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AIM: Deprescribing is the systematic process of discontinuing medications when the harms outweigh the benefits. This study aimed to identify barriers and facilitators in people with chronic non-cancer pain when deprescribing opioid analgesics, and their views on resources that assist with deprescribing.METHODS: A purposive sampling strategy was used to recruit 19 adults with chronic non-cancer pain from the community who were, or had been, on long-term opioid therapy. Recruitment continued until thematic saturation was achieved. Semi-structured telephone interviews were conducted. A five-step framework and thematic analysis method identified themes for each study aim.RESULTS: Themes identifying barriers to opioid deprescribing raised challenges of a lack of available alternatives, managing opioid dependency and withdrawal symptoms or inability to function without opioids when in extreme pain. Facilitating themes described the value of support networks, including a trusting doctor-patient relationship and finding individual coping strategies to address deprescribing barriers. We explored a variety of resources from electronic forms such as websites and apps to paper-based or face to face. Participants expressed that whatever the form, resources need to be educational but also simple and engaging.CONCLUSIONS: Most people suffering from chronic non-cancer pain expressed dissatisfaction with being on opioids but most were still unwilling to deprescribe due to insufficient alternatives, a lack of support from their doctors and lack of information about the deprescribing process. Deprescribing can be facilitated by improving supportive networks and strategies and providing simple and positive educational resources.

The emerging issue of rising gabapentinoid misuse is being recognised 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 23rd February 2022 without restrictions. Eligible studies included randomised, non-randomised 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 type of intervention, prescribing rates, cessations, patient outcomes, and adverse events. Extracted outcome data was categorised as either short (≤ 3 months), intermediate (>3 but

Background Patients presenting to Emergency Department (ED) with non-specific low back pain can receive more unnecessary, intensive and costly care than is recommended. The COVID-19 pandemic has provided an unprecedented opportunity to examine how health systems prioritise necessary care that provides clear benefits to patients. The purpose of this study was to examine the impact of COVID-19 on care of low back pain in the ED. Methods We performed a retrospective analysis of electronic medical record data on care for low back pain from three public hospitals in Sydney. We included patients diagnosed with spinal conditions who presented between March and May in 2019 and in 2020. Outcomes were the total number of patients presenting with spinal conditions to ED, the proportion diagnosed with non-specific low back pain, and the proportion receiving potentially unnecessary aspects of care (ambulance use, imaging, opioids, hospital admissions). We calculated relative risk with 95% CIs and examined plots with locally weighted smoothed curves. Results Presentations for spinal conditions over a three-month period to three EDs reduced from 694 in 2019 to 475 in 2020 (31% reduction, 95% CI = 26%–37%). The proportion of patients diagnosed with non-specific low back pain (83% in 2019 vs 86% in 2020), or receiving potentially unnecessary care were similar in 2019 and 2020 (Imaging = 25% vs 25%; Opioids = 54% vs 56%; Admitted = 18% vs 20%; pathology test = 24% vs 23%). The proportion of patients arriving by ambulance was higher during the pandemic; 29% in 2019 vs 41% in 2020 (RR = 1.39, 95% CI = 1.19–1.63). Conclusions ED presentations for low back pain associated with spinal conditions decreased substantially during the COVID-19 pandemic. Use of potentially unnecessary aspects of care did not change or increased during the pandemic.

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.

