The Isle of Man is a self-governing British Crown Dependency situated equidistantly from England, Scotland and Ireland. In 1991, its population of ~75 000 comprised ~50% indigenous Manx and 50% immigrants, mainly from the surrounding countries. It was invited to join the European Longitudinal Study of Pregnancy and Childhood. The aim of the study was to enrol all pregnant women resident on the Island with an expected date of delivery in the 18-month period of January 1991–June 1992. A total of 1314 livebirths formed the eligible cohort. Questionnaires were completed by mothers and their partners during pregnancy and subsequently at 6 weeks, 6 months, 18 months, 3, 5, 7 and 15/16 years. Hands-on examination of the children occurred at age 7 years, when biological samples were collected. Teachers completed questionnaires at 7 and 15 years; medical records were extracted for the obstetric and childhood periods. Response rates varied from >80% from teachers and children at 15 years to only 23% from partners when their children were aged 7 years. Selected data sets are available to collaborators, although many of the data need funds for further collaboration.
The Stockholm Public Health Cohort was set up within the Stockholm County Council public health surveys to inform on determinants and consequences of significant contributors to the current burden of disease. Participants are 89 268 randomly selected individuals from the adult population of Stockholm County. Baseline surveys took place in 2002, 2006 and 2010 via self-administered questionnaires. So far, participants recruited in 2002 were re-surveyed twice, in 2007 and 2010, and those enrolled in 2006 were re-surveyed once, in 2010. Self-reported data are regularly supplemented by information from national and regional health data and administrative registers, for study participants and their relatives (including their offspring). Available data are extensive and include a wide array of health, lifestyle, perinatal, demographic, socio-economic and familial factors. The cohort is an international resource for epidemiological research, and the data available to the research community for specific studies obtained approval from the Stockholm Public Health Cohort Steering Committee and the Stockholm Regional Ethical Review Board.
The STEPS Study aims to search for the precursors and causes of problems in child health and well-being by using a multidisciplinary approach. The cohort consists of all mothers (Finnish or Swedish speaking) who had live deliveries in the Hospital District of Southwest Finland from January 2008 to April 2010 and their children (n = 9811 mothers, n = 9936 children). Of these, 1797 mothers and their 1827 children were recruited to an intensive follow-up group during the first trimester of pregnancy or soon after delivery. Information about the whole study cohort is based on pregnancy follow-up data from maternity clinics, National Longitudinal Census Files and child welfare clinics. Data from multiple sources are used to obtain a picture of the overall well-being of the child and the family. After birth, study visits include several clinical examinations. Collaboration is encouraged, and access to the data will be available when the data set is complete.
The CARTaGENE (CaG) study is both a population-based biobank and the largest ongoing prospective health study of men and women in Quebec. In population-based cohorts, participants are not recruited for a particular disease but represent a random selection among the population, minimizing the need to correct for bias in measured phenotypes. CaG targeted the segment of the population that is most at risk of developing chronic disorders, that is 40–69 years of age, from four metropolitan areas in Quebec. Over 20 000 participants consented to visiting 1 of 12 assessment sites where detailed health and socio-demographic information, physiological measures and biological samples (blood, serum and urine) were captured for a total of 650 variables. Significant correlations of diseases and chronic conditions are observed across these regions, implicating complex interactions, some of which we describe for major chronic conditions. The CaG study is one of the few population-based cohorts in the world where blood is stored not only for DNA and protein based science but also for gene expression analyses, opening the door for multiple systems genomics approaches that identify genetic and environmental factors associated with disease-related quantitative traits. Interested researchers are encouraged to submit project proposals on the study website (www.cartagene.qc.ca).
The Shahroud Eye Cohort Study was set up to determine the prevalence and incidence of visual impairment and major eye conditions in the 40–64-year-old population of Shahroud as a Middle Eastern population. The first phase of the study was conducted in 2009–10. Using random cluster sampling, 6311 Shahroud inhabitants were invited for ophthalmologic examinations; of these, 5190 participants completed phase 1 (participation rate of 82.2%). All participants were interviewed to collect data on participants’ demographics, occupation status, socioeconomic status, history of smoking, and medical and ophthalmic history, as well as history of medication, and the quality and duration of their insurance. DNA and plasma samples, as well as four dots of whole blood were collected from participants. Extensive optometric and ophthalmologic examinations were performed for each participant, including lensometry of current glasses, testing near and far visual acuity; determining objective and subjective refraction; eye motility; cycloplegic refraction; colour vision test; slit-lamp biomicroscopy and intraocular pressure measurement; direct and indirect fundoscopy; perimetry test; ocular biometry; corneal topography; lens and fundus photography; and the Schirmer's (1008 participants) and tear breakup time tests (1013 participants). The study data are available for collaborative research at Noor Ophthalmology Research Center, Tehran, Iran.
