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2.  Cohort Profile: The International Collaboration of Incident HIV and Hepatitis C in Injecting Cohorts (InC3) Study 
The International Collaboration of Incident HIV and Hepatitis C in Injecting Cohorts (InC3) Study is an international multi-cohort project of pooled biological and behavioural data from nine prospective cohorts of people who inject drugs (PWID). InC3 brings together researchers from Australia, Canada, USA and the Netherlands with expertise in epidemiology, biostatistics, clinical and behavioural sciences, virology and immunology to investigate research questions relevant to hepatitis C virus (HCV) and HIV outcomes. InC3 was established to: (i) create a merged multi-cohort study of pooled data from well-characterized cohorts of PWID with prospective data on HIV and HCV infections, with a particular focus on HCV; (ii) facilitate new studies not possible within individual cohorts; and (iii) bring together researchers across disciplines to answer a broad range of research questions. Study cohorts identify acute HCV cases through follow-up of high-risk HCV antibody–negative PWID or through clinical referral networks. To date, data from 1986 to 2010 have been received from all contributing cohorts, with 821 HCV-infected and 1216 HCV-uninfected participants (overall, n = 2037). Data collected include demographics, host genetics, HCV ribonucleic acid testing, alanine aminotransferase testing, HIV/hepatitis B virus testing, HCV therapy, loss to follow-up and mortality. Potential collaborators should contact the InC3 PI Dr Kimberley Page (kPage@psg.ucsf.edu) for further information.
doi:10.1093/ije/dys167
PMCID: PMC3887561  PMID: 23203695
3.  Cohort Profile: The Skin Cancer After Organ Transplant Study 
The Skin Cancer after Organ Transplant (SCOT) study was designed to investigate the link between genus beta human papillomavirus (HPV) and squamous cell skin cancer (SCSC). We focused on a population receiving immunosuppressive therapy for extended periods, transplant patients, as they are at extremely high risk for developing SCSC. Two complementary projects were conducted in the Seattle area: (i) a retrospective cohort with interview data from 2004 recipients of renal or cardiac transplants between 1995 and 2010 and (ii) a prospective cohort with interview data from 328 people on the transplant waiting lists between 2009 and 2011. Within the retrospective cohort, we developed a nested case–control study (172 cases and 337 control subjects) to assess risk of SCSC associated with markers of HPV in SCSC tumour tissue and eyebrow hair bulb DNA (HPV genotypes) and blood (HPV antibodies). In the prospective cohort, 135 participants had a 1-year post-transplant visit and 71 completed a 2-year post-transplant visit. In both arms of the cohort, we collected samples to assess markers of HPV infection such as acquisition of new types, proportion positive for each type, persistence of types at consecutive visits and number of HPV types detected. In the prospective cohort, we will also examine these HPV markers in relation to levels of cell-mediated immunity. The goal of the SCOT study is to use the data we collected to gain a more complete understanding of the role of immune suppression in HPV kinetics and of genus beta HPV types in SCSC. For more information, please contact the principal investigator through the study website: http://www.fhcrc.org/science/phs/cerc/The_SCOT_Study.html.
doi:10.1093/ije/dys179
PMCID: PMC3887562  PMID: 23171871
4.  The association of pattern of lifetime alcohol use and cause of death in the European Prospective Investigation into Cancer and Nutrition (EPIC) study 
Background There is limited evidence for an association between the pattern of lifetime alcohol use and cause-specific risk of death.
Methods Multivariable hazard ratios were estimated for different causes of death according to patterns of lifetime alcohol consumption using a competing risks approach: 111 953 men and 268 442 women from eight countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study were included. Self-reported alcohol consumption at ages 20, 30, 40 or 50 years and at enrolment were used for the analysis; 26 411 deaths were observed during an average of 12.6 years of follow-up.
Results The association between lifetime alcohol use and death from cardiovascular diseases was different from the association seen for alcohol-related cancers, digestive, respiratory, external and other causes. Heavy users (>5 drinks/day for men and >2.5 drinks/day for women), regardless of time of cessation, had a 2- to 5-times higher risk of dying due to alcohol-related cancers, compared with subjects with lifetime light use (≤1 and ≤0.5 drink/week for men and women, respectively). Compared with lifetime light users, men who used <5 drinks/day throughout their lifetime had a 24% lower cardiovascular disease mortality (95% confidence interval 2-41). The risk of death from coronary heart disease was also found to be 34–46% lower among women who were moderate to occasionally heavy alcohol users compared with light users. However, this relationship was only evident among men and women who had no chronic disease at enrolment.
