Emergency Regulatory Procedures, Pharmaceutical Regulatory Politics, and the Political Economy of Vaccine Regulation in the COVID-19 Pandemic.

CONTEXT: Regulatory approaches to COVID-19 vaccine authorizations varied substantially across countries. Facing a common public health threat, what accounts for regulatory variation? This study focuses on emergency pharmaceutical and vaccine regulatory procedures and whether and how regulators' emergency pharmaceutical regulatory procedures going into the pandemic shaped regulatory processes and decisions during the pandemic. METHODS: The authors conducted an analysis of seven high-impact national and international pharmaceutical regulators with case studies from Brazil, China, India, Russia, the United Kingdom, the United States, and the European Medicines Agency. The authors analyzed evidence from primary source executive and legislative branch regulations and statutes as well as national and international scientific and general press reporting; they also drew on the secondary analysis of scholars, practitioners, and international organizations. FINDINGS: Inherited emergency pharmaceutical and vaccine regulatory procedures substantially shaped COVID-19 vaccine regulation during the pandemic. Variation in the presence and content of emergency regulatory procedures affected the quality of pandemic regulatory processes, outcomes, and procedural updates and differentially empowered policy-making experts and elected politicians. CONCLUSIONS: Emergency regulatory procedures affect key features of regulatory political economy and public health practices during crises. To improve future public health crisis responses, the authors provide policy recommendations for (1) establishing clear emergency pharmaceutical regulatory procedures, and (2) international collaboration.

The impact of voluntary folate fortification of corn masa flour on US pregnancies complicated by neural tube defects.

INTRODUCTION: In 1996, the US Food and Drug Administration (FDA) mandated folic acid fortification for all enriched cereal grains. This resulted in a reduction of neural tube defect (NTD)-affected pregnancies. However, Hispanic women continued to be twice as likely to give birth to a child affected by NTD compared to non-Hispanic White women. Some hypotheses explaining this difference focus on cultural variation in dietary intake of cereal grains. In 2016, the FDA approved voluntary folic acid fortification for corn masa flour products to focus on the Hispanic diet staple. This study investigates rates of NTDs in predominantly Hispanic-populated zip codes before and after the voluntary fortification of corn masa flour with folic acid. METHODS: Normal pregnancies and those complicated by NTDs between 1/1/2016 and 9/30/2020 were identified using ICD-9 and ICD-10 codes in an all-payor claims database. The post-fortification period began 12 months after the fortification recommendation. The US Census data was used to stratify pregnancies in predominantly Hispanic zip codes (≥ 75% of households) vs. non-Hispanic zip codes. The causal impact of the FDA's recommendation was assessed by means of a Bayesian structural time series model. RESULTS: A total of 2,584,366 pregnancies were identified among females aged 15-50 years. Of these, 365,983 took place in predominantly Hispanic zip codes. Mean quarterly NTDs per 100,000 pregnancies did not significantly differ between predominantly Hispanic zip codes and predominantly non-Hispanic zip codes pre-FDA recommendation (184.5 vs. 175.6; p = 0.427), nor post-recommendation (188.2 vs. 185.9; p = 0.713). Rates of NTDs predicted to occur if no FDA recommendation had been made were compared to the actual rate post-recommendation: no significant difference was observed in predominantly Hispanic zip codes (p = 0.245) or overall (p = 0.116). CONCLUSIONS: Rates of neural tube defects were not significantly reduced in predominantly Hispanic zip codes following the 2016 FDA approval of voluntary folic acid fortification of corn masa flour. Further research and implementation of comprehensive approaches to advocacy, policy, and public health are necessary to decrease preventable congenital disease rates. Mandatory rather than voluntary fortification of corn masa flour products may achieve more substantial prevention of neural tube defects in at-risk US populations.

The role of bone mineral density in adult spinal deformity patients undergoing corrective surgery: a matched analysis.

