The Choice of Spinal Cord Stimulation Versus Targeted Drug Delivery in the Management of Chronic Pain: Validation of an Outcomes Predictive Formula.

OBJECTIVE: In 2020, Mekhail et al published a formula that predicted the likelihood of a successful outcome for those who undergo spinal cord stimulation (SCS) for long-term pain management, based on retrospectively collected clinical and demographic data from one major medical center. The aim of this study is to validate such a predictive formula, prospectively, in a cohort of patients from multiple medical practices that are more representative of real-life clinical practice. MATERIALS AND METHODS: For the study, 939 patients who underwent successful SCS or targeted drug delivery (TDD) trials at multiple independent medical centers in the USA were enrolled into the Medtronic product surveillance registry data base before they underwent SCS or TDD device implantation, from 2018 to 2020. The registry data were collected prospectively but not specifically for this study. The data examined included demographic information, pain diagnosis, pain scores (visual analog scale [VAS]), Oswestry Disability Index scores, and quality-of-life scores at baseline and six months after implant. Because our goal is to validate the previously published predictive formula, in addition to the outcomes data previously mentioned, we collected the variables necessary for such a task: sex, age, depression, the presence of neuropathic pain, spine-related pain diagnosis, and persistent spinal pain syndrome "post laminectomy syndrome." Spine-related pain diagnosis included subjects with chronic spine pain who never had back surgery and whose pain was not radicular nor neuropathic. RESULTS: Of 619 patients with SCS, 138 (22%) achieved ≥ 50% reductions of the baseline VAS at six months. The logistic model predicts SCS success with an area under the receiver operating characteristic curve (AUC) of 80% in the current validation data set. Of 320 patients with TDD, 147 (46%) achieved ≥ 50% reduction of the baseline VAS at six months. The logistic model predicts TDD success with an AUC of 78% in the current validation data set. CONCLUSION: The study provides real life validation of the previously published predictive formula(4).

Impact of biological sex on the outcomes of spinal cord stimulation in patients with chronic pain.

BACKGROUND: Spinal cord stimulation (SCS) continues to gain increasing popularity in the pain management field for the treatment of different painful conditions; however, to-date, the correlation between the SCS effectiveness and biological sex has not been fully established. We aimed to investigate the correlation between the biological sex and SCS outcomes. METHODS: Following Institutional Review Board approval, a retrospective cohort study was performed by collecting data for patients treated with SCS at a tertiary academic center between the years 2002 and 2019. Data was assessed with multivariable linear regression to investigate the association between biological sex and pain scores at baseline, 6-, and 12- months following SCS implantation. Propensity score matching (PSM) was performed based on a set of covariates including age, duration of pain, time since implant, BMI, opioid medications use, smoking, depression and history of alcohol, or substance abuse. RESULTS: Of the patients treated with SCS implants, 418 patients fit the inclusion and exclusion criteria, out of which the majority were females (272, 65%). The pre-matching data reported a significant difference in history of diabetes and depression and was also significant for greater opioid use in male patients at baseline, 6-, and 12-months post-SCS implant. Propensity score matching (PSM) was performed based on the above mentioned covariant. After matching, no statistical difference was found among the variables, in both groups. Furthermore, after matching no significant differences in the pain scores at baseline, 6-, and 12-months post-SCS implant were observed. CONCLUSION: No biological sex-based differences in the analgesic response to SCS therapy was detected at 6- and 12-months post-SCS implant between groups with similar demographics, biomedical, and psychological values.

Cost-Effectiveness of Dorsal Root Ganglion Stimulation or Spinal Cord Stimulation for Complex Regional Pain Syndrome.

