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Background: Up to 15% of survivors of COVID-19 infection experience long-term health effects, including fatigue, myalgia and impaired cognitive function, termed post-COVID-19 condition or long COVID. Several trials that study the benefits and harms of various interventions to manage long COVID have been published and hundreds more are planned or are ongoing. Trustworthy systematic reviews that clarify the benefits and harms of interventions are critical to promote evidence-based practice., Objective: To create and maintain a living systematic review and network meta-analysis addressing the benefits and harms of pharmacologic and non-pharmacologic interventions for the treatment and management of long COVID., Methods: Eligible trials will randomise adults with long COVID to pharmacologic or non-pharmacologic interventions, placebo, sham or usual care. We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, PsycINFO, AMED and CENTRAL from inception, without language restrictions.Reviewers will work independently and in duplicate to screen search records, collect data from eligible trials, including trial and patient characteristics and outcomes of interest and assess risk of bias. Our outcomes of interest will include patient-reported fatigue, pain, postexertional malaise, changes in education or employment status, cognitive function, mental health, dyspnoea, quality of life, physical function, recovery and serious adverse events.For each outcome, when possible, we will perform a frequentist random-effects network meta-analysis. When there are compelling reasons to suspect that certain interventions are only applicable or effective for a subtype of long COVID, we will perform separate network meta-analyses. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach will guide our assessment of the certainty of evidence.We will update our living review biannually, on the publication of a seminal trial, or when new evidence emerges that may change clinical practice., Conclusion: This living systematic review and network meta-analysis will provide comprehensive, trustworthy and up-to-date summaries of the evidence addressing the benefits and harms of interventions for the treatment and management of long COVID. We will make our findings available publicly and work with guideline-producing organisations to inform their recommendations., Ethics and Dissemination: The study describes the protocol for a systematic review that uses data from published trial reports. Therefore, the study is exempt from ethics review. We intend to deposit all data in a public repository and publish each iteration of the living review online., Competing Interests: Competing interests: RSM has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Neurawell, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie and Atai Life Sciences. RSM is a CEO of Braxia Scientific., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To address the efficacy and safety of proactive therapeutic drug monitoring of biologic drugs for patients with inflammatory bowel disease, inflammatory arthritis, and psoriasis., Design: Systematic review and meta-analysis., Data Sources: Medline, Embase, Central, and CINAHL, from database inception to 23 May 2024., Eligibility Criteria for Selecting Studies: Trials including people with inflammatory bowel disease, inflammatory arthritis, and psoriasis were selected. Selected trials also randomly assigned people to either proactive therapeutic drug monitoring of tumour necrosis factor-alpha inhibitors or other biologic drugs in the intervention group, and to either no therapeutic drug monitoring or standard care in the control group. Reviewers worked independently and in duplicate to screen search records and collect data from eligible trials. For each outcome, a frequentist, pairwise, random effects meta-analysis was done and the certainty of evidence was assessed using GRADE (grading of recommendations, assessment, development, and evaluations)., Results: Of 10 eligible trials identified, reporting on 2383 patients, two investigated induction with infliximab (533 patients), four assessed maintenance with infliximab (901 patients), and three assessed maintenance with adalimumab (710 patients). One trial was of maintenance with infliximab, adalimumab, and etanercept (239 patients). For patients who had induction with infliximab, the effects of proactive therapeutic drug monitoring on remission and adverse events were uncertain. Low certainty evidence suggested that proactive therapeutic drug monitoring may have little or no effect on disease activity, physical function, mental health, and quality of life. For patients who had maintenance with infliximab, low certainty evidence suggested that proactive therapeutic drug monitoring may increase the proportion of patients who had sustained disease control or remission (relative risk 1.26 (95% confidence interval (CI) 1.14 to 1.40), absolute risk difference of 146 more per 1000 patients treated for one year (95% CI 78 to 224). Additionally, this treatment and monitoring may reduce disease worsening, and may have little or no effect on disease activity, physical function, mental health, and quality of life. The effects of proactive therapeutic drug monitoring of infliximab on adverse events and formation of anti-drug antibodies were uncertain. For patients who had maintenance with adalimumab, the effects of proactive therapeutic drug monitoring were uncertain., Conclusion: Proactive therapeutic drug monitoring of infliximab during maintenance may help patients to have sustained disease control or remission. No compelling evidence supported the effectiveness of proactive therapeutic drug monitoring of infliximab during induction or proactive therapeutic drug monitoring of adalimumab during maintenance., Systematic Review Registration: