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The use of traditional, complementary, and alternative medicine (TCAM) can lead to delays and interruptions in the HIV continuum of care. This study explores reasons for TCAM use in people living with HIV on antiretroviral therapy (ART) in Eswatini and compares interrupted care between different types of TCAM users. Data were collected using surveys in the MaxART study (a test-and-treat trial) between 2014 and 2017 to assess the exposure, namely visiting a TCAM provider. Additionally, visit dates were retrieved from clinic records to assess the outcome, interrupted care. Open-ended questions were analysed with qualitative content analysis (n = 602) and closed questions with bivariable and multivariable analysis (n = 202). Out of 202 participants, 145 (72%) never used TCAM, 40 (20%) ever used, and 17 (8%) is currently using TCAM (diviners, herbalists, and religious healers). No differences in interrupted care were found comparing never (reference category), past (Odds Ratio: 1.31, 95% confidence interval: 0.63–2.72), and current users (1.34, 0.47–3.77), while adjusting for gender, time since HIV diagnosis, and time on ART. Contextual factors affecting the choice for TCAM were the influence of family, advice from the health facility, and religious beliefs. Individual factors include trust in biomedical care, type of illness, no need for additional care, and practical reasons such as financial means. In conclusion, individual and contextual factors influence the choice for TCAM. Interrupted care does not differ between never, past, and current users. [ABSTRACT FROM AUTHOR]

Background: Anaemia is common among HIV-infected children and iron supplementation is prescribed routinely for the prevention and management of anaemia among children. Limited evidence suggests iron supplementation may have adverse effects among HIV-infected populations. We aimed to estimate the effect of iron supplement use on mortality, disease progression and haematological outcomes among HIV-infected children in Dar es Salaam, Tanzania.Methods: A prospective cohort study was conducted among HIV-infected children (aged 0-14 years) receiving antiretroviral treatment or supportive care between October 2004 and September 2014. Clinical data were recorded on morbidity and vital status, haematological status and prescriptions at each clinical visit. Cox proportional hazards models adjusted for time-varying covariates were used to estimate the association of time-varying iron supplementation on the hazard rate of mortality, HIV disease stage progression, tuberculosis incidence and anaemia and microcytosis persistence.Results: In all, 4229 children were observed during 149 260 clinic visits for a mean follow-up of 2.9 years. After adjustment for time-varying clinical covariates, time-varying iron supplementation was associated with a 2.87 times higher hazard rate of mortality (95% CI: 1.70, 4.87) and a 1.48 times higher hazard rate of HIV disease stage progression (95% CI: 1.10, 1.98). Iron supplementation was also associated with a lower rate of anaemia persistence (HR = 0.47; 95% CI: 0.37, 0.61). No differences in the association between iron supplementation and clinical outcomes were observed by antiretroviral therapy or anaemia status.Conclusions: Iron supplementation may increase the risk of HIV disease stage progression and mortality among HIV-infected children, while reducing the risk of anaemia. [ABSTRACT FROM AUTHOR]

Objectives: Only one community-based study has assessed religious group involvement and health outcomes among South Asians in the U.S., with mixed results. Here, using a large, South Asian community-based sample, the effects of six religious group involvement predictors – religious tradition, attendance, group prayer, giving/receiving congregational emotional support, congregational neglect, and congregational criticism – were examined in relation to four health outcomes: self-rated health, positive mental health functioning, trait anxiety, and trait anger. Design: The study used a new religion/spirituality questionnaire in the Mediators of Atherosclerosis Among South Asians Living in America (MASALA), the largest study of mental and physical well-being among U.S. South Asians. Associations were assessed cross-sectionally using OLS regression in both the full sample (N = 928) and a subsample of congregation members (N = 312). Results: Jains reported better self-rated health compared to Hindus and Muslims. Group prayer involvement, when measured ordinally, was positively associated with self-rated health and mental health functioning. In reference group comparisons, individuals who participated in group prayer once/day or more had lower levels of anxiety and anger compared to several comparison groups in which individuals prayed less than once a day. Religious service attendance was associated with higher levels of anxiety. Giving/receiving congregational emotional support was positively associated with self-rated health and mental health functioning, and inversely associated with anxiety. Congregational criticism was associated with higher levels of anger and anxiety. Conclusions: This study provided a new assessment of religious group involvement and health in the U.S. South Asian population. Religious group participation was associated with mental and self-rated health in well-controlled models, indicating this is a fruitful area for further research. Group religious involvement may be a health-promoting resource for U.S. South Asians who are religiously active, but it is not an unalloyed boon. [ABSTRACT FROM AUTHOR]

Because it describes the proportion of disease cases that could be prevented if an exposure were entirely eliminated from a target population as a result of an intervention, estimation of the population attributable risk (PAR) has become an important goal of public health research. In epidemiologic studies, categorical covariates are often misclassified. We present methods for obtaining point and interval estimates of the PAR and the partial PAR (pPAR) in the presence of misclassification, filling an important existing gap in public health evaluation methods. We use a likelihood-based approach to estimate parameters in the models for the disease and for the misclassification process, under main study/internal validation study and main study/external validation study designs, and various plausible assumptions about transportability. We assessed the finite sample perf ormance of this method via a simulation study, and used it to obtain corrected point and interval estimates of the pPAR for high red meat intake and alcohol intake in relation to colorectal cancer incidence in the HPFS, where we found that the estimated pPAR for the two risk factors increased by up to 317% after correcting for bias due to misclassification. [ABSTRACT FROM AUTHOR]

Background/objectives: Screening and diagnosis of iron deficiency anemia (IDA) is cumbersome as it may require testing for hemoglobin, ferritin, and an inflammatory biomarker. The aim of this study was to compare the diagnostic capacity of hematologic biomarkers to detect IDA among pregnant women in Tanzania.Subjects/methods: We pooled data from an iron supplementation trial of 1500 iron-replete pregnant woman and a prospective cohort of 600 iron-deficient pregnant women. Receiver operating characteristic curves (ROC) for hematologic biomarkers were used to assess the sensitivity, specificity, and area under the curve (AUC) for iron deficiency (ID) and iron deficiency anemia (IDA), crude, or corrected for inflammation. Regression models assessed the relationship of baseline biomarker categories (gestational age <27 weeks) and IDA at delivery.Results: Hemoglobin had the largest AUC for crude ID (0.96), while hepcidin had the largest AUC for corrected ID (0.80). The optimal hepcidin cutoff for the diagnosis of corrected IDA based on maximal sensitivity and specificity was ≤1.6 µg/L. An hepcidin cutoff of <4.3 µg/L had a sensitivity of 95% for regression-corrected ID. Among iron-replete women who did not receive iron, the association of baseline hemoglobin >110 g/L with IDA at delivery (RR = 0.73; 95% CI: 0.47, 1.13) was attenuated. Baseline hepcidin >1.6 µg/L was associated with reduced risk of anemia at delivery by 49% (95% CI: 27%, 45%).Conclusions: Ascertaining hemoglobin and hepcidin levels may improve the targeting of iron supplementation programs in resource-limited countries, though hepcidin's high costs may limit its use. [ABSTRACT FROM AUTHOR]

