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1.  Predictive and Prognostic Analysis of PIK3CA Mutation in Stage III Colon Cancer Intergroup Trial 
Background
Somatic mutations in PIK3CA (phosphatidylinositol-4,5-bisphosphonate 3-kinase [PI3K], catalytic subunit alpha gene) activate the PI3K-AKT signaling pathway and contribute to pathogenesis of various malignancies, including colorectal cancer.
Methods
We examined associations of PIK3CA oncogene mutation with relapse, survival, and treatment efficacy in 627 stage III colon carcinoma case subjects within a randomized adjuvant chemotherapy trial (5-fluorouracil and leucovorin [FU/LV] vs irinotecan [CPT11], fluorouracil and leucovorin [IFL]; Cancer and Leukemia Group B 89803 [Alliance]). We detected PIK3CA mutation in exons 9 and 20 by polymerase chain reaction and pyrosequencing. Cox proportional hazards model was used to assess prognostic and predictive role of PIK3CA mutation, adjusting for clinical features and status of routine standard molecular pathology features, including KRAS and BRAF mutations and microsatellite instability (mismatch repair deficiency). All statistical tests were two-sided.
Results
Compared with PIK3CA wild-type cases, overall status of PIK3CA mutation positivity or the presence of PIK3CA mutation in either exon 9 or 20 alone was not statistically significantly associated with recurrence-free, disease-free, or overall survival (log-rank P > .70; P > .40 in multivariable regression models). There was no statistically significant interaction between PIK3CA and KRAS (or BRAF) mutation status in survival analysis (P interaction > .18). PIK3CA mutation status did not appear to predict better or worse response to IFL therapy compared with FU/LV therapy (P interaction > .16).
Conclusions
Overall tumor PIK3CA mutation status is not associated with stage III colon cancer prognosis. PIK3CA mutation does not appear to serve as a predictive tumor molecular biomarker for response to irinotecan-based adjuvant chemotherapy.
doi:10.1093/jnci/djt298
PMCID: PMC3848984  PMID: 24231454
2.  Occupational factors and risk of preterm birth in nurses 
Objective
We evaluated the risk of first-trimester exposures among nurses and the risk of preterm birth among participants of the Nurses’ Health Study II.
Study Design
Log binomial regression was used to estimate the relative risk (RR) for preterm birth in relation to occupational risk factors, adjusting for age, parity, work schedule, physical factors, and exposures to chemicals and x-rays.
Results
Part-time work (<= 20 hours a week) was associated with a lower risk for preterm birth [RR=0.7, 95% confidence interval (CI) = 0.6–0.9]. Self-reported exposure to sterilizing agents was associated with an increased risk (RR=1.9, 95% CI = 1.1–3.4). Other exposures, including shift work, physical factors, anesthetic gases, antineoplastic drugs, antiviral drugs, and x-ray radiation were not associated with risk of preterm birth.
Conclusions
These data suggest that sterilizing agents may be related to preterm birth, while physically demanding work and work schedule are not strong predictors.
doi:10.1016/j.ajog.2008.08.006
PMCID: PMC4249587  PMID: 18976732
Nurses; Occupational Exposure; Pregnancy; Preterm Birth; Work Schedule Tolerance
3.  Optimal combination of number of participants and number of repeated measurements in longitudinal studies with time-varying exposure 
Statistics in medicine  2013;32(27):10.1002/sim.5870.
In the context of observational longitudinal studies, we explored the values of the number of participants and the number of repeated measurements that maximize the power to detect the hypothesized effect, given the total cost of the study. We considered two different models, one that assumes a transient effect of exposure and one that assumes a cumulative effect. Results were derived for a continuous response variable, whose covariance structure was assumed to be damped exponential, and a binary time-varying exposure. Under certain assumptions, we derived simple formulas for the approximate solution to the problem in the particular case in which the response covariance structure is assumed to be compound symmetry. Results showed the importance of the exposure intraclass correlation in determining the optimal combination of the number of participants and the number of repeated measurements, and therefore the optimized power. Thus, incorrectly assuming a time-invariant exposure leads to inefficient designs. We also analyzed the sensitivity of results to dropout, mis-specification of the response correlation structure, allowing a time-varying exposure prevalence and potential confounding impact. We illustrated some of these results in a real study. In addition, we provide software to perform all the calculations required to explore the combination of the number of participants and the number of repeated measurements.
doi:10.1002/sim.5870
PMCID: PMC3808503  PMID: 23740818
optimal design; longitudinal study; sample size; intraclass correlation
4.  Methylmercury Exposure and Incident Diabetes in U.S. Men and Women in Two Prospective Cohorts 
Diabetes Care  2013;36(11):3578-3584.
OBJECTIVE
Emerging in vitro and animal evidence suggests that methylmercury could increase type 2 diabetes, but little evidence exists in humans. We aimed to prospectively determine associations of mercury exposure, as assessed by biomarker measurement, with incident diabetes.
