Karri, Jay

Abstract Objective Genicular nerve radiofrequency (gRF) treatment is a widely used intervention for chronic pain from knee osteoarthritis (KOA). This systematic review and meta-analysis focuses on RCTs utilizing image guidance to address inconsistencies in previous reviews and provide higher-quality evidence. Design, Setting, and Methods This study included RCTs that compared gRF techniques (conventional, cooled, pulsed, bipolar) to non-gRF treatments, including sham procedures, intra-articular injections, ozone therapy, and oral medications. Primary and secondary outcomes were changes in pain and total WOMAC scores at 3, 6, and 12 months post-gRF treatments. Subgroup analyses explored differences by lesion size, use of prognostic blocks, industry sponsorship, and study location. Statistical heterogeneity was assessed via I 2 statistics. Results Eleven RCTs with 868 knee osteoarthritis patients (435 gRF, 433 non-gRF) were included. At 3 months, gRF significantly reduced pain (SMD -1.65, 95% CI: -3.20 to -0.10, I 2 = 98%, P = 0.040), but not at 6 months or 12 months. Secondary analyses showed no significant differences in total WOMAC scores between the gRF and control groups at 3, 6, and 12 months. Subgroup analysis showed that industry-sponsored studies reported significant 3-month pain reduction, whereas non-sponsored studies did not. This effect was independent of study location. Conclusions GRF provides short-term pain relief (up to 3 months) but neither functional improvement nor sustained pain reduction compared to non-gRF treatments. Our findings do not support the routine use of gRF for long-term chronic pain due to KOA.

Background Knee osteoarthritis (OA) is a leading cause of chronic pain and disability, with limited disease modifying therapies. While glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have established cardiometabolic benefits and have been associated with reductions in knee OA related pain, it is unclear whether they can reduce progression to total knee arthroplasty (TKA). Methods We conducted a retrospective cohort study using the TriNetX Global Research Network, identifying adults with knee OA diagnosed between January 1, 2010, and December 31, 2024. Patients were stratified by GLP-1 RA exposure class (any GLP-1 RA or new generation agents, semaglutide or tirzepatide) and treatment duration (1 or 3 years), and then compared with propensity score matched non-exposed cohorts balanced for age, sex, race, musculoskeletal diagnoses, obesity related conditions, body mass index, and proxies for healthcare access. The primary outcome was cumulative incidence of TKA at 1, 3, 5, and 8 years. Hazard ratios (HRs) were estimated by Cox proportional hazards models and absolute risk differences from Kaplan–Meier curves, expressed as exposed minus non-exposed. Results After propensity score matching, cohort sizes ranged from 13 351 (new generation GLP-1 RA, 3 year exposure) to 42 062 patients (any GLP-1 RA, 1 year exposure). GLP-1 RA use was associated with significantly lower cumulative TKA incidence across all exposure classes, durations, and follow-up intervals (all p<0.001). With 1 year exposure to any GLP-1 RA, the absolute risk difference at 8 years was −2.80 percentage points (HR 0.90, 95% CI 0.83 to 0.98). Risk reductions were greater with new generation agents and longer duration: 3 year exposure to semaglutide or tirzepatide gave an absolute risk difference of −4.71 percentage points at 8 years (HR 0.72, 95% CI 0.67 to 0.78). Conclusions In this large, multicenter, real world cohort study, GLP-1 RA use was associated with a significantly reduced long term risk of TKA in patients with knee OA, with effects that were greater with longer treatment duration and newer generation agents. These duration and agent dependent associations are consistent with potential disease modifying activity beyond weight loss alone, although prospective trials are needed to establish causality and define optimal treatment targets.

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.