Seizure-related deaths in children: The expanding spectrum.

Although seizures are common in children, they are often overlooked as a potential cause of death. Febrile and nonfebrile seizures can be fatal in children with or without an epilepsy diagnosis and may go unrecognized by parents or physicians. Sudden unexpected infant deaths, sudden unexplained death in childhood, and sudden unexpected death in epilepsy share clinical, neuropathological, and genetic features, including male predominance, unwitnessed deaths, death during sleep, discovery in the prone position, hippocampal abnormalities, and variants in genes regulating cardiac and neuronal excitability. Additionally, epidemiological studies reveal that miscarriages are more common among individuals with a personal or family history of epilepsy, suggesting that some fetal losses may result from epileptic factors. The spectrum of seizure-related deaths in pediatrics is wide and underappreciated; accurately estimating this mortality and understanding its mechanism in children is critical to developing effective education and interventions to prevent these tragedies.

Mortality in tuberous sclerosis complex.

We studied mortality in tuberous sclerosis complex (TSC) by analyzing data from the Tuberous Sclerosis Alliance Natural History Database of 2233 patients from 18 United States TSC centers. Among 31 decedents with data; mean age of death was 29 years. Cause of death could be determined in 26 cases: 11 definitely related to TSC, 14 possibly related to TSC, and 1 unrelated to TSC. Causes of death included SUDEP in 11 (35.5%; Definite (5), Probable (4), Possible (2)), respiratory conditions in 6 (23.1%; lymphangiomyelomatosis in one), tumors in 3 (11.5%), suicide in 2 (7.7%), cardiopulmonary in 2 (7.7%), shunt malfunction in one, and drowning in one. For SUDEP cases, mean age of epilepsy onset was 7 months and 10/11 were treated with multiple anti-seizure medications (ASMs) at death; 7 had intractable epilepsy and 3 were controlled with ASMs. Patients with TSC and their families should be counseled about ASM adherence and lifestyle factors, and the potential role of nocturnal supervision or seizure detection devices to prevent SUDEP.

Widening Racial Disparities During COVID-19 Telemedicine Transition: A Study of Child Mental Health Services at Two Large Children's Hospitals.

OBJECTIVE: To examine whether racial disparities in access to pediatric mental health care were affected during the COVID-19 telemedicine transition at both The Children's Hospital of Philadelphia (CHOP) and Boston Children's Hospital (BCH). METHOD: Electronic health records were queried for all unique outpatient visits from a pre-pandemic period in 2019 and a within-pandemic period in 2020. Changes in the proportion of patients were compared based on insurance status, clinic location, and racial identification. Hypotheses were tested via logistic regression analyses. RESULTS: At CHOP, from 2019 to 2020, the proportion of racially minoritized patients significantly declined within a 1-month period from 62% to 51%, whereas the proportion of White-identifying patients increased from 38% to 49% (ß = 0.47; z = 3.60; p =.0003), after controlling for insurance status and clinic location. At BCH, the proportion of racially minoritized patients significantly declined within a longer 6-month period between 2019 and 2020, from 62% to 59%, whereas the proportion of White-identifying patients increased from 38% to 41% (ß = 0.13; z = 2.8; p = .006), after controlling for insurance status. CONCLUSION: At CHOP and BCH, the COVID-19 telemedicine transition exacerbated pre-existing racial disparities in pediatric mental health services. Our findings suggest that racially minoritized patients receiving services in urban areas may be particularly at risk for losing access when telemedicine is implemented. Although there are limitations to this racial dichotomization, examining differences between White and racially minoritized patients can highlight ways in which White-identifying individuals have disproportionately received enhanced access to healthcare resources.

Racial and Social Determinants of Health Disparities in Spine Surgery Affect Preoperative Morbidity and Postoperative Patient Reported Outcomes: Retrospective Observational Study.

STUDY DESIGN: Retrospective observational study. OBJECTIVE: To elucidate racial and socioeconomic factors driving preoperative disparities in spine surgery patients. SUMMARY OF BACKGROUND DATA: There are racial and socioeconomic disparities in preoperative health among spine surgery patients, which may influence outcomes for minority and low socioeconomic status (SES) populations. METHODS: Presenting, postoperative day 90 (POD90), and 12-month (12M) outcome scores (PROMIS global physical and mental [GPH, GMH] and visual analog scale pain [VAS]) were collected for patients undergoing deformity arthrodesis or cervical, thoracic, or lumbar laminotomy or decompression/fusion; these procedures were the most common in our cohort. Social determinants of health for a patient's neighborhood (county, zip code, or census tract) were extracted from public databases. Multivariable linear regression with stepwise selection was used to quantify the association between a patient's preoperative GPH score and sociodemographic variables. RESULTS: Black patients presented with 1 to 3 point higher VAS pain scores (7-8 vs. 5-6) and lower (worse) GPH scores (6.5-10 vs. 11-12) than White patients (P < 0.05 for all comparisons); similarly, lower SES patients presented with 1.5 points greater pain (P < 0.0001) and 3.5 points lower GPH (P < 0.0001) than high SES patients. Patients with lowest-quartile presenting GPH scores reported 36.8% and 37.5% lower (worse) POD-90 GMH and GPH scores than the highest quartile, respectively (GMH: 12 vs. 19, P < 0.0001; GPH: 15 vs. 24, P < 0.0001); this trend extended to 12 months (GMH: 19.5 vs. 29.5, P < 0.0001; GPH: 22 vs. 30, P < 0.0001). Reduced access to primary care (B = -1.616, P < 0.0001) and low SES (B = -1.504, P = 0.001), proxied by median household value, were independent predictors of worse presenting GPH scores. CONCLUSION: Racial and socioeconomic disparities in patients' preoperative physical and mental health at presentation for spine surgery are associated adversely with postoperative outcomes. Renewed focus on structural factors influencing preoperative presentation, including timeliness of care, is essential.Level of Evidence: 3.

