Javed, Saba

Importance Chronic pain is a leading cause of disability, and many affected patients rely on long-term opioid therapy despite its unfavorable adverse effect profile. Spinal cord stimulation is an established therapy for chronic pain that may secondarily reduce opioid consumption by providing sustained analgesia. Objective To quantify changes in opioid use following spinal cord stimulation implantation for the treatment of chronic pain through a systematic review and meta-analysis. Data sources We conducted a comprehensive search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus from each database’s inception to July 1, 2024. Study selection We included studies describing patients who underwent spinal cord stimulator implantation for the treatment of chronic pain. A total of 2,784 potential studies were identified and screened by multiple independent reviewers, yielding a final total of 43 studies included in the systematic review. Data extraction and synthesis Data extraction was completed by multiple independent reviewers following Preferred Reporting Items for Systematic Reviews and Meta-Analysis and Meta-analysis Of Observational Studies in Epidemiology guidelines. A random effects model with Hartung-Knapp-Sidik-Jonkman adjustment was used to estimate pooled estimates. Certainty assessment was performed following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Main outcome(s) and measure(s) The primary outcomes were change in continuous opioid use (ie, morphine milligram equivalent (MME)) and categorical opioid use (yes/no) from preimplantation to 12 months following spinal cord stimulator implantation. Results Meta-analysis of 12 month continuous MME use comprising 22 study comparisons (1,666 individuals) revealed a weighted mean difference of −18.06 MME (95% CI −24.41 to −11.70; 95% prediction interval −38.29 to 2.17; p<0.001). Meta-analysis of categorical opioid use at 12 months comprising 24 study comparisons (1,527 individuals) revealed an OR of 0.47 (95% CI 0.30 to 0.75; 95% prediction interval 0.10 to 2.11; p=0.003), signifying lower odds of opioid continuation. Conclusions and relevance Spinal cord stimulation is associated with reduced opioid dose consumption and increased odds of opioid cessation at 12 months postimplantation compared with baseline in patients with chronic pain; however, both of these conclusions are supported by evidence of very low GRADE certainty. PROSPERO registration number CRD42024574921.

Background/importance Spinal cord stimulation (SCS) is an established therapy for chronic pain conditions when conventional treatments fail. However, global research implementation varies significantly due to patient demographics, healthcare infrastructure, and economic factors, creating disparities in access that directly impact patient care and public health outcomes. Objective To evaluate the global landscape of SCS research by analyzing patient demographics, geographic distribution, funding sources, and pain conditions treated across chronic pain populations aged 18 years and older, with primary focus on associations between geographic regions and patient age demographics. Evidence review We conducted a systematic literature review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, searching five major databases through October 2024. Studies from 2000 onward reporting SCS in adults with chronic pain lasting 3 months or longer were included. We included randomized trials, comparative studies, and case series with at least 10 patients, excluding commentaries, reviews, and insurance databases. Findings Analysis of 187 studies revealed heterogeneity in age distributions across geographic regions, with Asian studies showing higher mean ages compared to North America, while European showed lower mean ages. Research concentration was predominantly in high-income regions, with 57% of studies receiving industry funding and significant associations between funding source and geographic origin. Post-surgical pain syndrome-thoracolumbar emerged as the most prevalent condition globally, representing 44.9% of cases. Conclusions Significant associations exist between geographic regions and patient demographics in SCS research, with notable disparities in research concentration highlighting the need for broader investigation in underrepresented areas to optimize global application of this chronic pain management therapy. PROSPERO registration number CRD42025635147.

