Search

Background: Utilizing cannabis as a therapeutic option for chronic pain (CP) has increased significantly. However, data regarding the potential immunomodulatory effects of cannabis in CP patients remain scarce. We aimed at exploring the relationship between cannabis use and inflammatory cytokines and chemokines among a cohort of CP patients. Methods: Adult patients with a CP diagnosis and medical authorization of cannabis were enrolled. Patients completed validated clinical questionnaires and self-reported the effectiveness of cannabis for symptom management. Patients' blood and cannabis samples were analyzed for the presence of four major cannabinoids, two major cannabinoid metabolites, 29 different cytokines/chemokines, and cortisol. The multivariable linear regression model was used to identify cannabis and patient factors associated with immune markers. Results: Fifty-six patients (48±15 years; 64% females) were included, with dried cannabis (53%) being the most common type of cannabis consumed. Seventy percent of products were considered delta-9-tetrahydrocannabinol (Δ 9 -THC)-dominant. The majority of patients (96%) self-reported effective pain management, and 76% reported a significant decrease in analgesic medication usage ( p ≤0.001). Compared with males, female patients had higher plasma levels of cannabidiol (CBD), cannabidiolic acid, Δ 9 -THC, and 11-hydroxy-Δ 9 -tetrahydrocannabinol but lower concentrations of delta-9-tetrahydrocannabinolic acid and 11-nor-9-carboxy-Δ 9 -tetrahydrocannabinol (THC-COOH). Females had significantly lower eotaxin levels ( p =0.04) in comparison to male patients. The regression analysis indicated that high cannabis doses were related to increased levels of interleukin (IL)-12p40 ( p =0.02) and IL-6 ( p =0.01), whereas female sex was associated with decreased eotaxin ( p ≤0.01) concentrations. Blood CBD levels were associated with lower vascular endothelial growth factor ( p =0.04) concentrations, and THC-COOH was a factor related to decreased tumor necrosis factor alpha ( p =0.02) and IL-12p70 ( p =0.03). Conclusion: This study provides further support for the patient-perceived effectiveness of cannabis in managing CP symptoms and reducing analgesic medication consumption. The results suggest a potential sex difference in metabolizing cannabinoids, and the varying immune marker concentrations may support a possible immunomodulatory effect associated with patient sex and cannabis product type. These preliminary findings provide grounds for further validation using larger, well-designed studies with longer follow-up periods.

Abstract: Interpatient variability is frequently observed among individuals with chronic low back pain (cLBP). This review aimed at identifying phenotypic domains and characteristics that account for interpatient variability in cLBP. We searched MEDLINE ALL (through Ovid), Embase Classic and EMBASE (through Ovid), Scopus, and CINAHL Complete (through EBSCOhost) databases. Studies that aimed to identify or predict cLBP different phenotypes were included. We excluded studies that focused on specific treatments. The methodological quality was assessed using an adaptation of the Downs and Black tool. Forty-three studies were included. Although the patient and pain-related characteristics used to identify phenotypes varied considerably across studies, the following were among the most identified phenotypic domains and characteristics that account for interpatient variability in cLBP: pain-related characteristics (including location, severity, qualities, and duration) and pain impact (including disability, sleep, and fatigue), psychological domains (including anxiety and depression), behavioral domains (including coping, somatization, fear avoidance, and catastrophizing), social domains (including employment and social support), and sensory profiling (including pain sensitivity and sensitization). Despite these findings, our review showed that the evidence on pain phenotyping still requires further investigation. The assessment of the methodological quality revealed several limitations. We recommend adopting a standard methodology to enhance the generalizability of the results and the implementation of a comprehensive and feasible assessment framework to facilitate personalized treatments in clinical settings., (Copyright © 2023 International Association for the Study of Pain.)

