inconsistent condom use in a cross-sectional analysis of 145 sexually active HIV-serodiscordant heterosexual couples who participated in the California Partners Study II. All couples were aware of their HIV-serodiscordant status. Forty-five percent of couples reported having had unprotected vaginal or anal sex in the previous 6 months. In the multivariate couple-level analyses, factors independently associated with inconsistent (i.e., <100%) condom use in the previous 6 months included lower educational level, unemployment, African-American ethnicity, and practice of anal sex by the couple. Injection drug use was associated with inconsistent condom use among couples with younger HIV-infected partners. In addition, couples with HIV-infected partners who had higher CD4 cell counts and couples in which the HIV-infected male partner ever had sex with a man were more likely to use condoms inconsistently. Consistency of condom use did not depend on the gender of the HIV-infected partner or duration of sexual relationship. The findings suggest that many HIV-serodiscordant heterosexual couples remain at high risk of HIV transmission and may benefit not only from behavioral interventions but also from structural interventions aimed at improving their social and economic conditions.

Risk factors for hospitalization among adults with asthma: the influence of sociodemographic factors and asthma severity.

BACKGROUND: The morbidity and mortality from asthma have markedly increased since the late 1970s. The hospitalization rate, an important marker of asthma severity, remains substantial. METHODS: In adults with health care access, we prospectively studied 242 with asthma, aged 18-50 years, recruited from a random sample of allergy and pulmonary physician practices in Northern California to identify risk factors for subsequent hospitalization. RESULTS: Thirty-nine subjects (16%) reported hospitalization for asthma during the 18-month follow-up period. On controlling for asthma severity in multiple logistic regression analysis, non-white race (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1-8.8) and lower income (OR, 1.1 per $10,000 decrement; 95% CI, 0.9-1.3) were associated with a higher risk of asthma hospitalization. The severity-of-asthma score (OR, 3.4 per 5 points; 95%, CI 1.7-6.8) and recent asthma hospitalization (OR, 8.3; 95%, CI, 2.1-33.4) were also related to higher risk, after adjusting for demographic characteristics. Reliance on emergency department services for urgent asthma care was also associated with a greater likelihood of hospitalization (OR, 3.2; 95% CI, 1.0-9.8). In multivariate analysis not controlling for asthma severity, low income was even more strongly related to hospitalization (OR, 1.2 per $10,000 decrement; 95% CI, 1.02-1.4). CONCLUSION: In adult asthmatics with access to health care, non-white race, low income, and greater asthma severity were associated with a higher risk of hospitalization. Targeted interventions applied to high-risk asthma patients may reduce asthma morbidity and mortality.

Predictors of cigarette smoking and smoking cessation among adults with asthma.

OBJECTIVES: This study sought to determine the predictors of smoking and time until smoking cessation in a cohort of adults with asthma. METHODS: Adults with asthma (n = 374) in northern California completed structured telephone interviews at baseline and 18-month follow-up. RESULTS: Of the 374 subjects, 156 reported ever having smoked, and 39 indicated that they currently smoked. Earlier birth cohort, lower educational attainment. White race, and presence in childhood residence of an adult who smoked were associated with a greater risk of ever smoking. Lower educational attainment, early smoking initiation, higher daily cigarette consumption, and late-childhood-onset asthma were associated with a longer interval until smoking cessation. CONCLUSIONS: Persons with asthma at high risk of cigarette smoking and delayed quitting can be identified on the basis of clinical and demographic characteristics.

Trends in oral cancer rates in the United States, 1973-1996.

