Barriers to Alzheimer Disease Clinical Trial Participation in a Minority Population.

BACKGROUND: Alzheimer disease (AD), the most common neurodegenerative disorder in the United States, disproportionately burdens minority populations. OBJECTIVE: To explore barriers to AD clinical trial participation by Asian and Native Hawaiian patients diagnosed with AD or mild cognitive impairment. METHOD: We surveyed 187 patients with a Mini-Mental State Examination score ≥14 between January 2022 and June 2022. The score cutoff for clinical trial eligibility was set by the institution. Individuals also completed a 15-question telephone survey that assessed demographics, barriers to clinical trial participation, and clinical trial improvement methods. RESULTS: Forty-nine patients responded, with a response rate of 26%. Asian and Native Hawaiian patients were less likely than White patients to participate in AD trials. The main barrier to participation was a lack of information about AD trials. Providing additional information regarding AD trials to patients and family members were listed as the top two reasons patients would consider participating in a clinical trial. CONCLUSION: Insufficient information about AD clinical trials is the primary barrier to participation among Asian and Native Hawaiian patients, followed by difficulty coordinating transportation and, in the case of Asians, the time required for clinical trials. Increased outreach, education, and assistance with logistics in these populations should be pursued to improve rates of participation in clinical trials.

A randomized phase 2b efficacy study in patients with seizure episodes with a predictable pattern using Staccato® alprazolam for rapid seizure termination.

OBJECTIVE: Alprazolam administered via the Staccato® breath-actuated device is delivered into the deep lung for rapid systemic exposure and is a potential therapy for rapid epileptic seizure termination (REST). We conducted an inpatient study (ENGAGE-E-001 [NCT03478982]) in patients with stereotypic seizure episodes with prolonged or repetitive seizures to determine whether Staccato alprazolam rapidly terminates seizures in a small observed population after administration under direct supervision. METHODS: Adult patients with established diagnosis of focal and/or generalized epilepsy with a documented history of seizure episodes with a predictable pattern were enrolled. They were randomized 1:1:1 to double-blind treatment of a single seizure event with one dose of Staccato alprazolam 1.0 mg or 2.0 mg, or Staccato placebo in an inpatient unit. The primary end point of the study was the proportion of responders in each treatment group achieving seizure activity cessation within 2 min after administration of study drug and no recurrence of seizure activity within 2 h. RESULTS: A total of 273 patients were screened, and 116 randomized patients received treatment with the study drug in the double-blind part. The proportion of treated patients who were responders was 65.8% for each of Staccato alprazolam 1.0 mg (n = 38; p = .0392) and 2.0 mg (n = 38; p = .0392), compared with 42.5% for Staccato placebo (n = 40). Staccato alprazolam was well tolerated when administered as a single dose of 1.0 or 2.0 mg: cough and somnolence were the most common adverse events (AEs) (both 14.5%), followed by dysgeusia (13.2%). AEs were mostly mild or moderate in intensity; there were no treatment-related serious AEs. SIGNIFICANCE: Both 1.0 mg and 2.0 mg doses of Staccato alprazolam demonstrated efficacy in rapidly terminating seizures in an inpatient setting and were well tolerated. The next step is a Phase 3 confirmatory study to demonstrate efficacy and safety of Staccato alprazolam for rapid cessation of seizures in an outpatient setting.

Use of second doses of Valtoco® (diazepam nasal spray) across 24 hours after the initial dose for out-of-hospital seizure clusters: Results from a phase 3, open-label, repeat-dose safety study.

