Lessons from a Pilot Study of a Culturally Tailored Financial Well-Being Intervention Among Latino Family Caregivers.

TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT05292248).

The clinical and genetic spectrum of paediatric speech and language disorders.

Speech and language disorders are known to have a substantial genetic contribution. Although frequently examined as components of other conditions, research on the genetic basis of linguistic differences as separate phenotypic subgroups has been limited so far. Here, we performed an in-depth characterization of speech and language disorders in 52 143 individuals, reconstructing clinical histories using a large-scale data-mining approach of the electronic medical records from an entire large paediatric healthcare network. The reported frequency of these disorders was the highest between 2 and 5 years old and spanned a spectrum of 26 broad speech and language diagnoses. We used natural language processing to assess the degree to which clinical diagnoses in full-text notes were reflected in ICD-10 diagnosis codes. We found that aphasia and speech apraxia could be retrieved easily through ICD-10 diagnosis codes, whereas stuttering as a speech phenotype was coded in only 12% of individuals through appropriate ICD-10 codes. We found significant comorbidity of speech and language disorders in neurodevelopmental conditions (30.31%) and, to a lesser degree, with epilepsies (6.07%) and movement disorders (2.05%). The most common genetic disorders retrievable in our analysis of electronic medical records were STXBP1 (n = 21), PTEN (n = 20) and CACNA1A (n = 18). When assessing associations of genetic diagnoses with specific linguistic phenotypes, we observed associations of STXBP1 and aphasia (P = 8.57 × 10-7, 95% confidence interval = 18.62-130.39) and MYO7A with speech and language development delay attributable to hearing loss (P = 1.24 × 10-5, 95% confidence interval = 17.46-infinity). Finally, in a sub-cohort of 726 individuals with whole-exome sequencing data, we identified an enrichment of rare variants in neuronal receptor pathways, in addition to associations of UQCRC1 and KIF17 with expressive aphasia, MROH8 and BCHE with poor speech, and USP37, SLC22A9 and UMODL1 with aphasia. In summary, our study outlines the landscape of paediatric speech and language disorders, confirming the phenotypic complexity of linguistic traits and novel genotype-phenotype associations. Subgroups of paediatric speech and language disorders differ significantly with respect to the composition of monogenic aetiologies.

Quantitative EEG Spectral Features Differentiate Genetic Epilepsies and Predict Neurologic Outcomes.

EEG plays an integral part in the diagnosis and management of children with genetic epilepsies. Nevertheless, how quantitative EEG features differ between genetic epilepsies and neurological outcomes remains largely unknown. Here, we aimed to identify quantitative EEG biomarkers in children with epilepsy and a genetic diagnosis in STXBP1, SCN1A, or SYNGAP1, and to assess how quantitative EEG features associate with neurological outcomes in genetic epilepsies more broadly. We analyzed individuals with pathogenic variants in STXBP1 (95 EEGs, n=20), SCN1A (154 EEGs, n=68), and SYNGAP1 (46 EEGs, n=21) and a control cohort of individuals without epilepsy or known cerebral disease (847 EEGs, n=806). After removing artifacts and epochs with excess noise or altered state from EEGs, we extracted spectral features. We validated our preprocessing pipeline by comparing automatically-detected posterior dominant rhythm (PDR) to annotations from clinical EEG reports. Next, as a coarse measure of pathological slowing, we compared the alpha-delta bandpower ratio between controls and the different genetic epilepsies. We then trained random forest models to predict a diagnosis of STXBP1, SCN1A, and SYNGAP1. Finally, to understand how EEG features vary with neurological outcomes, we trained random forest models to predict seizure frequency and motor function. There was strong agreement between the automatically-calculated PDR and clinical EEG reports (R 2=0.75). Individuals with STXBP1-related epilepsy have a significantly lower alpha-delta ratio than controls (P<0.001) across all age groups. Additionally, individuals with a missense variant in STXBP1 have a significantly lower alpha-delta ratio than those with a protein-truncating variant in toddlers (P<0.001), children (P=0.02), and adults (P<0.001). Models accurately predicted a diagnosis of STXBP1 (AUC=0.91), SYNGAP1 (AUC=0.82), and SCN1A (AUC=0.86) against controls and from each other in a three-class model (accuracy=0.74). From these models, we isolated highly correlated biomarkers for these respective genetic disorders, including alpha-theta ratio in frontal, occipital, and parietal electrodes with STXBP1, SYNGAP1, and SCN1A, respectively. Models were unable to predict seizure frequency (AUC=0.53). Random forest models predicted motor scores significantly better than age-based null models (P<0.001), suggesting spectral features contain information pertinent to gross motor function. In summary, we demonstrate that STXBP1-, SYNGAP1-, and SCN1A-related epilepsies have distinct quantitative EEG signatures. Furthermore, EEG spectral features are predictive of some functional outcome measures in patients with genetic epilepsies. Large-scale retrospective quantitative analysis of clinical EEG has the potential to discover novel biomarkers and to quantify and track individuals' disease progression across development.