Objectives: In a cohort of workers disabled by a work-related injury or illness, this study aimed to: (i) compare pre-injury prevalence estimates for common chronic conditions to chronic condition prevalence in a representative sample of working adults; (ii) calculate the incidence of chronic conditions post-injury; and (iii) estimate the association between persistent pain symptoms and the incidence of common chronic conditions., Methods: Eighteen months post-injury, 1832 workers disabled by a work-related injury or illness in Ontario, Canada, completed an interviewer-administered survey. Participants reported pre- and post-injury prevalence of seven physician-diagnosed chronic conditions, and demographic, employment, and health characteristics. Pre-injury prevalence estimates were compared to estimates from a representative sample of workers. Multivariable logistic regression was used to examine the association of persistent pain with post-injury chronic condition incidence., Results: Age-standardized pre-injury prevalence rates for diabetes, hypertension, arthritis, and back problems were similar to prevalence rates observed among working adults in Ontario, while prevalence rates for mood disorder, asthma and migraine were moderately elevated. Post-injury prevalence rates of mood disorder, migraine, hypertension, arthritis, and back problems were elevated substantially in this cohort. High persistent pain symptoms were strongly associated with the 18-month incidence of these conditions., Conclusions: The incidence of five chronic conditions over an 18-month follow-up period post injury was substantial. Persistent pain at 18 months was associated with this elevated incidence, with population attributable fraction estimates suggesting that 37-39% of incident conditions may be attributed to exposure to high levels of persistent pain.

Importance: Opioid use for chronic nonmalignant pain can be harmful., Objective: To test whether a multicomponent, group-based, self-management intervention reduced opioid use and improved pain-related disability compared with usual care., Design, Setting, and Participants: Multicentered, randomized clinical trial of 608 adults taking strong opioids (buprenorphine, dipipanone, morphine, diamorphine, fentanyl, hydromorphone, methadone, oxycodone, papaveretum, pentazocine, pethidine, tapentadol, and tramadol) to treat chronic nonmalignant pain. The study was conducted in 191 primary care centers in England between May 17, 2017, and January 30, 2019. Final follow-up occurred March 18, 2020., Intervention: Participants were randomized 1:1 to either usual care or 3-day-long group sessions that emphasized skill-based learning and education, supplemented by 1-on-1 support delivered by a nurse and lay person for 12 months., Main Outcomes and Measures: The 2 primary outcomes were Patient-Reported Outcomes Measurement Information System Pain Interference Short Form 8a (PROMIS-PI-SF-8a) score (T-score range, 40.7-77; 77 indicates worst pain interference; minimal clinically important difference, 3.5) and the proportion of participants who discontinued opioids at 12 months, measured by self-report., Results: Of 608 participants randomized (mean age, 61 years; 362 female [60%]; median daily morphine equivalent dose, 46 mg [IQR, 25 to 79]), 440 (72%) completed 12-month follow-up. There was no statistically significant difference in PROMIS-PI-SF-8a scores between the 2 groups at 12-month follow-up (-4.1 in the intervention and -3.17 in the usual care groups; between-group difference: mean difference, -0.52 [95% CI, -1.94 to 0.89]; P = .15). At 12 months, opioid discontinuation occurred in 65 of 225 participants (29%) in the intervention group and 15 of 208 participants (7%) in the usual care group (odds ratio, 5.55 [95% CI, 2.80 to 10.99]; absolute difference, 21.7% [95% CI, 14.8% to 28.6%]; P < .001). Serious adverse events occurred in 8% (25/305) of the participants in the intervention group and 5% (16/303) of the participants in the usual care group. The most common serious adverse events were gastrointestinal (2% in the intervention group and 0% in the usual care group) and locomotor/musculoskeletal (2% in the intervention group and 1% in the usual care group). Four people (1%) in the intervention group received additional medical care for possible or probable symptoms of opioid withdrawal (shortness of breath, hot flushes, fever and pain, small intestinal bleed, and an overdose suicide attempt)., Conclusions and Relevance: In people with chronic pain due to nonmalignant causes, compared with usual care, a group-based educational intervention that included group and individual support and skill-based learning significantly reduced patient-reported use of opioids, but had no effect on perceived pain interference with daily life activities., Trial Registration: isrctn.org Identifier: ISRCTN49470934.

