Opioid analgesics for nociceptive cancer pain: A comprehensive review.

Pain is one of the most burdensome symptoms in people with cancer, and opioid analgesics are considered the mainstay of cancer pain management. For this review, the authors evaluated the efficacy and toxicities of opioid analgesics compared with placebo, other opioids, nonopioid analgesics, and nonpharmacologic treatments for background cancer pain (continuous and relatively constant pain present at rest), and breakthrough cancer pain (transient exacerbation of pain despite stable and adequately controlled background pain). They found a paucity of placebo-controlled trials for background cancer pain, although tapentadol or codeine may be more efficacious than placebo (moderate-certainty to low-certainty evidence). Nonsteroidal anti-inflammatory drugs including aspirin, piroxicam, diclofenac, ketorolac, and the antidepressant medicine imipramine, may be at least as efficacious as opioids for moderate-to-severe background cancer pain. For breakthrough cancer pain, oral transmucosal, buccal, sublingual, or intranasal fentanyl preparations were identified as more efficacious than placebo but were more commonly associated with toxicities, including constipation and nausea. Despite being recommended worldwide for the treatment of cancer pain, morphine was generally not superior to other opioids, nor did it have a more favorable toxicity profile. The interpretation of study results, however, was complicated by the heterogeneity in the study populations evaluated. Given the limited quality and quantity of research, there is a need to reappraise the clinical utility of opioids in people with cancer pain, particularly those who are not at the end of life, and to further explore the effects of opioids on immune system function and quality of life in these individuals.

Secular trends in gabapentinoid dispensing by compensated workers with low back pain: a retrospective cohort study.

OBJECTIVES: The increase in gabapentinoid prescribing is paralleling the increase in serious harms. To describe the low back pain workers compensation population whose management included a gabapentinoid between 2010 and 2017, and determine secular trends in, and factors associated with gabapentinoid use. METHODS: We analysed claim-level and service-level data from the Victorian workers' compensation programme between 1 January 2010 and 31 December 2017 for workers with an accepted claim for a low back pain injury and who had programme-funded gabapentinoid dispensing. Secular trends were calculated as a proportion of gabapentinoid dispensings per year. Poisson, negative binomial and Cox hazards models were used to examine changes over time in incidence and time to first dispensing. RESULTS: Of the 17 689 low back pain claimants, one in seven (14.7%) were dispensed at least one gabapentinoid during the first 2 years (n=2608). The proportion of workers who were dispensed a gabapentinoid significantly increased over time (7.9% in 2010 to 18.7% in 2017), despite a reduction in the number of claimants dispensed pain-related medicines. Gabapentinoid dispensing was significantly associated with an opioid analgesic or anti-depressant dispensing claim, but not claimant-level characteristics. The time to first gabapentinoid dispensing significantly decreased over time from 311.9 days (SD 200.7) in 2010 to 148.2 days (SD 183.1) in 2017. CONCLUSIONS: The proportion of claimants dispensed a gabapentinoid more than doubled in the period 2010-2017; and the time to first dispensing halved during this period.

Deprescribing interventions for gabapentinoids in adults: A scoping review.

The emerging issue of rising gabapentinoid misuse is being recognized alongside the lack of current evidence supporting the safe and effective deprescribing of gabapentinoids. This scoping review aimed to assess the extent and nature of gabapentinoid deprescribing interventions in adults, either in reducing dosages, or prescribing of, gabapentinoids. Electronic databases were searched on 23 February 2022 without restrictions. Eligible studies included randomized, non-randomized and observational studies that assessed an intervention aimed at reducing/ceasing the prescription/use of a gabapentinoid in adults for any indication in a clinical setting. The research outcomes investigated the type of intervention, prescribing rates, cessations, patient outcomes and adverse events. Extracted outcome data were categorized as either short (≤3 months), intermediate (>3 but <12 months) or long (≥12 months) term. A narrative synthesis was conducted. The four included studies were conducted in primary and acute care settings. Interventions were of dose-reducing protocols, education and/or pharmacological-based approaches. In the randomized trials, gabapentinoid use could be ceased in at least one third of participants. In the two observational trials, gabapentinoid prescribing rates decreased by 9%. Serious adverse events and adverse events specifically related to gabapentinoids were reported in one trial. No study included patient-focused psychological interventions in the deprescribing process, nor provided any long-term follow-up. This review highlights the lack of existing evidence in this area. Due to limited available data, our review was unable to make any firm judgements on the most effective gabapentinoid deprescribing interventions in adults, highlighting the need for more research in this area.

