{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T10:08:24Z","timestamp":1780567704739,"version":"3.54.1"},"reference-count":127,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"unspecified","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,9,20]]},"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Millions of persons with chronic pain across North America and Europe use opioids. While the immunosuppressive properties of opioids are associated with risks of infections, these outcomes could be mitigated through careful patient selection and monitoring practices when appropriate. It is important to recognise that some patients do benefit from a carefully tailored opioid therapy. Enough primary studies have been published to date regarding the role of opioids in potential immunosuppression presenting as an increased rate of infection acquisition, infectious complications and mortality. There is thus a critical need for a consensus in this area.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>The methodology is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, the MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies and the Cochrane Handbook for Systematic Reviews of Interventions. We plan to systematically search Ovid MEDLINE, CINAHL, PsycINFO, EMB Review, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and Google Scholar databases from their inception date to December 2023. Full-text primary studies that report measurable outcomes in adults with chronic pain, all routes of opioid use, all types of infections and all settings will be included. We will identify a scope of reported infections and the evidence on the association of opioid use (including specific opioid, dosage, formulation and duration of use) with the risk of negative infectious outcomes. Opioid use-associated outcomes, comparing opioid use with another opioid or a non-opioid medication, will be reported. The meta-analysis will incorporate individual risk factors. If data are insufficient, the results will be synthesised narratively. Publication bias and confounding evaluation will be performed. The Grading of Recommendations Assessment, Development and Evaluation framework will be used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Approval for the use of published data is not required. The results will be published, presented at conferences and discussed in deliberative dialogue groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO registration number<\/jats:title>\n                    <jats:p>CRD42023402812.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2023-083791","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:48:01Z","timestamp":1729039681000},"page":"e083791","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Risk of infections among persons treated with opioids for chronic pain: a systematic review and meta-analysis protocol"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0764-4004","authenticated-orcid":false,"given":"Irina","family":"Kudrina","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Health Sciences, Family Medicine Department, McGill University, Montreal, Qu\u00e9bec, Canada"},{"name":"Alan Edwards Pain Management Unit, Anesthesia Department, Faculty of Medicine and Health Sciences, McGill University, Montreal, Qu\u00e9bec, Canada"},{"name":"Division of Secondary Care, Faculty of Medicine and Health Sciences, McGill University, Montreal, Qu\u00e9bec, Canada"},{"name":"BRAiN & neurosciences, Research Institute, McGill University Health Centre, Montreal, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7742-2717","authenticated-orcid":false,"given":"M Gaberielle","family":"Page","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, Qu\u00e9bec, Canada"},{"name":"Canada Research center, Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montreal, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Choini\u00e8re","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, Qu\u00e9bec, Canada"},{"name":"Canada Research center, Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montreal, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoram","family":"Shir","sequence":"additional","affiliation":[{"name":"Alan Edwards Pain Management Unit, Anesthesia Department, Faculty of Medicine and Health Sciences, McGill University, Montreal, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1296-0661","authenticated-orcid":false,"given":"Mark J","family":"Eisenberg","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Qu\u00e9bec, Canada"},{"name":"Faculty