The Manhiça Health Research Centre, established in 1996 in a rural area of southern Mozambique, currently follows around 92 000 individuals living in approximately 20 000 enumerated and geo-positioned households. Its main strength is the possibility of linking demographic data and clinical data to promote and conduct biomedical research in priority health areas. Socio-demographic data are updated twice a year and clinical data are collected on a daily basis. The data collected in Manhiça HDSS comprises household and individual characteristics, household socio-economic assets, vital data, migration, individual health history and cause of death, among others. Studies conducted in this HDSS contributed to guide the health authorities and decision-making bodies to define or adjust health policies such as the introduction of Mozambique’s expanded programme of immunization with different vaccines (Haemophilus influenzae type b, Pneumococcus) or the development of the concept of Intermittent Preventive Treatment for Infants (IPTi) that led to the World Health Organization recommendation of this method as best practice for the control of malaria among infants. Manhiça’s data can be accessed through a formal request to Diana Quelhas (email@example.com) accompanied by a proposal that will be analysed by the Manhiça HDSS internal scientific and ethics committees.
The 1991 Canadian Census Cohort is the largest population-based cohort in Canada (N = 2 734 835). Prior to the creation of this Cohort, no national population-based Canadian cohort was available to examine mortality by socioeconomic indicators. The 1991 Canadian Census Cohort was created via the linkage of a sub-sample of respondents from the mandatory 1991 Canadian Census long-form to historical tax summary files, Canadian Mortality Database, Canadian Cancer Database, 1991 Health and Activity Limitation Survey and a sub-sample of the Longitudinal Worker File. Overall ascertainment of mortality and cancer is anticipated to be nearly complete and the Cohort is broadly representative of most groups in the Canadian population. The Cohort has been used to examine mortality outcomes by different indicators of socioeconomic status, occupational categories, ethnic groups, educational attainment, and for exposure to ambient air pollution. Results have shown that the estimated remaining years of life at age 25 differed substantially by income adequacy quintile, educational attainment, housing type and Aboriginal ancestry.
The developmental origins of health and disease hypothesis suggests that small birth size in conjunction with rapid compensatory childhood growth might yield a greater risk of developing chronic diseases in later life. For example, there is evidence that people who developed coronary heart disease and diabetes experienced different growth trajectories from those who did not develop these diseases. However, some of the methods used in these articles may have been flawed. We critically evaluate proposed approaches for identifying the growth trajectories distinctive to those developing later disease and identifying critical phases of growth during the early lifecourse. Among the approaches we examined (tracing the z-scores, lifecourse plots and models, lifecourse path analysis, conditional body size analysis, multilevel analysis, latent growth curve models and growth mixture models) conditional body size analysis, multilevel analysis, latent growth curve models and growth mixture models are least prone to collinearity problems caused by repeated measures. Multilevel analysis is more flexible when body size is not measured at the same age for all cohort members. Strengths and weaknesses of each approach are illustrated using real data. Demonstrating the influence of growth trajectories on later disease is complex and challenging; therefore, it is likely that a combination of approaches will be required to unravel the complexity in lifecourse research.
Background Low- and middle-income countries continue to experience a large burden of stunting; 148 million children were estimated to be stunted, around 30–40% of all children in 2011. In many of these countries, foetal growth restriction (FGR) is common, as is subsequent growth faltering in the first 2 years. Although there is agreement that stunting involves both prenatal and postnatal growth failure, the extent to which FGR contributes to stunting and other indicators of nutritional status is uncertain.
Methods Using extant longitudinal birth cohorts (n = 19) with data on birthweight, gestational age and child anthropometry (12–60 months), we estimated study-specific and pooled risk estimates of stunting, wasting and underweight by small-for-gestational age (SGA) and preterm birth.