Objectives: To describe the design, development and pilot of a multicomponent intervention aimed at supporting withdrawal of opioids for people with chronic non-malignant pain for future evaluation in the Improving the Wellbeing of people with Opioid Treated CHronic pain (I-WOTCH) randomised controlled trial., Design: The I-WOTCH intervention draws on previous literature and collaboration with stakeholders (patient and public involvement). Intervention mapping and development activities of Behaviour Change Taxonomy are described., Setting: The intervention development was conducted by a multidisciplinary team with clinical, academic and service user perspectives. The team had expertise in the development and testing of complex health behaviour interventions, opioid tapering and pain management in primary and secondary care, I.T programming, and software development-to develop an opioid tapering App., Participants: The I-WOTCH trial participants are adults (18 years and over) with chronic non-malignant pain using strong opioids for at least 3 months and on most days in the preceding month., Outcomes: A multicomponent self-management support package to help people using opioids for chronic non-malignant pain reduce opioid use., Interventions and Results: Receiving information on the impact of long-term opioid use, and potential adverse effects were highlighted as important facilitators in making the decision to reduce opioids. Case studies of those who have successfully stopped taking opioids were also favoured as a facilitator to reduce opioid use. Barriers included the need for a 'trade-off to fill the deficit of the effect of the drug'. The final I-WOTCH intervention consists of an 8-10 week programme incorporating: education; problem-solving; motivation; group and one to one tailored planning; reflection and monitoring. A detailed facilitator manual was developed to promote consistent delivery of the intervention across the UK., Conclusions: We describe the development of an opioid reduction intervention package suitable for testing in the I-WOTCH randomised controlled trial., Trial Registration Number: ISRCTN49470934., Competing Interests: Competing interests: SE is the Chair of the specialised pain CRG at NHS England, he is Chief investigator and principal investigator of a number of NIHR and Industry funded trials, he has received personal fees from Medtronic Ltd, Mainstay Medical, Boston Scientific Corp for consultancy work. His department has received research funding from the National Institute of Health Research, Medtronic Ltd and Boston Scientific Corp. HS is director of Health Psychology Services Ltd, providing psychological services for a range of health related conditions. NKYT is chief investigator or coinvestigator of other chronic pain related projects funded by the NIHR, MRC, Warwick-Wellcome Translational Partnership. MU is chief investigator or coinvestigator on multiple previous and current research grants from the UK National Institute for Health Research, Arthritis Research UK and is a coinvestigator on grants funded by the Australian NHMRC. He was an NIHR Senior Investigator until March 2021. He has received travel expenses for speaking at conferences from the professional organisations hosting the conferences. He is a director and shareholder of Clinvivo Ltd that provides electronic data collection for health services research. He is part of an academic partnership with Serco Ltd, funded by the European Social Fund, related to return to work initiatives. He receives some salary support from University Hospitals Coventry and Warwickshire. He is a coinvestigator on three NIHR funded studies receiving additional support from Stryker Ltd. He has accepted honoraria for teaching/lecturing from consortium for advanced research training in Africa. Until March 2020, he was an editor of the NIHR journal series, and a member of the NIHR Journal Editors Group, for which he received a fee. ADF is author of the My Opioid Manager book and App distributed in iTunes and Google Play. Both book and app are free of charge. She is author of the Opioid Manager App, a paid app distributed only in iTunes for healthcare professionals. The app is owned by UHN, the hospital where ADF works. ADF does not get any financial benefit from the sales of the app. ADF has a monetized YouTube channel since January 2021 that contains some videos about opioids and opioid tapering. Since April 2021, ADF has an unrestricted educational grant to maintain an online self-assessment opioid course for healthcare professionals in Canada. The funding is provided by the Canadian Generics Pharmaceutical Association (CGPA). The funding organisation has no role in the preparation, approval, recruitment of participants, or data analysis of the course content. Responsibility for the course content is solely that of the authors. ST is chief investigator or coinvestigator on multiple previous and current research grants from the UK National Institute for Health Research., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Clinically focused interventions for people living with pain, such as health professional education, clinical decision support systems, prescription drug monitoring programs, and multidisciplinary care to support opioid tapering, have all been promoted as important solutions to the North American opioid crisis. Yet none have so far delivered substantive beneficial opioid-related population health outcomes. In fact, while total opioid prescribing has leveled off or reduced in many jurisdictions, population-level harms from opioids have continued to increase dramatically. We attribute this failure partly to a poor recognition of the epistemic and ethical complexities at the interface of clinical and population health. We draw on a framework of knowledge networks in wicked problems to identify 3 strategies to help navigate these complexities: (1) designing and evaluating clinically focused interventions as complex interventions, (2) reformulating evidence to make population health dynamics apparent, and (3) appealing to the inseparability of facts and values to support decision-making in uncertainty. We advocate that applying these strategies will better equip clinically focused interventions as complements to structural and public health interventions to achieve the desired beneficial population health effects. ( Am J Public Health . 2022;112(S1):S56-S65. https://doi.org/10.2105/AJPH.2021.306500).

