Search

Research on mortality associated with exposure to the Holocaust is relevant for a better understanding of the effects of genocides on survivors. To our knowledge, previous studies have not investigated the long-term cause-specific mortality of Holocaust survivors. We compared mortality rates among Israelis born in European countries controlled by the Nazis during World War II with those among Israelis of European descent who did not have this exposure. Records of 22,671 people (45% women; 5,042 survivors) from the population-based Jerusalem Perinatal Study (1964–1976) were linked to the Israeli Population Registry, which was updated through 2016. Cox models were used for analysis, with 2-sided tests of statistical significance. Risk of all-cause mortality was higher among exposed women (hazard ratio (HR) = 1.15, 95% confidence interval (CI): 1.05, 1.27) than in unexposed women. No association was found between Holocaust exposure and male all-cause mortality. In both sexes, survivors had higher cancer-specific mortality (HR = 1.17 (95% CI: 1.01, 1.35) in women and HR = 1.14 (95% CI: 1.01, 1.28) in men). Exposed men also had excess mortality due to coronary heart disease (HR = 1.39, 95% CI: 1.09, 1.77) and lower mortality from other known causes combined (HR = 0.86, 95% CI: 0.75, 0.99). In summary, experiencing the Holocaust was associated with excess all-cause and cancer-specific mortality in women and cancer- and coronary heart disease–specific mortality in men. [ABSTRACT FROM AUTHOR]

Decline in both telomere length and physical fitness over the life course may contribute to increased risk of several chronic diseases. The relationship between telomere length and aerobic and muscular fitness is not well characterized. We examined whether there are cross-sectional associations of mean relative leukocyte telomere length (LTL) with objective measures of aerobic fitness, muscle strength, and muscle endurance, using data on 31-year-old participants of the Northern Finland Birth Cohort 1966 (n = 4,952-5,205, varying by exposureoutcome analysis). Aerobic fitness was assessed by means of heart rate measurement following a standardized submaximal step test; muscular fitness was assessed by means of a maximal isometric handgrip strength test and a test of lower-back trunk muscle endurance. Longer LTL was associated with higher aerobic fitness and better trunk muscle endurance in models including adjustment for age, sex, body mass index, socioeconomic position, diet, smoking, alcohol consumption, physical activity level, and C-reactive protein. In a sex-stratified analysis, LTL was not associated with handgrip strength in either men or women. LTL may relate to aspects of physical fitness in young adulthood, but replication of these findings is required, along with further studies to help assess directions and causality in these associations. [ABSTRACT FROM AUTHOR]

Indoor tanning is associated with increased risk of melanoma, but most evidence comes from case-control studies. Using data from the Norwegian Women and Cancer Study, a large prospective cohort study, we investigated the associations of age at initiation of indoor tanning, duration of tanning-device use, and dose response with melanoma risk and examined the role of indoor tanning in age at melanoma diagnosis. We used Poisson regression to estimate relative risks and 95% confidence intervals for the relationship of indoor tanning to melanoma risk and linear regression to examine age of indoor tanning initiation in relation to age at diagnosis. During follow-up of 141,045 women (1991-2012; mean duration follow-up = 13.7 years), 861 women were diagnosed with melanoma. Melanoma risk increased with increasing cumulative number of tanning sessions (for highest tertile of use vs. never use, adjusted relative risk = 1.32, 95% confidence interval (CI): 1.08,1.63); P-trend = 0.006. Age at initiation <30 years was associated with a higher risk in comparison with never use (adjusted relative risk = 1.31, 95% CI: 1.07, 1.59). Moreover, women who started indoor tanning prior to 30 years of age were 2.2 years (95% CI: 0.9, 3.4) younger at diagnosis, on average, than never users. This cohort study provides strong evidence of a dose-response association between indoor tanning and risk of melanoma and supports the hypothesis that vulnerability to the harmful effects of indoor tanning is greater at a younger age. [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]