RESEARCH DESIGN AND METHODS
We used neutron activation analysis to measure toenail mercury, an objective biomarker of methylmercury exposure, in 9,267 adults free of diabetes at baseline in two separate U.S. prospective cohorts. Incident diabetes was identified from biennial questionnaires and confirmed by validated supplementary questionnaire using symptoms, diagnostic tests, and medical therapy. Associations of mercury exposure with incident diabetes were assessed using Cox proportional hazards.
RESULTS
During mean ± SD follow-up of 19.7 ± 7.0 years, 1,010 new cases of diabetes were diagnosed. The 95th percentile of toenail mercury was 1.32 μg/g in men and 0.76 μg/g in women, corresponding to exposures ∼3.5-fold and 2-fold higher than the U.S. Environmental Protection Agency reference dose. In multivariable analyses, toenail mercury concentrations were not associated with higher incidence of diabetes in women, men, or both cohorts combined. Comparing the highest to lowest quintile of exposure, the hazard ratio (95% CI) for incident diabetes was 0.86 (0.66–1.11) in women, 0.69 (0.42–1.15) in men, and 0.77 (0.61–0.98) in the combined cohorts. Findings were similar when more extreme categories (deciles) of mercury were compared, and in analyses stratified by fish or omega-3 consumption, BMI, and age.
CONCLUSIONS
These findings from two separate large prospective cohorts do not support adverse effects of methylmercury on development of diabetes in men or women at usual levels of exposure seen in these populations.
doi:10.2337/dc13-0894
PMCID: PMC3816920  PMID: 24026556
5.  Can efficiency be gained by correcting for misclassification? 
Journal of statistical planning and inference  2013;143(11):10.1016/j.jspi.2013.06.010.
This paper considers 2×2 tables arising from case-control studies in which the binary exposure may be misclassified. We found circumstances under which the inverse matrix method provides a more efficient odds ratio estimator than the naive estimator. We provide some intuition for the findings, and also provide a formula for obtaining the minimum size of a validation study such that the variance of the odds ratio estimator from the inverse matrix method is smaller than that of the naive estimator, thereby ensuring an advantage for the misclassification corrected result. As a corollary of this result, we show that correcting for misclassification does not necessarily lead to a widening of the confidence intervals, but, rather, in addition to producing a consistent estimate, can also produce one that is more efficient.
doi:10.1016/j.jspi.2013.06.010
PMCID: PMC3810993  PMID: 24187429
2×2 table; Case control study; Misclassification; Odds ratio; Validation study design
6.  Plasma free 25-hydroxyvitamin D, vitamin D binding protein, and risk of breast cancer in the Nurses’ Health Study II 
Cancer causes & control : CCC  2014;25(7):819-827.
Purpose
Prior prospective studies, including our own, have evaluated total plasma 25-hydroxyvitamin D [25(OH)D] and breast cancer risk with inconsistent results. However, recent studies suggest that some vitamin D functions may be more relevant to the unbound (free) fraction of 25(OH)D. Vitamin D binding protein (DBP) influences the free 25(OH)D levels and thus possibly the biological activities of vitamin D.
Methods
We conducted a case–control study nested within the Nurses’ Health Study II to evaluate the association of plasma free 25(OH)D and DBP with breast cancer risk in predominantly premenopausal women. Plasma samples were assayed for 25(OH)D and DBP in 584 case–control pairs. Free 25(OH)D levels were calculated based on plasma levels of total 25(OH)D, DBP, and a constant value representing average albumin levels. Conditional logistic regression was used to estimate relative risks (RRs) and 95 % confidence intervals (CIs).
Results
We found no association between plasma calculated free 25(OH)D and risk of breast cancer overall (highest vs. lowest quartile RR 1.21, 95 % CI 0.83–1.77, trend test p value = 0.50). No association was observed for plasma DBP as well (highest vs. lowest quartile RR 0.95, 95 % CI 0.67–1.36, trend test p value = 0.96). Results were similar by tumor hormone receptor status. Neither the total nor the calculated free 25(OH)D and breast cancer association substantially varied by plasma DBP levels.