STUDY DESIGN: Retrospective cohort. BACKGROUND: Over 44 million adults are estimated to have either osteoporosis or osteopenia. Adult spinal deformity (ASD) is estimated to affect between 32 and 68% of the elderly population. OBJECTIVE: Retrospective investigation comparing rates of postoperative complications following thoracolumbar scoliosis surgery in patients with normal bone mineral density (BMD) to those with osteopenia or osteoporosis in addition to analyzing the effects of pretreatment with anti-osteoporotic medications in patients with low BMD. METHODS: Using administrative database of Humana beneficiaries, ICD-9 and ICD-10 diagnosis codes were used to identify ASD patients undergoing multilevel thoracolumbar fusions between 2007 and 2017. RESULTS: The propensity matched population analyzed in this study contained 1044 patients equally represented by those with a history of osteopenia, osteoporosis, or normal BMD. Osteopenia and osteoporosis were associated with increased odds of revision surgery (OR 2.01 95% CI 1.36-2.96 and OR 1.57, 95% CI 1.05-2.35), respectively. Similarly, there was an almost twofold increased odds of proximal and distal junctional kyphosis in patients with osteopenia and osteoporosis (OR 1.95, 95% CI 1.40-2.74 and OR 1.88, 95% CI 1.34-2.64), respectively. A total of 258 (37.1%) patients with osteoporosis were pretreated with anti-osteoporotic medications and there was no statistically significant decrease in odds of proximal or distal junctional kyphosis or revision surgery in these patients. CONCLUSION: Patients with ASD undergoing multilevel thoracolumbar fusion surgery have significantly higher rates of postoperative pseudarthrosis, proximal and distal junctional kyphosis, and revision surgery rates compared to patients with normal BMD.

The impact of volunteering with a student-run free clinic on medical student specialty selection.

BACKGROUND: The shortage of primary care physicians in the United States is expected to grow to 17,800-48,000 physicians by 2034. Student Run Free Clinics are an increasingly popular component of medical schools and may provide an avenue for increasing medical student interest in primary care specialties. However, there is limited research on the impact of Student Run Free Clinics on medical student specialty choice. This investigation sought to determine whether volunteering with the Interprofessional Community Clinic (ICC), the Student Run Free Clinic associated with Chicago Medical School, was associated with an increased likelihood of matching into primary care specialties. Secondarily, the authors investigated associations between volunteering and matching into family practice. Finally, the authors explored associations between volunteering and the competitiveness of specialty choice. METHODS: This retrospective review utilized data on medical school graduates from 2015 - 2021 including their matched specialties, the number of ICC shifts they volunteered for, and whether they held an ICC leadership position (executive officers). Primary care specialties were defined as internal medicine, family practice, pediatrics, or combined internal medicine/pediatrics. Residency fill rate was used as a proxy for competitiveness. RESULTS: This analysis included 506 medical students (254 ICC volunteers and 252 non-volunteers). Among ICC volunteers, 47.2% matched into a primary care specialty compared to 36.5% of non-volunteers (RR 1.29, 95% CI 1.05-1.59). Each additional shift worked at the ICC was correlated with increased odds of matching into family practice by a factor of 1.042 (95% CI 1.005-1.079). CONCLUSIONS: Medical students who volunteered with the ICC were more likely to match into primary care residencies. Students who volunteered more frequently were more likely to match into family practice. Further investigation is warranted to determine whether these associations are causative and could thus be leveraged to encourage medical students to pursue primary care careers.

Evaluation of subchronic administration of antiseizure drugs in spontaneously seizing rats.

OBJECTIVE: Approximately 30% of patients with epilepsy do not experience full seizure control on their antiseizure drug (ASD) regimen. Historically, screening for novel ASDs has relied on evaluating efficacy following a single administration of a test compound in either acute electrical or chemical seizure induction. However, the use of animal models of spontaneous seizures and repeated administration of test compounds may better differentiate novel compounds. Therefore, this approach has been instituted as part of the National Institute of Neurological Disorders and Stroke Epilepsy Therapy Screening Program screening paradigm for pharmacoresistant epilepsy. METHODS: Rats were treated with intraperitoneal kainic acid to induce status epilepticus and subsequent spontaneous recurrent seizures. After 12 weeks, rats were enrolled in drug screening studies. Using a 2-week crossover design, selected ASDs were evaluated for their ability to protect against spontaneous seizures, using a video-electroencephalographic monitoring system and automated seizure detection. Sixteen clinically available compounds were administered at maximally tolerated doses in this model. Dose intervals (1-3 treatments/d) were selected based on known half-lives for each compound. RESULTS: Carbamazepine (90 mg/kg/d), phenobarbital (30 mg/kg/d), and ezogabine (15 mg/kg/d) significantly reduced seizure burden at the doses evaluated. In addition, a dose-response study of topiramate (20-600 mg/kg/d) demonstrated that this compound reduced seizure burden at both therapeutic and supratherapeutic doses. However, none of the 16 ASDs conferred complete seizure freedom during the testing period at the doses tested. SIGNIFICANCE: Despite reductions in seizure burden, the lack of full seizure freedom for any ASD tested suggests that this screening paradigm may be useful for testing novel compounds with potential utility in pharmacoresistant epilepsy.