Effectiveness of Opioid Analgesic Medicines Prescribed in or at Discharge From Emergency Departments for Musculoskeletal Pain : A Systematic Review and Meta-analysis.

BACKGROUND: The comparative benefits and harms of opioids for musculoskeletal pain in the emergency department (ED) are uncertain. PURPOSE: To evaluate the comparative effectiveness and harms of opioids for musculoskeletal pain in the ED setting. DATA SOURCES: Electronic databases and registries from inception to 7 February 2022. STUDY SELECTION: Randomized controlled trials of any opioid analgesic compared with placebo or a nonopioid analgesic administered or prescribed to adults in or on discharge from the ED. DATA EXTRACTION: Pain and disability were rated on a scale of 0 to 100 and pooled using a random-effects model. Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. DATA SYNTHESIS: Forty-two articles were included (n = 6128). In the ED, opioids were statistically but not clinically more effective in reducing pain in the short term (about 2 hours) than placebo and paracetamol (acetaminophen) but were not clinically or statistically more effective than nonsteroidal anti-inflammatory drugs (NSAIDs) or local or systemic anesthetics. Opioids may carry higher risk for harms than placebo, paracetamol, or NSAIDs, although evidence is very uncertain. There was no evidence of difference in harms associated with local or systemic anesthetics. LIMITATIONS: Low or very low GRADE ratings for some outcomes, unexplained heterogeneity, and little information on long-term outcomes. CONCLUSION: The risk-benefit balance of opioids versus placebo, paracetamol, NSAIDs, and local or systemic anesthetics is uncertain. Opioids may have equivalent pain outcomes compared with NSAIDs, but evidence on comparisons of harms is very uncertain and heterogeneous. Although factors such as route of administration or dosage may explain some heterogeneity, more work is needed to identify which subgroups will have a more favorable benefit-risk balance for one analgesic over another. Longer-term pain management once dose thresholds are reached is also uncertain. PRIMARY FUNDING SOURCE: None. (PROSPERO: CRD42021275293).

Assessing the role for nailfold videocapillaroscopy in interstitial lung disease classfication: a systematic review and meta-analysis.

OBJECTIVES: The nailfold videocapillaroscopy (NVC) has been known to assist with interstitial lung disease (ILD) classification. However, evidence on its diagnostic efficacy is limited, particularly in some connective tissue disease-related interstitial lung diseases (CTD-ILD), and in interstitial pneumonia with autoimmune features (IPAF). This study aimed to address this limitation by conducting a meta-analysis on the efficacy of the NVC in ILD subgroups of CTD-ILD, IPAF and idiopathic pulmonary fibrosis (IPF). METHODS: MEDLINE, EMBASE, CENTRAL were screened from inception to December 2020 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies that report prevalence of nailfold abnormalities (NVC+) in CTD-ILD, IPAF and IPF cohorts were included. Data were presented as prevalence ratio (PR) with 95% CI using a random-effects model. Quality of evidence was assessed using GRADE criteria. RESULTS: Twenty-one studies were eligible. Prevalence of NVC+ was highest in CTD-ILD; PR (95 CI%) 80.4% (74.3%, 85.3%), followed by IPAF; 27.4% (10.9%, 53.7%), and IPF; 13.8% (5.7%, 29.9%). Late scleroderma pattern was the most prevalent nailfold pattern; 40.4% (28.1%, 54.1%) in our CTD-ILD cohort. Quality of evidence was low for CTD-ILD, IPAF and IPF cohorts, moderate for the late scleroderma pattern cohort. CONCLUSION: NVC can increase the diagnostic accuracy of ILD when used in a multi-disciplinary setting, and appears to have greatest utility in CTD-ILD, followed by IPAF and IPF. The Late Scleroderma Pattern was the most frequent nailfold capillary pattern in SSc-ILD. Future research will allow for greater understanding of the prognostic value of the NVC in ILD.