Background Peripheral nerve stimulation (PNS) is an emerging neuromodulation therapy for chronic pain, yet its use in clinical practice varies significantly. Although temporary PNS is widely incorporated, either as a screening trial or a treatment itself, the evidence supporting the use of temporary PNS prior to permanent implantation is limited. We aimed to compare pain relief, opioid consumption, and adverse events between an approach implementing temporary PNS before permanent implantation (temporary-to-permanent (TTP)) vs proceeding directly to permanent PNS implantation (direct-to-permanent (DTP)). Methods A multicenter retrospective study was undertaken at seven major academic institutions from January 1, 2014, to January 1, 2024. Adult patients who underwent permanent PNS implantation for the treatment of chronic pain conditions were included and were divided into TTP or DTP cohorts based on their clinical approach. The dual primary outcomes were pain relief and opioid consumption (in oral morphine equivalents) at 6 months compared with baseline before any PNS therapy. Multivariable Tobit regression analysis was performed to identify predictors of pain relief at 6 months using a stepwise approach. Results A total of 130 patients were analyzed (54 in TTP approach, 76 in DTP approach). Patient-reported percentage pain relief was 56.7%±27.9% at 6 months compared with baseline (before PNS implantation) in the TTP cohort, and 45.1%±33.6% in the DTP cohort. The estimated mean percentage pain relief at 6 months was similar in the TTP and DTP cohorts (between-group difference 15.24%; 95% CI −0.32 to 30.80, p=0.052), with consistent findings after sensitivity analysis with multiple imputation. Opioid consumption declined similarly in the TTP (−3.1±9.9 mg) and DTP (−2.1±8.1 mg) cohorts at 6 months with no statistical difference between cohorts (mean between-group difference: −1.00, 95% CI −4.57 to 2.57, p=0.580), and with consistent findings after sensitivity analysis. Device explantation rates and adverse event profiles were comparable between cohorts. Conclusion Although temporary PNS is widely performed prior to permanent PNS implantation, there was no evidence that the TTP approach is associated with superior analgesic outcomes compared with the DTP approach. Further, patients in both approaches achieved clinically meaningful pain relief at 6 months compared with baseline status prior to PNS therapy.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adult Cancer Pain provide recommendations for the comprehensive management of pain in patients with cancer. This article will focus on methods for screening for pain, safe and appropriate prescription of opioid and miscellaneous analgesics, and the optimization of nonpharmacologic interventions including integrative and interventional strategies for treatment of cancer-related pain. Additionally, the NCCN Guidelines discuss methods for the safe reduction of opioids when appropriate, as well as techniques for encouraging the judicious use of opioids. The complete version of the NCCN Guidelines for Adult Cancer Pain addresses additional issues that are not covered here, including management of pain during a pain crisis, management of procedure-related pain and anxiety, pain management for cancer survivors, and the use of nonopioid and adjuvant analgesics for cancer-related pain.

Introduction Although the prevalence of chemotherapy-induced peripheral neuropathy (CIPN) has been reported, the proportion of patients with CIPN who report chronic moderate-to-severe neuropathy or chronic painful neuropathy remains poorly understood, despite its significant impact on patients’ quality of life and treatment outcomes. Methods A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome was the pooled prevalence of chronic (≥3 months) moderate-to-severe CIPN or painful CIPN among patients diagnosed with CIPN. Estimates from each study were transformed using a double-arcsine transformation and pooled in a meta-analysis using an inverse variance heterogeneity model. Subgroup analysis was conducted based on geographical region, sex, chemotherapy regimen, primary cancer type, and funding source; metaregression analysis was conducted based on study design, human development index (HDI), and publication year. Results 76 studies from 29 countries, encompassing 13 635 patients with CIPN, were included. Among patients diagnosed with CIPN, the pooled prevalence of those reporting chronic moderate-to-severe CIPN or painful CIPN was estimated at 47.76% (95% CI 37.50 to 58.08; 95% prediction interval 24.68–71.84). Substantial heterogeneity was observed across studies ( I² =97.45%; 95% CI for I 2 97.15 to 97.72). Subgroup analysis revealed that patients treated with platinum-based agents and taxanes had the highest prevalence of chronic moderate-to-severe CIPN or painful CIPN (44.47% and 55.68%, respectively), and among primary cancers, those with breast cancer, multiple myeloma, and lung cancer reported the highest prevalence of chronic moderate-to-severe CIPN or painful CIPN (61.31%, 53.55%, and 50.85%, respectively). Study design, HDI, and publication year were non-significant moderators of prevalence estimates. Based on our Grading of Recommendations, Assessment, Development, and Evaluation assessment, the certainty of evidence was considered “very low.” Sensitivity analysis restricted to studies explicitly measuring painful CIPN (40.78%; 95% CI 29.08 to 52.74) or moderate-to-severe CIPN (49.04%; 95% CI 37.16 to 60.95) yielded similar prevalence estimates. Conclusion This study provides the first comprehensive global estimate of the prevalence of chronic moderate-to-severe CIPN or painful CIPN, highlighting its significant burden on patients worldwide. The variation in prevalence across geographical regions, chemotherapy regimens, and primary cancers underscores the need for tailored management strategies and further research to address potential disparities.

