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American Journal of Epidemiology
Journal Prestige (SJR): 2.713
Citation Impact (citeScore): 3
Number of Followers: 266  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0002-9262 - ISSN (Online) 1476-6256
Published by Oxford University Press Homepage  [415 journals]
  • A Note From the Editors

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      Pages: 1971 - 1971
      Abstract: In celebration of our 100th anniversary, the American Journal of Epidemiology is requesting submissions for a new series highlighting members of our field to elevate the different areas of epidemiology.
      Authors are invited to submit up to 300 words describing the life and work of an influential epidemiologist whose contribution to the discipline has expanded fundamental knowledge of the breadth and depth of the field. Self-nominations are also welcome. We hope to increase awareness about all aspects of epidemiology. In addition, these articles will be used to help expand Wikipedia coverage of epidemiologists, especially those from historically overlooked populations. We therefore strongly encourage contributions highlighting the work of women, minoritized individuals, and individuals from low- or middle-income countries.
      PubDate: Wed, 01 Sep 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab210
      Issue No: Vol. 190, No. 10 (2021)
       
  • Food Fortification With Folic Acid for Prevention of Spina Bifida and
           Anencephaly: The Need for a Paradigm Shift in Evidence Evaluation for
           Policy-Making

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      Authors: Martinez H; Pachón H, Kancherla V, et al.
      Pages: 1972 - 1976
      Abstract: AbstractContext-specific evidence evaluation is advocated in modern epidemiology to support publichealth policy decisions, avoiding excessive reliance on experimental study designs. Here we present the rationale for a paradigm shift in evaluation of the evidence derived from independent studies, as well as systematic reviews and meta-analyses of observational studies, applying Hill’s criteria (including coherence, plausibility, temporality, consistency, magnitude of effect, and dose-response) to evaluate food fortification as an effective public health intervention against folic acid–preventable (FAP) spina bifida and anencephaly (SBA). A critical appraisal of evidence published between 1983 and 2020 supports the conclusion that food fortification with folic acid prevents FAP SBA. Policy-makers should be confident that with mandatory legislation, effective implementation, and periodic evaluation, food fortification assures that women of reproductive age will safely receive daily folic acid to significantly reduce the risk of FAP SBA. Current evidence should suffice to generate the political will to implement programs that will save thousands of lives each year in over 100 countries.
      PubDate: Wed, 17 Mar 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab061
      Issue No: Vol. 190, No. 10 (2021)
       
  • A System for Phenotype Harmonization in the National Heart, Lung, and
           Blood Institute Trans-Omics for Precision Medicine (TOPMed) Program

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      Authors: Stilp A; Emery L, Broome J, et al.
      Pages: 1977 - 1992
      Abstract: AbstractGenotype-phenotype association studies often combine phenotype data from multiple studies to increase statistical power. Harmonization of the data usually requires substantial effort due to heterogeneity in phenotype definitions, study design, data collection procedures, and data-set organization. Here we describe a centralized system for phenotype harmonization that includes input from phenotype domain and study experts, quality control, documentation, reproducible results, and data-sharing mechanisms. This system was developed for the National Heart, Lung, and Blood Institute’s Trans-Omics for Precision Medicine (TOPMed) program, which is generating genomic and other -omics data for more than 80 studies with extensive phenotype data. To date, 63 phenotypes have been harmonized across thousands of participants (recruited in 1948–2012) from up to 17 studies per phenotype. Here we discuss challenges in this undertaking and how they were addressed. The harmonized phenotype data and associated documentation have been submitted to National Institutes of Health data repositories for controlled access by the scientific community. We also provide materials to facilitate future harmonization efforts by the community, which include 1) the software code used to generate the 63 harmonized phenotypes, enabling others to reproduce, modify, or extend these harmonizations to additional studies, and 2) the results of labeling thousands of phenotype variables with controlled vocabulary terms.
      PubDate: Fri, 16 Apr 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab115
      Issue No: Vol. 190, No. 10 (2021)
       
  • The Causal Interpretation of “Overall Vaccine Effectiveness”
           in Test-Negative Studies

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      Authors: Feng S; Sullivan S, Tchetgen Tchetgen E, et al.
      Pages: 1993 - 1999
      Abstract: AbstractTest-negative studies are commonly used to estimate influenza vaccine effectiveness (VE). In a typical study, an “overall VE” estimate based on data from the entire sample may be reported. However, there may be heterogeneity in VE, particularly by age. Therefore, in this article we discuss the potential for a weighted average of age-specific VE estimates to provide a more meaningful measure of overall VE. We illustrate this perspective first using simulations to evaluate how overall VE would be biased when certain age groups are overrepresented. We found that unweighted overall VE estimates tended to be higher than weighted VE estimates when children were overrepresented and lower when elderly persons were overrepresented. Then we extracted published estimates from the US Flu VE network, in which children are overrepresented, and some discrepancy between unweighted and weighted overall VE was observed. Differences in weighted versus unweighted overall VE estimates could translate to substantial differences in the interpretation of individual risk reduction among vaccinated persons and in the total averted disease burden at the population level. Weighting of overall estimates should be considered in VE studies in the future.
      PubDate: Thu, 08 Apr 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab101
      Issue No: Vol. 190, No. 10 (2021)
       
  • Prediction of Cardiovascular Disease Risk Accounting for Future Initiation
           of Statin Treatment