Immunomodulatory effects of pharmaceutical opioids and antipyretic analgesics: Mechanisms and relevance to infection.

Understanding how pharmaceutical opioids and antipyretic analgesics interact with the immune system potentially has major clinical implications for management of patients with infectious diseases and surgical and critical care patients. An electronic search was carried out on MEDLINE, EMBASE, PsycINFO, CENTRAL and the Cochrane library to identify reports describing the immunomodulatory effects of opioid analgesics and antipyretic analgesics, and their effects in infectious diseases. In adaptive immunity, nonsteroidal anti-inflammatory drugs have divergent effects: augmenting cell-mediated immunity but inhibiting humoral immunity. Nonsteroidal anti-inflammatory drugs have demonstrated a beneficial role in Mycobacterium tuberculosis infection and histoplasmosis in animals, and may be plausible adjuvants to antimicrobial agents in these diseases. There is a need to evaluate these findings rigorously in human clinical trials. There is preliminary evidence demonstrating antiviral effects of indomethacin in SARS CoV-2 in vitro; however, uncertainty regarding its clinical benefit in humans needs to be resolved in large clinical trials. Certain opioid analgesics are associated with immunosuppressive effects, with a developing understanding that fentanyl, morphine, methadone and buprenorphine suppress innate immunity, whilst having diverse effects on adaptive immunity. Morphine suppresses key cells of the innate immunity and is associated with greater risk of infection in the postsurgical setting. Efforts are needed to achieve adequate analgesia whilst avoiding suppression of the innate immunity in the immediate postoperative period caused by certain opioids, particularly in cancer surgery.

Efficacy, safety, and dose-dependence of the analgesic effects of opioid therapy for people with osteoarthritis: systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of opioids for analgesic therapy for people with osteoarthritis. STUDY DESIGN: Systematic review and meta-analysis of randomised, placebo-controlled trials of opioid therapies for treating the pain of osteoarthritis. The primary outcome was medium term pain relief (six weeks to less than 12 months). Quality of evidence was assessed with GRADE criteria. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and Central Register of Controlled Trials, CINAHL, PsycINFO, AMED, and the WHO International Clinical Trials Registry; trials published to 31 October 2020. DATA SYNTHESIS: We extracted pain, disability, health-related quality of life, and adverse events data for 36 eligible trials (overall dose range: 10-210 oral morphine milligram equivalents [MME] per day). Continuous pain and disability outcomes were converted to common 0-100-point scales; changes of less than ten points were deemed to be very small effects. Differences in dichotomous outcomes were expressed as risk ratios. Data were pooled for meta-analysis in random effects models. The evidence from 19 trials (8965 participants; dose range, 10-126 MME/day) for very small medium term pain relief (mean difference [MD], -4.59 points; 95% CI, -7.17 to -2.02 points) was low quality, as was that from 16 trials (6882 participants; dose range, 10-126 MME/day) for a very small effect on disability (MD, -4.15 points; 95% CI, -6.94 to -1.35 points). Opioid dose was not statistically significantly associated with either degree of pain relief or incidence of adverse events in a meta-regression analysis. Evidence that opioid therapy increased the risk of adverse events (risk ratio, 1.43; 95% CI, 1.29-1.59) was of very low quality. CONCLUSIONS: Opioid medications may provide very small pain and disability benefits for people with osteoarthritis, but may also increase the risk of adverse events. PROSPERO REGISTRATION: CRD42019142813 (prospective).

The efficacy and safety of paracetamol for pain relief: an overview of systematic reviews.