OBJECTIVES: To explore changes in demographic distribution, incidence and survival rates of oral cancer in the United States from 1973 through 1996. METHODS: From the Surveillance, Epidemiology, and End Results (SEER) data, we computed the proportion of oral cancer by demographic characteristics, site, and stage at diagnosis for 1973-84 and 1985-96. We estimated incidence and 5-year relative survival rates of oral cancer by age, gender, and race/ethnicity, and compared survival rates between the two periods. The estimated annual percent change (EAPC) was used to explore trends in incidence rate from 1973 through 1996. RESULTS: Most of the tongue and floor of mouth cancers (>54%) reported during 1973-84 and 1985-96 had spread to a distant site at time of diagnosis. The age-adjusted annual incidence rates of oral cancer decreased among white men from 1973 through 1996, but increased among black men aged 65-69 years, and among young white men (aged 30-34 years) and women (aged 25-29 years). These changes in trend were all statistically significant (testing EAPC=0 at the 0.05 level). Overall, there was no improvement in the 5-year relative survival rate of either whites or blacks with oral cancer. CONCLUSION: There was little change in early detection of oral cancer or in 5-year relative survival rates between 1973-84 and 1985-96 in nine SEER regions. This suggests a deficiency in professional and public education regarding early diagnosis of oral cancer. Furthermore, the increasing trend of oral cancer among older black men and among younger whites merits further investigation.

Epidemiologic evidence for time variation in HIV infectivity.

Data from three epidemiologic studies of heterosexual transmission of HIV among monogamous couples are used to assess evidence for time variation in HIV infectivity, possibly related to varying levels of infectiousness following infection in the primary infected partner. Analyses are based on statistical techniques that account for the inherent incompleteness of exposure information from such studies, and that allow direct assessment of the hypotheses that infectivity varies with time since infection and across partnerships. Data include findings from 302 couples from the California Partners' Study and 51 and 31 couples, respectively, from two U.S. Center for Disease Control and Prevention (CDC)-sponsored studies of infection in partners of transfusion recipients. Results indicate weak evidence for higher infectivity following infection of the primary partner, decreasing to relatively lower levels from 2 to 10 years after. Although these findings are consistent with biologic observations of time variation in viral levels, other explanations of the observed pattern (e.g., heterogeneity of infectivity) are equally plausible, pointing out some inherent limitations of data from such studies.

Environmental tobacco smoke and adult asthma. The impact of changing exposure status on health outcomes.

The effect of environmental tobacco smoke (ETS) exposure on adults with asthma has not been well characterized. In a prospective cohort study of 451 nonsmoking adults with asthma, we evaluated the impact of ETS exposure on asthma severity, health status, and health care utilization over 18 mo. There were 129 subjects (29%; 95% CI, 25-33%) who reported regular ETS exposure, falling into three categories: exposure at baseline but none at follow-up (n = 43, 10%), no baseline exposure and new exposure at follow-up (n = 56, 12%), and exposure at both baseline and follow-up (n = 30, 7%). In cross-sectional analyses, subjects with baseline ETS exposure had greater severity-of-asthma scores (score difference, 1.7; 95% CI, 0. 2-3.1), worse asthma-specific quality of life scores (score difference, 3.5; 95% CI, 0.03-7.0), and worse scores on the Medical Outcomes Study SF-36 physical component summary (score difference, 3. 0; 95% CI, 0-6.0) than unexposed subjects. They also had greater odds of emergency department visits (odds ratio [OR] = 2.1; 95% CI, 1.2-3.5), urgent physician visits (OR = 1.9; 95% CI, 1.1-3.3), and hospitalizations (OR = 1.9; 95% CI, 1.02-3.6). In longitudinal follow-up, subjects reporting ETS cessation showed improvement in severity-of-asthma scores (score reduction, -3.2; 95% CI, -4.4 to -2. 0) and physical component summary scores (score increase, 5.3; 95% CI, 2.6-8.1). Environmental tobacco smoke cessation decreased the odds of emergency department visits (OR = 0.4; 95% CI, 0.2-0.97) and hospitalizations (OR = 0.2; 95% CI, 0.04-0.97) after adjustment for covariates. Environmental tobacco smoke initiation was associated with greater asthma severity only in subjects with high-level (>= 3 h/wk) exposure (score increase, 1.4; 95% CI, 0.03-2.7). In conclusion, self-reported ETS exposure is associated with greater asthma severity, worse health status, and increased health care utilization in adults with asthma.

Generalized additive models for current status data.