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      Authors: Xu Z; Arnold M, Stevens D, et al.
      Pages: 2000 - 2014
      Abstract: AbstractCardiovascular disease (CVD) risk-prediction models are used to identify high-risk individuals and guide statin initiation. However, these models are usually derived from individuals who might initiate statins during follow-up. We present a simple approach to address statin initiation to predict “statin-naive” CVD risk. We analyzed primary care data (2004–2017) from the UK Clinical Practice Research Datalink for 1,678,727 individuals (aged 40–85 years) without CVD or statin treatment history at study entry. We derived age- and sex-specific prediction models including conventional risk factors and a time-dependent effect of statin initiation constrained to 25% risk reduction (from trial results). We compared predictive performance and measures of public-health impact (e.g., number needed to screen to prevent 1 event) against models ignoring statin initiation. During a median follow-up of 8.9 years, 103,163 individuals developed CVD. In models accounting for (versus ignoring) statin initiation, 10-year CVD risk predictions were slightly higher; predictive performance was moderately improved. However, few individuals were reclassified to a high-risk threshold, resulting in negligible improvements in number needed to screen to prevent 1 event. In conclusion, incorporating statin effects from trial results into risk-prediction models enables statin-naive CVD risk estimation and provides moderate gains in predictive ability but had a limited impact on treatment decision-making under current guidelines in this population.
      PubDate: Wed, 17 Feb 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab031
      Issue No: Vol. 190, No. 10 (2021)
       
  • Invited Commentary: Treatment Drop-in—Making the Case for Causal
           Prediction

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      Authors: Sperrin M; Diaz-Ordaz K, Pajouheshnia R.
      Pages: 2015 - 2018
      Abstract: AbstractClinical prediction models (CPMs) are often used to guide treatment initiation, with individuals at high risk offered treatment. This implicitly assumes that the probability quoted from a CPM represents the risk to an individual of an adverse outcome in absence of treatment. However, for a CPM to correctly target this estimand requires careful causal thinking. One problem that needs to be overcome is treatment drop-in: where individuals in the development data commence treatment after the time of prediction but before the outcome occurs. In this issue of the Journal, Xu et al. (Am J Epidemiol. 2021;190(10):2000–2014) use causal estimates from external data sources, such as clinical trials, to adjust CPMs for treatment drop-in. This represents a pragmatic and promising approach to address this issue, and it illustrates the value of utilizing causal inference in prediction. Building causality into the prediction pipeline can also bring other benefits. These include the ability to make and compare hypothetical predictions under different interventions, to make CPMs more explainable and transparent, and to improve model generalizability. Enriching CPMs with causal inference therefore has the potential to add considerable value to the role of prediction in healthcare.
      PubDate: Wed, 17 Feb 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab030
      Issue No: Vol. 190, No. 10 (2021)
       
  • Body Mass Index and Mortality Among Adults With Incident Myocardial
           Infarction

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      Authors: Al-Shaar L; Li Y, Rimm E, et al.
      Pages: 2019 - 2028
      Abstract: AbstractThe relationship between body mass index (BMI; weight (kg)/height (m)2) and mortality among survivors of myocardial infarction (MI) remains controversial. We examined the relationships of BMI before and after MI and change in weight with all-cause mortality among participants in the Nurses’ Health Study (1980–2016) and Health Professionals Follow-up Study (1988–2016) cohorts. During a follow-up period of up to 36 years, we documented 4,856 participants with incident nonfatal MI, among whom 2,407 died during follow-up. For pre-MI and post-MI BMI, overweight was not associated with lower mortality. Obesity (BMI ≥30) was associated with higher risk of mortality. Compared with participants with post-MI BMI of 22.5–24.9, hazard ratios were 1.16 (95% confidence interval (CI): 1.01, 1.34) for BMI 30.0–34.9 and 1.52 (95% CI: 1.27, 1.83) for BMI ≥35.0 (P for trend < 0.001). Compared with stable weight from before MI to after MI, a reduction of more than 4 BMI units was associated with increased mortality (hazard ratio = 1.53, 95%: CI: 1.28, 1.83). This increase was seen only among participants who lost weight without improving their physical activity or diet. Our findings showed no survival benefit of excess adiposity in relation to risk of mortality. Weight loss from before to after MI without lifestyle improvement may reflect reverse causation and disease severity.
      PubDate: Tue, 27 Apr 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab126
      Issue No: Vol. 190, No. 10 (2021)
       
  • Dietary Vitamin K Intake and the Risk of Pancreatic Cancer: A Prospective
           Study of 101,695 American Adults

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      Authors: Yu D; Li Q, Cheng L, et al.
      Pages: 2029 - 2041
      Abstract: AbstractNo epidemiologic studies have been conducted to assess the association of intake of dietary vitamin K with the risk of pancreatic cancer. We used prospective data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial between 1993 and 2009 to fill this gap. A total of 101,695 subjects were identified. Dietary intakes of phylloquinone (vitamin K1), menaquinones (vitamin K2), and dihydrophylloquinone (dihydrovitamin K1) were assessed using a food frequency questionnaire. Cox regression was applied to calculate hazard ratios and 95% confidence intervals. During a mean follow-up of 8.86 years (900,744.57 person-years), 361 cases of pancreatic cancer were documented. In the fully adjusted model, dietary intakes of phylloquinone (for quartile 4 vs. quartile 1, hazard ratio (HR) = 0.57, 95% confidence interval (CI): 0.39, 0.83; P for trend = 0.002) and dihydrophylloquinone (for quartile 4 vs. quartile 1, HR = 0.59; 95% CI: 0.41, 0.85; P for trend = 0.006), but not menaquinones (for quartile 4 vs. quartile 1, HR = 0.93; 95% CI: 0.65, 1.33; P for trend = 0.816), were found to be inversely associated with the risk of pancreatic cancer in a nonlinear dose–response manner (all P values for nonlinearity < 0.05), and this was not modified by predefined stratification factors and remained in sensitivity analyses. In conclusion, dietary intakes of phylloquinone and dihydrophylloquinone, but not menaquinones, confer a lower risk of pancreatic cancer. Future studies should confirm our findings.
      PubDate: Tue, 04 May 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab131
      Issue No: Vol. 190, No. 10 (2021)
       