Results We grouped children according to four combinations of SGA and gestational age: adequate size-for-gestational age (AGA) and preterm; SGA and term; SGA and preterm; and AGA and term (the reference group). Relative to AGA and term, the OR (95% confidence interval) for stunting associated with AGA and preterm, SGA and term, and SGA and preterm was 1.93 (1.71, 2.18), 2.43 (2.22, 2.66) and 4.51 (3.42, 5.93), respectively. A similar magnitude of risk was also observed for wasting and underweight. Low birthweight was associated with 2.5–3.5-fold higher odds of wasting, stunting and underweight. The population attributable risk for overall SGA for outcomes of childhood stunting and wasting was 20% and 30%, respectively.
Conclusions This analysis estimates that childhood undernutrition may have its origins in the foetal period, suggesting a need to intervene early, ideally during pregnancy, with interventions known to reduce FGR and preterm birth.
Background There is substantial debate as to whether moderate alcohol use during pregnancy could have subtle but important effects on offspring, by impairing later cognitive function and thus school performance. The authors aimed to investigate the unconfounded effect of moderately increased prenatal alcohol exposure on cognitive/educational performance.
Methods We used mother-offspring pairs participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) and performed both conventional observational analyses and Mendelian randomization using an ADH1B variant (rs1229984) associated with reduced alcohol consumption. Women of White European origin with genotype and self-reported prenatal alcohol consumption, whose offspring’s IQ score had been assessed in clinic (N = 4061 pairs) or Key Stage 2 (KS2) academic achievement score was available through linkage to the National Pupil Database (N = 6268), contributed to the analyses.
Results Women reporting moderate drinking before and during early pregnancy were relatively affluent compared with women reporting lighter drinking, and their children had higher KS2 and IQ scores. In contrast, children whose mothers’ genotype predisposes to lower consumption or abstinence during early pregnancy had higher KS2 scores (mean difference +1.7, 95% confidence interval +0.4, +3.0) than children of mothers whose genotype predisposed to heavier drinking, after adjustment for population stratification.
Conclusions Better offspring cognitive/educational outcomes observed in association with prenatal alcohol exposure presumably reflected residual confounding by factors associated with social position and maternal education. The unconfounded Mendelian randomization estimates suggest a small but potentially important detrimental effect of small increases in prenatal alcohol exposure, at least on educational outcomes.
Background Foetal smoke exposure might lead to foetal developmental adaptations that permanently affect the cardiovascular system. We assessed the associations of both maternal and paternal smoking during pregnancy with childhood cardiovascular structures and function.
Method In a prospective cohort study among 5565 children, we examined whether maternal and paternal smoking during pregnancy are associated with blood pressure, carotid-femoral pulse wave velocity and left cardiac structures and function in 6-year-old children.
Results As compared with children from non-smoking mothers, children from mothers who smoked more than 10 cigarettes per day had a higher diastolic blood pressure [difference 1.43 mmHg (95% confidence interval: 0.22, 2.63)]. Maternal smoking during pregnancy was not associated with systolic blood pressure, childhood carotid-femoral pulse wave velocity or left cardiac structures. Maternal smoking of 10 or more cigarettes per day was associated with a higher fractional shortening in childhood [difference 1.01% (95% confidence interval: 0.18, 1.84)]. Among mothers who did not smoke during pregnancy, paternal smoking was associated with aortic root diameter but not with other cardiovascular outcomes.
Conclusions Maternal smoking during pregnancy is associated with higher diastolic blood pressure and fractional shortening, although the effect estimates are small. The stronger effect estimates for maternal smoking compared with paternal smoking might suggest that direct intrauterine adaptive responses are involved as underlying mechanisms.
Background We investigated the association of early life social factors—maternal age, single motherhood, socioeconomic position, birth order and family size—with future risk of suicide in Taiwan.
Methods Using a nested case-control design, we used linked data from Taiwan’s Birth Registry (1978–93) and Taiwan’s Death Registry (1993–2008) and identified 3984 suicides aged 15–30 years. For each suicide, 30 controls matched by age and sex were randomly selected, using incidence density sampling. Conditional logistic regression models were estimated to assess the association of early life risk factors with suicide.