OBJECTIVES: ACCURATE, a randomized controlled trial, compared safety and effectiveness of stimulation of the dorsal root ganglion (DRG) vs. conventional spinal cord stimulation (SCS) in complex regional pain syndrome (CRPS-I and II) of the lower extremities. This analysis compares cost-effectiveness of three modalities of treatment for CRPS, namely DRG stimulation, SCS, and comprehensive medical management (CMM). MATERIALS AND METHODS: The retrospective cost-utility analysis combined ACCURATE study data with claims data to compare cost-effectiveness between DRG stimulation, SCS, and CMM. Cost-effectiveness was evaluated using a Markov cohort model with ten-year time horizon from the U.S. payer perspective. Incremental cost-effectiveness ratio (ICER) was reported as cost in 2017 U.S. dollars per gain in quality-adjusted life years (QALYs). Willingness-to-pay thresholds of $50,000/QALY and $100,000/QALY were used to define highly cost-effective and cost-effective therapies. RESULTS: Both DRG and SCS provided an increase in QALYs (4.96 ± 1.54 and 4.58 ± 1.35 QALYs, respectively) and an increase in costs ($153,992 ± $36,651 and $128,269 ± $27,771, respectively) compared to CMM (3.58 ± 0.91 QALYs, $106,173 ± $27,005) over the ten-year model lifetime. Both DRG stimulation ($34,695 per QALY) and SCS ($22,084 per QALY) were cost-effective compared to CMM. In the base case, ICER for DRG v SCS was $68,095/QALY. CONCLUSIONS: DRG and SCS are cost-effective treatments for chronic pain secondary to CRPS-I and II compared to CMM. DRG accrued higher cost due to higher conversion from trial to permanent implant and shorter battery life, but DRG was the most beneficial therapy due to more patients receiving permanent implants and experiencing higher quality of life compared to SCS. New DRG technology has improved battery life, which we expect to make DRG more cost-effective compared to both CMM and SCS in the future.

Diagnosis of Sacroiliac Joint Pain: Predictive Value of Three Diagnostic Clinical Tests.

INTRODUCTION: To date, there have been no acceptable and accurate diagnostic criteria or standards of care for the management of sacroiliac joint (SIJ) pain. Several studies have yielded different contributions of clinical presentation, history, and physical examination in the diagnosis of SIJ pain. Our goal in this study was to assess the sensitivity and specificity of the diagnostic clinical tests and their predictive value in accurately diagnosing SIJ pain. METHODOLOGY: Upon enrolling 200 eligible patients with SIJ pain as their primary diagnosis, they were re-evaluated and their verbal rating scale (VRS) pain scores and demographic data were obtained. Thereafter, three SIJ diagnostic tests were performed: the thigh thrust test, the Patrick test, and a modified version of the Gaenslen test that is referred to as the Mekhail test. Subsequently, the patients were taken to the procedure room to undergo SIJ injection, for which a confirmative result was ≥50% pain relief. The physicians performing the procedure were blinded of the results of the 3 tests performed. Results from the 3 tests were incorporated with the procedure results, from which we drew statistical and medical conclusions determining their predictive value and degree of aid to physicians in diagnosing SIJ pain. RESULTS: We found that the cumulative effect of adding simultaneous tests increased the sensitivity of the testing but decreased the specificity, which generates a powerful screening tool. The combination of the Patrick and Mekhail tests demonstrated the best accuracy, with 94% sensitivity, 17% specificity, 81% positive predictive value, and 44% negative predictive value. The Patrick test was better than other tests for differentiating patients with SIJ pain from those with non-SIJ pain. No combination yielded both significant sensitivity and specificity. Generally, the overall predictive value of any of the tests on their own or their combination did not vary significantly from the predictive value of baseline demographics, including pre-injection pain score and pain referral diagram. CONCLUSION: In conclusion, our study results were similar to those of previous investigators who found that physical examination plays a limited role in diagnosing SIJ pain. Specifically, we found that the clinical tests and/or their combinations added no significant predictive capacity compared to patients' baseline characteristics in predicting the response to diagnostic SIJ injection, albeit the combination of the Mekhail and Patrick tests yielded high sensitivity (94%), making them viable for consecutive screening, possibly reducing the unnecessary costs of diagnostic SIJ injection procedures.

Anesthetic Management and 30-Day Outcomes After Renal Autotransplantation.

Background: Renal autotransplantation is a complex procedure performed for various indications such as treatment of renal vascular and urologic lesions and loin pain hematuria syndrome (LPHS). Because of the rarity of the procedure, few reports have been published, and little is known about anesthetic management and postoperative outcomes of patients with LPHS. The goal of this study was to review and describe all cases of renal autotransplantation performed at Cleveland Clinic during a specified period, focusing on anesthetic management and postoperative 30-day outcomes. Methods: We performed a retrospective review of the records of all patients who underwent renal autotransplantation from 2005 to 2014 at the Cleveland Clinic and collected demographic, anesthetic, surgical, and postoperative data. Results: A total of 64 patients underwent renal autotransplantation from 2005 to 2014. The most frequent indications were nephrolithiasis and LPHS. General endotracheal anesthesia with epidural for pain control was used in 47% of cases. Median duration of anesthesia was 528 minutes. Most patients were sent to a regular nursing floor postoperatively, but 28% of patients required intensive care unit admission. Two patients developed graft ischemia, and 1 patient developed graft failure requiring nephrectomy. No anesthetic-related complications and no mortality were associated with this procedure during the study. Conclusion: Renal autotransplantation is a safe option for patients with LPHS. Additional studies are needed to assess the effect of intraoperative anesthetic management on outcomes in this patient population.

