Comparison of Clinical Outcomes and Complications Between Percutaneous Endoscopic and Minimally Invasive Transforaminal Lumbar Interbody Fusion for Degenerative Lumbar Disease: A Systematic Review and Meta-Analysis

BACKGROUND: Percutaneous endoscopic transforaminal lumbar interbody fusion (PE-TLIF) has been increasingly used to treat degenerative lumbar disease in recent years. However, there are still controversies about whether PE-TLIF is superior to minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). OBJECTIVES: To compare clinical outcomes and complications of PE-TLIF and MIS-TLIF in treating degenerative lumbar disease. STUDY DESIGN: A systematic review and meta-analysis. METHODS: A comprehensive search of online databases including PubMed, Embase, and the Cochrane Library was performed to identify related studies reporting the outcomes and complications of PE-TLIF and MIS-TLIF for degenerative lumbar disease. The clinical outcomes were assessed by the Visual Analog Scale and Oswestry Disability Index. In addition, the operative time, intraoperative blood loss, time to ambulation, length of hospital stay, fusion rate, and surgery-related complications were summarized. Forest plots were constructed to investigate the results. RESULTS: A total of 28 studies involving 1,475 patients were included in this meta-analysis. PE-TLIF significantly reduced operative time, intraoperative blood loss, time to ambulation, and length of hospital stay compared to MIS-TLIF. Moreover, PE-TLIF was superior to MIS-TLIF in the early postoperative relief of back pain. However, there were no significant differences in medium to long-term clinical outcomes, fusion rate, and incidence of complications between PE-TLIF and MIS-TLIF. LIMITATIONS: The current evidence is heterogeneous and most studies included in this meta-analysis are nonrandomized controlled trials. CONCLUSIONS: The present meta-analysis indicates that medium to long-term clinical outcomes and complication rates of PE-TLIF were similar to MIS-TLIF for the treatment of degenerative lumbar disease. However, PE-TLIF shows advantages in less surgical trauma, faster recovery, and early postoperative relief of back pain. KEY WORDS: Percutaneous endoscopic transforaminal lumbar interbody fusion, minimally invasive transforaminal lumbar interbody fusion, degenerative lumbar disease, chronic pain, systematic review, meta-analysis

The Added Value of Sensitivity to Nonnoxious Stimuli to Predict an Individual’s Sensitivity to Pain

BACKGROUND: Simple tools are needed to predict postoperative pain. Questionnaire-based tools such as the Pain Sensitivity Questionnaire (PSQ) are validated for this purpose, but prediction could be improved by incorporating other parameters. OBJECTIVES: To explore the potency of sensitivity to nonpainful stimuli and biometric data to improve prediction of pain. STUDY DESIGN: Transversal exploratory study. SETTING: Single clinical investigation center. METHODS. Eighty-five healthy volunteers of both genders underwent a multimodal exploration including biometry, questionnaire-based assessment of anxiety, depression, pain catastrophizing, sensitivity to smell, and the PSQ, followed by a psychophysical assessment of unpleasantness thresholds for light and sound, and sensitivity to mechanical, heat, and cold pain. These last 3 parameters were used to calculate a composite pain score. After a multi-step selection, multivariable analyses identified the explanative factors of experimental pain sensitivity, by including biometric, questionnaire-based, and psychophysical nonnociceptive sensitivity parameters, with the aim of having each domain represented. RESULTS: Female gender predicted mechanical pain, a younger age and dark eyes predicted cold pain, and the PSQ predicted heat pain. Sensitivity to unpleasantness of sound predicted mechanical and heat pain, and sensitivity to unpleasantness of light predicted cold pain. Sensitivity to smell was unrelated. The predictors of the composite pain score were the PSQ, the light unpleasantness threshold, and an interaction between gender and eye color, the score being lower in light-eyed men and higher in all women. The final multivariable multi-domain model was more predictive of pain than the PSQ alone (R2 = 0.301 vs 0.122, respectively). LIMITATIONS: Sensitivity to smell was only assessed by a short questionnaire and could lack relevance. Healthy volunteers were unlikely to elicit psychological risk factors such as anxiety, depression, or catastrophizing. These results have not been validated in a clinical setting (e.g., perioperative). CONCLUSION: The predictive potential of the PSQ can be improved by including information about gender, eye color, and light sensitivity. However, there is still a need for a technique suitable for routine clinical use to assess light sensitivity. KEY WORDS: Personalized medicine, postoperative pain, senses, prediction, photophobia, hyperacusis, eye color, hypervigilance, sensory over-responsivity