In many public health and medical research settings, information on key covariates may not be readily available or too expensive to gather for all individuals in the study. In such settings, the two-phase design provides a way forward by first stratifying an initial (large) phase I sample on the basis of covariates readily available (including, possibly, the outcome), and sub-sampling participants at phase II to collect the expensive measure(s). When the outcome of interest is binary, several methods have been proposed for estimation and inference for the parameters of a logistic regression model, including weighted likelihood, pseudo-likelihood and maximum likelihood. Although these methods yield consistent estimation and valid inference, they do so solely on the basis of the phase I stratification and the detailed covariate information obtained at phase II. Moreover, they ignore any additional information that is readily available at phase I but was not used as part of the stratified sampling design. Motivated by the potential for efficiency gains, especially concerning parameters corresponding to the additional phase I covariates, we propose a novel augmented pseudo-likelihood estimator for two-phase studies that makes use of all available information. In contrast to recently-proposed weighted likelihood-based methods that calibrate to the influence function of the model of interest, the methods we propose do not require the development of additional models and, therefore, enjoy a degree of robustness. In addition, we expand the broader framework for pseudo-likelihood based estimation and inference to permit link functions for binary regression other than the logit link. Comprehensive simulations, based on a one-time cross sectional survey of 82,887 patients undergoing anti-retroviral therapy in Malawi between 2005 and 2007, illustrate finite sample properties of the proposed methods and compare their performance competing approaches. The proposed method yields the lowest standard errors when the model is correctly specified. Finally, the methods are applied to a large implementation science project examining the effect of an enhanced community health worker program to improve adherence to WHO guidelines for at least four antenatal visits, in Dar es Salaam, Tanzania. [ABSTRACT FROM AUTHOR]

Background: Zinc and vitamin A supplementation have both been shown to affect iron status, hemoglobin (Hb) concentration, and anemia in animal and human studies. However, evidence on their combined use in pregnancy, in the context of iron-folic acid (IFA) supplementation, remains limited.Objective: This study determined the effects of prenatal zinc, vitamin A, and iron supplementation on maternal hematologic and micronutrient status at delivery in Tanzania.Methods: We analyzed 2 large randomized controlled trials, using generalized estimating equations, and examined the effect of daily zinc (25 mg) and vitamin A (2500 IU) supplementation starting in the first trimester of pregnancy compared with placebo (n = 2500), and separately evaluated the safety and efficacy of daily iron (60 mg) supplementation among iron-replete pregnant women (n = 1500). Blood samples from baseline and delivery were tested for Hb, serum ferritin, soluble transferrin receptor, plasma zinc, and zinc protoporphyrin.Results: Zinc and vitamin A supplementation were associated with lower Hb concentrations at delivery of  -0.26 g/dL (95% CI: -0.50, -0.02 g/dL) and -0.25 g/dL (95% CI: -0.49, -0.01 g/dL), respectively. Vitamin A increased mean ferritin concentrations at delivery (14.3 μg/L, 95% CI: 1.84, 29.11 μg/L), but was associated with increased risk of severe anemia (RR: 1.41; 95% CI: 1.06, 1.88). Among women who were iron replete at baseline, iron supplementation reduced the risk of iron depletion at delivery by 47% (RR: 0.53; 95% CI: 0.43, 0.65). There was no effect of zinc or iron supplements on plasma zinc concentrations.Conclusions: Our findings support existing WHO guidelines on prenatal iron, vitamin A, and zinc supplementation among pregnant women. In this setting, scaling uptake of prenatal iron supplements is warranted, but prenatal zinc and vitamin A supplementation did not benefit maternal hematologic status at delivery. In settings where vitamin A deficiency is endemic, the efficacy and safety of the WHO recommended prenatal vitamin A supplementation require further evaluation. [ABSTRACT FROM AUTHOR]

In stepped wedge designs (SWD), clusters are randomized to the time period during which new patients will receive the intervention under study in a sequential rollout over time. By the study's end, patients at all clusters receive the intervention, eliminating ethical concerns related to withholding potentially efficacious treatments. This is a practical option in many large-scale public health implementation settings. Little statistical theory for these designs exists for binary outcomes. To address this, we utilized a maximum likelihood approach and developed numerical methods to determine the asymptotic power of the SWD for binary outcomes. We studied how the power of a SWD for detecting risk differences varies as a function of the number of clusters, cluster size, the baseline risk, the intervention effect, the intra-cluster correlation coefficient, and the time effect. We studied the robustness of power to the assumed form of the distribution of the cluster random effects, as well as how power is affected by variable cluster size. % SWD power is sensitive to neither, in contrast to the parallel cluster randomized design which is highly sensitive to variable cluster size. We also found that the approximate weighted least square approach of Hussey and Hughes (2007, Design and analysis of stepped wedge cluster randomized trials. Contemporary Clinical Trials 28, 182-191) for binary outcomes under-estimates the power in some regions of the parameter spaces, and over-estimates it in others. The new method was applied to the design of a large-scale intervention program on post-partum intra-uterine device insertion services for preventing unintended pregnancy in the first 1.5 years following childbirth in Tanzania, where it was found that the previously available method under-estimated the power. [ABSTRACT FROM AUTHOR]

Background: Growing laboratory and animal model evidence supports the potentially carcinogenic effects of some phthalates, chemicals used as plasticizers in a wide variety of consumer products, including cosmetics, medications, and vinyl flooring. However, prospective data on whether phthalates are associated with human breast cancer risk are lacking.Methods: We conducted a nested case-control study within the Women's Health Initiative (WHI) prospective cohort (n = 419 invasive case subjects and 838 control subjects). Control subjects were matched 2:1 to case subjects on age, enrollment date, follow-up time, and WHI study group. We quantified 13 phthalate metabolites and creatinine in two or three urine samples per participant over one to three years. Multivariable conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer risk associated with each phthalate biomarker up to 19 years of follow-up.Results: Overall, we did not observe statistically significant positive associations between phthalate biomarkers and breast cancer risk in multivariable analyses (eg, 4th vs 1st quartile of diethylhexyl phthalate, OR = 1.03, 95% CI = 0.91 to 1.17). Results were generally similar in analyses restricted to disease subtypes, to nonusers of postmenopausal hormone therapy, stratified by body mass index, or to case subjects diagnosed within three, five, or ten years.Conclusions: In the first prospective analysis of phthalates and postmenopausal breast cancer, phthalate biomarker concentrations did not result in an increased risk of developing invasive breast cancer. [ABSTRACT FROM AUTHOR]

Objectives: In a large cohort of HIV-infected Tanzanians, we assessed: (i) rates of first-line treatment failure and switches to second-line ART; (ii) the effect of switching to second-line ART on death and loss to follow-up; and (iii) treatment outcomes on second-line ART by regimen.Methods: HIV-1-infected adults (≥15 years) initiated on first-line ART between November 2004 and September 2012, and who remained on initial therapy for at least 24 weeks before switching, were studied. Survival analyses were conducted to examine the effect of second-line ART on mortality and loss to follow-up in: (i) the whole cohort; (ii) all patients eligible for second-line ART by immunological failure (IF) and/or virological failure (VF) criteria; and (iii) patients eligible by VF criteria.Results: In total, 47 296 HIV-infected patients [mean age 37.5 (SD 9.5) years, CD4 175 (SD 158) cells/mm 3 , 71% female] were included in the analyses. Of these, 1760 (3.7%) patients switched to second-line ART (incidence rate = 1.7/100 person-years). Higher rates of mortality were observed in switchers versus non-switchers in all patients and patients with ART failure using IF/VF criteria. Switching only protected against mortality in patients with ART failure defined virologically and with the highest level of adherence [switching versus non-switching; >95% adherence; adjusted HR = 0.50 (95% CI = 0.26-0.93); P  =   0.03].Conclusions: Switching patients to second-line ART may only be beneficial in a select group of patients who are virologically monitored and demonstrate good adherence. Our data emphasize the need for routine viral load monitoring and aggressive adherence interventions in HIV programmes in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