Conclusions
Our study does not support an important role of either calculated circulating free 25(OH)D or circulating DBP levels in breast cancer risk among predominantly premenopausal women.
doi:10.1007/s10552-014-0383-5
PMCID: PMC4191840  PMID: 24748579
Free 25-hydroxyvitamin D; Vitamin D binding protein; Breast cancer; Epidemiology; Prospective
7.  Risk Factors for Preterm Birth among HIV-Infected Tanzanian Women: A Prospective Study 
Premature delivery, a significant cause of child mortality and morbidity worldwide, is particularly prevalent in the developing world. As HIV is highly prevalent in much of sub-Saharan Africa, it is important to determine risk factors for prematurity among HIV-positive pregnancies. The aims of this study were to identify risk factors of preterm (<37 weeks) and very preterm (<34 weeks) birth among a cohort of 927 HIV positive women living in Dar es Salaam, Tanzania, who enrolled in the Tanzania Vitamin and HIV Infection Trial between 1995 and 1997. Multivariable relative risk regression models were used to determine the association of potential maternal risk factors with premature and very premature delivery. High rates of preterm (24%) and very preterm birth (9%) were found. Risk factors (adjusted RR (95% CI)) for preterm birth were mother <20 years (1.46 (1.10, 1.95)), maternal illiteracy (1.54 (1.10, 2.16)), malaria (1.42 (1.11, 1.81)), Entamoeba coli (1.49 (1.04, 2.15)), no or low pregnancy weight gain, and HIV disease stage ≥2 (1.41 (1.12, 1.50)). Interventions to reduce pregnancies in women under 20, prevent and treat malaria, reduce Entamoeba coli infection, and promote weight gain in pregnant women may have a protective effect on prematurity.
doi:10.1155/2014/261689
PMCID: PMC4195401  PMID: 25328529
8.  Confidence Intervals for Heterogeneity Measures in Meta-analysis 
American Journal of Epidemiology  2013;178(6):993-1004.
Two methods of quantifying heterogeneity between studies in meta-analysis were studied. One method quantified the proportion of the total variance of the effect estimate due to variation between studies (RI), and the other calibrated the variance between studies to the size of the effect itself through a between-study coefficient of variation (CVB). Bootstrap and asymptotic confidence intervals for RI and CVB were derived and evaluated in an extensive simulation study that covered a wide range of scenarios likely to be encountered in practice. The best performance was given by asymptotic Wald confidence intervals developed for RI and CVB. The use of these heterogeneity measures together with their confidence intervals was illustrated in 5 typical meta-analyses. A new user-friendly SAS macro (SAS Institute, Inc., Cary, North Carolina) is provided to implement these methods for routine use and can be downloaded at the last author's website.
doi:10.1093/aje/kwt060
PMCID: PMC3775542  PMID: 23921232
confidence intervals; heterogeneity; meta-analysis; statistical methods
9.  Evaluation of a community health worker intervention and the World Health Organization’s Option B versus Option A to improve antenatal care and PMTCT outcomes in Dar es Salaam, Tanzania: study protocol for a cluster-randomized controlled health systems implementation trial 
Trials  2014;15(1):359.
Background
Mother-to-child transmission of HIV remains an important public health problem in sub-Saharan Africa. As HIV testing and linkage to PMTCT occurs in antenatal care (ANC), major challenges for any PMTCT option in developing countries, including Tanzania, are delays in the first ANC visit and a low overall number of visits. Community health workers (CHWs) have been effective in various settings in increasing the uptake of clinical services and improving treatment retention and adherence. At the beginning of this trial in January 2013, the World Health Organization recommended either of two medication regimens, Option A or B, for prevention of mother-to-child transmission of HIV (PMTCT). It is still largely unclear which option is more effective when implemented in a public healthcare system. This study aims to determine the effectiveness, cost-effectiveness, acceptability, and feasibility of: (1) a community health worker (CWH) intervention and (2) PMTCT Option B in improving ANC and PMTCT outcomes.
Methods/Design
This study is a cluster-randomized controlled health systems implementation trial with a two-by-two factorial design. All 60 administrative wards in the Kinondoni and Ilala districts in Dar es Salaam were first randomly allocated to either receiving the CHW intervention or not, and then to receiving either Option B or A. Under the standard of care, facility-based health workers follow up on patients who have missed scheduled appointments for PMTCT, first through a telephone call and then with a home visit. In the wards receiving the CHW intervention, the CHWs: (1) identify pregnant women through home visits and refer them to antenatal care; (2) provide education to pregnant women on antenatal care, PMTCT, birth, and postnatal care; (3) routinely follow up on all pregnant women to ascertain whether they have attended ANC; and (4) follow up on women who have missed ANC or PMTCT appointments.
Trial registration
ClinicalTrials.gov: EJF22802. Registration date: 14 May 2013.
Electronic supplementary material
The online version of this article (doi:10.1186/1745-6215-15-359) contains supplementary material, which is available to authorized users.
doi:10.1186/1745-6215-15-359
PMCID: PMC4247663  PMID: 25224756
Study protocol; HIV; Antenatal care; Prevention of mother-to-child transmission; Community health workers; Uptake; Retention
10.  Sexual orientation differences in teen pregnancy and hormonal contraceptive use: An examination across two generations 
Objectives
To examine whether sexual orientation is associated with disparities in teen pregnancy and hormonal contraception use among adolescent females in two intergenerational cohorts.