Results Younger maternal age (<25 years), single motherhood, lower paternal educational level and higher birth order were independently associated with increased risk of suicide. Stratified analyses suggest that lower paternal educational level was associated with male, but not female suicide risk (Pinteraction = 0.02). Single motherhood was a stronger risk factor for suicide in female than in male offspring [odds ratios (95% confidence interval) = 2.30 (1.47, 3.58) vs. 1.50 (1.01, 2.20), Pinteraction = 0.12]. There was a suggestion that in families with large sibship size (≥4 siblings), the excess in suicide risk was greater among later born daughters compared with later born sons (Pinteraction = 0.05).
Conclusions Our findings provide support for the results of European studies, suggesting that early life social circumstances influence future risk of suicide. Factors specific to Taiwanese culture, such as a preference for male offspring, may have influenced gender-specific patterns of risk.
Background Previous studies on the association of malaria and stunted growth delivered inconsistent results. These conflicting results may be due to different levels of confounding and to considerable difficulties in elucidating a causal relationship. Randomized experiments are impractical and previous observational studies have not fully controlled for potential confounding including nutritional deficiencies, breastfeeding habits, other infectious diseases and socioeconomic status.
Methods This study aims to estimate the causal effect between malaria episodes and stunted growth by applying a combination of Mendelian randomization, using the sickle cell trait, and matching. We demonstrate the method on a cohort of children in the Ashanti Region, Ghana.
Results We found that the risk of stunting increases by 0.32 (P-value: 0.004, 95% CI: 0.09, 1.0) for every malaria episode. The risk estimate based on Mendelian randomization substantially differs from the multiple regression estimate of 0.02 (P-value: 0.02, 95% CI: 0.003, 0.03). In addition, based on the sensitivity analysis, our results were reasonably insensitive to unmeasured confounders.
Conclusions The method applied in this study indicates a causal relationship between malaria and stunting in young children in an area of high endemicity and demonstrates the usefulness of the sickle cell trait as an instrument for the analysis of conditions that might be causally related to malaria.
Background Adverse childhood experiences (maltreatment and household dysfunction) are associated with adult cardiovascular disease (CVD). One possible pathway is through physical development, which has been linked to CVD risk. Our aim was to examine whether adverse childhood experiences are associated with child-to-adult height trajectories.
Method The 1958 British birth cohort (n = 17 638) includes all born in one week in March 1958, followed up to mid adulthood. Height was measured at 7, 11 and 16 years (y) and adulthood (converted to standard deviation scores (SDS); ≥1 height measurement n = 16 444, adult leg length n = 9180). Multivariate response models were used to examine the associations between childhood experiences (ascertained at 7 y and self-reported at 45 y) and child-to-adult height.
Results Childhood neglect, prospectively assessed at 7 y, was associated with shorter stature throughout childhood: for each increment across a score ranging 0–7, average height reduced by 0.06 SDS (males) and 0.05 SDS (females) at 7 y (0.3 cm), with smaller deficits (0.03 SDS, 0.2 cm) in adulthood, after adjustment for parental height, birthweight and socio-economic factors. In males, the adult deficit was mainly due to shorter leg length. Household dysfunction was associated with shorter stature at 7–11 y, with adjusted deficits from 0.04 to 0.07 SDS per increment across a score ranging 0–7, but not at later ages. Adjusted models showed no associations for retrospectively reported abuse or neglect to 16 y.
Conclusions Those with a higher neglect score by 7 y grew more slowly, with deficits through to adulthood. No associations were found for abuse over the longer period to 16 y. Deficits associated with early life neglect and household dysfunction might have implications for adult CVD risks.
There has been an increased focus on non-communicable diseases (NCDs) in India, especially on cardiovascular diseases and associated risk factors. In this essay, we scrutinize the prevailing narrative that cardiovascular risk factors (CVRF) and cardiovascular disease (CVD) are no longer confined to the economically advantaged groups but are an increasing burden among the poor in India. We conducted a comprehensive review of studies reporting the association between socioeconomic status (SES) and CVRF, CVD, and CVD-related mortality in India. With the exception of smoking and low fruit and vegetable intake, the studies clearly suggest that CVRF/CVD is more prevalent among high SES groups in India than among the low SES groups. Although CVD-related mortality rates appear to be higher among the lower SES groups, the proportion of deaths from CVD-related causes was found to be greatest among higher SES groups. The studies on SES and CVRF/CVD also reveal a substantial discrepancy between the data presented and the authors’ interpretations and conclusions, along with an unsubstantiated claim that a reversal in the positive SES-CVRF/CVD association has occurred or is occurring in India. We conclude our essay by emphasizing the need to prioritize public health policies that are focused on the health concerns of the majority of the Indian population. Resource allocation in the context of efforts to make health care in India free and universal should reflect the proportional burden of disease on different population groups if it is not to entrench inequity.