  • Associations Between Kidney Function, Proteinuria, and the Risk of Kidney
           Cancer: A Nationwide Cohort Study Involving 10 Million Participants

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      Authors: Park J; Shin D, Han K, et al.
      Pages: 2042 - 2052
      Abstract: AbstractChronic kidney disease in its later stages is associated with increased risk of kidney cancer. We investigated whether chronic kidney disease at milder stages is associated with increased kidney cancer risk, using a retrospectively selected cohort of 9,809,317 adults in the Republic of Korea who participated in a nationwide health screening (2009–2016). We examined the impact of estimated glomerular filtration rate (eGFR), dipstick proteinuria, and interactive associations between the 2 factors on the risk of incident kidney cancer. During a median follow-up period of 7.3 years, 10,634 kidney cancers were identified. After adjustment for multiple confounders, participants with a reduced eGFR had an increased risk of kidney cancer (for eGFR <30 mL/minute/1.73 m2, adjusted hazard ratio = 1.18 (95% confidence interval: 1.01, 1.39); for eGFR 30–59 mL/minute/1.73 m2, adjusted hazard ratio = 1.22 (95% confidence interval: 1.14, 1.31)) compared with those with an eGFR of 60–89 mL/minute/1.73 m2. A dose-response relationship between the severity of proteinuria and incident kidney cancer was observed. Analyses of joint effects of eGFR and dipstick proteinuria showed that with the presence of proteinuria, kidney cancer incidence was markedly increased along with decreasing eGFR. Reduced eGFR and proteinuria are significantly associated with subsequent risk of kidney cancer, possibly in a synergistic manner.
      PubDate: Wed, 12 May 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab140
      Issue No: Vol. 190, No. 10 (2021)
       
  • Comparison of Relative Survival and Cause-Specific Survival in Men With
           Prostate Cancer According to Age and Risk Category: A Nationwide,
           Population-Based Study

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      Authors: Orrason A; Garmo H, Styrke J, et al.
      Pages: 2053 - 2063
      Abstract: AbstractNet survival, estimated in a relative survival (RS) or cause-specific survival (CSS) framework, is a key measure of the effectiveness of cancer management. We compared RS and CSS in men with prostate cancer (PCa) according to age and risk category, using Prostate Cancer data Base Sweden, including 168,793 men younger than age 90 years, diagnosed 1998–2016 with PCa. RS and CSS were compared according to age and risk category based on TNM (tumor, nodes, and metastases) stage, Gleason score, and prostate-specific antigen level. Each framework requires assumptions that are unlikely to be appropriate for PCa. Ten-year RS was substantially higher than CSS in men aged 80–89 with low-risk PCa: 125% (95% confidence interval: 113, 138) versus 85% (95% confidence interval: 82, 88). In contrast, RS and CSS were similar for men under age 70 and for all men with regional or distant metastases. Both RS and CSS produce biased estimates of net survival for men with low- and intermediate-risk PCa, in particular for men over 80. Due to biases, net survival is overestimated in analysis of RS but underestimated in analysis of CSS. These results highlight the importance of evaluating the underlying assumptions for each method, because the “true” net survival is expected to lie between the limits of RS and CSS.
      PubDate: Wed, 19 May 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab146
      Issue No: Vol. 190, No. 10 (2021)
       
  • Clarifying the Trade-Offs of Risk-Stratified Screening for Prostate
           Cancer: A Cost-Effectiveness Study

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      Authors: Hendrix N; Gulati R, Jiao B, et al.
      Pages: 2064 - 2074
      Abstract: AbstractCancer risk prediction is necessary for precision early detection, which matches screening intensity to risk. However, practical steps for translating risk predictions to risk-stratified screening policies are not well established. We used a validated population prostate-cancer model to simulate the outcomes of strategies that increase intensity for men at high risk and reduce intensity for men at low risk. We defined risk by the Prompt Prostate Genetic Score (PGS) (Stratify Genomics, San Diego, California), a germline genetic test. We first recalibrated the model to reflect the disease incidence observed within risk strata using data from a large prevention trial where some participants were tested with Prompt PGS. We then simulated risk-stratified strategies in a population with the same risk distribution as the trial and evaluated the cost-effectiveness of risk-stratified screening versus universal (risk-agnostic) screening. Prompt PGS risk-adapted screening was more cost-effective when universal screening was conservative. Risk-stratified strategies improved outcomes at a cost of less than $100,000 per quality-adjusted life year compared with biennial screening starting at age 55 years, but risk stratification was not cost-effective compared with biennial screening starting at age 45. Heterogeneity of risk and fraction of the population within each stratum were also important determinants of cost-effectiveness.
      PubDate: Sat, 22 May 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab155
      Issue No: Vol. 190, No. 10 (2021)
       
  • Transportability From Randomized Trials to Clinical Care: On Initial HIV
           Treatment With Efavirenz and Suicidal Thoughts or Behaviors

