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Objective: To assess the effectiveness of mesenchymal stem cells (MSCs) for chronic knee pain secondary to osteoarthritis (OA)., Methods: We searched MEDLINE, EMBASE, CINAHL, and Cochrane Central to September 2023 for trials that (1) enrolled patients with chronic pain associated with knee OA, and (2) randomized them to MSC therapy vs. placebo or usual care. We performed random-effects meta-analysis and used Grading of Recommendations, Assessment, Development, and Evaluation to assess the certainty of evidence., Results: We included 16 trials (807 participants). At 3-6 months, MSC therapy probably results in little to no difference in pain relief (weighted mean difference [WMD] -0.74 cm on a 10 cm visual analog scale [VAS], 95% confidence interval [95%CI] -1.16 to -0.33; minimally important difference [MID] 1.5 cm) or physical functioning (WMD 2.23 points on 100-point 36-item Short Form Survey (SF-36) physical functioning subscale, 95%CI -0.97 to 5.43; MID 10-points; both moderate certainty). At 12 months, injection of MSCs probably results in little to no difference in pain (WMD -0.73 cm on a 10 cm VAS, 95%CI -1.69 to 0.24; moderate certainty) and may improve physical functioning (WMD 19.36 points on 100-point SF-36 PF subscale, 95%CI -0.19 to 38.9; low certainty). MSC therapy may increase risk of any adverse events (risk ratio [RR] 2.67, 95%CI 1.19 to 5.99; low certainty) and pain and swelling of the knee joint (RR 1.58, 95%CI 1.04 to 2.38; low certainty)., Conclusions: Intra-articular injection of MSCs for chronic knee pain associated with OA probably provides little to no improvement in pain or physical function., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Assessment of the certainty of evidence (CoE) from network meta-analysis is critical to convey the strength of inferences for clinical decision-making. Both the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group (GWG) and the Confidence in Network Meta-Analysis (CINeMA) framework have been designed to assess the CoE of treatment effects informed by network meta-analysis; however, the concordance of results is uncertain., Study Design and Setting: We assessed the CoE for treatment effects of individual opioids on pain relief and physical functioning from a network meta-analysis for chronic noncancer pain using the GWG approach and the CINeMA framework. Both approaches evaluate the CoE as high, moderate, low or very low. We quantified the number of discrepant CoE ratings between approaches and the magnitude of the difference (ie, one level, two levels, or three levels)., Results: Across 105 comparisons among individual opioids for pain relief, the GWG and CINeMA approaches provided different CoE ratings in 34% of cases (36 of 105). Across 66 comparisons for physical functioning, there was discordance in 17% of cases (11 of 66). All discrepancies were separated by one level. The CINeMA framework typically provided lower CoE ratings compared to the GWG approach, predominantly because of differences in the assessment of transitivity and heterogeneity., Conclusion: Our findings suggest there are differences between the CoE ratings provided by the GWG and CINeMA approaches when applied to network meta-analyses. Further research is needed to replicate or refute our findings in other network meta-analyses and assess the implications for clinical decision-making., Competing Interests: Declaration of competing interest BS and GHG are members of the GRADE working group. GHG is a member of the JCE Editorial Board. There are no competing interests for any other author., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Chronic postsurgical pain (CPSP) is common following musculoskeletal and orthopedic surgeries and is associated with impairment and reduced quality of life. Several interventions have been proposed to reduce CPSP; however, there remains uncertainty regarding which, if any, are most effective. We will perform a systematic review and network meta-analysis of randomised trials to assess the comparative benefits and harms of perioperative pharmacological and psychological interventions directed at preventing chronic pain after musculoskeletal and orthopedic surgeries., Methods: We will search MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to present, without language restrictions. We will include randomised controlled trials that as follows: (1) enrolled adult patients undergoing musculoskeletal or orthopedic surgeries; (2) randomized them to any pharmacological or psychological interventions, or their combination directed at reducing CPSP, placebo, or usual care; and (3) assessed pain at 3 months or more after surgery. Screening for eligible trials, data extraction, and risk-of-bias assessment using revised Cochrane risk-of-bias tool (RoB 2.0) will be performed in duplicate and independently. Our main outcome of interest will be the proportion of surgical patients reporting any pain at ≥ 3 months after surgery. We will also collect data on other patient important outcomes, including pain severity, physical functioning, emotional functioning, dropout rate due to treatment-related adverse event, and overall dropout rate. We will perform a frequentist random-effects network meta-analysis to determine the relative treatment effects. When possible, the modifying effect of sex, surgery type and duration, anesthesia type, and veteran status on the effectiveness of interventions will be investigated using network meta-regression. We will use the GRADE approach to assess the certainty evidence and categorize interventions from most to least beneficial using GRADE minimally contextualised approach., Discussion: This network meta-analysis will assess the comparative effectiveness of pharmacological and psychological interventions directed at preventing CPSP after orthopedic surgery. Our findings will inform clinical decision-making and identify promising interventions for future research., Systematic Review Registration: PROSPERO CRD42023432503., (© 2024. The Author(s).)

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.)

