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Opioid Therapy in the 21st Century, Second Edition provides clinicians with up-to-date, evidence-based information about appropriate opioid use, including the potential benefits and adverse affects of the therapy.

Glucocorticoids as a component of multimodal analgesia have been studied for many years and their post-operative analgesic effects appear to be dose-dependent. We conducted a systematic review of randomized controlled trials (RCTs) to evaluate the evidence of peri-operative high dose corticosteroid therapy in comparison to placebo (placebo drug) or control group (no treatment) for improving the quality of post-operative analgesia as indicated by a reduction of 10 mm in 100 mm Visual Analogue Scale (VAS) or reduction of 1 point in a 0–10 point VAS scale, or a reduction of 1 point in an 11-point Numerical Rating Scale (NRS) score, or reduction of rescue opioid analgesia, in patients undergoing all types of surgery. Systematic review of RCTs with meta-analysis. Acute postoperative pain treatment in non-obese adult population. Perioperative administration of high dose of Dexamethasone (≥ 0,2 mg/Kg or ≥ 15 mg), or a corresponding dose of a systemic glucocorticoid. Primary outcomes were postoperative pain measured in 0–100 mm VAS score at 24 h after surgery upon rest and movement. Secondary outcomes were postoperative pain 0–100 mm VAS score 48 h after surgery, postoperative rescue analgesic requirement, postoperative nausea and vomiting (PONV), relevant adverse events. 47 RCT's were included (3943 patients). The Mean Difference (MD) of 100 mm VAS scores for pain at rest 24 h after surgery was −6.18 mm 95% CI [−8.53, −3.83], at motion −8.86 mm 95% CI [−11.82, −5.89]. Opioid analgesic requirements evaluated in Oral Morphine Equivalents (OME) was −10.00 mg 95% CI [−13.65, −6.34]. PONV events Odds Ratio of 0.29 95%CI [0.24, 0.36]. Major adverse events OR was 0.88 95% CI [0.65, 1.19]. Minor adverse events OR 1.29 95% CI [0.86, 1.92]. High doses of glucocorticoids are one of the many possible tools available in multimodal postoperative analgesia, possibly reducing opioids consumption and recurrence of PONV but with no relevant effects in terms of reduction of postoperative VAS score. Available data show a safe therapeutic profile, without increase adverse events. Protocol registration: CRD42020137119. •First meta-analysis on high dose glucocorticoids in acute postoperative pain•High dose of glucocorticoids reduces postoperative morphine consumption.•Postoperative pain 24 h after surgery slightly reduced by high dose glucocorticoids.•Confirmed role of glucocorticoids in treatment of postoperative nausea and vomiting.•Major postoperative adverse events don't seem increased by high dose glucocorticoids.

This systematic review and meta-analysis aimed to assess interventions to reduce opioid use for patients with chronic non-cancer pain (CNCP) versus usual care or active controls in primary care settings. In this registered study (PROSPERO: CRD42022338458), we searched MEDLINE, Embase PsycInfo, CINAHL, and Cochrane Library from inception to December 28th 2021, and updated on Dec 14th 2023 for randomized controlled trials (RCTs) and cohort studies with no restrictions. Methodological quality was assessed using the Cochrane Risk of Bias tool for RCTs and Newcastle Ottawa Scale for cohort studies. Primary outcomes included mean reduction in morphine equivalent daily dose (reported as mean differences [MDs] mg/day; 95% confidence intervals [95%CIs]) and/or opioid cessation proportion. Secondary outcomes were mean changes in pain severity (reported as standardized mean difference [SMDs]; 95%CIs) and (serious) adverse events. Meta-analyses were performed using random-effects models. We identified 3,826 records, of which five RCTs (953 participants) and five cohort studies (901 participants) were included. Overall, opioid dosage was significantly reduced in intervention groups compared to controls (MD: -28.63 mg/day, 95%CI: -39.77 to -17.49; I2 = 31.25%; eight studies). Subgroup analyses revealed significant opioid dose reductions with mindfulness (MD: -29.36 mg/day 95%CI: -40.55 to -18.17; I2 = 0.00%; two trials) and CBT-based multimodalities (MD: -41.68 mg/day; 95%CI: -58.47 to -24.89; I2 = 0.00%; two cohort studies), respectively, compared to usual care. No significant differences were observed in opioid cessation (Odds ratio: 1.10, 95%CI: -0.48 to 2.67, I2 = 58.59%; two trials) or pain severity (SMD: -0.13, 95%CI: -0.37 to 0.11; I2 = 33.51%; three trials). Adverse events were infrequently examined, with withdrawal symptoms commonly reported. The studied interventions were effective in reducing opioid dosage for people with CNCP in primary care. They highlighted the importance of multidisciplinary collaboration. Large-scale RCTs measuring the long-term effects and cost of these interventions are needed before their implementation.