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      Authors: Mollan K; Pence B, Xu S, et al.
      Pages: 2075 - 2084
      Abstract: AbstractIn an analysis of randomized trials, use of efavirenz for treatment of human immunodeficiency virus (HIV) infection was associated with increased suicidal thoughts/behaviors. However, analyses of observational data have found no evidence of increased risk. To assess whether population differences might explain this divergence, we transported the effect of efavirenz use from these trials to a specific target population. Using inverse odds weights and multiple imputation, we transported the effect of efavirenz on suicidal thoughts/behaviors in these randomized trials (participants were enrolled in 2001–2007) to a trials-eligible cohort of US adults initiating antiretroviral therapy while receiving HIV clinical care at medical centers between 1999 and 2015. Overall, 8,291 cohort participants and 3,949 trial participants were eligible. Prescription of antidepressants (19% vs. 13%) and injection drug history (16% vs. 10%) were more frequent in the cohort than in the trial participants. Compared with the effect in trials, the estimated hazard ratio for efavirenz on suicidal thoughts/behaviors was attenuated in our target population (trials: hazard ratio (HR) = 2.3 (95% confidence interval (CI): 1.2, 4.4); transported: HR = 1.8 (95% CI: 0.9, 4.4)), whereas the incidence rate difference was similar (trials: HR = 5.1 (95% CI: 1.6, 8.7); transported: HR = 5.4 (95% CI: −0.4, 11.4)). In our target population, there was greater than 20% attenuation of the hazard ratio estimate as compared with the trials-only estimate. Transporting results from trials to a target population is informative for addressing external validity.
      PubDate: Mon, 10 May 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab136
      Issue No: Vol. 190, No. 10 (2021)
       
  • The Challenge of Achieving Immunity Through Multiple-Dose Vaccines in
           Madagascar

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      Authors: Jones F; Mensah K, Heraud J, et al.
      Pages: 2085 - 2093
      Abstract: AbstractAdministration of many childhood vaccines requires that multiple doses be delivered within a narrow time window to provide adequate protection and reduce disease transmission. Accurately quantifying vaccination coverage is complicated by limited individual-level data and multiple vaccination mechanisms (routine and supplementary vaccination programs). We analyzed 12,541 vaccination cards from 6 districts across Madagascar for children born in 2015 and 2016. For 3 vaccines—pentavalent diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine (DTP-HB-Hib; 3 doses), 10-valent pneumococcal conjugate vaccine (PCV10; 3 doses), and rotavirus vaccine (2 doses)—we used dates of vaccination and birth to estimate coverage at 1 year of age and timeliness of delivery. Vaccination coverage at age 1 year for the first dose was consistently high, with decreases for subsequent doses (DTP-HB-Hib: 91%, 81%, and 72%; PCV10: 82%, 74%, and 64%; rotavirus: 73% and 63%). Coverage levels between urban districts and their rural counterparts did not differ consistently. For each dose of DTP-HB-Hib, the overall percentage of individuals receiving late doses was 29%, 7%, and 6%, respectively; estimates were similar for other vaccines. Supplementary vaccination weeks, held to help children who had missed routine care to catch up, did not appear to increase the likelihood of being vaccinated. Maintaining population-level immunity with multiple-dose vaccines requires a robust stand-alone routine immunization program.
      PubDate: Sat, 22 May 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab145
      Issue No: Vol. 190, No. 10 (2021)
       
  • Outcome-Stratified Analysis of Biomarker Trajectories for Patients
           Infected With Severe Acute Respiratory Syndrome Coronavirus 2

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      Authors: Bowring M; Wang Z, Xu Y, et al.
      Pages: 2094 - 2106
      Abstract: AbstractLongitudinal trajectories of vital signs and biomarkers during hospital admission of patients with COVID-19 remain poorly characterized despite their potential to provide critical insights about disease progression. We studied 1884 patients with severe acute respiratory syndrome coronavirus 2 infection from April 3, 2020, to June 25, 2020, within 1 Maryland hospital system and used a retrospective longitudinal framework with linear mixed-effects models to investigate relevant biomarker trajectories leading up to 3 critical outcomes: mechanical ventilation, discharge, and death. Trajectories of 4 vital signs (respiratory rate, ratio of oxygen saturation (Spo2) to fraction of inspired oxygen (Fio2), pulse, and temperature) and 4 laboratory values (C-reactive protein (CRP), absolute lymphocyte count (ALC), estimated glomerular filtration rate, and D-dimer) clearly distinguished the trajectories of patients with COVID-19. Before any ventilation, log(CRP), log(ALC), respiratory rate, and Spo2-to-Fio2 ratio trajectories diverge approximately 8–10 days before discharge or death. After ventilation, log(CRP), log(ALC), respiratory rate, Spo2-to-Fio2 ratio, and estimated glomerular filtration rate trajectories again diverge 10–20 days before death or discharge. Trajectories improved until discharge and remained unchanged or worsened until death. Our approach characterizes the distribution of biomarker trajectories leading up to competing outcomes of discharge versus death. Moving forward, this model can contribute to quantifying the joint probability of biomarkers and outcomes when provided clinical data up to a given moment.
      PubDate: Wed, 12 May 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab138
      Issue No: Vol. 190, No. 10 (2021)
       
  • California’s Mental Health Services Act and Mortality Due to Suicide,
           Homicide, and Acute Effects of Alcohol: A Synthetic Control Application

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      Authors: Zimmerman S; Matthay E, Rudolph K, et al.
      Pages: 2107 - 2115
      Abstract: AbstractCalifornia’s Mental Health Services Act (MHSA) substantially expanded funding of county mental health services through a state tax, and led to broad prevention efforts and intensive services for individuals experiencing serious mental disorders. We estimated the associations between MHSA and mortality due to suicide, homicide, and acute effects of alcohol. Using annual cause-specific mortality data for each US state and the District of Columbia from 1976–2015, we used a generalization of the quasi-experimental synthetic control method to predict California’s mortality rate for each outcome in the absence of MHSA using a weighted combination of comparison states. We calculated the association between MHSA and each outcome as the absolute difference and percentage difference between California’s observed and predicted average annual rates over the postintervention years (2007–2015). MHSA was associated with modest decreases in average annual rates of homicide (−0.81/100,000 persons, corresponding to a 13% reduction) and mortality from acute alcohol effects (−0.35/100,000 persons, corresponding to a 12% reduction). Placebo test inference suggested that the associations were unlikely to be due to chance. MHSA was not associated with suicide. Protective associations with mortality due to homicide and acute alcohol effects provide evidence for modest health benefits of MHSA at the population level.
      PubDate: Wed, 21 Apr 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab123
      Issue No: Vol. 190, No. 10 (2021)
       