Objectives: Incorporating health equity considerations into guideline development often requires information beyond that gathered through traditional evidence synthesis methodology. This article outlines an operationalization plan for the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-equity criterion to gather and assess evidence from primary studies within systematic reviews, enhancing guideline recommendations to promote equity. We demonstrate its use in a clinical guideline on medical cannabis for chronic pain., Study Design and Setting: We reviewed GRADE guidance and resources recommended by team members regarding the use of evidence for equity considerations, drafted an operationalization plan, and iteratively refined it through team discussion and feedback and piloted it on a medicinal cannabis guideline., Results: We propose a seven-step approach: 1) identify disadvantaged populations, 2) examine available data for specific populations, 3) evaluate population baseline risk for primary outcomes, 4) assess representation of these populations in primary studies, 5) appraise analyses, 6) note barriers to implementation of effective interventions for these populations, and 7) suggest supportive strategies to facilitate implementation of effective interventions., Conclusion: Our approach assists guideline developers in recognizing equity considerations, particularly in resource-constrained settings. Its application across various guideline topics can verify its feasibility and necessary adjustments., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: We explored the comparative effectiveness of available therapies for chronic pain associated with temporomandibular disorders (TMD)., Design: Systematic review and network meta-analysis of randomised clinical trials (RCTs)., Data Sources: MEDLINE, EMBASE, CINAHL, CENTRAL, and SCOPUS were searched to May 2021, and again in January 2023., Study Selection: Interventional RCTs that enrolled patients presenting with chronic pain associated with TMD., Data Extraction and Synthesis: Pairs of reviewers independently identified eligible studies, extracted data, and assessed risk of bias. We captured all reported patient-important outcomes, including pain relief, physical functioning, emotional functioning, role functioning, social functioning, sleep quality, and adverse events. We conducted frequentist network meta-analyses to summarise the evidence and used the GRADE approach to rate the certainty of evidence and categorise interventions from most to least beneficial., Results: 233 trials proved eligible for review, of which 153-enrolling 8713 participants and exploring 59 interventions or combinations of interventions-were included in network meta-analyses. All subsequent effects refer to comparisons with placebo or sham procedures. Effects on pain for eight interventions were supported by high to moderate certainty evidence. The three therapies probably most effective for pain relief were cognitive behavioural therapy (CBT) augmented with biofeedback or relaxation therapy (risk difference (RD) for achieving the minimally important difference (MID) in pain relief of 1 cm on a 10 cm visual analogue scale: 36% (95% CI 33 to 39)), therapist-assisted jaw mobilisation (RD 36% (95% CI 31 to 40)), and manual trigger point therapy (RD 32% (29 to 34)). Five interventions were less effective, yet more effective than placebo, showing RDs ranging between 23% and 30%: CBT, supervised postural exercise, supervised jaw exercise and stretching, supervised jaw exercise and stretching with manual trigger point therapy, and usual care (such as home exercises, self stretching, reassurance).Moderate certainty evidence showed four interventions probably improved physical functioning: supervised jaw exercise and stretching (RD for achieving the MID of 5 points on the short form-36 physical component summary score: 43% (95% CI 33 to 51)), manipulation (RD 43% (25 to 56)), acupuncture (RD 42% (33 to 50)), and supervised jaw exercise and mobilisation (RD 36% (19 to 51)). The evidence for pain relief or physical functioning among other interventions, and all evidence for adverse events, was low or very low certainty., Conclusion: When restricted to moderate or high certainty evidence, interventions that promote coping and encourage movement and activity were found to be most effective for reducing chronic TMD pain., Registration: PROSPERO (CRD42021258567)., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form and declare: no financial support from any industry for the submitted work; no other relationships or activities that could appear to have influenced the submitted work., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Clinical Question: What is the comparative effectiveness of available therapies for chronic pain associated with temporomandibular disorders (TMD)?, Current Practice: TMD are the second most common musculoskeletal chronic pain disorder after low back pain, affecting 6-9% of adults globally. TMD are associated with pain affecting the jaw and associated structures and may present with headaches, earache, clicking, popping, or crackling sounds in the temporomandibular joint, and impaired mandibular function. Current clinical practice guidelines are largely consensus-based and provide inconsistent recommendations., Recommendations: For patients living with chronic pain (≥3 months) associated with TMD, and compared with placebo or sham procedures, the guideline panel issued: (1) strong recommendations in favour of cognitive behavioural therapy (CBT) with or without biofeedback or relaxation therapy, therapist-assisted mobilisation, manual trigger point therapy, supervised postural exercise, supervised jaw exercise and stretching with or without manual trigger point therapy, and usual care (such as home exercises, stretching, reassurance, and education); (2) conditional recommendations in favour of manipulation, supervised jaw exercise with mobilisation, CBT with non-steroidal anti-inflammatory drugs (NSAIDS), manipulation with postural exercise, and acupuncture; (3) conditional recommendations against reversible occlusal splints (alone or in combination with other interventions), arthrocentesis (alone or in combination with other interventions), cartilage supplement with or without hyaluronic acid injection, low level laser therapy (alone or in combination with other interventions), transcutaneous electrical nerve stimulation, gabapentin, botulinum toxin injection, hyaluronic acid injection, relaxation therapy, trigger point injection, acetaminophen (with or without muscle relaxants or NSAIDS), topical capsaicin, biofeedback, corticosteroid injection (with or without NSAIDS), benzodiazepines, and β blockers; and (4) strong recommendations against irreversible oral splints, discectomy, and NSAIDS with opioids., How This Guideline Was Created: An international guideline development panel including patients, clinicians with content expertise, and methodologists produced these recommendations in adherence with standards for trustworthy guidelines using the GRADE approach. The MAGIC Evidence Ecosystem Foundation (MAGIC) provided methodological support. The panel approached the formulation of recommendations from the perspective of patients, rather than a population or health system perspective., The Evidence: Recommendations are informed by a linked systematic review and network meta-analysis summarising the current body of evidence for benefits and harms of conservative, pharmacologic, and invasive interventions for chronic pain secondary to TMD., Understanding the Recommendation: These recommendations apply to patients living with chronic pain (≥3 months duration) associated with TMD as a group of conditions, and do not apply to the management of acute TMD pain. When considering management options, clinicians and patients should first consider strongly recommended interventions, then those conditionally recommended in favour, then conditionally against. In doing so, shared decision making is essential to ensure patients make choices that reflect their values and preference, availability of interventions, and what they may have already tried. Further research is warranted and may alter recommendations in the future., Competing Interests: Competing interests: All authors have completed the BMJ Rapid Recommendations interests disclosure form, and a detailed, contextualised description of all disclosures is reported in appendix 1. As with all BMJ Rapid Recommendations, the executive team and The BMJ judged that no panel member had any financial conflict of interest. Personal, professional, and academic interests were minimised as much as possible, while maintaining necessary expertise on the panel to make fully informed decisions., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Higher doses of opioids, mental health comorbidities, co-prescription of sedatives, lower socioeconomic status and a history of opioid overdose have been reported as risk factors for opioid overdose; however, the magnitude of these associations and their credibility are unclear. We sought to identify predictors of fatal and nonfatal overdose from prescription opioids., Methods: We systematically searched MEDLINE, Embase, CINAHL, PsycINFO and Web of Science up to Oct. 30, 2022, for observational studies that explored predictors of opioid overdose after their prescription for chronic pain. We performed random-effects meta-analyses for all predictors reported by 2 or more studies using odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Twenty-eight studies (23 963 716 patients) reported the association of 103 predictors with fatal or nonfatal opioid overdose. Moderate- to high-certainty evidence supported large relative associations with history of overdose (OR 5.85, 95% CI 3.78-9.04), higher opioid dose (OR 2.57, 95% CI 2.08-3.18 per 90-mg increment), 3 or more prescribers (OR 4.68, 95% CI 3.57-6.12), 4 or more dispensing pharmacies (OR 4.92, 95% CI 4.35-5.57), prescription of fentanyl (OR 2.80, 95% CI 2.30-3.41), current substance use disorder (OR 2.62, 95% CI 2.09-3.27), any mental health diagnosis (OR 2.12, 95% CI 1.73-2.61), depression (OR 2.22, 95% CI 1.57-3.14), bipolar disorder (OR 2.07, 95% CI 1.77-2.41) or pancreatitis (OR 2.00, 95% CI 1.52-2.64), with absolute risks among patients with the predictor ranging from 2-6 per 1000 for fatal overdose and 4-12 per 1000 for nonfatal overdose., Interpretation: We identified 10 predictors that were strongly associated with opioid overdose. Awareness of these predictors may facilitate shared decision-making regarding prescribing opioids for chronic pain and inform harm-reduction strategies SYSTEMATIC REVIEW REGISTRATION: Open Science Framework (https://osf.io/vznxj/)., Competing Interests: Competing interests: Corey Hayes reports support from the National Institute on Drug Abuse Clinical Trials Network (5UG1DA013732-23S3). David Juurlink is an unpaid member of Physicians for Responsible Opioid Prescribing. David Juurlink is also a member of the American College of Medical Toxicology. David Juurlink has received payment for lectures from Texas Tech University Health Sciences Centre and payment for expert testimony regarding analgesics, including opioids. He has received travel support for presentations and scientific meetings from the Canadian Institutes of Health Research, Stanford University and Texas Tech University Health Sciences Centre. Jason Busse is the Principal Investigator for the update of the 2017 Canadian Opioid Guideline, which is funded by Health Canada. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Introduction: Chronic pain is a debilitating problem that disproportionately affects military veterans. We completed a qualitative study that identified 20 research priorities of Canadian veterans living with chronic noncancer pain. The aim of this study was to establish the generalizability of these priorities., Materials and Methods: From January to March 2021, we emailed a 45-item survey to a list of Canadian veterans living with chronic noncancer pain that asked about the relative importance of 20 research priorities., Results: Overall, 313 of 701 Canadian military veterans living with chronic noncancer pain returned a completed survey (45% response rate). All 20 research priorities listed in the survey were endorsed by ≥75% of respondents, and four received ≥95% endorsement: (1) optimizing chronic pain management after release from the military; (2) establishing the effectiveness of self-care; and (3) identifying and (4) treating mental illness among veterans living with chronic pain. One research priority differed significantly by gender; 50% more females than males rated improving chronic pain care while in the military as important (99% vs. 49%, P < .001)., Conclusions: Our survey established research priorities among Canadian veterans living with chronic noncancer pain. These findings should be considered by granting agencies when formulating calls for proposals and by researchers who wish to undertake research that will address the needs of military veterans living with chronic pain., (© The Association of Military Surgeons of the United States 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Emerging evidence suggests that access to chiropractic care may reduce the likelihood of initiating an opioid prescription for spinal pain; however, the impact of chiropractic care for patients already prescribed opioids is uncertain. We undertook a sequential explanatory mixed methods study to evaluate the association between initiating chiropractic care and continued opioid use among adult patients attending an Ontario community health centre (CHC) and receiving opioid therapy for chronic non-cancer spinal pain., Methods: We conducted a retrospective cohort study of 210 patient records between January 1, 2014 and December 31, 2020. We used generalized estimating equations, adjusted for patient demographics, co-morbidities, visit frequency, and calendar year, to evaluate the association between receipt versus non-receipt of chiropractic services and continued opioid use (e.g., unique opioid fills, number of refills, and dosages) up to one year following the index chiropractic visit. We also completed follow-up interviews with 14 patients and nine general practitioners from the CHC and integrated these data with our quantitative findings., Results: Over 12-month follow-up, there were lower rates of opioid fills (incidence rate ratio [IRR] = 0.66; 95% confidence interval [CI], 0.52-0.83) and refills (IRR = 0.27; 95% CI, 0.17-0.42) among chiropractic recipients (n = 49) versus non-recipients (n = 161). Although patients who did and did not receive chiropractic care began the study with the same dose of opioids, recipients were less likely to be prescribed higher-dose opioids (i.e., ≥ 50 mg morphine equivalents daily) compared to non-recipients at three months (odds ratio [OR] = 0.14; 95% CI, 0.04-0.47), six months (OR = 0.14; 95% CI, 0.05-0.40), nine months (OR = 0.19; 95% CI, 0.07-0.57), and 12 months (OR = 0.22; 95% CI, 0.08-0.62). Interviews suggested that patient self-efficacy, limited effectiveness of opioids for chronic pain, stigma regarding use of opioids, and access to chiropractic treatment were important influencing factors., Conclusion: We found that continued prescription opioid use among patients with chronic non-cancer spinal pain who received chiropractic care was lower than in patients who did not receive chiropractic care. Four themes emerged in our qualitative interviews to help provide a richer understanding of this association. Randomized controlled trials are needed to establish the effect of chiropractic care on opioid use for chronic spinal pain., (© 2022. The Author(s).)

