scholarly journals Exploring selection bias in COVID-19 research: Simulations and prospective analyses of two UK cohort studies

Author(s):  
Louise AC Millard ◽  
Alba Fernández-Sanlés ◽  
Alice R Carter ◽  
Rachael Hughes ◽  
Kate Tilling ◽  
...  

ABSTRACTBackgroundNon-random selection into analytic subsamples could introduce selection bias in observational studies of SARS-CoV-2 infection and COVID-19 severity (e.g. including only those have had a COVID-19 PCR test). We explored the potential presence and impact of selection in such studies using data from self-report questionnaires and national registries.MethodsUsing pre-pandemic data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (mean age=27.6 (standard deviation [SD]=0.5); 49% female) and UK Biobank (UKB) (mean age=56 (SD=8.1); 55% female) with data on SARS-CoV-2 infection and death-with-COVID-19 (UKB only), we investigated predictors of selection into COVID-19 analytic subsamples. We then conducted empirical analyses and simulations to explore the potential presence, direction, and magnitude of bias due to selection when estimating the association of body mass index (BMI) with SARS-CoV-2 infection and death-with-COVID-19.ResultsIn both ALSPAC and UKB a broad range of characteristics related to selection, sometimes in opposite directions. For example, more educated participants were more likely to have data on SARS-CoV-2 infection in ALSPAC, but less likely in UKB. We found bias in many simulated scenarios. For example, in one scenario based on UKB, we observed an expected odds ratio of 2.56 compared to a simulated true odds ratio of 3, per standard deviation higher BMI.ConclusionAnalyses using COVID-19 self-reported or national registry data may be biased due to selection. The magnitude and direction of this bias depends on the outcome definition, the true effect of the risk factor, and the assumed selection mechanism.Key messagesObservational studies assessing the association of risk factors with SARS-CoV-2 infection and COVID-19 severity may be biased due to non-random selection into the analytic sample.Researchers should carefully consider the extent that their results may be biased due to selection, and conduct sensitivity analyses and simulations to explore the robustness of their results. We provide code for these analyses that is applicable beyond COVID-19 research.

2021 ◽  
pp. 1-8
Author(s):  
M. Florencia Ricci ◽  
Alastair Fung ◽  
Diane Moddemann ◽  
Victoria Micek ◽  
Gwen Y. Bond ◽  
...  

Abstract This comparison study of two groups within an inception cohort aimed to compare the frequency of motor impairment between preschool children with univentricular and biventricular critical congenital heart disease (CHD) not diagnosed with cerebral palsy/acquired brain injury, describe and compare their motor profiles and explore predictors of motor impairment in each group. Children with an intellectual quotient <70 or cerebral palsy/acquired brain injury were excluded. Motor skills were assessed with the Movement Assessment Battery for Children-2. Total scores <5th percentile indicated motor impairment. Statistical analysis included χ2 test and multiple logistic regression analysis. At a mean age of 55.4 (standard deviation 3.77) months, motor impairment was present in 11.8% of those with biventricular critical CHD, and 32.4% (p < 0.001) of those with univentricular critical CHD. The greatest difference between children with biventricular and univentricular CHD was seen in total test scores 8.73(2.9) versus 6.44(2.8) (p < 0.01) and in balance skills, 8.84 (2.8) versus 6.97 (2.5) (p = 0.001). Manual dexterity mean scores of children with univentricular CHD were significantly below the general population mean (>than one standard deviation). Independent odds ratio for motor impairment in children with biventricular critical CHD was presence of chromosomal abnormality, odds ratio 10.9 (CI 2.13–55.8) (p = 0.004); and in children with univentricular critical CHD odds ratio were: postoperative day 1–5 highest lactate (mmol/L), OR: 1.65 (C1.04–2.62) (p = 0.034), and dialysis requirement any time before the 4.5-year-old assessment, OR: 7.8 (CI 1.08–56.5) (p = 0.042). Early assessment of motor skills, particularly balance and manual dexterity, allows for intervention and supports that can address challenges during the school years.