The mental health toll of the Iraq and Afghanistan Wars on military veterans has been considerable, yet little is known about the persistence of these adverse outcomes, especially relative to predeployment status. We pro-spectively examined posttraumatic stress disorder (PTSD) as a long-term consequence of warzone deployment, integrating data collected from 2003-2014. In the Neurocognition Deployment Health Study, we measured PTSD symptoms in US Army soldiers before and shortly after Iraq War deployment. We used the PTSD Checklist-Civilian Version and a structured clinical interview (i.e., Clinician-Administered PTSD Scale) to reassess PTSD in 598 service members and military veterans a median of 7.9 years (interquartile range, 7.2-8.5 years) after an index Iraq deployment. At long-term follow-up, 24.7% (95% confidence interval (CI): 21.5, 28.4) of participants met the case definition for PTSD, which was an absolute increase of 14.2% from the percentage assessed post-deployment (10.5%; 95% CI: 7.8, 13.7) and of 17.3% from the percentage assessed predeployment (7.4%; 95% CI: 5.5, 9.8). These findings highlight that PTSD is an enduring consequence of warzone participation among contemporary military personnel and veterans. The largest increase in PTSD cases occurred between the post-deployment and long-term follow-up assessments, which suggests that adverse stress reactions cannot necessarily be expected to dissipate over time and actually may increase. [ABSTRACT FROM AUTHOR]

Diet quality index scores on Healthy Eating Index 2010 (HEI-2010), Alternative HEI-2010, alternative Mediterranean Diet Index, and the Dietary Approaches to Stop Hypertension (DASH) index have been inversely associated with all cause and cancer-specific death. This study assessed the association between these scores and colorectal cancer (CRC) incidence as well as CRC-specific mortality in the Women's Health Initiative Observational Study (1993-2012), a US study of postmenopausal women. During an average of 12.4 years of follow-up, there were 938 cases of CRC and 238 CRC-specific deaths. We estimated multivariate hazard ratios and 95% confidence intervals for relationships between quintiles of diet scores (from baseline food frequency questionnaires) and outcomes. HEI-2010 score (hazard ratios were 0.81, 0.77, and 0.73 with P values of 0.04, 0.01, and <0.01 for quintiles 3-5 vs. quintile 1, respectively) and DASH score (hazard ratios were 0.72, 0.74, and 0.78 with P values of <0.01, <0.01, and 0.03 for quintiles 3-5 vs. quintile 1, respectively), but not other diet scores, were associated with a lower risk of CRC in adjusted models. No diet scores were significantly associated with CRC-specific mortality. Closer adherence to HEI-2010 and DASH dietary recommendations was inversely associated with risk of CRC in this large cohort of postmenopausal women. [ABSTRACT FROM AUTHOR]

There has been a worldwide epidemic of obesity in recent decades. In animal studies, there is convincing evidence that light exposure causes weight gain, even when calorie intake and physical activity are held constant. Disruption of sleep and circadian rhythms by exposure to light at night (LAN) might be one mechanism contributing to the rise in obesity, but it has not been well-investigated in humans. Using multinomial logistic regression, we examined the association between exposure to LAN and obesity in questionnaire data from over 100,000 women in the Breakthrough Generations Study, a cohort study of women aged 16 years or older who were living in the United Kingdom and recruited during 2003–2012. The odds of obesity, measured using body mass index, waist:hip ratio, waist:height ratio, and waist circumference, increased with increasing levels of LAN exposure (P < 0.001), even after adjustment for potential confounders such as sleep duration, alcohol intake, physical activity, and current smoking. We found a significant association between LAN exposure and obesity which was not explained by potential confounders we could measure. While the possibility of residual confounding cannot be excluded, the pattern is intriguing, accords with the results of animal experiments, and warrants further investigation. [ABSTRACT FROM PUBLISHER]

