{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:39:50Z","timestamp":1791581990915,"version":"4.3.4"},"reference-count":21,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n High-dose inactivated influenza vaccine (HD-IIV) was developed to enhance immune responses in older adults and has demonstrated superior protection against laboratory-confirmed influenza (LCI) and severe outcomes vs standard-dose inactivated influenza vaccine (SD-IIV). A comprehensive meta-analysis of recent large-scale trials is warranted.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To synthesize all evidence from randomized clinical trials comparing HD-IIV with SD-IIV for prevention of hospitalization events and mortality in older adults.<\/jats:p>\n <\/jats:sec>\n \n Data Sources<\/jats:title>\n Studies published between December 31, 2009, and September 15, 2025, on PubMed and Embase. Additional data were obtained from trial sponsors.<\/jats:p>\n <\/jats:sec>\n \n Study Selection<\/jats:title>\n Randomized clinical trials comparing HD-IIV with SD-IIV in older adults during at least 1 influenza season were eligible.<\/jats:p>\n <\/jats:sec>\n \n Data Extraction and Synthesis<\/jats:title>\n Two reviewers independently screened studies, extracted data, and assessed risk of bias according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. Unpublished subgroup and outcome data were obtained to enable detailed analyses. Combined relative vaccine effectiveness (rVE) estimates were calculated with fixed-effects models, with sensitivity analyses using random-effects models.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Hospitalizations for influenza, LCI, pneumonia or influenza, cardiorespiratory disease, and all causes and all-cause mortality. Primary analyses included adults 65 years or older, and secondary analyses included prespecified subgroups by age and cardiovascular disease.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Eight randomized clinical trials including 605\u202f098 participants were identified, with 5 enrolling older adults from the general population (aged \u226565 years), 2 enrolling nursing home residents (aged \u226565 years), and 1 enrolling patients with cardiovascular disease. Compared with SD-IIV, HD-IIV was associated with significantly reduced hospitalizations for influenza (rVE, 38.5%; 95% CI, 26.5%-48.5%), LCI (rVE, 31.2%; 95% CI, 19.3%-41.4%), pneumonia or influenza (rVE, 11.5%; 95% CI, 5.9%-16.8%), cardiorespiratory disease (rVE, 7.5%; 95% CI, 4.7%-10.3%), and all causes (rVE, 3.3%; 95% CI, 1.8%-4.8%). Mortality did not differ significantly between groups (rVE, 0.9%; 95% CI, \u22122.1% to 3.8%). Results were overall consistent across subgroup and sensitivity analyses.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This meta-analysis provides a comprehensive synthesis of evidence from randomized clinical trials comparing HD-IIV with SD-IIV in older adults. HD-IIV was associated with improved protection against hospitalization outcomes, from LCI to all causes, but was not associated with improvement of all-cause mortality. These findings may inform decision-makers in developing vaccine recommendations and policies.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.14620","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T15:02:17Z","timestamp":1779807737000},"page":"e2614620","source":"Crossref","is-referenced-by-count":3,"title":["High-Dose vs Standard-Dose Influenza Vaccines in Older Adults"],"prefix":"10.1001","volume":"9","author":[{"given":"Kristoffer Grundtvig","family":"Skaarup","sequence":"first","affiliation":[{"name":"Department of Cardiology, Copenhagen University Hospital\u2013Herlev and Gentofte, Copenhagen, Denmark"},{"name":"Center for Translational Cardiology and Pragmatic Randomised Trials, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mats C. 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