Study Design
Data were collected from 91,003 women in the Nurses’ Health Study II (NHSII),born between 1947–1964, and 6,463 of their children, born between 1982–1987, enrolled in the Growing Up Today Study (GUTS). Log-binomial models were used to estimate risk ratios (RR) for teen pregnancy and hormonal contraception use in sexual minorities compared to heterosexuals and meta-analysis techniques were used to compare the two cohorts.
Results
Overall, teen hormonal contraception use was lower and teen pregnancy was higher in NHSII than GUTS. In both cohorts, lesbians were less likely, whereas the other sexual minorities were more likely, to use hormonal contraception as teenagers compared to their heterosexual peers. All sexual minority groups in both cohorts, except NHSII lesbians, were at significantly increased risk for teen pregnancy, with RRs ranging from 1.61 (95%CI 0.40, 6.55) to 5.82 (95%CI 2.89, 11.73). Having a NHSII mother who was pregnant as a teen was not associated with teen pregnancy in GUTS participants. Finally, significant heterogeneity was found between the two cohorts.
Conclusions
Adolescent sexual minorities have been, and continue to be, at increased risk for pregnancy. Public health and clinical efforts are needed to address teen pregnancy in this population.
doi:10.1016/j.ajog.2013.06.036
PMCID: PMC3758403  PMID: 23796650
Bisexuality; Contraceptive Agents; Healthcare Disparities; Homosexuality; Sexual Behavior; Pregnancy in Adolescence
11.  Particulate Matter Air Pollution Exposure, Distance to Road, and Incident Lung Cancer in the Nurses’ Health Study Cohort 
Environmental Health Perspectives  2014;122(9):926-932.
Background: A body of literature has suggested an elevated risk of lung cancer associated with particulate matter and traffic-related pollutants.
Objective: We examined the relation of lung cancer incidence with long-term residential exposures to ambient particulate matter and residential distance to roadway, as a proxy for traffic-related exposures.
Methods: For participants in the Nurses’ Health Study, a nationwide prospective cohort of women, we estimated 72-month average exposures to PM2.5, PM2.5–10, and PM10 and residential distance to road. Follow-up for incident cases of lung cancer occurred from 1994 through 2010. Cox proportional hazards models were adjusted for potential confounders. Effect modification by smoking status was examined.
Results: During 1,510,027 person-years, 2,155 incident cases of lung cancer were observed among 103,650 participants. In fully adjusted models, a 10-μg/m3 increase in 72-month average PM10 [hazard ratio (HR) = 1.04; 95% CI: 0.95, 1.14], PM2.5 (HR = 1.06; 95% CI: 0.91, 1.25), or PM2.5–10 (HR = 1.05; 95% CI: 0.92, 1.20) was positively associated with lung cancer. When the cohort was restricted to never-smokers and to former smokers who had quit at least 10 years before, the associations appeared to increase and were strongest for PM2.5 (PM10: HR = 1.15; 95% CI: 1.00, 1.32; PM2.5: HR = 1.37; 95% CI: 1.06, 1.77; PM2.5–10: HR = 1.11; 95% CI: 0.90, 1.37). Results were most elevated when restricted to the most prevalent subtype, adenocarcinomas. Risks with roadway proximity were less consistent.
Conclusions: Our findings support those from other studies indicating increased risk of incident lung cancer associated with ambient PM exposures, especially among never- and long-term former smokers.
Citation: Puett RC, Hart JE, Yanosky JD, Spiegelman D, Wang M, Fisher JA, Hong B, Laden F. 2014. Particulate matter air pollution exposure, distance to road, and incident lung cancer in the Nurses’ Health Study Cohort. Environ Health Perspect 122:926–932; http://dx.doi.org/10.1289/ehp.1307490
doi:10.1289/ehp.1307490
PMCID: PMC4154215  PMID: 24911062
12.  Effect of multivitamin supplements on weight gain during pregnancy among HIV-negative women in Tanzania 
Maternal & child nutrition  2012;10.1111/mcn.12018.
Multivitamin supplementation has been shown to reduce the risk of low birthweight. This effect could be mediated through gestational weight gain. However, the effect of multivitamin supplementation on weight gain during pregnancy has not been fully studied. The objective of this study was to examine the effects of multivitamins on pregnancy weight gain. We enrolled 8468 HIV-negative women from Dar es Salaam, Tanzania, in a randomised, placebo-controlled trial of multivitamins on birth outcomes. Women were randomly assigned to receive either a daily oral dose of multivitamin tablets or a placebo and were weighed every 4 weeks from enrolment until the last visit before delivery. Intent-to-treat analyses were carried out to examine the effects of multivitamins on pregnancy weight gain. Multivariate linear and binomial regression models with the log-link function were used to examine the association of weight gain during pregnancy to birthweight. The overall total weight gain was 253 g (SE: 69, P: 0.0003) more, while the overall 4 weekly weight gain was 59 g greater (SE: 18, P: 0.005) among women who received multivitamins compared to placebo. Women in the lowest quartile of gestational weight gain had babies with an average birthweight of 3030 g (SD: 524), while women in the highest quartile had babies weighing 3246 g (SD: 486), on average. Prenatal multivitamin supplements increased gestational weight gain, which was a significant predictor of birthweight.
doi:10.1111/mcn.12018
PMCID: PMC3874066  PMID: 23253638
weight; pregnancy; multivitamins; birthweight; Africa
13.  Nutritional Predictors of Acute Respiratory Infections Among Children Born to HIV-Infected Women in Tanzania 
Journal of Tropical Pediatrics  2013;59(3):203-208.