Objective Peripheral nerve stimulation (PNS) is an emerging neuromodulation modality, yet there remains limited data highlighting its long-term effectiveness. The objective of this study was to report real-world data on pain intensity and opioid consumption after temporary and permanent PNS for chronic pain up to 24 months postimplantation. Methods A retrospective study was conducted on all patients who received PNS implants at a multi-centered enterprise between January 1, 2014 and February 24, 2022. The two co-primary outcomes were: (1) change in pain intensity (11-point Numerical Rating Scale) from baseline to 12 months postimplant; and (2) comparison of the change in pain intensity between temporary and permanent PNS cohorts 12 months postimplant. Results 126 patients were included in this analysis. Pain intensity significantly decreased 12 months postimplant in the overall cohort (mean difference (MD) −3.0 (95% CI −3.5 to −2.4), p<0.0001). No significant difference in this reduction was identified between temporary and permanent PNS cohorts (MD 0.0 (95% CI −1.1 to 1.0), p=1.00) 12 months postimplantation. Pain intensity significantly decreased in the overall, temporary, and permanent cohorts at all secondary time points (3, 6, and 24 months). No change in daily opioid consumption was observed at 6 and 12 months postimplant in the overall cohort. Conclusion This study found that both temporary and permanent PNS may be effective for reducing pain intensity in patients with chronic pain up to 24 months postimplantation, although no changes in opioid consumption were observed. The decrease in pain intensity was comparable between patients receiving temporary versus permanent implants, highlighting that temporary PNS may achieve long-lasting clinical benefits. However, given the substantial loss to follow-up, further large-scale studies are needed to solidify conclusions about the efficacy of PNS.

Abstract Background Gabapentin, a widely prescribed medication for various neuropathic pain conditions, has demonstrated efficacy in managing diverse neurological disorders. While conventional side effects are well‐documented, a growing body of evidence suggests the existence of atypical side effects, necessitating comprehensive exploration. This paper aims to systematically review and summarize the literature on the atypical side effects of gabapentin, shedding light on manifestations beyond the conventional spectrum. Methods A systematic review was conducted, encompassing peer‐reviewed articles published up to the knowledge cutoff date in November 2023. Databases, specifically PubMed, were searched for relevant studies, focusing on atypical side effects such as myoclonus, ataxia, pediatric aggression, respiratory depression, pneumonia, pregnancy complications, sleep interference, encephalopathy, peripheral edema, suicidal ideation, dyskinesia, anorgasmia, and myopathy. Inclusion criteria comprised studies with a focus on gabapentin‐related atypical side effects, published in recognized journals and involving human subjects. Results The review identified a spectrum of atypical side effects associated with gabapentin use, ranging from neurological manifestations like myoclonus and ataxia to behavioral changes such as pediatric aggression and suicidal ideation. Additionally, respiratory complications, pregnancy‐related issues, sleep disturbances, and rare complications like encephalopathy and myopathy were observed. Literature synthesis provided insights into the incidence, clinical presentation, and potential mechanisms underlying these atypical side effects. Conclusion This comprehensive review highlights the diverse range of atypical side effects associated with gabapentin use, expanding beyond conventional knowledge. Healthcare practitioners must be cognizant of these manifestations, recognizing their potential impact on patient well‐being. As clinical decision‐making relies on a thorough understanding of a medication's side effect profile, this review contributes to enhancing awareness and fostering informed practices in the prescription and management of gabapentin. Further research is warranted to elucidate the mechanisms and risk factors associated with these atypical side effects, refining our understanding of gabapentin's safety profile.