of Medicine and Health Sciences, McGill University, Montreal, Qu\u00e9bec, Canada"},{"name":"Departments of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Qu\u00e9bec, Canada"},{"name":"Division of Cardiology, Jewish General Hospital, McGill University, Montreal, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maayan","family":"Ben-Sasson","sequence":"additional","affiliation":[{"name":"Alan Edwards Pain Management Unit, Anesthesia Department, Faculty of Medicine and Health Sciences, McGill University, Montreal, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1273-9393","authenticated-orcid":false,"given":"Bertrand","family":"Lebouch\u00e9","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, Family Medicine Department, McGill University, Montreal, Qu\u00e9bec, Canada"},{"name":"Division of Secondary Care, Faculty of Medicine and Health Sciences, McGill University, Montreal, Qu\u00e9bec, Canada"},{"name":"Centre for Outcomes Research & Evaluation, Research Institute of the McGill University Health Centre, Montreal, Qu\u00e9bec, Canada"},{"name":"Chronic Viral Illness Service, Division of Infectious Disease, Department of Medicine, McGill University Health Centre, Montreal, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Puzhko","sequence":"additional","affiliation":[{"name":"Department of General Practice and Family Medicine, University of Bielefeld, Bielefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,10,15]]},"reference":[{"key":"2025121409530193000_14.10.e083791.1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ajem.2022.03.048","article-title":"Opioid usage and COVID-19 prognosis: A systematic review and meta-analysis","volume":"56","author":"Ao","year":"2022","journal-title":"Am J Emerg Med"},{"key":"2025121409530193000_14.10.e083791.2","unstructured":"Canada Go . Restricting the marketing and advertising of opioids. 2021. Available: https:\/\/www.canada.ca\/en\/health-canada\/services\/opioids\/responding-canada-opioid-crisis\/advertising-opioid-medications.html"},{"key":"2025121409530193000_14.10.e083791.3","doi-asserted-by":"publisher","DOI":"10.1136\/rapm-2022-103591"},{"key":"2025121409530193000_14.10.e083791.4","doi-asserted-by":"publisher","DOI":"10.2174\/138945012799201612"},{"key":"2025121409530193000_14.10.e083791.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(03)00085-6"},{"key":"2025121409530193000_14.10.e083791.6","doi-asserted-by":"crossref","first-page":"115417","DOI":"10.1016\/j.bcp.2023.115417","article-title":"Immunosuppression by opioids: Mechanisms of action on innate and adaptive immunity","volume":"209","author":"Sun","year":"2023","journal-title":"Biochem Pharmacol"},{"key":"2025121409530193000_14.10.e083791.7","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001384"},{"key":"2025121409530193000_14.10.e083791.8","doi-asserted-by":"crossref","DOI":"10.1097\/PR9.0000000000000779","article-title":"Prevalence of chronic pain in developing countries: systematic review and meta-analysis","volume":"4","author":"S\u00e1","year":"2019","journal-title":"Pain Rep"},{"key":"2025121409530193000_14.10.e083791.9","unstructured":"Force CPT . Chronic pain in Canada: Laying a foundation for action: a report by the Canadian Pain Task Force. 2019."},{"key":"2025121409530193000_14.10.e083791.10","doi-asserted-by":"crossref","first-page":"e972","DOI":"10.1097\/j.pain.0000000000002541","article-title":"The prevalence of chronic pain in young adults: a systematic review and meta-analysis","volume":"163","author":"Murray","year":"2022","journal-title":"Pain"},{"key":"2025121409530193000_14.10.e083791.11","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.12659\/MSM.911260","article-title":"Prevalence of Chronic Pain, Particularly with Neuropathic Component, and Its Effect on Overall Functioning of Elderly Patients","volume":"25","author":"Stomp\u00f3r","year":"2019","journal-title":"Med Sci Monit"},{"key":"2025121409530193000_14.10.e083791.12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr7103a1","article-title":"CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022","volume":"71","author":"Dowell","year":"2022","journal-title":"MMWR Recomm Rep"},{"key":"2025121409530193000_14.10.e083791.13","unstructured":"Morris SP , Fawcett G , Brisebois L , et al . A demographic, employment and income profile of canadians with disabilities aged 15 years and over, 2017. Statistics Canada= Statistque Canada; 2018."