Objective: Although there is growing interest in medically authorized cannabis for chronic pain, little is known about patients' perspectives. We explored perceptions of people living with chronic pain regarding benefits and concerns surrounding their use of cannabis for therapeutic purposes., Setting: A hospital-based clinic in Hamilton and two community-based interdisciplinary pain clinics in Burlington, Ontario, Canada., Methods: In this qualitative descriptive study, we conducted semi-structured interviews with 13 people living with chronic pain who used cannabis therapeutically, living in Ontario, Canada. We used thematic analysis, with data collection, coding, and analysis occurring concurrently., Results: People living with chronic pain reported important benefits associated with use of cannabis for therapeutic purposes, including reduced pain, improved functionality, and less risk of harms compared to prescription opioids. Most patients also acknowledged harms, such as grogginess and coughing, and there was considerable variability in patient experiences. Financial costs and stigma were identified as important barriers to use of cannabis., Conclusion: Evidence-based guidance that incorporates patients' values and preferences may be helpful to inform the role of cannabis in the management of chronic pain., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Most systematic reviews of opioids for chronic pain have pooled treatment effects across individual opioids under the assumption they provide similar benefits and harms. We examined the comparative effects of individual opioids for chronic non-cancer pain through a network meta-analysis of randomised controlled trials., Methods: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials to March 2021 for studies that enrolled patients with chronic non-cancer pain, randomised them to receive different opioids, or opioids vs placebo, and followed them for at least 4 weeks. Certainty of evidence was evaluated using the GRADE approach., Results: We identified 82 eligible trials (22 619 participants) that evaluated 14 opioids. Compared with placebo, several opioids showed superiority to others for analgesia and improvement in physical function; however, when restricted to pooled-effect estimates supported by moderate certainty evidence, no differences between opioids were evident. Among opioids with moderate certainty evidence, all increased the risk of gastrointestinal adverse events compared with placebo, although no opioids were more harmful than others. Low to very low certainty evidence suggests that extended-release vs immediate-release opioids may provide similar benefits for pain relief and physical functioning, and gastrointestinal harms., Conclusions: Our findings support the pooling of effect estimates across different types and formulations of opioids to inform effectiveness for chronic non-cancer pain., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To establish the prevalence of long-term and serious harms of medical cannabis for chronic pain., Design: Systematic review and meta-analysis., Data Sources: MEDLINE, EMBASE, PsycINFO and CENTRAL from inception to 1 April 2020., Study Selection: Non-randomised studies reporting on harms of medical cannabis or cannabinoids in adults or children living with chronic pain with ≥4 weeks of follow-up., Data Extraction and Synthesis: A parallel guideline panel provided input on the design and interpretation of the systematic review, including selection of adverse events for consideration. Two reviewers, working independently and in duplicate, screened the search results, extracted data and assessed risk of bias. We used random-effects models for all meta-analyses and the Grades of Recommendations, Assessment, Development and Evaluation approach to evaluate the certainty of evidence., Results: We identified 39 eligible studies that enrolled 12 143 adult patients with chronic pain. Very low certainty evidence suggests that adverse events are common (prevalence: 26.0%; 95% CI 13.2% to 41.2%) among users of medical cannabis for chronic pain, particularly any psychiatric adverse events (prevalence: 13.5%; 95% CI 2.6% to 30.6%). Very low certainty evidence, however, indicates serious adverse events, adverse events leading to discontinuation, cognitive adverse events, accidents and injuries, and dependence and withdrawal syndrome are less common and each typically occur in fewer than 1 in 20 patients. We compared studies with <24 weeks and ≥24 weeks of cannabis use and found more adverse events reported among studies with longer follow-up (test for interaction p<0.01). Palmitoylethanolamide was usually associated with few to no adverse events. We found insufficient evidence addressing the harms of medical cannabis compared with other pain management options, such as opioids., Conclusions: There is very low certainty evidence that adverse events are common among people living with chronic pain who use medical cannabis or cannabinoids, but that few patients experience serious adverse events., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Study Objectives: We conducted a systematic review to explore the effectiveness of medical cannabis for impaired sleep., Methods: We searched MEDLINE, EMBASE, CENTRAL, and PsychINFO to January 2021 for randomized trials of medical cannabis or cannabinoids for impaired sleep vs. any non-cannabis control. When possible, we pooled effect estimates for all patient-important sleep-related outcomes and used the GRADE approach to appraise the certainty of evidence., Results: Thirty-nine trials (5100 patients) were eligible for review, of which 38 evaluated oral cannabinoids and 1 administered inhaled cannabis. The median follow-up was 35 days, and most trials (33 of 39) enrolled patients living with chronic cancer or noncancer chronic pain. Among patients with chronic pain, moderate certainty evidence found that medical cannabis probably results in a small improvement in sleep quality versus placebo (modeled risk difference [RD] for achieving the minimally important difference [MID], 8% [95% CI, 3 to 12]). Moderate to high certainty evidence shows that medical cannabis vs. placebo results in a small improvement in sleep disturbance for chronic non-cancer pain (modeled RD for achieving the MID, 19% [95% CI, 11 to 28]) and a very small improvement in sleep disturbance for chronic cancer pain (weighted mean difference of -0.19 cm [95%CI, -0.36 to -0.03 cm]; interaction p = .03). Moderate to high certainty evidence shows medical cannabis, versus placebo, results in a substantial increase in the risk of dizziness (RD 29% [95%CI, 16 to 50], for trials with ≥3 months follow-up), and a small increase in the risk of somnolence, dry mouth, fatigue, and nausea (RDs ranged from 6% to 10%)., Conclusion: Medical cannabis and cannabinoids may improve impaired sleep among people living with chronic pain, but the magnitude of benefit is likely small., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Emerging evidence from a number of primary care centres suggests that integration of chiropractic services into chronic pain management is associated with improved clinical outcomes and high patient satisfaction as well as with reductions in physician visits, specialist referrals use of advanced imaging and prescribing of analgesics. However, formal assessments of the integration of chiropractic services into primary care settings are sparse, and the impact of such integration on prescription opioid use in chronic pain management remains uncertain. To help address this knowledge gap, we will conduct a mixed methods health service evaluation of an integrated chiropractic back pain programme in an urban community health centre in Ontario, Canada. This centre provides services to vulnerable populations with high unemployment rates, multiple comorbidities and musculoskeletal disorders that are commonly managed with prescription opioids., Methods and Analysis: We will use a sequential explanatory mixed methods design, which consists of a quantitative phase followed by a qualitative phase. In the quantitative phase, we will conduct a retrospective chart review and evaluate whether receipt of chiropractic services is associated with reduced opioid use among patients already prescribed opioid therapy for chronic pain. We will measure opioid prescriptions (ie, opioid fills, number of refills and dosages) by reviewing electronic medical records of recipients and non-recipients of chiropractic services between 1 January 2014 and 31 December 2020 and use multivariable regression analysis to examine the association. In the qualitative phase, we will conduct in-depth, one-on-one interviews of patients and their general practitioners to explore perceptions of chiropractic integration and its impact on opioid use., Ethics and Dissemination: This study was approved by the Hamilton Integrated Research Ethics Board at McMaster University (approval number 2021-10930). The results will be disseminated via peer-reviewed publications, conference presentations and in-person or webinar presentations to community members and healthcare professionals., Competing Interests: Competing interests: PCE is supported by research grants from McMaster University and the NCMIC Foundation for graduate studies outside of the submitted work., (© 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.)