The authors evaluated the validity of a 152-item semiquantitative food frequency questionnaire (SFFQ) by comparing it with two 7-day dietary records (7DDRs) or up to 4 automated self-administered 24-hour recalls (ASA24s) over a 1-year period in the women's Lifestyle Validation Study (2010-2012), conducted among subgroups of the Nurses' Health Studies. Intakes of energy and 44 nutrients were assessed using the 3 methods among 632 US women. Compared with the 7DDRs, SFFQ responses tended to underestimate sodium intake but overestimate intakes of energy, macronutrients, and several nutrients in fruits and vegetables, such as carotenoids. Spearman correlation coefficients between energy-adjusted intakes from 7DDRs and the SFFQ completed at the end of the data-collection period ranged from 0.36 for lauric acid to 0.77 for alcohol (mean r = 0.53). Correlations of the end-period SFFQ were weaker when ASA24s were used as the comparison method (mean r = 0.43). After adjustment for within-person variation in the comparison method, the correlations of the final SFFQ were similar with 7DDRs (mean r = 0.63) and ASA24s (mean r = 0.62). These data indicate that this SFFQ provided reasonably valid estimates for intakes of a wide variety of dietary variables and that use of multiple 24-hour recalls or 7DDRs as a comparison method provided similar conclusions if day-to-day variation was taken into account. [ABSTRACT FROM AUTHOR]

We examined the proportions of multiple types of breast cancers in the population that were attributable to established risk factors, focusing on behaviors that are modifiable at menopause. We estimated the full and partial population attributable risk percentages (PAR%) by combining the relative risks and the observed prevalence rates of the risk factors of interest. A total of 8,421 cases of invasive breast cancer developed in postmenopausal women (n = 121,700) in the Nurses' Health Study from 1980-2010. We included the following modifiable risk factors in our analyses: weight change since age 18 years, alcohol consumption, physical activity level, breastfeeding, and menopausal hormone therapy use. Additionally, the following nonmodifiable factors were included: age, age at menarche, height, a combination of parity and age at first birth, body mass index at age 18 years, family history of breast cancer, and prior benign breast disease. When we considered all risk factors (and controlled for age), the PAR% for invasive breast cancers was 70.0% (95% confidence interval: 55.0, 80.7). When considering only modifiable factors, we found that changing the risk factor profile to the lowest weight gain, no alcohol consumption, high physical activity level, breastfeeding, and no menopausal hormone therapy use was associated with a PAR% of 34.6% (95% confidence interval: 22.7, 45.4). The PAR% for modifiable factors was higher for estrogen receptor-positive breast cancers (PAR% = 39.7%) than for estrogen receptor-negative breast cancers (PAR% = 27.9%). Risk factors that are modifiable at menopause account for more than one-third of postmenopausal breast cancers; therefore, a substantial proportion of breast cancer in the United States is preventable. [ABSTRACT FROM AUTHOR]

Background: : Neonatal vitamin A supplementation (NVAS) is an intervention hypothesized to reduce infant morbidity and mortality. The objective of this study was to assess the efficacy of neonatal vitamin A supplementation in reducing infant morbidity and mortality and assess potential sources of heterogeneity of the effect of NVAS.Methods: : We completed an individually randomized, double-blind, placebo-controlled trial in Tanzania. Infants were randomized within 3 days of birth to a single dose of vitamin A (50 000 IU) or placebo. We assessed infants at 1 and 3 days after supplementation, as well as 1, 3, 6 and 12 months after supplementation. We included all live births in the analysis and used relative risks (RR) and 95% confidence intervals (CI) to assess the risks of mortality and hospitalization by 12 months. We used general estimating equations to assess the incidence of morbidities during infancy.Results: : A total of 31 999 infants were enrolled in the study between August 2010 and March 2013. At 12 months, vitamin A did not reduce all-cause infant mortality (RR 1.04; 95% CI 0.92-1.16), nor affect hospitalization (RR 1.09; 95% CI 0.97-1.22) or all-cause morbidity (RR 1.00; 95% CI 0.96-1.05). Postpartum maternal vitamin A supplementation modified the effect of neonatal vitamin A supplementation on mortality at 12 months ( P -value, test for interaction = 0.04). Among infants born to women who received a mega-dose of vitamin A after delivery, NVAS appeared to increase the risk of death (RR 1.12; 95% CI 0.98-1.29), whereas the risk of death among infants born to women who did not receive a mega-dose was reduced (RR 0.86; 95% CI 0.70-1.06). We noted no modification of the effect of NVAS by infant gender, birthweight or maternal HIV status.Conclusion: : NVAS did not affect the risk of death or incidence of common childhood morbidities. However, this study sheds light on potential sources of heterogeneity of the effect of neonatal vitamin A supplementation which should be further examined in a pooled analysis of all NVAS trials. [ABSTRACT FROM AUTHOR]

Antenatal and post‐natal depression has demonstrated a significant burden in sub‐Saharan Africa, with rates ranging from 10% to 35%. However, perinatal women living with HIV in Tanzania have reported an even greater prevalence of depression (43–45%). The primary goal of this study was to examine the relationship between maternal depression and infant malnutrition among women living with HIV. The design was a retrospective cohort study within the context of a randomised controlled trial among women living with HIV and their infants. Within this trial, 699 mother–child pairs were analysed for the present study. Although antenatal depression was not associated with infant malnutrition and post‐natal depression was negatively associated [relative risk (RR = 0.80, P = 0.04], cumulative depression demonstrated a positive association with infant wasting (RR = 1.08, P < 0.01) and underweight (RR = 1.03, P < 0.01) after controlling for confounding factors. Variation in the association between depression and infant nutritional status was observed for episodic vs. chronic depression. These findings suggest that providing evidence‐based services for persistent depression among women living with HIV may have an effect on infant malnutrition. In addition, other positive outcomes may be related to infant cognitive development as well as HIV disease prognosis and survival among women. [ABSTRACT FROM AUTHOR]

Background: Plant-based diets have been recommended to reduce the risk of type 2 diabetes (T2D). However, not all plant foods are necessarily beneficial. We examined the association of an overall plant-based diet and hypothesized healthful and unhealthful versions of a plant-based diet with T2D incidence in three prospective cohort studies in the US.Methods and Findings: We included 69,949 women from the Nurses' Health Study (1984-2012), 90,239 women from the Nurses' Health Study 2 (1991-2011), and 40,539 men from the Health Professionals Follow-Up Study (1986-2010), free of chronic diseases at baseline. Dietary data were collected every 2-4 y using a semi-quantitative food frequency questionnaire. Using these data, we created an overall plant-based diet index (PDI), where plant foods received positive scores, while animal foods (animal fats, dairy, eggs, fish/seafood, poultry/red meat, miscellaneous animal-based foods) received reverse scores. We also created a healthful plant-based diet index (hPDI), where healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, vegetable oils, tea/coffee) received positive scores, while less healthy plant foods (fruit juices, sweetened beverages, refined grains, potatoes, sweets/desserts) and animal foods received reverse scores. Lastly, we created an unhealthful plant-based diet index (uPDI) by assigning positive scores to less healthy plant foods and reverse scores to healthy plant foods and animal foods. We documented 16,162 incident T2D cases during 4,102,369 person-years of follow-up. In pooled multivariable-adjusted analysis, both PDI and hPDI were inversely associated with T2D (PDI: hazard ratio [HR] for extreme deciles 0.51, 95% CI 0.47-0.55, p trend < 0.001; hPDI: HR for extreme deciles 0.55, 95% CI 0.51-0.59, p trend < 0.001). The association of T2D with PDI was considerably attenuated when we additionally adjusted for body mass index (BMI) categories (HR 0.80, 95% CI 0.74-0.87, p trend < 0.001), while that with hPDI remained largely unchanged (HR 0.66, 95% CI 0.61-0.72, p trend < 0.001). uPDI was positively associated with T2D even after BMI adjustment (HR for extreme deciles 1.16, 95% CI 1.08-1.25, p trend < 0.001). Limitations of the study include self-reported diet assessment, with the possibility of measurement error, and the potential for residual or unmeasured confounding given the observational nature of the study design.Conclusions: Our study suggests that plant-based diets, especially when rich in high-quality plant foods, are associated with substantially lower risk of developing T2D. This supports current recommendations to shift to diets rich in healthy plant foods, with lower intake of less healthy plant and animal foods. [ABSTRACT FROM AUTHOR]