  • Urban Densification and Physical Activity Change: A 12-Year Longitudinal
           Study of Australian Adults

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      Authors: Chandrabose M; Owen N, Hadgraft N, et al.
      Pages: 2116 - 2123
      Abstract: AbstractUrbanization, a major force driving changes in neighborhood environments, may affect residents’ health by influencing their daily activity levels. We examined associations of population density changes in urban areas with adults’ physical activity changes over 12 years using data from the Australian Diabetes, Obesity and Lifestyle Study (1999–2012). The analytical sample contained 2,354 participants who remained at the same residential address throughout the study period in metropolitan cities and regional cities (42 study areas). Census-based population density measures were calculated for 1-km–radius buffers around their homes. Population density change was estimated using linear growth models. Two-level linear regression models were used to assess associations between changes in population density and changes in self-reported walking and physical activity durations. The average change in population density was 0.8% per year (range, −4.1 to 7.8) relative to baseline density. After adjustment for confounders, each 1% annual increase in population density was associated with 8.5-minutes/week (95% confidence interval: 0.6, 16.4) and 19.0-minutes/week (95% confidence interval: 3.7, 34.4) increases in walking and physical activity, respectively, over the 12-year study period. Increasing population density through urban planning policies of accommodating population growth within the existing urban boundary, rather than expanding city boundaries, could assist in promoting physical activity at the population level.
      PubDate: Wed, 12 May 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab139
      Issue No: Vol. 190, No. 10 (2021)
       
  • Unemployment Insurance and Mortality Among the Long-Term Unemployed: A
           Population-Based Matched-Cohort Study

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      Authors: Shahidi F; Parnia A.
      Pages: 2124 - 2137
      Abstract: AbstractUnemployment insurance is hypothesized to play an important role in mitigating the adverse health consequences of job loss. In this prospective cohort study, we examined whether receiving unemployment benefits is associated with lower mortality among the long-term unemployed. Census records from the 2006 Canadian Census Health and Environment Cohort (n = 2,105,595) were linked to mortality data from 2006–2016. Flexible parametric survival analysis and propensity score matching were used to model time-varying relationships between long-term unemployment (≥20 weeks), unemployment-benefit recipiency, and all-cause mortality. Mortality was consistently lower among unemployed individuals who reported receiving unemployment benefits, relative to matched nonrecipients. For example, mortality at 2 years of follow-up was 18% lower (95% confidence interval (CI): 9, 26) among men receiving benefits and 30% lower (95% CI: 18, 40) among women receiving benefits. After 10 years of follow-up, unemployment-benefit recipiency was associated with 890 (95% CI: 560, 1,230) fewer deaths per 100,000 men and 1,070 (95% CI: 810, 1,320) fewer deaths per 100,000 women. Our findings indicate that receiving unemployment benefits is associated with lower mortality among the long-term unemployed. Expanding access to unemployment insurance may improve population health and reduce health inequalities associated with job loss.
      PubDate: Fri, 14 May 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab144
      Issue No: Vol. 190, No. 10 (2021)
       
  • Association Between Hurricane Sandy and Emergency Department Visits in New
           York City by Age and Cause

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      Authors: Weinberger K; Kulick E, Boehme A, et al.
      Pages: 2138 - 2147
      Abstract: AbstractThe magnitude, timing, and etiology of morbidity associated with tropical cyclones remains incompletely quantified. We examined the relative change in cause-specific emergency department (ED) visits among residents of New York City during and after Hurricane Sandy, a tropical cyclone that affected the northeastern United States in October 2012. We used quasi-Poisson constrained distributed lag models to compare the number of ED visits on and after Hurricane Sandy with all other days, 2005–2014, adjusting for temporal trends. Among residents aged ≥65 years, Hurricane Sandy was associated with a higher rate of ED visits due to injuries and poisoning (relative risk (RR) = 1.19, 95% confidence interval (CI): 1.10, 1.28), respiratory disease (RR = 1.35, 95% CI: 1.21, 1.49), cardiovascular disease (RR = 1.10, 95% CI: 1.02, 1.19), renal disease (RR = 1.44, 95% CI: 1.22, 1.72), and skin and soft tissue infections (RR = 1.20, 95% CI: 1.03, 1.39) in the first week following the storm. Among adults aged 18–64 years, Hurricane Sandy was associated with a higher rate of ED visits for renal disease (RR = 2.15, 95% CI: 1.79, 2.59). Among those aged 0–17 years, the storm was associated with lower rates of ED visits for up to 3 weeks. These results suggest that tropical cyclones might result in increased health-care utilization due to a wide range of causes, particularly among older adults.
      PubDate: Wed, 28 Apr 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab127
      Issue No: Vol. 190, No. 10 (2021)
       
  • Associations of Reduced Ambient PM2.5 Level With Lower Plasma Glucose
           Concentration and Decreased Risk of Type 2 Diabetes in Adults: A
           Longitudinal Cohort Study