Accurate detection of spontaneous seizures using a generalized linear model with external validation.

OBJECTIVE: Seizure detection is a major facet of electroencephalography (EEG) analysis in neurocritical care, epilepsy diagnosis and management, and the instantiation of novel therapies such as closed-loop stimulation or optogenetic control of seizures. It is also of increased importance in high-throughput, robust, and reproducible pre-clinical research. However, seizure detectors are not widely relied upon in either clinical or research settings due to limited validation. In this study, we create a high-performance seizure-detection approach, validated in multiple data sets, with the intention that such a system could be available to users for multiple purposes. METHODS: We introduce a generalized linear model trained on 141 EEG signal features for classification of seizures in continuous EEG for two data sets. In the first (Focal Epilepsy) data set consisting of 16 rats with focal epilepsy, we collected 1012 spontaneous seizures over 3 months of 24/7 recording. We trained a generalized linear model on the 141 features representing 20 feature classes, including univariate and multivariate, linear and nonlinear, time, and frequency domains. We tested performance on multiple hold-out test data sets. We then used the trained model in a second (Multifocal Epilepsy) data set consisting of 96 rats with 2883 spontaneous multifocal seizures. RESULTS: From the Focal Epilepsy data set, we built a pooled classifier with an Area Under the Receiver Operating Characteristic (AUROC) of 0.995 and leave-one-out classifiers with an AUROC of 0.962. We validated our method within the independently constructed Multifocal Epilepsy data set, resulting in a pooled AUROC of 0.963. We separately validated a model trained exclusively on the Focal Epilepsy data set and tested on the held-out Multifocal Epilepsy data set with an AUROC of 0.890. Latency to detection was under 5 seconds for over 80% of seizures and under 12 seconds for over 99% of seizures. SIGNIFICANCE: This method achieves the highest performance published for seizure detection on multiple independent data sets. This method of seizure detection can be applied to automated EEG analysis pipelines as well as closed loop interventional approaches, and can be especially useful in the setting of research using animals in which there is an increased need for standardization and high-throughput analysis of large number of seizures.

Correction of medication nonadherence results in better seizure outcomes than dose escalation in a novel preclinical epilepsy model of adherence.

OBJECTIVE: Medication nonadherence directly contributes to poor seizure control. A lack of emphasis on correcting poor adherence and failures in patient adherence can result in unwarranted alterations to a patient's drug regimen. We have modeled nonadherent patients in an animal model of epilepsy to study how alterations to pharmacotherapy, made without consideration of a patient's adherence, result in changes to seizure control. METHODS: Newly diagnosed rats with epilepsy were treated with carbamazepine (CBZ) during a 4-week baseline period to establish their baseline seizure rate in the presence of 50% adherence. Next, animals were randomized to one of three treatment interventions and monitored for 6 weeks. Groups included: (1) no change in therapy-rats continued the 50% adherent paradigm; (2) dose escalation-the dose of CBZ was doubled, and the 50% adherent paradigm continued; and (3) nonadherence corrected-rats continued the initial dose of CBZ, but the adherence rate was adjusted to 100% (ie, fully adherent). RESULTS: The rats in the no change in therapy arm displayed a 61% increase in seizure burden over the 6-week intervention phase. Similarly, rats in the dose escalation arm had a 66% worsening of their daily seizure burden. In contrast, rats in the nonadherence corrected arm displayed a 33% reduction in their daily seizure burden; a significant improvement when compared to the normalized seizure burden scores of rats in the other two treatment arms (P < 0.01). SIGNIFICANCE: We found that failure to correct medication nonadherence resulted in an increase in daily seizure burden in rats, even following dose escalation. In the presence of nonadherence, dose escalation worsened seizure control. In contrast, correcting nonadherence alone resulted in improved seizure control. These findings suggest that improving adherence should be prioritized over dose escalation in the clinical management of uncontrolled epilepsy.

