{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:09:44Z","timestamp":1772168984760,"version":"3.50.1"},"reference-count":36,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T00:00:00Z","timestamp":1604016000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Taylor's University Malaysia","award":["Taylor\u2019s Ageing Flagship Grant"],"award-info":[{"award-number":["Taylor\u2019s Ageing Flagship Grant"]}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    <ns3:bold>Background:<\/ns3:bold>\n                    Fever is suppressed with drugs due to discomfort and risk of organ damage. However, there is some compelling evidence for the benefits of fever. The elderly are a special population in this regard as they have a blunted fever response. The benefit-harm balance of antipyretic use in this population is unclear. \u00a0\n                  <\/ns3:p>\n                  <ns3:p>This study aims to provide the synthesized best evidence regarding long-term health effects of antipyretic treatment in the elderly during infections, investigating the onset\/worsening of common chronic diseases, for e.g., thyroid disorders, connective tissue diseases and chronic obstructive pulmonary disease\/asthma.<\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Methods:<\/ns3:bold>\n                    A systematic review will be performed to establish the best evidence available regarding antipyretic treatment in the elderly, searching databases such as Medline, Embase and Cochrane CENTRAL from their inception till date for all types of studies. Studies that consider the drugs in analgesic role will be excluded. The search will be reported following the \u2018Preferred Reporting Items for Systematic Reviews and Meta-Analyses\u2019 (PRISMA) guidelines. Randomized control trials, quasi experimental studies, observational studies, case series and reports will be included. The primary outcome measure being onset\/worsening of chronic inflammatory diseases. Other outcomes include relief of symptoms, length of hospital stay, patient satisfaction, mortality, blood\/immune parameters indicative of morbidity and complications of the infection.\n                  <\/ns3:p>\n                  <ns3:p>Risk of biases in randomized studies will be assessed through the Cochrane risk of bias tool. For other study types, appropriate tools such as CASP\/QUIPS\/Cochrane non-randomised studies tool will be used. Meta-analysis will be conducted on the Cochrane RevMan software and where pooling of data is not possible, a narrative synthesis will be performed. Overall certainty of evidence will be assessed through the GRADE approach.<\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Discussion:<\/ns3:bold>\n                    The study aims to provide evidence regarding benefit-harm balance of antipyretic use in the elderly population to inform clinical practice and future research.\u00a0\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Systematic review registration:<\/ns3:bold>\n                    PROSPERO\n                    <ns3:ext-link xmlns:ns4=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" ns4:href=\"https:\/\/www.crd.york.ac.uk\/prospero\/display_record.php?RecordID=160854\">CRD42020160854<\/ns3:ext-link>\n                  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Werf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahesh","family":"Mallappa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9118-8306","authenticated-orcid":false,"given":"George","family":"Vithoulkas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nai Ming","family":"Lai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2020,10,30]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"1459-544","DOI":"10.1016\/S0140-6736(16)31012-1","article-title":"Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015.","volume":"388","year":"2016","journal-title":"Lancet."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"1736-88","DOI":"10.1016\/S0140-6736(18)32203-7","article-title":"Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017.","volume":"392","year":"2018","journal-title":"Lancet."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"e105536","DOI":"10.1371\/journal.pone.0105536","article-title":"Distribution and determinants of non communicable diseases among elderly Uyghur ethnic group in Xinjiang, China.","volume":"9","author":"L Feng","year":"2014","journal-title":"PLoS One."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"1-5","DOI":"10.14336\/AD.2014.1210","article-title":"The Critical Need to Promote Research of Aging and Aging-related Diseases to Improve Health and Longevity of the Elderly Population.","volume":"6","author":"K Jin","year":"2014","journal-title":"Aging Dis."