Conclusions Limiting alcohol use throughout life is associated with a lower risk of death, largely due to cardiovascular disease but also other causes. However, the potential health benefits of alcohol use are difficult to establish due to the possibility of selection bias and competing risks related to diseases occurring later in life.
doi:10.1093/ije/dyt154
PMCID: PMC3887563  PMID: 24415611
Prospective study; lifetime alcohol use; cause-specific mortality; EPIC
7.  Arsenic metabolism efficiency has a causal role in arsenic toxicity: Mendelian randomization and gene-environment interaction 
Background Arsenic exposure through drinking water is a serious global health issue. Observational studies suggest that individuals who metabolize arsenic efficiently are at lower risk for toxicities such as arsenical skin lesions. Using two single nucleotide polymorphisms (SNPs) in the 10q24.32 region (near AS3MT) that show independent associations with metabolism efficiency, Mendelian randomization can be used to assess whether the association between metabolism efficiency and skin lesions is likely to be causal.
Methods Using data on 2060 arsenic-exposed Bangladeshi individuals, we estimated associations for two 10q24.32 SNPs with relative concentrations of three urinary arsenic species (representing metabolism efficiency): inorganic arsenic (iAs), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). SNP-based predictions of iAs%, MMA% and DMA% were tested for association with skin lesion status among 2483 cases and 2857 controls.
Results Causal odds ratios for skin lesions were 0.90 (95% confidence interval [CI]: 0.87, 0.95), 1.19 (CI: 1.10, 1.28) and 1.23 (CI: 1.12, 1.36) for a one standard deviation increase in DMA%, MMA% and iAs%, respectively. We demonstrated genotype-arsenic interaction, with metabolism-related variants showing stronger associations with skin lesion risk among individuals with high arsenic exposure (synergy index: 1.37; CI: 1.11, 1.62).
Conclusions We provide strong evidence for a causal relationship between arsenic metabolism efficiency and skin lesion risk. Mendelian randomization can be used to assess the causal role of arsenic exposure and metabolism in a wide array of health conditions. Developing interventions that increase arsenic metabolism efficiency are likely to reduce the impact of arsenic exposure on health.
doi:10.1093/ije/dyt182
PMCID: PMC3887566  PMID: 24536095
Arsenic; arsenic metabolism; Mendelian randomization; gene-environment interaction; AS3MT
8.  Prenatal paracetamol exposure and child neurodevelopment: a sibling-controlled cohort study 
Background Paracetamol is used extensively during pregnancy, but studies regarding the potential neurodevelopmental sequelae of foetal paracetamol exposure are lacking.
Method Between 1999 and 2008 all pregnant Norwegian women were eligible for recruitment into the prospective Norwegian Mother and Child Cohort Study. The mothers were asked to report on their use of paracetamol at gestational weeks 17 and 30 and at 6 months postpartum. We used data on 48 631 children whose mothers returned the 3-year follow-up questionnaire by May 2011. Within this sample were 2919 same-sex sibling pairs who were used to adjust for familial and genetic factors. We modelled psychomotor development (communication, fine and gross motor development), externalizing and internalizing behaviour problems, and temperament (emotionality, activity, sociability and shyness) based on prenatal paracetamol exposure using generalized linear regression, adjusting for a number of factors, including febrile illness, infections and co-medication use during pregnancy.
Results The sibling-control analysis revealed that children exposed to prenatal paracetamol for more than 28 days had poorer gross motor development [β 0.24, 95% confidence interval (CI) 0.12–0.51], communication (β 0.20, 95% CI 0.01–0.39), externalizing behaviour (β 0.28, 95% CI 0.15–0.42), internalizing behaviour (β 0.14, 95% CI 0.01–0.28), and higher activity levels (β 0.24, 95% CI 0.11–0.38). Children exposed prenatally to short-term use of paracetamol (1–27 days) also had poorer gross motor outcomes (β 0.10, 95% CI 0.02–0.19), but the effects were smaller than with long-term use. Ibuprofen exposure was not associated with neurodevelopmental outcomes.