The impact of nonadherence to antiseizure drugs on seizure outcomes in an animal model of epilepsy.

OBJECTIVE: Nonadherence to prescribed dosing regimens is a significant problem in the treatment of pediatric and adult chronic epilepsy, and can result in severe consequences to patient outcomes. In this first-of-kind preclinical study, the impact of nonadherence on seizure control was studied by simulating human patterns of nonadherence in an animal epilepsy model. METHODS: In study 1, three different patterns of nonadherence were modeled in newly diagnosed epileptic rats treated with carbamazepine: perfect adherence (100% of pellets contained carbamazepine), variable nonadherence (50% of pellets contained carbamazepine with different dosing patterns between animals), and complete nonadherence (0% of pellets contained carbamazepine). In study 2, a cohort of newly diagnosed epileptic rats were subjected to a "drug holiday" nonadherence paradigm, that is, a 2-week on (100%), 2-week off (0%), and 2-week on (100%) carbamazepine paradigm. RESULTS: In the first experiment, the 100% (0.3 ± 0.2 SD convulsive seizures per day) adherent cohort demonstrated better seizure control than either the 0% (1.1 ± 0.8 SD) or 50% (0.8 ± 0.6 SD) adherent cohorts, which had similar levels of seizure control. In the second study, poor seizure control was exhibited during the second 2 weeks; that is, the drug holiday epoch; however, this did not negatively affect restoration of seizure control upon reinstatement of CBZ. SIGNIFICANCE: The results from this pilot investigation suggest that nonadherence to carbamazepine is associated with significant negative but reversible effects on seizure control in an animal model of epilepsy. Furthermore, these results demonstrate that animal studies of nonadherence can yield potentially important and translatable insights into the consequences of nonadherence on seizure control.

Development and pharmacologic characterization of the rat 6 Hz model of partial seizures.

OBJECTIVE: The mouse 6 Hz model of psychomotor seizures is a well-established and commonly used preclinical model for antiseizure drug (ASD) discovery. Despite its widespread use both in the identification and differentiation of novel ASDs in mice, a corresponding assay in rats has not been developed. We established a method for 6 Hz seizure induction in rats, with seizure behaviors similar to those observed in mice including head nod, jaw clonus, and forelimb clonus. METHODS: A convulsive current that elicits these seizure behaviors in 97% of rats (CC97 ) was determined using a Probit analysis. Numerous prototype ASDs were evaluated in this model using stimulus intensities of 1.5× and 2× the CC97 , which is comparable to the approach used in the mouse 6 Hz seizure model (e.g., 32 and 44 mA stimulus intensities). The ASDs evaluated include carbamazepine, clobazam, clonazepam, eslicarbazepine, ethosuximide, ezogabine, gabapentin, lacosamide, lamotrigine, levetiracetam, phenobarbital, phenytoin, rufinamide, tiagabine, topiramate, and sodium valproate. Median effective dose (ED50 ) and median toxic (motor impairment) dose (TD50 ) values were obtained for each compound. RESULTS: Compounds that were effective at the 1.5 × CC97 stimulus intensity at protective index (PI) values >1 included clobazam, ethosuximide, ezogabine, levetiracetam, phenobarbital, and sodium valproate. Compounds that were effective at the 2 × CC97 stimulus intensity at PI values >1 included ezogabine, phenobarbital, and sodium valproate. SIGNIFICANCE: In a manner similar to the use of the mouse 6 Hz model, development of a rat 6 Hz test will aid in the differentiation of ASDs, as well as in study design and dose selection for chronic rat models of pharmacoresistant epilepsy. The limited number of established ASDs with demonstrable efficacy at the higher stimulus intensity suggests that, like the mouse 6 Hz 44 mA model, the rat 6 Hz seizure model may be a useful screening tool for pharmacoresistant seizures.