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      Authors: Bo Y; Chang L, Guo C, et al.
      Pages: 2148 - 2157
      Abstract: AbstractIt remains unknown whether reduced air pollution levels can prevent type 2 diabetes mellitus. In this study, we investigated the associations between dynamic changes in long-term exposure to ambient fine particulate matter, defined as particulate matter with an aerodynamic diameter ≤2.5 μm (PM2.5), and changes in fasting plasma glucose (FPG) levels and incidence of type 2 diabetes. A total of 151,398 adults (ages ≥18 years) were recruited in Taiwan between 2001 and 2014. All participants were followed up for a mean duration of 5.0 years. Change in PM2.5 (ΔPM2.5) was defined as the value at a follow-up visit minus the corresponding value at the immediately preceding visit. The PM2.5 concentration in Taiwan increased during 2002–2004 and began to decrease in 2005. Compared with participants with little or no change in PM2.5 exposure, those with the largest decrease in PM2.5 had a decreased FPG level (β = −0.39, 95% confidence interval: −0.47, −0.32) and lower risk of type 2 diabetes (hazard ratio = 0.86, 95% confidence interval: 0.80, 0.93). The sensitivity analysis and analyses stratified by sex, age, body mass index, smoking, alcohol drinking, and hypertension generally yielded similar results. Improved PM2.5 air quality is associated with a better FPG level and a decreased risk of type 2 diabetes development.
      PubDate: Thu, 27 May 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab159
      Issue No: Vol. 190, No. 10 (2021)
       
  • Herpes Simplex Virus Type 2 Seroprevalence and Incidence and Growth of
           Ultrasound-Diagnosed Uterine Fibroids in a Large Population of Young
           African-American Women

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      Authors: Moore K; Harmon Q, Baird D.
      Pages: 2158 - 2162
      Abstract: AbstractReproductive tract infections have long been hypothesized to be risk factors for development of uterine fibroids, but few studies have investigated the issue. In our 2016 cross-sectional analysis from the Study of Environment, Lifestyle and Fibroids (2010–2018), a large Detroit, Michigan, community-based cohort study of 23- to 35-year-old African-American women with ultrasound fibroid screening, we found no association between a very prevalent reproductive tract infection, herpes simplex virus type 2 (HSV-2), and fibroids. With prospective data from the cohort (ultrasounds performed every 20 months over 5 years), we examined HSV-2’s associations with fibroid incidence (among 1,208 women who were fibroid-free at baseline) and growth (among women with fibroids at baseline or diagnosed during the study). Using Cox proportional hazards models, we computed adjusted hazard ratios and 95% confidence intervals for fibroid incidence comparing HSV-2–seropositive women with HSV-2–seronegative women. The influence of HSV-2 infection on growth was assessed on the basis of the difference in fibroid size between successive ultrasounds (1,323 growth measures) using a linear mixed model, estimating the percent difference in growth scaled to 18 months. HSV-2 seropositivity was not associated with fibroid incidence (adjusted hazard ratio = 0.88, 95% confidence interval: 0.69, 1.12) or growth (estimated growth difference = 3.1%, 95% confidence interval: −5.8, 13.0). Women can be reassured that HSV-2 infection is unlikely to increase their risk of fibroid-related health problems, given these longitudinal measures.
      PubDate: Thu, 27 May 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab160
      Issue No: Vol. 190, No. 10 (2021)
       
  • Extension of Mendelian Randomization to Identify Earliest Manifestations
           of Alzheimer Disease: Association of Genetic Risk Score for Alzheimer
           Disease With Lower Body Mass Index by Age 50 Years

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      Authors: Brenowitz W; Zimmerman S, Filshtein T, et al.
      Pages: 2163 - 2171
      Abstract: AbstractWeight loss or lower body mass index (BMI) could be an early symptom of Alzheimer disease (AD), but when this begins to emerge is difficult to estimate with traditional observational data. In an extension of Mendelian randomization, we leveraged variation in genetic risk for late-onset AD risk to estimate the causal effect of AD on BMI and the earliest ages at which AD-related weight loss (or lower BMI as a proxy) occurs. We studied UK Biobank participants enrolled in 2006–2010, who were without dementia, aged 39–73, with European genetic ancestry. BMI was calculated with measured height/weight (weight (kg)/height (m)2). An AD genetic risk score (AD-GRS) was calculated based on 23 genetic variants. Using linear regressions, we tested the association of AD-GRS with BMI, stratified by decade, and calculated the age of divergence in BMI trends between low and high AD-GRS. AD-GRS was not associated with BMI in 39- to 49-year-olds (β = 0.00, 95% confidence interval (CI): −0.03, 0.03). AD-GRS was associated with lower BMI in 50- to 59-year-olds (β = −0.03, 95% CI: −0.06, −0.01) and 60- to 73-year-olds (β = −0.09, 95% CI:−0.12, −0.07). Model-based BMI age curves for high versus low AD-GRS began to diverge after age 47 years. Sensitivity analyses found no evidence for pleiotropy or survival bias. Longitudinal replication is needed; however, our findings suggest that AD genes might begin to reduce BMI decades prior to dementia diagnosis.
      PubDate: Mon, 12 Apr 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab103
      Issue No: Vol. 190, No. 10 (2021)
       
  • Code Review as a Simple Trick to Enhance Reproducibility, Accelerate
           Learning, and Improve the Quality of Your Team’s Research

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      Authors: Vable A; Diehl S, Glymour M.
      Pages: 2172 - 2177
      Abstract: AbstractProgramming for data wrangling and statistical analysis is an essential technical tool of modern epidemiology, yet many epidemiologists receive limited formal training in strategies to optimize the quality of our code. In complex projects, coding mistakes are easy to make, even for skilled practitioners. Such mistakes can lead to invalid research claims that reduce the credibility of the field. Code review is a straightforward technique used by the software industry to reduce the likelihood of coding bugs. The systematic implementation of code review in epidemiologic research projects could not only improve science but also decrease stress, accelerate learning, contribute to team building, and codify best practices. In the present article, we argue for the importance of code review and provide some recommendations for successful implementation for 1) the research laboratory, 2) the code author (the initial programmer), and 3) the code reviewer. We outline a feasible strategy for implementation of code review, though other successful implementation processes are possible to accommodate the resources and workflows of different research groups, including other practices to improve code quality. Code review isn’t always glamorous, but it is critically important for science and reproducibility. Humans are fallible; that’s why we need code review.
      PubDate: Thu, 08 Apr 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab092
      Issue No: Vol. 190, No. 10 (2021)
       