OBJECTIVE: To evaluate the efficacy and safety of paracetamol as an analgesic medication in a range of painful conditions. STUDY DESIGN: Systematic review of systematic reviews of the analgesic effects of paracetamol in randomised, placebo-controlled trials. Conduct of systematic reviews was assessed with AMSTAR-2; confidence in effect estimates (quality of evidence) was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. DATA SOURCES: MEDLINE, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews; systematic reviews published 1 January 2010 - 30 April 2020. DATA SYNTHESIS: We extracted pain and adverse events outcomes from 36 systematic reviews that assessed the efficacy of paracetamol in 44 painful conditions. Continuous pain outcomes were expressed as mean differences (MDs; standardised 0-10-point scale); dichotomous outcomes were expressed as risk ratios (RRs). There is high quality evidence that paracetamol provides modest pain relief for people with knee or hip osteoarthritis (MD, -0.3 points; 95% CI, -0.6 to -0.1 points) and after craniotomy (MD, -0.8 points; 95% CI, -1.4 to -0.2 points); there is moderate quality evidence for its efficacy in tension-type headache (pain-free at 2 hours: RR, 1.3; 95% CI, 1.1-1.4) and perineal pain soon after childbirth (patients experiencing 50% pain relief: RR, 2.4; 95% CI, 1.5-3.8). There is high quality evidence that paracetamol is not effective for relieving acute low back pain (MD, 0.2 points; 95% CI, -0.1 to 0.4 points). Evidence regarding efficacy in other conditions was of low or very low quality. Frequency of adverse events was generally similar for people receiving placebo or paracetamol, except that transient elevation of blood liver enzyme levels was more frequent during repeated administration of paracetamol to patients with spinal pain (RR, 3.8; 95% CI, 1.9-7.4). CONCLUSIONS: For most conditions, evidence regarding the effectiveness of paracetamol is insufficient for drawing firm conclusions. Evidence for its efficacy in four conditions was moderate to strong, and there is strong evidence that paracetamol is not effective for reducing acute low back pain. Investigations that evaluate more typical dosing regimens are required. PROSPERO REGISTRATION: CRD42015029282 (prospective).

Is the use of metformin in patients undergoing dialysis hazardous for life? A systematic review of the safety of metformin in patients undergoing dialysis.

AIMS: Metformin may have clinical benefits in dialysis patients; however, its safety in this population is unknown. This systematic review evaluated the safety of metformin in dialysis patients. METHODS: MEDLINE, Embase, CENTRAL, PsycINFO and the Cochrane Library were searched for randomised controlled trials and observational studies evaluating metformin use in dialysis patients. Three authors reviewed the studies and extracted data. The primary outcomes were mortality, occurrence of lactic acidosis and myocardial infarction (MI) in patients taking metformin during dialysis treatment for ≥12 months (long term). Risk of bias was assessed using Risk Of Bias In Nonrandomised Studies of Interventions (ROBINS-1). Overall quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Fifteen observational studies were eligible; 7 were prospective observational studies and 8 were case reports/case series. No randomised controlled trials were identified. The 7 prospective observational studies (n = 194) reported on cautious metformin use in patients undergoing maintenance dialysis. Only 3 provided long-term follow-up data. In 2 long-term studies of metformin therapy (≤1000 mg/d) in patients undergoing peritoneal dialysis (PD), 1 reported 6 deaths (6/83; 7%) due to major cardiovascular events (3 MI) and the other reported no deaths (0/35). One long-term study of metformin therapy (250 mg to 500 mg thrice weekly) in patients undergoing haemodialysis reported 4 deaths (4/61; 7%) due to major cardiovascular events (2 MI). These findings provide very low-quality evidence as they come from small observational studies. CONCLUSION: The evidence regarding the safety of metformin in people undergoing dialysis is inconclusive. Appropriately designed randomised controlled trials are needed to resolve this uncertainty.

Paracetamol for low back pain.