},{"key":"2025121409530193000_14.10.e083791.14","unstructured":"Campbell F , Hudspith M , Choini\u00e8re M . Working together to better understand, prevent, and manage chronic pain: what we heard. A report by the Canadian Pain Task Force. 2020."},{"key":"2025121409530193000_14.10.e083791.15","first-page":"11","article-title":"Significant factors associated with problematic use of opioid pain relief medications among the household population","volume":"32","author":"Carriere","year":"2018","journal-title":"Health Rep"},{"key":"2025121409530193000_14.10.e083791.16","doi-asserted-by":"crossref","first-page":"e335","DOI":"10.1016\/S2468-2667(22)00013-5","article-title":"Global, regional, and national trends in opioid analgesic consumption from 2015 to 2019: a longitudinal study","volume":"7","author":"Ju","year":"2022","journal-title":"The Lancet Public Health"},{"key":"2025121409530193000_14.10.e083791.17","doi-asserted-by":"crossref","first-page":"e498","DOI":"10.1016\/S2468-2667(19)30128-8","article-title":"Trends in use and misuse of opioids in the Netherlands: a retrospective, multi-source database study","volume":"4","author":"Kalkman","year":"2019","journal-title":"The Lancet Public Health"},{"key":"2025121409530193000_14.10.e083791.18","unstructured":"Canada S . Pain relief medication containing opioids. 2018. Available: https:\/\/www150.statcan.gc.ca\/n1\/pub\/82-625-x\/2019001\/article\/00008-eng.htm"},{"key":"2025121409530193000_14.10.e083791.19","unstructured":"Canada Go . Opioid- and stimulant-related harms in canada published:(June 2023). 2023 Available: https:\/\/health-infobase.canada.ca\/substance-related-harms\/opioids-stimulants"},{"key":"2025121409530193000_14.10.e083791.20","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s13690-021-00583-7","article-title":"Chronic disease multimorbidity among the Canadian population: prevalence and associated lifestyle factors","volume":"79","author":"Geda","year":"2021","journal-title":"Arch Public Health"},{"key":"2025121409530193000_14.10.e083791.21","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaa758"},{"key":"2025121409530193000_14.10.e083791.22","doi-asserted-by":"crossref","DOI":"10.1097\/PR9.0000000000000640","article-title":"Postoperative opioids, endocrine changes, and immunosuppression","volume":"3","author":"Haroutounian","year":"2018","journal-title":"Pain Rep"},{"key":"2025121409530193000_14.10.e083791.23","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1002\/ejp.1506","article-title":"The effects of long-term opioid treatment on the immune system in chronic non-cancer pain patients: A systematic review","volume":"24","author":"Diasso","year":"2020","journal-title":"Eur J Pain"},{"key":"2025121409530193000_14.10.e083791.24","unstructured":"CDC . Trends and geographic patterns in drug and synthetic opioid overdose deaths \u2014 United States. 2013."},{"key":"2025121409530193000_14.10.e083791.25","unstructured":"WHO WHO . Social determinants of health. 2023. Available: https:\/\/www.who.int\/health-topics\/social-determinants-of-health"},{"key":"2025121409530193000_14.10.e083791.26","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2018.00316","article-title":"Inflammation-Nature\u2019s Way to Efficiently Respond to All Types of Challenges: Implications for Understanding and Managing \u201cthe Epidemic\u201d of Chronic Diseases","volume":"5","author":"Bennett","year":"2018","journal-title":"Front Med (Lausanne)"},{"key":"2025121409530193000_14.10.e083791.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2007.09.006"},{"key":"2025121409530193000_14.10.e083791.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2014.07.009"},{"key":"2025121409530193000_14.10.e083791.29","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1700"},{"key":"2025121409530193000_14.10.e083791.30","first-page":"911","article-title":"Posttraumatic Stress Disorder and Incident Infections","volume":"30","author":"Jiang","year":"2019","journal-title":"Epidemiol (Sunnyvale)"},{"key":"2025121409530193000_14.10.e083791.31","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.dsx.2020.06.016","article-title":"Metabolic syndrome and COVID-19: An update on the associated comorbidities and proposed therapies","volume":"14","author":"Costa","year":"2020","journal-title":"Diabetes Metab Syndr"},{"key":"2025121409530193000_14.10.e083791.32","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv333"},{"key":"2025121409530193000_14.10.e083791.33","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kes305"},{"key":"2025121409530193000_14.10.e083791.34","unstructured":"Page GG . The immune-suppressive effects of pain. Madame Curie bioscience database. Landes Bioscience, 2013."