Background: The purpose of this study was to determine the incidence, characteristics, impact, and risk factors associated with persistent incisional pain. The hypothesis was that patient demographics and perioperative interventions are associated with persistent pain., Methods: This was a secondary analysis of an international prospective cohort study from 2012 to 2014. This study included patients who were 45 yr of age or older who underwent major inpatient noncardiac surgery. Data were collected perioperatively and at 1 yr after surgery to assess for the development of persistent incisional pain (pain present around incision at 1 yr after surgery)., Results: Among 14,831 patients, 495 (3.3%; 95% CI, 3.1 to 3.6) reported persistent incisional pain at 1 yr, with an average pain intensity of 3.6 ± 2.5 (0 to 10 numeric rating scale), with 35% and 14% reporting moderate and severe pain intensities, respectively. More than half of patients with persistent pain reported needing analgesic medications, and 85% reported interference with daily activities (denominator = 495 in the above proportions). Risk factors for persistent pain included female sex (P = 0.007), Asian ethnicity (P < 0.001), surgery for fracture (P < 0.001), history of chronic pain (P < 0.001), coronary artery disease (P < 0.001), history of tobacco use (P = 0.048), postoperative patient-controlled analgesia (P < 0.001), postoperative continuous nerve block (P = 0.010), insulin initiation within 24 h of surgery (P < 0.001), and withholding nonsteroidal anti-inflammatory medication or cyclooxygenase-2 inhibitors on the day of surgery (P = 0.029 and P < 0.001, respectively). Older age (P < 0.001), endoscopic surgery (P = 0.005), and South Asian (P < 0.001), Native American/Australian (P = 0.004), and Latin/Hispanic ethnicities (P < 0.001) were associated with a lower risk of persistent pain., Conclusions: Persistent incisional pain is a common complication of inpatient noncardiac surgery, occurring in approximately 1 in 30 adults. It results in significant morbidity, interferes with daily living, and is associated with persistent analgesic consumption. Certain demographics, ethnicities, and perioperative practices are associated with increased risk of persistent pain., (Copyright © 2021, the American Society of Anesthesiologists. All Rights Reserved.)

Clinical Question: What is the role of medical cannabis or cannabinoids for people living with chronic pain due to cancer or non-cancer causes?, Current Practice: Chronic pain is common and distressing and associated with considerable socioeconomic burden globally. Medical cannabis is increasingly used to manage chronic pain, particularly in jurisdictions that have enacted policies to reduce use of opioids; however, existing guideline recommendations are inconsistent, and cannabis remains illegal for therapeutic use in many countries., Recommendation: The guideline expert panel issued a weak recommendation to offer a trial of non-inhaled medical cannabis or cannabinoids, in addition to standard care and management (if not sufficient), for people living with chronic cancer or non-cancer pain., How This Guideline Was Created: An international guideline development panel including patients, clinicians with content expertise, and methodologists produced this recommendation in adherence with standards for trustworthy guidelines using the GRADE approach. The MAGIC Evidence Ecosystem Foundation (MAGIC) provided methodological support. The panel applied an individual patient perspective., The Evidence: This recommendation is informed by a linked series of four systematic reviews summarising the current body of evidence for benefits and harms, as well as patient values and preferences, regarding medical cannabis or cannabinoids for chronic pain., Understanding the Recommendation: The recommendation is weak because of the close balance between benefits and harms of medical cannabis for chronic pain. It reflects a high value placed on small to very small improvements in self reported pain intensity, physical functioning, and sleep quality, and willingness to accept a small to modest risk of mostly self limited and transient harms. Shared decision making is required to ensure patients make choices that reflect their values and personal context. Further research is warranted and may alter this recommendation., Competing Interests: Competing interests: All authors have completed the BMJ Rapid Recommendations interests disclosure form and a detailed, contextualised description of all disclosures is reported in appendix 2. As with all BMJ Rapid Recommendations, the executive team and The BMJ judged that no panel member had any financial conflict of interest. Personal, professional, and academic interests were minimised as much as possible, while maintaining necessary expertise on the panel to make fully informed decisions., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To determine the benefits and harms of medical cannabis and cannabinoids for chronic pain., Design: Systematic review and meta-analysis., Data Sources: MEDLINE, EMBASE, AMED, PsycInfo, CENTRAL, CINAHL, PubMed, Web of Science, Cannabis-Med, Epistemonikos, and trial registries up to January 2021., Study Selection: Randomised clinical trials of medical cannabis or cannabinoids versus any non-cannabis control for chronic pain at ≥1 month follow-up., Data Extraction and Synthesis: Paired reviewers independently assessed risk of bias and extracted data. We performed random-effects models meta-analyses and used GRADE to assess the certainty of evidence., Results: A total of 32 trials with 5174 adult patients were included, 29 of which compared medical cannabis or cannabinoids with placebo. Medical cannabis was administered orally (n=30) or topically (n=2). Clinical populations included chronic non-cancer pain (n=28) and cancer related pain (n=4). Length of follow-up ranged from 1 to 5.5 months. Compared with placebo, non-inhaled medical cannabis probably results in a small increase in the proportion of patients experiencing at least the minimally important difference (MID) of 1 cm (on a 10 cm visual analogue scale (VAS)) in pain relief (modelled risk difference (RD) of 10% (95% confidence interval 5% to 15%), based on a weighted mean difference (WMD) of -0.50 cm (95% CI -0.75 to -0.25 cm, moderate certainty)). Medical cannabis taken orally results in a very small improvement in physical functioning (4% modelled RD (0.1% to 8%) for achieving at least the MID of 10 points on the 100-point SF-36 physical functioning scale, WMD of 1.67 points (0.03 to 3.31, high certainty)), and a small improvement in sleep quality (6% modelled RD (2% to 9%) for achieving at least the MID of 1 cm on a 10 cm VAS, WMD of -0.35 cm (-0.55 to -0.14 cm, high certainty)). Medical cannabis taken orally does not improve emotional, role, or social functioning (high certainty). Moderate certainty evidence shows that medical cannabis taken orally probably results in a small increased risk of transient cognitive impairment (RD 2% (0.1% to 6%)), vomiting (RD 3% (0.4% to 6%)), drowsiness (RD 5% (2% to 8%)), impaired attention (RD 3% (1% to 8%)), and nausea (RD 5% (2% to 8%)), but not diarrhoea; while high certainty evidence shows greater increased risk of dizziness (RD 9% (5% to 14%)) for trials with <3 months follow-up versus RD 28% (18% to 43%) for trials with ≥3 months follow-up; interaction test P=0.003; moderate credibility of subgroup effect)., Conclusions: Moderate to high certainty evidence shows that non-inhaled medical cannabis or cannabinoids results in a small to very small improvement in pain relief, physical functioning, and sleep quality among patients with chronic pain, along with several transient adverse side effects, compared with placebo. The accompanying BMJ Rapid Recommendation provides contextualised guidance based on this body of evidence. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/3pwn2., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form www.icmje.org/disclosure-of-interest/ and declare: no financial support from any industry for the submitted work; IP and SU have received research funds from Northern Green Canada; IP has been a paid consultant for Northern Green Science, Northern Green Canada, Monk-E psychedelics, and Evergreen Pacific Insurance Corporation; SU and IP received honoraria from Spectrum Therapeutics and Tilray Inc. for educational presentations; MAW is the chief medical officer for Canopy Growth Corporation., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To explore values and preferences towards medical cannabis among people living with chronic pain., Design: Mixed-methods systematic review., Data Sources: We searched MEDLINE, EMBASE and PsycINFO from inception to 17 March 2020., Study Selection: Pairs of reviewers independently screened search results and included quantitative, qualitative and mixed-methods studies reporting values and preferences towards medical cannabis among people living with chronic pain., Review Methods: We analysed data using meta-narrative synthesis (quantitative findings were qualitised) and tabulated review findings according to identified themes. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess certainty of evidence., Results: Of 1838 initial records, 15 studies proved eligible for review. High to moderate certainty evidence showed that patient's use of medical cannabis for chronic pain was influenced by both positive (eg, support from friends and family) and negative social factors (eg, stigma surrounding cannabis use). Most patients using medical cannabis favoured products with balanced ratios of tetrahydrocannabinol (THC) and cannabidiol (CBD), or high levels of CBD, but not high THC preparations. Many valued the effectiveness of medical cannabis for symptom management even when experiencing adverse events related to concentration, memory or fatigue. Reducing use of prescription medication was a motivating factor for use of medical cannabis, and concerns regarding addiction, losing control or acting strangely were disincentives. Out-of-pocket costs were a barrier, whereas legalisation of medical cannabis improved access and incentivised use.Low to very low certainty evidence suggested highly variable values towards medical cannabis among people living with chronic pain. Individuals with pain related to life-limiting disease were more willing to use medical cannabis, and preferred oral over inhaled administration., Conclusions: Our findings highlight factors that clinicians should consider when discussing medical cannabis. The variability of patients' values and preferences emphasise the need for shared decision making when considering medical cannabis for chronic pain., 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.)

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.)