We prospectively determined the association between undernutrition and incidence of acute respiratory infections (ARIs) among 711 children born to HIV-infected women. Overall, underweight was associated with a 58% increased risk of ARI. Similarly, wasting (54%), very low birth weight (88%) and child HIV infection (62%) were significantly associated with increased risk of ARI during the first 2 years. Breastfeeding was associated with 52% reduction in risk of ARI only during the first 12 months of life. Among HIV-exposed, but uninfected, children, underweight, wasting and stunting were associated with 73%, 61% and 33% increased risk of ARI, respectively. Very low birthweight and advanced maternal disease stage were also associated with increased risk of ARI. Similar results were observed among HIV-infected children, except for stunting and very low birth weight. Prevention of child undernutrition could have major impact in reducing child ARI morbidity in settings of high HIV prevalence.
doi:10.1093/tropej/fmt004
PMCID: PMC3667589  PMID: 23400399
nutrition; pediatrics; respiratory; infections
14.  Plasma Phospholipid Saturated Fatty Acids and Incident Atrial Fibrillation: The Cardiovascular Health Study 
Background
Prior studies suggest that circulating fatty acids may influence the risk of atrial fibrillation (AF), but little is known about the associations of circulating saturated fatty acids with risk of AF.
Methods and Results
The study population included 2899 participants from the Cardiovascular Health Study, a community‐based longitudinal cohort of adults aged 65 years or older in the United States who were free of prevalent coronary heart disease and AF in 1992. Cox regression was used to assess the association of all the long‐chain saturated fatty acids—palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0)—with incident AF. During a median of 11.2 years of follow‐up, 707 cases of incident AF occurred. After adjustment for other AF risk factors, higher levels of circulating 16:0 were associated with a higher risk of AF (hazard ratio comparing highest and lowest quartiles: 1.48; 95% CI: 1.18, 1.86). In contrast, higher levels of circulating 18:0, 20:0, 22:0, and 24:0 were each associated with a lower risk of AF. The hazard ratios (95% CI) for AF in the top and bottom quartiles were 0.76 (95% CI: 0.61, 0.95) for 18:0; 0.78 (95% CI: 0.63, 0.97) for 20:0; 0.62 (95% CI: 0.50, 0.78) for 22:0; and 0.68 (95% CI: 0.55, 0.85) for 24:0.
Conclusions
Results from this prospective cohort study of older adults demonstrate divergent associations of circulating 16:0 versus longer‐chain saturated fatty acids with incident AF, highlighting the need to investigate both determinants of these levels and potential pathways of the observed differential risk.
doi:10.1161/JAHA.114.000889
PMCID: PMC4309088  PMID: 24970268
atrial fibrillation; epidemiology; fatty acid
15.  Regression Calibration Is Valid When Properly Applied 
Epidemiology (Cambridge, Mass.)  2013;24(3):466-467.
doi:10.1097/EDE.0b013e31828b284b
PMCID: PMC4035111  PMID: 23549186
16.  Approaches to Uncertainty in Exposure Assessment in Environmental Epidemiology 
Uncertainty in assessment of individual exposure levels leads to bias, often, but not always, toward the null in estimates of health effects, and to underestimation of the variability of the estimates, leading to anticonservative p-values. In the absence of data on the uncertainty in individual exposure estimates, sensitivity analysis, also known as uncertainty analysis and bias analysis, is available. Hypothesized values of key parameters of the model relating the observed exposure to the true exposure are used to assess the resulting amount of bias in point and interval estimates. In general, the relative risk estimates can vary from zero to infinity as the hypothesized values of key parameters of the measurement error model vary. Thus, we recommend that exposure validation data be used to empirically adjust point and interval estimates of health effects for measurement error. The remainder of this review gives an overview of available methods for doing so. Just as we routinely adjust for confounding, we can and should routinely adjust for measurement error.
doi:10.1146/annurev.publhealth.012809.103720
PMCID: PMC4035123  PMID: 20070202
measurement error; misclassification; validation study; regression calibration
17.  Corrected score estimation in the proportional hazards model with misclassified discrete covariates 
Statistics in medicine  2008;27(11):1911-1933.
