{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:12:37Z","timestamp":1772169157318,"version":"3.50.1"},"reference-count":28,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T00:00:00Z","timestamp":1587945600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Trust","award":["101143"],"award-info":[{"award-number":["101143"]}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background:<\/ns4:bold>\n                    Mice receiving angiotensin converting enzyme inhibitor (ACEI) drugs show increased susceptibility to infection by\n                    <ns4:italic>Staphylococcus aureus<\/ns4:italic>\n                    (\n                    <ns4:italic>S. aureus<\/ns4:italic>\n                    ). We sought to investigate whether humans using ACEI were at increased risk of\n                    <ns4:italic>S. aureus<\/ns4:italic>\n                    infection, comparing them to users of Angiotensin II Receptor Blockers (ARB) with multiple control outcomes to assess the potential for residual confounding.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    Using the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics between 1997 and 2017, we identified adults starting ACEI or ARB (as an active comparator drug). We regarded prescription of ACEI or ARB as time-dependent exposure and used a Cox regression model to compare incidence of first hospitalisation with infection due to\n                    <ns4:italic>S. aureus<\/ns4:italic>\n                    in periods with ACEI to periods with ARB prescriptions. We repeated the analysis using control outcomes that we did not expect to be associated with use of ACEI versus ARB (Gram-negative sepsis, hip fracture and herpes zoster) and one that we did (dry cough).\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results:<\/ns4:bold>\n                    We identified 445,341 new users of ACEI (mean age 64.0\u00b114.0, male 51.7%) and 41,824 new users of ARB (mean age 64.1\u00b114.0, male 45.5%). The fully adjusted hazard ratio for\n                    <ns4:italic>S. aureus<\/ns4:italic>\n                    infection (ACEI vs. ARB) was 1.18 (95% CI 1.10\u20131.27), consistent across sensitivity analyses. However, we also found associations with all control outcomes; rates of Gram-negative sepsis, hip fracture and dry cough were also increased during periods of time treated with ACEI compared to ARB while herpes zoster was more common during time treated with ARB.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions:<\/ns4:bold>\n                    Our results suggest that although ARB users appear an ideal control for analyses of ACEI effects, there is residual confounding even after multivariable adjustment. This has implications for observational analyses comparing users of these drug classes, in particular the effect of these drugs in relation to COVID-19 infection.\n                  <\/ns4:p>","DOI":"10.12688\/wellcomeopenres.15873.1","type":"journal-article","created":{"date-parts":[[2020,4,27]],"date-time":"2020-04-27T13:38:01Z","timestamp":1587994681000},"page":"77","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparisons of Staphylococcus aureus infection and other outcomes between users of angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers: lessons for COVID-19 from a nationwide cohort study"],"prefix":"10.12688","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7644-2030","authenticated-orcid":false,"given":"Patrick","family":"Bidulka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7079-0640","authenticated-orcid":false,"given":"Masao","family":"Iwagami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn E.","family":"Mansfield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fotini","family":"Kalogirou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8618-7333","authenticated-orcid":false,"given":"Angel Y. S.","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian J.","family":"Douglas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9168-6022","authenticated-orcid":false,"given":"Liam","family":"Smeeth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7269-2873","authenticated-orcid":false,"given":"Charlotte","family":"Summers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8848-9493","authenticated-orcid":false,"given":"Laurie A.","family":"Tomlinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2020,4,27]]},"reference":[{"key":"ref-1","article-title":"Hypertension in 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.17410.r38536, Daniel Morales, Population Health and Genomics Division, University of Dundee, Dundee, UK, 20 May 2020, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-77\/v1#referee-response-38536","order":0,"name":"referee-response-38536","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.17410.r38729, Chien-Chang Lee, Wan-Ting Hsu, Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan, 29 May 2020, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-77\/v1#referee-response-38729","order":1,"name":"referee-response-38729","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Laurie Tomlinson<\/b>; \n<i>Posted: 29 May 2020<\/i>; We thank the reviewers very much for their review, and for drawing our attention to their relevant paper. We agree that we must be cautious about extrapolating our results to the current pandemic: however our attention with the paper was merely to discuss potential epidemiological pitfalls and considerations related to comparisons of these drugs in future work. Therefore the aim of the title was to highlight its relevance in this time when information needs to be accessed quickly.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-77\/v1#referee-comment-4193","order":2,"name":"referee-comment-4193","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by Wellcome [101143; Intermediate Clinical Fellowship to LT]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}