Neurosarcoidosis complicated by systemic vasculitis.

A 62-year-old woman with medical history of hypertension, diabetes mellitus, coronaropathy, neurosarcoidosis, s/p craniotomy (brain mass resection) presented with worsening headaches, generalized weakness, vomiting, and hyporexia over two weeks. Brain MRI showed worsening of the known right cavernous sinus mass, vasculitis panel was negative. Patient received IV steroids; during hospitalization, she had a syncopal episode, CT Head was normal, EKG showed new T-wave inversion with troponin elevation. She experienced worsening mentation, left-sided hemiparesis; CT head showed acute hypodensity in the right MCA territory, CTA revealed bilateral distal M1 segment stenosis. Ineligible for thrombolysis/thrombectomy, she was started on aspirin. Echocardiograms were normal. Ischemic signs in her right toes prompted an aortogram showing arterial obstructions in the RLE, necessitating SFA stent placement, and clopidogrel. IV cyclophosphamide was added without additional vascular complications. This case illustrates neurosarcoidosis complicated by systemic vasculitis of medium-large vessels, responding to aggressive immunosuppression with glucocorticoids and cytotoxic agents.

NeuroRoots, a bio-inspired, seamless brain machine interface for long-term recording in delicate brain regions.

Scalable electronic brain implants with long-term stability and low biological perturbation are crucial technologies for high-quality brain-machine interfaces that can seamlessly access delicate and hard-to-reach regions of the brain. Here, we created "NeuroRoots," a biomimetic multi-channel implant with similar dimensions (7 µm wide and 1.5 µm thick), mechanical compliance, and spatial distribution as axons in the brain. Unlike planar shank implants, these devices consist of a number of individual electrode "roots," each tendril independent from the other. A simple microscale delivery approach based on commercially available apparatus minimally perturbs existing neural architectures during surgery. NeuroRoots enables high density single unit recording from the cerebellum in vitro and in vivo. NeuroRoots also reliably recorded action potentials in various brain regions for at least 7 weeks during behavioral experiments in freely-moving rats, without adjustment of electrode position. This minimally invasive axon-like implant design is an important step toward improving the integration and stability of brain-machine interfacing.

The role of personal recovery and internalised stigma on the expression of symptomatology in severe mental disorders: Mediating and moderating effects.

OBJECTIVE: Given the relevance of internalised stigma in people suffering from a mental disorder, in the present study, the possible mediating and moderating role of self-stigma in the relationship between personal recovery and symptomatology has been studied. METHOD: 265 participants with severe mental disorder completed the following instruments: ISMI (self-stigma), REE (personal recovery) and HoNOS, CGI, GAF and EuroQol (symptomatology). RESULTS: both the mediation and moderation analyses show significant results, which would indicate that internalised stigma has an effect on the relationship between personal recovery and symptomatology. Also, people with lower level of personal recovery and greater self-stigma have greater symptomatology than those who are in more advanced personal recovery processes and have a lower perception of internalised stigma. DISCUSSION: the findings of this study suggest that self-stigma has an effect, and the improvement at personal recovery and symptomatology is accentuated when people with a severe mental disorder have a better management of internalised stigma. Therefore, it may be interesting to include this variable in recovery interventions.

Clinical signatures of genetic epilepsies precede diagnosis in electronic medical records of 32,000 individuals.