SUMMARY
We consider Cox proportional hazards regression when the covariate vector includes error-prone discrete covariates along with error-free covariates, which may be discrete or continuous. The misclassification in the discrete error-prone covariates is allowed to be of any specified form. Building on the work of Nakamura and his colleagues, we present a corrected score method for this setting. The method can handle all three major study designs (internal validation design, external validation design, and replicate measures design), both functional and structural error models, and time-dependent covariates satisfying a certain ‘localized error’ condition. We derive the asymptotic properties of the method and indicate how to adjust the covariance matrix of the regression coefficient estimates to account for estimation of the misclassification matrix. We present the results of a finite-sample simulation study under Weibull survival with a single binary covariate having known misclassification rates. The performance of the method described here was similar to that of related methods we have examined in previous works. Specifically, our new estimator performed as well as or, in a few cases, better than the full Weibull maximum likelihood estimator. We also present simulation results for our method for the case where the misclassification probabilities are estimated from an external replicate measures study. Our method generally performed well in these simulations. The new estimator has a broader range of applicability than many other estimators proposed in the literature, including those described in our own earlier work, in that it can handle time-dependent covariates with an arbitrary misclassification structure. We illustrate the method on data from a study of the relationship between dietary calcium intake and distal colon cancer.
doi:10.1002/sim.3159
PMCID: PMC4035127  PMID: 18219700
errors in variables; nonlinear models; proportional hazards
19.  Obesity epidemic has emerged among Nigerians 
BMC Public Health  2014;14:455.
Background
Data from the WHO shows that the prevalence of overweight and obesity increased by ~20% between 2002 and 2010 in Nigeria. We conducted this study to examine the correlates of this fast growing epidemic.
Methods
We conducted a cross-sectional study among a random sample of 1058 adults, who were visitors and staff of a government worksite in Abuja, an urban city in Nigeria. The study participants had varying socio-economic status and a wide range of occupations, including skilled labor and professionals. Log-binomial regression models were used to estimate the multivariable-adjusted associations of potential determinants with the prevalence of overweight and obesity.
Result
The mean age and body-mass index of the study population were 42 years ± (9.3) and 27 kg/m2 ± (4.8). The overall prevalence of overweight or obesity (body-mass index ≥ 25 kg/m2) was 64% (74% of the women and 57% of the men). For women compared to men, the prevalence ratio (PR) and (95% confidence interval, CI) was 1.24 (95% CI 1.08, 1.43, p = 0.004), for overweight, and 2.54 (95% CI 2.08, 3.10, p = <0.0001), for obesity. Individuals aged 40 – 49 years were more likely to be overweight or obese. The PR for overweight and obesity was 1.45 (95% CI 1.07, 1.97), p for age trend = 0.002 and 8.07(95% CI 3.01, 21.66, p for age trend = <0.0001) for those aged 40 – 49 years, compared with those aged <30 years. Compared with the individuals in the lower socio-economic status, the PR for obesity among those in the middle and high socio-economic statuses, were 1.39 (95% CI 1.13, 1.72) and 1.24 (95% CI 0.97, 1.59) respectively, p for trend = 0.003.
Conclusion
About two-thirds of urban, professional, high socio-economic status Nigerian adults are either overweight or obese. The prevalence of overweight and obesity among this population of adult Nigerians, is as high as it is in the United Kingdom. Female gender and older age were independent predictors of overweight and obesity; while middle or high socio-economic status were independently associated with obesity.
doi:10.1186/1471-2458-14-455
PMCID: PMC4060067  PMID: 24886022
Overweight; Obesity; Nigeria
20.  Intimate Partner Violence and Incidence of Type 2 Diabetes in Women 
Diabetes Care  2013;36(5):1159-1165.
OBJECTIVE
We sought to estimate the association between intimate partner violence, a prevalent psychosocial stressor, and the incidence of type 2 diabetes in women.
RESEARCH DESIGN AND METHODS
In 2001, 68,376 Nurses’ Health Study II participants answered questions on physical, sexual, and psychological intimate partner violence in adulthood (age ≥18 years) and reported the years in which any abuse occurred. We used Cox proportional hazards models to estimate the associations between intimate partner violence exposures and incidence of type 2 diabetes from 2001 to 2007. We also estimated effects of duration and time since intimate partner violence on type 2 diabetes incidence.
RESULTS
Of 68,376 respondents, 64,732 met inclusion criteria at the 2001 baseline; of these, 23% reported lifetime physical intimate partner violence, 11% reported lifetime sexual intimate partner violence, and 8% reported moderate and <2% reported severe psychological intimate partner violence. Hazard ratios (HRs) and 95% CIs for type 2 diabetes, adjusted for potential confounders, were 1.18 (1.00–1.39) and 1.08 (0.86–1.35) for more than one lifetime episode of physical and sexual intimate partner violence, respectively, and 1.78 (1.21–2.61) for severe psychological abuse. Addition of updated BMI and other diabetes risk factors reduced the physical intimate partner violence HR to 1.12 (0.94–1.33) and the psychological intimate partner violence HR to 1.61 (1.09–2.38).
