Hussain, Nasir

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.

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.

Background The efficacy of spinal cord stimulation (SCS) in chronic pain studies is traditionally assessed by pain scores, which do not reflect the multidimensional nature of pain perception. Despite the evidence of SCS’s influence on emotional functioning comprehensive assessments of its effect remain lacking. Objective To assess changes in emotional and psychosocial functioning in patients who underwent SCS implantation for chronic pain. Evidence review Ovid MEDLINE, EMBASE, PsychINFO, Cochrane CENTRAL and Scopus databases were searched for original peer-reviewed publications reporting emotional functioning after SCS. The primary outcomes were a pooled mean difference (MD) in anxiety, depression, global functioning, mental well-being and pain catastrophizing at 12 months. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to determine the quality of evidence. Findings Thirty-two studies were included in the primary analysis. Statistically significant improvements were observed in anxiety (MD −2.16; 95% CI −2.84 to −1.49; p<0.001), depression (MD −4.66; 95% CI −6.26 to −3.06; p<0.001), global functioning (MD 20.30; 95% CI 14.69 to 25.90; p<0.001), mental well-being (MD 4.95; 95% CI 3.60 to 6.31; p<0.001), and pain catastrophizing (MD −12.09; 95% CI −14.94 to −9.23; p<0.001). Subgroup analyses revealed differences in Global Assessment of Functioning and mental well-being based on study design and in depression based on waveform paradigm. Conclusion The results highlight the statistically and clinically significant improvements in emotional and psychosocial outcomes in patients with chronic pain undergoing SCS therapy. However, these results need to be interpreted with caution due to the very low certainty of evidence per the GRADE criteria. PROSPERO registration CRD42023446326.

Summary Non‐steroidal anti‐inflammatory drugs (NSAIDs) are one of the mainstays of multimodal pain management. While effective for acute pain control, recent pre‐clinical evidence has raised concerns regarding an association between NSAIDs and chronic pain and potential opioid use. Our objective was to explore the association between peri‐operative use of prescription NSAIDs and the need for continued opioid prescriptions lasting 90–180 days in previously opioid‐naïve patients undergoing total knee arthroplasty. A database of health claims in the USA was used to identify all opioid‐naïve adult patients who underwent primary knee arthroplasty between January 2010 and October 2021. We evaluated the magnitude of association between peri‐operative prescription NSAID claims and claims for opioids at 90 days postoperatively using multivariable logistic regression models. Secondary outcomes included: the magnitude of association between peri‐operative NSAID prescription and claims for opioids at 180 days postoperatively; and identifying other potential factors associated with opioid claims at 90 days postoperatively. After risk adjustment using multivariable logistic regression models in the 789,736‐patient cohort, the adjusted odds ratio (95%CI) for a continuous claim of opioids at 90 and 180 days postoperatively among patients with a peri‐operative NSAID prescription within 30 days was 1.32 (1.30–1.35), p < 0.001; and 1.12 (1.10–1.15), p < 0.001, respectively. This estimate of effect remained robust at 90 days after accounting for known potential confounders, including pre‐existing knee pain and acute postoperative pain severity. Similar analysis of other pain medications (e.g. paracetamol) did not detect such an association. This population‐based cohort study suggests that peri‐operative prescription NSAID use may be associated with continued opioid prescription claims at 90 and 180 days after knee arthroplasty, even after adjusting for other observed covariates for continuous opioid claims. These novel findings can inform clinical decision‐making for post‐surgical pain management, risk–benefit discussions with patients and future research.

Background A growing number of meta-analyses (MA) have investigated the use of spinal cord stimulation (SCS) as a treatment modality for chronic pain. The quality of these MAs has not been assessed by validated appraisal tools. Objective To examine the methodological characteristics and quality of MAs related to the use of SCS for chronic pain syndromes. Evidence review An online literature search was conducted in Ovid MEDLINE(R), Ovid EMBASE, Ovid Cochrane Database of Systematic Reviews, and Scopus databases (January 1, 2000 through June 30, 2023) to identify MAs that investigated changes in pain intensity, opioid consumption, and/or physical function after SCS for the treatment of chronic pain. MA quality was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR-2) critical appraisal tool. Findings Twenty-five MAs were appraised in the final analysis. Three were considered “high” quality, three “low” quality, and 19 “critically low” quality, per the AMSTAR-2 criteria. There was no association between the publication year and AMSTAR-2 overall quality (β 0.043; 95% CI −0.008 to 0.095; p=0.097). There was an association between the impact factor and AMSTAR-2 overall quality (β 0.108; 95% CI 0.044 to 0.172; p=0.002), such that studies published in journals with higher impact factors were associated with higher overall quality. There was no association between the effect size and AMSTAR-2 overall quality (β −0.168; 95% CI −0.518 to 0.183; p=0.320). According to our power analysis, three studies were adequately powered (>80%) to reject the null hypothesis, while the remaining studies were underpowered (<80%). Conclusions The study demonstrates a critically low AMSTAR-2 quality for most MAs published on the use of SCS for treating chronic pain. Future MAs should improve study quality by implementing the AMSTAR-2 checklist items. PROSPERO registration number CRD42023431155.