Conclusion Children exposed to long-term use of paracetamol during pregnancy had substantially adverse developmental outcomes at 3 years of age.
doi:10.1093/ije/dyt183
PMCID: PMC3887567  PMID: 24163279
Paracetamol; acetaminophen; ibuprofen; neurodevelopment; sibling design; Norwegian Mother and Child Cohort Study; MoBa
9.  Systematic evaluation of environmental and behavioural factors associated with all-cause mortality in the United States National Health and Nutrition Examination Survey 
Background Environmental and behavioural factors are thought to contribute to all-cause mortality. Here, we develop a method to systematically screen and validate the potential independent contributions to all-cause mortality of 249 environmental and behavioural factors in the National Health and Nutrition Examination Survey (NHANES).
Methods We used Cox proportional hazards regression to associate 249 factors with all-cause mortality while adjusting for sociodemographic factors on data in the 1999–2000 and 2001–02 surveys (median 5.5 follow-up years). We controlled for multiple comparisons with the false discovery rate (FDR) and validated significant findings in the 2003–04 survey (median 2.8 follow-up years). We selected 249 factors from a set of all possible factors based on their presence in both the 1999–2002 and 2003–04 surveys and linkage with at least 20 deceased participants. We evaluated the correlation pattern of validated factors and built a multivariable model to identify their independent contribution to mortality.
Results We identified seven environmental and behavioural factors associated with all-cause mortality, including serum and urinary cadmium, serum lycopene levels, smoking (3-level factor) and physical activity. In a multivariable model, only physical activity, past smoking, smoking in participant’s home and lycopene were independently associated with mortality. These three factors explained 2.1% of the variance of all-cause mortality after adjusting for demographic and socio-economic factors.
Conclusions Our association study suggests that, of the set of 249 factors in NHANES, physical activity, smoking, serum lycopene and serum/urinary cadmium are associated with all-cause mortality as identified in previous studies and after controlling for multiple hypotheses and validation in an independent survey. Whereas other NHANES factors may be associated with mortality, they may require larger cohorts with longer time of follow-up to detect. It is possible to use a systematic association study to prioritize risk factors for further investigation.
doi:10.1093/ije/dyt208
PMCID: PMC3887569  PMID: 24345851
All-cause mortality; exposure; behaviour; environment-wide association study
11.  Cohort Profile: The English Longitudinal Study of Ageing 
The English Longitudinal Study of Ageing (ELSA) is a panel study of a representative cohort of men and women living in England aged ≥50 years. It was designed as a sister study to the Health and Retirement Study in the USA and is multidisciplinary in orientation, involving the collection of economic, social, psychological, cognitive, health, biological and genetic data. The study commenced in 2002, and the sample has been followed up every 2 years. Data are collected using computer-assisted personal interviews and self-completion questionnaires, with additional nurse visits for the assessment of biomarkers every 4 years. The original sample consisted of 11 391 members ranging in age from 50 to 100 years. ELSA is harmonized with ageing studies in other countries to facilitate international comparisons, and is linked to financial and health registry data. The data set is openly available to researchers and analysts soon after collection (http://www.esds.ac.uk/longitudinal/access/elsa/l5050.asp).
doi:10.1093/ije/dys168
PMCID: PMC3900867  PMID: 23143611
Ageing; cohort; longitudinal; UK
12.  Physical activity levels in three Brazilian birth cohorts as assessed with raw triaxial wrist accelerometry 
Background: Data on objectively measured physical activity are lacking in low- and middle-income countries. The aim of this study was to describe objectively measured overall physical activity and time spent in moderate-to-vigorous physical activity (MVPA) in individuals from the Pelotas (Brazil) birth cohorts, according to weight status, socioeconomic status (SES) and sex.
Methods: All children born in 1982, 1993 and 2004 in hospitals in the city of Pelotas, Brazil, constitute the sampling frame; of these 99% agreed to participate. The most recent follow-ups were conducted between 2010 and 2013. In total, 8974 individuals provided valid data derived from raw triaxial wrist accelerometry. The average acceleration is presented in milli-g (1 mg = 0.001g), and time (min/d) spent in MVPA (>100 mg) is presented in 5- and 10-min bouts.