BACKGROUND: Arsenic has been linked to disrupted immune function and greater infection susceptibility in highly exposed populations. Well arsenic levels above the U.S. EPA limit occur in our U.S. study area and are of particular concern for pregnant women and infants. OBJECTIVES: We investigated whether in utero arsenic exposure affects the risk of infections and respiratory symptoms over the first year of life. METHODS: We prospectively obtained information on infant infections and symptoms, including their duration and treatment (n = 412) at 4, 8, and 12 months using a parental telephone survey. Using generalized estimating equation models adjusted for potential confounders, we evaluated the association between maternal pregnancy urinary arsenic and infant infections and symptoms over the first year. RESULTS: Each doubling of maternal urinary arsenic was related to increases in the total number of infections requiring prescription medication in the first year [relative risk (RR) = 1.1; 95% CI: 1.0, 1.2]. Urinary arsenic was related specifically to respiratory symptoms (difficulty breathing, wheezing, and cough) lasting ≥ 2 days or requiring prescription medication (RR = 1.1; 95% CI: 1.0, 1.2; and RR = 1.2; 95% CI: 1.0, 1.5, respectively), and wheezing lasting ≥ 2 days, resulting in a doctor visit or prescription medication treatment (RR = 1.3; 95% CI: 1.0, 1.7; RR = 1.3; 95% CI: 1.0, 1.8, and RR = 1.5; 95% CI: 1.0, 2.2, respectively). Associations also were observed with diarrhea (RR = 1.4; 95% CI: 1.1, 1.9) and fever resulting in a doctor visit (RR = 1.2; 95% CI: 1.0, 1.5). CONCLUSIONS: In utero arsenic exposure was associated with a higher risk of infection during the first year of life in our study population, particularly infections requiring medical treatment, and with diarrhea and respiratory symptoms. [ABSTRACT FROM AUTHOR]

Background: Although obesity has been linked to an increased risk of colorectal cancer (CRC), the risk associated with long-term status or change of body fat distribution has not been fully elucidated.Methods: Using repeated anthropometric assessments in the Nurses' Health Study and Health Professionals Follow-up Study, we prospectively investigated cumulative average waist circumference, hip circumference and waist-to-hip ratio, as well as their 10-year changes over adulthood, in relation to CRC risk over 23-24 years of follow-up. Cox proportional hazards models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI).Results: High waist circumference, hip circumference and waist-to-hip ratio were all associated with a higher CRC risk in men, even after adjusting for body mass index. The association was attenuated to null in women after adjusting for body mass index. Ten-year gain of waist circumference was positively associated with CRC risk in men (P for trend = 0.03), but not in women (P for trend = 0.34).Compared with men maintaining their waist circumference, those gaining waist circumference by ≥ 10 cm were at a higher risk of CRC, with a multivariable-adjusted HR of 1.59 (95% CI, 1.01-2.49). This association appeared to be independent of weight change.Conclusions: Abdominal adiposity, independent of overall obesity, is associated with an increased CRC risk in men but not in women. Our findings also provide the first prospective evidence that waist circumference gain during adulthood may be associated with higher CRC risk in men, thus highlighting the importance of maintaining a healthy waist for CRC prevention. [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]

To determine the prevalence and predictors of cervical squamous intraepithelial lesions (SIL) among HIV-infected women in Tanzania, a cross-sectional study was conducted among HIV-infected women at HIV care and treatment clinics. A Papanicolaou (Pap) smear was used as a screening tool for detection of cervical SIL. From December 2006 to August 2009, 1365 HIV-infected women received cervical screening. The median age was 35 (interquartile range [IQR]: 30-42) years, and the median CD4 + cell count was 164 (IQR: 80-257) cells/mm(3). The prevalence of cervical SIL was 8.7% (119/1365). In multivariate analysis, older age (≥50 versus 30-<40 years: prevalence ratio [PR], 2.36; 95% confidence interval [CI], 1.45-3.84, p for trend = 0.001), lower CD4 + cell counts (<100 versus ≥200 cells/mm(3): PR, 1.55; 95% CI, 1.01-2.36, p for trend = 0.03) and cervical inflammation (PR, 1.73; 95% CI, 1.16-2.60, p = 0.008) were associated with an increased risk of cervical SIL. Women with advanced WHO HIV disease stage (IV versus I/II: PR, 3.45; 95% CI, 1.35-8.85, p for trend = 0.01) had an increased risk for high-grade SIL. In resource-limited settings where it is not feasible to provide cervical cancer prevention services to all HIV-infected women, greater efforts should focus on scaling-up services among those who are older than 50 years, with lower CD4 cell counts and advanced HIV disease stage. [ABSTRACT FROM AUTHOR]

A fundamental goal of epidemiologic research is to investigate the relationship between exposures and disease risk. Cases of the disease are often considered a single outcome and assumed to share a common etiology. However, evidence indicates that many human diseases arise and evolve through a range of heterogeneous molecular pathologic processes, influenced by diverse exposures. Pathogenic heterogeneity has been considered in various neoplasms such as colorectal, lung, prostate, and breast cancers, leukemia and lymphoma, and non-neoplastic diseases, including obesity, type II diabetes, glaucoma, stroke, cardiovascular disease, autism, and autoimmune disease. In this article, we discuss analytic options for studying disease subtype heterogeneity, emphasizing methods for evaluating whether the association of a potential risk factor with disease varies by disease subtype. Methods are described for scenarios where disease subtypes are categorical and ordinal and for cohort studies, matched and unmatched case-control studies, and case-case study designs. For illustration, we apply the methods to a molecular pathological epidemiology study of alcohol intake and colon cancer risk by tumor LINE-1 methylation subtypes. User-friendly software to implement the methods is publicly available. [ABSTRACT FROM AUTHOR]

Background: Over half a million children worldwide develop active tuberculosis (TB) each year. Early-life nutritional exposures have rarely been examined in relation to pediatric TB among HIV-exposed children. We therefore investigated independent associations of early-life nutritional exposures with active TB among HIV-exposed children up to 2 years of age.Methods: Participants were children from a randomized controlled multivitamin supplementation trial conducted in Dar es Salaam, Tanzania, from August 2004 to May 2008, who received daily multivitamin supplements or placebo for 24 months.Results: Lower mean corpuscular volumes [relative risks (RR): 0.48, 95% confidence interval (CI): 0.27, 0.87] and higher birth weights (RR: 0.61, 95% CI: 0.37, 0.99) were protective against active TB, whereas multivitamin supplementation was not associated with TB risk (RR: 0.87, 95% CI: 0.65, 1.16).Conclusions: Knowledge of nutrition-related risk and protective factors for TB in HIV-exposed children could enhance preventive and case-finding activities in this population, contributing to efforts to reduce the global TB burden. [ABSTRACT FROM AUTHOR]

Background: Not much is known about the relations of circulating saturated fatty acids (SFAs), which are influenced by both metabolic and dietary determinants, with total and cause-specific mortality.Objective: We examined the associations of plasma phospholipid SFAs with total and cause-specific mortality among 3941 older adults from the Cardiovascular Health Study, a population-based prospective study of adults aged ≥65 y who were followed from 1992 through 2011.Methods: The relations of total and cause-specific mortality with plasma phospholipid palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) were assessed using Cox proportional hazards models.Results: During 45,450 person-years of follow-up, 3134 deaths occurred. Higher concentrations of the plasma phospholipid SFAs 18:0, 22:0, and 24:0 were associated with a lower risk of total mortality [multivariable-adjusted HRs (95% CIs)] for the top compared with the bottom quintile: 0.85 (0.75, 0.95) for 18:0; 0.85 (0.75, 0.95) for 22:0; and 0.80 (0.71, 0.90) for 24:0. In contrast, plasma 16:0 concentrations in the highest quintile were associated with a higher risk of total mortality compared with concentrations in the lowest quintile [1.25 (1.11, 1.41)]. We also found no association of plasma phospholipid 20:0 with total mortality.Conclusions: These findings suggest that the associations of plasma phospholipid SFAs with the risk of death differ according to SFA chain length and support future studies to better characterize the determinants of circulating SFAs and to explore the mechanisms underlying these relations. [ABSTRACT FROM AUTHOR]