Chronic pain is a complex multidimensional condition that requires management with multiple professions' expertise. Healthcare training programs tend to adhere to curricula within their own profession with very few interactions with other groups. Project ECHO (Extension for Community Healthcare Outcomes) Chronic Pain and Opioid Stewardship is a model for interprofessional education, using tele-mentoring, case-base discussions and clinically focused presentations. The goal is to improve competency and confidence in managing complex cases in primary care. This qualitative study engaged twenty healthcare practitioners from multiple professions who had participated in ECHO in focus group discussions about managing patients with chronic pain, about their reasons for and the effect of participating in Project ECHO Ontario Chronic Pain/Opioid Stewardship, and about their perspectives on interprofessional care. The results show that participating in ECHO resulted in personal and professional benefit, and increased understanding about their own roles and limitations, as well as other healthcare professionals' roles. The participants described changes in their attitudes toward patients with chronic pain, and their colleagues from other professions. Non-physician participants were more likely to approach physicians to discuss their assessment and diagnosis as well as prescriptions. The interprofessional nature of the program was seen as positive and contributed to perceived changes in practice collaboration. These results show that healthcare professionals from multiple professions expressed mainly positive views of ECHO's emphasis on interprofessional care, with different professions appreciating different aspects of that approach.

Background: Chronic nonspecific low back pain (LBP) is very common; it is defined as pain without a recognizable etiology that lasts for more than three months. Some clinical practice guidelines suggest that acupuncture can offer an effective alternative therapy. This review is a split from an earlier Cochrane review and it focuses on chronic LBP., Objectives: To assess the effects of acupuncture compared to sham intervention, no treatment, or usual care for chronic nonspecific LBP., Search Methods: We searched CENTRAL, MEDLINE, Embase, CINAHL, two Chinese databases, and two trial registers to 29 August 2019 without restrictions on language or publication status. We also screened reference lists and LBP guidelines to identify potentially relevant studies., Selection Criteria: We included only randomized controlled trials (RCTs) of acupuncture for chronic nonspecific LBP in adults. We excluded RCTs that investigated LBP with a specific etiology. We included trials comparing acupuncture with sham intervention, no treatment, and usual care. The primary outcomes were pain, back-specific functional status, and quality of life; the secondary outcomes were pain-related disability, global assessment, or adverse events., Data Collection and Analysis: Two review authors independently screened the studies, assessed the risk of bias and extracted the data. We meta-analyzed data that were clinically homogeneous using a random-effects model in Review Manager 5.3. Otherwise, we reported the data qualitatively. We used the GRADE approach to assess the certainty of the evidence., Main Results: We included 33 studies (37 articles) with 8270 participants. The majority of studies were carried out in Europe, Asia, North and South America. Seven studies (5572 participants) conducted in Germany accounted for 67% of the participants. Sixteen trials compared acupuncture with sham intervention, usual care, or no treatment. Most studies had high risk of performance bias due to lack of blinding of the acupuncturist. A few studies were found to have high risk of detection, attrition, reporting or selection bias. We found low-certainty evidence (seven trials, 1403 participants) that acupuncture may relieve pain in the immediate term (up to seven days) compared to sham intervention (mean difference (MD) -9.22, 95% confidence interval (CI) -13.82 to -4.61, visual analogue scale (VAS) 0-100). The difference did not meet the clinically important threshold of 15 points or 30% relative change. Very low-certainty evidence from five trials (1481 participants) showed that acupuncture was not more effective than sham in improving back-specific function in the immediate term (standardized mean difference (SMD) -0.16, 95% CI -0.38 to 0.06; corresponding to the Hannover Function Ability Questionnaire (HFAQ, 0 to 100, higher values better) change (MD 3.33 points; 95% CI -1.25 to 7.90)). Three trials (1068 participants) yielded low-certainty evidence that acupuncture seemed not to be more effective clinically in the short term for quality of life (SMD 0.24, 95% CI 0.03 to 0.45; corresponding to the physical 12-item Short