Results: Mean acceleration in the 1982 (mean age 30.2 years), 1993 (mean age 18.4 years) and 2004 (mean age 6.7 years) cohorts was 35 mg, 39 mg and 60 mg, respectively. Time spent in MVPA was 26 [95% confidence interval (CI) 25; 27], 43 (95% CI 42; 44) and 45 (95% CI 43; 46) min/d in the three cohorts, respectively, using 10-min bouts. Mean MVPA was on average 42% higher when using 5-min bouts. Males were more active than females and physical activity was inversely associated with age of the cohort and SES. Normal-weight individuals were more active than underweight, overweight and obese participants.
Conclusions: Overall physical activity and time spent in MVPA differed by cohort (age), sex, weight status and SES. Higher levels of activity in low SES groups may be explained by incidental physical activity.
doi:10.1093/ije/dyu203
PMCID: PMC4276065  PMID: 25361583
Activity monitor; cohort studies; motor activity; movement
13.  Interaction between passive smoking and two HLA genes with regard to multiple sclerosis risk 
Background: The recently described interaction between smoking, human leukocyte antigen (HLA) DRB1*15 and absence of HLA-A*02 with regard to multiple sclerosis (MS) risk shows that the risk conveyed by smoking differs depending on genetic background. We aimed to investigate whether a similar interaction exists between passive smoking and HLA genotype.
Methods: We used one case-control study with incident cases of MS (736 cases, 1195 controls) and one with prevalent cases (575 cases, 373 controls). Never-smokers with different genotypes and passive smoking status were compared with regard to occurrence of MS, by calculating odds ratios (ORs) with 95% confidence intervals (CIs). The potential interaction between different genotypes and passive smoking was evaluated by calculating the attributable proportion (AP) due to interaction.
Results: An interaction was observed between passive smoking and carriage of HLA-DRB1*15 (AP 0.3, 95% CI 0.02–0.5 in the incident study, and AP 0.4, 95% CI 0.1–0.7 in the prevalent study), as well as between passive smoking and absence of HLA-A*02. Compared with non-smokers without any of these two genetic risk factors, non-exposed subjects with the two risk genotypes displayed an OR of 4.5 (95% CI 3.3–6.1) whereas the same genotype for subjects exposed to passive smoking rendered an OR of 7.7 (95% CI 5.5–10.8).
Conclusions: The risk of developing MS associated with different HLA genotypes may be influenced by exposure to passive smoking. The finding supports our hypothesis that priming of the immune response in the lungs may subsequently lead to MS in people with a genetic susceptibility to the disease.
doi:10.1093/ije/dyu195
PMCID: PMC4276064  PMID: 25324153
Multiple sclerosis; smoking; passive smoking; HLA genotype; gene-environment interaction; case-control study; immunology
14.  Household organophosphorus pesticide use and Parkinson’s disease 
Background Household pesticide use is widespread in the USA. Since the 1970s, organophosphorus chemicals (OPs) have been common active ingredients in these products. Parkinson’s disease (PD) has been linked to pesticide exposures but little is known about the contributions of chronic exposures to household pesticides. Here we investigate whether long-term use of household pesticides, especially those containing OPs, increases the odds of PD.
Methods In a population-based case-control study, we assessed frequency of household pesticide use for 357 cases and 807 controls, relying on the California Department of Pesticide Regulation product label database to identify ingredients in reported household pesticide products and the Pesticide Action Network pesticide database of chemical ingredients. Using logistic regression we estimated the effects of household pesticide use.
Results Frequent use of any household pesticide increased the odds of PD by 47% [odds ratio (OR) = 1.47, (95% confidence interval (CI): 1.13, 1.92)]; frequent use of products containing OPs increased the odds of PD more strongly by 71% [OR = 1.71, (95% CI: 1.21, 2.41)] and frequent organothiophosphate use almost doubled the odds of PD. Sensitivity analyses showed that estimated effects were independent of other pesticide exposures (ambient and occupational) and the largest odds ratios were estimated for frequent OP users who were carriers of the 192QQ paraoxonase genetic variant related to slower detoxification of OPs.
