Pharmacoepidemiology, Machine Learning and COVID-19: An intent-to-treat analysis of hydroxychloroquine, with or without azithromycin, and COVID-19 outcomes amongst hospitalized US Veterans

{ 'indexed': {'date-parts': [[2023, 12, 9]], 'date-time': '2023-12-09T06:23:04Z', 'timestamp': 1702102984905}, 'reference-count': 57, 'publisher': 'Oxford University Press (OUP)', 'issue': '11', 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'published-print': {'date-parts': [[2021, 11, 2]]}, 'abstract': '<jats:title>Abstract</jats:title>\n' ' <jats:p>Hydroxychloroquine (HCQ) was proposed as an early therapy for ' 'coronavirus disease 2019 (COVID-19) after in vitro studies indicated possible benefit. ' 'Previous in vivo observational studies have presented conflicting results, though recent ' 'randomized clinical trials have reported no benefit from HCQ among patients hospitalized with ' 'COVID-19. We examined the effects of HCQ alone and in combination with azithromycin in a ' 'hospitalized population of US veterans with COVID-19, using a propensity score–adjusted ' 'survival analysis with imputation of missing data. According to electronic health record data ' 'from the US Department of Veterans Affairs health care system, 64,055 US Veterans were tested ' 'for the virus that causes COVID-19 between March 1, 2020 and April 30, 2020. Of the 7,193 ' 'veterans who tested positive, 2,809 were hospitalized, and 657 individuals were prescribed ' 'HCQ within the first 48-hours of hospitalization for the treatment of COVID-19. There was no ' 'apparent benefit associated with HCQ receipt, alone or in combination with azithromycin, and ' 'there was an increased risk of intubation when HCQ was used in combination with azithromycin ' '(hazard ratio = 1.55; 95% confidence interval: 1.07, 2.24). In conclusion, we assessed the ' 'effectiveness of HCQ with or without azithromycin in treatment of patients hospitalized with ' 'COVID-19, using a national sample of the US veteran population. Using rigorous study design ' 'and analytic methods to reduce confounding and bias, we found no evidence of a survival ' 'benefit from the administration of HCQ.</jats:p>', 'DOI': '10.1093/aje/kwab183', 'type': 'journal-article', 'created': {'date-parts': [[2021, 6, 21]], 'date-time': '2021-06-21T19:13:37Z', 'timestamp': 1624302817000}, 'page': '2405-2419', 'source': 'Crossref', 'is-referenced-by-count': 5, 'title': 'Pharmacoepidemiology, Machine Learning, and COVID-19: An Intent-to-Treat Analysis of ' 'Hydroxychloroquine, With or Without Azithromycin, and COVID-19 Outcomes Among Hospitalized US ' 'Veterans', 'prefix': '10.1093', 'volume': '190', 'author': [ {'given': 'Hanna', 'family': 'Gerlovin', 'sequence': 'first', 'affiliation': []}, {'given': 'Daniel C', 'family': 'Posner', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yuk-Lam', 'family': 'Ho', 'sequence': 'additional', 'affiliation': []}, {'given': 'Christopher T', 'family': 'Rentsch', 'sequence': 'additional', 'affiliation': []}, {'given': 'Janet P', 'family': 'Tate', 'sequence': 'additional', 'affiliation': []}, { 'suffix': 'Jr.', 'given': 'Joseph T', 'family': 'King', 'sequence': 'additional', 'affiliation': []}, {'given': 'Katherine E', 'family': 'Kurgansky', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ioana', 'family': 'Danciu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Lauren', 'family': 'Costa', 'sequence': 'additional', 'affiliation': []}, {'given': 'Franciel A', 'family': 'Linares', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ian D', 'family': 'Goethert', 'sequence': 'additional', 'affiliation': []}, {'given': 'Daniel A', 'family': 'Jacobson', 'sequence': 