BACKGROUND: Analgesic medication is the most frequently prescribed treatment for low back pain (LBP), of which paracetamol (acetaminophen) is recommended as the first choice medication. However, there is uncertainty about the efficacy of paracetamol for LBP. OBJECTIVES: To investigate the efficacy and safety of paracetamol for non-specific LBP. SEARCH METHODS: We conducted searches on the Cochrane Central Register of Controlled Trials (CENTRAL, which includes the Back and Neck Review Group trials register), MEDLINE, EMBASE, CINAHL, AMED, Web of Science, LILACS, and IPA from their inception to 7 August 2015. We also searched the reference lists of eligible papers and trial registry websites (WHO ICTRP and ClinicalTrials.gov). SELECTION CRITERIA: We only considered randomised trials comparing the efficacy of paracetamol with placebo for non-specific LBP. The primary outcomes were pain and disability. We also investigated quality of life, function, adverse effects, global impression of recovery, sleep quality, patient adherence, and use of rescue medication as secondary outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently performed the data extraction and assessed risk of bias in the included studies. We also evaluated the quality of evidence using the GRADE approach. We converted scales for pain intensity to a common 0 to 100 scale. We quantified treatment effects using mean difference for continuous outcomes and risk ratios for dichotomous outcomes. We used effect sizes and 95% confidence intervals as a measure of treatment effect for the primary outcomes. When the treatment effects were smaller than 9 points on a 0 to 100 scale, we considered the effect as small and not clinically important. MAIN RESULTS: Our searches retrieved 4449 records, of which three trials were included in the review (n = 1825 participants), and two trials were included in the meta-analysis. For acute LBP, there is high-quality evidence for no difference between paracetamol (4 g per day) and placebo at 1 week (immediate term), 2 weeks, 4 weeks, and 12 weeks (short term) for the primary outcomes. There is high-quality evidence that paracetamol has no effect on quality of life, function, global impression of recovery, and sleep quality for all included time periods. There were also no significant differences between paracetamol and placebo for adverse events, patient adherence, or use of rescue medication. For chronic LBP, there is very low-quality evidence (based on a trial that has been retracted) for no effect of paracetamol (1 g single intravenous dose) on immediate pain reduction. Finally, no trials were identified evaluating patients with subacute LBP. AUTHORS' CONCLUSIONS: We found that paracetamol does not produce better outcomes than placebo for people with acute LBP, and it is uncertain if it has any effect on chronic LBP.

Pharmacists' views on implementing a disease state management program for low back pain.

Pharmacists have the potential to take a lead role in the primary care management of people with acute low back pain. The aim of this study was to investigate pharmacists' views on implementing a care program for people with acute low back pain in the community pharmacy. Recruitment of pharmacists for this study took place between July 2012 and March 2013. A convenience sample of 30 pharmacists who collaborated in recruiting participants for a low back pain clinical trial in Sydney (n=15 pharmacist recruiters and n=15 non-recruiters) completed an open-ended questionnaire. There was no marked variation in responses between the two groups. Participating pharmacists were receptive to the idea of implementing a care program for people with low back pain, highlighting the need for adequate reimbursement and adequate training of staff to ensure it is successful. Pharmacists identified that the follow up of people receiving such a service is dependent on several factors such as effective reminder systems and the proximity of patients to the pharmacy.

Knowledge and satisfaction of pharmacists attending an educational workshop on evidence-based management of low back pain.

Pharmacists are well positioned to provide quality care to people with low back pain (LBP). Education and training can equip pharmacists with the knowledge to optimally manage LBP in primary care. The aim of this study was to investigate the knowledge and satisfaction of pharmacists who attended a 2-h educational workshop on the evidence-based management of LBP. Case-based learning, underpinned by key adult learning principles, was one teaching method used to deliver important educational messages. Knowledge was assessed using a questionnaire consisting of multiple-choice, true/false questions and a written vignette based on a real-life clinical case scenario. Written feedback from pharmacists was used to gauge the success and limitations of the intervention. One hundred and ninety-three pharmacists completed the in-house assessment. Pharmacists demonstrated an accurate understanding of evidence-based pharmacological management of LBP, with all identifying paracetamol as the first-line drug choice for non-specific LBP. Ninety-nine per cent of pharmacists identified the symptoms presented in the vignette as a syndrome representing a significant clinical red flag requiring urgent referral. This educational intervention has delivered key messages on LBP management to pharmacists. There is a continued need for educational interventions addressing common conditions.

Opioids for Acute Musculoskeletal Pain: A Systematic Review with Meta-Analysis.