Conclusions We provide evidence that household use of OP pesticides is associated with an increased risk of developing PD.
doi:10.1093/ije/dyt170
PMCID: PMC3807617  PMID: 24057998
Environmental exposures; household pesticide use; organophosphorus pesticides; paraoxonase; Parkinson’s disease; United States; California
15.  Calculating statistical power in Mendelian randomization studies 
In Mendelian randomization (MR) studies, where genetic variants are used as proxy measures for an exposure trait of interest, obtaining adequate statistical power is frequently a concern due to the small amount of variation in a phenotypic trait that is typically explained by genetic variants. A range of power estimates based on simulations and specific parameters for two-stage least squares (2SLS) MR analyses based on continuous variables has previously been published. However there are presently no specific equations or software tools one can implement for calculating power of a given MR study. Using asymptotic theory, we show that in the case of continuous variables and a single instrument, for example a single-nucleotide polymorphism (SNP) or multiple SNP predictor, statistical power for a fixed sample size is a function of two parameters: the proportion of variation in the exposure variable explained by the genetic predictor and the true causal association between the exposure and outcome variable. We demonstrate that power for 2SLS MR can be derived using the non-centrality parameter (NCP) of the statistical test that is employed to test whether the 2SLS regression coefficient is zero. We show that the previously published power estimates from simulations can be represented theoretically using this NCP-based approach, with similar estimates observed when the simulation-based estimates are compared with our NCP-based approach. General equations for calculating statistical power for 2SLS MR using the NCP are provided in this note, and we implement the calculations in a web-based application.
doi:10.1093/ije/dyt179
PMCID: PMC3807619  PMID: 24159078
Power; Mendelian randomization; non-centrality parameter; instrumental variable
19.  DataSHIELD: taking the analysis to the data, not the data to the analysis 
Background: Research in modern biomedicine and social science requires sample sizes so large that they can often only be achieved through a pooled co-analysis of data from several studies. But the pooling of information from individuals in a central database that may be queried by researchers raises important ethico-legal questions and can be controversial. In the UK this has been highlighted by recent debate and controversy relating to the UK’s proposed ‘care.data’ initiative, and these issues reflect important societal and professional concerns about privacy, confidentiality and intellectual property. DataSHIELD provides a novel technological solution that can circumvent some of the most basic challenges in facilitating the access of researchers and other healthcare professionals to individual-level data.
Methods: Commands are sent from a central analysis computer (AC) to several data computers (DCs) storing the data to be co-analysed. The data sets are analysed simultaneously but in parallel. The separate parallelized analyses are linked by non-disclosive summary statistics and commands transmitted back and forth between the DCs and the AC. This paper describes the technical implementation of DataSHIELD using a modified R statistical environment linked to an Opal database deployed behind the computer firewall of each DC. Analysis is controlled through a standard R environment at the AC.
Results: Based on this Opal/R implementation, DataSHIELD is currently used by the Healthy Obese Project and the Environmental Core Project (BioSHaRE-EU) for the federated analysis of 10 data sets across eight European countries, and this illustrates the opportunities and challenges presented by the DataSHIELD approach.
Conclusions: DataSHIELD facilitates important research in settings where: (i) a co-analysis of individual-level data from several studies is scientifically necessary but governance restrictions prohibit the release or sharing of some of the required data, and/or render data access unacceptably slow; (ii) a research group (e.g. in a developing nation) is particularly vulnerable to loss of intellectual property—the researchers want to fully share the information held in their data with national and international collaborators, but do not wish to hand over the physical data themselves; and (iii) a data set is to be included in an individual-level co-analysis but the physical size of the data precludes direct transfer to a new site for analysis.
doi:10.1093/ije/dyu188
PMCID: PMC4276062  PMID: 25261970
DataSHIELD; pooled analysis; ELSI; privacy; confidentiality; disclosure; distributed computing; intellectual property; bioinformatics
20.  Data Resource Profile: Pathways to Health and Social Equity for Children (PATHS Equity for Children) 
The PATHS Data Resource is a unique database comprising data that follow individuals from the prenatal period to adulthood. The PATHS Resource was developed for conducting longitudinal epidemiological research into child health and health equity. It contains individual-level data on health, socioeconomic status, social services and education. Individuals’ data are linkable across these domains, allowing researchers to follow children through childhood and across a variety of sectors. PATHS includes nearly all individuals that were born between 1984 and 2012 and registered with Manitoba’s universal health insurance programme at some point during childhood. All PATHS data are anonymized. Key concepts, definitions and algorithms necessary to work with the PATHS Resource are freely accessible online and an interactive forum is available to new researchers working with these data. The PATHS Resource is one of the richest and most complete databases assembled for conducting longitudinal epidemiological research, incorporating many variables that address the social determinants of health and health equity. Interested researchers are encouraged to contact [mchp_access@cpe.umanitoba.ca] to obtain access to PATHS to use in their own programmes of research.