'additional', 'affiliation': []}, {'given': 'Matthew S', 'family': 'Freiberg', 'sequence': 'additional', 'affiliation': []}, {'given': 'Edmon', 'family': 'Begoli', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sumitra', 'family': 'Muralidhar', 'sequence': 'additional', 'affiliation': []}, {'given': 'Rachel B', 'family': 'Ramoni', 'sequence': 'additional', 'affiliation': []}, {'given': 'Georgia', 'family': 'Tourassi', 'sequence': 'additional', 'affiliation': []}, {'given': 'J Michael', 'family': 'Gaziano', 'sequence': 'additional', 'affiliation': []}, {'given': 'Amy C', 'family': 'Justice', 'sequence': 'additional', 'affiliation': []}, {'given': 'David R', 'family': 'Gagnon', 'sequence': 'additional', 'affiliation': []}, {'given': 'Kelly', 'family': 'Cho', 'sequence': 'additional', 'affiliation': []}], 'member': '286', 'published-online': {'date-parts': [[2021, 6, 24]]}, 'reference': [ { 'key': '2021110206552741700_ref1', 'doi-asserted-by': 'crossref', 'DOI': '10.1016/j.micpath.2020.104228', 'article-title': 'In vitro testing of combined hydroxychloroquine and azithromycin on ' 'SARS-CoV-2 shows synergistic effect', 'volume': '145', 'author': 'Andreani', 'year': '2020', 'journal-title': 'Microb Pathog'}, { 'issue': '6485', 'key': '2021110206552741700_ref2', 'doi-asserted-by': 'crossref', 'first-page': '1412', 'DOI': '10.1126/science.367.6485.1412', 'article-title': 'Race to find COVID-19 treatments accelerates', 'volume': '367', 'author': 'Kupferschmidt', 'year': '2020', 'journal-title': 'Science'}, { 'issue': '3', 'key': '2021110206552741700_ref3', 'doi-asserted-by': 'crossref', 'DOI': '10.1016/j.ijantimicag.2020.106078', 'article-title': 'A pharmacological perspective of chloroquine in SARS-CoV-2 infection: ' 'an old drug for the fight against a new coronavirus?', 'volume': '56', 'author': 'Oscanoa', 'year': '2020', 'journal-title': 'Int J Antimicrob Agents'}, { 'issue': '6', 'key': '2021110206552741700_ref4', 'doi-asserted-by': 'crossref', 'first-page': '715', 'DOI': '10.1007/s13318-020-00640-6', 'article-title': 'Pharmacokinetic basis of the hydroxychloroquine response in COVID-19: ' 'implications for therapy and prevention', 'volume': '45', 'author': 'Tarek', 'year': '2020', 'journal-title': 'Eur J Drug Metab Pharmacokinet'}, {'key': '2021110206552741700_ref5', 'author': 'Bright'}, {'key': '2021110206552741700_ref6', 'author': 'Disbrow'}, { 'key': '2021110206552741700_ref7', 'article-title': 'FDA drug safety communication: FDA cautions against use of ' 'hydroxychloroquine or chloroquine for COVID-19 outside of the hospital ' 'setting or a clinical trial due to risk of heart rhythm problems', 'author': 'US Food Drug Administration', 'year': '24, 2020'}, {'key': '2021110206552741700_ref8', 'author': 'Kiley', 'year': '20, 2020'}, {'key': '2021110206552741700_ref9', 'author': 'Recovery Collaborative Group'}, { 'key': '2021110206552741700_ref10', 'author': 'World Health Organization', 'year': '4, 2020'}, { 'key': '2021110206552741700_ref11', 'article-title': 'Repurposed antiviral drugs for COVID-19—interim WHO SOLIDARITY trial ' 'results', 'author': 'Pan', 'year': '2020'}, { 'issue': '21', 'key': '2021110206552741700_ref12', 'doi-asserted-by': 'crossref', 'first-page': '2030', 'DOI': '10.1056/NEJMoa2022926', 'article-title': 'Effect of hydroxychloroquine in hospitalized patients with Covid-19', 'volume': '383', 'author': 'Recovery Collaborative Group', 'year': '2020', 'journal-title': 'N Engl J Med'}, { 'issue': '21', 'key': '2021110206552741700_ref13', 'doi-asserted-by': 'crossref', 'first-page': '2165', 'DOI': '10.1001/jama.2020.22240', 'article-title': 'Effect of hydroxychloroquine on clinical status at 