OBJECTIVE: An exploratory analysis from a long-term, phase 3, open-label, repeat-dose safety study of diazepam nasal spray for acute treatment of seizure clusters assessed the use of a second dose up to 24 hours after the initial dose and effectiveness in potentially reducing the number of seizures. METHODS: Seizures and doses were recorded in diaries. RESULTS: Of 175 patients enrolled, 163 received ≥1 dose of diazepam nasal spray and were included in the safety population; those patients received a total of 4390 doses for a total of 3853 seizure clusters. Less than half of these patients used a second dose a least once during the study (79 patients [48.5%]), with a total of 485 second doses for seizure clusters (12.6% of all seizure clusters). Among these 79 patients, 33 (41.8%) used only one second dose during the study (range: 1-82). The proportion of seizure clusters treated with a second dose over time was consistently low across 24 h: 0-4 h, 152 (3.9%); 4-6 h, 72 (1.9%); 6-8 h, 39 (1.0%); 8-12 h, 55 (1.4%); 12-16 h, 42 (1.1%); 16-20 h, 42 (1.1%); 20-24 h, 83 (2.2%). Rates of treatment-emergent adverse events (TEAEs) and treatment-related TEAEs occurring within 1 day of a second dose were low (15.2% and 5.1%, respectively). SIGNIFICANCE: Patients with epilepsy may experience seizure clusters lasting up to 24 hours, and little is known about the effectiveness of rescue therapies for that duration. The current labeling of the US Food and Drug Administration (FDA)-approved outpatient treatments for seizure clusters (rectal diazepam, intranasal midazolam, and diazepam nasal spray) allows for a second dose, if needed, for control. These findings support the safety profile of second doses, and the low use supports the effectiveness of diazepam nasal spray across 24 hours.

Native Hawaiian and Other Pacific Islanders' Leading Risk Factors for Ischemic Stroke: A Comparative Ethnographic Study.

INTRODUCTION: Hawaii is a multicultural state with many different ethnicities, including Native Hawaiians and other Pacific Islanders (NHOPI). This demographic has not been thoroughly studied, despite its significantly higher prevalence of stroke. This study aimed to characterize risk factors for ischemic stroke in NHOPI compared to other ethnicities. METHODS: An Institutional Review Board (IRB) sanctioned retrospective chart review was conducted at a multi-site community neurology clinic from June 2017 through June 2019. Prospective patients were identified from the database using the International Classification of Diseases 10th Edition (ICD-10) codes for ischemic stroke. 326 patients (99 NHOPI, 116 Asian, 111 Caucasian) with a history of ischemic stroke met the inclusion criteria. Risk factors were determined based on the American Stroke Association guidelines; ethno-racial grouping was based on self-identification; and average household income levels were estimated based on patient zip codes US Census Bureau data. Continuous variable risk factors were analyzed using an analysis of variance (ANOVA) and post-hoc pairwise comparisons using Tukey-Kramer; a multivariate analysis was conducted. RESULTS: Compared to Asians and Caucasians, NHOPI patients were on average 11 years younger at the onset of stroke and more likely to be women. The NHOPI group also had the highest rates of diabetes and obesity. NHOPI average income was significantly lower compared to the Caucasian group. Hypertension and hyperlipidemia were found to be higher in the Asian population. Alcohol consumption was reported more frequently among Caucasian patients. CONCLUSIONS: These results better-characterized risk factors for ischemic stroke among NHOPI in Hawaii. The younger age of stroke onset in NHOPI patients is likely due to the higher burden of cardiovascular risk factors like obesity, smoking, and diabetes. Identifying such disparities in associated risk for NHOPI and other ethnicities can allow targeted stroke prevention and outpatient care in a multicultural setting.

Final results from a Phase 3, long-term, open-label, repeat-dose safety study of diazepam nasal spray for seizure clusters in patients with epilepsy.

OBJECTIVE: A Phase 3 open-label safety study (NCT02721069) evaluated long-term safety of diazepam nasal spray (Valtoco) in patients with epilepsy and frequent seizure clusters. METHODS: Patients were 6-65 years old with diagnosed epilepsy and seizure clusters despite stable antiseizure medications. The treatment period was 12 months, with study visits at Day 30 and every 60 days thereafter, after which patients could elect to continue. Doses were based on age and weight. Seizure and treatment information was recorded in diaries. Treatment-emergent adverse events (TEAEs), nasal irritation, and olfactory changes were recorded. RESULTS: Of 163 patients in the safety population, 117 (71.8%) completed the study. Duration of exposure was ≥12 months for 81.6% of patients. There was one death (sudden unexpected death in epilepsy) and one withdrawal owing to a TEAE (major depression), both considered unlikely to be related to treatment. Diazepam nasal spray was administered 4390 times for 3853 seizure clusters, with 485 clusters treated with a second dose within 24 h; 53.4% of patients had monthly average usage of one to two doses, 41.7% two to five doses, and 4.9% more than five doses. No serious TEAEs were considered to be treatment related. TEAEs possibly or probably related to treatment (n = 30) were most commonly nasal discomfort (6.1%); headache (2.5%); and dysgeusia, epistaxis, and somnolence (1.8% each). Only 13 patients (7.9%) showed nasal irritation, and there were no relevant olfactory changes. The safety profile of diazepam nasal spray was generally similar across subgroups based on age, monthly usage, concomitant benzodiazepine therapy, or seasonal allergy/rhinitis. SIGNIFICANCE: In this large open-label safety study, the safety profile of diazepam nasal spray was consistent with the established profile of rectal diazepam, and the high retention rate supports effectiveness in this population. A second dose was used in only 12.6% of seizure clusters.