Author(s):  
Ieuan Evans ◽  
Jon Heron ◽  
Joseph Murray ◽  
Matthew Hickman ◽  
Gemma Hammerton

Experimental studies support the conventional belief that people behave more aggressively whilst under the influence of alcohol. To examine how these experimental findings manifest in real life situations, this study uses a method for estimating evidence for causality with observational data—‘situational decomposition’ to examine the association between alcohol consumption and crime in young adults from the Avon Longitudinal Study of Parents and Children. Self-report questionnaires were completed at age 24 years to assess typical alcohol consumption and frequency, participation in fighting, shoplifting and vandalism in the previous year, and whether these crimes were committed under the influence of alcohol. Situational decomposition compares the strength of two associations, (1) the total association between alcohol consumption and crime (sober or intoxicated) versus (2) the association between alcohol consumption and crime committed while sober. There was an association between typical alcohol consumption and total crime for fighting [OR (95% CI): 1.47 (1.29, 1.67)], shoplifting [OR (95% CI): 1.25 (1.12, 1.40)], and vandalism [OR (95% CI): 1.33 (1.12, 1.57)]. The associations for both fighting and shoplifting had a small causal component (with the association for sober crime slightly smaller than the association for total crime). However, the association for vandalism had a larger causal component.


Author(s):  
Jolien Rijlaarsdam ◽  
Charlotte A. M. Cecil ◽  
J. Marieke Buil ◽  
Pol A. C. van Lier ◽  
Edward D. Barker

AbstractAlthough there is mounting evidence that the experience of being bullied associates with both internalizing and externalizing symptoms, it is not known yet whether the identified associations are specific to these symptoms, or shared between them. The primary focus of this study is to assess the prospective associations of bullying exposure with both general and specific (i.e., internalizing, externalizing) factors of psychopathology. This study included data from 6,210 children participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Child bullying was measured by self-report at ages 8 and 10 years. Child psychopathology symptoms were assessed by parent-interview, using the Development and Well-being Assessment (DAWBA) at ages 7 and 13 years. Bullying exposure significantly associated with the general psychopathology factor in early adolescence. In particular, chronically victimized youth exposed to multiple forms of bullying (i.e., both overt and relational) showed higher levels of general psychopathology. Bullying exposure also associated with both internalizing and externalizing factors from the correlated-factors model. However, the effect estimates for these factors decreased considerably in size and dropped to insignificant for the internalizing factor after extracting the shared variance that belongs to the general factor of psychopathology. Using an integrative longitudinal model, we found that higher levels of general psychopathology at age 7 also associated with bullying exposure at age 8 which, in turn, associated with general psychopathology at age 13 through its two-year continuity. Findings suggest that exposure to bullying is a risk factor for a more general vulnerability to psychopathology.


2018 ◽  
Vol 103 (10) ◽  
pp. 3729-3736 ◽  
Author(s):  
Arash Derakhshan ◽  
Tim I M Korevaar ◽  
Peter N Taylor ◽  
Deborah Levie ◽  
Monica Guxens ◽  
...  

Abstract Context Thyroperoxidase antibody (TPOAb) positivity is a major risk factor for gestational thyroid dysfunction. During the first 18 to 20 weeks of pregnancy, high concentrations of human chorionic gonadotropin (hCG) stimulate the thyroid to ensure adequate thyroid hormone availability for the developing fetus. However, TPOAb-positive women have an impaired thyroidal response to hCG stimulation. Objective To study the association of maternal TPOAb positivity during pregnancy with child IQ. Design, Setting, and Participants This study was embedded in two prospective birth cohorts: Generation R (Rotterdam, the Netherlands) and Avon Longitudinal Study of Parents and Children (ALSPAC; United Kingdom). Mother-child pairs with available data on early pregnancy TPOAb (≤18 weeks of gestation) and offspring IQ were included (n = 3637 for Generation R and n = 2396 for ALSPAC). Main Outcome Measures Child IQ at 5 to 10 years of age. Results In Generation R, TPOAb positivity was associated with a 2.0 ± 0.9-point lower mean child IQ (P = 0.03). Sensitivity analyses showed negative effect estimates already from TPOAb concentrations considerably lower than currently used manufacturer cutoffs. In ALSPAC, neither TPOAb positivity nor TPOAb concentrations below manufacturer cutoffs were associated with child IQ (TPOAb positivity: 0.7 ± 1.0; P = 0.45). Adjustment for maternal TSH or free T4 concentrations or urinary iodine/creatinine ratio did not change the results. Conclusion TPOAb positivity during pregnancy was associated with lower child IQ in Generation R but not in ALSPAC. Further studies are needed to elucidate whether differences between the study populations, such as maternal iodine status, could be the underlying cause for these differences.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2218
Author(s):  
Shuai Yuan ◽  
Paul Carter ◽  
Amy M. Mason ◽  
Stephen Burgess ◽  
Susanna C. Larsson

