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 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

Values and preferences relate to the importance that patients place on health outcomes (eg, bleeding, having a deep venous thrombosis) and are essential when weighing benefits and harms in guideline recommendations. To inform the American Society of Hematology guidelines for management of venous thromboembolism (VTE) disease, we conducted a systematic review of patients’ values and preferences related to VTE. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature from inception to April of 2018 (PROSPERO-CRD42018094003). We included quantitative and qualitative studies. We followed Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance for rating the certainty and presenting findings for quantitative research about the relative importance of health outcomes and a grounded theory approach for qualitative thematic synthesis. We identified 14 quantitative studies (2465 participants) describing the relative importance of VTE-related health states in a widely diverse population of patients, showing overall small to important impact on patients’ lives (certainty of the evidence from low to moderate). Additionally, evidence from 34 quantitative studies (6424 participants) and 15 qualitative studies (570 participants) revealed that patients put higher value on VTE risk reduction than on the potential harms of the treatment (certainty of evidence from low to moderate). Studies also suggested a clear preference for oral medication over subcutaneous medication (moderate certainty). The observed variability in health state values may be a result of differences in the approaches used to elicit them and the diversity of included populations rather than true variability in values. This finding highlights the necessity to explore the variability induced by different approaches to ascertain values.

ObjectiveTo assess the efficacy and harms of adding medical cannabis to prescription opioids among people living with chronic pain.DesignSystematic review.Data sourcesCENTRAL, EMBASE and MEDLINE.Main outcomes and measuresOpioid dose reduction, pain relief, sleep disturbance, physical and emotional functioning and adverse events.Study selection criteria and methodsWe 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.ResultsEligible 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).ConclusionOpioid-sparing effects of medical cannabis for chronic pain remain uncertain due to very low certainty evidence.PROSPERO registration numberCRD42018091098.

Introduction Existing reviews exploring cannabis effectiveness have numerous limitations including narrow search strategies. We systematically explored cannabis effects on PTSD symptoms, quality of life (QOL), and return to work (RTW). We also investigated harm outcomes such as adverse effects and dropouts due to adverse effects, inefficacy, and all-cause dropout rates. Methods Our search in MEDLINE, EMBASE, PsycInfo, CINAHL, Web of Science, CENTRAL, and PubMed databases, yielded 1 eligible RCT and 10 observational studies (n = 4672). Risk of bias (RoB) was assessed with the Cochrane risk of bias tool and ROBINS-I. Results Evidence from the included studies was mainly based on non-randomized studies with no comparators. Results from unpooled, high RoB studies showed that cannabis was associated with a reduction in overall PTSD symptoms and improved QOL. Dry mouth, headaches, and psychoactive effects such as agitation and euphoria were the commonly reported adverse effects. In most studies, cannabis was well tolerated, but small proportions of patients experienced a worsening of PTSD symptoms. Conclusion Evidence in the current study primarily stems from low quality and high RoB observational studies. Further RCTs investigating cannabis effects on PTSD treatment should be conducted with larger sample sizes and explore a broader range of patient-important outcomes.

Objective Approximately one in four total knee replacement patients develop persistent pain. Identification of those at higher risk could help inform optimal management. Methods We searched MEDLINE, EMBASE, CINAHL, AMED, SPORTDiscus and PsycINFO for observational studies that explored the association between risk factors and persistent pain (≥3 months) after total knee replacement. We pooled estimates of association for all independent variables reported by &gt; 1 study. Results Thirty studies (26,517 patients) reported the association of 151 independent variables with persistent pain after knee replacement. High certainty evidence demonstrated an increased risk of persistent pain with pain catastrophizing (absolute risk increase [ARI] 23%, 95% CI 12 to 35), younger age (ARI for every 10-year decrement from age 80, 4%, 95% CI 2 to 6), and moderate-to-severe acute post-operative pain (ARI 30%, 95% CI 20 to 39). Moderate certainty evidence suggested an association with female sex (ARI 7%, 95% CI 3 to 11) and higher pre-operative pain (ARI 35%, 95% CI 7 to 58). Studies did not adjust for both peri-operative pain severity and pain catastrophizing, which are unlikely to be independent. High to moderate certainty evidence demonstrated no association with pre-operative range of motion, body mass index, bilateral or unilateral knee replacement, and American Society of Anesthesiologists score. Conclusions Rigorously conducted observational studies are required to establish the relative importance of higher levels of peri-operative pain and pain catastrophizing with persistent pain after knee replacement surgery. Systematic review registration PROSPERO CRD42018065943

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Study Design. Qualitative study. Objective. The objective of this study was to compare the perceptions of patients and surgeons regarding the risks and benefits of lumbar decompressive surgery for sciatica following a consultation meeting. Summary of Background Data. Evidence regarding pain improvement in patients following lumbar decompressive surgery for sciatica is inconsistent. Given this inconsistency, patients choosing to undergo lumbar decompressive surgery must accept the risks associated with the surgery despite uncertainty regarding benefits. This raises questions as to the nature of informed decision-making for patients choosing to undergo surgery for sciatica. Methods. We undertook a qualitative descriptive study with 12 adult lumbar decompressive surgery candidates and six of their spine surgeons and analyzed data using inductive content analysis. Results. Our analysis revealed that most patients were satisfied with the consultation despite limited understanding of lumbar decompressive surgery. We found discrepancies between patients’ preoperative expectations and understanding of information provided by surgeons and what surgeons believed they had conveyed. Surgeons and patients disagreed on how much information is needed about postsurgical activity modifications and long-term outcomes to make a decision about whether or not to undergo surgery, with patients desiring more information. As a result, for most patients, the decision-making process extended beyond the information provided by surgeons and incorporated information from family members, friends, family doctors, and the internet. Conclusion. Our results highlight misunderstandings between patients and surgeons, particularly in regard to prognosis and activity modifications. Since this information is important for patients choosing whether to undergo a surgical intervention, our study provides guidance to improve informed decisions about sciatica and, potentially, other elective surgeries. Level of Evidence: 4