ObjectiveTo investigate the effectiveness and safety of surgery compared with non-surgical treatment for sciatica.DesignSystematic review and meta-analysis.Data sourcesMedline, Embase, CINAHL, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and the World Health Organisation International Clinical Trials Registry Platform from database inception to June 2022.Eligibility criteria for selecting studiesRandomised controlled trials comparing any surgical treatment with non-surgical treatment, epidural steroid injections, or placebo or sham surgery, in people with sciatica of any duration due to lumbar disc herniation (diagnosed by radiological imaging).Data extraction and synthesisTwo independent reviewers extracted data. Leg pain and disability were the primary outcomes. Adverse events, back pain, quality of life, and satisfaction with treatment were the secondary outcomes. Pain and disability scores were converted to a scale of 0 (no pain or disability) to 100 (worst pain or disability). Data were pooled using a random effects model. Risk of bias was assessed with the Cochrane Collaboration’s tool and certainty of evidence with the grading of recommendations assessment, development, and evaluation (GRADE) framework. Follow-up times were into immediate term (≤six weeks), short term (>six weeks and ≤three months), medium term (>three and Results24 trials were included, half of these investigated the effectiveness of discectomy compared with non-surgical treatment or epidural steroid injections (1711 participants). Very low to low certainty evidence showed that discectomy, compared with non-surgical treatment, reduced leg pain: the effect size was moderate at immediate term (mean difference −12.1 (95% confidence interval −23.6 to −0.5)) and short term (−11.7 (−18.6 to −4.7)), and small at medium term (−6.5 (−11.0 to −2.1)). Negligible effects were noted at long term (−2.3 (−4.5 to −0.2)). For disability, small, negligible, or no effects were found. A similar effect on leg pain was found when comparing discectomy with epidural steroid injections. For disability, a moderate effect was found at short term, but no effect was observed at medium and long term. The risk of any adverse events was similar between discectomy and non-surgical treatment (risk ratio 1.34 (95% confidence interval 0.91 to 1.98)).ConclusionVery low to low certainty evidence suggests that discectomy was superior to non-surgical treatment or epidural steroid injections in reducing leg pain and disability in people with sciatica with a surgical indication, but the benefits declined over time. Discectomy might be an option for people with sciatica who feel that the rapid relief offered by discectomy outweighs the risks and costs associated with surgery.Systematic review registrationPROSPERO CRD42021269997.

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.

Spinal cord stimulators are used to treat intractable pain. Placebo-controlled trials of spinal cord stimulators typically involve short-term treatment and follow-up, so long-term safety and efficacy are unclear.The aim of the study was to describe the adverse events relating to spinal cord stimulators reported to the Therapeutic Goods Administration of Australia between July 2012 and January 2019.Adverse events were coded by seriousness, severity, body system affected, type of event, action taken, and attribution of fault. Data on the number of stimulators implanted and removed were sourced from the Admitted Patient Care Minimum Data Set.Five hundred twenty adverse events were reported for spinal cord stimulators. Most events were rated as severe (79%) or life-threatening (13%). Device malfunction was the most common event (56.5%). The most common action taken in response to an adverse event was surgical intervention with or without antibiotics (80%). The ratio of removals to implants was 4 per every 10 implanted.Spinal cords stimulators have the potential for serious harm, and each year in Australia, many are removed. In view of the low certainty evidence of their long-term safety and effectiveness, our results raise questions about their role in providing long-term management of intractable pain.

The increasing number of gabapentinoid (pregabalin and gabapentin) harms, including deaths observed across countries is concerning to health-care professionals and policy makers. However, it is unclear if the public shares these concerns. This study aimed to describe posts related to gabapentinoids, conduct a content analysis to identify common themes and describe adverse events or symptoms.Keywords of 'pregabalin' or 'Lyrica' or 'gabapentin' or 'Neurontin' were used to search for related tweets posted by people in the community between 8 March and 7 May 2021. Eligible tweets included a keyword in the post. We extracted de-identified data which included descriptive data of the total number of posts over time; and data on individual tweets including date, number of re-tweets and post content. Data were exported separately for pregabalin- and gabapentin-related tweets. A 20% random sample was used for the thematic analysis.There were 2931 pregabalin-related tweets and 2736 gabapentin-related tweets. Thematic analysis revealed three themes (sharing positive experiences and benefits of taking gabapentinoids, people voicing their negative experiences, and people seeking opinions and sharing information). Positive experiences of gabapentinoids were related to sharing stories and giving advice. This was contrasted to negative experiences including ineffectiveness, withdrawals, side effects and frustration related to cost and insurance coverage. Brain fog was the most common adverse symptom reported. Gabapentinoid-related deaths were only mentioned in three tweets.The increasing public health concern of gabapentinoid-related deaths was not translated to Twitter discussions.

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.

The comparative benefits and harms of opioids for musculoskeletal pain in the emergency department (ED) are uncertain.To evaluate the comparative effectiveness and harms of opioids for musculoskeletal pain in the ED setting.Electronic databases and registries from inception to 7 February 2022.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.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.Forty-two articles were included (Low or very low GRADE ratings for some outcomes, unexplained heterogeneity, and little information on long-term outcomes.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.None. (PROSPERO: CRD42021275293).