PURPOSE: An early genetic diagnosis can guide the time-sensitive treatment of individuals with genetic epilepsies. However, most genetic diagnoses occur long after disease onset. We aimed to identify early clinical features suggestive of genetic diagnoses in individuals with epilepsy through large-scale analysis of full-text electronic medical records. METHODS: We extracted 89 million time-stamped standardized clinical annotations using Natural Language Processing from 4,572,783 clinical notes from 32,112 individuals with childhood epilepsy, including 1925 individuals with known or presumed genetic epilepsies. We applied these features to train random forest models to predict SCN1A-related disorders and any genetic diagnosis. RESULTS: We identified 47,774 age-dependent associations of clinical features with genetic etiologies a median of 3.6 years before molecular diagnosis. Across all 710 genetic etiologies identified in our cohort, neurodevelopmental differences between 6 to 9 months increased the likelihood of a later molecular diagnosis 5-fold (P < .0001, 95% CI = 3.55-7.42). A later diagnosis of SCN1A-related disorders (area under the curve [AUC] = 0.91) or an overall positive genetic diagnosis (AUC = 0.82) could be reliably predicted using random forest models. CONCLUSION: Clinical features predictive of genetic epilepsies precede molecular diagnoses by up to several years in conditions with known precision treatments. An earlier diagnosis facilitated by automated electronic medical records analysis has the potential for earlier targeted therapeutic strategies in the genetic epilepsies.

The clinical and genetic spectrum of paediatric speech and language disorders in 52,143 individuals.

Speech and language disorders are known to have a substantial genetic contribution. Although frequently examined as components of other conditions, research on the genetic basis of linguistic differences as separate phenotypic subgroups has been limited so far. Here, we performed an in-depth characterization of speech and language disorders in 52,143 individuals, reconstructing clinical histories using a large-scale data mining approach of the Electronic Medical Records (EMR) from an entire large paediatric healthcare network. The reported frequency of these disorders was the highest between 2 and 5 years old and spanned a spectrum of twenty-six broad speech and language diagnoses. We used Natural Language Processing to assess to which degree clinical diagnosis in full-text notes were reflected in ICD-10 diagnosis codes. We found that aphasia and speech apraxia could be easily retrieved through ICD-10 diagnosis codes, while stuttering as a speech phenotype was only coded in 12% of individuals through appropriate ICD-10 codes. We found significant comorbidity of speech and language disorders in neurodevelopmental conditions (30.31%) and to a lesser degree with epilepsies (6.07%) and movement disorders (2.05%). The most common genetic disorders retrievable in our EMR analysis were STXBP1 (n=21), PTEN (n=20), and CACNA1A (n=18). When assessing associations of genetic diagnoses with specific linguistic phenotypes, we observed associations of STXBP1 and aphasia (P=8.57 × 10-7, CI=18.62-130.39) and MYO7A with speech and language development delay due to hearing loss (P=1.24 × 10-5, CI=17.46-Inf). Finally, in a sub-cohort of 726 individuals with whole exome sequencing data, we identified an enrichment of rare variants in synaptic protein and neuronal receptor pathways and associations of UQCRC1 with expressive aphasia and WASHC4 with abnormality of speech or vocalization. In summary, our study outlines the landscape of paediatric speech and language disorders, confirming the phenotypic complexity of linguistic traits and novel genotype-phenotype associations. Subgroups of paediatric speech and language disorders differ significantly with respect to the composition of monogenic aetiologies.

Prevalence of sexually risky behaviors among Mexican medical students.

University students are at high risk of sexually transmitted infections due to the lack of adequate sexual education, as well as multiple associated factors, which lead to risky sexual practices. It is important to update data about sexual behaviors to identify the main factors associated with sexually risky behaviors. The present study aimed to evaluate the current prevalence of sexually risky practices in medical students. A cross-sectional study was conducted among medical students through an anonymous self-administered online questionnaire including demographic characteristics and sexual behaviors. We used descriptive statistics and multivariable regression to analyze the data collected. A total of 1520 undergraduate medical students aged between 18 and 28 years old were included in the study. Sixty percent of the students were sexually active with a higher proportion in men (70%), likewise, they had an earlier sexual debut (16.5 vs 16.9 years old), and a greater number of lifetime sexual partners than women (3.8 vs 2.2). The main sexual activity in both groups was vaginal sex with high use of condoms (75%), however, most of them (67%) reported having unprotected oral sex. Logistic regression analysis showed that condomless sex was associated with having oral sex, anal sex, and being female. The findings of this study showed that medical university students are involved in risky sexual behaviors, the major risk factor was unprotected oral sex. Based on these results, we recommended designing interventions to improve sexual education and preventive approaches from early stages such as in middle school students to mitigate sexually transmitted infections among medical university students.