We show that, in the presence of uncontrolled environmental confounding, joint tests for the presence of a main genetic effect and gene-environment interaction will be biased if the genetic and environmental factors are correlated, even if there is no effect of either the genetic factor or the environmental factor on the disease. When environmental confounding is ignored, such tests will in fact reject the joint null of no genetic effect with a probability that tends to 1 as the sample size increases. This problem with the joint test vanishes under gene-environment independence, but it still persists if estimating the gene-environment interaction parameter itself is of interest. Uncontrolled environmental confounding will bias estimates of gene-environment interaction parameters even under gene-environment independence, but it will not do so if the unmeasured confounding variable itself does not interact with the genetic factor. Under gene-environment independence, if the interaction parameter without controlling for the environmental confounder is nonzero, then there is gene-environment interaction either between the genetic factor and the environmental factor of interest or between the genetic factor and the unmeasured environmental confounder. We evaluate several recently proposed joint tests in a simulation study and discuss the implications of these results for the conduct of gene-environment interaction studies. [ABSTRACT FROM PUBLISHER]

A genetic variant within the CHRNA5-CHRNA3-CHRNB4 region (rs1051730), previously associated with smoking quantity, was recently shown to interact with smoking on obesity predisposition. We attempted to replicate this finding in the Gene-Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk (GLACIER) Study, a prospective cohort study of adults from northern Sweden (n = 16,426). We also investigated whether a similar interaction is apparent between rs1051730 and snus, a type of moist oral tobacco, to determine whether this interaction is driven by factors that cigarettes and snus have in common, such as nicotine. Main effects of smoking, snus, and the rs1051730 variant and pairwise interaction terms (smoking × rs1051730 and snus × rs1051730) were tested in relation to body mass index (BMI; calculated as weight (kg)/height (m)2) through the use of multivariate linear models adjusted for age and sex. Smoking status and BMI were inversely related (β = −0.46 kg/m2, standard error (SE) = 0.08; P < 0.0001). Snus use and BMI were positively related (β = 0.35 kg/m2, SE = 0.12; P = 0.003). The rs1051730 variant was not significantly associated with smoking status or snus use (P > 0.05); the T allele was associated with lower BMI in the overall cohort (β = −0.10 kg/m2, SE = 0.05; P = 0.03) and with smoking quantity in those in whom this was measured (n = 5,304) (β = 0.08, SE = 0.01; P < 0.0001). Neither smoking status (Pinteraction = 0.29) nor snus use (Pinteraction = 0.89) modified the association between the rs1051730 variant and BMI. [ABSTRACT FROM PUBLISHER]

In this study, we compared the relationships of body mass index (BMI) and body adiposity index (BAI) with body fat percentage (BF%) in a Caucasian, European population. BF% was measured by dual-energy x-ray absorptiometry in a population-based cross-sectional study of 5,193 middle-aged (47–49 years) and elderly (71–74 years) men and women from the Hordaland Health Study in western Norway from 1997 to 1999. In the total population, the correlation between BAI and BF% was stronger (r = 0.78) than the correlation between BMI and BF% (r = 0.56) with similar results in the middle-aged and elderly groups. However, in men and women separately, BMI was a better correlate of BF% (for men, r = 0.76; for women, r = 0.81) than was BAI (for men, r = 0.57; for women, r = 0.72). BMI was also a better correlate of BF% than was BAI assessed by partial correlations adjusted for sex (for BMI-BF%, r = 0.79; for BAI-BF%, r = 0.67). Bland-Altman plots and BF%-stratified analyses showed that BAI tended to overestimate BF% in lean subjects and to underestimate it in those with higher proportions of body fat, but that it predicted BF% well for those whose BMI was in a normal range. At the individual level and in population studies adjusted for sex, BMI outperforms BAI as a predictor of BF%. [ABSTRACT FROM PUBLISHER]

Modified Poisson regression, which combines a log Poisson regression model with robust variance estimation, is a useful alternative to log binomial regression for estimating relative risks. Previous studies have shown both analytically and by simulation that modified Poisson regression is appropriate for independent prospective data. This method is often applied to clustered prospective data, despite a lack of evidence to support its use in this setting. The purpose of this article is to evaluate the performance of the modified Poisson regression approach for estimating relative risks from clustered prospective data, by using generalized estimating equations to account for clustering. A simulation study is conducted to compare log binomial regression and modified Poisson regression for analyzing clustered data from intervention and observational studies. Both methods generally perform well in terms of bias, type I error, and coverage. Unlike log binomial regression, modified Poisson regression is not prone to convergence problems. The methods are contrasted by using example data sets from 2 large studies. The results presented in this article support the use of modified Poisson regression as an alternative to log binomial regression for analyzing clustered prospective data when clustering is taken into account by using generalized estimating equations. [ABSTRACT FROM PUBLISHER]