Background and aims: Opioids are commonly prescribed to patients with chronic low back pain (LBP) despite risks of harms. We conducted a discrete choice experiment (DCE) to determine factors contributing to a general practitioner’s (GP’s) decision to prescribe either an opioid or an NSAID to a patient with chronic LBP. Methods: GPs recruited through an online survey distributed in Australia were presented with 12 questions that represented hypothetical clinical scenarios of a patient with chronic LBP. The clinical scenario varied by two patient attributes; LBP with or without referred leg pain (sciatica) and comorbidities. Participants chose their preferred alternative either an opioid, NSAID or neither (“opt-out”). Each alternative varied by three clinical attributes: the type of opioid or NSAID, the degree of pain reduction and number of adverse events. Results: 210 GPs participated in the survey. Overall, GPs preferred to prescribe an NSAID (45.2%, 95% CI 38.7% to 51.7%) over an opioid (28.8%, 95% CI 23.0% to 34.7%). However, there was no difference between the type of NSAID or opioid preferred. Patient attributes of comorbidities (zero, one, two or three), and the presence of referred leg pain (sciatica) did not influence prescribing preferences, nor did clinical attributes of pain reduction and adverse events. Conclusions: GPs prefer to prescribe an NSAID over an opioid for a patient with chronic LBP. This preference appeared fixed and was not changed by clinical (drug type, degree of pain reduction or number of adverse events) or patient attributes (comorbidities or presence of referred leg pain).

Clinical practice guidelines consistently discourage opioid therapy in people with musculoskeletal pain related to any cause. Adverse outcomes related to opioid therapy for pain management have been reported in the literature. The main aim of this review is to summarise the prevalence of continued opioid use, opioid overdose, and serious adverse events following the provision of opioid therapy in or at discharge from emergency departments for the management of musculoskeletal pain.

Objectives: To provide a comprehensive overview of the efficacy, safety, and tolerability of antidepressants for pain conditions.Design: Overview of systematic reviews.Data sources: PubMed, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trials from inception to June 20, 2022.Eligibility criteria: Systematic reviews comparing any antidepressant to placebo for any pain condition in adults.Data extraction and synthesis: Two reviewers independently extracted data. Pain was our primary outcome; for headache disorders it was headache frequency. When reviews reported pain on a continuous scale, we converted scores to a scale of 0 (no pain) to 100 (worst pain) and presented results as mean differences (MD) and 95% confidence intervals (95% CI). We converted dichotomous outcomes to risk ratios (RR) (95% CI). We extracted data from the time point closest to the end of treatment. When end of treatment was too variable across trials for a pain condition review, we extracted data from the outcome or time point with the largest number of trials and participants. Safety and tolerability (withdrawals because of adverse events) were secondary outcomes. We classified findings from each comparison as either efficacious, not efficacious, or inconclusive. Certainty of evidence was assessed with the GRADE framework.Results: We included 26 reviews (158 unique trials and over 26,000 participants). These reviews reported on the efficacy of 8 antidepressant classes covering 22 pain conditions (43 distinct comparisons). 46% of trials had industry ties. No review provided high certainty evidence on the efficacy of antidepressants for pain for any condition. We found 11 comparisons (10 conditions) where antidepressants were efficacious, five with moderate certainty evidence: serotonin-norepinephrine reuptake inhibitors (SNRI) for back pain (MD: -5.3, 95% CI -7.3 to -3.3), postoperative pain (MD: -7.2, 95% CI -12.2 to -2.2), neuropathic pain (MD: -6.9, 95% CI -9 to -4.8), and fibromyalgia (RR: 1.4, 95% CI 1.3 to 1.6); and selective serotonin reuptake inhibitors (SSRI) for people with depression and comorbid chronic pain (standardised mean difference: -0.24, 95% CI -0.36 to -0.13). For the other 32 comparisons presented in this review, antidepressants were either not efficacious (5 comparisons) or the evidence was inconclusive (27 comparisons).Conclusions: Some antidepressants, particularly SNRIs, are efficacious in selected pain conditions. For most comparisons in this review, antidepressants were either inefficacious or there was inconclusive evidence on their efficacy. Our findings suggest a more nuanced approach to prescribing antidepressants for pain is needed.

