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ObjectiveTo update a previous individual participant data meta-analysis and determine the accuracy of the Patient Health Questionnaire-9 (PHQ-9), the most commonly used depression screening tool in general practice, for detecting major depression overall and by study or participant subgroups.DesignSystematic review and individual participant data meta-analysis.Data sourcesMedline, Medline In-Process, and Other Non-Indexed Citations via Ovid, PsycINFO, Web of Science searched through 9 May 2018.Review methodsEligible studies administered the PHQ-9 and classified current major depression status using a validated semistructured diagnostic interview (designed for clinician administration), fully structured interview (designed for lay administration), or the Mini International Neuropsychiatric Interview (MINI; a brief interview designed for lay administration). A bivariate random effects meta-analytic model was used to obtain point and interval estimates of pooled PHQ-9 sensitivity and specificity at cut-off values 5-15, separately, among studies that used semistructured diagnostic interviews (eg, Structured Clinical Interview for Diagnostic and Statistical Manual), fully structured interviews (eg, Composite International Diagnostic Interview), and the MINI. Meta-regression was used to investigate whether PHQ-9 accuracy correlated with reference standard categories and participant characteristics.ResultsData from 44 503 total participants (27 146 additional from the update) were obtained from 100 of 127 eligible studies (42 additional studies; 79% eligible studies; 86% eligible participants). Among studies with a semistructured interview reference standard, pooled PHQ-9 sensitivity and specificity (95% confidence interval) at the standard cut-off value of ≥10, which maximised combined sensitivity and specificity, were 0.85 (0.79 to 0.89) and 0.85 (0.82 to 0.87), respectively. Specificity was similar across reference standards, but sensitivity in studies with semistructured interviews was 7-24% (median 21%) higher than with fully structured reference standards and 2-14% (median 11%) higher than with the MINI across cut-off values. Across reference standards and cut-off values, specificity was 0-10% (median 3%) higher for men and 0-12 (median 5%) higher for people aged 60 or older.ConclusionsResearchers and clinicians could use results to determine outcomes, such as total number of positive screens and false positive screens, at different PHQ-9 cut-off values for different clinical settings using the knowledge translation tool atwww.depressionscreening100.com/phq.Study registrationPROSPERO CRD42014010673.

Background: \ud Men and women are increasingly likely to stay sexually active into later life, but research shows that sexual activity and satisfaction decrease with increasing age. Ill health and medical treatments may affect sexual activity but there is little research on why some older people with a health problem affecting their sexual activity are satisfied with their sex life, and others are not.\ud \ud Methods: \ud A mixed method study integrating data and analyses from the third British National Survey of Sexual Attitudes and Lifestyles (n = 3343 aged 55–74 years) and from follow-up in-depth interviews with 23 survey participants who reported having a health condition or taking medication affecting their sex life.\ud \ud Results: \ud Overall, 26.9% of men and 17.1% of women aged 55–74 reported having a health condition that affected their sex life. Among this group, women were less likely than men to be sexually active in the previous 6 months (54.3% vs 62.0%) but just as likely to be satisfied with their sex life (41.9% vs 42.1%). In follow-up interviews, participants sometimes struggled to tease out the effects of ill health from those of advancing age. Where effects of ill health were identified, they tended to operate through the inclination and capacity to be sexually active, the practical possibilities for doing so and the limits placed on forms of sexual expression. In close relationships partners worked to establish compensatory mechanisms, but in less close relationships ill health provided an excuse to stop sex or deterred attempts to resolve difficulties. Most fundamentally, ill health may influence whether individuals have a partner with whom to have sex.\ud \ud Conclusion: \ud The data show complex interactions between health, lifestyle and relationship factors that affect sexual activity/satisfaction. When dealing with sexual problems in older people, practitioners need to take account of individual lifestyle, needs and preferences.

Growing evidence from both epidemiology and basic science suggest an inverse association between Alzheimer’s disease (AD) and cancer. We examined the genetic relationship between AD and various cancer types using GWAS summary statistics from the IGAP and GAME-ON consortia. Sample size ranged from 9931 to 54,162; SNPs were imputed to the 1000 Genomes European panel. Our results based on cross-trait LD Score regression showed a significant positive genetic correlation between AD and five cancers combined (colon, breast, prostate, ovarian, lung; r g = 0.17, P = 0.04), and specifically with breast cancer (ER-negative and overall; r g = 0.21 and 0.18, P = 0.035 and 0.034) and lung cancer (adenocarcinoma, squamous cell carcinoma and overall; r g = 0.31, 0.38 and 0.30, P = 0.029, 0.016, and 0.006). Estimating the genetic correlation in specific functional categories revealed mixed positive and negative signals, notably stronger at annotations associated with increased enhancer activity. This suggests a role of gene expression regulators in the shared genetic etiology between AD and cancer, and that some shared variants modulate disease risk concordantly while others have effects in opposite directions. Due to power issues, we did not detect cross-phenotype associations at individual SNPs. This genetic overlap is not likely driven by a handful of major loci. Our study is the first to examine the co-heritability of AD and cancer leveraging large-scale GWAS results. The functional categories highlighted in this study need further investigation to illustrate the details of the genetic sharing and to bridge between different levels of associations.