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.3389\/fimmu.2019.01699","article-title":"Activation of Resolution Pathways to Prevent and Fight Chronic Inflammation: Lessons From Asthma and Inflammatory Bowel Disease.","volume":"10","author":"C Barnig","year":"2019","journal-title":"Front Immunol."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"160","DOI":"10.3389\/fimmu.2016.00160","article-title":"Resolution of Inflammation: What Controls Its Onset?","volume":"7","author":"M Sugimoto","year":"2016","journal-title":"Front Immunol."},{"key":"ref-7","first-page":"SR7-15","article-title":"The \"continuum\" of a unified theory of diseases.","volume":"16","author":"G Vithoulkas","year":"2010","journal-title":"Med Sci Monit."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"851-7","DOI":"10.1016\/s1286-4579(01)01443-5","article-title":"Immunosenescence and infectious diseases.","volume":"3","author":"L Ginaldi","year":"2001","journal-title":"Microbes Infect."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"177-88","DOI":"10.1007\/s12026-009-8122-9","article-title":"Fine-tuning immune surveillance by fever-range thermal stress.","volume":"46","author":"D Fisher","year":"2010","journal-title":"Immunol Res."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"212-27","DOI":"10.1016\/j.it.2019.01.007","article-title":"Mediators of the Resolution of the Inflammatory Response.","volume":"40","author":"M Sugimoto","year":"2019","journal-title":"Trends Immunol."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"23-9","DOI":"10.1111\/irv.12316","article-title":"Should clinical case definitions of influenza in hospitalized older adults include fever?","volume":"9 Suppl 1","author":"A Falsey","year":"2015","journal-title":"Influenza Other Respir Viruses."},{"key":"ref-12","first-page":"6-10","article-title":"[Pathogenetic mechanisms responsible for producing a secondary immunodeficiency state].","volume":"6 Suppl 3","author":"G Corti","year":"1994","journal-title":"J Chemother."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"244-54","DOI":"10.1111\/j.1749-6632.2000.tb06651.x","article-title":"Inflamm-aging. An evolutionary perspective on immunosenescence.","volume":"908","author":"C Franceschi","year":"2000","journal-title":"Ann N Y Acad Sci."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"148-51","DOI":"10.1086\/313896","article-title":"Fever in the elderly.","volume":"31","author":"D Norman","year":"2000","journal-title":"Clin Infect Dis."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1186\/s13054-016-1510-3","article-title":"Risk factors, host response and outcome of hypothermic sepsis.","volume":"20","author":"M Wiewel","year":"2016","journal-title":"Crit Care."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"302-9","DOI":"10.1016\/j.neuropharm.2017.08.025","article-title":"Therapeutic hypothermia for ischemic stroke; pathophysiology and future promise.","volume":"134","author":"K Kurisu","year":"2018","journal-title":"Neuropharmacology."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"557-63","DOI":"10.1056\/NEJMoa003289","article-title":"Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia.","volume":"346","author":"S Bernard","year":"2002","journal-title":"N Engl J Med."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"520-4","DOI":"10.1093\/infdis\/145.4.520","article-title":"Elevation of nasal viral levels by suppression of fever in ferrets infected with influenza viruses of differing virulence.","volume":"145","author":"R Husseini","year":"1982","journal-title":"J Infect Dis."},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"1229-38","DOI":"10.1084\/jem.157.4.1229","article-title":"Fever and immunoregulation. III. Hyperthermia augments the primary in vitro humoral immune response.","volume":"157","author":"H Jampel","year":"1983","journal-title":"J Exp Med."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"296-8","DOI":"10.1097\/00007611-199703000-00006","article-title":"Community-acquired pneumonia in the elderly: association of mortality with lack of fever and leukocytosis.","volume":"90","author":"S Ahkee","year":"1997","journal-title":"South Med J."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"2215-24","DOI":"10.1056\/NEJMoa1508375","article-title":"Acetaminophen for Fever in Critically Ill Patients with Suspected Infection.","volume":"373","author":"P Young","year":"2015","journal-title":"N Engl J Med."