Deprescribing is the systematic process of discontinuing drugs when harms outweigh the benefits. We conducted semistructured telephone interviews with 22 general practitioners (GPs) who had prescribed or deprescribed opioids in patients with chronic noncancer pain within the past 6 months to investigate the barriers and facilitators to deprescribing opioid analgesics in patients with chronic noncancer pain. We also explored GPs' perspectives on the available resources to assist them with opioid deprescribing. Interviews were audio-recorded, transcribed verbatim, and then coded using an iterative process until data saturation reached. The thematic analysis process identified themes, first as concepts, and then refined to overarching themes after the merging of similar subthemes. Themes exploring barriers to deprescribing highlighted the difficulties GPs face while considering patient factors and varying prescribing practices within the confines of the health system. Patient motivation and doctor-patient rapport were central factors to facilitate deprescribing and GPs considered the most important deprescribing resource to be a multidisciplinary network of clinicians to support themselves and their patients. Therefore, although GPs emphasised the importance of deprescribing opioid analgesics, they also expressed many barriers relating to managing complex pain conditions, patient factors, and varying prescribing practices between clinicians. Some of these barriers could be mitigated by GPs having time and resources to educate and build rapport with their patients. This suggests the need for further development of multimodal resources and improved support through the public health system to enable GPs to prioritise patient-centred care.

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).

Because pharmacological therapies may play an important role in managing musculoskeletal pain, the appropriate use of medicines for common conditions like low back pain (LBP) is critical. New evidence on the effects and safety of paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), opioid analgesics, muscle relaxants, antibiotics, and antidepressants for LBP warrants an updated overview for musculoskeletal clinicians on this topic.How effective and safe are paracetamol, NSAIDs, opioid analgesics, muscle relaxants, antibiotics, and antidepressants compared with placebo for treating LBP?For acute LBP (12 weeks), muscle relaxants and NSAIDs may be superior to placebo for reducing pain, but the effects of opioids, antibiotics, and antidepressants are unknown. Paracetamol provides no additional benefit for acute LBP. For chronic LBP (12 weeks), NSAIDs, antidepressants, and opioids may be superior to placebo for reducing pain, but opioids have an established profile of harms. Antibiotics may also reduce pain for people with chronic LBP with Modic type 1 changes, although the risks may outweigh their benefits. The effects of paracetamol and muscle relaxants for chronic LBP were unclear.NSAIDs may have a role in managing acute and chronic LBP, with cautious use in people who may be at greater risk of experiencing adverse events. Paracetamol, opioid analgesics, antibiotics, muscle relaxants, and antidepressants should only be prescribed following a discussion between the treating clinician and the patient, considering the risks and possible benefits, and after or in conjunction with recommended nonpharmacological strategies for improving LBP.

Objective Use of specific medications may accelerate the progression of radiographic knee OA (RKOA). Our aim was to examine the effect of medication use on the progression of RKOA. Methods We used longitudinal data from the Osteoarthritis Initiative (OAI), an observational study of risk factors for knee OA. At baseline, we selected participants with RKOA (Kellgren–Lawrence grade ≥2) and excluded those with a history of knee-related injury/surgery and other musculoskeletal disorders. Current medication use (use/non-use in the previous 30 days) and radiographic medial minimum joint space width (mJSW) data were available at baseline and annually up to 96 months follow-up. We used random effects, panel regression to assess the association between current medication use (non-users as reference group) and change in mJSW. Results Of 2054 eligible participants, 2003 participants with baseline mJSW data were included [55.7% female, mean age 63.3 (s.d. 8.98) years]. Of seven medication classes, at baseline NSAIDs were the most frequently used analgesia (14.7%), anti-histamine (10.4%) use was frequent and the following comorbidity medications were used most frequently: statins (27.4%), anti-hypertensives (up to 15.0%), anti-depressant/anxiolytics/psychotropics (14.0%), osteoporosis-related medication (10.9%) and diabetes-related medication (6.9%). Compared with current non-users, current use of NSAIDs was associated with a loss of mJSW (b = −0.042, 95% CI −0.08, −0.0004). No other associations were observed. Conclusions In current users of NSAIDs, mJSW loss was increased compared with current non-users in participants with RKOA. Clinical trials are required to assess the potential disease-modifying effects of these medications.