},{"key":"2025121409530193000_14.10.e083791.35","doi-asserted-by":"crossref","unstructured":"Gowing L , Farrell M , Bornemann R , et al . Substitution treatment of injecting opioid users for prevention of HIV infection. Cochrane Database Syst Rev 2004.:Cd004145. doi:10.1002\/14651858.CD004145.pub2","DOI":"10.1002\/14651858.CD004145.pub2"},{"key":"2025121409530193000_14.10.e083791.36","unstructured":"Linda G , Michael FF , Reinhard B , et al . Oral substitution treatment of injecting opioid users for prevention of HIV infection. Cochrane Database Syst Rev 2011.:CD004145."},{"key":"2025121409530193000_14.10.e083791.37","doi-asserted-by":"crossref","unstructured":"Jackson KA , Bohm MK , Brooks JT , et al . Invasive methicillin-resistant Staphylococcus aureus infections among persons who inject drugs\u2014six sites, 2005\u20132016. Morbidity and Mortality Weekly Report 2018;67.","DOI":"10.15585\/mmwr.mm6722a2"},{"key":"2025121409530193000_14.10.e083791.38","doi-asserted-by":"publisher","DOI":"10.1377\/hlthaff.2015.1424"},{"key":"2025121409530193000_14.10.e083791.39","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-011-9292-5"},{"key":"2025121409530193000_14.10.e083791.40","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-005-9009-8"},{"key":"2025121409530193000_14.10.e083791.41","doi-asserted-by":"crossref","unstructured":"Tahamtan A , Tavakoli-Yaraki M , Mokhtari-Azad T , et al . Opioids and Viral Infections: A Double-Edged Sword. Front Microbiol 2016;7. doi:10.3389\/fmicb.2016.00970","DOI":"10.3389\/fmicb.2016.00970"},{"key":"2025121409530193000_14.10.e083791.42","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2019.02904","article-title":"The Role of Opioid Receptors in Immune System Function","volume":"10","author":"Eisenstein","year":"2019","journal-title":"Front Immunol"},{"key":"2025121409530193000_14.10.e083791.43","first-page":"70","article-title":"Opioids and Immunosuppression: Clinical Evidence, Mechanisms of Action, and Potential Therapies","volume":"5","author":"Bettinger","year":"2024","journal-title":"Palliat Med Rep"},{"key":"2025121409530193000_14.10.e083791.44","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0044103","article-title":"The impact of infection on population health: results of the Ontario burden of infectious diseases study","volume":"7","author":"Kwong","year":"2012","journal-title":"PLoS One"},{"key":"2025121409530193000_14.10.e083791.45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13756-018-0336-y","article-title":"Estimating the burden of antimicrobial resistance: a systematic literature review","volume":"7","author":"Naylor","year":"2018","journal-title":"Antimicrob Resist Infect Control"},{"key":"2025121409530193000_14.10.e083791.46","unstructured":"Employees CUoP . Health care associated infections: a backgrounder . Canadian Union of Public Employees, 2009."},{"key":"2025121409530193000_14.10.e083791.47","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1186\/s13643-021-01852-w","article-title":"Effectiveness of interventions for prevention of common infections in people who use opioids: a protocol for a systematic review of systematic reviews","volume":"10","author":"Kudrina","year":"2021","journal-title":"Syst Rev"},{"key":"2025121409530193000_14.10.e083791.48","doi-asserted-by":"crossref","DOI":"10.3389\/fpubh.2022.749033","article-title":"Effectiveness of Interventions for Prevention of Common Infections Among Opioid Users: A Systematic Review of Systematic Reviews","volume":"10","author":"Puzhko","year":"2022","journal-title":"Front Public Health"},{"key":"2025121409530193000_14.10.e083791.49","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.1464"},{"key":"2025121409530193000_14.10.e083791.50","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.170363"},{"key":"2025121409530193000_14.10.e083791.51","unstructured":"Kumar P , Jethwa R , Roycroft G . Chronic pain: supporting safer prescribing of analgesics. Brit Med Assoc 2017."