Purpose There is no consensus in the current literature on the analgesic role of duloxetine after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Thus, we designed this meta-analysis to reveal the analgesic effectiveness and safety of duloxetine in TKA or THA. Methods As of October 2022, two authors (L.C. and W.Q.J.) independently searched five main databases (EMBASE, Web of Science, PubMed, Cochrane Library, and Google Scholar) to find relevant studies. Duloxetine vs. placebo in randomized controlled trials (RCTs) for THA or TKA were included. We set perioperative total opioid consumption as the primary outcome. Secondary outcomes included resting or dynamic pain scores over time, gastrointestinal adverse events, neurological adverse events, and other adverse reactions. Results Eight RCTs with 695 patients were incorporated in our study. This meta-analysis showed high evidence that duloxetine was effective in reducing perioperative opioid consumption (Standard mean difference [SMD] = − 0.50, 95% confidence intervals [CI]: −0.70 to − 0.31, P  < 0.00001) and low to moderate evidence that duloxetine could reduce pain within three weeks after surgery. Low to high evidence showed no differences between the two groups for most adverse events. Substantial evidence suggests that duloxetine can reduce nausea and vomiting after surgery (Risk ratio [RR] = 0.69, 95% CI: 0.50 to 0.95, P  = 0.02, I 2  = 4%). However, moderate evidence suggested that duloxetine might be associated with increased postoperative drowsiness (RR = 1.83, 95% CI: 1.08 to 3.09, P  = 0.02, I 2  = 0%). Conclusion Duloxetine reduced overall opioid consumption in the perioperative period and relieved pain within three weeks after surgery without increasing the risk of adverse drug events. Duloxetine can be part of a multimodal management regimen in patients with THA and TKA.

Pain management for hip and proximal femoral fractures includes oral and parenteral opioids and various regional anesthesia techniques. Fascia iliaca compartment blocks (FICB) are commonly used for these patients. At present, a unified view of the analgesic effect of FICB has not been reached. In addition, the comparison between single shot FICB and continuous FICB has not elicited clear evidence-based results. We will compare the efficacy and safety of systemic analgesics, single shot or continuous FICB in the pain management, complication prevention and satisfaction, in our systematic review and network meta-analysis. China National Knowledge Infrastructure, Chinese Biomedical Literatures database, PubMed, the Cochrane Central Register of Controlled Trials, Physiotherapy Evidence Database, EMBASE, and Web of Science will be searched until June 2023. Two authors will independently screen the studies for eligibility and perform data extraction. The Cochrane risk of bias tool (RoB 2) will be used to assess the quality of evidence. We will use the GRADE approach to assess the certainty of the evidence across studies included in this review. All the statistical analyses will be conducted using Rev Man 5.3, WinBUGS 1.4.3, and Stata 13. Our review involves a secondary analysis of existing published studies, therefore there is no need for formal research ethics approval. We will disseminate our findings through publication in a peer-reviewed journal. PROSPERO, CRD42023425282.

