UNASSIGNED: There is emerging evidence that posttraumatic-stress disorder may have mediating effects in development of chronic-non-cancer-pain and opioid-use-disorder independently, but its impact on the development of opioid-use-disorder in people with chronic-non-cancer pain is still unclear.
UNASSIGNED: (i) Estimate the risk of opioid-use-disorder among individuals with chronic-non-cancer-pain and posttraumatic-stress disorder, relative to those with chronic-non-cancer-pain only, and (ii) identify potential correlates of opioid-use-disorder among people with chronic-non-cancer-pain and posttraumatic-stress disorder.
UNASSIGNED: This systematic review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Longitudinal, epidemiological, cohort, follow-up, retrospective, prospective and cross-sectional studies reporting measures of variance on the likelihood of developing opioid-use-disorder with posttraumatic-stress disorder among individuals with chronic-non-cancer-pain were identified from six-electronic databases (Medline, Embase, Evidence-based Medicine reviews, PsycINFO, Scopus and Web of Science) until December 2022.
UNASSIGNED: Three out of the four studies, which met the selection criteria for this analysis reported statistically significant positive association between risk of developing opioid-use-disorder with posttraumatic-stress disorder among chronic-non-cancer-pain cohort (unadjusted Relative-Risk range: 1.51-5.27) but this association was not evident in the fourth study (adjusted Relative-Risk: 0.96; statistically non-significant), when adjusted for sociodemographic variables. The increased risk was noted particularly with females and chronic musculoskeletal pain conditions.
UNASSIGNED: Posttraumatic-stress disorder can increase the risk of development of opioid-use-disorder among people with chronic-non-cancer-pain and a better understanding of this relationship will help to predict and prevent the development of opioid-use-disorder and may also help in reducing the disability and burden associated with chronic-non-cancer-pain.
UNASSIGNED: This review quantifies the risk of developing opioid-use-disorder in the context of posttraumatic-stress disorder among individuals with chronic-non-cancer-pain. Awareness and subsequent practice change will reduce the increasing global burden associated with the chronic-non-cancer-pain.

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.

The body of evidence regarding self-management programs (SMPs) for adult chronic non-cancer pain (CNCP) is steadily growing, and regular updates are needed for effective decision-making.
To systematically identify, critically appraise, and summarize the findings from randomized controlled trials (RCTs) of SMPs for CNCP.
We searched relevant databases from 2009 to August 2021 and included English-language RCT publications of SMPs compared with usual care for CNCP among adults (18+ years old). The primary outcome was health-related quality of life (HR-QoL). We conducted meta-analysis using an inverse variance, random-effects model and calculated the standardized mean difference (SMD) and associated 95% confidence interval (CI) and statistical heterogeneity using the I2 statistic.
From 8538 citations, we included 28 RCTs with varying patient populations, standards for SMPs, and usual care. No RCTs were classified as having a low risk of bias. There was no evidence of a significant improvement in overall HR-QoL, irrespective of pain type, immediately post-intervention (SMD 0.01, 95%CI -0.21 to 0.24; I2 57%; 11 RCTs; 979 participants), 1-4 months post-intervention (SMD 0.02, 95%CI -0.16 to 0.20; I2 48.7%; 12 RCTs; 1160 participants), and 6-12 months post-intervention (SMD 0.07, 95%CI -0.06 to 0.21; I2 26.1%; 9 RCTs; 1404 participants). Similar findings were made for physical and mental HR-QoL, and for specific QoL assessment scales (e.g., SF-36).
There is a lack of evidence that SMPs are efficacious for CNCP compared with usual care. Standardization of SMPs for CNCP and better planned/conducted RCTs are needed to confirm these conclusions.