We consider measurement error problem in the Cox model, where the underlying association between the true exposure and its surrogate is unknown, but can be estimated from a validation study. Under this framework, one can accommodate general distributional structures for the error-prone covariates, not restricted to a linear additive measurement error model or Gaussian measurement error. The proposed copula-based approach enables us to fit flexible measurement error models, and to be applicable with an internal or external validation study. Large sample properties are derived and finite sample properties are investigated through extensive simulation studies. The methods are applied to a study of physical activity in relation to breast cancer mortality in the Nurses' Health Study. [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]

Background: The insidious pace of long-term weight gain (∼ 1 lb/y or 0.45 kg/y) makes it difficult to study in trials; long-term prospective cohorts provide crucial evidence on its key contributors. Most previous studies have evaluated how prevalent lifestyle habits relate to future weight gain rather than to lifestyle changes, which may be more temporally and physiologically relevant.Objective: Our objective was to evaluate and compare different methodological approaches for investigating diet, physical activity (PA), and long-term weight gain.Methods: In 3 prospective cohorts (total n = 117,992), we assessed how lifestyle relates to long-term weight change (up to 24 y of follow-up) in 4-y periods by comparing 3 analytic approaches: 1) prevalent diet and PA and 4-y weight change (prevalent analysis); 2) 4-y changes in diet and PA with a 4-y weight change (change analysis); and 3) 4-y change in diet and PA with weight change in the subsequent 4 y (lagged-change analysis). We compared these approaches and evaluated the consistency across cohorts, magnitudes of associations, and biological plausibility of findings.Results: Across the 3 methods, consistent, robust, and biologically plausible associations were seen only for the change analysis. Results for prevalent or lagged-change analyses were less consistent across cohorts, smaller in magnitude, and biologically implausible. For example, for each serving of a sugar-sweetened beverage, the observed weight gain was 0.01 lb (95% CI: -0.08, 0.10) [0.005 kg (95% CI: -0.04, 0.05)] based on prevalent analysis; 0.99 lb (95% CI: 0.83, 1.16) [0.45 kg (95% CI: 0.38, 0.53)] based on change analysis; and 0.05 lb (95% CI: -0.10, 0.21) [0.02 kg (95% CI: -0.05, 0.10)] based on lagged-change analysis. Findings were similar for other foods and PA.Conclusions: Robust, consistent, and biologically plausible relations between lifestyle and long-term weight gain are seen when evaluating lifestyle changes and weight changes in discrete periods rather than in prevalent lifestyle or lagged changes. These findings inform the optimal methods for evaluating lifestyle and long-term weight gain and the potential for bias when other methods are used. [ABSTRACT FROM AUTHOR]

Objectives were to examine the growth patterns of preterm and growth‐restricted infants and to evaluate the associations of prematurity and intrauterine growth restriction (IUGR) with risk of stunting, wasting and underweight. Data from a cohort of HIV‐negative pregnant women–infant pairs were collected prospectively in Tanzania. Small for gestational age [SGA, birthweight (BW) <10th percentile] was used as proxy for IUGR. Anthropometry was measured monthly until 18 months. Length‐for‐age (LAZ), weight‐for‐length (WLZ), and weight‐for‐age (WAZ) z‐scores were calculated using the 2006 World Health Organization (WHO) Child Growth Standards. Stunting, wasting and underweight were defined as binary outcomes using a cut‐off of <−2 SD of the respective z‐scores. Multivariate Cox proportional hazard models were used to assess the associations between preterm and SGA to time to stunting, wasting and underweight. The study included 6664 singletons. Preterm and appropriate for gestational age (AGA) infants had slightly better nutritional status than term‐SGA infants and despite some catch‐up growth, preterm‐SGA infants had the poorest nutritional status. The gap in LAZ and WAZ z‐scores among the groups remained similar throughout the follow‐up. Compared with term‐AGA babies, relative risk (RR) of stunting among preterm‐AGA babies was 2.13 (95% confidence interval (CI) 1.93–2.36), RR among term‐SGA was 2.21 (95% CI 2.02–2.41) and the highest risk was among the babies who were both preterm and SGA (RR = 7.58, 95% CI 5.41–10.64). Similar magnitude of RR of underweight was observed among the three groups. Preterm and SGA infants should be closely monitored for growth failure. Intervention to reduce preterm and SGA birth may lower risk of undernutrition in resource‐limited settings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Prospective data on the relation of magnesium, potassium, and calcium intakes with stroke risk are inconsistent, and to our knowledge, the effect of a combined mineral diet score has not been examined. Objective: We examined associations between intakes of magnesium, potassium, and calcium and risk of incident stroke in 86,149 women in the Nurses' Health Study (NHS) I and 94,715 women in the NHS II. Design: In this prospective cohort study, we calculated HRs of stroke by quintiles of intake for each mineral and for a combined diet score of all 3 minerals by using multivariate Cox proportional hazard models. In addition, we updated meta-analyses on dietary intakes of these minerals and risk of stroke. Results: During follow-up (30 y in the NHS I; 22 y in the NHS II) a total of 3780 incident stroke cases were documented. Pooled multivariate RRs of total stroke for women in the highest compared with the lowest quintiles were 0.87 (95% CI: 0.78, 0.97) for total magnesium, 0.89 (95% CI: 0.80, 0.99) for total potassium, and 0.97 (95% CI: 0.87, 1.09) for total calcium intake. Pooled RRs for women in the highest compared with the lowest quintiles of a combined mineral diet score were 0.72 (95% CI: 0.65, 0.81) for total stroke, 0.78 (95% CI: 0.66, 0.92) for ischemic stroke, and 0.80 (95% CI: 0.61, 1.04) for hemorrhagic stroke. In the updated meta-analyses of all prospective studies to date, the combined RR of total stroke was 0.87 (95% CI: 0.83, 0.92) for a 100-mg/d increase in magnesium intake, 0.91 (95% CI: 0.88, 0.94) for a 1000-mg/d increase in potassium intake, and 0.98 (95% CI: 0.94, 1.02) for a 300-mg/d increase in calcium intake. Conclusions: A combined mineral diet score was inversely associated with risk of stroke. High intakes of magnesium and potassium but not calcium were also significantly associated with reduced risk of stroke in women. [ABSTRACT FROM AUTHOR]