Evaluation of diazepam nasal spray in patients with epilepsy concomitantly using maintenance benzodiazepines: An interim subgroup analysis from a phase 3, long-term, open-label safety study.

OBJECTIVE: Diazepam nasal spray (Valtoco), indicated for acute treatment of frequent seizure activity (seizure clusters) in patients with epilepsy ≥6 years of age, is designed to be a rapid, noninvasive, socially acceptable route of administration. This interim analysis evaluated the safety profile of diazepam nasal spray in patients with and without concomitant use of benzodiazepines, with use of a second dose for a seizure cluster as a proxy for effectiveness. METHODS: A long-term, phase 3, open-label safety study enrolled patients with epilepsy who had seizures despite a stable antiseizure medication regimen. RESULTS: Among 175 patients enrolled by October 31, 2019, a total of 158 were treated with diazepam nasal spray (aged 6-65 years; 53.8% female). Of those, 119 (75.3%) received concomitant benzodiazepines (60, chronic; 59, intermittent); 39 (24.7%) did not. Use of a second dose was similar in patients using chronic concomitant benzodiazepines (second dose in 11.1% [144/1299]) and those with no concomitant benzodiazepines (second dose in 10.3% [41/398]). Treatment emergent adverse events (TEAEs) occurred for 80.0% with chronic use of concomitant benzodiazepines and 61.5% without. Cardiorespiratory depression was not reported, and no serious TEAEs were treatment related. Study retention was high: 83.3% in the chronic benzodiazepine group and 76.9% in the no-benzodiazepine group. Findings were similar in a sub-analysis of patients who were (n = 44) or were not (n = 75) taking clobazam. SIGNIFICANCE: This analysis of patients from a long-term study shows a similar safety profile of diazepam nasal spray in patients with and without concomitant benzodiazepines, and consistent with the established profile for diazepam. Use of a single dose of diazepam nasal spray and high study retention rates suggest the effectiveness of diazepam nasal spray in patients irrespective of chronic daily benzodiazepine use. Results were similar in the clobazam sub-analysis. These results support the safety and effectiveness of diazepam nasal spray in patients with concomitant benzodiazepine use.

Early impact of the COVID-19 pandemic on outpatient migraine care in Hawaii: Results of a quality improvement survey.

OBJECTIVE: A survey was implemented for early assessment of pandemic-related practice processes and quality improvement (QI). BACKGROUND: In response to the public health measures in Hawaii to curtail the coronavirus 2019 pandemic, Hawaii Pacific Neuroscience (HPN) adapted their patient care to ensure continuity of neurological treatment. METHODS: The telephone survey was conducted on patients seen at HPN during the period of April 22, 2020-May 18, 2020 to address four areas related to patients' outpatient experience: delivery of care, general well-being, experience with telemedicine, and disease-specific questions. RESULTS: A total of 928 patients were contacted of which 429 (46.2%) patients responded and 367 (85.5%) agreed to participate. A total of 133 patients with migraine and 234 patients with other neurological conditions provided responses. Our migraine patients' survey responses suggest that their well-being was disproportionately negatively affected by the pandemic. Survey respondents with migraine were significantly more likely than their non-migraine peers to report worsening anxiety and sleep problems [62/132 (47.0%) vs. 78/234 (33.3%), χ2  = 6.64, p = 0.010, and 64/132 (48.5%) vs. 73/234 (31.2%), χ2  = 10.77, p = 0.001]; migraine patients also reported worsening of depression as a result of the pandemic more than patients with other diagnoses, though this was not statistically significant [44/132 (33.3%) vs. 57/234 (24.4%), χ2  = 3.40, p = 0.065]. In regard to access to healthcare, significantly more migraine patients reported running out of medications than those with other diagnoses [20/133 (15.0%) vs. 18/234 (7.7%), χ2  = 4.93, p = 0.026]. More avoided seeking medical help for new health problems because of the pandemic [30/133 (22.6%) vs. 30/234 (12.8%), χ2  = 5.88, p = 0.015]. Migraine patients were also significantly impacted economically by the pandemic; 43/132 (32.4%) of migraine patients reported losing their jobs as the result of the pandemic versus 34/234 (14.5%) of their peers (χ2  = 11.20, p < 0.001). An increase in headache severity or frequency was reported in 39/118 (33.1%) of respondents and 19/118 (16.1%) reported to using more abortive therapy than usual. Telemedicine was well received by almost all patients who took advantage of the option. Most of those patients found telemedicine to be easy to use and as valuable as an in-person visit. Migraine patients indicated with more frequency that without the telemedicine option, they would have missed their medical appointments [37/68 (54.4%) vs. 56/144 (38.6%), χ2  = 4.31, p = 0.038]; a majority would prefer or consider telemedicine for future appointments over in-person visits. CONCLUSIONS: Insights gained from this QI survey to the practice's new pandemic-related processes include stressing lifestyle modification, optimizing treatment plans, and continuing the option of telemedicine.