OBJECTIVE: To evaluate the efficacy of opioids for people with acute musculoskeletal pain against placebo. STUDY DESIGN: Systematic review and meta-analyses of randomised, placebo-controlled trials of opioid analgesics for acute musculoskeletal pain in any setting. The primary outcomes were pain and disability at the immediate timepoint (< 24 h). DATA SOURCES: Multiple databases were searched from their inception to February 22nd, 2023. DATA SYNTHESIS: Continuous outcomes were converted to a 0-100 scale. Dichotomous outcomes were presented as risk differences. Risk of bias and certainty of evidence was assessed. RESULTS: We located 17 trials (1 intravenous and 16 oral route of administration). For adults, high certainty evidence from 11 comparisons shows that oral opioids provide small benefits relative to placebo in the immediate term for pain (mean difference [MD] - 8.8 95% confidence interval [CI] - 12.0 to - 5.6). For disability, the difference is uncertain (MD - 6.2, 95% CI - 17.8 to 5.4). Opioid groups were at higher risk of adverse events (MD 14.3%, 95% CI 8.3-20.4%, very low certainty). There was moderate certainty evidence of a large effect of IV morphine on sciatica pain (MD -42.5, 95% CI - 49.9 to - 35.1, n = 197, 1 study). In paediatric populations, moderate certainty evidence from 3 trials shows that oral opioids probably do not provide benefit beyond that of placebo for pain (MD 6.1, 95% CI - 1.7 to 12.8) and there was no evidence for disability. There was low certainty evidence that there may be no difference in adverse events (MD 10.4%, 95% CI - 0.6 to 21.4%). DISCUSSION: Intravenous morphine likely offers benefits, but oral opioids may not provide clinically meaningful benefits. PROSPERO REGISTRATION: CRD42021249346.

Disseminated Mycobacterium chelonae infection complicating rheumatoid arthritis: A case report and review of the literature.

INTRODUCTION: Rheumatoid arthritis (RA) may predispose patients to opportunistic infections-either from innate immune dysregulation, or as a result of immunosuppressant use to treat the RA. Particularly concerning opportunistic infections are those caused by non-tuberculous mycobacterial (NTM) organisms, the incidence of which has been increasing in epidemiological studies. Despite this, guidelines on the management of patients with RA who develop NTM infections are scarce, particularly with respect to immunosuppressant regimen modulation and duration of antibiotic therapy. CASE REPORT: Herein, we present a case of disseminated Mycobacterium chelonae infection, manifesting as arthralgia and cutaneous nodules. DISCUSSION: In addition, a review of the literature was conducted to Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines to identify similar cases in the literature-revealing that all RA-associated M. Chelonae infections occurred in immunosuppressed patients (the majority with corticosteroids or tumor necrosis factor inhibitors), and considerable heterogeneity in management approaches. Further research regarding risk factors, preventative approaches and best management of such NTM infections in vulnerable patients with RA is required in order to establish consensus guidelines and consistency.

Efficacy, safety, and tolerability of antidepressants for pain in adults: overview of systematic reviews.

OBJECTIVE: To provide a comprehensive overview of the efficacy, safety, and tolerability of antidepressants for pain according to condition. DESIGN: Overview of systematic reviews. DATA SOURCES: PubMed, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials from inception to 20 June 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews comparing any antidepressant with placebo for any pain condition in adults. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data. The main outcome measure was pain; for headache disorders it was frequency of headaches. Continuous pain outcomes were converted into a scale of 0 (no pain) to 100 (worst pain) and were presented as mean differences (95% confidence intervals). Dichotomous outcomes were presented as risk ratios (95% confidence intervals). Data were extracted from the time point closest to the end of treatment. When end of treatment was too variable across trials in a review, data were extracted from the outcome or time point with the largest number of trials and participants. Secondary outcomes were safety and tolerability (withdrawals because of adverse events). Findings were classified from each comparison as efficacious, not efficacious, or inconclusive. Certainty of evidence was assessed with the grading of recommendations assessment, development, and evaluation framework. RESULTS: 26 reviews (156 unique trials and >25 000 participants) were included. These reviews reported on the efficacy of eight antidepressant classes covering 22 pain conditions (42 distinct comparisons). No review provided high certainty evidence on the efficacy of antidepressants for pain for any condition. 11 comparisons (nine conditions) were found where antidepressants were efficacious, four with moderate certainty evidence: serotonin-norepinephrine reuptake inhibitors (SNRIs) for back pain (mean difference -5.3, 95% confidence interval -7.3 to -3.3), postoperative pain (-7.3, -12.9 to -1.7), neuropathic pain (-6.8, -8.7 to -4.8), and fibromyalgia (risk ratio 1.4, 95% confidence interval 1.3 to 1.6). For the other 31 comparisons, antidepressants were either not efficacious (five comparisons) or the evidence was inconclusive (26 comparisons). CONCLUSIONS: Evidence of efficacy of antidepressants was found in 11 of the 42 comparisons included in this overview of systematic reviews-seven of the 11 comparisons investigated the efficacy of SNRIs. For the other 31 comparisons, antidepressants were either inefficacious or evidence on efficacy was inconclusive. The findings suggest that a more nuanced approach is needed when prescribing antidepressants for pain conditions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022311073.