Diagnostic Yield of CSF Testing in Infants for Disorders of Biogenic Amine Neurotransmitter Metabolism.

BACKGROUND AND OBJECTIVES: Biochemical testing of CSF for neurotransmitter metabolites and their cofactors is often used in the diagnostic evaluation of infants with neurologic disorders but requires an invasive, labor-intensive procedure with many potential sources of error. Our aim was to determine the diagnostic yield of CSF testing for biogenic amines (serotonin, norepinephrine, epinephrine, and dopamine) and their cofactors in identifying inborn errors of neurotransmitter metabolism among infants. METHODS: We evaluated all infants aged 1 year or younger who underwent CSF biogenic amine neurotransmitter (CSFNT) testing at Children's Hospital of Philadelphia (CHOP) and Boston Children's Hospital (BCH) between 2008 and 2017 in this cross-sectional study. The primary outcome was the proportion of individuals who received a diagnostic result from CSFNT testing. Secondary assessments included the proportion of infants who obtained a diagnostic result from other types of diagnostic testing. RESULTS: The cohort included 323 individuals (191 from CHOP and 232 from BCH). The median age at presentation was 110 days (range 36-193). The most common presenting features were seizures (71%), hypotonia (47%), and developmental delay (43%). The diagnostic yield of CSFNT testing was zero. When CSF pyridoxal-5-phosphate level was assayed with CSFNT testing, 1 patient had a diagnostic result. An etiologic diagnosis was identified in 163 patients (50%) of the cohort, with genetic testing having the highest yield (120 individuals, 37%). DISCUSSION: Our findings support the case for deimplementation of CSFNT testing as a standard diagnostic test of etiology in infants aged 1 year or younger presenting with neurologic disorders.

Parahippocampal neurons encode task-relevant information for goal-directed navigation.

A behavioral strategy crucial to survival is directed navigation to a goal, such as a food or home location. One potential neural substrate for supporting goal-directed navigation is the parahippocampus, which contains neurons that represent an animal's position, orientation, and movement through the world, and that change their firing activity to encode behaviorally relevant variables such as reward. However, little prior work on the parahippocampus has considered how neurons encode variables during goal-directed navigation in environments that dynamically change. Here, we recorded single units from rat parahippocampal cortex while subjects performed a goal-directed task. The maze dynamically changed goal-locations via a visual cue on a trial-to-trial basis, requiring subjects to use cue-location associations to receive reward. We observed a mismatch-like signal, with elevated neural activity on incorrect trials, leading to rate-remapping. The strength of this remapping correlated with task performance. Recordings during open-field foraging allowed us to functionally define navigational coding for a subset of the neurons recorded in the maze. This approach revealed that head-direction coding units remapped more than other functional-defined units. Taken together, this work thus raises the possibility that during goal-directed navigation, parahippocampal neurons encode error information reflective of an animal's behavioral performance.

Novel anti-psoriasis agent-associated cardiotoxicity, analysis of the FDA adverse event reporting system (FAERS).

INTRODUCTION: Psoriasis is a chronic skin condition characterized by hyperproliferation of epidermal keratinocytes, resulting in erythematous and scaling lesions. The US Food and Drug Administration (FDA) has approved nine biologic agents to address the burden of psoriasis, but their cardiovascular risks remain poorly studied. METHODS: This retrospective pharmacovigilance study utilized the FDA Adverse Event Reporting System (FAERS) database to analyze adverse events associated with newly approved therapeutic agents for psoriasis. We employed disproportionally signal analysis, calculating the reporting odds ratio (ROR) with a 95% confidence interval. RESULTS: Among the vast FAERS database, which contained >25 million adverse events, a total of 334,399 events were associated with newly approved therapeutic agents for psoriasis. Cardiac adverse events accounted for 3852 cases, including pericarditis, atrial fibrillation, and coronary artery disease. Secukinumab had the highest number of reported adverse events, followed by brodalumab, while tildrakizumab had the lowest. Coronary artery disease was the most reported adverse event (1438 cases), followed by pericarditis (572 cases) and atrial fibrillation (384 cases). Secukinumab had the highest incidence of coronary artery disease, pericarditis, and atrial fibrillation. Risankizumab was significantly associated with an increased risk of coronary artery disease and atrial fibrillation, while tildrakizumab and Ixekizumab were associated with atrial fibrillation. Secukinumab was associated with an elevated risk of pericarditis. CONCLUSIONS: The study uncovers the cardiovascular adverse effects related to biologic agents used in psoriasis treatment. These findings emphasize the importance of monitoring and evaluating the cardiovascular safety profiles of biological agents used in psoriasis treatment.