Objective. Although low-dose ketamine has been shown to be generally beneficial in terms of pain control in a variety of major surgery, there is no consensus regarding the effectiveness of supplemental ketamine analgesic use exclusively in spine surgery. The objective of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to assess the efficacy and safety of perioperative low-dose ketamine for pain management and analgesic consumption in patients undergoing spine surgery. Methods. A comprehensive literature search was performed for relevant studies using PubMed, EMBASE, Web of Science, and Cochrane Library. Patients who received perioperative low-dose ketamine were compared to the control group in terms of postoperative pain intensity, opioid consumption, and adverse events. Patients were further categorized by ages and administration times for subgroup analysis. Results. A total of 30 RCTs comprising 1,865 patients undergoing elective spine surgery were included. Significantly lower pain intensity and less opioid consumption at 12 h, 24 h, and 48 h postoperatively and lower incidence of postoperative nausea and vomiting (PONV) were observed in the ketamine group (all P<0.05). There was no significant difference of central nervous system (CNS) adverse events between groups. However, different efficacy of low-dose ketamine was detected when patients were categorized by ages and administration times. Conclusion. Perioperative low-dose ketamine demonstrated analgesic and morphine-sparing effect with no increased adverse events after spine surgery. However, this effect was not significant in pediatric patients. Only postoperative or intraoperative and postoperative administration could prolong the analgesic time up to 48 h postoperatively. Further studies should focus on the optimal protocol of ketamine administration and its effect on old age participants.

IntroductionDexmedetomidine is a promising pharmaceutical strategy to minimise opioid use during surgery. Despite its growing use, it is uncertain whether dexmedetomidine can improve patient-centred outcomes such as quality of recovery and pain.Methods and analysisWe will conduct a systematic review and meta-analysis following the recommendations of the Cochrane Handbook for Systematic Reviews. We will search MEDLINE, Embase, CENTRAL, Web of Science and CINAHL approximately in October 2023. We will include randomised controlled trials evaluating the impact of systemic intraoperative dexmedetomidine on patient-centred outcomes. Patient-centred outcome definition will be based on the consensus definition established by the Standardised Endpoints in Perioperative Medicine initiative (StEP-COMPAC). Our primary outcome will be the quality of recovery after surgery. Our secondary outcomes will be patient well-being, function, health-related quality of life, life impact, multidimensional assessment of postoperative acute pain, chronic pain, persistent postoperative opioid use, opioid-related adverse events, hospital length of stay and adverse events. Two reviewers will independently screen and identify trials and extract data. We will evaluate the risk of bias of trials using the Cochrane Risk of Bias Tool (RoB 2.0). We will synthesise data using a random effects Bayesian model framework, estimating the probability of achieving a benefit and its clinical significance. We will assess statistical heterogeneity with the tau-squared and explore sources of heterogeneity with meta-regression. We have involved patient partners, clinicians, methodologists, and key partner organisations in the development of this protocol, and we plan to continue this collaboration throughout all phases of this systematic review.Ethics and disseminationOur systematic review does not require research ethics approval. It will help inform current clinical practice guidelines and guide development of future randomised controlled trials. The results will be disseminated in open-access peer-reviewed journals, presented at conferences and shared among collaborators and networks.PROSPERO registration numberCRD42023439896.

