Hussain, Nasir

Background Peripheral nerve stimulation (PNS) has emerged as a promising neurostimulation modality, yet its effectiveness and durability for chronic pain remain uncertain. We conducted a systematic review and meta-analysis to evaluate changes in pain intensity following implantable PNS therapy. Methods Eligible studies included adults (≥18 years) with chronic pain treated with an implantable PNS system, and pain intensity was assessed at baseline and follow-up time points. The primary outcome was change in pain intensity from baseline to 6 months after PNS implantation. Secondary outcomes included changes in pain intensity at 3, 12 and 24 months after PNS implantation. Standardized mean differences (Hedges’ g ) were pooled using a random-effects model. Results A total of 106 studies comprising 9272 patients were included. PNS was associated with large, statistically significant reductions in pain intensity from baseline to all time points: 3 months (Hedges’ g 2.92; 95% CI 2.62 to 3.21), 6 months (Hedges’ g 3.08; 95% CI 2.68 to 3.48), 12 months (Hedges’ g 2.68; 95% CI 2.30 to 3.05) and 24 months (Hedges’ g 2.08; 95% CI 1.68 to 2.48) (all p<0.001). However, the certainty of evidence as assessed by the Grading of Recommendations Assessment, Development and Evaluation criteria was rated as low for the primary outcome, due to pooling from observational studies, risk of bias, and heterogeneity (statistical, clinical and methodological). Subgroup analyses revealed no differences by study design or device type, while smaller effect sizes were reported in industry-funded studies and those with declared conflicts of interest. The largest effect sizes were observed in pelvic and upper extremity pain, whereas the smallest in truncal pain. Conclusion Implantable PNS provides persistent and clinically meaningful analgesia for chronic pain, with benefits sustained up to 24 months. These findings support broader clinical adoption and provide evidence to inform pay0r coverage and policy decisions.

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.

Background Randomized clinical trials (RCTs) are considered the gold standard for evaluating the efficacy of healthcare interventions. However, conflicts of interest (COIs) can compromise the scientific integrity in these trials. This study characterized COIs in RCTs on spinal cord stimulation for chronic pain, focusing on the prevalence, disclosure, and monetary value of COIs. Methods This cross-sectional study analyzed RCTs published from January 1, 2013 to July 27, 2023. Primary outcomes included the presence, disclosure, and monetary value of COIs, while secondary outcomes assessed the presence of direct/indirect COIs, sponsor access to data, and associations between COIs and select variables, including journal impact factor, publication year, and study outcomes. Results Of 38 RCTs, 30 (78.9%) reported COIs. On average, 35.6% of authors per RCT had at least one COI, with a mean of 0.7 COIs per author. The mean annual monetary value of COIs was US$41,157.83 per author per RCT. 29 RCTs (76.3%) had undisclosed COIs, with an average of 24.2% of authors per RCT having undisclosed COIs. Sponsor access to data was reported in 67.6% of RCTs. No associations were observed between the mean percentage of authors with COIs and the monetary value of COIs and select dependent variables (impact factor, publication year, and study outcomes). Conclusions A substantial majority of RCTs reported COIs with many authors having undisclosed conflicts, highlighting the need for stringent COI disclosure guidelines to maintain research integrity. Expanding COI registry systems globally and increasing non-industry funding are crucial steps toward enhancing transparency and reducing biases in medical research.