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Background: Intervention packages may result in a greater public health impact than single interventions. Understanding the separate impact of each component on the overall package effectiveness can improve intervention delivery. Methods: We adapted an approach to evaluate the effects of a time-varying intervention package in a network-randomized study. In some network-randomized studies, only a subset of participants in exposed networks receive the intervention themselves. The spillover effect contrasts average potential outcomes if a person was not exposed to themselves under intervention in the network versus no intervention in a control network. We estimated the effects of components of the intervention package in HIV Prevention Trials Network 037, a Phase III network-randomized HIV prevention trial among people who inject drugs and their risk networks using marginal structural models to adjust for time-varying confounding. The index participant in an intervention network received a peer education intervention initially at baseline, then boosters at 6 and 12 months. All participants were followed to ascertain HIV risk behaviors. Results: There were 560 participants with at least one follow-up visit, 48% of whom were randomized to the intervention, and 1,598 participant visits were observed. The spillover effect of the boosters in the presence of initial peer education training was a 39% rate reduction (rate ratio = 0.61; 95% confidence interval = 0.43, 0.87). Conclusions: These methods will be useful for evaluating intervention packages in studies with network features. [ABSTRACT FROM AUTHOR]

Regression calibration as developed by Rosner, Spiegelman, and Willett is used to adjust the bias in effect estimates due to measurement error in continuous exposures. The method involves two models: a measurement error model relating the mismeasured exposure to the true (or gold-standard) exposure and an outcome model relating the mismeasured exposure to the outcome. However, no comprehensive guidance exists for determining which covariates should be included in each model. In this article, we investigate the selection of the minimal and most efficient covariate adjustment sets under a causal inference framework. We show that to address the measurement error, researchers must adjust for, in both measurement error and outcome models, any common causes (1) of true exposure and the outcome and (2) of measurement error and the outcome. We also show that adjusting for so-called prognostic variables that are independent of true exposure and measurement error in the outcome model, may increase efficiency, while adjusting for any covariates that are associated only with true exposure generally results in efficiency loss in realistic settings. We apply the proposed covariate selection approach to the Health Professional Follow-up Study dataset to study the effect of fiber intake on cardiovascular disease. Finally, we extend the originally proposed estimators to a nonparametric setting where effect modification by covariates is allowed. [ABSTRACT FROM AUTHOR]

Background: Four of the largest HIV prevention trials have been conducted in sub-Saharan Africa, enrolling hundreds of thousands of participants in catchment areas of millions of people. The trials have focused on community-level interventions to increase diagnosis and initiation of antiretroviral therapy (ART) to improve health and reduce HIV transmission. Universal test-and-treat strategies are deployed to achieve viral suppression thereby reducing risk to uninfected persons, known as treatment as prevention (TasP). Purpose: We review the work that found HIV plasma load to correlate with transmission risk, demonstrated that ART could reduce genital tract viral expression, and showed early treatment to be beneficial for persons living with HIV, and that HIV-uninfected sexual partners were protected from infection. We review the seemingly inconsistent findings of the major TasP trials: the TasP [National Agency for AIDS Research (ANRS) 12249] study in South Africa, the SEARCH trial in Kenya and Uganda, the Botswana Combination Prevention Project Ya Tsie study, and the HIV Prevention Trials Network 071 (PopART) trial in Zambia and South Africa. Findings: All the trials reinforce the critical need to identify approaches to optimize programs and incentivize uptake and engagement in HIV testing and ART-based care in ways that consistently reduce HIV transmission. That other chronic conditions can be screened for and treated in the same infrastructures suggests added value of HIV investments. Conclusions: Implementation challenges are a principal frontier in the global struggle to reduce HIV transmission and mortality using TasP, complementing efforts to find a cure for HIV and an effective, deployable vaccine. [ABSTRACT FROM AUTHOR]