},{"key":"2025121409530193000_14.10.e083791.52","unstructured":"NHS SCCG . Opioid prescribing for chronic pain: resource pack. 2022. Available: https:\/\/nenc-sunderland.icb.nhs.uk\/wp-content\/uploads\/2023\/02\/Opioid-resource-pack.pdf?x99445"},{"key":"2025121409530193000_14.10.e083791.53","doi-asserted-by":"crossref","unstructured":"Loret A . Usage Probl\u00e9matique Des Traitements Opiac\u00e9s Dans l\u2019indication Douleur Chronique Non Canc\u00e9reuse d\u2019origine Ost\u00e9o-Articulaire: Etude Descriptive Prospective En Soins Courants. UNIVERSIT\u00c9 DE TOURS, 2022.","DOI":"10.1016\/j.rhum.2023.10.026"},{"key":"2025121409530193000_14.10.e083791.54","doi-asserted-by":"crossref","DOI":"10.3390\/jcm11061594","article-title":"Prevalence of Opioid Use Disorder among Patients with Cancer-Related Pain: A Systematic Review","volume":"11","author":"Preux","year":"2022","journal-title":"J Clin Med"},{"key":"2025121409530193000_14.10.e083791.55","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41380-020-0661-4","article-title":"The changing opioid crisis: development, challenges and opportunities","volume":"26","author":"Volkow","year":"2021","journal-title":"Mol Psychiatry"},{"key":"2025121409530193000_14.10.e083791.56","unstructured":"Cicero TJ , Ellis MS . The prescription opioid epidemic: a review of qualitative studies on the progression from initial use to abuse. Dialogues Clin Neurosci 2022."},{"key":"2025121409530193000_14.10.e083791.57","doi-asserted-by":"crossref","unstructured":"Evans CJ , Cahill CM . Neurobiology of opioid dependence in creating addiction vulnerability. F1000Res 2016;5. doi:10.12688\/f1000research.8369.1","DOI":"10.12688\/f1000research.8369.1"},{"key":"2025121409530193000_14.10.e083791.58","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000003403"},{"key":"2025121409530193000_14.10.e083791.59","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1097\/j.pain.0000000000001043","article-title":"Discovery of endogenous opioid systems: What it has meant for the clinician\u2019s understanding of pain and its treatment","volume":"158","author":"Ballantyne","year":"2017","journal-title":"Pain Pain"},{"key":"2025121409530193000_14.10.e083791.60","doi-asserted-by":"crossref","DOI":"10.6061\/clinics\/2020\/e1554","article-title":"Opioid-induced immunosuppression and carcinogenesis promotion theories create the newest trend in acute and chronic pain pharmacotherapy","volume":"75","author":"Kosciuczuk","year":"2020","journal-title":"Clinics (Sao Paulo)"},{"key":"2025121409530193000_14.10.e083791.61","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(95)00002-3"},{"key":"2025121409530193000_14.10.e083791.62","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1007\/s11481-012-9396-6","article-title":"Regulation of mu opioid receptor expression in developing T cells","volume":"7","author":"Zhang","year":"2012","journal-title":"J Neuroimmune Pharmacol"},{"key":"2025121409530193000_14.10.e083791.63","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.3390\/ijms21041499","article-title":"Identification of MOR-Positive B Cell as Possible Innovative Biomarker (Mu Lympho-Marker) for Chronic Pain Diagnosis in Patients with Fibromyalgia and Osteoarthritis Diseases","volume":"21","author":"Raffaeli","year":"2020","journal-title":"IJMS"},{"key":"2025121409530193000_14.10.e083791.64","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.bbi.2019.10.011","article-title":"Morphine decreases the function of primary human natural killer cells by both TLR4 and opioid receptor signaling","volume":"83","author":"Maher","year":"2020","journal-title":"Brain Behav Immun"},{"key":"2025121409530193000_14.10.e083791.65","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.00300","article-title":"Opioid Receptors in Immune and Glial Cells-Implications for Pain Control","volume":"11","author":"Machelska","year":"2020","journal-title":"Front Immunol"},{"key":"2025121409530193000_14.10.e083791.66","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2016.06.029"},{"key":"2025121409530193000_14.10.e083791.67","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2019.02914","article-title":"Do All Opioid Drugs Share the Same Immunomodulatory Properties? A Review From Animal and Human Studies","volume":"10","author":"Franchi","year":"2019","journal-title":"Front Immunol"},{"key":"2025121409530193000_14.10.e083791.68","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jhin.2014.10.001","article-title":"Remifentanil-based anaesthesia increases the incidence of postoperative surgical site infection","volume":"89","author":"Inagi","year":"2015","journal-title":"J Hosp Infect"},{"key":"2025121409530193000_14.10.e083791.69","doi-asserted-by":"publisher","DOI":"10.1016\/j.suponc.2012.05.002"},{"key":"2025121409530193000_14.10.e083791.70","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s11864-022-00985-x","article-title":"Complex Persistent Opioid Dependence-an Opioid-induced Chronic Pain Syndrome","volume":"23","author":"Manhapra","year":"2022","journal-title":"Curr Treat Options Oncol"},{"key":"2025121409530193000_14.10.e083791.71","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jpain.2007.08.005","article-title":"Opioid endocrinopathy in women consuming prescribed sustained-action opioids for control of nonmalignant pain","volume":"9","author":"Daniell","year":"2008","journal-title":"J Pain"},{"key":"2025121409530193000_14.10.e083791.