doi:10.1093/ije/dyu190
PMCID: PMC4190523  PMID: 25212478
21.  Testing for non-linear causal effects using a binary genotype in a Mendelian randomization study: application to alcohol and cardiovascular traits 
Background: Mendelian randomization studies have so far restricted attention to linear associations relating the genetic instrument to the exposure, and the exposure to the outcome. In some cases, however, observational data suggest a non-linear association between exposure and outcome. For example, alcohol consumption is consistently reported as having a U-shaped association with cardiovascular events. In principle, Mendelian randomization could address concerns that the apparent protective effect of light-to-moderate drinking might reflect ‘sick-quitters’ and confounding.
Methods: The Alcohol-ADH1B Consortium was established to study the causal effects of alcohol consumption on cardiovascular events and biomarkers, using the single nucleotide polymorphism rs1229984 in ADH1B as a genetic instrument. To assess non-linear causal effects in this study, we propose a novel method based on estimating local average treatment effects for discrete levels of the exposure range, then testing for a linear trend in those effects. Our method requires an assumption that the instrument has the same effect on exposure in all individuals. We conduct simulations examining the robustness of the method to violations of this assumption, and apply the method to the Alcohol-ADH1B Consortium data.
Results: Our method gave a conservative test for non-linearity under realistic violations of the key assumption. We found evidence for a non-linear causal effect of alcohol intake on several cardiovascular traits.
Conclusions: We believe our method is useful for inferring departure from linearity when only a binary instrument is available. We estimated non-linear causal effects of alcohol intake which could not have been estimated through standard instrumental variable approaches.
doi:10.1093/ije/dyu187
PMCID: PMC4276061  PMID: 25192829
Mendelian randomization; instrumental variables; causal inference; local average treatment effects; alcohol consumption; cardiovascular disease
22.  Record-linkage comparison of verbal autopsy and routine civil registration death certification in rural north-east South Africa: 2006–09 
Background: South African civil registration (CR) provides a key data source for local health decision making, and informs the levels and causes of mortality in data-lacking sub-Saharan African countries. We linked mortality data from CR and the Agincourt Health and Socio-demographic Surveillance System (Agincourt HDSS) to examine the quality of rural CR data.
Methods: Deterministic and probabilistic techniques were used to link death data from 2006 to 2009. Causes of death were aggregated into the WHO Mortality Tabulation List 1 and a locally relevant short list of 15 causes. The matching rate was compared with informant-reported death registration. Using the VA diagnoses as reference, misclassification patterns, sensitivity, positive predictive values and cause-specific mortality fractions (CSMFs) were calculated for the short list.
Results: A matching rate of 61% [95% confidence interval (CI): 59.2 to 62.3] was attained, lower than the informant-reported registration rate of 85% (CI: 83.4 to 85.8). For the 2264 matched cases, cause agreement was 15% (kappa 0.1083, CI: 0.0995 to 0.1171) for the WHO list, and 23% (kappa 0.1631, CI: 0.1511 to 0.1751) for the short list. CSMFs were significantly different for all but four (tuberculosis, cerebrovascular disease, other heart disease, and ill-defined natural) of the 15 causes evaluated.
Conclusion: Despite data limitations, it is feasible to link official CR and HDSS verbal autopsy data. Data linkage proved a promising method to provide empirical evidence about the quality and utility of rural CR mortality data. Agreement of individual causes of death was low but, at the population level, careful interpretation of the CR data can assist health prioritization and planning.
doi:10.1093/ije/dyu156
PMCID: PMC4276059  PMID: 25146564
Mortality; data quality; causes of death; vital statistics; verbal autopsy; data linkage; Agincourt Health and Demographic Surveillance System; Statistics South Africa; rural South Africa
23.  Season and outdoor temperature in relation to detection and control of hypertension in a large rural Chinese population 
Background: In many Western populations, blood pressure varies moderately with season and outdoor temperature. Relatively little is known about effects of seasonal changes in blood pressure on the detection and control of hypertension in general populations, especially in low- and middle-income countries.