An altered hormonal or chronic systemic inflammatory milieu characterizing endometriosis may result in a higher risk of hypercholesterolemia and hypertension. Conversely, elevated low-density lipoprotein in hypercholesterolemia and chronic systemic inflammation resulting from hypertension may increase the risk of endometriosis. We assessed the association of laparoscopically confirmed endometriosis with hypercholesterolemia and hypertension in a large prospective cohort study. In 1989, 116 430 registered female nurses aged 25 to 42 completed the baseline questionnaire and were followed for 20 years. Multivariable Cox proportional hazards models were applied. In 1989, there were 4244 women with laparoscopically confirmed endometriosis and 91 554 women without. After adjusting for demographic, anthropometric, family history, reproductive, dietary, and lifestyle risk factors prospectively, comparing women with laparoscopically confirmed endometriosis to women without, the relative risks were 1.25 (95% confidence interval, 1.21-1.30) for development of hypercholesterolemia and 1.14 (95% confidence interval, 1.09-1.18) for hypertension. Conversely, the relative risks of developing laparoscopically confirmed endometriosis were 1.22 (95% confidence interval, 1.15-1.31) comparing women with hypercholesterolemia to women without and 1.29 (95% confidence interval, 1.18-1.41) comparing women with hypertension to women without. The strength of associations of laparoscopically confirmed endometriosis with hypercholesterolemia or hypertension was strongest among women aged ≤40 and weakened as age increased (P values for interaction <0.001). We observed that ≈45% of the associations between endometriosis and hypercholesterolemia and hypertension could be accounted for by treatment factors after endometriosis diagnosis, including greater frequency of hysterectomy/oophorectomy and earlier age for this surgery. In this large cohort study, laparoscopically confirmed endometriosis was prospectively associated with increased risk of hypercholesterolemia and hypertension. Conversely, hypercholesterolemia and hypertension were prospectively associated with higher risk of laparoscopically confirmed endometriosis. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a prevalent gynecologic disease associated with systemic chronic inflammation, heightened oxidative stress, and atherogenic lipid profile that may increase women's risk for coronary heart disease (CHD).Methods and Results: We examined the prospective association between laparoscopically confirmed endometriosis and subsequent CHD among 116 430 women in the Nurses' Health Study II (1989-2009). Participants with a history of heart disease and stroke were excluded. When compared with women without endometriosis, women with laparoscopically confirmed endometriosis had a higher risk of myocardial infarction (relative risk, 1.52; 95% confidence interval, 1.17-1.98), angiographically confirmed angina (1.91; 1.59-2.29), coronary artery bypass graft surgery/coronary angioplasty procedure/stent (1.35; 1.08-1.69), or any of these CHD end points combined (1.62; 1.39-1.89), independent of potential demographic, anthropometric, family history, reproductive, and lifestyle confounders. Relative risk for the combined CHD end point was highest among women aged ≤40 years (3.08; 2.02-4.70) and decreased as age increased (40< age ≤50 years, 1.65; 1.35-2.02; 50< age ≤55 years, 1.44; 1.07-1.94; and age >55 years, 0.98; 0.56-1.72; P value, test for heterogeneity=0.001). Having had a hysterectomy/oophorectomy was associated with higher risk of combined CHD compared with not having had a hysterectomy/oophorectomy (1.51; 1.34-1.71). A percentage of 42 of the association between endometriosis and CHD could be explained by greater frequency of hysterectomy/oophorectomy and earlier age at surgery after endometriosis diagnosis.Conclusions: In this large, prospective cohort, laparoscopically confirmed endometriosis was associated with increased risk of CHD. The association was strongest among young women. Hysterectomy/oophorectomy was associated with higher risk of CHD and could partially explain the association between endometriosis and CHD. [ABSTRACT FROM AUTHOR]

Most statistical methods that adjust analyses for dietary measurement error treat an individual's usual intake as a fixed quantity. However, usual intake, if defined as average intake over a few months, varies over time. We describe a model that accounts for such variation and for the proximity of biomarker measurements to self-reports within the framework of a meta-analysis, and apply it to the analysis of data on energy, protein, potassium, and sodium from a set of five large validation studies of dietary self-report instruments using recovery biomarkers as reference instruments. We show that this time-varying usual intake model fits the data better than the fixed usual intake assumption. Using this model, we estimated attenuation factors and correlations with true longer-term usual intake for single and multiple 24-hour dietary recalls (24HRs) and food frequency questionnaires (FFQs) and compared them with those obtained under the "fixed" method. Compared with the fixed method, the estimates using the time-varying model showed slightly larger values of the attenuation factor and correlation coefficient for FFQs and smaller values for 24HRs. In some cases, the difference between the fixed method estimate and the new estimate for multiple 24HRs was substantial. With the new method, while four 24HRs had higher estimated correlations with truth than a single FFQ for absolute intakes of protein, potassium, and sodium, for densities the correlations were approximately equal. Accounting for the time element in dietary validation is potentially important, and points toward the need for longer-term validation studies. [ABSTRACT FROM AUTHOR]