Current status data arise in studies where the target measurement is the time of occurrence of some event, but observations are limited to indicators of whether or not the event has occurred at the time the sample is collected--only the current status of each individual with respect to event occurrence is observed. Examples of such data arise in several fields, including demography, epidemiology, econometrics and bioassay. Although estimation of the marginal distribution of times of event occurrence is well understood, techniques for incorporating covariate information are not well developed. This paper proposes a semiparametric approach to estimation for regression models of current status data, using techniques from generalized additive modeling and isotonic regression. This procedure provides simultaneous estimates of the baseline distribution of event times and covariate effects. No parametric assumptions about the form of the baseline distribution are required. The results are illustrated using data from a demographic survey of breastfeeding practices in developing countries, and from an epidemiological study of heterosexual Human Immunodeficiency Virus (HIV) transmission.

Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study.

To examine rates of and risk factors for heterosexual transmission of human immunodeficiency virus (HIV), the authors conducted a prospective study of infected individuals and their heterosexual partners who have been recruited since 1985. Participants were recruited from health care providers, research studies, and health departments throughout Northern California, and they were interviewed and examined at various study clinic sites. A total of 82 infected women and their male partners and 360 infected men and their female partners were enrolled. Over 90% of the couples were monogamous for the year prior to entry into the study; < 3% had a current sexually transmitted disease (STD). The median age of participants was 34 years, and the majority were white. Over 3,000 couple-months of data were available for the follow-up study. Overall, 68 (19%) of the 360 female partners of HIV-infected men (95% confidence interval (CI) 15.0-23.3%) and two (2.4%) of the 82 male partners of HIV-infected women (95% CI 0.3-8.5%) were infected. History of sexually transmitted diseases was most strongly associated with transmission. Male-to-female transmission was approximately eight-times more efficient than female-to-male transmission and male-to-female per contact infectivity was estimated to be 0.0009 (95% CI 0.0005-0.001). Over time, the authors observed increased condom use (p < 0.001) and no new infections. Infectivity for HIV through heterosexual transmission is low, and STDs may be the most important cofactor for transmission. Significant behavior change over time in serodiscordant couples was observed.

Clofazimine as prophylaxis for disseminated Mycobacterium avium complex infection in AIDS.

A randomized, prospective, open-label, treatment versus no treatment community-based clinical trial was conducted to evaluate the safety and efficacy of clofazimine as prophylaxis for disseminated Mycobacterium avium complex (MAC) infection in patients with human immunodeficiency virus (HIV) disease. Subjects were 110 patients with a first episode of Pneumocystis carinii pneumonia 2-4 months before enrollment or CD4 lymphocyte counts < or = 100/mm3; they were randomized to receive 50 mg of clofazimine daily or no treatment. Seven patients randomized to clofazimine developed disseminated MAC infection, compared with 6 patients receiving no treatment. Seventeen patients died: 9 in the treatment group and 8 receiving no treatment. Clofazimine at a dose of 50 mg/day is well tolerated by patients with HIV disease. Reduction in CD4 lymphocyte count to < 50/mm3 is a significant predictor of the development of disseminated MAC infection.

Risk factors for hepatitis C virus seropositivity in heterosexual couples.

OBJECTIVES: To determine the risk of heterosexual transmission of hepatitis C virus (HCV) and to identify other risk factors for HCV seropositivity in heterosexual couples. DESIGN: Retrospective cross-sectional study comparing HCV-seropositive and HCV-seronegative heterosexual men and women. SETTING: Couples recruited from the community and screened for participation in a study of the heterosexual transmission of human immunodeficiency virus. PARTICIPANTS: A total of 340 subjects, 170 men and 170 women in sexual partnerships, aged 18 through 61 years. MAIN OUTCOME MEASURE: Seropositivity for HCV antibodies. RESULTS: Overall, 31 (18%) of the 170 women and 56 (33%) of the 170 men were positive by a four-antigen HCV immunoblot. Injection drug use and hemophilia were strongly associated with HCV seropositivity. Sixty-four percent of injection drug users were positive (odds ratio [OR], 27.0; 95% confidence interval [CI], 13.4 to 56.1; P < .0001), as were all four hemophiliacs in the study. History of blood transfusion was significantly associated with HCV seropositivity (OR, 2.7; 95% CI, 1.1 to 7.0; P = .02). Positivity for HCV was not associated with measures of sexual behavior within couples or with numbers of other sexual partners, history of sexually transmitted diseases, or human immunodeficiency virus seropositivity. However, two of the 31 women without parenteral risk but with a long-term HCV-positive male partner were HCV seropositive compared with none of 81 women with an HCV-negative male partner (P = .07). CONCLUSIONS: These results provide little evidence of HCV sexual transmission but are consistent with infrequent sexual transmission. They corroborate the importance of injection drug use and transfusion of blood or blood products in transmitting HCV and underscore the importance of ascertaining parenteral exposures when examining sexual transmission of HCV.