The Antioxidant Effect of Selenium on Succinylcholine-related Myalgia After Adult Sinuscopies: Randomized Controlled Double-Blind Trial

BACKGROUND: Succinylcholine has a fast onset, short duration of action, and is considered the choice for rapid sequence intubation. However, it produces muscle stiffness and postoperative myalgia (POM) as adverse effects. We hypothesized that the antioxidant selenium might affect POM incidence and severity. OBJECTIVES: The study aimed to investigate the antioxidant effect of selenium (against free radicals’ release) in minimizing the frequency of succinylcholine-related POM, measured by the 4-point myalgia score. The severity of fasciculations and the postoperative analgesic profile were recorded. The correlation between fasciculations and POM was also observed. STUDY DESIGN: A prospective randomized controlled double-blind clinical study. SETTING: Assiut University Hospitals. METHODS: The current study included 80 adult patients scheduled for sinuscopies and randomly assigned into 2 equal groups. Two hours before the induction of general anesthesia, patients in the control group received oral placebo tablets, while patients in the selenium group received oral selenium 200 µg. The primary outcome of this trial was the POM score at 24 hours. Secondary outcomes included the intensity of fasciculations, Numeric Rating Scale (NRS), rescue analgesic consumption, and adverse effects of the studied drugs. RESULTS: Myalgia scores were significantly decreased after selenium administration throughout the follow-up period (P = 0.023). No significant difference was reported regarding the incidence or degree of fasciculations (P = 0.511). A mild correlation was noticed between fasciculations and POM with r = 0.176 and P < 0.061. The NRS values were significant between groups at 6 hours after the procedure. There were significant differences (P < 0.05) regarding postoperative supplement analgesia, time to the first rescue analgesia, and the mean total number of analgesic claims. Significant differences were recorded for potassium levels only 30 minutes and creatine kinase levels at 6 and 24 hours postoperatively. LIMITATIONS: This study was applied on a single surgical category and other types of surgical procedures may have an effect on outcomes. Additional larger sample size studies and various doses of selenium may help to validate our results. Selenium is quite a significant element of the enzymatic antioxidant process through glutathione peroxidase. We did not measure the glutathione peroxidase level in blood. CONCLUSIONS: Oral selenium effectively reduced the succinylcholine-induced postoperative myalgia. It prolonged the time to first required analgesia and decreased the analgesic consumption throughout the whole study period without affecting the hemodynamics or any serious adverse effects. KEY WORDS: Adult sinuscopy, fasciculation, postoperative myalgia, succinylcholine, selenium

Efficacy of Intrawound Treatments to Prevent Surgical Site Infection after Spine Surgery: A Systematic Review and Network Meta-analysis