14 days in ' 'hospitalized patients with COVID-19: a randomized clinical trial', 'volume': '324', 'author': 'Self', 'year': '2020', 'journal-title': 'JAMA'}, { 'issue': '25', 'key': '2021110206552741700_ref14', 'doi-asserted-by': 'crossref', 'first-page': '1878', 'DOI': '10.1056/NEJM200006223422506', 'article-title': 'A comparison of observational studies and randomized, controlled trials', 'volume': '342', 'author': 'Benson', 'year': '2000', 'journal-title': 'N Engl J Med'}, { 'key': '2021110206552741700_ref15', 'doi-asserted-by': 'crossref', 'first-page': '120', 'DOI': '10.1016/j.jclinepi.2020.04.016', 'article-title': 'COVID-19 coronavirus research has overall low methodological quality ' 'thus far: case in point for chloroquine/hydroxychloroquine', 'volume': '123', 'author': 'Alexander', 'year': '2020', 'journal-title': 'J Clin Epidemiol'}, { 'issue': '1', 'key': '2021110206552741700_ref16', 'doi-asserted-by': 'crossref', 'first-page': '19', 'DOI': '10.1016/j.cmi.2020.08.022', 'article-title': 'Effect of hydroxychloroquine with or without azithromycin on the ' 'mortality of coronavirus disease 2019 (COVID-19) patients: a systematic ' 'review and meta-analysis', 'volume': '27', 'author': 'Fiolet', 'year': '2021', 'journal-title': 'Clin Microbiol Infect'}, { 'issue': '4', 'key': '2021110206552741700_ref17', 'doi-asserted-by': 'crossref', 'first-page': '589', 'DOI': '10.1016/j.dsx.2020.05.017', 'article-title': 'Hydroxychloroquine in patients with COVID-19: a systematic review and ' 'meta-analysis', 'volume': '14', 'author': 'Singh', 'year': '2020', 'journal-title': 'Diabetes Metab Syndr'}, { 'issue': '4', 'key': '2021110206552741700_ref18', 'doi-asserted-by': 'crossref', 'first-page': '287', 'DOI': '10.7326/M20-2496', 'article-title': 'Hydroxychloroquine or chloroquine for treatment or prophylaxis of ' 'COVID-19: a living systematic review', 'volume': '173', 'author': 'Hernandez', 'year': '2020', 'journal-title': 'Ann Intern Med'}, { 'key': '2021110206552741700_ref19', 'doi-asserted-by': 'crossref', 'DOI': '10.1016/j.lfs.2020.117775', 'article-title': 'Masand N. A systematic review on use of aminoquinolines for the ' 'therapeutic management of COVID-19: efficacy, safety and clinical ' 'trials', 'volume': '254', 'author': 'Patil', 'year': '2020', 'journal-title': 'Life Sci'}, { 'key': '2021110206552741700_ref20', 'first-page': '114', 'volume-title': 'Med (N Y)', 'author': 'Magagnoli', 'year': '2020'}, { 'issue': '12', 'key': '2021110206552741700_ref21', 'doi-asserted-by': 'crossref', 'first-page': '819', 'DOI': '10.7326/M20-1223', 'article-title': 'A rush to judgment? Rapid reporting and dissemination of results and ' 'its consequences regarding the use of hydroxychloroquine for COVID-19', 'volume': '172', 'author': 'Kim', 'year': '2020', 'journal-title': 'Ann Intern Med'}, { 'issue': '8', 'key': '2021110206552741700_ref22', 'doi-asserted-by': 'crossref', 'first-page': '825', 'DOI': '10.1002/pds.5029', 'article-title': 'Considerations for pharmacoepidemiological analyses in the SARS-CoV-2 ' 'pandemic', 'volume': '29', 'author': 'Pottegård', 'year': '2020', 'journal-title': 'Pharmacoepidemiol Drug Saf'}, { 'issue': '9', 'key': '2021110206552741700_ref23', 'doi-asserted-by': 'crossref', 'first-page': '1145', 'DOI': '10.1001/jamainternmed.2020.2402', 'article-title': 'Need for transparency and reliable evidence in emergency use ' 'authorizations for coronavirus disease 2019 (COVID-19) therapies', 'volume': '180', 'author': 'Zhai', 'year': '2020', 'journal-title': 'JAMA Intern Med'}, { 'issue': '3', 'key': '2021110206552741700_ref24', 'doi-asserted-by': 'crossref', 'first-page': '399', 'DOI': '10.1080/00273171.2011.568786', 