CONCLUSIONS
Physical intimate partner violence is modestly associated with incidence of type 2 diabetes in this population. Severe psychological violence may substantially increase type 2 diabetes risk.
doi:10.2337/dc12-1082
PMCID: PMC3631851  PMID: 23248189
21.  Carotenoid Intake and Risk of Colorectal Adenomas in a Cohort of Male Health Professionals 
Cancer causes & control : CCC  2013;24(4):705-717.
Purpose
Carotenoids have been hypothesized to prevent carcinogenesis through their antioxidant and pro-vitamin A properties. We examined associations between intakes of specific carotenoids and risk of colorectal adenomas.
Methods
Among 29,363 men who reported having a lower bowel endoscopy between 1986–2006, 3,997 cases of colorectal adenoma were identified in the Health Professionals Follow-up Study. Participants completed food frequency questionnaires every 4 years; dietary information was cumulatively updated. The associations between carotenoid intakes and risk of colorectal adenomas overall and by anatomic site, stage, smoking status and alcohol consumption were investigated using multivariate logistic regression models.
Results
Total β-carotene and dietary β-carotene, lycopene and lutein/zeaxanthin intakes and the total carotenoid score were inversely associated with colorectal adenoma risk. The odds ratios (95% confidence intervals) comparing the highest vs. lowest quintile of intake were 0.78 (0.69–0.88) for total β-carotene, 0.72 (0.64–0.81) for dietary β-carotene, 0.83 (0.74–0.93) for lycopene, 0.86 (0.76–0.96) for lutein/zeaxanthin, and 0.87 (0.77–0.97) for the total carotenoid score. Associations for α-carotene and β-cryptoxanthin intakes were null. We did not find significant differences in the associations between intakes of each carotenoid and risk of colorectal adenoma by anatomic site or stage (all p-values, test for common effects > 0.10). The inverse associations we observed for total β-carotene and dietary β-carotene, lycopene, and lutein/zeaxanthin intakes and the total carotenoid score with adenoma risk also did not vary by smoking status and alcohol consumption.
Conclusion
This study found that a diet high in carotenoids was associated with a reduced risk of colorectal adenomas.
doi:10.1007/s10552-013-0151-y
PMCID: PMC3767390  PMID: 23371557
carotenoids; nutrition; colorectal adenomas; colorectal cancer; epidemiology
22.  An Examination of Sexual Orientation Group Patterns in Mammographic and Colorectal Screening in a Cohort of U.S. Women 
Cancer causes & control : CCC  2012;24(3):539-547.
Purpose
Underutilization of cancer screening has been found especially to affect socially marginalized groups. We investigated sexual orientation group patterns in breast and colorectal cancer screening adherence.
Methods
Data on breast and colorectal cancer screening, sexual orientation, and sociodemographics were gathered prospectively from 1989 through 2005 from 85,759 U.S. women in the Nurses' Health Study II. Publicly available data on state-level health care quality and sexual orientation-related legal protections were also gathered. Multivariable models were used to estimate sexual orientation-group differences in breast and colorectal cancer screening, controlling for sociodemographics and state-level health care quality and legal protections for sexual minorities.
Results
Receipt of a mammogram in the past two years was common though not universal and differed only slightly by sexual orientation: heterosexual 84%; bisexual 79%; lesbian 82%. Fewer than half of eligible women had ever received a colonoscopy or sigmoidoscopy, and rates did not differ by sexual orientation: heterosexual 39%; bisexual 39%; lesbian 42%. In fully adjusted models, state-level health care quality score, though not state-level legal protections for sexual minorities, was positively associated with likelihood of being screened for all women regardless of sexual orientation.
Conclusions
Concerns have been raised that unequal health care access for sexual orientation minorities may adversely affect cancer screening. We found small disparities in mammography and none in colorectal screening, though adherence to colorectal screening recommendations was uniformly very low. Interventions are needed to increase screening in women of all sexual orientation groups, particularly in areas with poor health care policies.
doi:10.1007/s10552-012-9991-0
PMCID: PMC3959888  PMID: 22729931
breast cancer; colorectal cancer; screening; sexual orientation; bisexual; lesbian
23.  Anemia at the Initiation of Tuberculosis Therapy Is Associated with Delayed Sputum Conversion among Pulmonary Tuberculosis Patients in Dar-es-Salaam, Tanzania 
PLoS ONE  2014;9(3):e91229.
Background
Pulmonary tuberculosis and anemia are both prevalent in Tanzania. There is limited and inconsistent literature on the association between anemia and sputum conversion following tuberculosis treatment.