Semaglutide exposure and its association with adverse outcomes in diabetic patients undergoing transforaminal lumbar interbody fusion for lumbar degenerative disc disease.

OBJECTIVE: Semaglutide, a novel glucagon-like peptide-1 receptor agonist, has transformed the therapeutic landscape for type 2 diabetes mellitus. However, its effect on osteoclast activity and its potential to induce weight-related muscle loss raises concerns about its impact on spine surgery outcomes. As such, evaluating semaglutide's influence on transforaminal lumbar interbody fusion (TLIF) is imperative, given the procedure's reliance on successful bony fusion to prevent postoperative instability and further interventions. METHODS: Using an all-payer database (MARINER), the authors analyzed data from patients with type 2 diabetes mellitus who were 18-74 years of age and who underwent short-segment fusion (≤ 3-level) TLIFs between January 2018 and October 2022. Patients were either exposed to semaglutide or not. A comprehensive 1:3 (exposure vs no exposure) matching was performed based on age, sex, obesity, hypertension, coronary artery disease, chronic kidney disease, smoking status, osteoporosis, levels of surgery, and basal-bolus insulin dependence. Kaplan-Meier survival curves and log-rank testing were performed to study the probability of additional lumbar fusion surgery within 1 year. RESULTS: After the 1:3 matching, 1781 patients were identified, with 447 in the semaglutide-exposed cohort and 1334 in the nonexposed cohort. Most patients in both groups were 55-69 years old, and 59.3% were female. Analysis showed that the likelihood of undergoing additional lumbar fusion surgery within 1 year post-TLIF was significantly higher in the semaglutide-exposed group than in the nonexposed group (OR 11.79, 95% CI 8.17-17.33). Kaplan-Meier plots and log-rank testing further confirmed a statistically significant divergent probability in the need for additional surgery within 1 year between the cohorts (log-rank, p < 0.001). CONCLUSIONS: Semaglutide exposure appears to be associated with a higher likelihood of additional lumbar fusion surgeries within 1 year post-TLIF, especially in patients receiving the medication for longer durations. Although the mechanisms remain speculative, potential impacts on bone turnover and the onset of muscle loss may be contributory factors. Further research is needed to elucidate the exact mechanisms and to develop strategies for optimizing surgical outcomes in these patients.

5-year stroke rates in nonvalvular atrial fibrillation after watchman compared to direct oral anticoagulants.

BACKGROUND: The WATCHMAN device (Boston Scientific; Marlborough, MA, USA) is noninferior to warfarin in preventing ischemic strokes while reducing bleeding risks associated with long term anticoagulation in nonvalvular atrial fibrillation (AFib). The device's performance compared to direct oral anticoagulants (DOAC) is less well known. OBJECTIVE: To compare 5-year major bleeding and ischemic stroke rates in patients with nonvalvular AFib who received a WATCHMAN device or DOAC therapy after a major bleeding event. METHODS: This retrospective, multicenter, 1:1 matched cohort study was derived from the PearlDiver Mariner database from 2010 to 2020. Patients with nonvalvular AFib on oral anticoagulation who had a major bleeding event were identified. Those who received either WATCHMAN or DOAC after resolution of the bleeding event were selected. The two groups were exactly matched 1:1 based on various comorbidities. Rates of ischemic stroke, transient ischemic attack (TIA), major bleeding, and hemorrhagic stroke were compared over 5 years. RESULTS: Each cohort consisted of 2248 patients after 1:1 matching. The mean CHADS2-VASC score was 4.81 ±â€¯1.25. At 5 years, the WATCHMAN cohort had significantly lower rates of major bleeding events [OR 0.24 (0.21, 0.27)], TIAs [OR 0.75 (0.58, 0.95)], and ischemic strokes [OR 0.72 (0.61, 0.86)]. There was no significant difference in hemorrhagic strokes [OR 1.14 (0.83, 1.58)]. CONCLUSION: Even in a high-risk population, the WATCHMAN is comparable to DOAC therapy in the primary prevention of hemorrhagic strokes and may provide benefit in the rates of bleeding events, TIAs, and ischemic strokes.