To investigate the proportion of patients with low back pain who receive an opioid analgesic prescription on hospital discharge, the proportion using opioid analgesics 4 weeks after discharge, and to identify predictors of continued opioid analgesic use at 4 weeks after an ED presentation in opioid-naïve patients.An observational cohort study nested within a randomised controlled trial in four EDs in New South Wales, Australia. Participants were adults who presented to the ED with non-specific low back pain or low back pain with lower limb neurological signs and symptoms. Electronic medical records supplemented the patient-reported pain and use of opioid analgesics at 4-week follow up.Of the 104 patients included, 33 (31.7%, 95% confidence interval [CI] 22.9-41.6) received an opioid analgesic prescription at hospital discharge and 38 (36.5%, 95% CI 27.3-46.6) reported taking an opioid analgesic for pain 4 weeks after the ED presentation. Among opioid-naïve patients (n = 85), older age (odds ratio [OR] 1.04, 95% CI 1.00-1.08, P = 0.031) was the only predictor for continued opioid analgesic use at 4 weeks post-ED presentation.About one-third of patients who present to the ED with low back pain receive an opioid analgesic prescription on discharge and are taking an opioid analgesic 4 weeks later. These findings justify future research to identify strategies to reduce the risk of long-term opioid use in patients who present to the ED with low back pain.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To determine the benefits and harms of antibiotic therapy, compared with placebo or another comparison treatment, in people with low back pain or radicular pain, or both.

To evaluate the efficacy and safety of opioids for analgesic therapy for people with osteoarthritis.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.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.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.Opioid medications may provide very small pain and disability benefits for people with osteoarthritis, but may also increase the risk of adverse events.CRD42019142813 (prospective).

BACKGROUND Sciatica can be a debilitating condition and there is limited guidance on the use of glucocorticoids administered via the oral, intramuscular or intravenous route for this condition. These represent viable treatment options in the primary care setting. OBJECTIVE To evaluate the evidence on efficacy and harms of oral, IM and IV glucocorticoid administration for sciatica. DATABASES AND DATA TREATMENT MEDLINE, EMBASE, CENTRAL, CINAHL, PsycINFO (inception to October 2018) were searched for randomised placebo-controlled trials evaluating oral, IV or IM glucocorticoid administration for sciatica. Two authors extracted outcomes data. Continuous pain and disability outcomes were converted to a 0 (no pain/disability) to 100 (worst pain/disability) scale. Data were pooled using a random effects model. Overall quality of evidence was assessed using GRADE. Primary outcomes were leg pain and disability. Primary follow-up period was the immediate-term (

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.

International clinical practice guidelines for low back pain (LBP) contain consistent recommendations including universal provision of information and advice to remain active, discouraging routine referral for imaging, and limited prescription of opioids. This systematic review describes usual care provided by first-contact physicians to patients with LBP. Studies that reported the assessments and care provided to people with LBP in family practice and emergency departments (EDs) from January 2000 to May 2019 were identified by searches of PubMed, EMBASE, and CINAHL. Study quality was assessed with reference to representativeness of samples, potential misclassification of patients, potential misclassification of outcomes, inconsistent data and precision of the estimate, and the findings of high-quality studies were prioritized in the data synthesis. We included 26 studies that reported data from almost 195,000 patients: 18 from family practice, and 8 from EDs. Less than 20% of patients with LBP received evidence-based information and advice from their family practitioner. Around 1 in 4 patients with LBP received referral for imaging in family practice and 1 in 3 in EDs. Up to 30% of patients with LBP were prescribed opioids in family practice and up to 60% in EDs. Large numbers of patients who saw a physician for LBP received care that is inconsistent with evidence-based clinical practice guidelines. Usual care included overuse of imaging and opioid prescription and underuse of advice and information. Suboptimal care may contribute to the massive burden of the condition worldwide.

What you need to know A 65 year old patient has been troubled with intermittent low back pain for years, for which you prescribed ibuprofen 400 mg up to three times daily as needed. For the past four months, persistent knee pain, not associated with stiffness, has limited his mobility. He is overweight, physically inactive, and has recently been diagnosed with hypertension. Paracetamol has had little benefit. He asks if taking ibuprofen regularly might ease his knee pain. NSAIDs are commonly used for pain management. They reduce inflammation and pain by reducing the activity of cyclo-oxygenase (or COX) enzymes and inhibiting prostaglandin synthesis.1 The National Institute for Health and Care Excellence (NICE) guidelines recommend NSAIDs as first line analgesics for low back pain and sciatica2 and osteoarthritis.3 They are also used for musculoskeletal pain from acute injury. In England there were about 11.5 million prescriptions for oral NSAIDs in 2018.4 In the US around 60% of patients with osteoarthritis or chronic low back pain are prescribed NSAIDs, based on analysis of records in a claims database in 2008.5 ### Search strategy We searched PubMed (NLM database) and the Cochrane Library with the terms “non-steroidal anti-inflammatory drugs” OR “NSAIDs” AND “spinal pain” OR …