https://osf.io/x4m28/., Competing Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the European Union’s Horizon Europe research and innovation programme for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; DZ is a member of the editorial board of BMJ Medicine, but had no involvement in the editorial decisions or peer review process regarding this manuscript; all editorial procedures, including the handling of this submission, were conducted independently; no other relationships or activities that could appear to have influenced the submitted work., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: The objective of this study is to evaluate the comparative benefits and harms of opioids and cannabis for medical use for chronic non-cancer pain., Design: Systematic review and network meta-analysis., Data Sources: EMBASE, MEDLINE, CINAHL, AMED, PsycINFO, PubMed, Web of Science, Cannabis-Med, Epistemonikos and the Cochrane Library (CENTRAL) from inception to March 2021., Study Selection: Randomised trials comparing any type of cannabis for medical use or opioids, against each other or placebo, with patient follow-up ≥4 weeks., Data Extraction and Synthesis: Paired reviewers independently extracted data. We used Bayesian random-effects network meta-analyses to summarise the evidence and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to evaluate the certainty of evidence and communicate our findings., Results: Ninety trials involving 22 028 patients were eligible for review, among which the length of follow-up ranged from 28 to 180 days. Moderate certainty evidence showed that opioids provide small improvements in pain, physical functioning and sleep quality versus placebo; low to moderate certainty evidence supported similar effects for cannabis versus placebo. Neither was more effective than placebo for role, social or emotional functioning (all high to moderate certainty evidence). Moderate certainty evidence showed there is probably little to no difference between cannabis for medical use and opioids for physical functioning (weighted mean difference (WMD) 0.47 on the 100-point 36-item Short Form Survey physical component summary score, 95% credible interval (CrI) -1.97 to 2.99), and cannabis resulted in fewer discontinuations due to adverse events versus opioids (OR 0.55, 95% CrI 0.36 to 0.83). Low certainty evidence suggested little to no difference between cannabis and opioids for pain relief (WMD 0.23 cm on a 10 cm Visual Analogue Scale (VAS), 95% CrI -0.06 to 0.53) or sleep quality (WMD 0.49 mm on a 100 mm VAS, 95% CrI -4.72 to 5.59)., Conclusions: Cannabis for medical use may be similarly effective and result in fewer discontinuations than opioids for chronic non-cancer pain., Prospero Registration Number: CRD42020185184., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Chronic non-cancer pain is common among military veterans; however, the prevalence is uncertain. This information gap complicates policy decisions and resource planning to ensure veterans have access to healthcare services that align with their needs., Methods: Following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols, we searched MEDLINE, EMBASE, PsycINFO, CINAHL and Web of Science from inception to 9 February 2023 for observational studies reporting the prevalence of chronic non-cancer pain among military veterans. We performed random-effects meta-analysis to pool pain prevalence data across studies and used the Grading of Recommendations, Assessment, Development and Evaluation approach to evaluate the certainty of evidence., Results: Forty-two studies that included 14 305 129 veterans were eligible for review, of which 28 studies (n=5 011 634) contributed to our meta-analysis. Most studies (90%; 38 of 42) enrolled US veterans, the median of the mean age among study participants was 55 years (IQR 45-62) and 85% were male. The pooled prevalence of chronic non-cancer pain was 45%; however, we found evidence of a credible subgroup effect based on representativeness of the study population. Moderate certainty evidence found the prevalence of chronic pain among studies enrolling military veterans from the general population was 30% (95% CI 23% to 37%) compared with 51% (95% CI 38% to 64%) among military veterans sampled from populations with high rates of conditions associated with chronic pain (p=0.005)., Conclusion: We found moderate certainty evidence that 3 in every 10 military veterans from the general population live with chronic non-cancer pain. These findings underscore the importance of ensuring access to evidence-based care for chronic pain for veterans, and the need for prevention and early management to reduce transition from acute to chronic pain. Further research, employing a standardised assessment of chronic pain, is needed to disaggregate meaningful subgroups; for example, the proportion of veterans living with moderate to severe pain compared with mild pain., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Accurate measurement of health status is essential to assess veterans' needs and the effects of interventions directed at improving veterans' well-being. We conducted a systematic review to identify instruments that measure subjective health status, considering four components (ie, physical, mental, social or spiritual well-being)., Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we searched CINAHL, MEDLINE, Embase, PsycINFO, Web of Science, JSTOR, ERIC, Social Sciences Abstracts and ProQuest in June 2021 for studies reporting on the development or evaluation of instruments measuring subjective health among outpatient populations. We assessed risk of bias with the Consensus-based Standards for the Selection of Health Measurement Instruments tool and engaged three veteran partners to independently assess the clarity and applicability of identified instruments., Results: Of 5863 abstracts screened, we identified 45 eligible articles that reported