Context: This study is a systematic review of interventions to improve adherence to guideline recommendations for prescribing opioids for chronic noncancer pain., Evidence Acquisition: Investigators searched CINAHL, Embase, MEDLINE, PsycINFO, the Cochrane Library, and Joanna Briggs Institute Evid Based Pract database from inception until June 3, 2019. Interventional studies to improve adherence to recommendations made by opioid guidelines for chronic noncancer pain in North America were eligible if outcomes included adherence to guideline recommendations or change in quantity of opioids prescribed. Data were extracted independently and in duplicate. Quantitative synthesis was performed using random effects meta-analysis. Confidence in evidence was determined using the Grades of Recommendation, Assessment, Development, and Evaluation., Evidence Synthesis: A total of 20 studies (8 controlled and 12 prospective cohort) involving 1,491 providers and 72 clinics met inclusion. Interventions included education, audit and feedback, interprofessional support, shared decision making, and multifaceted strategies. Multifaceted interventions improved the use of urine drug testing (n=2, or =2.31, 95% CI=1.53, 3.49, z=3.98, p<0.01; high-certainty evidence), treatment agreements (n=2, or =1.96, 95% CI=1.47, 2.61, z=4.56, p<0.01; moderate-certainty evidence), and mental health screening (n=2, 2.57-fold, 95% CI=1.56, 4.24, z=2.32, p=0.02; low-certainty evidence) when prescribing opioids for chronic noncancer pain. Very low-certainty evidence suggests that several interventions improved the use of treatment agreements, urine drug testing, and prescription drug monitoring programs., Conclusions: Mostly very low-certainty evidence supports a number of interventions for improving adherence to risk management strategies when prescribing opioids for chronic noncancer pain; however, the effect on patient important outcomes (e.g., overdose, addiction, death) is uncertain., (Copyright © 2020 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The prevalence and intensity of persistent post-surgical pain (PPSP) after breast cancer surgery are uncertain. We conducted a systematic review and meta-analysis to further elucidate this issue., Methods: We searched MEDLINE, Embase, CINAHL, and PsycINFO, from inception to November 2018, for observational studies reporting persistent pain (≥3 months) after breast cancer surgery. We used random-effects meta-analysis and the Grading of Recommendations, Assessment, Development and Evaluations approach to rate quality of evidence., Results: We included 187 observational studies with 297 612 breast cancer patients. The prevalence of PPSP ranged from 2% to 78%, median 37% (inter-quartile range: 22-48%); the pooled prevalence was 35% (95% confidence interval [CI]: 32-39%). The pooled pain intensity was 3.9 cm on a 10 cm visual analogue scale (95% CI: 3.6-4.2 cm). Moderate-quality evidence supported the subgroup effects of PPSP prevalence for localized pain vs any pain (29% vs 44%), moderate or greater vs any pain (26% vs 44%), clinician-assessed vs patient-reported pain (23% vs 36%), and whether patients underwent sentinel lymph node biopsy vs axillary lymph node dissection (26% vs 43%). The adjusted analysis found that the prevalence of patient-reported PPSP (any severity/location) was 46% (95% CI: 36-56%), and the prevalence of patient-reported moderate-to-severe PPSP at any location was 27% (95% CI: 10-43%)., Conclusions: Moderate-quality evidence suggests that almost half of all women undergoing breast cancer surgery develop persistent post-surgical pain, and about one in four develop moderate-to-severe persistent post-surgical pain; the higher prevalence was associated with axillary lymph node dissection. Future studies should explore whether nerve sparing for axillary procedures reduces persistent post-surgical pain after breast cancer surgery., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objective: This review quantified prescriber adherence to opioid prescribing guidelines for chronic noncancer pain (CNCP)., Method: We searched CINAHL, Embase, MEDLINE, PsycINFO, the Cochrane Library, and the Joanna Briggs Institute EBP Database from inception until June 3, 2019. Studies that focused on provider adherence to opioids guidelines for CNCP in North America were eligible. Four reviewers screened studies, extracted data, and assessed study quality., Results: Thirty-eight studies were eligible, comprising 17 cross-sectional studies ( n = 11,835 providers) and 22 chart reviews ( n = 22,512 patients). Survey data indicated that adherence was 49% (95% CI [40, 59]) for treatment agreements, 33% (95% CI [19%, 47%]) for urine drug testing, 48% (95% CI [26%, 71%]) for consultation with drug monitoring program, 57% (95% CI [35%, 79%]) for assessing risk of aberrant medication-taking behavior, and 61% (95% CI [35%, 87%]) for mental health screening. Chart review data indicated that the proportion of patients with documentation was 40% (95% CI [29, 51]) for treatment agreements, 41% (95% CI [32%, 50%]) for urine drug testing, 40% (95% CI [2%, 78%]) for consultation with drug monitoring program, 41% (95% CI [20%, 64%]) for assessing risk of aberrant medication-taking behavior, and 22% (95% CI [9%, 33%]) for mental health screening. Year of publication, practice guideline referenced, and risk of bias explained significant heterogeneity. No study evaluated whether nonadherence to recommendations reflected well-justified deviations to care., Conclusions: Adherence to guideline recommendations for opioids for CNCP is low. It is unclear whether nonadherence reflects thoughtful deviations in care. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Objectives: Opioid-induced hyperalgesia (OIH) is a phenomenon whereby opioids increase patients' pain sensitivity, complicating their use in analgesia. We explored practitioners' attitudes towards, and knowledge concerning diagnosis, risk factors, and treatment of OIH., Materials and Methods: We administered an 18-item cross-sectional survey to 850 clinicians that managed chronic pain with opioid therapy., Results: The survey response rate was 37% (318/850). Most respondents (240/318, 76%) reported they had observed patients with OIH in their practice, of which 38% (84/222) reported OIH affected >5% of their chronic pain patients. The majority (133/222, 60%) indicated that OIH could result from any dose of opioid therapy. The most commonly endorsed chronic pain conditions associated with the development of OIH were fibromyalgia (109/216, 51%) and low back pain (91/216, 42%), while 42% (91/216) indicated that no individual chronic pain condition was associated with greater risk of OIH. The most commonly endorsed opioids associated with the development of OIH were oxycodone (94/216, 44%), fentanyl (86/216, 40%), and morphine (84/216, 39%); 27% (59/216) endorsed that no specific opioid was more likely to result in OIH. Respondents commonly managed OIH by opioid dose reduction (147/216, 68%), administering a nonopioid adjuvant (133/216, 62%), or discontinuing opioids (95/216, 44%)., Discussion: Most clinicians agreed that OIH is a complication of opioid therapy, but were divided regarding the prevalence of OIH, etiological factors, and optimal management.

Purpose: The use of interventional pain management (IPM) modalities to alleviate chronic pain is increasing despite the lack of high-quality evidence. We undertook this survey to explore patterns, training, and attributes of IPM practice., Methods: We administered a 32-item survey via seven Canadian physician member organizations, whose members were engaged in the management of chronic pain., Results: Of 777 physicians contacted, 256 (33%) responded: 45 (6%) declined to participate and 211 (27%) agreed to participate; the number of participants answering any given question varied. One hundred and sixty-nine of 194 (87%) practiced IPM and 103 of 194 (53%) managed only non-cancer pain. Pain management training of ≥ six months was associated with higher odds of IPM training (odds ratio [OR], 2.98; 95% confidence interval [CI], 1.32 to 6.7), but not necessarily ongoing IPM practice (OR, 1.97; 95% CI, 0.74 to 5.3). A substantial percentage of physicians (108 of 168 [64%]) practiced IPM based only on training received during either their base residency program or courses. Only 48 of 186 (26%) felt that there were adequate opportunities for IPM training, and 69 of 186 (37%) believed that their colleagues practiced IPM in accordance with the best current evidence., Conclusions: Our survey indicates that IPM practice and training were not uniform, and that interventional therapies for chronic pain may not be performed in accordance with the best available evidence. Our survey highlights a lack of IPM training opportunities, which may result in substandard training. Concerted efforts involving physician organizations and regulators are needed to standardize IPM training and develop clinical guidelines to optimize evidence-based practice.

Background: Physician adherence to guideline recommendations for the use of opioids to manage chronic pain is often limited., Objective: In February 2018, we administered a 28-item online survey to explore perceptions of the 2017 Canadian guideline for opioid therapy and chronic noncancer pain and if physicians had altered practices in response to recommendations., Results: We invited 34,322 Canadian physicians to complete our survey, and 1,128 responded for a response rate of 3%; 687 respondents indicated they prescribed opioids for noncancer pain and answered survey questions about the guideline and their practice. Almost all were aware of the guideline, 94% had read the document, and 89% endorsed the clarity as good or excellent. The majority (86%) felt the guideline was feasible to implement, but 66% highlighted resistance by patients, and 63% the lack of access to effective nonopioid treatment as barriers. Thirty-six percent of respondents mistakenly believed the guideline recommended mandatory tapering for patients using high-dose opioid therapy (≥90 mg morphine equivalent per day), and 58% felt they would benefit from support for opioid tapering. Seventy percent of respondents had changed practices to align with guideline recommendations, with 51% engaging some high-dose patients in opioid tapering and 43% reducing the number of new opioid starts., Conclusion: There was high awareness of the 2017 Canadian opioid guideline among respondents, and preliminary evidence that recommendations have changed practice to better align with the evidence. Ongoing education is required to avoid the misunderstanding that opioid tapering is mandatory, and research to identify effective strategies to manage chronic noncancer pain is urgently needed., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Jason W. Busse et al.)