Objective To investigate the efficacy and safety of antidepressants for back and osteoarthritis pain compared with placebo. Design Systematic review and meta-analysis. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, CINAHL, International Pharmaceutical Abstracts, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from inception to 15 November and updated on 12 May 2020. Eligibility criteria for study selection Randomised controlled trials comparing the efficacy or safety, or both of any antidepressant drug with placebo (active or inert) in participants with low back or neck pain, sciatica, or hip or knee osteoarthritis. Data extraction and synthesis Two independent reviewers extracted data. Pain and disability were primary outcomes. Pain and disability scores were converted to a scale of 0 (no pain or disability) to 100 (worst pain or disability). A random effects model was used to calculate weighted mean differences and 95% confidence intervals. Safety (any adverse event, serious adverse events, and proportion of participants who withdrew from trials owing to adverse events) was a secondary outcome. Risk of bias was assessed with the Cochrane Collaboration’s tool and certainty of evidence with the grading of recommendations assessment, development and evaluation (GRADE) framework. Results 33 trials (5318 participants) were included. Moderate certainty evidence showed that serotonin-noradrenaline reuptake inhibitors (SNRIs) reduced back pain (mean difference −5.30, 95% confidence interval −7.31 to −3.30) at 3-13 weeks and low certainty evidence that SNRIs reduced osteoarthritis pain (−9.72, −12.75 to −6.69) at 3-13 weeks. Very low certainty evidence showed that SNRIs reduced sciatica at two weeks or less (−18.60, −31.87 to −5.33) but not at 3-13 weeks (−17.50, −42.90 to 7.89). Low to very low certainty evidence showed that tricyclic antidepressants (TCAs) did not reduce sciatica at two weeks or less (−7.55, −18.25 to 3.15) but did at 3-13 weeks (−15.95, −31.52 to −0.39) and 3-12 months (−27.0, −36.11 to −17.89). Moderate certainty evidence showed that SNRIs reduced disability from back pain at 3-13 weeks (−3.55, −5.22 to −1.88) and disability due to osteoarthritis at two weeks or less (−5.10, −7.31 to −2.89), with low certainty evidence at 3-13 weeks (−6.07, −8.13 to −4.02). TCAs and other antidepressants did not reduce pain or disability from back pain. Conclusion Moderate certainty evidence shows that the effect of SNRIs on pain and disability scores is small and not clinically important for back pain, but a clinically important effect cannot be excluded for osteoarthritis. TCAs and SNRIs might be effective for sciatica, but the certainty of evidence ranged from low to very low. Systematic review registration PROSPERO CRD42020158521.

Background: Chemoprevention with NSAIDs, including aspirin, and anti-platelet therapy (APT), has been suggested to reduce the incidence and recurrence of hepatocellular carcinoma (HCC). This meta-analysis aimed to determine whether NSAIDs and APT use affected HCC incidence, HCC recurrence and liver-related mortality in at-risk populations with chronic liver disease. Method: Electronic databases including Pubmed, Scopus, Medline, Embase and Cochrane Library were searched (from inception to 1 October 2020) for eligible studies evaluating the impacts of NSAID or APT use on HCC incidence, recurrence and mortality. Data on HCC incidence, recurrence, liver-related mortality or bleeding complications had to be available. Studies were included if they evaluated adults with newly diagnosed HBV, HCV, ALD or NASH that were administered at least one NSAID or APT for a defined period of time and were followed for at least six-months. The primary outcome was HCC incidence. Secondary outcomes included: HCC recurrence, liver-related mortality and bleeding complications. Data were pooled using a random effects model with hazards ratios (HR) or odds ratio (OR), and 95% confidence intervals (CI) presented. Results: Of 3614 articles screened, 16 studies were included, with a total of 111,096 participants. Aspirin use significantly reduced the risk of HCC incidence (HR: 0.47, 95% CI: 0.32-0.71); and improved liver-related mortality (OR: 0.38, 95% CI: 0.29-0.49), with a small increased risk of gastrointestinal bleeding events (OR: 1.141, 95% CI: 1.06-1.23). With respect to HCC recurrence following treatment, analysis of all NSAID treatment (including aspirin-only, non-aspirin NSAIDs-only and combination NSAIDs groups) were associated with a decreased risk of HCC recurrence (HR: 0.80, 95% CI: 0.75-0.86). By stratified analysis, only the non-aspirin NSAID group showed statistical significance in risk reduction (HR: 0.73, 95% CI: 0.63-0.84). Conclusion: This study supports the use of aspirin in at-risk individuals to reduce the incidence of HCC and liver-related mortality. Funding Statement: NSW Cancer Council Linkage grant RG163222. Declaration of Interests: None of the authors declare any conflict of interest.