Natural language processing methods are sensitive to sub-clinical linguistic differences in schizophrenia spectrum disorders.

Computerized natural language processing (NLP) allows for objective and sensitive detection of speech disturbance, a hallmark of schizophrenia spectrum disorders (SSD). We explored several methods for characterizing speech changes in SSD (n = 20) compared to healthy control (HC) participants (n = 11) and approached linguistic phenotyping on three levels: individual words, parts-of-speech (POS), and sentence-level coherence. NLP features were compared with a clinical gold standard, the Scale for the Assessment of Thought, Language and Communication (TLC). We utilized Bidirectional Encoder Representations from Transformers (BERT), a state-of-the-art embedding algorithm incorporating bidirectional context. Through the POS approach, we found that SSD used more pronouns but fewer adverbs, adjectives, and determiners (e.g., "the," "a,"). Analysis of individual word usage was notable for more frequent use of first-person singular pronouns among individuals with SSD and first-person plural pronouns among HC. There was a striking increase in incomplete words among SSD. Sentence-level analysis using BERT reflected increased tangentiality among SSD with greater sentence embedding distances. The SSD sample had low speech disturbance on average and there was no difference in group means for TLC scores. However, NLP measures of language disturbance appear to be sensitive to these subclinical differences and showed greater ability to discriminate between HC and SSD than a model based on clinical ratings alone. These intriguing exploratory results from a small sample prompt further inquiry into NLP methods for characterizing language disturbance in SSD and suggest that NLP measures may yield clinically relevant and informative biomarkers.

Systematic review of racial disparities in clozapine prescribing.

OBJECTIVE: To conduct a systematic review of published evidence on clozapine prescribing disparities across racial and ethnic categories, estimate the size of these disparities, and assess possible causes to inform future monitoring and intervention. METHODS: Electronic databases (MEDLINE, Embase, PsycINFO, Web of Science) were searched for directly relevant studies. Three independent reviewers selected studies: (1) of US samples; (2) directly addressed ethnic and/or racial disparities in prescribing of antipsychotic medications; (3) identified specific ethnic and/or racial groups (e.g. White, Blacks, Hispanics, non-Hispanic etc.); (4) reported clozapine prescription rates and (5) reported relevant covariates (i.e. gender, age, co-morbidities etc.). FINDINGS: 16 studies met our eligibility criteria. All studies reported clozapine underutilization in ethnic and racial minority patients when compared to their white counterparts. These findings remained consistent despite different time periods, designs, data set types, and after controlling for relevant covariates such as: length of hospital stay, institutional setting, and disease severity. CONCLUSION: The reasons for underutilization of clozapine in minority patients remain unclear. Various contributors can be categorized as: clinician-related factors (e.g. prescriber lack of experience), patient-related factors (e.g. distrust or suspicion of clinician), and institution-related factors (e.g. state operated facilities). Direct examination of these factors can help inform efforts to reduce clozapine prescription disparities.

Differential Effects of Antiretroviral Drugs on Neurons In Vitro: Roles for Oxidative Stress and Integrated Stress Response.

Mounting evidence suggests that antiretroviral drugs may contribute to the persistence of HIV-associated neurocognitive disorders (HAND), which impact 30%-50% of HIV-infected patients in the post-antiretroviral era. We previously reported that two first generation HIV protease inhibitors, ritonavir and saquinavir, induced oxidative stress, with subsequent neuronal death in vitro, which was reversed by augmentation of the endogenous antioxidant response by monomethyl fumarate. We herein determined whether two newer-generation PIs, darunavir and lopinavir, were deleterious to neurons in vitro. Further, we expanded our assessment to include three integrase strand transfer inhibitors, raltegravir, dolutegravir, and elvitegravir. We found that only lopinavir and elvitegravir were neurotoxic to primary rat neuroglial cultures as determined by the loss of microtubule-associated protein 2 (MAP2). Intriguingly, lopinavir but not elvitegravir led to oxidative stress and induced the endogenous antioxidant response (EAR). Furthermore, neurotoxicity of lopinavir was blocked by pharmacological augmentation of the endogenous antioxidant heme oxygenase-1 (HO-1), expanding our previous finding that protease inhibitor-induced neurotoxicity was mediated by oxidative stress. Conversely, elvitegravir but not lopinavir led to increased eIF2α phosphorylation, indicating the activation of a common adaptive pathway termed the integrated stress response (ISR), and elvitegravir-mediated neurotoxicity was partially alleviated by the ISR inhibitor trans-ISRIB, suggesting ISR as a promoter of elvitegravir-associated neurotoxicity. Overall, we found that neurotoxicity was induced only by a subset of protease inhibitors and integrase strand transfer inhibitors, providing evidence for class- and drug-specific neurotoxic effects of antiretroviral drugs. Future in vivo studies will be critical to confirm the neurotoxicity profiles of these drugs for incorporation of these findings into patient management. The EAR and ISR pathways are potential access points for the development of adjunctive therapies to complement antiretroviral therapies and limit their contribution to HAND persistence.