Lack of observed tolerance to diazepam nasal spray (Valtoco®) after long-term rescue therapy in patients with epilepsy: Interim results from a phase 3, open-label, repeat-dose safety study.

OBJECTIVE: Tolerance is a known consideration for maintenance use of benzodiazepines and other antiseizure drugs; however, clinical experience suggests that tolerance may not be anticipated with long-term intermittent use of benzodiazepines as rescue therapy. Diazepam nasal spray (Valtoco®) is a proprietary intranasal formulation approved for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) in patients with epilepsy aged ≥6 years. Reported here are exploratory analyses investigating whether there was evidence of development of tolerance in an interim analysis of a long-term, phase 3, open-label safety study of diazepam nasal spray. METHODS: Patients and care partners were trained to administer 5, 10, 15, or 20 mg of diazepam nasal spray (age- and weight-based dosing), with a second dose administered 4-12 hours later if needed. A series of analyses were performed to assess evidence of tolerance using 2 equal, adjacent time periods and data for each patient to compare the proportion of events for which second doses of diazepam nasal spray (as a proxy for effectiveness) were administered in period 1 compared with period 2. RESULTS: A total of 175 patients were enrolled at interim cutoff, and 158 were treated with diazepam nasal spray for 3370 seizure-cluster events. For 73.4% of patients, duration of exposure to diazepam nasal spray was ≥12 months. A total of 191 analyses were conducted; the proportion of analyses in which second doses in period 2 were lower than in period 1 was 72.8%. Only 5 analyses showed nominally statistically significant changes (P < 0.05); this is fewer than expected by chance, and these differences were not directionally consistent. There was no safety signal with continued use. CONCLUSIONS: These analyses found no statistical evidence of tolerance with the use of diazepam nasal spray over time based on use of a second dose in an initial period of the study compared with a subsequent period for each patient. These results are in agreement with prior studies of benzodiazepine rescue therapy.

Effectiveness of dual migraine therapy with CGRP inhibitors and onabotulinumtoxinA injections: case series.

AIMS: Clinical trials for calcitonin gene-related peptide (CGRP) inhibitors excluded the concomitant use of onabotulinumtoxinA; thus, there is a lack of efficacy and safety data of the combined therapies. Our study aims to examine the effectiveness of CGRP inhibitors with onabotulinumtoxinA by evaluating migraine reductions in headache days and severity. METHODS: Seventeen patients with chronic migraines were identified who had a partial or poor response to onabotulinumtoxinA, and were placed on dual therapy with a CGRP inhibitor. Patients' initial headache days and severity ratings were compared to final values taken 1-6 months after adding the CGRP inhibitor to their treatment regime. Comparisons between headache days and severity ratings prior to and during dual treatment were performed utilizing the Kruskal-Wallis test. The significance was set at p < 0.05. RESULTS: Of 17 patients (16F/1 M), n = 9 were taking fremanezumab, n = 4 were taking erenumab, and n = 4 were taking galcanezumab. Patients' average headache days per month was reduced from 27.6 ± 4.8 initially to 18.6 ± 9.4 post-treatment (p = 0.00651), and their average pain level was reduced from 8.4 ± 1.4 out of 10 to 5.4 ± 2.5 (p = 0.00074). No serious adverse side effects were reported from patients on dual therapy. CONCLUSION: Patients with suboptimal response to onabotulinumtoxinA may benefit from CGRP inhibitors' addition to their migraine regimens. Placebo-controlled randomized studies are advised to corroborate this finding.