Questions What is the effect of advice/education compared with placebo or no advice/education on pain and disability in people with non-specific spinal pain? To what extent do characteristics of the patients, trial or intervention modify the estimate of the treatment effects? Design A systematic review with meta-analyses of randomised controlled trials. Participants Adults with non-specific back and/or neck pain with or without radiating leg/arm pain of any duration were included. Trials recruiting pregnant women or surgical patients in the immediate postoperative phase were ineligible. Intervention Advice or education. Outcome measures The primary outcomes were self-reported pain and disability, and the secondary outcome was adverse events. The following potential effect modifiers were examined: risk of bias, duration of pain, location of pain, intensity of intervention and mode of intervention. Results Twenty-seven trials involving 7,006 participants were included. Eighteen of the included trials were assessed as being at low risk of bias (≥ 6 on the PEDro scale). There was low-quality evidence that advice had a small effect on pain (MD −8.2, 95% CI −12.5 to −3.9, n = 2,241) and moderate-quality evidence that advice had a small effect on disability (MD −4.5, 95% CI −7.9 to −1.0, n = 2,579) compared with no advice or placebo advice in the short-term. None of the items that were assessed modified the treatment effects. Conclusion Advice provides short-term improvements in pain and disability in non-specific spinal pain, but the effects are small and may be insufficient as the sole treatment for patients with spinal pain. Registration PROSPERO CRD42020162008.

In August 2020, the National Institute for Health and Care Excellence (NICE) published the draft guidance on chronic pain, which perhaps controversially advises against the use of all drugs except antidepressants.1 The committee cite an absence of evidence on effectiveness, their experience, information in product summaries, and the established or possible risk of harm as justification for their negative recommendations. Public reaction perhaps reflects the assumption the guidelines apply to all chronic pain conditions. This is not the case. The guideline explicitly does not cover pain conditions that have existing NICE guidelines including headache, low back pain (LBP) and irritable bowel syndrome (IBS).1–6 This creates an interesting tension, since some recommendations are discordant (Box 1). | Drug class | Draft NICE guideline: chronic pain in over 16s, August 20201 | NICE guideline: low back pain and sciatica in over 16s, updated September 20205 | NICE guideline: headache in over 12s, updated November 20154,a | NICE guideline: irritable bowel syndrome in adults, updated April 20176 | NICE guideline: osteoarthritis, updated February 20148 | |:--------------------------- | --------------------------------------------------------------------------------------------------------------- | ---------------------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ----------------------------------------------------------------------------------------------------------------------------- | -------------------------------------------------------------------------------------------- | | Opioids | Do not offer | Do not offer | Be alert to the possibility of medication overuse headache in people whose headache developed or worsened while they were taking the following drugs for ≥3 months: | No specific recommendation | If paracetamol or topical NSAIDs are insufficient consider the addition of opioid analgesics | | NSAIDs | Do not offer | Consider oral NSAIDs (conditions apply) | No specific recommendation | Where paracetamol or topical NSAIDs are ineffective consider substitution with (or addition of) an oral NSAID/COX-2 inhibitor | | Paracetamol (acetaminophen) | Do not offer | Do not offer paracetamol alone | No specific recommendation | Consider offering paracetamol in addition to core treatments. | | Antidepressants | Consider an antidepressant, either duloxetine, fluoxetine, paroxetine, citalopram, sertraline, or amitriptyline | Do not offer SSRIs, serotonin–norepinephrine reuptake inhibitors, or tricyclic antidepressants | Consider amitriptyline for the prophylactic treatment of migraine | Consider TCAs as second line treatment for people with IBS. Consider SSRIs for people with IBS only if TCAs are ineffective | No specific recommendation | | Anticonvulsants | Do not offer | Do not offer | Do not offer gabapentin for prophylactic management of migraine | No specific recommendation | No specific recommendation | Box 1. Concordance between drug recommendations in draft NICE chronic pain guideline and NICE guidelines for low back pain, headache, irritable bowel syndrome, and osteoarthritis The guideline committee used the International Classification …