BACKGROUND: Intrawound treatments have been reported to have favorable efficacy for preventing surgical site infection (SSI); however, the best strategy remains unknown. OBJECTIVE: The aim of this systematic review and network meta-analysis was to evaluate the efficacy of intrawound treatments to prevent SSI after spine surgery. STUDY DESIGN: A systematic review and network meta-analysis. METHODS: We searched the Cochrane Library, EMbase, PubMed, Chinese Science and Technology Periodical Database (VIP), China National Knowledge Infrastructure (CNKI), and Wanfang Data from the date of inception to March 2, 2020. The randomized controlled trials (RCTs) and cohort studies were identified and extracted by 2 reviewers independently. We performed a traditional pairwise meta-analysis to evaluate overall efficacy of intrawound treatments. Meanwhile, a network meta-analysis was performed to compare and rank the treatment efficacy using frequentist approach. RESULTS: Thirty-three publications (6 RCTs and 27 retrospective cohort studies) were included, involving 22,763 patients. For pairwise meta-analysis, the combined results showed that the intrawound treatment had a significantly lower SSI rate than the control group (CG) (odds ratio [OR] = 0.41; 95% confidence interval [CI], 0.31–0.55). For network meta-analysis, the treatment of vancomycin (VA) (OR = 0.53; 95% CI, 0.39-0.71), povidone-iodine (PI) (OR = 0.10; 95% CI, 0.04 - 0.23), and vancomycin + povidone-iodine (VA+PI) (OR = 0.25; 95% CI, 0.11-0.58) were found to be significantly more efficacious than CG on reduction of SSI rate. PI ranked first on reducing SSI, followed by PI+HP, VA+PI, gentamicin (GM), VA, and hydrogen peroxide (HP); CG ranked last. LIMITATIONS: Firstly, only 6 RCTs are included in this systematic review. Retrospective cohort studies tend to exaggerate the real results, although most of them are high-quality according to the Newcastle-Ottawa Quality Assessment Scale (NOQAS). More high-quality RCTs need to be included to obtain convincing conclusions. Secondly, the population of this study involves both adult and pediatric cohorts, patients with tumor, congenital disease, or degenerative disease. There is no subgroup analysis for ages and type of diseases, which might have influence on the overall pooled analysis. Thirdly, we define the application of saline solution and no intrawound treatment as the control group, which might ignore their heterogeneity. Fourthly, follow-up periods are variable and the sample size of HP is small. Finally, additional research is needed to compare the complications of different treatments and the benefits of various dosages. CONCLUSION: We found that VA and PI show promising results on reducing SSI. PI is recommended as the most efficacious intrawound treatment to prevent SSI after spine surgery. KEY WORDS: Intrawound treatments, network meta-analysis, spine, surgery, surgical site infection

Transition from Compounded to Monotherapy Intrathecal Pain Medication Reduces Drug Costs: Retrospective Analysis of Patient Billing Data

BACKGROUND: Chronic pain accounts for several hundred billion dollars in total treatment costs, and lost productivity annually. Selecting cost-effective pain treatments can reduce the financial burden on both individuals and society. Targeted drug delivery (TDD), whereby medications used to treat pain are delivered directly to the intrathecal space, remains an important treatment modality for chronic pain refractory to oral medication management. These medications can be administered alone (monotherapy), or in conjunction with other medications to give a synergistic affect (compounded therapy). While compounded therapy is often prescribed for pain refractory to both oral management and intrathecal monotherapy, compounded administration has not been approved by the United States Food and Drug Administration (FDA), and is thought to be more expensive. In this study, we hypothesized that TDD delivering monotherapy vs compounded therapy would differ significantly in cost. OBJECTIVES: In 2015, a pharmacy-led initiative resulted in an institution-wide policy requiring that all TDD patients, being treated with compounded therapy, be transitioned to FDA-approved intrathecal monotherapy. The intent of this new policy was to eliminate use of non-FDA approved, “off-label” medications. During this transition, our practice used the opportunity to retrospectively analyze and compare the costs of monotherapy vs compounded therapy. STUDY DESIGN: Billing, drug dosing, and pain data were collected from 01/2015 to 01/2019, and reviewed retrospectively for patients originally on compounded intrathecal medication therapy, and compared before and after transition to monotherapy. SETTING: A multidisciplinary hospital-based spine center within an academic tertiary care facility. METHODS: Electronic medical records from the institutional TDD program were retrospectively reviewed to identify all patients on compounded drug therapy before the transition period (2015-2016). Patients were excluded from the study if they chose to switch their care to another practice rather than transitioning from compounded therapy to monotherapy. Cost per medications refill, cost per year, and reported pain scale before and after the transition were computed, and differences were compared using unpaired t tests. Refill costs of individual drugs were also compared. RESULTS: Of 46 patients originally on compounded therapy, 26 patients met inclusion criteria. The most common pre-transition drugs administered as compounded therapy were bupivacaine (n = 17), morphine (n = 15), and clonidine (n = 14), while hydromorphone (n = 10), baclofen (n = 5), and fentanyl (n = 1) were less common. There was a 51.3% decrease in cost per refill (P = 0.135) and a 50.0% decrease in cost per year (P = 0.283) after transition. Morphine and clonidine were both significantly more expensive than hydromorphone and bupivacaine (P < 0.05). After removing cases in which hydromorphone was the baseline opiate, there was a 64.8% decrease in cost per refill (P = 0.041) and a 66.8% decrease in cost per year (P = 0.190). There was no significant difference in the average reported pain scale across the transition (P = 0.323), suggesting stable pain management efficacy. LIMITATIONS: This retrospective study is limited by its small cohort size and lack of a control group. CONCLUSIONS: Based on single-institutional billing data, transition from compounded therapy to monotherapy TDD resulted in cost savings, dependent on the specific combination of drugs initially used for therapy. A larger multi-institutional study is indicated. KEY WORDS: Low back pain, intrathecal pain management, implantable drug pump, cost analysis, morphine, hydromorphone, fentanyl, clonidine, baclofen, bupivacaine