Methods: We analysed cross-sectional data of 57 375 (42% men) participants aged 30–79 (mean 52.3) years who were enrolled during 2004–08, as part of the China Kadoorie Biobank, from a rural county in the south-east costal Zhejiang Province. Analyses related daily mean outdoor temperature, obtained from local Meteorological Bureau, to mean systolic (SBP) and diastolic blood pressure (DBP), rate of newly detected hypertension and, among those with self-reported physician-diagnosed hypertension, rate of adequate blood pressure control, using multiple linear and logistic regression models.
Results: The overall mean blood pressure was 135.9 mmHg for SBP and 80.5 mmHg for DBP. Daily outdoor temperature ranged between −2.9 and 33.7°C, with July being the hottest month (mean 29.4°C) and January the coldest (mean 4.0°C). Comparing January (the coldest month) with July (the warmest), the differences in the adjusted SBP/DBP were 19.2/7.7 mmHg. Each 10°C lower ambient temperature was associated with 6.9/2.9 mmHg higher SBP/DBP,14.1% higher prevalence of newly detected hypertension and, among those with pre-diagnosed hypertension, 13.0% lower hypertension control rate.
Conclusion: In rural China, lower outdoor temperature is strongly associated with higher mean blood pressure and hypertension prevalence as well as poorer hypertension control, and should be considered when conducting population-based hypertension surveys and providing treatment for hypertensive patients.
doi:10.1093/ije/dyu158
PMCID: PMC4276060  PMID: 25135908
Blood pressure; outdoor temperature; season; hypertension detection; hypertension control; China
24.  Cohort Profile: Longitudinal Investigations into Supportive and Ancillary health services 
The Longitudinal Investigations into Supportive and Ancillary health services (LISA) study is a cohort of people living with HIV/AIDS who have ever accessed anti-retroviral therapy (ART) in British Columbia, Canada. The LISA study was developed to better understand the outcomes of people living with HIV with respect to supportive services use, socio-demographic factors and quality of life. Between July 2007 and January 2010, 1000 participants completed an interviewer-administered questionnaire that included questions concerning medical history, substance use, social and medical support services, food and housing security and other social determinants of health characteristics. Of the 1000 participants, 917 were successfully linked to longitudinal clinical data through the provincial Drug Treatment Program. Within the LISA cohort, 27% of the participants are female, the median age is 39 years and 32% identify as Aboriginal. Knowledge translation activities for LISA include the creation of plain language summaries, internet resources and arts-based engagement activities such as Photovoice.
doi:10.1093/ije/dys035
PMCID: PMC3780992  PMID: 22461127
25.  The impact of neighbourhood deprivation on adolescent violent criminality and substance misuse: A longitudinal, quasi-experimental study of the total Swedish population 
Background A number of studies suggest associations between neighbourhood characteristics and criminality during adolescence and young adulthood. However, the causality of such neighbourhood effects remains uncertain.
Methods We followed all children born in Sweden from 1975–1989 who lived in its three largest cities by the age of 15 years and for whom complete information was available about individual and contextual factors (N = 303 465). All biological siblings were identified in the sample (N = 179 099). Generalized linear mixed-effects models were used to assess the effect of neighbourhood deprivation on violent criminality and substance misuse between the ages of 15 and 20 years, while taking into account the cross-classified data structure (i.e. siblings in the same families attending different schools and living in different neighbourhoods at age 15).
Results In the crude model, an increase of 1 SD in neighbourhood deprivation was associated with a 57% increase in the odds of being convicted of a violent crime (95% CI 52%–63%). The effect was greatly attenuated when adjustment was made for a number of observed confounders (OR 1.09, 95% CI 1.06–1.11). When we additionally adjusted for unobserved familial confounders, the effect was no longer present (OR 0.96, 95% CI 0.84–1.10). Similar results were observed for substance misuse. The results were not due to poor variability either between neighbourhoods or within families.
Conclusions We found that the adverse effect of neighbourhood deprivation on adolescent violent criminality and substance misuse in Sweden was not consistent with a causal inference. Instead, our findings highlight the need to control for familial confounding in multilevel studies of criminality and substance misuse.
doi:10.1093/ije/dyt066
PMCID: PMC3780994  PMID: 24062294
Violence; substance-related disorders; residence characteristics; socio-economic factors; multi-level analysis; confounding factors

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