'article-title': 'An introduction to propensity score methods for reducing the effects of ' 'confounding in observational studies', 'volume': '46', 'author': 'Austin', 'year': '2011', 'journal-title': 'Multivariate Behav Res'}, { 'issue': '3', 'key': '2021110206552741700_ref25', 'doi-asserted-by': 'crossref', 'first-page': '337', 'DOI': '10.1002/sim.3782', 'article-title': 'Improving propensity score weighting using machine learning', 'volume': '29', 'author': 'Lee', 'year': '2010', 'journal-title': 'Stat Med'}, { 'issue': '4', 'key': '2021110206552741700_ref26', 'doi-asserted-by': 'crossref', 'first-page': '403', 'DOI': '10.1037/1082-989X.9.4.403', 'article-title': 'Propensity score estimation with boosted regression for evaluating ' 'causal effects in observational studies', 'volume': '9', 'author': 'McCaffrey', 'year': '2004', 'journal-title': 'Psychol Methods'}, { 'issue': '6', 'key': '2021110206552741700_ref27', 'doi-asserted-by': 'crossref', 'first-page': '802', 'DOI': '10.1097/EDE.0000000000000734', 'article-title': 'The right tool for the job: choosing between covariate-balancing and ' 'generalized boosted model propensity scores', 'volume': '28', 'author': 'Setodji', 'year': '2017', 'journal-title': 'Epidemiology'}, { 'issue': '3', 'key': '2021110206552741700_ref28', 'doi-asserted-by': 'crossref', 'first-page': '360', 'DOI': '10.1016/j.gie.2019.04.236', 'article-title': 'Propensity score methods to control for confounding in observational ' 'cohort studies: a statistical primer and application to endoscopy ' 'research', 'volume': '90', 'author': 'Yang', 'year': '2019', 'journal-title': 'Gastrointest Endosc'}, { 'issue': '8', 'key': '2021110206552741700_ref29', 'doi-asserted-by': 'crossref', 'first-page': '826', 'DOI': '10.1016/j.jclinepi.2009.11.020', 'article-title': 'Propensity score estimation: machine learning and classification ' 'methods as alternatives to logistic regression', 'volume': '63', 'author': 'Westreich', 'year': '2011', 'journal-title': 'J Clin Epidemiol'}, { 'issue': '6', 'key': '2021110206552741700_ref30', 'doi-asserted-by': 'crossref', 'first-page': '398', 'DOI': '10.7326/M18-3079', 'article-title': 'Graphical depiction of longitudinal study designs in health care ' 'databases', 'volume': '170', 'author': 'Schneeweiss', 'year': '2019', 'journal-title': 'Ann Intern Med'}, { 'key': '2021110206552741700_ref31', 'article-title': 'A natural language processing system for national COVID-19 surveillance ' 'in the US Department of Veterans Affairs', 'author': 'Chapman', 'year': '2020'}, { 'issue': '1', 'key': '2021110206552741700_ref32', 'doi-asserted-by': 'crossref', 'first-page': '2', 'DOI': '10.1186/1478-7954-4-2', 'article-title': 'Accuracy and completeness of mortality data in the Department of ' 'Veterans Affairs', 'volume': '4', 'author': 'Sohn', 'year': '2006', 'journal-title': 'Popul Health Metr'}, { 'issue': '8', 'key': '2021110206552741700_ref33', 'doi-asserted-by': 'crossref', 'first-page': '1257', 'DOI': '10.1093/gerona/gly232', 'article-title': 'The burden of frailty among U.S. veterans and its association with ' 'mortality, 2002–2012', 'volume': '74', 'author': 'Orkaby', 'year': '2019', 'journal-title': 'J Gerontol A Biol Sci Med Sci'}, { 'key': '2021110206552741700_ref34', 'volume-title': 'R: A Language and Environment for Statistical Computing, release 3.6.1', 'author': 'R Core Team', 'year': '2019'}, { 'key': '2021110206552741700_ref35', 'doi-asserted-by': 'crossref', 'first-page': '92', 'DOI': '10.1016/j.csda.2013.10.025', 'article-title': 'Recursive partitioning for missing data imputation in the presence of ' 'interaction effects', 'volume': '72', 'author': 