Transcranial Direct Current Stimulation for the Management of Neuropathic Pain: A Narrative Review

BACKGROUND: Neuropathic pain (NP) is common and often resistant to conventional analgesics. Among different types of noninvasive brain stimulation techniques, transcranial direct current stimulation (tDCS) has been widely used to mitigate pain in patients with NP. OBJECTIVE: The aim of this study was to review the effects of tDCS on the management of various types of NP. STUDY DESIGN: Narrative review. METHODS: A PubMed search was conducted for articles published until October 1, 2020, using tDCS to treat NP. The key search phrase, transcranial direct current stimulation and pain, was used to identify potentially relevant articles. The following inclusion criteria were applied for article selection: (1) studies involving patients with NP and (2) studies that used tDCS to treat NP. Review articles were excluded from the analysis. RESULTS: A total of 524 potentially relevant articles were identified. After reading the titles and abstracts and assessing eligibility based on the full-text articles, 34 publications were included in our review. Overall, our results suggest that tDCS induced pain reduction in patients with NP due to stroke or spinal cord injury, multiple sclerosis, or trigeminal neuralgia. There is insufficient evidence to validate the efficacy of tDCS for treating other painful conditions, such as complex regional pain syndrome, phantom pain, or NP of various origins. LIMITATIONS: The review did not include studies indexed in databases other than PubMed. CONCLUSION: The results of the included studies suggest that tDCS may be beneficial in treating patients with NP due to stroke, spinal cord injury, multiple sclerosis, and trigeminal neuralgia. Further studies are recommended to validate the efficacy of tDCS in treating other types of NPs. KEY WORDS: Transcranial direct current stimulation, neuropathic pain, central post-stroke pain, spinal cord injury, multiple sclerosis, complex regional pain syndrome, phantom pain, trigeminal neuralgia

Chronic Opioid Therapy Utilization Following an Acute Pain Prescription Supply Restriction Law: An Interrupted Time Series Analysis

BACKGROUND: Florida House Bill 21 (HB21) was implemented in July 2018 to limit Schedule II opioids prescriptions for patients with acute pain to a 3-day supply. Little is known about the potential unintended effects that such opioid restriction policies may have on chronic pain patients, who are exempt from the law. OBJECTIVE: We aimed to evaluate the effect of HB21 on opioid utilization measures among a cohort of chronic opioid therapy (COT) patients. STUDY DESIGN: A quasi-experimental design with interrupted time series analyses. SETTING: Pharmacy claims from January 1, 2015 to June 31, 2019 from a large employer-based health plan in Florida. METHODS: COT patients were those who received a >= 70 days’ supply of opioids in the prior 90 days, representing 15,310 patients. Interrupted time series analyses were conducted to compare the following monthly measures among COT patients before and after HB21 implementation: 1) number of COT patients, 2) daily Morphine Milligram Equivalents [MMEs], 3) days’ supply of prescriptions. RESULTS: There was a significant 25% reduction in the trend (pre-HB21 RR: 0.95, 95% CI: 0.93, 0.96 versus post-HB21 RR: 0.70, 95% CI: 0.65, 0.76) and an 8% immediate decrease (RR: 0.92, 95% CI: 0.88, 0.97) in the monthly prevalence of COT patients after HB21 implementation. However, no significant change was observed in trends for monthly number of days supplied per prescription, monthly MMEs per COT patient-day, or total MMEs per prescription. LIMITATIONS: Our study used data from employer-based private health insurance and did not include a longer post-policy period to adjust for implementation lag. CONCLUSION: Fewer patients received COT after HB21; however, patients who continued to receive COT experienced no significant changes in their regimen. The study did not assess whether COT patients were appropriately tapered or if therapeutic alternatives were initiated for new chronic pain patients. KEY WORDS: Prescription opioids, health policy evaluation, chronic opioid therapy, drug utilization