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"203-215","DOI":"10.24875\/BMHIM.M18000020","article-title":"Fever and antipyretic therapy in the septic patient in the intensive care unit: an update","volume":"75","author":"A Donoso","year":"2018"},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"179-92","DOI":"10.1007\/978-3-319-92336-9_7","article-title":"Febrile Seizures.","author":"A El-Radhi","year":"2018"},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"507137","DOI":"10.1101\/507137","article-title":"Causes of death among hospitalized adults with dengue fever in Tainan, 2015: emphasis on cardiac events and bacterial infections.","author":"J Lee","year":"2018","journal-title":"bioRxiv."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"2377-93","DOI":"10.1111\/j.1365-2702.2010.03258.x","article-title":"Literature review: should antipyretic therapies routinely be administered to patients with [corrected] fever?","volume":"19","author":"J Carey","year":"2010","journal-title":"J Clin Nurs."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"10","DOI":"10.21037\/jeccm.2018.01.09","article-title":"Management of fever in critically ill patients with infection.","volume":"2","author":"M Egi","year":"2018","journal-title":"J Emerg Crit Care Med."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"421-5","DOI":"10.1038\/sj.bjc.6602386","article-title":"Fever therapy revisited.","volume":"92","author":"U Hobohm","year":"2005","journal-title":"Br J Cancer."},{"key":"ref-28","doi-asserted-by":"publisher","first-page":"610-8","DOI":"10.12968\/bjon.2019.28.10.610","article-title":"Antipyretic drugs in patients with fever and infection: literature review.","volume":"28","author":"J Ludwig","year":"2019","journal-title":"Br J Nurs."},{"key":"ref-29","article-title":"Extended data_SeemaMahesh.","author":"S Mahesh","year":"2020","journal-title":"figshare."},{"key":"ref-30","article-title":"Men Ageing And Health Achieving health across the life span 01WHO\/NMH\/ (e book)","year":"2001"},{"key":"ref-31","article-title":"ICD-10: international statistical classification of diseases and related health problems: tenth revision","year":"2004"},{"key":"ref-32","doi-asserted-by":"publisher","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration's tool for assessing risk of bias in randomised trials.","volume":"343","author":"J Higgins","year":"2011","journal-title":"BMJ."},{"key":"ref-33","article-title":"Review Manager (RevMan) 5.3 [program]. 5.3. 5 (Build Date: 30\/10\/14 11: 54) version","year":"2014"},{"key":"ref-34","article-title":"Cochrane Consumers and Communication Review Group: data synthesis and analysis.","author":"R Ryan","year":"2013","journal-title":"Cochrane Consumers and Communication Review Group."},{"key":"ref-35","article-title":"GRADE handbook for grading quality of evidence and strength of recommendations.","author":"H Sch\u00fcnemann","year":"2013"},{"key":"ref-36","doi-asserted-by":"publisher","first-page":"199-207","DOI":"10.1124\/mi.6.4.6","article-title":"COX-2 in inflammation and resolution.","volume":"6","author":"R Rajakariar","year":"2006","journal-title":"Mol 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.29987.r80627, Sylwia El\u017cbieta Wrotek, Department of Immunology, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Torun, Poland, 22 Mar 2021, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/9-1288\/v1#referee-response-80627","order":0,"name":"referee-response-80627","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Seema Mahesh<\/b>; \n<i>Posted: 22 Mar 2021<\/i>; Thank you Dr Wrotek for your valuable suggestions. We will revise the paper accordingly and publish Thanking you Seema Mahesh Corresponding author","URL":"https:\/\/f1000research.com\/articles\/9-1288\/v1#referee-comment-6482","order":1,"name":"referee-comment-6482","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.29987.r128427, Atakan Yilmaz, Department of Emergency Medicine, Pamukkale University Hospital, Pamukkale University of Medical Science, Kinikli, Denizli, Turkey, 28 Apr 2022, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/9-1288\/v1#referee-response-128427","order":2,"name":"referee-response-128427","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Seema Mahesh<\/b>; \n<i>Posted: 28 Apr 2022<\/i>; Thank you very much for the review. The revision is now complete and I am awaiting it's publication. I will update the link here once it is published.  Dr Seema Mahesh","URL":"https:\/\/f1000research.com\/articles\/9-1288\/v1#referee-comment-8164","order":3,"name":"referee-comment-8164","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Taylor\u2019s Ageing Flagship Grant of Taylor\u2019s University, Subang Jaya, Malaysia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"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"}]}}