Background: Opioids are frequently prescribed for the management of patients with chronic non-cancer pain (CNCP). Previous meta-analyses of efficacy and harms have combined treatment effects across all opioids; however, specific opioids, pharmacokinetic properties (ie, long acting vs short acting), or the type of formulation (ie, immediate vs extended release) may be a source of heterogeneity for pooled effects., Methods: We will conduct a network meta-analysis (NMA) of randomized controlled trials evaluating opioids for CNCP. We will acquire eligible studies through systematic searches of EMBASE, MEDLINE, CINAHL, AMED, PsycINFO, and the Cochrane Central Registry of Controlled Trials (CENTRAL). Eligible studies will have randomly allocated adult CNCP patients to an oral or transdermal opioid versus another type of opioid (or formulation) or placebo, and follow patients for ≥ 4 weeks. We will collect outcome data for pain intensity, physical function, nausea, vomiting, and constipation. Pairs of reviewers will, independently and in duplicate, abstract data from eligible trials and assess risk of bias using a modified Cochrane tool. We will assess coherence of our networks through both a global test, and by comparing direct and indirect evidence for each comparison with node-splitting., Results: Using a frequentist approach, we will conduct random effects multiple treatment meta-analysis to establish treatment effects of individual opioids for each outcome. The certainty of evidence for pooled treatment effects will be assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. We will categorize interventions from most to least effective based on the effect estimates obtained from NMAs and their associated certainty of evidence, as follows: superior to both placebo and alternatives; superior to placebo, but inferior to alternatives; and no better than placebo., Conclusion: This NMA will determine the relative effectiveness and adverse effects of individual opioids among patients with CNCP. Our results will help inform the appropriateness of assuming similar beneficial and adverse effects of varying opioid formulations., Systematic Review Registration: This systematic review is registered with Prospective Register of Systematic Reviews, an international prospective register of systematic reviews (registration no.: CRD42018110331), available at https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=110331.

Introduction: Approximately 400 000 Americans and 36 000 Canadians undergo cardiac surgery annually, and up to 56% will develop chronic postsurgical pain (CPSP). The primary aim of this study is to explore the association of pain-related beliefs and gender-based pain expectations on the development of CPSP. Secondary goals are to: (A) explore risk factors for poor functional status and patient-level cost of illness from a societal perspective up to 12 months following cardiac surgery; and (B) determine the impact of CPSP on quality-adjusted life years (QALYs) borne by cardiac surgery, in addition to the incremental cost for one additional QALY gained, among those who develop CPSP compared with those who do not., Methods and Analyses: In this prospective cohort study, 1250 adults undergoing cardiac surgery, including coronary artery bypass grafting and open-heart procedures, will be recruited over a 3-year period. Putative risk factors for CPSP will be captured prior to surgery, at postoperative day 3 (in hospital) and day 30 (at home). Outcome data will be collected via telephone interview at 6-month and 12-month follow-up. We will employ generalised estimating equations to model the primary (CPSP) and secondary outcomes (function and cost) while adjusting for prespecified model covariates. QALYs will be estimated by converting data from the Short Form-12 (version 2) to a utility score., Ethics and Dissemination: This protocol has been approved by the responsible bodies at each of the hospital sites, and study enrolment began May 2015. We will disseminate our results through CardiacPain.Net, a web-based knowledge dissemination platform, presentation at international conferences and publications in scientific journals., Trial Registration Number: NCT01842568., Competing Interests: Competing interests: M­­­­HM and PJD are members of a research group with a policy of not accepting honorariums or other payments from industry for their own personal financial gain. They do accept honorariums/payments from industry to support research endeavours and costs to participate in meetings. Based on study questions, PJD has originated and grants he has written, he has received grants from Abbott Diagnostics, Boehringer Ingelheim, Covidien, Octapharma, Philips Healthcare, Roche Diagnostics and Stryker. PJD has participated in an consultancy advisory board meeting for Boehringer Ingelheim., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To systematically review evidence addressing the efficacy of testosterone replacement therapy (TRT) and opioid tapering for opioid-induced hypogonadism among patients with chronic noncancer pain., Study Design: Systematic review of randomized controlled trials (RCTs) and observational studies., Methods: We searched MEDLINE, CINAHL, AMED, CENTRAL, CINAHL, DARE, EMBASE, and PsycINFO through August 2017. Eligible studies enrolled ≥10 patients with chronic noncancer pain and opioid-induced hypogonadism and reported the effect of TRT or opioid tapering on a patient-important outcome collected ≥14 days after treatment. Pairs of reviewers independently screened for eligible studies, assessed risk of bias, and extracted data. We used the GRADE approach to rate quality of evidence., Results: Of 666 abstracts reviewed, five studies including one RCT (N = 84) and four observational studies (N = 157) were eligible. No studies explored the effect of opioid tapering for opioid-induced hypogonadism. Very low-quality evidence found that TRT was associated with improvements in pain (median reduction of 2 points on the 11-point numerical rating scale for pain; 95% confidence interval [CI] = -1.4 to -2.6; minimally important difference [MID] = 2 points), and emotional functioning (mean increase of 9 points on the 100-point SF-36 Mental Component Summary score; 95% CI = 4.40 to 13.60; MID = 5 points). Low-quality evidence suggested that TRT had no effect on sleep quality, sexual function, physical functioning, role functioning, or social functioning; very low-quality evidence suggested no association with depressive symptoms., Conclusions: Low-quality to very low-quality evidence suggests that TRT may improve pain and emotional functioning, but not other outcomes, in chronic noncancer pain patients with opioid-induced hypogonadism., (© 2018 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Harms and benefits of opioids for chronic noncancer pain remain unclear., Objective: To systematically review randomized clinical trials (RCTs) of opioids for chronic noncancer pain., Data Sources and Study Selection: The databases of CENTRAL, CINAHL, EMBASE, MEDLINE, AMED, and PsycINFO were searched from inception to April 2018 for RCTs of opioids for chronic noncancer pain vs any nonopioid control., Data Extraction and Synthesis: Paired reviewers independently extracted data. The analyses used random-effects models and the Grading of Recommendations Assessment, Development and Evaluation to rate the quality of the evidence., Main Outcomes and Measures: The primary outcomes were pain intensity (score range, 0-10 cm on a visual analog scale for pain; lower is better and the minimally important difference [MID] is 1 cm), physical functioning (score range, 0-100 points on the 36-item Short Form physical component score [SF-36 PCS]; higher is better and the MID is 5 points), and incidence of vomiting., Results: Ninety-six RCTs including 26 169 participants (61% female; median age, 58 years [interquartile range, 51-61 years]) were included. Of the included studies, there were 25 trials of neuropathic pain, 32 trials of nociceptive pain, 33 trials of central sensitization (pain present in the absence of tissue damage), and 6 trials of mixed types of pain. Compared with placebo, opioid use was associated with reduced pain (weighted mean difference [WMD], -0.69 cm [95% CI, -0.82 to -0.56 cm] on a 10-cm visual analog scale for pain; modeled risk difference for achieving the MID, 11.9% [95% CI, 9.7% to 14.1%]), improved physical functioning (WMD, 2.04 points [95% CI, 1.41 to 2.68 points] on the 100-point SF-36 PCS; modeled risk difference for achieving the MID, 8.5% [95% CI, 5.9% to 11.2%]), and increased vomiting (5.9% with opioids vs 2.3% with placebo for trials that excluded patients with adverse events during a run-in period). Low- to moderate-quality evidence suggested similar associations of opioids with improvements in pain and physical functioning compared with nonsteroidal anti-inflammatory drugs (pain: WMD, -0.60 cm [95% CI, -1.54 to 0.34 cm]; physical functioning: WMD, -0.90 points [95% CI, -2.69 to 0.89 points]), tricyclic antidepressants (pain: WMD, -0.13 cm [95% CI, -0.99 to 0.74 cm]; physical functioning: WMD, -5.31 points [95% CI, -13.77 to 3.14 points]), and anticonvulsants (pain: WMD, -0.90 cm [95% CI, -1.65 to -0.14 cm]; physical functioning: WMD, 0.45 points [95% CI, -5.77 to 6.66 points])., Conclusions and Relevance: In this meta-analysis of RCTs of patients with chronic noncancer pain, evidence from high-quality studies showed that opioid use was associated with statistically significant but small improvements in pain and physical functioning, and increased risk of vomiting compared with placebo. Comparisons of opioids with nonopioid alternatives suggested that the benefit for pain and functioning may be similar, although the evidence was from studies of only low to moderate quality.