'Doove', 'year': '2014', 'journal-title': 'Comput Stat Data Anal'}, { 'key': '2021110206552741700_ref36', 'doi-asserted-by': 'crossref', 'article-title': 'Mice: multivariate imputation by chained equations', 'author': 'Buuren', 'DOI': '10.18637/jss.v045.i03'}, { 'issue': '4', 'key': '2021110206552741700_ref37', 'doi-asserted-by': 'crossref', 'first-page': '585', 'DOI': '10.1002/sim.4780100410', 'article-title': 'Multiple imputation in health-care databases: an overview and some ' 'applications', 'volume': '10', 'author': 'Rubin', 'year': '1991', 'journal-title': 'Stat Med'}, { 'key': '2021110206552741700_ref38', 'first-page': '1', 'volume-title': 'In: The Elements of Statistical Learning. Springer Series in Statistics', 'author': 'Hastie', 'year': '2009'}, { 'key': '2021110206552741700_ref39', 'article-title': 'Gbm: generalized boosted regression models', 'author': 'Greenwell'}, { 'key': '2021110206552741700_ref40', 'article-title': 'WeightIt: weighting for covariate balance in observational studies', 'author': 'Greifer'}, { 'key': '2021110206552741700_ref41', 'article-title': 'Cobalt: covariate balance tables and plots', 'author': 'Greifer'}, { 'issue': 'Dec', 'key': '2021110206552741700_ref42', 'first-page': '21', 'article-title': 'Gradient boosting machines, a tutorial', 'volume': '7', 'author': 'Natekin', 'year': '2013', 'journal-title': 'Front Neurorobot'}, { 'key': '2021110206552741700_ref43', 'article-title': 'Survival: a package for survival analysis in S', 'author': 'Therneau'}, { 'issue': '19', 'key': '2021110206552741700_ref44', 'doi-asserted-by': 'crossref', 'first-page': '3388', 'DOI': '10.1002/sim.5753', 'article-title': 'A tutorial on propensity score estimation for multiple treatments using ' 'generalized boosted models', 'volume': '32', 'author': 'McCaffrey', 'year': '2013', 'journal-title': 'Stat Med'}, { 'issue': '12', 'key': '2021110206552741700_ref45', 'doi-asserted-by': 'crossref', 'first-page': '1513', 'DOI': '10.1002/pds.4325', 'article-title': 'Comparison of the ability of double-robust estimators to correct bias ' 'in propensity score matching analysis. A Monte Carlo simulation study', 'volume': '26', 'author': 'Nguyen', 'year': '2017', 'journal-title': 'Pharmacoepidemiol Drug Saf.'}, {'key': '2021110206552741700_ref46'}, { 'issue': '28', 'key': '2021110206552741700_ref47', 'doi-asserted-by': 'crossref', 'first-page': '3661', 'DOI': '10.1002/sim.6607', 'article-title': 'Moving towards best practice when using inverse probability of ' 'treatment weighting (IPTW) using the propensity score to estimate ' 'causal treatment effects in observational studies', 'volume': '34', 'author': 'Austin', 'year': '2015', 'journal-title': 'Stat Med'}, { 'issue': '24', 'key': '2021110206552741700_ref48', 'doi-asserted-by': 'crossref', 'first-page': '2493', 'DOI': '10.1001/jama.2020.8630', 'article-title': 'Association of treatment with hydroxychloroquine or azithromycin with ' 'in-hospital mortality in patients with COVID-19 in New York state', 'volume': '323', 'author': 'Rosenberg', 'year': '2020', 'journal-title': 'JAMA'}, { 'issue': '10', 'key': '2021110206552741700_ref49', 'doi-asserted-by': 'crossref', 'first-page': '1514', 'DOI': '10.1158/2159-8290.CD-20-0941', 'article-title': 'Utilization of COVID-19 treatments and clinical outcomes among patients ' 'with cancer: a COVID-19 and Cancer Consortium (CCC19) cohort study', 'volume': '10', 'author': 'Rivera', 'year': '2020', 'journal-title': 'Cancer Discov'}, { 'key': '2021110206552741700_ref50', 'doi-asserted-by': 'crossref', 'article-title': 'Hydroxychloroquine with or without azithromycin and in-hospital ' 'mortality or discharge in patients hospitalized