Background Household characteristics are important influences on the risk of child death. However, little is known about this influence in HIV-endemic areas. We describe the effects of household characteristics on children’s risk of dying in rural South Africa.
Methods We use data describing the mortality of children younger than 5 years living in the Agincourt health and socio-demographic surveillance system study population in rural northeast South Africa during the period 1994–2008. Using discrete time event history analysis we estimate children’s probability of dying by child characteristics and household composition (other children and adults other than parents) (N = 924 818 child-months), and household socio-economic status (N = 501 732 child-months).
Results Children under 24 months of age whose subsequent sibling was born within 11 months experience increased odds of dying (OR 2.5; 95% CI 1.1–5.7). Children also experience increased odds of dying in the period 6 months (OR 2.1; 95% CI 1.2–3.6), 3–5 months (OR 3.0; 95% CI 1.5–5.9), and 2 months (OR 11.8; 95% CI 7.6–18.3) before another household child dies. The odds of dying remain high at the time of another child’s death (OR 11.7; 95% CI 6.3–21.7) and for the 2 months following (OR 4.0; 95% CI 1.9–8.6). Having a related but non-parent adult aged 20–59 years in the household reduces the odds (OR 0.6; 95% CI 0.5–0.8). There is an inverse relationship between a child’s odds of dying and household socio-economic status.
Conclusions This detailed household profile from a poor rural setting where HIV infection is endemic indicates that children are at high risk of dying when another child is very ill or has recently died. Short birth intervals and additional children in the household are further risk factors. Presence of a related adult is protective, as is higher socio-economic status. Such evidence can inform primary health care practice and facilitate targeting of community health worker efforts, especially when covering defined catchment areas.
Background Anxiety or depression symptoms may increase the risk of developing asthma, and their interaction with obesity is not known. We aimed to assess the association of anxiety or depression symptoms and the joint association of these symptoms and obesity with incident asthma.
Methods We conducted a prospective cohort study of 23 599 adults who were 19–55 years old and free from asthma at baseline in the Norwegian Nord–Trøndelag Health Study. The Hospital Anxiety and Depression Scale was used to measure anxiety or depression symptoms. Obesity was defined as a body mass index ≥30.0 kg/m2. Incident asthma was self-reported new cases of asthma during the 11-year follow-up.
Results Having anxiety or depression symptoms was associated with incident asthma [odds ratio (OR) 1.39, 95% confidence interval (CI) 1.09–1.78). Obese participants with anxiety or depression symptoms had a substantially higher risk of incident asthma (OR 2.93, 95% CI 2.20–3.91) than any other group (non-obese participants without anxiety or depression symptoms [reference], non-obese participants with anxiety or depression symptoms (OR 1.20, 95% CI 1.00–1.45) and obese participants without anxiety or depression symptoms (OR 1.47, 95% CI 1.19–1.82)]. The relative excess risk for incident asthma due to interaction between anxiety or depression symptoms and obesity was 1.26 (95% CI 0.39–2.12).
Conclusions This study suggests that having anxiety or depression symptoms contributes to the development of asthma in adults. The risk of asthma may be further increased by the interaction between anxiety or depression symptoms and obesity.
Background Exhaled carbon monoxide (COex) level is positively associated with tobacco smoking and exposure to smoke from biomass/coal burning. Relatively little is known about its determinants in China despite the population having a high prevalence of smoking and use of biomass/coal.
Methods The China Kadoorie Biobank includes 512 000 participants aged 30-79 years recruited from 10 diverse regions. We used linear regression and logistic regression methods to assess the associations of COex level with smoking, exposures to indoor household air pollution and prevalent chronic respiratory conditions among never smokers, both overall and by seasons, regions and smoking status.