An Appraisal of the Quality of Development and Reporting of Predictive Models in Neurosurgery: A Systematic Review.

BACKGROUND AND OBJECTIVES: Significant evidence has indicated that the reporting quality of novel predictive models is poor because of confounding by small data sets, inappropriate statistical analyses, and a lack of validation and reproducibility. The Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) statement was developed to increase the generalizability of predictive models. This study evaluated the quality of predictive models reported in neurosurgical literature through their compliance with the TRIPOD guidelines. METHODS: Articles reporting prediction models published in the top 5 neurosurgery journals by SCImago Journal Rank-2 (Neurosurgery, Journal of Neurosurgery, Journal of Neurosurgery: Spine, Journal of NeuroInterventional Surgery, and Journal of Neurology, Neurosurgery, and Psychiatry) between January 1st, 2018, and January 1st, 2023, were identified through a PubMed search strategy that combined terms related to machine learning and prediction modeling. These original research articles were analyzed against the TRIPOD criteria. RESULTS: A total of 110 articles were assessed with the TRIPOD checklist. The median compliance was 57.4% (IQR: 50.0%-66.7%). Models using machine learning-based models exhibited lower compliance on average compared with conventional learning-based models (57.1%, 50.0%-66.7% vs 68.1%, 50.2%-68.1%, P = .472). Among the TRIPOD criteria, the lowest compliance was observed in blinding the assessment of predictors and outcomes (n = 7, 12.7% and n = 10, 16.9%, respectively), including an informative title (n = 17, 15.6%) and reporting model performance measures such as confidence intervals (n = 27, 24.8%). Few studies provided sufficient information to allow for the external validation of results (n = 26, 25.7%). CONCLUSION: Published predictive models in neurosurgery commonly fall short of meeting the established guidelines laid out by TRIPOD for optimal development, validation, and reporting. This lack of compliance may represent the minor extent to which these models have been subjected to external validation or adopted into routine clinical practice in neurosurgery.

The Impact of Preoperative Spinal Injection Timing on Postoperative Complications of Lumbar Decompression Surgery.

BACKGROUND AND OBJECTIVES: Epidural steroid injections (ESIs) are commonly used for lower back pain management. The effect of these injections on lumbar decompression surgery outcomes is hitherto underexplored. The study objective was to determine the impact of ESIs on postoperative rates of medical and surgical complications and to define the appropriate interval before lumbar decompression surgery. METHODS: This retrospective all-payer database analysis identified 587 651 adult patients undergoing one- to three-level laminectomies from January 2010 to October 2021. A 2:1 propensity score match accounting for comorbidities, levels of surgery, and demographics was performed to create two cohorts: (1) 43 674 patients who had received an ESI in the 90 days before laminectomy and (2) 87 348 patients who had not received an ESI. The primary outcome was the rates of medical and surgical complications between groups at 30 days postoperatively. Patients were divided into five cohorts based on injection time before surgery: 1 to 30 days, 31 to 45 days, 46 to 60 days, 61 to 75 days, and 76 to 90 days. Logistic regression was performed between groups to identify temporal associations of complication rates. Confidence intervals of 95% are provided when appropriate. P values < .01 were considered significant. RESULTS: Rates of medical complications within 30 days of surgery were significantly higher in those with ESI compared with control (4.83% vs 3.9%, P < .001). Cerebrospinal fluid (CSF) leak rates were increased in the ESI group at 0.28% vs 0.1% (P < .001), but surgical site infection rates were not significantly different between groups (1.31% vs 1.42% P = .11). ESI performed within 30 days was associated with increased odds of CSF leak (OR: 5.32, 95% CI: 3.96-7.15). CONCLUSION: Preoperative ESI increases the risk of CSF leak and medical complications after lumbar decompression. Because these complications were significantly associated with ESIs given 1 to 30 days before surgery, avoiding ESIs at least 30 days before surgery may be advisable.

Gastrostomy Sequence With Ventriculoperitoneal Shunting-Does It Matter?