We pooled data from 5 large validation studies (1999-2009) of dietary self-report instruments that used recovery biomarkers as referents, to assess food frequency questionnaires (FFQs) and 24-hour recalls (24HRs). Here we report on total potassium and sodium intakes, their densities, and their ratio. Results were similar by sex but were heterogeneous across studies. For potassium, potassium density, sodium, sodium density, and sodium:potassium ratio, average correlation coefficients for the correlation of reported intake with true intake on the FFQs were 0.37, 0.47, 0.16, 0.32, and 0.49, respectively. For the same nutrients measured with a single 24HR, they were 0.47, 0.46, 0.32, 0.31, and 0.46, respectively, rising to 0.56, 0.53, 0.41, 0.38, and 0.60 for the average of three 24HRs. Average underreporting was 5%-6% with an FFQ and 0%-4% with a single 24HR for potassium but was 28%-39% and 4%-13%, respectively, for sodium. Higher body mass index was related to under reporting of sodium. Calibration equations for true intake that included personal characteristics provided improved prediction, except for sodium density. In summary, self-reports capture potassium intake quite well but sodium intake less well. Using densities improves the measurement of potassium and sodium on an FFQ. Sodium:potassium ratio is measured much better than sodium itself on both FFQs and 24HRs. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that long-chain n-3 fatty acids derived from seafood are associated with a lower risk of mortality, CHD and stroke. Whether α-linolenic acid (ALA, 18 : 3n-3), a plant-derived long-chain essential n-3 fatty acid, is associated with a lower risk of these outcomes is unclear. The aim of the present study was to examine the associations of plasma phospholipid and dietary ALA with the risk of mortality, CHD and stroke among older adults who participated in the Cardiovascular Health Study, a cohort study of adults aged ≥ 65 years. A total of 2709 participants were included in the plasma phospholipid ALA analysis and 2583 participants were included in the dietary ALA analysis. Cox regression was used to assess the associations of plasma phospholipid and dietary ALA with the risk of mortality, incident CHD and stroke. In minimally and multivariable-adjusted models, plasma phospholipid ALA was found to be not associated with the risk of mortality, incident CHD or stroke. After adjustment for age, sex, race, enrolment site, education, smoking status, diabetes, BMI, alcohol consumption, treated hypertension and total energy intake, higher dietary ALA intake was found to be associated with a lower risk of total and non-cardiovascular mortality; on comparing the highest quintiles of dietary ALA with the lowest quintiles, the HR for total mortality and non-cardiovascular mortality were found to be 0·73 (95 % CI 0·61, 0·88) and 0·64 (95 % CI 0·52, 0·80), respectively. Dietary ALA was found to be not associated with the risk of cardiovascular mortality, incident CHD or stroke. In conclusion, the results of the present suggest study that dietary ALA, but not plasma phospholipid ALA, is associated with a lower risk of total and non-cardiovascular mortality in older adults. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Child stunting, wasting, and underweight have been individually associated with increased mortality. However, there has not been an analysis of the mortality risk associated with multiple anthropometric deficits. Objective: The objective was to quantify the association between combinations of stunting, wasting, and underweight and mortality among children <5 y of age. Design: We analyzed data from 10 cohort studies or randomized trials in low- and middle-income countries in Africa, Asia, and Latin America with 53,767 participants and 1306 deaths. Height-for-age, weight- for-height, and weight-for-age were calculated by using the 2006 WHO growth standards, and children were classified into 7 mutually exclusive combinations: no deficits; stunted only; wasted only; underweight only; stunted arid under-weight but not wasted; wasted and underweight but not stunted; and stunted, wasted, and under-weight (deficit defined as < -2 z scores). We calculated study- specific mortality HRs using Cox proportional hazards models and used a random-effects model to pool HRs across studies. Results: The risk of all-cause mortality was elevated among children with I, 2, and 3 anthroponetric deficits. In comparison with children with no deficits, the mortality HR5 were 3.4 (95% CI: 2.6, 4.3) among children who were stunted and underweight but not wasted; 4.7 (95% Cl: 3.1, 7.1) in those who were wasted and underweight but not stunted: and 12.3 (95% Cl: 7.7, 19.6) in those who were stunted, wasted, and underweight. Conclusion: Children with multiple deficits are at a heightened risk of mortality and may benefit most from nutrition and other child survival interventions. [ABSTRACT FROM AUTHOR]

Background: Despite the benefits of exclusive breastfeeding (EBF), exposure to HIV from breast milk has relegated EBF to an option only when formula feeding is not affordable, feasible, safe, and sustainable. Mixed feeding remains the norm in sub-Saharan Africa. Objective: We evaluated whether the duration of EBF was associated with mortality and HIV infection in children followed to ≤5 y of age. Methods: A total of 690 mother-infant pairs from the Trial of Vitamins with information on infant feeding, HIV status, and at least one visit in the first year were included in the analysis. The duration of EBF was defined in months as a time-varying covariate at each follow-up visit. Associations of the duration of EBF with mortality, HIV infection, and HIV infection or death were estimated by using Cox proportional hazards models and Kaplan-Meier survival curves. Results: A 1-mo increase in EBF was associated with a 49% reduction in early infant mortality in the first 6 mo of life (RR: 0.51 ; 95% CI: 0.28, 0.93) and a nonsignificant 15% reduction in risk of HIV infection or death (RR: 0.85; 95% CI: 0.71, 1.01; P = 0.07) over the first 5 y of life. EBF was not associated with HIV infection (RR: 0.93; 95% CI: 0.76, 1.15). Conclusion: Longer EBF by HIV-positive mothers was associated with reduced mortality in the first 6 mo of life without increased HIV infection, which makes EBF the best option for women who cannot sustain exclusive formula feeding. This trial was registered at clinicaltrials.gov as NCT00197743. [ABSTRACT FROM AUTHOR]

Fruit and vegetable intake may protect against pancreatic cancer, since fruits and vegetables are rich in potentially cancer-preventive nutrients. Most case-control studies have found inverse associations between fruit and vegetable intake and pancreatic cancer risk, although bias due to reporting error cannot be ruled out. In most prospective studies, inverse associations have been weaker and imprecise because of small numbers of cases. The authors examined fruit and vegetable intake in relation to pancreatic cancer risk in a pooled analysis of 14 prospective studies from North America, Europe, and Australia (study periods between 1980 and 2005). Relative risks and 2-sided 95% confidence intervals were estimated separately for the 14 studies using the Cox proportional hazards model and were then pooled using a random-effects model. Of 862,584 men and women followed for 7−20 years, 2,212 developed pancreatic cancer. The pooled multivariate relative risks of pancreatic cancer per 100-g/day increase in intake were 1.01 (95% confidence interval (CI): 0.99, 1.03) for total fruits and vegetables, 1.01 (95% CI: 0.99, 1.03) for total fruits, and 1.02 (95% CI: 0.99, 1.06) for total vegetables. Associations were similar for men and women separately and across studies. These results suggest that fruit and vegetable intake during adulthood is not associated with a reduced pancreatic cancer risk. [ABSTRACT FROM AUTHOR]

Prenatal iron supplementation may improve pregnancy outcomes and decrease the risk of child mortality. However, little is known about the importance of post-natal maternal iron status for child health and survival, particularly in the context of HIV infection. We examined the association of maternal anaemia and hypochromic microcytosis, an erythrocyte morphology consistent with iron deficiency, with child health and survival in the first two to five years of life. Repeated measures of maternal anaemia and hypochromic microcytosis from 840 HIV-positive women enrolled in a clinical trial of vitamin supplementation were prospectively related to child mortality, HIV infection and CD4 T-cell count. Median duration of follow-up for the endpoints of child mortality, HIV infection and CD4 cell count was 58, 17 and 23 months, respectively. Maternal anaemia and hypochromic microcytosis were associated with greater risk of child mortality [hazard ratio (HR) for severe anaemia = 2.58, 95% confidence interval (CI): 1.66-4.01, P trend < 0.0001; HR for severe hypochromic microcytosis = 2.36, 95% CI: 1.27-4.38, P trend = 0.001]. Maternal anaemia was not significantly associated with greater risk of child HIV infection (HR for severe anaemia = 1.46, 95% CI: 0.91, 2.33, P trend = 0.08) but predicted lower CD4 T-cell counts among HIV-uninfected children (difference in CD4 T-cell count/ µL for severe anaemia: −93, 95% CI: −204-17, P trend = 0.02). The potential child health risks associated with maternal anaemia and iron deficiency may not be limited to the prenatal period. Efforts to reduce maternal anaemia and iron deficiency during pregnancy may need to be expanded to include the post-partum period. [ABSTRACT FROM AUTHOR]