Longevity and Utilization Cost of Rechargeable and Non-Rechargeable Spinal Cord Stimulation Implants: A Comparative Study.

INTRODUCTION: Despite major advancements in features and capabilities of the implantable pulse generator (IPG), real-life longevity and cost-effectiveness studies to guide pain specialists to make the appropriate choice between rechargeable and non-rechargeable IPG are limited. Our study aimed to compare the longevity and cost effectiveness of rechargeable vs. non-rechargeable IPG and SCS systems. METHODS: Data were collected for all SCS implantations performed between 1994 and 2018. The primary goal was to determine IPG longevity, defined as the time interval between IPG implantation and elective replacement due to IPG end of life (EOL). On the other hand, SCS system longevity was defined as the time between SCS implantation and its removal or revision for any reason other than IPG EOL. Kaplan-Meier and log-rank tests were used to assess IPG and SCS system longevities. Cost analysis was performed for cost effectiveness. RESULTS: The median IPG longevity was significantly higher for rechargeable SCS devices than for non-rechargeable SCS devices (7.20 years and 3.68 years, respectively). The median cost per day was similar for both IPGs, $13.90 and $13.81 for non-rechargeable and rechargeable, respectively. The median cost for SCS systems was higher for the rechargeable group ($60.70) compared with the non-rechargeable group ($31.38). CONCLUSIONS: Rechargeable IPG had increased longevity compared to their non-rechargeable counterparts, yet there was no significant difference in the actual longevity due to premature revisions or explantations between both SCS systems. Furthermore, non-rechargeable SCS systems were found to be the more cost-effective option when compared with rechargeable SCS systems.

Choice of spinal cord stimulation versus targeted drug delivery in the management of chronic pain: a predictive formula for outcomes.

Contemporary nonmalignant pain treatment algorithms commence with conservative non-invasive strategies, later progressing from minimally invasive interventions to invasive techniques or implantable devices. The most commonly used implantable devices are spinal cord stimulation (SCS) systems or targeted drug delivery (TDD) devices. Historically, SCS had been considered in advance of TDD, positioning TDD behind SCS failures. Following Institutional Review Board approval, data were extracted from electronic medical records of patients who underwent SCS trial in the Department of Pain Management at Cleveland Clinic from 1994 to 2013. The sample size was analyzed in two cohorts: those who succeeded with SCS and those who failed SCS and consequently proceeded to TDD. Univariate and multivariate analyses were performed and a predictive formula for successful outcomes was created. 945 patients were included in the cohort of which 119 (12.6%) subjects achieved adequate pain relief with TDD after failure of SCS. Gender, age, depression and primary pain diagnosis were significantly different in this subgroup. Males were 52% less likely to experience pain relief with SCS. The odds of SCS success decreased as age increased by 6% per year. Patients with comorbid depression, interestingly, were 63% more likely to succeed with SCS. A logistic model was created to predict SCS success which was used to create a predictive formula. Older male patients diagnosed with spine-related pain were more likely to benefit from TDD than SCS. This observation potentially identifies a subgroup in whom consideration for TDD in advance of SCS failure could prove more efficient and cost effective. These retrospective findings warrant prospective comparative studies to validate this derived predictive formula.

The Impact of Tobacco Smoking on Spinal Cord Stimulation Effectiveness in Complex Regional Pain Syndrome Patients.