Prevalence of Nonsteroidal Antiinflammatory Drugs Prescribed for Osteoarthritis: A Systematic Review and Meta-Analysis of Observational Studies.

OBJECTIVE: Our systematic review aimed to investigate the proportion of participants with osteoarthritis who were prescribed nonsteroidal antiinflammatory drugs (NSAIDs) by their health care provider. METHODS: Electronic databases were searched for observational studies reporting NSAID prescribing to participants with diagnosed osteoarthritis of any region. Risk of bias was assessed using a tool designed for observational studies measuring prevalence. Random and fixed-effects meta-analysis was used. Meta-regression investigated study-level factors associated with prescribing. The overall evidence quality was assessed using Grading of Recommendations Assessment, Development, and Evaluation criteria. RESULTS: Fifty-one studies were included, published between 1989 and 2022, with 6,494,509 participants. The mean age of participants was 64.7 years (95% confidence interval [95% CI] 62.4, 67.0; n = 34 studies). Most studies were from Europe and Central Asia (n = 23 studies), and North America (n = 12 studies). Most studies were judged to be at low risk of bias (75%). Heterogeneity was eliminated when removing studies with a high risk of bias, to give a pooled estimate of NSAIDs prescribing to participants with osteoarthritis of 43.8% (95% CI 36.8, 51.1; moderate quality of evidence). Meta-regression determined that prescribing was associated with year (decreased prescribing over time; P = 0.05) and geographic region (P = 0.03; higher in Europe and Central Asia and in South Asia than in North America) but not with clinical setting. CONCLUSION: Data from over 6.4 million participants with osteoarthritis between 1989 and 2022 indicate that NSAID prescribing has decreased over time and that prescribing differs between geographic locations.

Continued Opioid Use and Adverse Events Following Provision of Opioids for Musculoskeletal Pain in the Emergency Department: A Systematic Review and Meta-Analysis.

BACKGROUND: The prevalence of continued opioid use or serious adverse events (SAEs) following opioid therapy in the emergency department (ED) for musculoskeletal pain is unclear. The aim of this review was to examine the prevalence of continued opioid use and serious adverse events (SAEs) following the provision of opioids for musculoskeletal pain in the emergency department (ED) or at discharge. METHODS: Records were searched from MEDLINE, EMBASE and CINAHL from inception to 7 October 2022. We included randomised controlled trials and observational studies enrolling adult patients with musculoskeletal pain who were administered and/or prescribed opioids in the ED. Continued opioid use and opioid misuse data after day 4 since ED discharge were extracted. Adverse events were coded using the Common Terminology Criteria for Adverse Events (CTCAE), and those rated as grades 3-4 (severe or life-threatening) and grade 5 (death) were considered SAEs. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. RESULTS: Seventy-two studies were included. Among opioid-naïve patients who received an opioid prescription, 6.8-7.0% reported recent opioid use at 3-12 months after discharge, 4.4% filled ≥ 5 opioid prescriptions and 3.1% filled > 90-day supply of opioids within 6 months. The prevalence of SAEs was 0.02% [95% confidence interval (CI) 0, 0.2%] in the ED and 0.1% (95% CI 0, 1.5%) within 2 days. One study observed 42.9% of patients misused opioids within 30 days after discharge. CONCLUSIONS: Around 7% of opioid-naïve patients with musculoskeletal pain receiving opioid therapy continue opioid use at 3-12 months after ED discharge. SAEs following ED administration of an opioid were uncommon; however, studies only monitored patients for 2 days. PROTOCOL REGISTRATION: 10.31219/osf.io/w4z3u.