Background People with low back pain (LBP) in the community often do not receive evidence-based advice and management. Community pharmacists can play an important role in supporting people with LBP as pharmacists are easily accessible to provide first-line care. However, previous research suggests that pharmacists may not consistently deliver advice that is concordant with guideline recommendations and may demonstrate difficulty determining which patients require prompt medical review. A clinical decision support system (CDSS) may enhance first-line care of LBP, but none exists to support the community pharmacist–client consultation. Objective This study aimed to develop a CDSS to guide first-line care of LBP in the community pharmacy setting and to evaluate the pharmacist-reported usability and acceptance of the prototype system. Methods A cross-platform Web app for the Apple iPad was developed in conjunction with academic and clinical experts using an iterative user-centered design process during interface design, clinical reasoning, program development, and evaluation. The CDSS was evaluated via one-to-one user-testing with 5 community pharmacists (5 case vignettes each). Data were collected via video recording, screen capture, survey instrument (system usability scale), and direct observation. Results Pharmacists’ agreement with CDSS-generated self-care recommendations was 90% (18/20), with medicines recommendations was 100% (25/25), and with referral advice was 88% (22/25; total 70 recommendations). Pharmacists expressed uncertainty when screening for serious pathology in 40% (10/25) of cases. Pharmacists requested more direction from the CDSS in relation to automated prompts for user input and page navigation. Overall system usability was rated as excellent (mean score 92/100, SD 6.5; 90th percentile compared with similar systems), with acceptance rated as good to excellent. Conclusions A novel CDSS (high-fidelity prototype) to enhance pharmacist care of LBP was developed, underpinned by clinical practice guidelines and informed by a multidisciplinary team of experts. User-testing revealed a high level of usability and acceptance of the prototype system, with suggestions to improve interface prompts and information delivery. The small study sample limits the generalizability of the findings but offers important insights to inform the next stage of system development.

Evidence has shown that programmed cell death ligand 1 (PD-L1) overexpression is associated with poor prognosis and resistance to immune therapies in several human cancers. However, data on the prognostic significance of PD-L1 expression in thyroid cancer are limited and remain controversial. This systematic review and meta-analysis aimed to evaluate comprehensively the clinicopathologic significance and prognostic value of PD-L1 expression in non-medullary thyroid cancers.Electronic databases, including Medline/PubMed, EMBASE, and the Cochrane Library, were searched up until July 5, 2017. In total, seven comparisons (from six articles) comprising 1421 patients were included in the pooled analysis.There was moderate quality evidence from four studies (n = 721) that shows positive PD-L1 expression was significantly associated with poor survival among thyroid cancer patients (pooled hazard ratio = 3.73 [confidence interval (CI) 2.75-5.06]). Increased PD-L1 expression was also found to be significantly associated with disease recurrence (odds ratio = 1.95 [CI 1.15-3.32]) and concurrent thyroiditis (odds ratio = 1.65 [CI 1.09-2.51]).The results confirm the prognostic significance of PD-L1 expression in thyroid cancer patients. PD-L1 expression has the potential to be implemented as a prognostic biomarker used to guide clinicians in identifying patients with more aggressive cancers, and for the selection of individuals that would derive durable clinical benefit from anti-PD-1/PD-L1 immunotherapy. Prospective clinical trials will be useful to support these findings.

SummaryObjective To investigate the use of an enriched study design on the estimates of treatment effect in analgesic trials for chronic musculoskeletal pain Methods Database searches were conducted from 2004 to 2014. We included randomised placebo-controlled trials evaluating pain medications for chronic musculoskeletal pain. Methodological quality was assessed using the PEDro scale. The estimates of treatment effect on pain and adverse events were compared between enriched and non-enriched designs. Meta-regression was used to assess the association between the effect size estimate and the study design controlling for analgesic dose and methodological quality Results We included 108 trials, of which 99 were included in the meta-analysis (n=44,171). There were no overall differences in effect sizes between enriched and non-enriched designs for pain intensity. There was a significant difference for a reduction in any adverse events favouring enriched designs for opioids, but not for other analgesics or the outcome serious adverse events. There was an association between effect size and methodological quality, with failure to blind the outcome assessor and failure to use intention-to-treat analysis being associated with larger effect sizes. Conclusions There is no evidence that the use of an enriched study design changes the treatment effect size estimate for pain. There is some evidence that clinical trials that employ enriched designs report a reduced risk of adverse events in trials for chronic musculoskeletal pain, but it is unclear whether enriched designs influence estimates of serious adverse events. Features of trial design and study quality were associated with treatment effect estimates.