Results The overall COex level (ppm) was much higher in current smokers than in never smokers (men: 11.5 vs 3.7; women: 9.3 vs 3.2). Among current smokers, it was higher among those who smoked more and inhaled more deeply. Among never smokers, mean COex was positively associated with levels of exposures to passive smoking and to biomass/coal burning, especially in rural areas and during winter. The odds ratios (OR) and 95% confidence interval (CI) of air flow obstruction (FEV1/FVC ratio <0.7) for never smokers with COex at 7–14 and ≥14 ppm, compared with those having COex <7, were 1.38 (1.31–1.45) and 1.65 (1.52–1.80), respectively (Ptrend <0.001). Prevalence of other self-reported chronic respiratory conditions was also higher among people with elevated COex (P <0.05).
Conclusion In adult Chinese, COex can be used as a biomarker for assessing current smoking and overall exposure to indoor household air pollution in combination with questionnaires.
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.
Background Sun exposure is the single most important risk factor for skin cancer, but sun exposure may also have beneficial effects on health. We tested the hypothesis that individuals with skin cancer (non-melanoma skin cancer and cutaneous malignant melanoma) have less myocardial infarction, hip fracture and death from any cause, compared with general population controls.
Methods We examined the entire Danish population above age 40 years from 1980 through 2006, comprising 4.4 million individuals. Diagnoses of non-melanoma skin cancer (n = 129 206), cutaneous malignant melanoma (n = 22107), myocardial infarction (n = 327 856), hip fracture (n = 129 419), and deaths from any cause (n = 1 629 519) were drawn from national registries.
Results In individuals with vs without non-melanoma skin cancer, multifactorially adjusted odds ratios were 0.96 (95% confidence interval: 0.94–0.98) for myocardial infarction and 1.15 (1.12–1.18) for hip fracture, and the multifactorially adjusted hazard ratio was 0.52 (0.52–0.53) for death from any cause. Risk of hip fracture was reduced (odds ratios were below 1.0) in individuals below age 90 years. In individuals with vs without cutaneous malignant melanoma, corresponding odds ratios were 0.79 (0.74–0.84) for myocardial infarction and 0.84 (0.76–0.93) for hip fracture, and the corresponding hazard ratio for death from any cause was 0.89 (0.87–0.91); however, cutaneous malignant melanoma was associated positively with death from any cause in some individuals.
Conclusions In this nationwide study, having a diagnosis of skin cancer was associated with less myocardial infarction, less hip fracture in those below age 90 years and less death from any cause. Causal conclusions cannot be made from our data. A beneficial effect of sun exposure per se needs to be examined in other 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.
Research on hospital-acquired infections (HAIs) requires the highest methodological standards to minimize the risk of bias and to avoid misleading interpretation. There are two major issues related specifically to studies in this area, namely the timing of infection and the occurrence of so-called competing risks, which deserve special attention. Just as a patient who acquires a serious infection during hospital admission needs appropriate antibiotic treatment, data being collected in studies on hospital-acquired infections need appropriate statistical analysis. We illustrate the urgent need for appropriate statistical treatment of hospital-acquired infections with some examples from recently conducted studies.The considerations presented are relevant for investigations on risk factors for HAIs as well as for outcome studies.
In epidemiological studies it is often necessary to disentangle the pathways that link an exposure to an outcome. Typically the aim is to identify the total effect of the exposure on the outcome, the effect of the exposure that acts through a given set of mediators of interest (indirect effect) and the effect of the exposure unexplained by those same mediators (direct effect). The traditional approach to mediation analysis is based on adjusting for the mediator in standard regression models to estimate the direct effect. However, several methodological papers have shown that under a number of circumstances this traditional approach may produce flawed conclusions. Through a better understanding of the causal structure of the variables involved in the analysis, with a formal definition of direct and indirect effects in a counterfactual framework, alternative analytical methods have been introduced to improve the validity and interpretation of mediation analysis. In this paper, we review and discuss the impact of the three main sources of potential bias in the traditional approach to mediation analyses: (i) mediator-outcome confounding;(ii) exposure-mediator interaction and (iii) mediator-outcome confounding affected by the exposure. We provide examples and discuss the impact these sources have in terms of bias.