Form Health Survey (SF-12, 0-100, higher values better) change (MD 2.33 points; 95% CI 0.29 to 4.37)). The reasons for downgrading the certainty of the evidence to either low to very low were risk of bias, inconsistency, and imprecision. We found moderate-certainty evidence that acupuncture produced greater and clinically important pain relief (MD -20.32, 95% CI -24.50 to -16.14; four trials, 366 participants; (VAS, 0 to 100), and improved back function (SMD -0.53, 95% CI -0.73 to -0.34; five trials, 2960 participants; corresponding to the HFAQ change (MD 11.50 points; 95% CI 7.38 to 15.84)) in the immediate term compared to no treatment. The evidence was downgraded to moderate certainty due to risk of bias. No studies reported on quality of life in the short term or adverse events. Low-certainty evidence (five trials, 1054 participants) suggested that acupuncture may reduce pain (MD -10.26, 95% CI -17.11 to -3.40; not clinically important on 0 to 100 VAS), and improve back-specific function immediately after treatment (SMD: -0.47; 95% CI: -0.77 to -0.17; five trials, 1381 participants; corresponding to the HFAQ change (MD 9.78 points, 95% CI 3.54 to 16.02)) compared to usual care. Moderate-certainty evidence from one trial (731 participants) found that acupuncture was more effective in improving physical quality of life (MD 4.20, 95% CI 2.82 to 5.58) but not mental quality of life in the short term (MD 1.90, 95% CI 0.25 to 3.55). The certainty of evidence was downgraded to moderate to low because of risk of bias, inconsistency, and imprecision. Low-certainty evidence suggested a similar incidence of adverse events immediately after treatment in the acupuncture and sham intervention groups (four trials, 465 participants) (RR 0.68 95% CI 0.46 to 1.01), and the acupuncture and usual care groups (one trial, 74 participants) (RR 3.34, 95% CI 0.36 to 30.68). The certainty of the evidence was downgraded due to risk of bias and imprecision. No trial reported adverse events for acupuncture when compared to no treatment. The most commonly reported adverse events in the acupuncture groups were insertion point pain, bruising, hematoma, bleeding, worsening of LBP, and pain other than LBP (pain in leg and shoulder)., Authors' Conclusions: We found that acupuncture may not play a more clinically meaningful role than sham in relieving pain immediately after treatment or in improving quality of life in the short term, and acupuncture possibly did not improve back function compared to sham in the immediate term. However, acupuncture was more effective than no treatment in improving pain and function in the immediate term. Trials with usual care as the control showed acupuncture may not reduce pain clinically, but the therapy may improve function immediately after sessions as well as physical but not mental quality of life in the short term. The evidence was downgraded to moderate to very low-certainty considering most of studies had high risk of bias, inconsistency, and small sample size introducing imprecision. The decision to use acupuncture to treat chronic low back pain might depend on the availability, cost and patient's preferences., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objectives: Opioid-related deaths continue to increase in North America, an epidemic that was initiated by high rates of opioid prescribing. We designed a multifaceted, theory-informed Opioid Self-Assessment (OSA) package, to increase adherence to the Canadian Opioid Guideline among family physicians. This study aimed to assess changes in Canadian family physicians' knowledge and practices after completing the OSA package., Design: We conducted a mixed-method evaluation using a pre-test and post-test design that involved the collection of both qualitative and quantitative data., Setting: This research was conducted in the primary care setting in Ontario, Canada., Participants: We recruited a purposive sample of nine family physicians in Ontario who use long-term opioid therapy to treat patients with chronic pain., Interventions: The OSA package included four components: an online knowledge test, an online learning programme, a safe medication practice self-assessment questionnaire and chart audit with feedback., Outcome Measures: Our measures included changes in knowledge, opioid safety practices and physicians' perspectives on the OSA package., Results: We found statistically significant improvements between pre-test and post-test knowledge scores at both baseline and 6-month follow-up. Physicians' scores improved significantly on five of the seven core characteristics of the practice self-assessment questionnaire. On the chart audits, we observed an improvement in patient education between baseline and 6 months. Qualitative interviews showed that participants appreciated embedded resources in the OSA package. The completion of