Methods
Newly diagnosed sputum smear positive pulmonary tuberculosis patients aged ≥15 years initiating on standard anti tuberculosis therapy were recruited from 14 of 54 tuberculosis clinics in Dar es Salaam. Patients were receiving medication according to the recommended short course Directly Observed Therapy (DOT) strategy and were followed up prospectively until completion of treatment (six months). Patients were evaluated before initiation of TB treatment by performing the following; clinical history, physical examination, complete blood counts, serum biochemistry and sputum microscopy. Sputum smears were re-examined at two months of anti-tuberculosis therapy for presence of acid fast bacilli. Anemia was defined as hemoglobin <13 g/dl (males) or <12 g/dl (females). Log-binomial regression was used to assess the association between anemia and sputum conversion at two months.
Results
Of the 1245 patients included in the study, 86% were anemic and 7% were sputum smear positive at two months of anti-tuberculosis therapy. Anemic patients were three times more likely to have sputum positive smear as compared to non-anemic patients at two months (RR = 3.05; 95% CI 1.11–8.40) p = 0.03. The risk for sputum positive smear results increased with severity of anemia (P for trend <0.01).
Conclusion
Baseline anemia is associated with increased risk for persistent positive sputum smears at two months of tuberculosis treatment. Future studies should evaluate the mechanisms for TB-associated anemia as well as the role of intervention for anemia among TB patients.
doi:10.1371/journal.pone.0091229
PMCID: PMC3958362  PMID: 24642636
24.  Fruit and Vegetable Intake and Risk of Breast Cancer by Hormone Receptor Status 
Background
Estrogen receptor–negative (ER−) breast cancer has few known or modifiable risk factors. Because ER− tumors account for only 15% to 20% of breast cancers, large pooled analyses are necessary to evaluate precisely the suspected inverse association between fruit and vegetable intake and risk of ER− breast cancer.
Methods
Among 993 466 women followed for 11 to 20 years in 20 cohort studies, we documented 19 869 estrogen receptor positive (ER+) and 4821 ER− breast cancers. We calculated study-specific multivariable relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression analyses and then combined them using a random-effects model. All statistical tests were two-sided.
Results
Total fruit and vegetable intake was statistically significantly inversely associated with risk of ER− breast cancer but not with risk of breast cancer overall or of ER+ tumors. The inverse association for ER− tumors was observed primarily for vegetable consumption. The pooled relative risks comparing the highest vs lowest quintile of total vegetable consumption were 0.82 (95% CI = 0.74 to 0.90) for ER− breast cancer and 1.04 (95% CI = 0.97 to 1.11) for ER+ breast cancer (P common-effects by ER status < .001). Total fruit consumption was non-statistically significantly associated with risk of ER− breast cancer (pooled multivariable RR comparing the highest vs lowest quintile = 0.94, 95% CI = 0.85 to 1.04).
Conclusions
We observed no association between total fruit and vegetable intake and risk of overall breast cancer. However, vegetable consumption was inversely associated with risk of ER− breast cancer in our large pooled analyses.
doi:10.1093/jnci/djs635
PMCID: PMC3593764  PMID: 23349252
25.  Disparities in Child Abuse Victimization in Lesbian, Bisexual, and Heterosexual Women in the Nurses’ Health Study II 
Journal of women's health (2002)  2008;17(4):597-606.
A growing body of research documents multiple health disparities by sexual orientation among women, yet little is known about the possible causes of these disparities. One underlying factor may be heightened risk for abuse victimization in childhood in lesbian and bisexual women. Using survey data from 63,028 women participating in the Nurses’ Health Study II, we investigated sexual orientation group differences in emotional, physical, and sexual abuse in childhood and adolescence. Multivariable log-binomial and linear regression models were used to examine orientation group differences in prevalence and severity of abuse, with heterosexual as the referent and controlling for sociodemographics. Results showed strong evidence of elevated frequency, severity, and persistence of abuse experienced by lesbian and bisexual women. Comparing physical abuse victimization occurring in both childhood and adolescence, lesbian (30%; prevalence ratio [PR] 1.61; 95% confidence interval [CI] 1.40, 1.84) and bisexual (24%; PR 1.26; 95% CI 1.00, 1.60) women were more likely to report victimization than were heterosexual women (19%). Similarly, comparing sexual abuse victimization occurring in both age periods, lesbian (19%; PR 2.16; 95% CI 1.80, 2.60) and bisexual (20%; PR 2.29; 95% CI 1.76, 2.98) women were more likely to report victimization than were heterosexual women (9%). This study documents prevalent and persistent abuse disproportionately experienced by lesbian and bisexual women.
doi:10.1089/jwh.2007.0450
PMCID: PMC3912575  PMID: 18447763
bisexual; child abuse; lesbian; sexual orientation; victimization

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