Abstract Background Context Surgical decompression is the definitive treatment for managing symptomatic lumbar spinal stenosis; however, select patients are poor surgical candidates. Consequently, minimally invasive procedures have gained popularity, but there exists the potential for failure of therapy necessitating eventual surgical decompression. Purpose To evaluate the incidence and characteristics of patients who require surgical decompression following minimally invasive procedures to treat lumbar spinal stenosis. Study Design/Setting Retrospective review. Patient Sample Patients who underwent minimally invasive procedures for lumbar spinal stenosis (Percutaneous Image‐guided Lumbar Decompression [PILD] or interspinous spacer device [ISD]) and progressed to subsequent surgical decompression within 5 years. Outcome Measures The primary outcome was the rate of surgical decompression within 5 years following the minimally invasive approach. Secondary outcomes included demographic and comorbid factors associated with increased odds of requiring subsequent surgery. Methods Patient data were collected using the PearlDiver‐Mariner database. The rate of subsequent decompression was described as a percentage while univariable and multivariable regression analysis was used for the analysis of predictors. Results A total of 5278 patients were included, of which 3222 (61.04%) underwent PILD, 1959 (37.12%) underwent ISD placement, and 97 (1.84%) had claims for both procedures. Overall, the incidence of subsequent surgical decompression within 5 years was 6.56% (346 of 5278 patients). Variables associated with a significantly greater odds ratio (OR) [95% confidence interval (CI)] of requiring subsequent surgical decompression included male gender and a prior history of surgical decompression by 1.42 ([1.14, 1.77], p = 0.002) and 2.10 times ([1.39, 3.17], p < 0.001), respectively. In contrast, age 65 years and above, a diagnosis of obesity, and a Charlson Comorbidity Index score of three or greater were associated with a significantly reduced OR [95% CI] by 0.64 ([0.50, 0.81], p < 0.001), 0.62 ([0.48, 0.81], p < 0.001), and 0.71 times ([0.56, 0.91], p = 0.007), respectively. Conclusions Minimally invasive procedures may provide an additional option to treat symptomatic lumbar spinal stenosis in patients who are poor surgical candidates or who do not desire open decompression; however, there still exists a subset of patients who will require subsequent surgical decompression. Factors such as gender and prior surgical decompression increase the likelihood of subsequent surgery, while older age, obesity, and a higher Charlson Comorbidity Index score reduce it. These findings aid in selecting suitable surgical candidates for better outcomes in the elderly population with lumbar spinal stenosis.

Background The analgesic effectiveness of contemporary motor-sparing nerve blocks used in combination for analgesia in total knee arthroplasty is unclear. This network meta-analysis was conducted to evaluate the analgesic effectiveness of adding single-injection or continuous adductor canal block (ACB) with or without infiltration of the interspace between the popliteal artery and the capsule of the posterior knee (iPACK) to intraoperative local infiltration analgesia (LIA), compared to LIA alone, after total knee arthroplasty. Methods Randomized trials examining the addition of single-injection or continuous ACB with or without single-injection block at the iPACK to LIA for total knee arthroplasty were considered. The two primary outcomes were area-under-the-curve pain scores over 24 to 48 h and postoperative function at greater than 24 h. Secondary outcomes included rest pain scores at 0, 6, 12, and 24 h; opioid consumption (from 0 to 24 h and from 25 to 48 h); and incidence of nausea/vomiting. Network meta-analysis was conducted using a frequentist approach. Results A total of 27 studies (2,317 patients) investigating the addition of (1) single-injection ACB, (2) continuous ACB, (3) single-injection ACB and single-injection block at the iPACK, and (4) continuous ACB and single-injection block at the iPACK to LIA, as compared to LIA alone, were included. For area-under-the-curve 24- to 48-h pain, the addition of continuous ACB with single-injection block at the iPACK displayed the highest P -score probability (89%) of being most effective for pain control. The addition of continuous ACB without single-injection block at the iPACK displayed the highest P -score probability (87%) of being most effective for postoperative function. Conclusions The results suggest that continuous ACB, but not single-injection ACB and/or single-injection block at the iPACK, provides statistically superior analgesia when added to LIA for total knee arthroplasty compared to LIA alone. However, the magnitude of these additional analgesic benefits is clinically questionable. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Spinal cord stimulation (SCS) has emerged as an important treatment for chronic pain disorders. While there is evidence supporting improvement in pain intensity with SCS therapy, efforts to synthesize the evidence on physical functioning are lacking. Objective The primary objective of this meta-analysis was to assess long-term physical function following 12 months of SCS for chronic back pain. Evidence review PubMed, EMBASE, Scopus, and CENTRAL databases were searched for original peer-reviewed publications investigating physical function following SCS. The primary outcome was physical function at 12 months following SCS therapy for chronic back pain compared with baseline. A random effects model with an inverse variable method was used. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) framework was used to determine the certainty of evidence. Findings A total of 518 studies were screened, of which 36 were included. Twenty-two studies were pooled in the meta-analysis. There was a significant reduction in Oswestry Disability Index (ODI) scores at all time frames up to 24 months following implantation. Pooled results revealed significant improvement in ODI scores at 12 months with a mean difference of −17.00% (95% CI −23.07 to −10.94, p<0.001). There was a very low certainty of evidence in this finding as per the GRADE framework. There was no significant difference in subgroup analyses based on study design (randomised controlled trials (RCTs) vs non-RCTs), study funding, or stimulation type. Conclusion This meta-analysis highlights significant improvements in physical function after SCS therapy. However, this finding was limited by a very low GRADE certainty of evidence and high heterogeneity.