health-related instruments in the following categories: general health (n=19), mental health (n=7), physical health (n=8), social health (n=3) and spiritual health (n=8). We found evidence for adequate internal consistency for 39 instruments (87%) and good test-retest reliability for 24 (53%) instruments. Of these, our veteran partners identified five instruments for the measurement of subjective health (Military to Civilian Questionnaire (M2C-Q), Veterans RAND 36-Item Health Survey (VR-36), Short Form 36, Abbreviated World Health Organization Quality of Life questionnaire (WHOQOL-BREF) and Sleep Health Scale) as clear and very applicable to veterans. Of the two instruments developed and validated among veterans, the 16-item M2C-Q considered most components of health (mental, social and spiritual). Of the three instruments not validated among veterans, only the 26-item WHOQOL-BREF considered all four components of health., Conclusion: We identified 45 health measurement instruments of which, among those reporting adequate psychometric properties and endorsed by our veteran partners, 2 instruments showed the most promise for measurement of subjective health. The M2C-Q, which requires augmentation to capture physical health (eg, the physical component score of the VR-36), and the WHOQOL-BREF, which requires validation among veterans., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the efficacy and harms of adding medical cannabis to prescription opioids among people living with chronic pain., Design: Systematic review., Data Sources: CENTRAL, EMBASE and MEDLINE., Main Outcomes and Measures: Opioid dose reduction, pain relief, sleep disturbance, physical and emotional functioning and adverse events., Study Selection Criteria and Methods: We included studies that enrolled patients with chronic pain receiving prescription opioids and explored the impact of adding medical cannabis. We used Grading of Recommendations Assessment, Development and Evaluation to assess the certainty of evidence for each outcome., Results: Eligible studies included five randomised trials (all enrolling chronic cancer-pain patients) and 12 observational studies. All randomised trials instructed participants to maintain their opioid dose, which resulted in a very low certainty evidence that adding cannabis has little or no impact on opioid use (weighted mean difference (WMD) -3.4 milligram morphine equivalent (MME); 95% CI (CI) -12.7 to 5.8). Randomised trials provided high certainty evidence that cannabis addition had little or no effect on pain relief (WMD -0.18 cm; 95% CI -0.38 to 0.02; on a 10 cm Visual Analogue Scale (VAS) for pain) or sleep disturbance (WMD -0.22 cm; 95% CI -0.4 to -0.06; on a 10 cm VAS for sleep disturbance; minimally important difference is 1 cm) among chronic cancer pain patients. Addition of cannabis likely increases nausea (relative risk (RR) 1.43; 95% CI 1.04 to 1.96; risk difference (RD) 4%, 95% CI 0% to 7%) and vomiting (RR 1.5; 95% CI 1.01 to 2.24; RD 3%; 95% CI 0% to 6%) (both moderate certainty) and may have no effect on constipation (RR 0.85; 95% CI 0.54 to 1.35; RD -1%; 95% CI -4% to 2%) (low certainty). Eight observational studies provided very low certainty evidence that adding cannabis reduced opioid use (WMD -22.5 MME; 95% CI -43.06 to -1.97)., Conclusion: Opioid-sparing effects of medical cannabis for chronic pain remain uncertain due to very low certainty evidence. PROSPERO registration number CRD42018091098., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Chronic, non-cancer, axial or radicular spinal pain is a common condition associated with considerable socioeconomic burden. Clinicians frequently offer patients various interventional procedures for the treatment of chronic spine pain; however, the comparative effectiveness and safety of available procedures remains uncertain., Methods: We will conduct a systematic review of randomised controlled trials that explores the effectiveness and harms of interventional procedures for the management of axial or radicular, chronic, non-cancer, spine pain. We will identify eligible studies through a systematic search of Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and Web of Science from inception without language restrictions. Eligible trials will: (1) enrol primarily adult patients (≥18 years old) with axial or radicular, chronic, non-cancer, spine pain, (2) randomise patients to different, currently available, interventional procedures or to an interventional procedure and a placebo/sham procedure or usual care, and (3) measure outcomes at least 1 month after randomisation.Pairs of reviewers will independently screen articles identified through searches and extract information and assess risk of bias of eligible trials. We will use a modified Cochrane instrument to evaluate risk of bias. We will use frequentist random-effects network meta-analyses to assess the relative effects of interventional procedures, and five a priori hypotheses to explore between studies subgroup effects. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty in evidence for each outcome, including direct, indirect and network estimates., Ethics and Dissemination: No research ethics approval is required for this systematic review, as no confidential patient data will be used. We will disseminate our findings through publication in a peer-reviewed journal and conference presentations, and our review will support development of a BMJ Rapid Recommendations providing contextualised clinical guidance based on this body of evidence., Prospero Registration Number: CRD42020170667., Competing Interests: Competing interests: DNB and CJS declare intellectual and financial conflicts of interest, as pain physicians that perform interventional procedures for chronic spinal complaints as part of their practices. BS and TA are member of the GRADE Working Group., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)