HIV and malaria infections occur in the same individuals, particularly in sub-Saharan Africa. We examined whether daily multivitamin supplementation (vitamins B complex, C, and E) or vitamin A supplementation altered malaria incidence in HIV-infected women of reproductive age.HIV-infected pregnant Tanzanian women recruited into the study were randomly assigned to daily multivitamins (B complex, C, and E), vitamin A alone, both multivitamins and vitamin A, or placebo. Women received malaria prophylaxis during pregnancy and were followed monthly during the prenatal and postpartum periods. Malaria was defined in 2 ways: presumptive diagnosis based on a physician's or nurse's clinical judgment, which in many cases led to laboratory investigations, and periodic examination of blood smears for malaria parasites.Multivitamin supplementation compared with no multivitamins significantly lowered women's risk of presumptively diagnosed clinical malaria (relative risk: 0.78, 95% confidence interval: 0.67 to 0.92), although multivitamins increased their risk of any malaria parasitemia (relative risk: 1.24, 95% confidence interval: 1.02 to 1.50). Vitamin A supplementation did not change malaria incidence during the study.Multivitamin supplements have been previously shown to reduce HIV disease progression among HIV-infected women, and consistent with that, these supplements protected against development of symptomatic malaria. The clinical significance of increased risk of malaria parasitemia among supplemented women deserves further research, however. Preventive measures for malaria are warranted as part of an integrated approach to the care of HIV-infected individuals exposed to malaria. [ABSTRACT FROM AUTHOR]

This article describes a study which investigated the relationships between mercury exposure and incident hypertension in two separate U.S. cohorts of men and women free of hypertension at baseline. Researchers measured toenail mercury, a biomarker of long-term methylmercury exposure. After adjustment for demographic, clinical and lifestyle risk factors, the hazard ratio for incident hypertension was determined.

Background: Shift workers who experience sleep disturbances and exposure to light at night could be at increased risk for alterations in physiologic functions that are circadian in nature.Methods: We investigated rotating shift work and menstrual cycle patterns in the Nurses' Health Study II using cross-sectional data collected in 1993 from 71,077 nurses aged 28-45 years who were having menstrual periods and were not using oral contraceptives. Log-binomial regression was used to estimate relative risks (RRs) and 95% confidence intervals (CIs).Results: Eight percent of participants reported working rotating night shifts for 1-9 months, 4% for 10-19 months, and 7% for 20+ months during the previous 2 years. Irregular cycles (>7 days variability) were reported by 10% of participants. Seventy percent of women reported menstrual cycles of 26-31 days, 1% less than 21 days, 16% 21-25 days, 11% 32-39 days, and 1% 40+ days. Women with 20+ months of rotating shift work were more likely to have irregular cycles (adjusted RR = 1.23 [CI = 1.14-1.33]); they were also more likely to have cycle length <21 days (1.27 [0.99-1.62]) or 40+ days (1.49 [1.19-1.87]) (both compared with 26-31 days). For irregular patterns and for 40+ day cycles, there was evidence of a dose response with increasing months of rotating shift work. Moderately short (21-25 days) or long (32-39 days) cycle lengths were not associated with rotating shift work.Conclusions: Shift work was modestly associated with menstrual function, with possible implications for fertility and other cycle-related aspects of women's health. [ABSTRACT FROM AUTHOR]