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2006.04.011"},{"key":"2025121409530193000_14.10.e083791.73","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1093\/cid\/ciy809","article-title":"Long-acting Opioid Use and the Risk of Serious Infections: A Retrospective Cohort Study","volume":"68","author":"Wiese","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2025121409530193000_14.10.e083791.74","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.arth.2016.02.068","article-title":"Long-Acting Opioid Use Independently Predicts Perioperative Complication in Total Joint Arthroplasty","volume":"31","author":"Sing","year":"2016","journal-title":"J Arthroplasty"},{"key":"2025121409530193000_14.10.e083791.75","doi-asserted-by":"publisher","DOI":"10.1097\/SPC.0b013e3282f5272e"},{"key":"2025121409530193000_14.10.e083791.76","doi-asserted-by":"publisher","DOI":"10.1016\/S0192-0561(99)00025-9"},{"key":"2025121409530193000_14.10.e083791.77","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1007\/s11596-006-0427-5","article-title":"Effects of morphine, fentanyl and tramadol on human immune response","volume":"26","author":"Liu","year":"2006","journal-title":"J Huazhong Univ Sci Technolog Med Sci"},{"key":"2025121409530193000_14.10.e083791.78","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2009.11.006"},{"key":"2025121409530193000_14.10.e083791.79","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-005-9009-8"},{"key":"2025121409530193000_14.10.e083791.80","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701138"},{"key":"2025121409530193000_14.10.e083791.81","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1080\/17425255.2019.1634053","article-title":"Opioids and the Risk of Infection: A Critical Appraisal of the Pharmacologic and Clinical Evidence","volume":"15","author":"Khosrow-Khavar","year":"2019","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"2025121409530193000_14.10.e083791.82","doi-asserted-by":"crossref","first-page":"107533","DOI":"10.1016\/j.ypmed.2023.107533","article-title":"Racial differences in COVID-19 severity associated with history of substance use disorders and overdose: Findings from multi-site electronic health records in New York City","volume":"172","author":"Allen","year":"2023","journal-title":"Prev Med"},{"key":"2025121409530193000_14.10.e083791.83","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.jiac.2020.11.011","article-title":"Opioid use prior to admission for chemotherapy induced febrile neutropenia is associated with increased documented infection, sepsis, and death","volume":"27","author":"Eidenschink","year":"2021","journal-title":"J Infect Chemother"},{"key":"2025121409530193000_14.10.e083791.84","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2021-056436","article-title":"COVID-19 outcomes among adult patients treated with long-term opioid therapy for chronic non-cancer pain in the USA: a retrospective cohort study","volume":"11","author":"Tuan","year":"2021","journal-title":"BMJ Open"},{"key":"2025121409530193000_14.10.e083791.85","doi-asserted-by":"crossref","first-page":"6804","DOI":"10.3390\/ijerph18136804","article-title":"Musculoskeletal Disorders, Pain Medication, and in-Hospital Mortality among Patients with COVID-19 in South Korea: A Population-Based Cohort Study","volume":"18","author":"Oh","year":"2021","journal-title":"IJERPH"},{"key":"2025121409530193000_14.10.e083791.86","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000005141"},{"key":"2025121409530193000_14.10.e083791.87","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1097\/BRS.0000000000003405","article-title":"Chronic Opioid Use Is Associated With Surgical Site Infection After Lumbar Fusion","volume":"45","author":"Pirkle","year":"2020","journal-title":"Spine (Phila Pa 1976)"},{"key":"2025121409530193000_14.10.e083791.88","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1001\/jamainternmed.2018.6101","article-title":"Association of Prescribed Opioids With Increased Risk of Community-Acquired Pneumonia Among