BACKGROUND: Neurological injury requiring ventriculoperitoneal shunt (VPS) placement often necessitates gastrostomy for nutritional support. The sequence of these procedures is debated over concerns for shunt infection and displacement requiring revisional surgery as a consequence of gastrostomy. OBJECTIVE: To determine the optimal sequence of VPS shunt and gastrostomy tube placement in adults. METHODS: In an all-payer database, adult patients undergoing gastrostomy and VPS placement were identified within 15 days between January 2010 and October 2021. Patients were categorized as receiving gastrostomy before, on the same day as, or after shunt placement. The primary outcomes of this study were rates of revision and infection. All outcomes were evaluated within 30 months after index shunting. RESULTS: In total, 3015 patients were identified as undergoing VPS and gastrostomy procedures within 15 days. After a 1:1:1 match, 1080 patient records were analyzed. Revision rates at 30 months were significantly lower among patients who received VPS and gastrostomy procedures on the same day compared with gastrostomy after VPS (odds ratio [OR] 0.61, 95% CI 0.39-0.96). In addition, patients who received gastrostomy before VPS compared with those after had lower revision rates (OR 0.61, 95% CI 0.39-0.96) and infection (OR 0.46, 95% CI 0.21-0.99). No significant differences were noted in mechanical complication or shunt displacement rates. CONCLUSION: Patients requiring VPS and gastrostomy may benefit from undergoing both procedures concurrently or with gastrostomy before VPS placement, secondary to lower revision rates. Patients undergoing gastrostomy before VPS have the added benefit of decreased infection rates.

Postoperative Opioid Use Among Opioid-Naive Cannabis Users Following Single-Level Lumbar Fusions.

BACKGROUND: As the literature grows on opioid use, the impact of simultaneous cannabis use has hitherto been mostly unexplored. In this study, we assessed the effects of cannabis use on postoperative opioid utilization in opioid-naive patients undergoing single level fusions of the lumbar spine. METHODS: Using an all-payer claims database, the medical records of 91 million patients were analyzed to identify patients who had undergone single level lumbar fusions between January 2010 and October 2020. Rates of opioid utilization at 6 months following index procedure (morphine milligram equivalents/day), the development of opioid use disorder (OUD), and the rates of opioid overuse were assessed. RESULTS: Following examination of 87,958 patient records, 454 patients were matched and distributed equally into cannabis user and noncannabis user cohorts. At 6 months following index procedure, cannabis users were equal to nonusers in their rates of prescribed opioid utilization (49.78%, P > 0.99). Cannabis users used smaller daily dosages compared to nonusers (51.1 ± 35.05 vs. 59.72 ± 41, P = 0.003). On the other hand, the proportion of patients diagnosed with OUD was found to be significantly higher among patients using cannabis (18.94% vs. 3.96%, P < 0.0001). CONCLUSIONS: Compared to noncannabis users, opioid-naive patients who are cannabis users undergoing lumbar spinal fusions are at a higher risk of developing opioid dependence following surgery, despite having decreased daily dosages of opioids overall. Further studies should explore the factors associated with the development of OUD and the details of concurrent marijuana use to effectively treat pain while limiting the potential for abuse.

Outcomes Following 2-Level Cervical Interventions with Cage-and-Plate, Zero-Profile, or Arthroplasty Constructs.

BACKGROUND: Though cage-and-plate constructs are widely used for disk height restoration in surgery for cervical disc disease, concerns over range of motion limitations and adjacent disc space violations have fueled the development of artificial disc and zero-profile constructs. This study investigated the outcomes of patients undergoing two-level cervical interventions via arthroplasty, cage-and-plate, or zero-profile constructs. METHODS: Patients undergoing two-level anterior cervical procedures between 2010 and 2020 were identified using an all-payer claims database. Logistic regression models were utilized to develop criteria for a 1:1:1-exact match procedure. The primary outcome was the need for additional surgery within 30 months, and the secondary outcomes included medical and surgical complications observed within 30 days of index intervention. P values < 0.05 were considered statistically significant. RESULTS: 133,831 patients were identified as undergoing two-level anterior cervical interventions. Seven thousand three hundred seventy-one records were analyzed through a 1:1:1 match. Patients who received zero-profile versus cage-and-plate constructs had significantly decreased odds of requiring additional surgery within 30 months (Odds Ratio [OR] 0.64; 95% Confidence Interval [CI] 0.51-0.81). However, postoperative medical complications were increased among patients who received zero-profile constructs compared to cage-and-plate (OR 1.59; 95%CI 1.07-2.37). Patients who underwent arthroplasty also had decreased odds for additional surgery versus cage-and-plate (OR 0.75; 95%CI 0.60-0.93). There was no significant difference between arthroplasty and cage-and-plate constructs in developing postoperative surgical or medical complications. CONCLUSIONS: Among patients undergoing two-level interventions, cage-and-plate constructs were associated with increased odds of additional surgery within 30 months following index procedures when compared to zero-profile constructs or arthroplasty.