Coffee consumption has been linked to a lower risk of cardiovascular disease in observational studies, but whether the associations are causal is not known. We conducted a Mendelian randomization investigation to assess the potential causal role of coffee consumption in cardiovascular disease. Twelve independent genetic variants were used to proxy coffee consumption. Summary-level data for the relations between the 12 genetic variants and cardiovascular diseases were taken from the UK Biobank with up to 35,979 cases and the FinnGen consortium with up to 17,325 cases. Genetic predisposition to higher coffee consumption was not associated with any of the 15 studied cardiovascular outcomes in univariable MR analysis. The odds ratio per 50% increase in genetically predicted coffee consumption ranged from 0.97 (95% confidence interval (CI), 0.63, 1.50) for intracerebral hemorrhage to 1.26 (95% CI, 1.00, 1.58) for deep vein thrombosis in the UK Biobank and from 0.86 (95% CI, 0.50, 1.49) for subarachnoid hemorrhage to 1.34 (95% CI, 0.81, 2.22) for intracerebral hemorrhage in FinnGen. The null findings remained in multivariable Mendelian randomization analyses adjusted for genetically predicted body mass index and smoking initiation, except for a suggestive positive association for intracerebral hemorrhage (odds ratio 1.91; 95% CI, 1.03, 3.54) in FinnGen. This Mendelian randomization study showed limited evidence that coffee consumption affects the risk of developing cardiovascular disease, suggesting that previous observational studies may have been confounded.


2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 312-312
Author(s):  
Megan Mullins ◽  
Jasdeep Kler ◽  
Marissa Eastman ◽  
Mohammed Kabeto ◽  
Lauren P. Wallner ◽  
...  

312 Background: Population aging and improving cancer survival rates are resulting in a growing population of older cancer survivors in the United States (US). As a result, there is an increasing need for longitudinal, population-representative data for interdisciplinary cancer research among older adults. The US Health Retirement Study (HRS) is an ongoing population-representative cohort of US adults over age 50 that contains rich interview and biomarker data on health during aging. Interviews have collected self-reported cancer diagnoses since 1998, but these self-reports have not been validated. We compared first incident cancer diagnoses self-reported in HRS interviews against diagnostic claims from linked Medicare records. Methods: We examined the validity of first incident cancer diagnoses self-reported in biennial HRS interviews from 2000 through 2016 against ICD-9 and ICD-10 diagnostic claim records among 8,242 HRS participants aged ≥65 with 90% continuous enrollment in fee-for-service Medicare, using the claim records as the gold standard. We calculated the sensitivity, specificity, and k for first incident cancer diagnoses (all cancers combined, excluding non-melanoma skin cancer, and each of bladder, breast, colorectal/anal, uterine, kidney/renal, lung/bronchus, and prostate cancers) cumulatively over the follow-up, and at each biennial study interview. Results: Self-reports of first incident cancer diagnosis (agnostic of site) between 2000 and 2016 had 73.2% sensitivity and 96.2% specificity against Medicare claims (k = 0.73). For site-specific self-reports, sensitivities ranged from 44.7% (kidney) to 75.0% (breast), and specificities ranged from 99.2% (prostate) to 99.9% (bladder, uterine, and kidney). Results were similar in sensitivity analyses restricting to individuals with 100% continuous fee-for-service Medicare enrollment and when restricting to individuals with at least 24 months of Medicare enrollment. Conclusions: Self-reported cancer diagnoses in the HRS have reasonable validity for population-based research on cancer and aging across cancer types. Apart from breast cancer, cancer site specific analyses will greatly benefit from the improved validity of self-report with Medicare claim linkage.


2017 ◽  
Vol 52 (2) ◽  
pp. 181-191 ◽  
Author(s):  
Jordana K Bayer ◽  
Ruth Beatson ◽  
Lesley Bretherton ◽  
Harriet Hiscock ◽  
Melissa Wake ◽  
...  