Summary Background Sexual violence is increasingly recognised as a public health issue. Information about prevalence, associated factors, and consequences for health in the population of Britain (England, Scotland, and Wales) is scarce. The third National Survey of Sexual Health Attitudes and Lifestyles (Natsal-3) is the first of the Natsal surveys to include questions about sexual violence and the first population-based survey in Britain to explore the issue outside the context of crime. Methods Between Sept 6, 2010, and Aug 31, 2012, we did a probability sample survey of women and men aged 16–74 years living in Britain. We asked participants about their experience of sex against their will since age 13 years and the circumstances surrounding the most recent occurrence. We explored associations between ever experiencing non-volitional sex and a range of sociodemographic, health, and behavioural factors. We used logistic regression to estimate age-adjusted odds ratios to analyse factors associated with the occurrence of completed non-volitional sex in women and men. Findings We interviewed 15 162 people. Completed non-volitional sex was reported by 9·8% (95% CI 9·0–10·5) of women and 1·4% (1·1–1·7) of men. Median age (interdecile range) at most recent occurrence was 18 years (14–32) for women and 16 years (13–30) for men. Completed non-volitional sex varied by family structure and, in women, by age, education, and area-level deprivation. It was associated with poor health, longstanding illness or disability, and treatment for mental health conditions, smoking, and use of non-prescription drugs in the past year in both sexes, and with binge drinking in women. Completed non-volitional sex was also associated with reporting of first heterosexual intercourse before 16 years of age, same-sex experience, more lifetime sexual partners, ever being diagnosed with a sexually transmitted infection, and low sexual function in both sexes, and, in women, with abortion and pregnancy outcome before 18 years of age. In most cases, the person responsible was known to the individual, although the nature of the relationship differed by age at most recent occurrence. Participants who were younger at interview were more likely to have told someone about the event and to have reported it to the police than were older participants. Interpretation These data provide the first population prevalence estimates of non-volitional sex in Britain. We showed it to be mainly an experience of young age and strongly associated with a range of adverse health outcomes in both women and men. Funding Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health.

Background Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. Methods and Findings A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Conclusions Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers., In a Mendelian randomisation study Pierce and colleagues show a genetic association between adult height and increased risk of colorectal and lung cancer., Author Summary Why Was This Study Done? Several previous observational studies have examined the association between adult height and risk of cancers of the lung, colon/rectum, and prostate; however, it remains unclear whether adult height is indeed related to the risk of these cancers. What Did the Researchers Do and Find? We conducted a systematic review and meta-analysis of prospective cohort studies that examined the association between adult height and the risk of colorectal, lung, and prostate cancers. To overcome inherent limitations of observational study designs, we conducted Mendelian randomization analyses using genetic data generated from a large multi-center consortium study including 47,800 cases and 81,353 controls. In the meta-analysis of the prospective observational studies, we found a 12% increased risk of colorectal cancer, a 7% increased risk of prostate cancer, and a 6% increased risk of lung cancer for every ten-centimeter increase in height, and this increased risk was corroborated in the Mendelian randomization analyses for colorectal (58%) and lung cancer (10%). What Do These Findings Mean? Our study provides strong evidence for an association between adult height and risk of colorectal and lung cancer, and suggests that certain genetic and biological factors that affect height may also affect the risk of these cancers. However, our meta-analysis was limited to published studies, and the sample size for the Mendelian randomization analysis for colorectal cancer was relatively small, affecting the precision of the risk estimate.

Summary Background Unplanned pregnancy is a key public health indicator. We describe the prevalence of unplanned pregnancy, and associated factors, in a general population sample in Britain (England, Scotland, and Wales). Method We did a probability sample survey, the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), of 15 162 men and women aged 16–74 years in Britain, including 5686 women of child-bearing age (16–44 years) who were included in the pregnancy analysis, between Sept 6, 2010, and Aug 31, 2012. We describe the planning status of pregnancies with known outcomes in the past year, and report the annual population prevalence of unplanned pregnancy, using a validated, multicriteria, multi-outcome measure (the London Measure of Unplanned Pregnancy). We set the findings in the context of secular trends in reproductive health-related events, and patterns across the life course. Findings 9·7% of women aged 16–44 years had pregnancies with known outcome in the year before interview, of which 16·2% (95% CI 13·1–19·9) scored as unplanned, 29·0% (25·2–33·2) as ambivalent, and 54·8% (50·3–59·2) as planned, giving an annual prevalence estimate for unplanned pregnancy of 1·5% (1·2–1·9). Pregnancies in women aged 16–19 years were most commonly unplanned (45·2% [30·8–60·5]). However, most unplanned pregnancies were in women aged 20–34 years (62·4% [50·2–73·2]). Factors strongly associated with unplanned pregnancy were first sexual intercourse before 16 years of age (age-adjusted odds ratio 2·85 [95% CI 1·77–4·57], current smoking (2·47 [1·46–4·18]), recent use of drugs other than cannabis (3·41 [1·64–7·11]), and lower educational attainment. Unplanned pregnancy was also associated with lack of sexual competence at first sexual intercourse (1·90 [1·14–3·08]), reporting higher frequency of sex (2·11 [1·25–3·57] for five or more times in the past 4 weeks), receiving sex education mainly from a non-school-based source (1·84 [1·12–3·00]), and current depression (1·96 [1·10–3·47]). Interpretation The increasing intervals between first sexual intercourse, cohabitation, and childbearing means that, on average, women in Britain spend about 30 years of their life needing to avert an unplanned pregnancy. Our data offer scope for primary prevention aimed at reducing the rate of unplanned conceptions, and secondary prevention aimed at modification of health behaviours and health disorders in unplanned pregnancy that might be harmful for mother and child. Funding Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health.

INTRODUCTION: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years. METHODS: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. RESULTS: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P(trend) = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P(trend) = 0.005) but not cases (P(trend) = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P(het) = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (OR(het) = 0.84, 95% CI 0.75, 0.94; OR(hom) = 0.81, 95% CI 0.51, 1.30; P(trend) = 0.002) but not for those who had their menarche age ≤11 years (OR(het) = 1.06, 95% CI 0.95, 1.19, OR(hom) = 1.07, 95% CI 0.67, 1.72; P(trend) = 0.29). CONCLUSIONS: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.