Patients With and Without HIV","volume":"179","author":"Edelman","year":"2019","journal-title":"JAMA Intern Med"},{"key":"2025121409530193000_14.10.e083791.89","doi-asserted-by":"crossref","first-page":"e189","DOI":"10.1016\/j.bja.2019.03.032","article-title":"Preadmission chronic opioid usage and its association with 90-day mortality in critically ill patients: a retrospective cohort study","volume":"122","author":"Oh","year":"2019","journal-title":"Br J Anaesth"},{"key":"2025121409530193000_14.10.e083791.90","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.1016\/j.arth.2018.05.027","article-title":"Preoperative Opioids Increase the Risk of Periprosthetic Joint Infection After Total Joint Arthroplasty","volume":"33","author":"Bell","year":"2018","journal-title":"J Arthroplasty"},{"key":"2025121409530193000_14.10.e083791.91","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0190362","article-title":"Prescription opioids are associated with higher mortality in patients diagnosed with sepsis: A retrospective cohort study using electronic health records","volume":"13","author":"Zhang","year":"2018","journal-title":"PLoS ONE"},{"key":"2025121409530193000_14.10.e083791.92","doi-asserted-by":"crossref","first-page":"396","DOI":"10.7326\/M17-1907","article-title":"Opioid Analgesic Use and Risk for Invasive Pneumococcal Diseases","volume":"168","author":"Wiese","year":"2018","journal-title":"Ann Intern Med"},{"key":"2025121409530193000_14.10.e083791.93","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-311079"},{"key":"2025121409530193000_14.10.e083791.94","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1016\/j.arth.2017.04.002","article-title":"Preoperative Opiate Use Independently Predicts Narcotic Consumption and Complications After Total Joint Arthroplasty","volume":"32","author":"Rozell","year":"2017","journal-title":"J Arthroplasty"},{"key":"2025121409530193000_14.10.e083791.95","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/art.39462","article-title":"Opioid Analgesics and the Risk of Serious Infections Among Patients With Rheumatoid Arthritis: A Self-Controlled Case Series Study","volume":"68","author":"Wiese","year":"2016","journal-title":"Arthritis Rheumatol"},{"key":"2025121409530193000_14.10.e083791.96","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1001\/jamasurg.2015.5558","article-title":"Association of preoperative narcotic use with postoperative complications and prolonged length of hospital stay in patients with Crohn disease","volume":"151","author":"Li","year":"2016","journal-title":"JAMA Surg"},{"key":"2025121409530193000_14.10.e083791.97","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2012.218"},{"key":"2025121409530193000_14.10.e083791.98","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1111\/j.1532-5415.2011.03586.x","article-title":"Use of Opioids or Benzodiazepines and Risk of Pneumonia in Older Adults: A Population\u2010Based Case\u2013Control Study","volume":"59","author":"Dublin","year":"2011","journal-title":"J American Geriatrics Society"},{"key":"2025121409530193000_14.10.e083791.99","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjsurg.2006.01.001"},{"key":"2025121409530193000_14.10.e083791.100","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.15.2008"},{"key":"2025121409530193000_14.10.e083791.101","doi-asserted-by":"crossref","unstructured":"Higgins JP , Thomas J , Chandler J , et al . Cochrane handbook for systematic reviews of interventions. John Wiley & Sons, 2019.","DOI":"10.1002\/9781119536604"},{"key":"2025121409530193000_14.10.e083791.102","doi-asserted-by":"publisher","DOI":"10.1186\/2046-4053-4-1"},{"key":"2025121409530193000_14.10.e083791.103","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000160"},{"key":"2025121409530193000_14.10.e083791.104","unstructured":"Opioid oral morphine milligram equivalent (mme) conversion factors. Utah University; 2022."},{"key":"2025121409530193000_14.10.e083791.105","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2018.07.015"},{"key":"2025121409530193000_14.10.e083791.106","unstructured":"Zalikha Z . Accuracy and acceptability of deepl translate in translating legal document: UIN Sunan Gunung Djati Bandung. 2024."},{"key":"2025121409530193000_14.10.e083791.107","doi-asserted-by":"publisher","DOI":"10.5596\/c14-016"},{"key":"2025121409530193000_14.10.e083791.108","unstructured":"Cohen J . The effect size. Statistical power analysis for the behavioral sciences. 1988;77\u201383."