Objective: Shared-care decision-making between patients and clinicians involves making trade-offs between desirable and undesirable consequences of management strategies. Although patient values and preferences should provide the basis for these trade-offs, few guidelines consider the relevant evidence when formulating recommendations. To inform a guideline for use of opioids in patients with chronic noncancer pain, we conducted a systematic review of studies exploring values and preferences of affected patients toward opioid therapy., Methods: We searched MEDLINE, CINAHL, EMBASE, and PsycINFO from the inception of each database through October 2016. We included studies examining patient preferences for alternative approaches to managing chronic noncancer pain and studies that assessed how opioid-using chronic noncancer pain patients value alternative health states and their experiences with treatment. We compiled structured summaries of the results., Results: Pain relief and nausea and vomiting were ranked as highly significant outcomes across studies. When considered, the adverse effect of personality changes was rated as equally important. Constipation was assessed in most studies and was an important outcome, secondary to pain relief and nausea and vomiting. Of only two studies that evaluated addiction, both found it less important to patients than pain relief. No studies examined opioid overdose, death, or diversion., Conclusion: Our findings suggest that the adverse effects of opioids, especially nausea and vomiting, may reduce or eliminate any net benefit of opioid therapy unless pain relief is significant (>2 points on a 10-point scale). Further research should investigate patient values and preferences regarding opioid overdose, diversion, and death.

Background: Evidence from diverse areas of medicine (e.g., cardiovascular disease, diabetes) indicates that healthcare providers (HCPs) often do not adhere to clinical practice guidelines (CPGs) despite a clear indication to implement recommendations-a phenomenon commonly termed clinical inertia. There are a variety of reasons for clinical inertia, but HCP-related factors (e.g., knowledge, motivation, agreement with guidelines) are the most salient and amenable to intervention aimed to improve adherence. CPGs have been developed to support the safe and effective prescription of opioid medication for the management of chronic non-cancer pain. The extent of physician uptake and adherence to such guidelines is not yet well understood. The purpose of this review is to synthesize the published evidence about knowledge, attitudes, beliefs, and practices that HCPs hold regarding the prescription of opioids for chronic non-cancer pain., Methods: An experienced information specialist will perform searches of CINAHL, Embase, MEDLINE, and PsycINFO bibliographic databases. The Cochrane library, PROSPERO, and the Joanna Briggs Institute will be searched for systematic reviews. Searches will be performed from inception to the present. Quantitative and qualitative study designs that report on HCP knowledge, attitudes, beliefs, or practices in North America will be eligible for inclusion. Studies reporting on interventions to improve HCP adherence to opioid prescribing CPGs will also be eligible for inclusion. Two trained graduate-level research assistants will independently screen articles for inclusion, perform data extraction, and perform risk of bias and quality assessment using recommended tools. Confidence in qualitative evidence will be evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation-Confidence in the Evidence from Qualitative Reviews (GRADE-CERQual) approach. Confidence in quantitative evidence will be assessed using the GRADE approach., Discussion: The ultimate goal of this work is to support interventions aiming to optimize opioid prescribing practices in order to prevent opioid-related morbidity and mortality without restricting a HCP's ability to select the most appropriate treatment for an individual patient., Systematic Review Registration: PROSPERO CRD42018091640 .

Competing Interests: Competing interests: D. Norm Buckley and Jason Busse report grants from Health Canada during the conduct of the study. Jason Busse received grants from the Canadian Institutes of Health Research (CIHR) during the conduct of the study. D. Norm Buckley reports grants from Purdue Pharma and Janssen Inc. outside the submitted work. Chris Cull received personal fees from Indivior. David Juurlink reports grants from CIHR and from the Ontario Ministry of Health and Long-Term Care, and personal fees outside the submitted work. Sol Stern was a member of advisory boards for Astra Zeneca, Bristol-Myers Squibb and Johnson and Johnson; received fees for expert opinions from the Canadian Medical Protective Association; received consulting fees from mdBriefCase.com, Ethypharm and Sea Courses; and received honoraria for Continuing Medical Education presentations from Purdue Pharma and Paladin. No other competing interests were declared.

Background: Chronic noncancer pain (CNCP) refers to all pain disorders, not due to cancer, that persist for ≥3 months. The point prevalence of CNCP in the general population of Western countries is between 19 and 33 percent. Opioids are commonly prescribed for CNCP and are associated with both benefits and harms. The Canadian Guideline for Safe and Effective Use of Opioids for CNCP was published in 2010 to provide guidance for optimal opioid prescribing in patients with CNCP., Objectives: To investigate the attitudes toward, and use of, the Canadian Opioids Guideline among pain physicians., Design: A qualitative study using one-on-one, semistructured interviews with 12 pain physicians in Ontario, Canada, and thematic analysis of verbatim transcripts., Results: Major themes that emerged from interviews included: (1) generally positive attitudes toward the 2010 Canadian Opioids Guideline, but limited use-half (six of 12) reported they did not use the guideline in practice; (2) strongly contrasting views regarding the 200 mg/d morphine equivalent watchful dose; (3) recognition of gaps in the guideline, especially recommendations for urine drug screening and pain severity-specific therapy; (4) the guideline is excessively long and the format suboptimal; and (5) improved dissemination and education are needed to enhance guideline uptake., Conclusions: Despite its merits, the Canadian Opioids Guideline suffers from information gaps and from limited uptake, at least in part due to suboptimal format and suboptimal dissemination.

Background: Persistent pain after breast cancer surgery affects up to 60% of patients. Early identification of those at higher risk could help inform optimal management. We conducted a systematic review and meta-analysis of observational studies to explore factors associated with persistent pain among women who have undergone surgery for breast cancer., Methods: We searched the MEDLINE, Embase, CINAHL and PsycINFO databases from inception to Mar. 12, 2015, to identify cohort or case-control studies that explored the association between risk factors and persistent pain (lasting ≥ 2 mo) after breast cancer surgery. We pooled estimates of association using random-effects models, when possible, for all independent variables reported by more than 1 study. We reported relative measures of association as pooled odds ratios (ORs) and absolute measures of association as the absolute risk increase., Results: Thirty studies, involving a total of 19 813 patients, reported the association of 77 independent variables with persistent pain. High-quality evidence showed increased odds of persistent pain with younger age (OR for every 10-yr decrement 1.36, 95% confidence interval [CI] 1.24-1.48), radiotherapy (OR 1.35, 95% CI 1.16-1.57), axillary lymph node dissection (OR 2.41, 95% CI 1.73-3.35) and greater acute postoperative pain (OR for every 1 cm on a 10-cm visual analogue scale 1.16, 95% CI 1.03-1.30). Moderate-quality evidence suggested an association with the presence of preoperative pain (OR 1.29, 95% CI 1.01-1.64). Given the 30% risk of pain in the absence of risk factors, the absolute risk increase corresponding to these ORs ranged from 3% (acute postoperative pain) to 21% (axillary lymph node dissection). High-quality evidence showed no association with body mass index, type of breast surgery, chemotherapy or endocrine therapy., Interpretation: Development of persistent pain after breast cancer surgery was associated with younger age, radiotherapy, axillary lymph node dissection, greater acute postoperative pain and preoperative pain. Axillary lymph node dissection provides the only high-yield target for a modifiable risk factor to prevent the development of persistent pain after breast cancer surgery., (© 2016 Canadian Medical Association or its licensors.)

Background: Steroids are often combined with local anesthetic (LA) and injected to reduce pain associated with various chronic non-cancer pain (CNCP) complaints. The biological rationale behind injection of a steroid solution is unclear, and it is uncertain whether the addition of steroids offers any additional benefits over injection of LA alone. We propose to conduct a systematic review and meta-analysis to summarize the evidence for using steroids and LA vs. LA alone in the treatment of CNCP., Methods: An experienced librarian will perform a comprehensive search of EMBASE, MEDLINE, and the Cochrane Central Registry of Controlled Trials (CENTRAL) databases with search terms for clinical indications, LA, and steroid agents. We will review bibliographies of all relevant published reviews in the last 5 years for additional studies. Eligible trials will be published in English and randomly allocate patients with CNCP to treatment with steroid and LA injection therapy or injection with LA alone. We will use the guidelines published by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to inform the outcomes that we collect and present. Teams of reviewers will independently and in duplicate assess trial eligibility, abstract data, and assess risk of bias among eligible trials. We will prioritize intention to treat analysis and, when possible, pool outcomes across trials using random effects models. We will report our findings as risk differences, weighted mean differences, or standardized mean differences for individual outcomes. Further, to ensure interpretability of our results, we will present risk differences and measures of relative effect for pain reduction based on anchor-based minimally important clinical differences. We will conduct a priori defined subgroup analyses and use the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to evaluate the certainty of the evidence on an outcome-by-outcome basis., Discussion: Our review will evaluate both the effectiveness and the adverse events associated with steroid plus LA vs. LA alone for CNCP, evaluate the quality of the evidence using the GRADE approach, and prioritize patient-important outcomes guided by IMMPACT recommendations. Our results will facilitate evidence-based management of patients with chronic non-cancer pain and identify key areas for future research., Trial Registration: PROSPERO CRD42015020614.