Treatment Impact on Patient-Reported Outcomes in Peripheral Neuropathic Pain: Comparing Single Intervention With Topical High-Concentration Capsaicin to Daily Oral Pregabalin

BACKGROUND: Peripheral neuropathic pain (PNP) is a complex, subjective experience affecting both physical and psychological aspects of functioning. Assessing patient-reported outcomes (PROs) beyond pain relief is important and aligns with the recommendations of IMMPACT (Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials). Moreover, PRO data are key to clinical decision-making when evaluating treatment options. However, direct comparisons between such options are scarce. High-concentration capsaicin 179 mg (8% w/w) cutaneous patch (HCCP) is applied to the skin at minimum intervals of 90 days under physician supervision; alternative recommended treatments for PNP are mostly orally administered on a daily basis. The ELEVATE study directly compared HCCP with pregabalin and found noninferior efficacy of HCCP to pregabalin in relieving pain after 8 weeks, with a significantly faster onset of action and fewer systemic side effects. OBJECTIVES: The objective of this analysis was to compare PRO outcomes defined as secondary objectives of the ELEVATE study after a single intervention with HCCP to daily oral pregabalin for 8 weeks. STUDY DESIGN: ELEVATE was an open-label, randomized (1:1) multicenter study. SETTING: The study included 92 sites in 22 countries in Europe and Asia. METHODS: Five hundred fifty-nine non-diabetic patients with PNP received a single intervention with HCCP (n = 282; 1-4 patches at baseline) or oral daily pregabalin (n = 277; 150-600 mg, 8 weeks). At baseline (Day 0) and Week 8, patients completed the following PROs in addition to the regular pain assessments: Patient Global Impression of Change (PGIC), Medical Outcomes Study Cognitive Functioning scale (MOS-Cog), Medical Outcomes Study Sleep scale (MOS-Sleep), Treatment Satisfaction Questionnaire for Medication (TSQM), and EuroQol 5-Dimensions 5-levels (EQ-5D-5L) Utility Index (EQ-UI) and Visual Analog Scale (EQ-VAS). RESULTS: At Week 8, 76% and 75.9% of patients on HCCP and pregabalin, respectively, reported to be very much/much/minimally improved on the PGIC. HCCP application was associated with significant improvements from baseline vs. pregabalin in MOS-Cog (mean difference: 4.28 [95% CI: 2.90-5.66]; P < 0.001), EQ-VAS (3.11 [0.30-5.92]; P = 0.030), and TSQM global satisfaction (6.74 [2.29-11.20]; P = 0.029), particularly the side-effects dimension (21.23 [17.55-24.94]; P < 0.0001). No significant differences in improvements were noted for the MOS-Sleep, TSQM convenience, and EQ-UI. LIMITATIONS: The ELEVATE study has an open-label design, with only one comparator (pregabalin); it was limited to 8 weeks. The sample size was determined for the primary endpoint. CONCLUSIONS: A single intervention with HCCP showed benefits vs. daily pregabalin at Week 8 on several PROs. While HCCP has been approved in the United States for PNP treatment in diabetic and PHN patients, these observations provide information on how patients perceive the effects of distinct PNP treatments. They are complementing already existing knowledge on efficacy and safety of different treatment options with data on patient preferences and may help identify the appropriate treatment option in dialogue with the patients and shared decision-making. IRB Approval: At the time of the study, the trial was approved either nationally or at site level. All approvals were granted prior to the initiation of the trial. A list of Ethics Committees that approved the trial is included as a supplemental file. Clinical Trial Registration Number: NCT01713426. KEY WORDS: Capsaicin; comparative study; ELEVATE study; neuropathic pain; pain; pain measurement; patient outcome assessment; pregabalin