In previous studies among 1,144 cases and 1,256 controls recruited in stage 1 of the Shanghai Breast Cancer Study (SBCS I; 1996–1998), 18 known or potentially functional single nucleotide polymorphisms (SNPs) in 16 genes were found to be associated with breast cancer risk. The authors evaluated these associations among 1,918 cases and 1,819 controls recruited in stage 2 of the SBCS (SBCS II; 2002–2005) using genetic effect models and subgroup analyses predetermined from SBCS I results. Five SNPs (AHR rs2066853, ATM rs1003623, ESR1 rs2234693, GSTP1 rs1695, and SHBG rs6259) showed generally consistent results in SBCS I and SBCS II and statistically significant associations with breast cancer risk in combined analyses, mostly in subgroups defined by age or menopausal status. Further, the relation between breast cancer risk and SHBG rs6259 was found to vary by body mass index (weight (kg)/height (m)2) (P for interaction = 0.003). The strongest reduction in risk associated with SHBG rs6259 was found for lean (body mass index <23) postmenopausal minor allele carriers (odds ratio = 0.6, 95% confidence interval: 0.5, 0.8; P = 4.6 × 10−4). This biologically plausible and highly significant finding provides strong evidence for a true association among Asian women. This study also highlights the value of gene-environment interaction analyses in evaluating genetic factors for complex diseases. [ABSTRACT FROM PUBLISHER]

Although the September 11, 2001, terrorist attacks were the largest human-made disaster in US history, there is little extant research documenting the attacks’ consequences among those most directly affected, that is, persons who were in the World Trade Center towers. Data from a cross-sectional survey conducted 2–3 years after the attacks ascertained the prevalence of long-term, disaster-related posttraumatic stress symptoms and probable posttraumatic stress disorder (PTSD) in 3,271 civilians who evacuated World Trade Center towers 1 and 2. Overall, 95.6% of survivors reported at least 1 current posttraumatic stress symptom. The authors estimated the probable rate of PTSD at 15.0% by using the PTSD Checklist. Women and minorities were at an increased risk of PTSD. A strong inverse relation with annual income was observed. Five characteristics of direct exposure to the terrorist attacks independently predicted PTSD: being on a high floor in the towers, initiating evacuation late, being caught in the dust cloud that resulted from the tower collapses, personally witnessing horror, and sustaining an injury. Working for an employer that sustained fatalities also increased risk. Each addition of an experience of direct exposure resulted in a 2-fold increase in the risk of PTSD (odds ratio = 2.09, 95% confidence interval: 1.84, 2.36). Identification of these risk factors may be useful when screening survivors of large-scale terrorist events for long-term psychological sequelae. [ABSTRACT FROM PUBLISHER]

The worldwide incidence of gastric adenocarcinoma (GC) is lower in women than in men. Furthermore, cancer patients treated with estrogens have been reported to have a lower subsequent risk of GC. The authors conducted a prospective analysis of menstrual and reproductive factors, exogenous hormone use, and GC in 335,216 women from the European Prospective Investigation Into Cancer and Nutrition, a cohort study of individuals aged 35–70 years from 10 European countries. After a mean follow-up of 8.7 years (through 2004), 181 women for whom complete exposure data were available developed GC. Adjusted hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models. All statistical tests were 2-sided. Women who had ovariectomy had a 79% increased risk of GC (based on 25 cases) compared with women who did not (hazard ratio = 1.79, 95% confidence interval: 1.15, 2.78). Total cumulative years of menstrual cycling was inversely associated with GC risk (fifth vs. first quintile: hazard ratio = 0.55, 95% confidence interval: 0.31, 0.98; Ptrend = 0.06). No other reproductive factors analyzed were associated with risk of GC. The results of this analysis provide some support for the hypothesis that endogenous ovarian sex hormones lower GC incidence in women. [ABSTRACT FROM PUBLISHER]