Outcomes Following Endoscopic versus Open Carpal Tunnel Release-A Matched Study.

OBJECTIVE: Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy in the world. Surgical treatment can be performed in an open or endoscopic fashion. To date, similar rates of complications for both approaches have been described. We sought to compare the results of endoscopic carpal tunnel release (ECTR) with open carpal tunnel release (OCTR) in patients with CTS. METHODS: Patients with a diagnosis of CTS undergoing open or endoscopic surgical management were identified between January 2010 and October 2020. The primary outcome of the study was nerve injury within 30 days of the procedure. Secondary outcomes included readmission, wound-related complications, hematoma, seroma formation, and cost. RESULTS: A total of 735,631 patients were identified as undergoing CTR. Following a 1:1 match procedure, 292,626 patient records were analyzed. Patients undergoing OCTR versus ECTR had an increased odds of readmission at 30 days (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.73-2.06), developing an infection (OR 1.59, 95% CI 1.41-1.80), and experiencing wound complications (OR 1.97, 95% CI 1.74-2.23). No significant difference in odds of developing a seroma (OR 1.17, 95% CI 0.83-1.65), hematoma (OR 1.15, 95% CI 0.95-1.39), or nerve injury (OR 1.18, 95% CI 0.98-1.43) was noted. The reimbursement cost of ECTR was significantly greater than OCTR ($310.60 ± $1639.57 vs. $237.69 ± $1488.93, P < 0.001). CONCLUSIONS: In the largest study to date on the surgical management of CTR, OCTR was seen to be associated with an increased odds of readmission, infection, and wound complications, but reduced costs for the procedure alone.

The Impact of Social Determinants of Health in Pediatric Shunted Hydrocephalus.

BACKGROUND: Social risk factors have been shown to negatively affect health outcomes in children. However, this has not been characterized regarding pediatric shunted hydrocephalus. OBJECTIVE: To explore the impact of social risk factors on outcomes in pediatric shunted hydrocephalus with the goal of identifying specific areas of intervention that might improve the outcomes of children undergoing cerebrospinal fluid (CSF) diversion. METHODS: In an all-payer administrative database, records between January 2010 and October 2020 were analyzed to identify children undergoing CSF shunting procedures. Children with social risk factors were compared with those without regarding rates of infection, shunt-related interventions, and mortality within 5 years of their shunting procedure. RESULTS: Among the 5420 children who underwent first-time shunting procedures, 263 (4.9%) were identified to have social risk factors. Children with identified social risk factors had increased odds of central nervous system infection (odds ratio [OR] 2.06, 95% CI 1.45-2.91), revision (OR 2.43, 95% I 1.89-3.12), and mortality (OR 2.86, 95% CI 1.23-5.72). The mean numbers of computed tomography studies (14.60 ± 17.78 vs 6.34 ± 6.10), MRI studies (18.76 ± 24.37 vs 7.88 ± 24.37), and shunt series X-rays (17.22 ± 19.04 vs 7.66 ± 8.54) were increased among children with social risk factors. CONCLUSION: Children with social risk factors had increased rates of central nervous system infection, shunt-related interventions, and mortality within 5 years of CSF shunting. We underscore the importance of characterizing the impact of social risk factors in specific conditions, such as pediatric shunted hydrocephalus, and look to future directions aimed to mitigate these risk factors with coordination and direction of individualized resources, encouragement of advocacy, and community partnership.