Disparities in Alzheimer Disease and Mild Cognitive Impairment Among Native Hawaiians and Pacific Islanders.

BACKGROUND: Previous studies of racial differences in Alzheimer disease (AD) presentation have not included Native Hawaiians and Pacific Islanders (NHPI). OBJECTIVE: To explore the presentation of AD and mild cognitive impairment (MCI) in NHPI. METHOD: We conducted a retrospective review of patient records from Hawaii with a diagnosis of unspecified AD or MCI from September 2000 to September 2019. Variables of interest included age at diagnosis, gender, race, marital status, insurance, comorbidities, and scores on the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA). RESULTS: We reviewed the medical records of 598 patients, including 224 Asians, 202 Whites, 87 NHPI, and 85 Other. AD was more dominant than MCI across all of the groups, with the highest percentage in NHPI. Among the mean ages of diagnosis, NHPI were the youngest. Across all groups, a higher proportion of women than men had AD, with the highest female prevalence among NHPI. Hypertension, hyperlipidemia, and type II diabetes were highest among NHPI compared with the other groups. Of individuals with MMSE/MoCA scores, there were significant variations in scores by racial group. The mean MMSE/MoCA score was highest among Whites and lowest among NHPI. CONCLUSION: Compared with other racial groups, NHPI have a higher proportion of AD than MCI at diagnosis, are diagnosed at a younger age, have a higher female prevalence, have more comorbidities that may contribute to AD/MCI onset, and present with lower MMSE scores.

Presentation of psychogenic nonepileptic seizures in Hawaii's ethnoracially diverse population.

PURPOSE: This exploratory study compared the semiology of psychogenic nonepileptic seizures (PNES) between a diverse group of patients in the state of Hawaii. This study may expand understanding of PNES across different ethnocultural and gender groups. METHODS: A retrospective chart review of patients admitted to our Epilepsy Monitoring Unit (EMU) over a 4-year period was performed to compare semiology in different ethnic groups and gender. RESULTS: A total of 139 patients were included in this study, 37% (n = 51) with PNES, 34% (n = 47) with epilepsy only, and 29% (n = 41) with other non-PNES, nonepilepsy diagnosis. The number of Asians with PNES were found to differ when compared with the patients with epilepsy and the patients with non-PNES, nonepilepsy diagnosis. A positive trend was found in the number of Native Hawaiians and Caucasians with PNES in comparison with patients with non-PNES, nonepilepsy diagnosis. In addition, three semiology of PNES in Native Hawaiians were found to differ in comparison with other ethnic groups with PNES: rhythmic motor, mixed semiology, and nonepileptic aura. There is a significant difference in all motor manifestation between males and females in Native Hawaiians. Between patients with PNES, patients with epilepsy, and patients with non-PNES, nonepilepsy diagnosis, significant correlation was found in psychiatric disorders including posttraumatic stress disorder (PTSD), anxiety, and any psychiatric disorder. CONCLUSION: This cross-cultural study found significant differences in the expression of PNES across key ethnoracial groups for the Islands of Hawaii. These findings have implications to the diagnosis and treatment of PNES for Native Hawaiians and other Pacific Islanders in the United States.

Comparative prediction of nonepileptic events using MMPI-2 clinical scales, Harris Lingoes subscales, and restructured clinical scales.