the package stimulated identification of gaps or deficits in practice and served as a useful reminder to discuss risk and safety with patients. Participants described the chart review as helpful in prompting discussions with their patients, identifying deficits and strengths and a 'primary motivator' for project participation., Conclusions: The OSA package has the potential to improve medication safety practices in primary care related to opioid monitoring and adherence to current opioid guidelines., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Chronic non-malignant pain has a major impact on the well-being, mood and productivity of those affected. Opioids are increasingly prescribed to manage this type of pain, but with a risk of other disabling symptoms, when their effectiveness has been questioned. This trial is designed to implement and evaluate a patient-centred intervention targeting withdrawal of strong opioids in people with chronic pain., Methods and Analysis: A pragmatic, multicentre, randomised controlled trial will assess the clinical and cost-effectiveness of a group-based multicomponent intervention combined with individualised clinical facilitator led support for the management of chronic non-malignant pain against the control intervention (self-help booklet and relaxation compact disc). An embedded process evaluation will examine fidelity of delivery and investigate experiences of the intervention. The two primary outcomes are activities of daily living (measured by Patient-Reported Outcomes Measurement Information System Pain Interference Short Form (8A)) and opioid use. The secondary outcomes are pain severity, quality of life, sleep quality, self-efficacy, adverse events and National Health Service (NHS) healthcare resource use. Participants are followed up at 4, 8 and 12 months, with a primary endpoint of 12 months. Between-group differences will indicate effectiveness; we are looking for a difference of 3.5 points on our pain interference outcome (scale 40 to 77). We will undertake an NHS perspective cost-effectiveness analysis using quality adjusted life years., Ethics and Dissemination: Full approval was given by Yorkshire & The Humber - South Yorkshire Research Ethics Committee on 13 September, 2016 (16/YH/0325). Appropriate local approvals were sought for each area in which recruitment was undertaken. The current protocol version is 1.6 date 19 December 2018. Publication of results in peer- reviewed journals will inform the scientific and clinical community. We will disseminate results to patient participants and study facilitators in a study newsletter as well as a lay summary of results on the study website., Trial Registration Number: ISRCTN49470934; Pre-results., Competing Interests: Competing interests: MU was Chair of the NICE accreditation advisory committee until March 2017 for which he received a fee. He is the chief investigator or co-investigator on multiple previous and current research grants from the UK National Institute for Health Research, Arthritis Research UK and is co-investigator on grants funded by the Australian NHMRC. He is an NIHR Senior Investigator. He has received travel expenses for speaking at conferences from the professional organisations hosting the conferences. He is a director and shareholder of Clinvivo Ltd that provides electronic data collection for health services research. He is part of an academic partnership with Serco Ltd related to return to work initiatives. He is a co-investigator on a study receiving support in kind from Orthospace Ltd. He is an editor of the NIHR journal series, and a member of the NIHR Journal Editors Group, for which he receives a fee. SE is investigator on a number of NIHR and industry sponsored studies. He received travel expenses for speaking at conferences from the professional organisations. SE consults for Medtronic, Abbott, Boston Scientific and Mainstay Medical, none in relation to opioids. SE is chair of the BPS Science and Research Committee. SE is deputy Chair of the NIHR CRN Anaesthesia Pain and Perioperative Medicine National Specialty Group. SE’s department has received fellowship funding from Medtronic as well as nurse funding from Abbott. HS is director of Health Psychology Services Ltd, providing psychological services for a range of health related conditions. AF developed an app that is sold in iTunes for US$9.99 (Opioid Manager). The app is owned by the hospital (UHN) where Dr Furlan works, and Dr Furlan does not retain any profits of the sales of this app for herself. KS received grant funding as PI and CoI from NIHR for other projects. She was on the NIHR HS&DR Funding Board until January 2018. NT received grant funding as PI and CoI from NIHR for other projects and current funding as PI from the Medical Research Council., (© 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.)