OBJECTIVES: We aim to investigate the correlation of smoking and spinal cord stimulation (SCS) effectiveness for pain relief in complex regional pain syndrome (CRPS) patients while controlling for possible confounding factors including opioid intake. MATERIALS AND METHODS: Following Institutional Review Board approval, a retrospective cohort study was performed by collecting data for all CRPS patients treated with SCS at Cleveland Clinic between 1998 and 2013. We divided patients into three groups based on their smoking status at the time of SCS device implant: Current smokers, former smokers, or nonsmokers. We used a linear mixed modeling to assess the association between smoking status and pain score at baseline and at 3, 6, and 12 months. We then used pairwise t-tests for post hoc comparisons of pain scores. RESULTS: Of the 420 CRPS patients treated with SCS implants, the reduction in pain score was highest among nonsmokers. Nonsmokers demonstrated a consistent and steady decrease in pain scores over time, whereas the current and former smoker cohorts showed an initial reduction in pain at three months compared to baseline which was not sustained to the 12-months benchmark. Nonetheless, former smokers continued to report slightly lower pain scores than current smokers, although not statistically significant. The baseline opioid consumption was least among nonsmokers (30 [0, 62] oral mg morphine sulfate equivalent). We also found a statistically significant association between time postimplant and reported pain score (χ2 = 508.88, p < 0.001). The overall mean pain score for all three cohorts was highest at baseline (7.6 ± 1.7) and showed a decrease at the 3, 6, and 12 months postimplant time points with mean score of 5.7 ± 2.0, 5.6 ± 2.3, and 5.4 ± 2.5, respectively. CONCLUSION: Tobacco cigarette smoking was associated with reduced SCS effectiveness for pain relief.

The impact of obesity on the effectiveness of spinal cord stimulation in chronic spine-related pain patients.

BACKGROUND CONTEXT: Chronic pain and obesity are both on the rise. Spinal cord stimulation has gained increasing popularity in the pain management field for the treatment of spine-related chronic pain, however to-date, the correlation between the spinal cord stimulator effectiveness and increasing body mass index (BMI) has not been fully established. PURPOSE: We aimed to investigate the correlation between patients' BMI and the percentage of pain relief as well as opioid utilization in chronic spine-related pain patients treated with spinal cord stimulation. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Patients with chronic spine-related pain who were treated with a spinal cord stimulator. OUTCOME MEASURES: Eleven-point numeric rating scale for pain and opioid utilization. METHODS: Following Institutional Review Board approval, data from all eligible subjects who had undergone successful spinal cord stimulation (SCS)-trial defined as ≥50% decrease in pain followed by SCS implant were collected and statistically analyzed. Patients were divided into four groups according to BMI. Self-reported pain scores on the 11-point numerical rating scale were collected at baseline, 6 months and 12 months post SCS-implant visits. Opioid utilization, if any, was collected at baseline and 12 months post-SCS implant. RESULTS: In all, 181 patients were included. Thirty-three were under and/or normal weight (≤24.9 kg/m2), 72 overweight (25.0-29.9 kg/m2), 63 obese (30.0-39.9 kg/m2), and 13 morbidly obese (≥40.0 kg/m2). The estimated coefficients from multivariable linear regression analysis were -1.91% (95% CI: -2.82% to -0.991%) and -1.48% (95% CI: -2.30% to -0.660%) reduction in pain improvement per unit increase of BMI for 6 months and 12 months scores, respectively. The estimated coefficient of disability status was -15.3% (95% CI: -22.1% to -8.48%). The estimated coefficient for 12 month opioid equivalence was -0.08% (95% CI: -0.14 to -0.021), per` 1 mg unit increase of morphine opioid equivalency. The data showed a statistically significant negative association between increasing BMI and SCS effectiveness at 6 and 12 months post-SCS therapy with a 2% reduction in efficacy for every unit increase of BMI after adjusting for confounding factors and a 20% better response in underweight and/or normal patients over the morbidly obese individuals which was not related to baseline pain score level. The significant difference in pain scores at 6 months (p = .0003) and 12 months (p = .04) post-SCS implant between obese and nonobese patients was not attributable to differences in baseline pain scores. There was no significant change in opioid utilization between baseline and 12 months post-SCS therapy. CONCLUSION: A negative association between SCS effectiveness and increasing BMI was found, whereas, no significant difference was noted amongst the various BMI cohorts and the daily opioid consumption.

The Impact of Tobacco Cigarette Smoking on Spinal Cord Stimulation Effectiveness in Chronic Spine-Related Pain Patients.