Background The purpose of this study was to compare the effect of 300 mg of bupropion and 8 mg of buprenorphine per day on the treatment of methamphetamine withdrawal cravings over a 2-week treatment interval. Method Sixty-five methamphetamine-dependent men who met the DSM-IV-TR ( Diagnostic and Statistical Manual of Mental Disorders , 4th edition, text revision) criteria for methamphetamine dependence and withdrawal were randomly divided into two groups. Subjects randomly received 300 mg of bupropion or 8 mg of buprenorphine per day in a psychiatric ward. Of the 65 subjects, 35 (53.8%) received buprenorphine and 30 (46.2%) received bupropion. The subjects were assessed by using methamphetamine craving score, interview, and negative urine drug test. Findings There were no statistically significant differences between the two groups in regard to age, education, duration of methamphetamine dependency, marital status, employment, and income. The mean ages were 32.8 years (standard deviation (SD) = 7.26, range = 22 to 59) for the buprenorphine group and 32.21 years (SD = 8.45, range = 17 to 51) for the bupropion group. All 65 patients completed the 2-week study. Both medications were effective in the reduction of methamphetamine cravings. Reduction of craving in the buprenorphine group was significantly more than the bupropion group ( P = 0.011). Overall, a significant main effect of day ( P <0.001) and group ( P = 0.011) and a non-significant group-by-day interaction ( P >0.05) were detected. Conclusions The results support the safety and effectiveness of buprenorphine and bupropion in the treatment of methamphetamine withdrawal craving. Administration of 8 mg of buprenorphine per day can be recommended for the treatment of methamphetamine withdrawal cravings. We should note that it is to be expected that craving decreases over time without any medication. So the conclusion may not be that bupropion and buprenorphine both lower the craving. As the buprenorphine is superior to bupropion, only buprenorphine does so for sure. Trial registration Iranian Registry of Clinical Trials (IRCT) registration number: IRCT2015010320540N1 . Date registered: April 10, 2015.

Breakthrough pain (BTP) is episodic pain that emerges through the treatment of otherwise well-managed chronic background pain. Often called pain flare or transient pain, BTP negatively affects the function and quality of life of the patient and often results in a number of other physical, psychological and social problems. Breakthrough pain is a common occurrence affecting approximately two-thirds of the estimated 50 to 100 million chronic pain sufferers in the US. It can have multiple causes with various pathophysiologies, and can present with numerous clinical features and complications. The clinical features vary from individual to individual, and may vary within an individual over time. The successful management of breakthrough pain depends on proper assessment, treatment, and reassessment. Inadequate assessment can lead to ineffective or inappropriate treatment. Similarly, inadequate reassessment may lead to continuance of ineffective or even harmful treatment. In recent years, the need to educate physicians about pain management has been garnering increased attention from prominent medical associations and the media. Despite ongoing efforts to improve pain treatment, however, the need persists for evidence-based educational materials for physicians in the area of pain diagnosis and management. Part of the Oxford American Pain Library, this highly practical guide covers current approaches and new developments in the assessment and management of breakthrough pain, including both cancer-related pain and non-cancer chronic pain. It addresses the roles of opioid and non-opioid pharmacotherapy and presents non-pharmacologic interventions as well.

IntroductionInterventions targeting behaviours of physician prescribers of opioids for chronic non-cancer pain have been introduced to combat the opioid crisis. Systematic reviews have evaluated effects of specific interventions (eg, prescriber education, prescription drug monitoring programmes) on patient and population health outcomes and prescriber behaviour. Integration of findings across intervention types is needed to better understand the effects of prescriber-targeted interventions.Methods and analysisWe will conduct an overview of systematic reviews. Eligible systematic reviews will include primary studies that evaluated any intervention targeting the behaviours of physician prescribers of opioids for chronic non-cancer pain in an outpatient or mixed setting, compared with no intervention, usual practice or another active or control intervention. Eligible outcomes will pertain to the intervention effect on patient and population health or opioid prescribing behaviour. We will search MEDLINE, Embase and PsycInfo via Ovid; the Cochrane Database of Systematic Reviews and Epistemonikos from inception. We will also hand search reference lists for additional publications. Screening and data extraction will be conducted independently by two reviewers, with disagreements resolved by consensus or consultation with a third reviewer. The risk of bias of included systematic reviews will be assessed in duplicate by two reviewers using the Risk of Bias in Systematic Reviews tool. Results will be synthesised narratively by intervention type and grouped by outcome. To assist with result interpretation, outcomes will be labelled as intended or unintended according to intervention objectives, and as positive, negative, evidence of no effect or inconclusive evidence according to effect on the population (for patient and population health outcomes) or intervention objectives (for prescriber outcomes).Ethics and disseminationAs the proposed study will use published data, ethics approval is not required. Dissemination of results will be achieved through publication of a manuscript in a peer-reviewed journal and conference presentations.PROSPERO registration numberCRD42020156815.