Competing Interests: Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: HS: joint chief investigator for the I-WOTCH study and is co-applicant on other National Institute of Health Research (NIHR) funded studies. SE: grants from the NIHR, joint chief investigator on the I-WOTCH study. MU: multiple grants as chief investigator and co-applicant from NIHR, Arthritis Research UK, and National Medical and Health Research Council. Co-applicant on the I-WOTCH study. Until March 2017 he was chair of NICE Accreditation Advisory Committee for which he received a fee. He is a journal editor for NIHR, and a member of the NIHR Journal Editors Groups, for which he receives a fee. He is director and shareholder of Clinvivo Ltd He is part of an academic partnership with Serco Ltd AF: a co-investigator on the I-WOTCH study, and she acknowledges receipt of funding from the Canadian Institutes for Health Research. JN is a research fellow on the I-WOTCH study.

Competing Interests: Competing interests: Owen Williamson reports nonfinancial support from Health Canada and personal fees and nonfinancial support from Purdue Pharma (Canada), Mundipharma International Ltd. and INVIVO Communications Ltd., outside the submitted work. Andrea Furlan is acknowledged in the guideline published in this issue of CMAJ. She participated in the first meeting of the clinical experts in January 2016 but was not involved in the remaining development of the guideline.

Enriched enrolment, randomised withdrawal (EERW) pain trials select, before randomisation, patients who respond by demonstrating a predetermined degree of pain relief and acceptance of adverse events. There is uncertainty over the value of this design. We report a systematic review of EERW trials in chronic noncancer pain together with a critical appraisal of methods and potential biases in the methods used and recommendations for the design and reporting of future EERW trials. Electronic and other searches found 25 EERW trials published between 1995 and June 2014, involving 5669 patients in a randomised withdrawal phase comparing drug with placebo; 13 (median, 107 patients) had a randomised withdrawal phase of 6 weeks or less, and 12 (median, 334) lasted 12 to 26 weeks. Risks of bias included short duration, inadequate outcome definition, incomplete outcome data reporting, small size, and inadequate dose tapering on randomisation to placebo. Active treatment was usually better than placebo (22/25 trials). This review reduces the uncertainty around the value of EERW trials in pain. If properly designed, conducted, and reported, they are feasible and useful for making decisions about pain therapies. Shorter, small studies can be explanatory; longer, larger studies can inform practice. Current evidence is inadequate for valid comparisons in outcome between EERW and classical trials, although no gross differences were found. This systematic review provides a framework for assessing potential biases and the value of the EERW trials, and for the design of future studies by making recommendations for the conduct and reporting of EERW trials.

Chronic pain is a prevalent and serious problem in the province of Ontario. Frontline primary care providers (PCPs) manage the majority of chronic pain patients, yet receive minimal training in chronic pain. ECHO (Extension for Community Healthcare Outcomes) Ontario Chronic Pain & Opioid Stewardship aims to address the problem of chronic pain management in Ontario. This paper describes the development, operation, and evaluation of the ECHO Ontario Chronic Pain project. We discuss how ECHO increases PCP access and capacity to manage chronic pain, the development of a community of practice, as well as the limitations of our approach. The ECHO model is a promising approach for healthcare system improvement. ECHO's strength lies in its simplicity, adaptability, and use of existing telemedicine infrastructure to increase both access and capacity of PCPs in underserviced, rural, and remote communities.

Aims: The Opioid Manager (OM) is a point-of-care paper tool for physicians, which summarizes the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain. To evaluate the efficacy of the OM, there is a need to better understand how physicians are using the OM, and how it is relevant to their practice., Methods: Semistructured interviews were conducted with six family physicians in Ontario with clinical pain management experience. The interviews were analyzed using content analysis. The technique of "code-recode" was conducted by two analysts to verify content validity., Results: The following main themes emerged: 1) OM as a communication tool; 2) OM as an educational tool; 3) OM as a clinical tool; 4) OM content/design; 5) OM benefits; 6) who the OM is used with; 7) OM potential; and 8) challenges of pain management. Physicians' commented the OM was a useful reference for helping their clinical decision making regarding opioids, and used it to educate and communicate with their patients/colleagues. Although many felt the content/design of the OM had a number of good features, there was a need for modifications (ie, merge with other tools and create electronic version). Given the challenges associated with pain management, a number of benefits were derived from using the OM (ie, protection and building therapeutic alliance), and respondents' felt the tool had the potential to meet a number of unmet needs related to opioid management., Conclusions: Overall, the OM was viewed positively for improving pain management practices but further work is required to refine the tool's potential.