Metabolomic and Immunologic Discriminators of MIS-C at Emergency Room Presentation.

Multisystem Inflammatory Syndrome in Childhood (MIS-C) follows SARS-CoV-2 infection and frequently leads to intensive care unit admission. The inability to rapidly discriminate MIS-C from similar febrile illnesses delays treatment and leads to misdiagnosis. To identify diagnostic discriminators at the time of emergency department presentation, we enrolled 104 children who met MIS-C screening criteria, 14 of whom were eventually diagnosed with MIS-C. Before treatment, we collected breath samples for volatiles and peripheral blood for measurement of plasma proteins and immune cell features. Clinical and laboratory features were used as inputs for a machine learning model to determine diagnostic importance. MIS-C was associated with significant changes in breath volatile organic compound (VOC) composition as well as increased plasma levels of secretory phospholipase A2 (PLA2G2A) and lipopolysaccharide binding protein (LBP). In an integrated model of all analytes, the proportion of TCRVß21.3+ non-naive CD4 T cells expressing Ki-67 had a high sensitivity and specificity for MIS-C, with diagnostic accuracy further enhanced by low sodium and high PLA2G2A. We anticipate that accurate diagnosis will become increasingly difficult as MIS-C becomes less common. Clinical validation and application of this diagnostic model may improve outcomes in children presenting with multisystem febrile illnesses.

"I Lay Awake at Night": Latino Family Caregivers' Experiences Covering Out-of-Pocket Costs When Caring for Someone Living With Dementia.

BACKGROUND AND OBJECTIVES: The financial burden of caregiving has received less research attention than physical and emotional costs. This is especially true for underserved ethnic minorities. Financial strain affects mental and physical health and is unequally distributed across caregivers of different races and ethnicities. Although caregivers overall spend, on average, one quarter of their income on caregiving, Latino caregivers, the focus of this study, spend nearly half. RESEARCH DESIGN AND METHODS: To better understand this disparity, we conducted 11 qualitative interviews with 14 Latino caregivers of persons living with dementia located in either California or Texas. Interview transcripts were thematically coded, guided by a material-psychosocial-behavioral conceptual model of financial strain. RESULTS: We identified 3 themes: daily needs and costs, psychological distress caused by financial issues, and stressful barriers to accessing family and societal support. Furthermore, interviews revealed how Latino culture may influence spending patterns and management of costs. Findings suggest that preference by Latino families to care for a family member in the home may be met with a financial disadvantage due to the high out-of-pocket costs of care. DISCUSSION AND IMPLICATIONS: A better understanding of the factors contributing to high costs for Latino caregivers and how these costs affect caregivers will inform approaches at both the individual and policy levels and develop culturally relevant interventions to help Latino families to lower caregiving costs. This is especially important as the number of Latinos living with dementia is expected to increase over the next 4 decades and effective interventions are lacking.

Glutamato monosódico y suprasistema neuroendocrinoinmune murino

Introducción: El glutamato monosódico se emplea en humanos desde el pasado siglo como potenciador del sabor. Su inoculación parenteral en murinos durante el período neonatal causa lesiones en varios núcleos hipotalámicos. Objetivo: Describir los efectos del glutamato monosódico sobre el sistema neuroendocrinoinmune en murinos. Metodos: Se realizó una revisión de artículos de libre acceso en las bases de datos PubMed y SciELO entre enero de 2013 y julio de 2020. También se examinó el texto básico de la asignatura Sangre y Sistema Inmune de la carrera de medicina. Desarrollo: Con independencia de su efecto adictivo, varios estudios defienden la inocuidad del glutamato monosódico. Sin embargo, este compuesto puede atravesar la barrera hematoencefálica de neonatos de murinos, y ocasionar trastornos metabólicos, reproductivos y del sistema inmune. Conclusiones: El glutamato monosódico en roedores causa alteraciones en los órganos que integran el suprasistema neuroendocrinoinmune y, por tanto, afecta sus funciones homeostáticas. Los mecanismos patogénicos no se conocen con exactitud.