The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) has recommended that trialists evaluating treatments for chronic pain should consider reporting 9 patient-important outcome domains. We examined the extent to which clinical trials evaluating the effect of opioids for chronic non-cancer pain (CNCP) report outcome domains recommended by IMMPACT. We systematically searched electronic databases for English-language studies that randomized patients with CNCP to receive an opioid or a non-opioid control. In duplicate and independently, reviewers established the eligibility of each identified study and recorded all reported outcome domains from eligible trials. We conducted a priori regression analyses to explore factors that may be associated with IMMPACT-recommended outcome domains. Among 156 eligible trials, reporting of IMMPACT-recommended outcome domains was highly variable, ranging from 99% for pain to 7% for interpersonal functioning. Recently published trials were more likely to report the effect of treatment on physical functioning, emotional functioning, role functioning, sleep and fatigue, and participant disposition. Trials for which the corresponding author was from North America were more likely to report treatment effects on physical functioning and participant ratings of improvement and satisfaction with treatment. Trials published in higher impact journals were more likely to report treatment effects on emotional function, but less likely to report participant ratings of improvement and satisfaction with treatment. Most IMMPACT domains showed an increased rate of reporting over time, although many patient-important outcome domains remained unreported by over half of all trials evaluating the effects of opioids for CNCP.

Introduction: Chronic neuropathic pain is associated with reduced health-related quality of life and substantial socioeconomic costs. Current research addressing management of chronic neuropathic pain is limited. No review has evaluated all interventional studies for chronic neuropathic pain, which limits attempts to make inferences regarding the relative effectiveness of treatments., Methods and Analysis: We will conduct a systematic review of all randomised controlled trials evaluating therapies for chronic neuropathic pain. We will identify eligible trials, in any language, by a systematic search of CINAHL, EMBASE, MEDLINE, AMED, HealthSTAR, DARE, PsychINFO and the Cochrane Central Registry of Controlled Trials. Eligible trials will be: (1) enrol patients presenting with chronic neuropathic pain, and (2) randomise patients to alternative interventions (pharmacological or non-pharmacological) or an intervention and a control arm. Pairs of reviewers will, independently and in duplicate, screen titles and abstracts of identified citations, review the full texts of potentially eligible trials and extract information from eligible trials. We will use a modified Cochrane instrument to evaluate risk of bias of eligible studies, recommendations from the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to inform the outcomes we will collect, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to evaluate our confidence in treatment effects. When possible, we will conduct: (1) in direct comparisons, a random-effects meta-analysis to establish the effect of reported therapies on patient-important outcomes; and (2) a multiple treatment comparison meta-analysis within a Bayesian framework to assess the relative effects of treatments. We will define a priori hypotheses to explain heterogeneity between studies, and conduct meta-regression and subgroup analyses consistent with the current best practices., Ethics and Dissemination: We do not require ethics approval for our proposed review. We will disseminate our findings through peer-reviewed publications and conference presentations., Trial Registration Number: PROSPERO (CRD42014009212)., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Opioids are prescribed frequently and increasingly for the management of chronic non-cancer pain (CNCP). Current systematic reviews have a number of limitations, leaving uncertainty with regard to the benefits and harms associated with opioid therapy for CNCP. We propose to conduct a systematic review and meta-analysis to summarize the evidence for using opioids in the treatment of CNCP and the risk of associated adverse events., Methods and Design: Eligible trials will include those that randomly allocate patients with CNCP to treatment with any opioid or any non-opioid control group. We will use the guidelines published by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to inform the outcomes that we collect and present. We will use the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to evaluate confidence in the evidence on an outcome-by-outcome basis. Teams of reviewers will independently and in duplicate assess trial eligibility, abstract data, and assess risk of bias among eligible trials. To ensure interpretability of our results, we will present risk differences and measures of relative effect for all outcomes reported and these will be based on anchor-based minimally important clinical differences, when available. We will conduct a priori defined subgroup analyses consistent with current best practices., Discussion: Our review will evaluate both the effectiveness and the adverse events associated with opioid use for CNCP, evaluate confidence in the evidence using the GRADE approach, and prioritize patient-important outcomes with a focus on functional gains guided by IMMPACT recommendations. Our results will facilitate evidence-based management of patients with CNCP and identify key areas for future research., Trial Registration: Our protocol is registered on PROSPERO (CRD42012003023), http://www.crd.york.ac.uk/PROSPERO.

Background: Chronic pain has been estimated to affect 60% of patients with diabetes and is strongly associated with reduced activity tolerance. We systematically reviewed randomized controlled trials (RCTs) that explored interventions to improve physical activity among patients with diabetes to establish whether co-morbid chronic pain was captured at baseline or explored as an effect modifier and if trials reported a component designed to target chronic pain., Methodology/principal Findings: We searched CINAHL, Cochrane Central Registry of Controlled Trials, EMBASE, ERIC, MEDLINE, SPORTDiscus and PsycInfo from inception of each database to March 2012 for RCTs that enrolled patients with diabetes and randomly assigned them to an intervention designed to promote physical activity. Two reviewers independently selected trials and abstracted data. We identified 136 trials meeting our inclusion criteria, only one of which that reported capturing chronic pain measures at baseline. No trial reported on specific interventions to address chronic pain as a competing demand, or as an effect modifier., Conclusion/significance: Only 1 trial identified that aimed to promote physical activity among patients with diabetes reported that co-morbid chronic pain was captured at baseline. No trials reported exploring chronic pain as an effect modifier or targeting it as part of its intervention.

Background: Cannabis for medical purposes has been legal in Canada since 2001; however, physicians receive no formal training in this modality, and clinical use of cannabis remains controversial. This study aims to explore the values and preferences of people living with chronic pain (PLwCP) in using medical cannabis for chronic pain to inform guideline development and shared decision-making in clinical practice.Methods: We conducted a descriptive qualitative study using in-depth interviews with PLwCP. Using a deductive/inductive approach, we developed concepts and themes related to values and preferences of PLwCP on their use (or avoidance) of medical cannabis for chronic pain.Results: We interviewed 52 PLwCP, including current medical cannabis users (40), previous users (10) and non-users (2). Most PLwCP who used cannabis therapeutically reported the need for experimentation to determine what cannabis products, routes, and doses worked for them. Perceived benefits of medical cannabis among current users included relief from pain, better sleep, and improved mental health. Reasons for discontinuing use of medical cannabis included lack of improvement in pain or sleep or undesirable side effects. Cannabidiol (CBD) dominant products were reported to result in minimal adverse effects (eg, physical or mental impairment) compared to tetrahydrocannabinol (THC) dominant products. Perceived barriers or facilitators to use included social acceptability, availability or access, cost, and attitudes and knowledge among healthcare providers. Participants noted different routes of cannabis use including oral routes that provided longer-lasting pain relief with a slower onset and inhaled routes with a more rapid onset with shorter-lived effects.Conclusion: Participants' decisions to use medical cannabis for chronic pain were varied, which suggests these decisions are likely to be sensitive to individuals' values and preferences. There is a call for further research and information-sharing to help PLwCP understand the complexities of cannabis use for medical purposes, including ideal dosing and timing.Plain Language Summary: In Canada, cannabis for medical reasons has been legal since 2001. It has been used as one of the many strategies for chronic or ongoing pain, but doctors are not given consistent information regarding its use, and existing guidance does not include the patient point of view. We did this study to explore how people living with chronic pain feel about the use of medical cannabis. We asked 52 people living with chronic pain, including current medical cannabis users, previous users, and non-users. We found that many people who used cannabis for their pain had to experiment to determine what cannabis products, routes, and doses worked for them. Benefits of medical cannabis included relief from pain, better sleep, and improved mental health. Reasons for stopping medical cannabis included no to little improvement in pain and/or sleep or the presence of unwanted side effects. Cannabidiol (CBD) products resulted in fewer unwanted effects (eg, physical or mental impairment) compared to tetrahydrocannabinol (THC) products. People discussed different routes of cannabis use including oral routes that provided longer-lasting pain relief but with a slower onset and inhaled routes with a faster onset of relief but with shorter-lived effects. People's decisions regarding medical cannabis use for chronic pain were varied, suggesting these decisions are likely to be sensitive to individual's values and preferences. More research is needed to learn what doses, products, and routes work for specific chronic pain conditions. [ABSTRACT FROM AUTHOR]