From 1970 to 1988, thousands of children have been treated with human growth hormone (hGH) to supply pituitary gland deficiency. In France, 51 of the 968 children treated by hGH lots produced between January 1984 and March 1985 had developed Creutzfeldt-Jakob disease (CJD) by the end of 1996. The authors' objective was to investigate which of the 13 hGH lots produced during this period might be implicated in the iatrogenic transmission of CJD. In this paper, the authors describe a model tht was developed to compute the probability for each lot of being contaminated. The validity of the model was assessed by a simulation study that showed a good agreement between the estimated and the simulated number of contaminated lots. The model suggested that about half of the lots distributed during this period might have been contaminated by the infectious agent that causes CJD. The risk of iatrogenic CJD for patients exposed to contaminated hGHlots was estimated to be 0.06 (95% confidence interval 0.05–0.07). [ABSTRACT FROM AUTHOR]

To test the hypothesis that occupational lifting is a cause of hip osteoarthritis, the authors examined associations with lifting and other occupational activities in a case-control study. The study was performed in two English health districts (Portsmouth and North Staffordshire) from 1993 to 1995. A total of 611 patients (210 men and 401 women) listed for hip replacement because of osteoarthritis over an 18-month period were compared with an equal number of controls selected from the general population and ndividually matched for age, sex, and general practice. Information about suspected risk factors was obtained by a questionnaire administered at interview and a short physical examination. Analysis was by conditional logistic regression. After adjustment for potential confounders, the risk in men increased progressively with the duration and heaviness of occupational lifting. Relative to those with low exposure, men who had regularly lifted weights in excess of 50 kg for 10 years or longer had an odds ratio of 3.2 (95% confidence interval 1.6–6.5). No comparable association was found in women. Of the other occupational activities examined, only frequent climbing of stairs showed a pattern suggestive of a causal relation. These findings are consistent with the results of other studies, and there is now a strong case for regarding hip steoarthritis as an occupational disease in men whose work has involved prolonged and frequent heavy lifting. [ABSTRACT FROM AUTHOR]

Limited prospective data exist on how living arrangements are associated with change in functional health. This study evaluated whether elderly women living alone were less likely to experience functional decline when compared with women who lived with others. A total of 619 community-dwelling, white women from Baltimore, Maryland, aged 65–99 years at baseline were questioned annually from 1984 to 1986. Functional health was measured as the sum of limitations in seven physical and seven instrumental activities of daily living (Instrumental ADL). A total of 148 women experienced functional decline over the 2 years, primarily as a deterioration in Instrumental ADL The association between living arrangement and change in Instrumental ADL depended on the level of physical impairment. Among women without severe impairment, Instrumental ADL deterioration was significantly less for those living alone compared with those living with spouses (odds ratio (OR) = 0.60, 95% confidence interval (Cl) 0.45–0.92) or nonspouse others (OR = 0.62, 95% Cl 0.45–0.96). For women with severe impairment, however, those living alone had a greater decline in Instrumental ADL, especially when compared with those living with nonspouse others (OR = 5.13, 95% Cl 1.23–21.28). These results suggest that, unless severely physically impaired, women living independently have less deterioration in functional health when compared with peers in alternate living arrangements. Am J Epidemiol 1998; 147: 370–8. [ABSTRACT FROM AUTHOR]

The authors present algorithms to compute the confidence interval for a Poisson parameter (λ) and the p value for testing the hypothesis that λ is equal to a constant, which can be used to make inferences about the standardized mortality ratio and the standardized incidence ratio. The p value and confidence interval always agree, despite the discrete nature of the Poisson distribution. The authors also give simple equations to compute numeric approximations of the confidence limits that do not require the use of any probability distributions. An example based on data arising from a study of cancer incidence is given. [ABSTRACT FROM PUBLISHER]

A letter to the editor is presented in response to the article "Describing Data Requires No Adjustment for Multiple Comparisons" by David A. Savitz and Andrew F. Olshan.