BACKGROUND AND OBJECTIVES: Despite the observation that select nicotine receptor agonists have analgesic effects, smokers report higher pain scores and more functional impairments than lifelong nonsmokers, attributable to exaggerated stress responses, receptor desensitization, and altered pharmacokinetics compounded by accelerated structural damage resulting from impaired bone healing, osteoporosis, and advancement of disk disease. We hypothesized that smoking diminishes the analgesic response to spinal cord stimulation (SCS) in patients with chronic spine-related pain conditions. METHODS: A retrospective cohort study was performed at Cleveland Clinic by collecting and assessing data of 213 patients who had been implanted with SCS for spine-pain indications. History of tobacco smoking was subcategorized into 3 categories: past (former smoker), present (current smoker), or those who had never previously smoked (lifelong nonsmokers), and a multivariable linear regression was run to measure the correlation, if any, between smoking status and numerical rating scale pain score. In addition, opioid consumption at baseline and 12-month follow-up, expressed in milligram oral morphine equivalents, was collected and compared. RESULTS: Adjusted for differences, at 1-year follow-up, current smokers (n = 62) reported numerical rating scale pain score of 7.0, which is 1.93 (P < 0.001) and 1.32 (P = 0.001) points higher than those of lifelong nonsmokers (n = 77) and former smokers (n = 74), respectively. Opioid intake was 2.4 times higher (P = 0.004) in smokers than in lifelong nonsmokers. CONCLUSIONS: Among our SCS-implanted sample, a positive correlation was observed between tobacco use and degree of pain reduction as early as 12 months postimplant; this was evident by the reported higher pain scores and opioid use in current smokers in comparison with former smokers and lifelong nonsmokers.

Longevity and cost of implantable intrathecal drug delivery systems for chronic pain management: a retrospective analysis of 365 patients.

OBJECTIVES: Intrathecal drug delivery systems represent an important component of interventional strategies for refractory chronic pain syndromes. Continuous intrathecal administration of opioids results in higher subarachnoid drug concentrations, improved pain scores, and less frequent side effects when compared with systemic opioid administration. Substantial costs arise at the time of surgical implantation and at revision for battery depletion or treatment of a complication. Despite current widespread use, the real-world longevity and cost of implanted intrathecal pumps (ITP) has not been fully quantified. MATERIALS AND METHODS: Patients with an ITP implanted at Cleveland Clinic Pain Management Center between January 1998 and December 2012 were included. ITP longevity was calculated as the time between implant and explant for depletion of the system's battery. Using the 2013 fee schedule of the Centers for Medicare & Medicaid Services, the daily cost of having a functioning ITP was calculated. The costs of office visits for pump refills and the cost of intrathecal medications were not included, nor were the possible savings due to decreased utilization of alternate medical services. RESULTS: Three hundred sixty-five patients had 559 pumps implanted. Postlaminectomy syndrome was the most common indication (40%). The median system longevity for all pumps was 5.4 years (97.5% confidence interval: [5.0, 5.8]), including pumps extracted prematurely, as well as those that reached the elective replacement interval. The median ITP longevity was 5.9 years (95% confidence interval: [5.6, 6.1]) for pumps explanted for end of battery life. The median system cost per day was $10.46. The median cost per day of pumps explanted for end of battery life was $9.26, versus $44.59 for pumps explanted prematurely due to complications. CONCLUSIONS: Overall, the cohort experienced an increased incidence of pump-related complications and a device longevity that was within the range of the manufacturer's anticipated lifespan. Increasing the lifespan of the ITP and improving patient selection have the potential to significantly improve the cost-effectiveness of intrathecal therapy.

The appropriate use of neurostimulation: stimulation of the intracranial and extracranial space and head for chronic pain. Neuromodulation Appropriateness Consensus Committee.

INTRODUCTION: The International Neuromodulation Society (INS) has identified a need for evaluation and analysis of the practice of neurostimulation of the brain and extracranial nerves of the head to treat chronic pain. METHODS: The INS board of directors chose an expert panel, the Neuromodulation Appropriateness Consensus Committee (NACC), to evaluate the peer-reviewed literature, current research, and clinical experience and to give guidance for the appropriate use of these methods. The literature searches involved key word searches in PubMed, EMBASE, and Google Scholar dated 1970-2013, which were graded and evaluated by the authors. RESULTS: The NACC found that evidence supports extracranial stimulation for facial pain, migraine, and scalp pain but is limited for intracranial neuromodulation. High cervical spinal cord stimulation is an evolving option for facial pain. Intracranial neurostimulation may be an excellent option to treat diseases of the nervous system, such as tremor and Parkinson's disease, and in the future, potentially Alzheimer's disease and traumatic brain injury, but current use of intracranial stimulation for pain should be seen as investigational. CONCLUSIONS: The NACC concludes that extracranial nerve stimulation should be considered in the algorithmic treatment of migraine and other disorders of the head. We should strive to perfect targets outside the cranium when treating pain, if at all possible.