},{"key":"2025121409530193000_14.10.e083791.109","doi-asserted-by":"crossref","first-page":"276","DOI":"10.11613\/BM.2012.031","article-title":"Interrater reliability: the kappa statistic","volume":"22","author":"McHugh","year":"2012","journal-title":"Biochem Med"},{"key":"2025121409530193000_14.10.e083791.110","unstructured":"Practice CE , Care OO . EPOC resources for review authors. In: Cochrane effective practice and organization Care Oxford (UK). 2017."},{"key":"2025121409530193000_14.10.e083791.111","unstructured":"Project EPHP . Quality assessment tool for quantitative studies. 2023. Available: https:\/\/www.ephpp.ca\/quality-assessment-tool-for-quantitative-studies"},{"key":"2025121409530193000_14.10.e083791.112","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2004.04006.x"},{"key":"2025121409530193000_14.10.e083791.113","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2753.2010.01516.x"},{"key":"2025121409530193000_14.10.e083791.114","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2009.06.006"},{"key":"2025121409530193000_14.10.e083791.115","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.n160","article-title":"PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"2025121409530193000_14.10.e083791.116","unstructured":"Cochrane . ReviewManager (revman) is cochrane\u2019s bespoke software for writing cochrane reviews. 2020. Available: https:\/\/training.cochrane.org\/online-learning\/core-software\/revman"},{"key":"2025121409530193000_14.10.e083791.117","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1186"},{"key":"2025121409530193000_14.10.e083791.118","doi-asserted-by":"crossref","unstructured":"Deeks JJ , Higgins JP , Altman DG , et al . Analysing data and undertaking meta\u2010analyses. Cochrane Handb for Syst Rev of Interventions 2019;241\u201384. doi:10.1002\/9781119536604","DOI":"10.1002\/9781119536604.ch10"},{"key":"2025121409530193000_14.10.e083791.119","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/jrsm.1230","article-title":"Basics of meta\u2010analysis: I2 is not an absolute measure of heterogeneity","volume":"8","author":"Borenstein","year":"2017","journal-title":"Res Synth Methods"},{"key":"2025121409530193000_14.10.e083791.120","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2015-010247","article-title":"Plea for routinely presenting prediction intervals in meta-analysis","volume":"6","author":"IntHout","year":"2016","journal-title":"BMJ Open"},{"key":"2025121409530193000_14.10.e083791.121","doi-asserted-by":"crossref","first-page":"441","DOI":"10.4103\/joacp.JOACP_128_19","article-title":"Opioid free onco-anesthesia: Is it time to convict opioids? A systematic review of literature","volume":"35","author":"Thota","year":"2019","journal-title":"J Anaesthesiol Clin Pharmacol"},{"key":"2025121409530193000_14.10.e083791.122","first-page":"81","article-title":"Is Opioid-Free General Anesthesia More Superior for Postoperative Pain Versus Opioid General Anesthesia in Laparoscopic Cholecystectomy?","volume":"40","author":"Toleska","year":"2019","journal-title":"Pril (Maked Akad Nauk Umet Odd Med Nauki)"},{"key":"2025121409530193000_14.10.e083791.123","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000763"},{"key":"2025121409530193000_14.10.e083791.124","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s40278-016-14038-x","article-title":"New-onset depression linked to prolonged opioid use, not dose","volume":"1586","author":"Scherrer","year":"2016","journal-title":"React Wkly"},{"key":"2025121409530193000_14.10.e083791.125","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpain.2005.06.001"},{"key":"2025121409530193000_14.10.e083791.126","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1111\/j.1526-4637.2005.00072.x","article-title":"Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool","volume":"6","author":"Webster","year":"2005","journal-title":"Pain Med"},{"key":"2025121409530193000_14.10.e083791.127","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2010.09.011"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2023-083791","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T17:53:15Z","timestamp":1765734795000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2023-083791"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":127,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10,15]]},"published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1136\/bmjopen-2023-083791"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2023-083791","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10]]}}}