Objective: To determine whether a population-delivered parenting programme assists in preventing internalising problems at school entry for preschool children at-risk with temperamental inhibition. Methods: Design: a randomised controlled trial was used. Setting: the setting was 307 preschool services across eight socioeconomically diverse government areas in Melbourne, Australia. Participants: a total of 545 parents of inhibited 4-year-old children: 498 retained at 1-year follow up. Early intervention: Cool Little Kids parenting group programme was implemented. Primary outcomes: the primary outcomes were child DSM-IV anxiety disorders (assessor blind) and internalising problems. Secondary outcomes: the secondary outcomes were parenting practices and parent mental health. Results: At 1-year follow up (mean (standard deviation) age = 5.8 (0.4) years), there was little difference in anxiety disorders between the intervention and control arms (44.2% vs 50.2%; adjusted odds ratio = 0.86, 95% confidence interval = [0.60, 1.25], p = 0.427). Internalising problems were reduced in the intervention arm (Strengths and Difficulties Questionnaire: abnormal – 24.2% vs 33.0%; adjusted odds ratio = 0.56, 95% confidence interval = [0.35, 0.89], p = 0.014; symptoms – mean (standard deviation) = 2.5 (2.0) vs 2.9 (2.2); adjusted mean difference = –0.47, 95% confidence interval = [–0.81, –0.13], p = 0.006). Parents’ participation in the intervention was modest (29.4% attended most groups, 20.5% used skills most of the time during the year). A priori interaction tests suggested that for children with anxious parents, the intervention reduced anxiety disorders and internalising symptoms after 1 year. Conclusion: Offering Cool Little Kids across the population for inhibited preschoolers does not impact population outcomes after 1 year. Effects may be emerging for inhibited children at highest risk with parent anxiety. Trial outcomes will continue into mid-childhood.


JAMA ◽  
2007 ◽  
Vol 297 (19) ◽  
pp. 2077 ◽  
Author(s):  
Ilya Novikov ◽  
Ofra Kalter-Leibovici

2005 ◽  
Vol 23 (34) ◽  
pp. 8606-8612 ◽  
Author(s):  
Stefanos Bonovas ◽  
Kalitsa Filioussi ◽  
Nikolaos Tsavaris ◽  
Nikolaos M. Sitaras

Purpose A growing body of evidence suggests that statins may have chemopreventive potential against breast cancer. Laboratory studies demonstrate that statins induce apoptosis and reduce cell invasiveness in various cell lines, including breast carcinoma cells. However, the clinical relevance of these data remains unclear. The nonconclusive nature of the epidemiologic data prompted us to conduct a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. Patients and Methods A comprehensive search for articles published up until 2005 was performed; reviews of each study were conducted; and data were abstracted. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% CIs were calculated using the random and the fixed-effects models. Subgroup and sensitivity analyses were also performed. Results Seven large randomized trials and nine observational studies (five case-control and four cohort studies) contributed to the analysis. We found no evidence of publication bias or heterogeneity among the studies. Statin use did not significantly affect breast cancer risk (fixed effects model: RR = 1.03; 95% CI, 0.93 to 1.14; random effects model: RR = 1.02; 95% CI, 0.89 to 1.18). When the analyses were stratified into subgroups, there was no evidence that study design substantially influenced the estimate of effects. Furthermore, the sensitivity analysis confirmed the stability of our results. Conclusion Our meta-analysis findings do not support a protective effect of statins against breast cancer. However, this conclusion is limited by the relatively short follow-up times of the studies analyzed. Further studies are required to investigate the potential decrease in breast cancer risk among long-term statin users.


2013 ◽  
Vol 19 (11) ◽  
pp. 1382-1387 ◽  
Author(s):  
Sarah T Stahl ◽  
Salvatore P Insana

Criterion validity of a novel accelerometry device that measures caloric expenditure (Fitbit) was evaluated against a self-report estimation of caloric expenditure (Community Healthy Activities Model Program for Seniors) in older adults. Community Health Activities Model Program for Seniors and Fitbit estimates of total caloric expenditure per day were significantly correlated ( r = .61, p < .05). Bland–Altman plots indicated that 70 percent of participants’ data were within 1 standard deviation of the mean difference between measures. These preliminary findings suggest that the Fitbit may be considered a viable instrument for measuring daily caloric expenditure among older adults. However, further work is required to determine the optimal measurement technique for caloric expenditure among older adults.


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