Background: The use of opioids in the long-term management of chronic low-back pain (CLBP) has increased dramatically. Despite this trend, the benefits and risks of these medications remain unclear. This review is an update of a Cochrane review first published in 2007., Objectives: To determine the efficacy of opioids in adults with CLBP., Search Methods: We electronically searched the Cochrane Back Review Group's Specialized Register, CENTRAL, CINAHL and PsycINFO, MEDLINE, and EMBASE from January 2006 to October 2012. We checked the reference lists of these trials and other relevant systematic reviews for potential trials for inclusion., Selection Criteria: We included randomized controlled trials (RCTs) that assessed the use of opioids (as monotherapy or in combination with other therapies) in adults with CLBP that were at least four weeks in duration. We included trials that compared non-injectable opioids to placebo or other treatments. We excluded trials that compared different opioids only., Data Collection and Analysis: Two authors independently assessed the risk of bias and extracted data onto a pre-designed form. We pooled results using Review Manager (RevMan) 5.2. We reported on pain and function outcomes using standardized mean difference (SMD) or risk ratios with 95% confidence intervals (95% CI). We used absolute risk difference (RD) with 95% CI to report adverse effects., Main Results: We included 15 trials (5540 participants). Tramadol was examined in five trials (1378 participants); it was found to be better than placebo for pain (SMD -0.55, 95% CI -0.66 to -0.44; low quality evidence) and function (SMD -0.18, 95% CI -0.29 to -0.07; moderate quality evidence). Transdermal buprenorphine (two trials, 653 participants) may make little difference for pain (SMD -2.47, 95%CI -2.69 to -2.25; very low quality evidence), but no difference compared to placebo for function (SMD -0.14, 95%CI -0.53 to 0.25; very low quality evidence). Strong opioids (morphine, hydromorphone, oxycodone, oxymorphone, and tapentadol), examined in six trials (1887 participants), were better than placebo for pain (SMD -0.43, 95%CI -0.52 to -0.33; moderate quality evidence) and function (SMD -0.26, 95% CI -0.37 to -0.15; moderate quality evidence). One trial (1583 participants) demonstrated that tramadol may make little difference compared to celecoxib (RR 0.82, 95% CI 0.76 to 0.90; very low quality evidence) for pain relief. Two trials (272 participants) found no difference between opioids and antidepressants for either pain (SMD 0.21, 95% CI -0.03 to 0.45; very low quality evidence), or function (SMD -0.11, 95% -0.63 to 0.42; very low quality evidence). The included trials in this review had high drop-out rates, were of short duration, and had limited interpretability of functional improvement. They did not report any serious adverse effects, risks (addiction or overdose), or complications (sleep apnea, opioid-induced hyperalgesia, hypogonadism). In general, the effect sizes were medium for pain and small for function., Authors' Conclusions: There is some evidence (very low to moderate quality) for short-term efficacy (for both pain and function) of opioids to treat CLBP compared to placebo. The very few trials that compared opioids to non-steroidal anti-inflammatory drugs (NSAIDs) or antidepressants did not show any differences regarding pain and function. The initiation of a trial of opioids for long-term management should be done with extreme caution, especially after a comprehensive assessment of potential risks. There are no placebo-RCTs supporting the effectiveness and safety of long-term opioid therapy for treatment of CLBP.

Background: In May 2010, a new Canadian guideline on prescribing opioids for chronic noncancer pain (CNCP) was released. To assess changes in family physicians' (FPs) prescribing of opioids following the release of the guideline, it is necessary to know their practices before the guideline was widely disseminated., Objectives: To determine FPs' practices and knowledge in prescribing opioids for CNCP in relation to the Canadian guideline, and to determine factors that hinder or enable FPs in prescribing opioids for CNCP., Methods: An online survey was developed and FPs who manage CNCP were electronically contacted through the College of Family Physicians of Canada, university continuing medical education offices and provincial regulatory colleges., Results: A total of 710 responses were received. FPs followed a precautionary approach to prescribing opioids and already practiced in accordance with Canadian guideline recommendations by discussing adverse effects, monitoring for aberrant drug-related behaviour and advising caution when driving. However, FPs seldom discontinued opioids even if they were ineffective and were unaware of the 'watchful dose' of opioids, the daily dose at which patients may need reassessment or closer monitoring. Only two of nine knowledge questions were answered correctly by more than 40% of FPs. The main enabler to optimal opioid prescribing was having access to a patient's opioid history from a provincial prescription monitoring program. The main barriers to optimal prescribing were concerns about addiction and misuse., Conclusions: While FPs follow a precautionary approach to prescribing opioids for CNCP, there are substantial practice and knowledge gaps, with implications for patient safety and costs.

The Opioid Manager is designed to be used as a point-of-care tool for providers prescribing opioids for chronic noncancer pain. It condenses the key elements from the Canadian Opioid Guideline and can be used as a chart insert. The Opioid Manager has been validated and is available for download from the Guideline's Web site http://nationalpaincentre.mcmaster.ca/opioidmanager/. The Opioid Manager is divided into the following four parts: A) before you write the first script, B) initiation trial, C) maintenance and monitoring, and D) when is it time to decrease the dose or stop the opioid completely? The Opioid Manager has been downloaded by 1,432 users: 47 percent family physicians, 18 percent pharmacists, 13 percent other physicians, and 22 percent miscellaneous. To show how to use the Opioid Manager, the authors created a 10-minute video that is available on the Internet. The Opioid Manager is being translated to French, Spanish, Portuguese, and Farsi.