Background This study investigated the relationship between growing up in a violent home and developmental trajectories of body mass index (BMI) in a cohort of adolescents followed longitudinally from 1996 to 2003-4. Methods 6043 girls and 4934 boys aged 9-14 years in 1996 who reported height and weight at least two times and whose mothers completed intimate partner violence (IPV) questions at the 2001 Nurses' Health Study. Main exposure was experiencing the first family violence during early (0-5 years) or later (6-11 years) childhood, based on mother's year-specific exposure of IPV and the birth year of each participant. Mother's report of IPV was ascertained by the abuse assessment screen. Four distinct BMI trajectory groups were estimated from age-specific BMI (age 12-20 years), using general growth mixture modelling. Results Four distinct BMI trajectories were identified separately for girls and boys: healthy growth; healthy to obese; steady overweight and consistently obese. Compared with boys not exposed to violence at home, boys raised in violent homes before 5 years were at increased risk of being in the consistently obese (OR=2.0; 95% CI 1.2 to 3.5) and steady overweight (OR 1.4; 95% CI 1.1 to 1.9) groups after adjusting for confounders. Girls raised in violent homes were more likely to be in the steady overweight group, but associations did not maintain statistical significance after adjusting for confounding. Conclusion These data link children's exposure to domestic violence to a risk of unhealthy weight trajectories during adolescence in boys. Detrimental effects of exposure to a domestic violence environment may take root in the first few years of development for boys. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic studies examining associations between carotenoid intakes and risk of breast cancer by estrogen receptor (ER) and progesterone receptor (PR) status are limited. Objective: We investigated these associations in a pooled analysis of 18 cohort studies. Design: Of 1,028,438 participants followed for a maximum follow- up of 26 y across studies, 33,380 incident invasive breast cancers were identified. Study-specific RRs and 95% Cls were estimated by using Cox proportional hazards regression and then pooled by using a random-effects model. Results: α-Carotene, β-carotene, and lutein/zeaxanthin intakes were inversely associated with the risk of ER-negative (ER-) breast cancer (pooled multivariable RRs of the comparison between the highest and lowest quintiles): α-carotene (0.87; 95% CI: 0.78, 0.97), β-carotene (0.84; 95% CI: 0.77, 0.93), and lutein/zeaxanthin (0.87; 95% CI: 0.79, 0.95). These variables were not inversely associated with the risk of ER-positive (ER+) breast cancer (pooled multivariable RRs for the same comparison): α-carotene (1.04; 95% CI: 0.99, 1.09), β-carotene (1.04; 95% CI: 0.98, 1.10), and lutein/zeaxanthin (1.00; 95% CI: 0.93, 1.07). Although the pooled RRs for quintile 5 for β-cryptoxanthin were not significant, inverse trends were observed for ER- and ER+ breast cancer (P-trend ≤ 0.05). Nonsignificant associations were observed for lycopene intake. The associations were largely not appreciably modified by several breast cancer risk factors. Nonsignificant associations were observed for PR-positive and PR-negative breast cancer. Conclusions: Intakes of α-carotene, β-carotene, and lutein/zeaxanthin were inversely associated with risk of ER-, but not ER+, breast cancer. However, the results need to be interpreted with caution because it is unclear whether the observed association is real or due to other constituents in the same food sources. [ABSTRACT FROM AUTHOR]

Two methods for point and interval estimation of relative risk for log-linear exposure-response relations in meta-analyses of published ordinal categorical exposure-response data have been proposed. The authors compared the results of a meta-analysis of published data using each of the 2 methods with the results that would be obtained if the primary data were available and investigated the circumstances under which the approximations required for valid use of each meta-analytic method break down. They then extended the methods to handle nonlinear exposure-response relations. In the present article, methods are illustrated using studies of the relation between alcohol consumption and colorectal and lung cancer risks from the ongoing Pooling Project of Prospective Studies of Diet and Cancer. In these examples, the differences between the results of a meta-analysis of summarized published data and the pooled analysis of the individual original data were small. However, incorrectly assuming no correlation between relative risk estimates for exposure categories from the same study gave biased confidence intervals for the trend and biased P values for the tests for nonlinearity and between-study heterogeneity when there was strong confounding by other model covariates. The authors illustrate the use of 2 publicly available user-friendly programs (Stata and SAS) to implement meta-analysis for dose-response data. [ABSTRACT FROM AUTHOR]

Purpose: Case-control studies suggest increased sun exposure reduces non-Hodgkin lymphoma (NHL) risk. Evidence from prospective cohort studies, however, is limited and inconsistent. We evaluated the association between ambient ultraviolet radiation (UV) exposure and NHL in a nationwide cohort of women, the Nurses' Health Study (NHS).Methods: Between 1976 and 2006, we identified 1064 incident NHL cases among 115,482 women in the prospective NHS. Exposures assessed included average annual UV-B flux based on residence at various times during life, vitamin D intake, and predicted plasma 25-hydroxyvitamin D levels. We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) for risk of all NHL and histologic subtypes using Cox proportional hazards models.Results: NHL risk was increased for women residing in areas of high ambient UV radiation (UV-B flux >113 R-B count × 10(-4)) compared to those with lower exposure (<113), with positive linear trends at all time points. The multivariable-adjusted RR for high UV area at age 15 was 1.21 (95% CI: 1.00, 1.47; p-trend < 0.01). There was no evidence of statistical heterogeneity by subtype, although power was limited for subtype analyses. We observed no association between vitamin D measures and risk of NHL overall or by subtype.Conclusions: Our findings do not support the hypothesis of a protective effect of UV radiation exposure on NHL risk. We found no association between vitamin D and NHL risk. [ABSTRACT FROM AUTHOR]

Vitamin D has a potential role in preventing HIV-related complications, based on its extensive involvement in immune and metabolic function, including preventing osteoporosis and premature cardiovascular disease. However, this association has not been examined in large studies or in resource-limited settings. Vitamin D levels were assessed in 884 HIV-infected pregnant women at enrollment in a trial of multivitamin supplementation (excluding vitamin D) in Tanzania. Information on HIV related complications was recorded during follow-up (median, 70 months). Proportional hazards models and generalized estimating equations were used to assess the relationship of vitamin D status with these outcomes. Women with low vitamin D status (serum 25-hydroxyvitamin D<32 ng/mL) had 43% higher risk of reaching a body mass index (BMI) less than 18 kg/m2 during the first 2 years of follow-up, compared to women with adequate vitamin D levels (hazard ratio [HR]: 1.43; 95% confidence intervals: [1.03-1.99]). The relationship between continuous vitamin D levels and risk of BMI less than 18 kg/m2 during follow-up was inverse and linear ( p=0.03). Women with low vitamin D levels had significantly higher incidence of acute upper respiratory infections (HR: 1.27 [1.04-1.54]) and thrush (HR: 2.74 [1.29-5.83]) diagnosed during the first 2 years of follow-up. Low vitamin D status was a significant risk factor for wasting and HIV-related complications such as thrush during follow-up in this prospective cohort in Tanzania. If these protective associations are confirmed in randomized trials, vitamin D supplementation could represent a simple and inexpensive method to improve health and quality of life of HIV-infected patients, particularly in resource-limited settings. [ABSTRACT FROM AUTHOR]

Aspirin use decreases colon cancer risk, but this association may vary among population subgroups. The aspirin-colon cancer association was evaluated according to body mass index and physical activity in 1,701 incident colon cancer cases diagnosed during follow-up of 139,310 participants for up to 26 years in 2 US prospective cohort studies that began in 1980 and 1992, respectively. Whether plasma C-peptide levels modified the association was examined by using a nested case-control design (n = 384 cases, 749 controls). Multiplicative and additive interactions were tested. Body mass index did not modify the association; pooled multivariable relative risks for regular aspirin use versus nonuse ranged from 0.74 to 0.75 in the normal weight and obese groups (test for multiplicative interaction, P = 0.75; test for additive interaction, P = 0.66). Pooled multivariable relative risks for regular aspirin use were 0.86 (95% confidence interval (CI): 0.66, 1.11) in the low and 0.67 (95% CI: 0.58, 0.77) in the high physical activity groups with no interaction evident on either the multiplicative or additive scale (P > 0.10). Plasma C-peptide levels also did not modify the aspirin-colon cancer association, with multivariable relative risks of 0.74 (95% CI: 0.50, 1.10) for the low and 0.65 (95% CI: 0.46, 0.92) for the high group. Reductions in colon cancer risk associated with aspirin use were not significantly modified by body mass index, physical activity, or plasma C-peptide level in this study. [ABSTRACT FROM AUTHOR]