Background: Environmental exposure to polychlorinated biphenyls (PCBs) and p,p'-dichlorodiphenyldichloroethylene (p, p'-DDE) has been associated with the risk of non-Hodgkin lymphoma.Methods: We conducted a case-control study nested within the Physicians' Health Study, a prospective cohort established in 1982. We measured concentrations of PCBs and p,p'-DDE in baseline blood samples from 205 men later diagnosed with non-Hodgkin lymphoma and 409 age- and race-matched controls. Lipid-adjusted organochlorine concentrations were categorized into quintiles based on the distribution among controls. We used conditional logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for each quintile relative to the lowest quintile. We also evaluated these associations for major histologic subtypes of non-Hodgkin lymphoma.Results: The risk of non-Hodgkin lymphoma was positively associated with the sum of 51 PCB congeners assayed (SigmaPCB); the group of immunotoxic congeners; the individual congeners 118, 138, 153, and 180; and the sum of these 4 congeners. The simple OR for the highest quintile of lipid-adjusted SigmaPCB versus the lowest was 1.9 (95% CI = 1.1-3.2; test for trend, P = 0.001), with similar trends for individual congeners and groups defined as above. Adjustment for height, body mass index, alcohol intake, smoking, and fish intake did not substantially change the effect estimates. No association was observed for p,p'-DDE. There was no evidence of statistical heterogeneity in effects by histologic subtype of lymphoma; however, this analysis was underpowered.Conclusions: These results support the hypothesis of a positive association between PCB exposure and development of NHL in men. [ABSTRACT FROM AUTHOR]

Background: A potential role of prenatal and perinatal exposures in autoimmunity has been hypothesized, but few studies have examined the relation between various prenatal and perinatal factors and the risk of multiple sclerosis (MS).Methods: The study population included participants in the Nurses' Health Studies--2 prospective cohorts that together comprise 238,381 female nurses, who self-reported exposure to prenatal and perinatal factors. In addition, 35,815 nurses' mothers participated by providing detailed information regarding experiences surrounding their daughter's birth. The following prenatal and perinatal factors were studied in relation to MS: fetal growth, birth season, preterm birth, mode of delivery, maternal weight gain, medical conditions, medication use, diethylstilbestrol exposure, prenatal health care, maternal activity level, maternal obstetric history, parental age, and prenatal and childhood passive smoke exposure.Results: The sample included 723 confirmed MS cases, including 383 with diagnosis after reporting prenatal and perinatal factors. Few associations were observed. These included an increased risk among women whose mothers reported late initiation of prenatal care (after the first trimester) (27 cases; rate ratio = 1.6 [95% confidence interval = 1.0-2.4]), diabetes during pregnancy (2 cases; 10 [2.5-42]), and maternal prepregnancy overweight/obesity (20 cases; 1.7 [1.0-2.7]). Results also suggested a possible increase in incident MS risk among women with prenatal diethylstilbestrol exposure (9 cases; 1.8 [0.93-3.5]).Conclusions: This study provides modest support for a role of prenatal factors in MS risk. The results should be interpreted cautiously due to the limited statistical power, potential for exposure misclassification, and possibility of chance findings. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the total body bone mineral density (total BMD) of HIV-infected men and women. It states that total BMD was measured using the whole-body dual-energy absorptiometry (DXA) while the medical and behavioral histories of the patients were collected. Findings show that low body weight and catabolic steroid use may accelerate bone loss while tenofovir and didanosine may cause a harmful effect on BMD.

Background: Outdoor concentrations of soot and nitrogen dioxide (NO2) outside of schools have been associated with children's respiratory and eye symptoms. We assessed how adjustments for measurement error affect these associations.Methods: Concentrations of air pollutants outside children's schools were validated by personal measurements of exposure to traffic-related air pollution. We estimated prevalence ratios of 4 health outcomes (current wheeze, conjunctivitis, phlegm, and elevated total serum immunoglobulin E) using school outdoor measurements, and then adjusted for measurement error using the personal exposure data and applying a regression calibration method. The analysis adjusting for measurement error was carried out using a main study/external validation design.Results: Adjusting for measurement error produced effect estimates related to soot and NO2 that were 2 to 3 times higher than in the original study. The adjusted prevalence ratio for current phlegm was 5.3 (95% confidence interval = 1.2-23) for a 9.3 microg/m3 increase in soot, and 3.8 (1.0-14), for a 17.6 microg/m3 increase in NO2, compared with the original results of 2.2 (1.3-3.9) and 1.8 (1.1-2.8), respectively. Corrections were of similar magnitude for the prevalence of current wheeze, current conjunctivitis, and total elevated total immunoglobulin E.Conclusions: The estimated effects of outdoor air pollution on respiratory and other health effects in children may be substantially attenuated when based on exposure measurements outside schools instead of personal exposure. [ABSTRACT FROM AUTHOR]