Opioids, often prescribed for chronic non-cancer pain, may adversely affect cognition. Research has not been synthesized in recent years, during which time academic interest has increased. This study presents meta-analyses on cognitive performance in people taking opioids for chronic non-cancer pain (CNCP).
We ran systematic literature searches in EMBASE, Medline, and PsycINFO. Eligible studies included people taking opioids for CNCP, an opioid-free group (i.e., case-control) or session (e.g., pre-post), and objective cognitive assessments. Using random-effects meta-analyses, we computed pooled effect sizes for differential task performance for each study design across five domains (motor performance, attention, working memory, executive functions, memory).
Seventeen studies were included. Case-control studies covered three control types (healthy, CNCP, taper-off). Pre-post studies were grouped into five follow-ups (four to six and six to nine weeks; three, six, and 12 months). Effect sizes ranged from 0.02-0.62. Cases showed small magnitude impairments in attention and memory compared with healthy controls. Although limited by small sample sizes, there was no clear evidence of impairment in cases compared with opioid-free controls with CNCP. Cases showed some cognitive improvements from opioid-free baseline to follow-up. Effects were strongest for attention and working memory and were apparent from four weeks to six months follow-up. Other effects were small and nonsignificant.
Opioid therapy for CNCP did not worsen cognitive performance and improved it for some domains. People who take opioids for CNCP may evidence deficits in attention and memory, but this is unlikely to translate to global impairment and likely relates to pain more so than opioids.

To estimate all-cause and overdose crude mortality rates and standardized mortality ratios among people prescribed opioids for chronic noncancer pain and risk of overdose death in this population relative to people with similar clinical profiles but not prescribed opioids.
Systematic review and meta-analysis.
Medline, Embase, and PsycINFO were searched in February 2018 and October 2019 for articles published beginning 2009. Due to limitations in published studies, we revised our inclusion criteria to include cohort studies of people prescribed opioids, excluding those studies where people were explicitly prescribed opioids for the treatment of opioid use disorder or acute cancer or palliative pain. We estimated pooled all-cause and overdose crude mortality rates using random effects meta-analysis models. No studies reported standardized mortality ratios or relative risks.
We included 13 cohorts with 6,029,810 participants. The pooled all-cause crude mortality rate, based on 10 cohorts, was 28.8 per 1000 person-years (95% CI = 17.9-46.4), with substantial heterogeneity (I2 = 99.9%). The pooled overdose crude mortality rate, based on six cohorts, was 1.1 per 1000 person-years (95% CI = 0.4-3.4), with substantial heterogeneity (I2 = 99.5%), but indications for opioid prescribing and opioid exposure were poorly ascertained. We were unable to estimate mortality in this population relative to clinically similar populations not prescribed opioids.
Methodological limitations in the identified literature complicate efforts to determine the overdose mortality risk of people prescribed opioids. There is a need for large-scale clinical trials to assess adverse outcomes in opioid prescribing, especially for chronic noncancer pain.

Chronic non-cancer pain is common and long-term opioid therapy is frequently used in its management. While opioids can be effective, they are also associated with significant harm and misuse, and clinicians must weigh any expected benefits with potential risks when making decisions around prescribing. This review aimed to summarise controlled trials and systematic reviews that evaluate patient-related, provider-related, and system-related factors supporting responsible opioid prescribing for chronic non-cancer pain. A scoping review methodology was employed, and six databases were searched. Thirteen systematic reviews and nine controlled trials were included for analysis, and clinical guidelines were reviewed to supplement gaps in the literature. The majority of included studies evaluated provider-related factors, including prescribing behaviours and monitoring for misuse. A smaller number of studies evaluated system-level factors such as regulatory measures and models of healthcare delivery. Studies and guidelines emphasise the importance of careful patient selection for opioid therapy, development of a treatment plan, and cautious initiation and dose escalation. Lower doses are associated with reduced risk of harm and can be efficacious, particularly when used in the context of a multimodal interdisciplinary pain management program. Further research is needed around many elements of responsible prescribing, including instruments to monitor for misuse, and the role of policies and programs.