Introduction: Monosodium glutamate has been used in humans since the last century as a flavor enhancer. Its parenteral inoculation in murine during the neonatal period causes lesions in several hypothalamic nuclei. Objective: To describe the effects of monosodium glutamate on the neuroendocrine immune system in murine samples. Methods: A review of open access articles in the PubMed and SciELO databases was conducted between January 2013 and July 2020. The basic text of the Blood and Immune System course of the medical school was also reviewed. Development: Regardless of its addictive effect, several studies defend the safety of monosodium glutamate. However, this compound can cross the blood-brain barrier of murine neonates, causing metabolic, reproductive and immune system disorders. Conclusions: Monosodium glutamate in rodents causes alterations in the organs that make up the neuroendocrine-immune suprasystem and, therefore, affects their homeostatic functions. The pathogenic mechanisms are not known exactly.

Emergence and inversion of chirality in hierarchical assemblies of CdS nanocrystal fibers.

Arranging semiconducting nanocrystals into ordered superstructures is a promising platform to study fundamental light-matter interactions and develop programmable optical metamaterials. We investigated how the geometrical arrangement of CdS nanocrystals in hierarchical assemblies affects chiroptical properties. To create these structures, we controlled the evaporation of a colloidal CdS nanocrystal solution between two parallel plates. We combined in situ microscopy and computational modeling to establish a formation mechanism involving the shear-induced alignment of nanocrystal fibers and the subsequent mechanical relaxation of the stretched fibers to form Raman noodle-type band textures. The high linear anisotropy in these films shares many similarities with cholesteric liquid crystals. The films deposited on top and bottom surfaces exhibit opposite chirality. The mechanistic insights from this study are consequential to enable future advances in the design and fabrication of programmable optical metamaterials for further development of polarization-based optics toward applications in sensing, hyperspectral imaging, and quantum information technology.

Driving Skills at Licensure and Time to First Crash.

BACKGROUND AND OBJECTIVES: Young drivers are overrepresented in crashes, and newly licensed drivers are at high risk, particularly in the months immediately post-licensure. Using a virtual driving assessment (VDA) implemented in the licensing workflow in Ohio, this study examined how driving skills measured at the time of licensure contribute to crash risk post-licensure in newly licensed young drivers. METHODS: This study examined 16 914 young drivers (<25 years of age) in Ohio who completed the VDA at the time of licensure and their subsequent police-reported crash records. By using the outcome of time to first crash, a Cox proportional hazard model was used to estimate the risk of a crash during the follow-up period as a function of VDA Driving Class (and Skill Cluster) membership. RESULTS: The best performing No Issues Driving Class had a crash risk 10% lower than average (95% confidence interval [CI] 13% to 6%), whereas the Major Issues with Dangerous Behavior Class had a crash risk 11% higher than average (95% CI 1% to 22%). These results withstood adjusting for covariates (age, sex, and tract-level socioeconomic status indicators). At the same time, drivers licensed at age 18 had a crash risk 16% higher than average (95% CI 6% to 27%). CONCLUSIONS: This population-level study reveals that driving skills measured at the time of licensure are a predictor of crashes early in licensure, paving the way for better prediction models and targeted, personalized interventions. The authors of future studies should explore time- and exposure-varying risks.

A Comparison of Ketamine and Midazolam as First-Line Anesthetic Infusions for Pediatric Status Epilepticus.