The etiology of uterine leiomyoma (or fibroids) is poorly understood. Sex steroid hormones and growth factors have been hypothesized to play a role in their development, and anthropometric characteristics may influence uterine leiomyoma risk.We analyzed prospectively-collected data from the Nurses’ Health Study II, a cohort of 116,609 female registered nurses age 25 to 42 years at baseline. Incidence of uterine leiomyoma and anthropometric characteristics were assessed every 2 years. We calculated hazard ratios and 95% confidence intervals adjusted for known and suspected risk factors for uterine leiomyoma.Uterine leiomyomas were associated with current body mass index, change in weight since age 18, and waist-to-hip ratio. However, there was little evidence of their association with body mass index at age 18, childhood or adolescent body size, or adult height.Body mass and weight gain in adulthood may increase the risk of uterine leiomyoma, but body mass in early life does not. [ABSTRACT FROM AUTHOR]

There is inconsistent evidence as to whether work schedule (including rotating shifts and night work) can affect reproductive outcomes.We investigated the association between work schedule and risk of spontaneous abortion in U.S. nurses. The Nurses’ Health Study II is a prospective cohort study established in 1989. In 2001, information about occupational activities and exposures during pregnancy was collected from female nurses for the most recent pregnancy since 1993. Of 11,178 eligible respondents, 9547 (85%) indicated willingness to participate in the occupational study, and 8461 of those (89%) returned the questionnaire, for an overall participation rate of 76%. Of these, 7688 women had pregnancies that were eligible for analysis.Participants reported 6902 live births and 786 (10%) spontaneous abortions. Compared with women who reported usually working “days only” during their first trimester, women who reported usually working “nights only” had a 60% increased risk of spontaneous abortion (RR = 1.6; 95% confidence interval [CI] = 1.3-1.9). A rotating schedule, with or without night shifts, was not associated with an increase in risk (RR = 1.2 [CI = 0.9-1.5] and 1.0 [CI = 0.8-1.2], respectively). Women who reported working more than 40 hours per week during the first trimester were also at increased risk of spontaneous abortion (1.5; 1.3-1.7) compared with women working 21-40 hours, even after adjustment for work schedule.Nightwork and long work hours may be associated with an increased risk of spontaneous abortion. Further studies are needed to determine whether hormonal disturbances attributed to night work affect pregnancy outcome. [ABSTRACT FROM AUTHOR]

Background: Uterine leiomyomata are a major source of morbidity in black women. We prospectively investigated the risk of self-reported uterine leiomyomata in relation to body mass index (BMI), weight change, height, waist and hip circumferences, and waist-to-hip ratio in a large cohort of U.S black women.Methods: Data were derived from the Black Women's Health Study, a U.S. prospective cohort study of black women who complete biannual mailed health questionnaires. From 1997 through 2001, we followed 21,506 premenopausal women with intact uteri and no prior diagnosis of uterine leiomyomata. Cox regression models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs).Results: After 70,345 person-years of follow up, 2146 new cases of uterine leiomyomata confirmed by ultrasound (n = 1885) or hysterectomy (n = 261) were self-reported. Compared with the thinnest women (BMI <20.0 kg/m), the multivariate IRRs for women with BMIs of 20.0-22.4, 22.5-24.9, 25.0-27.4, 27.5-29.9, 30.0-32.4, and 32.5+ kg/m were 1.34 (95% CI = 1.02-1.75), 1.39 (1.07-1.81), 1.45 (1.12-1.89), 1.47 (1.11-1.93), 1.36 (1.02-1.80), and 1.21 (0.93-1.58), respectively. IRRs were larger among parous women. Weight gain since age 18 was positively associated with risk, but only among parous women. No other anthropometric measures were associated with risk.Conclusions: BMI and weight gain exhibited a complex relation with risk of uterine leiomyomata in the Black Women's Health Study. The BMI association was inverse J-shaped and findings were stronger in parous women. Weight gain was positively associated with risk among parous women only. [ABSTRACT FROM AUTHOR]