Faculty Bibliography

INTRODUCTION/UNASSIGNED:Older adults constitute a large and growing proportion of the population and have unique care needs in the emergency department (ED) setting. The geriatric ED accreditation program aims to improve emergency care provided to older adults by standardizing care provided across accredited geriatric EDs (GED) and through implementation of geriatric-specific care processes. The purpose of this study was to evaluate select care processes at accredited level 1 and level 2 GEDs. METHODS/UNASSIGNED:selected five GED care processes for analysis: initiatives related to delirium, screening for dementia, assessment of function and functional decline, geriatric falls, and minimizing medication-related adverse events. For all protocols, a trained research assistant abstracted information on the tool used or care process, which patients received the interventions, and staff members were involved in the care process; additional information was abstracted specific to individual care processes. RESULTS/UNASSIGNED:A total of 35 level 1 and 2 GEDs were included in this analysis. Among care processes studied, geriatric falls were the most common (31 GEDs, 89%) followed by geriatric pain management (25 GEDs, 71%), minimizing the use of potentially inappropriate medications (24 EDs, 69%), delirium (22 GEDs, 63%), medication reconciliation (21 GEDs, 60%), functional assessment (20 GEDs, 57%), and dementia screening (17 GEDs, 49%). For protocols related to delirium, dementia, function, and geriatric falls, sites used an array of different screening tools and there was heterogeneity in who performed the screening and which patients were assessed. Medication reconciliation protocols leveraged pharmacists, pharmacy technicians and/or nurses. Protocols on avoiding potentially inappropriate medication administration generally focused on ED administration of medications and used the BEERs criteria, and few sites indicated whether pain medications protocols had dosing modifications for age and/or renal function. CONCLUSION/UNASSIGNED:This study provides a snapshot of care processes implemented in level 1 and level 2 accredited GEDs and demonstrates significant heterogeny in how these care processes are implemented.

BACKGROUND:Tuberous sclerosis complex (TSC) and some focal cortical dysplasias (FCDs) are associated with dysfunctional mTOR signaling, resulting in increased cell growth and ribosomal S6 protein phosphorylation (phospho-S6). mTOR inhibitors can reduce TSC tumor growth and seizure frequency, and preclinical FCD studies indicate seizure suppression. This pilot study evaluated safety of mTOR inhibitor everolimus in treatment resistant (failure of >2 anti-seizure medications) TSC and FCD patients undergoing surgical resection and to assess mTOR signaling and molecular pathways. METHODS AND FINDINGS/RESULTS:We evaluated everolimus in 14 treatment resistant epilepsy patients undergoing surgical resection (4.5 mg/m2 daily for 7 days; n = 4 Active, mean age 18.3 years, range 4-26; n = 10, Control, mean age 13.1, range 3-45). Everolimus was well tolerated. Mean plasma everolimus in Active participants were in target range (12.4 ng/ml). Brain phospho-S6 was similar in Active and Control participants with a lower trend in Active participants, with Ser235/236 1.19-fold (p = 0.67) and Ser240/244 1.15-fold lower (p = 0.66). Histologically, Ser235/236 was 1.56-fold (p = 0.37) and Ser240/244 was 5.55-fold lower (p = 0.22). Brain proteomics identified 11 proteins at <15% false discovery rate associated with coagulation system (p = 1.45x10-9) and acute phase response (p = 1.23x10-6) activation. A weighted gene correlation network analysis (WGCNA) of brain proteomics and phospho-S6 identified 5 significant modules. Higher phospho-S6 correlated negatively with cellular respiration and synaptic transmission and positively with organophosphate metabolic process, nuclear mRNA catabolic process, and neuron ensheathment. Brain metabolomics identified 14 increased features in Active participants, including N-acetylaspartylglutamic acid. Plasma proteomics and cytokine analyses revealed no differences. CONCLUSIONS:Short-term everolimus before epilepsy surgery in TSC and FCD resulted in no adverse events and trending lower mTOR signaling (phospho-S6). Future studies should evaluate implications of our findings, including coagulation system activation and everolimus efficacy in FCD, in larger studies with long-term treatment to better understand molecular and clinical effects. CLINICAL TRIALS REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT02451696.

Background/UNASSIGNED:Although the incidence of radiographic Adjacent Segment Disease (ASD) following anterior cervical diskectomy/fusion (ACDF) or cervical disc arthroplasty (CDA) typically ranges from 2-4%/year, reportedly fewer patients are symptomatic, and even fewer require secondary surgery. Methods/UNASSIGNED:Multiple studies have documented a 2-4% incidence of radiographic ASD following either ACDF or CDA per year. However, fewer are symptomatic from ASD, and even fewer require additional surgery/reoperations. Results/UNASSIGNED:In a meta-analysis (2016) involving 83 papers, the incidence of radiographic ASD per year was 2.79%, but symptomatic disease was present in just 1.43% of patients with only 0.24% requiring secondary surgery. In another study (2019) involving 38,149 patients undergoing ACDF, 2.9% (1092 patients; 0.62% per year) had radiographic ASD within an average of 4.66 postoperative years; the younger the patient at the index surgery, the higher the reoperation rate (i.e. < 40 years of age 4.56 X reoperations vs. <70 at 2.1 X reoperations). In a meta-analysis of 32 articles focusing on ASD 12-24 months following CDA, adjacent segment degeneration (ASDeg) occurred in 5.15% of patients, but adjacent segment disease (AS Dis) was noted in just 0.2%/ year. Further, AS degeneration occurred in 7.4% of patients after 1-level vs. 15.6% following 2 level fusions, confirming that CDA's "motion-sparing" design did not produce the "anticipated" beneficial results. Conclusion/UNASSIGNED:The incidence of radiographic ASD ranges from 2-4% per year for ACDF and CDA. Additionally, both demonstrate lesser frequencies of symptomatic ASD, and the need for secondary surgery. Further, doubling the frequency of ASD following 2 vs. 1-level CDA, should prompt surgeons to limit surgery to only essential levels.

The California Verbal Learning Test-Second Edition (CVLT-II) Forced Choice Recognition (FC) and Brief Visuospatial Memory Test-Revised (BVMT-R) Recognition Discrimination Index (RD) are embedded performance validity tests (PVTs) assessing material-specific neuropsychological processes (i.e., verbal and visual memory, respectively). Prior research demonstrated the utility of these PVTs independently; however, no study has compared their diagnostic accuracy for identifying invalid performance relative to each other and in combination within a single sample. This cross-sectional study included an adult neuropsychiatric sample who underwent neuropsychological evaluation. Validity groups were determined via independent criterion PVT performance, and consisted of 103 participants with valid and 25 with invalid neurocognitive performance. FC and RD were not significantly correlated (r = .154), yet both differed between validity groups (η_p