  • Invited Commentary: Code Review—An Important Step Toward
           Reproducible Research

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      Authors: Platt R.
      Pages: 2178 - 2179
      Abstract: AbstractIn this issue of the Journal, Vable et al. (Am J Epidemiol. 2021;190(10):2172–2177) discuss a systematic approach to code review as a way to improve reproducibility in epidemiologic research. Reproducibility needs to become a cornerstone of our work. In the present commentary, I discuss some of the implications of their proposal, other methods to reduce coding mistakes, and other methods to improve reproducibility in research in general. Finally, I discuss the fact that no one of these approaches is sufficient on its own; rather, these different steps need to become part of a culture that prioritizes reproducibility in research.
      PubDate: Thu, 08 Apr 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab090
      Issue No: Vol. 190, No. 10 (2021)
       
  • Vable et al. Respond to “Code Review—A Step Toward
           Reproducibility”

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      Authors: Vable A; Diehl S, Glymour M.
      Pages: 2180 - 2180
      Abstract: We appreciate Dr. Platt’s thoughtful commentary (1) detailing many tangible things epidemiologists can do to enhance the reproducibility of their work (2). We agree that several tools are needed to address the reproducibility crisis. Code review can help mitigate just one piece of a complex problem. The first step in creating a research culture that effectively promotes reproducibility is enacting a discipline-wide commitment to this goal. We also need a shared definition of reproducibility and replication (3). Dr. Platt offers valuable additional suggestions, many of which merit much further discussion among researchers, universities, and funders regarding the feasibility of best practices and tradeoffs implicit in any workflow design decision. We consider normalizing code review as a routine component of research projects a valuable step toward such a culture.
      PubDate: Thu, 08 Apr 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab091
      Issue No: Vol. 190, No. 10 (2021)
       
  • The Use of Active Comparators in Self-Controlled Designs

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      Authors: Hallas J; Whitaker H, Delaney J, et al.
      Pages: 2181 - 2187
      Abstract: AbstractFor self-controlled studies of medication-related effects, time-varying confounding by indication can occur if the indication varies over time. We describe how active comparators might mitigate such bias, using an empirical example. Approaches to using active comparators are described for case-crossover design, case-time-control design, self-controlled case-series, and sequence symmetry analyses. In the empirical example, we used Danish data from 1996–2018 to study the association between penicillin and venous thromboembolism (VTE), using roxithromycin, a macrolide antibiotic, as comparator. Upper respiratory infection is a transient risk factor for VTE, thus representing time-dependent confounding by indication. Odds ratios for case-crossover analysis were 3.35 (95% confidence interval: 3.23, 3.49) for penicillin and 3.56 (95% confidence interval: 3.30, 3.83) for roxithromycin. We used a Wald-based method or an interaction term to estimate the odds ratio for penicillin with roxithromycin as comparator. These 2 estimates were 0.94 (95% confidence interval: 0.87, 1.03) and 1.03 (95% confidence interval: 0.95, 1.13). Results were similar for the case-time-control analysis, but both the self-controlled case-series and sequence symmetry analysis suggested a weak protective effect of penicillin, seemingly explained by VTE affecting future exposure exclusively for penicillin. The strong association of antibiotics with VTE suggests presence of confounding by indication. Such confounding can be mitigated by using an active comparator.
      PubDate: Fri, 16 Apr 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab110
      Issue No: Vol. 190, No. 10 (2021)
       
  • Hypothesis Generation During Foodborne-Illness Outbreak Investigations

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      Authors: White A; Smith K, Booth H, et al.
      Pages: 2188 - 2197
      Abstract: AbstractHypothesis generation is a critical, but challenging, step in a foodborne outbreak investigation. The pathogens that contaminate food have many diverse reservoirs, resulting in seemingly limitless potential vehicles. Identifying a vehicle is particularly challenging for clusters detected through national pathogen-specific surveillance, because cases can be geographically dispersed and lack an obvious epidemiologic link. Moreover, state and local health departments could have limited resources to dedicate to cluster and outbreak investigations. These challenges underscore the importance of hypothesis generation during an outbreak investigation. In this review, we present a framework for hypothesis generation focusing on 3 primary sources of information, typically used in combination: 1) known sources of the pathogen causing illness; 2) person, place, and time characteristics of cases associated with the outbreak (descriptive data); and 3) case exposure assessment. Hypothesis generation can narrow the list of potential food vehicles and focus subsequent epidemiologic, laboratory, environmental, and traceback efforts, ensuring that time and resources are used more efficiently and increasing the likelihood of rapidly and conclusively implicating the contaminated food vehicle.
      PubDate: Tue, 20 Apr 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab118
      Issue No: Vol. 190, No. 10 (2021)
       
  • Comparison of 2 Case Definitions for Ascertaining the Prevalence of Autism
           Spectrum Disorder Among 8-Year-Old Children