for COVID-19 infection: ' 'a cohort study of 4,642 in-patients in France', 'author': 'Sbidian', 'year': '2020', 'DOI': '10.1101/2020.06.16.20132597'}, { 'issue': '0', 'key': '2021110206552741700_ref51', 'doi-asserted-by': 'crossref', 'first-page': '396', 'DOI': '10.1016/j.ijid.2020.06.099', 'article-title': 'Treatment with hydroxychloroquine, azithromycin, and combination in ' 'patients hospitalized with COVID-19', 'volume': '97', 'author': 'Arshad', 'year': '2020', 'journal-title': 'Int J Infect Dis'}, { 'key': '2021110206552741700_ref52', 'doi-asserted-by': 'crossref', 'first-page': '216', 'DOI': '10.1016/j.ijid.2020.06.095', 'article-title': 'An observational cohort study of hydroxychloroquine and azithromycin ' "for COVID-19: (can't get no) satisfaction", 'volume': '98', 'author': 'Lee', 'year': '2020', 'journal-title': 'Int J Infect Dis'}, {'key': '2021110206552741700_ref53', 'volume-title': 'Catalogue of Bias 2017', 'author': ''}, { 'issue': '35', 'key': '2021110206552741700_ref54', 'doi-asserted-by': 'crossref', 'first-page': '1210', 'DOI': '10.15585/mmwr.mm6935a4', 'article-title': 'Hydroxychloroquine and chloroquine prescribing patterns by provider ' 'specialty following initial reports of potential benefit for COVID-19 ' 'treatment - United States, January-June 2020', 'volume': '69', 'author': 'Bull-Otterson', 'year': '2020', 'journal-title': 'MMWR Morb Mortal Wkly Rep'}, { 'issue': '9', 'key': '2021110206552741700_ref55', 'doi-asserted-by': 'crossref', 'DOI': '10.1371/journal.pmed.1003379', 'article-title': 'Patterns of COVID-19 testing and mortality by race and ethnicity among ' 'United States veterans: a nationwide cohort study', 'volume': '17', 'author': 'Rentsch', 'year': '2020', 'journal-title': 'PLoS Med'}, { 'issue': '25', 'key': '2021110206552741700_ref56', 'doi-asserted-by': 'crossref', 'first-page': '2411', 'DOI': '10.1056/NEJMoa2012410', 'article-title': 'Observational study of hydroxychloroquine in hospitalized patients with ' 'Covid-19', 'volume': '382', 'author': 'Geleris', 'year': '2020', 'journal-title': 'N Engl J Med'}, { 'issue': '1', 'key': '2021110206552741700_ref57', 'doi-asserted-by': 'crossref', 'first-page': '5', 'DOI': '10.1177/1740774507087703', 'article-title': 'Estimating effects from randomized trials with discontinuations: the ' 'need for intent-to-treat design and G-estimation', 'volume': '5', 'author': 'Greenland', 'year': '2008', 'journal-title': 'Clin Trials'}], 'container-title': 'American Journal of Epidemiology', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'http://academic.oup.com/aje/advance-article-pdf/doi/10.1093/aje/kwab183/40436006/kwab183.pdf', 'content-type': 'application/pdf', 'content-version': 'am', 'intended-application': 'syndication'}, { 'URL': 'http://academic.oup.com/aje/article-pdf/190/11/2405/41025403/kwab183.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'syndication'}, { 'URL': 'http://academic.oup.com/aje/article-pdf/190/11/2405/41025403/kwab183.pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2021, 11, 2]], 'date-time': '2021-11-02T06:56:36Z', 'timestamp': 1635836196000}, 'score': 1, 'resource': {'primary': {'URL': 'https://academic.oup.com/aje/article/190/11/2405/6308675'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2021, 6, 24]]}, 'references-count': 57, 'journal-issue': { 'issue': '11', 'published-online': {'date-parts': [[2021, 6, 24]]}, 'published-print': {'date-parts': [[2021, 11, 2]]}}, 'URL': 'http://dx.doi.org/10.1093/aje/kwab183', 'relation': {}, 'ISSN': ['0002-9262', '1476-6256'], 'subject': ['Epidemiology'], 'published-other': {'date-parts': [[2021, 11]]}, 'published': {'date-parts': [[2021, 6, 24]]}}