BACKGROUND: Pediatric refractory status epilepticus (RSE) often requires management with anesthetic infusions, but few data compare first-line anesthetics. This study aimed to compare the efficacy and adverse effects of midazolam and ketamine infusions as first-line anesthetics for pediatric RSE. METHODS: Retrospective single-center study of consecutive study participants treated with ketamine or midazolam as the first-line anesthetic infusions for RSE at a quaternary care children's hospital from December 1, 2017, until September 15, 2021. RESULTS: We identified 117 study participants (28 neonates), including 79 (68%) who received midazolam and 38 (32%) who received ketamine as the first-line anesthetic infusions. Seizures terminated more often in study participants administered ketamine (61%, 23/38) than midazolam (28%, 22/79; odds ratio [OR] 3.97, 95% confidence interval [CI] 1.76-8.98; P < 0.01). Adverse effects occurred more often in study participants administered midazolam (24%, 20/79) than ketamine (3%, 1/38; OR 12.54, 95% CI 1.61-97.43; P = 0.016). Study participants administered ketamine were younger, ketamine was used more often for children with acute symptomatic seizures, and midazolam was used more often for children with epilepsy. Multivariable logistic regression of seizure termination by first-line anesthetic infusion (ketamine or midazolam) including age at SE onset, SE etiology category, and individual seizure duration at anesthetic infusion initiation indicated seizures were more likely to terminate following ketamine than midazolam (OR 4.00, 95% CI 1.69-9.49; P = 0.002) and adverse effects were more likely following midazolam than ketamine (OR 13.41, 95% CI 1.61-111.04; P = 0.016). Survival to discharge was higher among study participants who received midazolam (82%, 65/79) than ketamine (55%, 21/38; P = 0.002), although treating clinicians did not attribute any deaths to ketamine or midazolam. CONCLUSIONS: Among children and neonates with RSE, ketamine was more often followed by seizure termination and less often associated with adverse effects than midazolam when administered as the first-line anesthetic infusion. Further prospective data are needed to compare first-line anesthetics for RSE.

Qualitative Evaluation of Family Caregivers' Experiences Participating in Knowledge and Interpersonal Skills to Develop Exemplary Relationships (KINDER): Web-Based Intervention to Improve Relationship Quality.

BACKGROUND: The onset of Alzheimer disease and related dementias (AD/ADRD) can alter relationships between family caregivers and persons living with AD/ADRD, such as through the occurrence of distressful behavioral and psychological symptoms of dementia. Poorly perceived relationship quality by caregivers contributes to negative outcomes for both care partners, such as low-quality caregiving and potential mistreatment of older adults. Knowledge and Interpersonal Skills to Develop Exemplary Relationships (KINDER) is a new, web-based, asynchronous psychoeducational intervention with content informed by focus groups with family caregivers. The program was developed to prevent low-quality caregiving and potential mistreatment of older adults by focusing on building healthy caregiving relationships. OBJECTIVE: The purpose of this study is to describe caregivers' experiences participating in KINDER to understand intervention acceptability. Of particular interest was learning how comfortable caregivers were viewing content addressing potential mistreatment, as well as whether asynchronous delivery created any barriers to participating in the intervention. Findings will inform future program refinements before efficacy testing. METHODS: Although 23 caregivers enrolled in the KINDER parent study, only 7 of them completed the 8-week intervention. In-depth, semistructured qualitative interviews were conducted with all participants who completed the program to understand their experiences while attending KINDER and to decipher barriers to participation. We also asked participants about which program elements were most valuable and which were least valuable to them, as well as how the program could be improved. Interview transcripts were analyzed by 2 coders using thematic analysis. RESULTS: Our findings indicate that caregivers were overall satisfied with KINDER's focus and content. Participants particularly liked how KINDER materials felt authentic and relevant to supporting healthy care relationships (Theme 1). The program's multiple components were found to be valuable, especially story-based video vignettes and readings (Theme 2). Most caregivers were comfortable viewing depictions of mistreatment and understood the importance of this content (Theme 3). Notably, while caregivers appreciated the convenience of participating in an asynchronous web-based intervention, several expressed a desire for more opportunities to speak with other caregivers (Theme 4). Technology challenges, such as a lack of clarity about automated intervention activities, deterred completion. CONCLUSIONS: Findings from this study suggest an asynchronous web-based intervention covering sensitive topics such as mistreatment is acceptable for at least some AD/ADRD caregivers. Caregivers' comments that materials felt authentic may suggest that the integration of caregiver voices before intervention development enhanced the relevance of content. To make KINDER easier to deliver and participate in, the investigators plan to reduce the use of automation and integrate more group-based programming, as recommended by participants. Further, given the higher-than-expected dropout rate, in future studies, the investigators will collect data to determine the reasons for participants not completing study activities.