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      Authors: Maenner M; Graves S, Peacock G, et al.
      Pages: 2198 - 2207
      Abstract: AbstractThe Autism and Developmental Disabilities Monitoring (ADDM) Network conducts population-based surveillance of autism spectrum disorder (ASD) among 8-year-old children in multiple US communities. From 2000 to 2016, investigators at ADDM Network sites classified ASD from collected text descriptions of behaviors from medical and educational evaluations which were reviewed and coded by ADDM Network clinicians. It took at least 4 years to publish data from a given surveillance year. In 2018, we developed an alternative case definition utilizing ASD diagnoses or classifications made by community professionals. Using data from surveillance years 2014 and 2016, we compared the new and previous ASD case definitions. Compared with the prevalence based on the previous case definition, the prevalence based on the new case definition was similar for 2014 and slightly lower for 2016. Sex and race/ethnicity prevalence ratios were nearly unchanged. Compared with the previous case definition, the new case definition’s sensitivity was 86% and its positive predictive value was 89%. The new case definition does not require clinical review and collects about half as much data, yielding more timely reporting. It also more directly measures community identification of ASD, thus allowing for more valid comparisons among communities, and reduces resource requirements while retaining measurement properties similar to those of the previous definition.
      PubDate: Tue, 13 Apr 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab106
      Issue No: Vol. 190, No. 10 (2021)
       
  • Development and Validation of a Large Synthetic Cohort for the Study of
           Cardiovascular Health Across the Life Span

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      Authors: Ning H; Krefman A, Zhao L, et al.
      Pages: 2208 - 2219
      Abstract: AbstractWe developed and validated a synthetic cohort approach to examine numbers of cardiovascular risk factors (CRFs) and adverse clinical events, including incident cardiovascular disease and all-cause mortality, across the life span from ages 20 years to 90 years. The current analysis included 40,875 participants from 7 large, population-based longitudinal epidemiologic studies (1948–2016). On the basis of a joint multilevel imputation model, we multiply imputed each participant’s life-span numbers of CRFs and events using available records. To validate the imputed values, we partially removed the observed data and then compared the imputed and observed values. The complete life-span synthetic data set reflected the original observed data trends well. In our validation sample, the distributions of imputed CRFs and events were close to the observed distributions but with less variability. Bland-Altman plots indicated that there was a slightly negative trend in general, and the agreement bias was relatively small for the continuous CRFs. The hypothetical linear regression model suggested that the relationships between the CRFs and events were preserved in the imputed data set. This approach generated valid estimates of CRFs and events across the life span for African-American and White participants. The synthetic cohort may be sufficiently accurate to be useful in assessing the origins and timing of accumulating cardiovascular risk that can inform efforts to avoid cardiovascular disease development.
      PubDate: Wed, 12 May 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab137
      Issue No: Vol. 190, No. 10 (2021)
       
  • The Longitudinal Association Between Retirement and Depression: A
           Systematic Review and Meta-Analysis

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      Authors: Li W; Ye X, Zhu D, et al.
      Pages: 2220 - 2230
      Abstract: AbstractThe purpose of this study was to collect evidence of the relationship between retirement and depression through meta-analysis and further analyze the heterogeneity of results. The quality of the studies was rated based on 10 predefined criteria. We searched for articles published between 1980 and 2020, and a total of 25 longitudinal studies were included in the meta-analysis. The meta-analysis results showed that retirement was associated with more depressive symptoms (d = 0.044, 95% confidence interval (CI): 0.008, 0.080). The association of more depressive symptoms with involuntary retirement (d = 0.180, 95% CI: 0.061, 0.299) was stronger than with voluntary retirement (d = 0.086, 95% CI: −0.018, 0.190) and regulatory retirement (d = 0.009, 95% CI: −0.079, 0.097). Retirement was significantly associated with more depressive symptoms in Eastern developed countries (d = 0.126, 95% CI: 0.041, 0.210), and the association was stronger than that in Western developed countries (d = 0.016, 95% CI: −0.023, 0.055). We found that the transition to retirement was associated with higher risk of depression, and this association varied by the type of retirement and country. Further empirical studies are needed to explore the mechanism of retirement and depression and whether such an association is linked with socioeconomic position.
      PubDate: Thu, 29 Apr 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab125
      Issue No: Vol. 190, No. 10 (2021)
       
  • ON THE USE OF NONPARAMETRIC BOUNDS FOR CAUSAL EFFECTS IN NULL RANDOMIZED
           TRIALS

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      Authors: Gabriel E; Sachs M.
      Pages: 2231 - 2231
      Abstract: The goal of randomized experiments is to estimate the causal effect of an intervention on a clinically relevant outcome. When study subjects are missing outcome information due to factors related to the intervention, compliance, or the outcome, the causal effect is not identifiable from the observed data alone (1). When there is no missing data, randomization allows identification of the effect of assignment to the intervention, sometimes called the intent-to-treat effect; this is only equivalent to the intervention effect if subjects comply with their assigned intervention as directed. When this is not the case, the intervention effect is nonidentifiable, even with no missing data, without making additional assumptions (2).
      PubDate: Fri, 21 May 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab153
      Issue No: Vol. 190, No. 10 (2021)
       
  • RE: THE ASSOCIATION BETWEEN AGE AT INITIATION OF ALCOHOL CONSUMPTION AND
           TYPE 2 DIABETES MELLITUS: A COHORT STUDY OF 0.5 MILLION PERSONS IN CHINA

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      Authors: Wilson A.
      Pages: 2233 - 2233
      Abstract: I read with interest the article “The Association Between Age at Initiation of Alcohol Consumption and Type 2 Diabetes Mellitus: A Cohort Study of 0.5 Million Persons in China”, (1), which was recently published in the American Journal of Epidemiology. The article was based on data from the China Kadoorie Biobank, and it looked at the unknown association between early age of initiation of alcohol consumption and the development of type 2 diabetes. The article was well-written and provided a clear understanding of the study and its findings; however, I would like to make some contributions.
      PubDate: Thu, 08 Apr 2021 00:00:00 GMT
      DOI: 10.1093/aje/kwab094
      Issue No: Vol. 190, No. 10 (2021)
       
 
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