BACKGROUND: The etiology of autism is unknown, although perinatal and neonatal exposures have been the focus of epidemiologic research for over 40 years. OBJECTIVE: To provide the first review and meta-analysis of the association between perinatal and neonatal factors and autism risk. METHODS: PubMed, Embase, and Psyclnfo databases were searched for studies that examined the association between perinatal and neonatal factors and autism through March 2007. Forty studies were eligible for the meta-analysis. For each exposure, a summary effect estimate was calculated using a random-effects model. Heterogeneity in effect estimates across studies was examined, and, if found, a meta- regression was conducted to identify measured methodological factors that could explain between-study variability. RESULTS: Over 60 perinatal and neonatal factors were examined. Factors associated with autism risk in the meta-analysis were abnormal presentation, umbilical-cord complications, fetal distress, birth injury or trauma, multiple birth, maternal hemorrhage, summer birth, low birth weight, small for gestational age, congenital malformation, low 5-minute Apgar score, feeding difficulties, meconium aspiration, neonatal anemia, ABO or Rh incompatibility, and hyperbilirubmemia. Factors not associated with autism risk included anesthesia, assisted vaginal delivery, postterm birth, high birth weight, and head circumference. CONCLUSIONS: There is insufficient evidence to implicate any 1 perinatal or neonatal factor in autism etiology, although there is some evidence to suggest that exposure to a broad class of conditions reflecting general compromises to perinatal and neonatal health may increase the risk. Methodological variations were likely sources of heterogeneity of risk factor effects across studies. [ABSTRACT FROM AUTHOR]

This paper examines predictors of breastfeeding cessation among a cohort of human immunodeficiency virus (HIV)-infected women. This was a prospective follow-up study of HIV-infected women who participated in a randomized micronutrient supplementation trial conducted in Dar es Salaam, Tanzania. 795 HIV-infected Tanzanian women with singleton newborns were utilized from the cohort for this analysis. The proportion of women breastfeeding declined from 95% at 12 months to 11% at 24 months. The multivariate analysis showed breastfeeding cessation was significantly associated with increasing calendar year of delivery from 1995 to 1997 [risk ratio (RR), 1.36; 95% confidence interval (CI) 1.13-1.63], having a new pregnancy (RR 1.33; 95% CI 1.10-1.61), overweight [body mass index (BMI) ≥25 kg m; RR 1.37; 95% CI 1.07-1.75], underweight (BMI <18.5 kg m; RR 1.29; 95% CI 1.00-1.65), introduction of cow's milk at infant's age of 4 months (RR 1.30; 95% CI 1.04-1.63). Material and social support was associated with decreased likelihood of cessation (RR 0.83; 95% CI 0.68-1.02). Demographic, health and nutritional factors among women and infants are associated with decisions by HIV-infected women to cease breastfeeding. The impact of breastfeeding counselling programs for HIV-infected African women should consider individual maternal, social and health contexts. [ABSTRACT FROM AUTHOR]

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]

It is not known whether reproductive factors early in the mother's life influence risk of autism spectrum disorders (ASD). We assessed maternal age at menarche, menstrual cycle characteristics during adolescence, oral contraceptive use prior to first birth, body shape, and body mass index (BMI) in association with ASD using binomial regression in a cohort study of 61,596 women, including 743 cases. Overall, early life factors were not associated with ASD, though early age at menarche (RR for age 10 or less = 1.54, 95% CI 1.18, 2.02, p = 0.0002) and BMI at age 18 of ≥30 (RR 2.03, 95% CI 1.34, 3.08, p = 0.0008) were significantly associated with increased risk of ASD. Further work should investigate the potential influence of these factors. [ABSTRACT FROM AUTHOR]

Repeat-biomarker measurement error models accounting for systematic correlated within-person error can be used to estimate the correlation coefficient (ρ) and deattenuation factor (λ), used in measurement error correction. These models account for correlated errors in the food frequency questionnaire (FFQ) and the 24-hour diet recall and random within-person variation in the biomarkers. Failure to account for within-person variation in biomarkers can exaggerate correlated errors between FFQs and 24-hour diet recalls. For 2 validation studies, ρ and λ were calculated for total energy and protein density. In the Automated Multiple-Pass Method Validation Study (n = 471), doubly labeled water (DLW) and urinary nitrogen (UN) were measured twice in 52 adults approximately 16 months apart (2002—2003), yielding intraclass correlation coefficients of 0.43 for energy (DLW) and 0.54 for protein density (UN/DLW). The deattenuated correlation coefficient for protein density was 0.51 for correlation between the FFQ and the 24-hour diet recall and 0.49 for correlation between the FFQ and the biomarker. Use of repeat-biomarker measurement error models resulted in a ρ of 0.42. These models were similarly applied to the Observing Protein and Energy Nutrition Study (1999—2000). In conclusion, within-person variation in biomarkers can be substantial, and to adequately assess the impact of correlated subject-specific error, this variation should be assessed in validation studies of FFQs. [ABSTRACT FROM AUTHOR]

The authors prospectively examined the relation of fruit and vegetable intake to breast cancer risk among 51,928 women aged 21–69 years at enrollment in 1995 in the Black Women's Health Study. Dietary intake was assessed by using a validated food frequency questionnaire. Cox proportional hazards models were used to estimate incidence rate ratios and 95% confidence intervals, adjusted for breast cancer risk factors. During 12 years of follow-up, there were 1,268 incident cases of breast cancer. Total fruit, total vegetable, and total fruit and vegetable intakes were not significantly associated with overall risk of breast cancer. However, total vegetable consumption was associated with a decreased risk of estrogen receptor-negative/progesterone receptor-negative breast cancer (incidence rate ratio = 0.57, 95% confidence interval: 0.38, 0.85, for ≥2 servings/day relative to <4/week; Ptrend = 0.02). In addition, there was some evidence of inverse associations with breast cancer risk overall for cruciferous vegetable intake (Ptrend = 0.06) and for carrot intake (Ptrend = 0.02). Study findings suggest that frequent consumption of vegetables is inversely associated with risk of estrogen receptor-negative/progesterone receptor-negative breast cancer, and that specific vegetables may be associated with a decreased risk of breast cancer overall. [ABSTRACT FROM PUBLISHER]

Objective: Prospective studies of tea and coffee intake and breast cancer risk have yielded inconsistent results. None of these studies has reported separately on African-American women. We prospectively examined the relation of tea and coffee consumption to risk of breast cancer among 52,062 women aged 21-69 at enrollment in 1995 in the Black Women's Health Study.Methods: Dietary intake was assessed in 1995 and 2001 using a validated food frequency questionnaire. Cox proportional hazards models were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI), adjusted for breast cancer risk factors.Results: During 12 years of follow-up through 2007, there were 1,268 incident cases of breast cancer. Intakes of tea, coffee, and caffeine were not significantly associated with the risk of breast cancer overall. The IRRs for consumption of ≥4 cups/day compared with none were 1.13 (95% CI 0.78-1.63) for tea and 1.03 (95% CI 0.77-1.39) for caffeinated coffee, and the IRR for the top quintile relative to the bottom quintile of caffeine intake was 1.04 (95% CI 0.87-1.24). Consumption of tea, coffee, and caffeine was not significantly associated with breast cancer risk according to menopausal status or hormone receptor status.Conclusion: Our findings suggest that intakes of tea, coffee, and caffeine are not associated with the risk of breast cancer among African-American women. [ABSTRACT FROM AUTHOR]