Despite common use, the benefit of adding steroids to local anaesthetics (SLA) for chronic non-cancer pain (CNCP) injections is uncertain. We performed a systematic review and meta-analysis of English-language RCTs to assess the benefit and safety of adding steroids to local anaesthetics (LA) for CNCP.
We searched MEDLINE, EMBASE, and CENTRAL databases from inception to May 2019. Trial selection and data extraction were performed in duplicate. Outcomes were guided by the Initiative in Methods, Measurements, and Pain Assessment in Clinical Trials (IMMPACT) statement with pain improvement as the primary outcome and pooled using random effects model and reported as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CIs).
Among 5097 abstracts, 73 trials were eligible. Although SLA increased the rate of success (42 trials, 3592 patients; RR=1.14; 95% CI, 1.03-1.25; number needed to treat [NNT], 13), the effect size decreased by nearly 50% (NNT, 22) with the removal of two intrathecal injection studies. The differences in pain scores with SLA were not clinically meaningful (54 trials, 4416 patients, MD=0.44 units; 95% CI, 0.24-0.65). No differences were observed in other outcomes or adverse events. No subgroup effects were detected based on clinical categories. Meta-regression showed no significant association with steroid dose or length of follow-up and pain relief.
Addition of cortico steroids to local anaesthetic has only small benefits and a potential for harm. Injection of local anaesthetic alone could be therapeutic, beyond being diagnostic. A shared decision based on patient preferences should be considered. If used, one must avoid high doses and series of steroid injections.
PROSPERO #: CRD42015020614.

There is growing interest in using cannabinoids for chronic pain. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the analgesic efficacy and adverse effects of cannabinoids for chronic non-cancer pain. PubMed, EMBASE, Web of Science, Cochrane CENTRAL and clinicaltrials.gov were searched up to December 2018. Information on the type, dosage, route of administration, pain conditions, pain scores, and adverse events were extracted for qualitative analysis. Meta-analysis of analgesic efficacy was performed. Meta-regression was performed to compare the analgesic efficacy for different pain conditions (neuropathic versus non-neuropathic pain). Risk of bias was assessed by The Cochrane Risk of Bias tool, and the strength of the evidence was assessed using the Grade of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Forty-three randomized controlled trials were included. Meta-analysis was performed for 33 studies that compared cannabinoids to placebo, and showed a mean pain score (scale 0-10) reduction of -0.70 (p < 0.001, random effect). Meta-regression showed that analgesic efficacy was similar for neuropathic and non-neuropathic pain (Difference = -0.14, p = 0.262). Inhaled, oral, and oromucosal administration all provided statistically significant, but small reduction in mean pain score (-0.97, -0.85, -0.45, all p < 0.001). Incidence of serious adverse events was rare, and non-serious adverse events were usually mild to moderate. Heterogeneity was moderate. The GRADE level of evidence was low to moderate. Pain intensity of chronic non-cancer patients was reduced by cannabinoids consumption, but effect sizes were small. Efficacy for neuropathic and non-neuropathic pain was similar.

Opioid prescribing to treat chronic non-cancer pain has rapidly increased, despite a lack of evidence for long-term safety and effectiveness. A pain review service was developed to work with patients taking opioids long-term to explore opioid use, encourage non-drug-based alternatives, and, where appropriate, support dose reduction.
To evaluate the service and its potential impact on opioid use, health and wellbeing outcomes, and quality of life (QoL).
Mixed-methods evaluation of a one-to-one service based in two GP practices in South Gloucestershire, England, which took place from September 2016 to December 2017.
Quantitative data were collected on baseline demographics; data on opioid use, misuse, and dose, health, wellbeing, QoL, and pain and interference with life measures were collected at baseline and follow-up. Twenty-five semi-structured interviews (n = 18 service users, n = 7 service providers) explored experiences of the service including perceived impacts and benefits.
Of 59 patients who were invited, 34 (57.6%) enrolled in the service. The median prescribed opioid dose reduced from 90 mg (average daily morphine equivalent; interquartile range [IQR] 60 to 240) at baseline to 72 mg (IQR 30 to 160) at follow-up (P<0.001); three service users stopped using opioids altogether. On average, service users showed improvement on most health, wellbeing, and QoL outcomes. Perceived benefits were related to wellbeing, for example, improved confidence and self-esteem, use of pain management strategies, changes in medication use, and reductions in dose.
The service was well received, and health and wellbeing outcomes suggest a potential benefit. Following further service development, a randomised controlled trial to test this type of care pathway is warranted.