Female-to-male transmission of human immunodeficiency virus.

OBJECTIVE: --To examine rates of heterosexual transmission of human immunodeficiency virus (HIV) and associated risk factors and to determine the relative efficiency of female-to-male and male-to-female transmission. DESIGN: --Survey of infected individuals and their heterosexual partners recruited since 1985. SETTING: --Participants were recruited from various HIV counseling and testing sites throughout California but were generally interviewed and tested in their homes. PARTICIPANTS: --Data from 379 couples at entry to the study are reported: 72 male partners of infected women and 307 female partners of infected men. The infected index case had a well-established source of risk; couples were eliminated if the direction of transmission could not be established. The majority of couples were monogamous since 1978, white, and in their 30s. Most partners did not know their serostatus at entry into the study. MAIN OUTCOME MEASURE: --HIV serostatus in the exposed sexual partner. RESULTS: --We observed one probable instance (1%) of female-to-male transmission compared with 20% transmission rates in the female partners of infected men. All couples were sampled in the same way. Male index cases were more likely to be symptomatic than female index cases. CONCLUSION: --The odds of male-to-female transmission were significantly greater than female-to-male transmission. The one case of female-to-male transmission was unique in that the couple reported numerous unprotected sexual contacts and noted several instances of vaginal and penile bleeding during intercourse.

CD8+ T lymphocytes and progression to AIDS in HIV-infected men: some observations.

The relationship between CD8+ lymphocyte counts and progression to AIDS was studied in 340 HIV-1-seropositive men participating in a population-based prospective study. Overall, the relative hazard for developing AIDS during 60 months of observation was slightly elevated (1.08, P = 0.003), indicating an 8% increase in risk of progression for every 100 CD8+ cell count increment. When the data were analyzed in relation to date of diagnosis, the relative hazard was depressed (0.90, P less than 0.001) for the period 6 months prior to diagnosis, but was close to 1.0 for the period 6-36 months prior to diagnosis. These findings suggest a complex relationship between CD8+ cell counts and progression to AIDS, with the possibility that various subsets of the CD8+ compartment play different roles.

Statistical analysis of HIV infectivity based on partner studies.

Partner studies produce data on the infection status of partners of individuals known or assumed to be infected with the human immunodeficiency virus (HIV) after a known or estimated number of contacts. Previous studies have assumed a constant probability of transmission (infectivity) of the virus at each contact. Recently, interest has focused on the possibility of heterogeneity of infectivity across partnerships. This paper develops parametric and nonparametric procedures based on partner data in order to examine the risk of infection after a given number of contacts. Graphical methods and inference techniques are presented that allow the investigator to evaluate the constant infectivity model and consider the impact of heterogeneity of infectivity, error in measurement of the number of contacts, and regression effects of other covariates. The majority of the methods can be computationally implemented easily with use of software to fit generalized linear models. The concepts and techniques are closely related to ideas from discrete survival analysis. A data set on heterosexual transmission is used to illustrate the methods.

The effect of number of exposures on the risk of heterosexual HIV transmission.

Several studies of the heterosexual transmission of human immunodeficiency virus have reported no association between transmission and number of exposures. In contrast, this study showed that for a susceptible sex partner, the number of exposures to an infected index case is indeed associated with transmission, but in a nonlinear fashion. Factors that can dilute an association between transmission and number of exposures include measurement error in calculating number of exposures, use of inappropriate statistical models, and failure to account for variations in transmission rates. For example, the practice of anal intercourse and the experience of bleeding during intercourse increase the likelihood of transmission. We also observed that transmission occurred with fewer exposures among couples who did not use condoms compared with couples who did. The number of exposures also affects the independent association between other risk factors and transmission and thus should be considered when analyzing other sources of risk.