The Minnesota Multiphasic Personality Inventory-2 (MMPI-2) is a psychological testing tool used to measure psychological and personality constructs. The MMPI-2 has proven helpful in identifying individuals with nonepileptic events/nonepileptic seizures. However, the MMPI-2 has had some updates that enhanced its original scales. The aim of this article was to test the utility of updated MMPI-2 scales in predicting the likelihood of non-epileptic seizures in individuals admitted to an EEG video monitoring unit. We compared sensitivity, specificity, and likelihood ratios of traditional MMPI-2 Clinical Scales against more homogenous MMPI-2 Harris-Lingoes subscales and the newer Restructured Clinical (RC) scales. Our results showed that the Restructured Scales did not show significant improvement over the original Clinical scales. However, one Harris-Lingoes subscale (HL4 of Clinical Scale 3) did show improved predictive utility over the original Clinical scales as well as over the newer Restructured Clinical scales. Our study suggests that the predictive utility of the MMPI-2 can be improved using already existing scales. This is particularly useful for those practitioners who are not invested in switching over to the newly developed MMPI-2 Restructured Form (MMPI-2 RF).

Diazepam nasal spray administration is effective to control seizure clusters irrespective of time of day.

Introduction: Neurologic circadian influences, including sleep/wake transitions, processes (e.g., hormonal variation), and behavioral patterns (e.g., consumption of food and oral medications), may affect seizure patterns. Specific circadian patterns of seizures have been reported depending on type, onset location, and severity; however, data on patterns for patients with seizure clusters and effectiveness of rescue therapy by time of day are limited. Methods: We conducted post hoc analyses using patient diary data from the phase 3 safety study of diazepam nasal spray, which is indicated for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. Patients were administered age- and weight-based doses; second doses could be administered if needed to control a seizure cluster. We assessed clock timing of seizure-cluster onset along with second-dose use as a proxy for effectiveness. Treatment-emergent adverse events were recorded. Results: Seizure-cluster onset was observed to be generally highest during mornings and late evenings and lowest in the early evening and middle of the night. Second-dose use was not consistently associated with a specific time of day. The safety profile was consistent with that expected from previous studies of diazepam nasal spray. Conclusion: These results suggest that diazepam nasal spray can be effectively administered at any time of day.

Exercise and Recovery Following Mild-to-Moderate Traumatic Brain Injury in the Community Setting.

Introduction The recommendations on return to exercise post-traumatic brain injury (TBI) remain debatable. As recent as 10 years ago, the conventional recovery modality for a mild TBI was to reduce neurostimulating activity and encourage rest until the symptoms subsided. However, emerging literature has challenged this notion, stating that returning to exercise early in the course of mild TBI recovery may be beneficial to the recovery timeline. This study surveys Hawaii's diverse population to identify trends in exercise and recovery for TBI patients to shape recommendations on return to exercise. Methods A single-center retrospective chart review of the patients with mild-to-moderate TBI was selected from a patient database at an outpatient neurology clinic between January 2020 and January 2022. The variables collected include demographics, the etiology of injury, and symptoms at diagnosis. Self-generated phone surveys were completed to evaluate exercise patterns post-TBI. Results The patients who recovered within two years displayed similar exercise patterns to the patients who took more than two years to recover. Exercise frequency, intensity, and duration did not differ significantly (p=0.75, p=0.51, and p=0.80, respectively; n=100). Hiking and walking were more common in the long recovery (LR) group (p=0.02), likely reflecting advanced age compared to the short recovery (SR) group (50 versus 39 years, p<0.01). Additionally, no correlation exists between exercise intensity and worsening symptoms (p=0.920), suggesting that the patients exhibit exercise patterns suitable for sub-symptomatic recovery. Conclusion Return to exercise does not appear to be a predictor for mild-to-moderate TBI recovery. The patients appear to self-regulate an exercise regimen that will not exacerbate their symptoms or recovery time; thus, it may be suitable to recommend return to exercise as tolerated. These, and other findings in the literature, suggest that patients should be encouraged to return to exercise shortly after a mild TBI so long as the exercise does not exacerbate their symptoms.

Racial/Ethnic Disparities in the Alzheimer's Disease Link with Cardio and Cerebrovascular Diseases, Based on Hawaii Medicare Data.

Background: There is an expanding body of literature implicating heart disease and stroke as risk factors for Alzheimer's disease (AD). Hawaii is one of the six majority-minority states in the United States and has significant racial health disparities. The Native-Hawaiians/Pacific-Islander (NHPI) population is well-known as a high-risk group for a variety of disease conditions. Objective: We explored the association of cardiovascular disease with AD development based on the Hawaii Medicare data, focusing on racial disparities. Methods: We utilized nine years of Hawaii Medicare data to identify subjects who developed heart failure (HF), ischemic heart disease (IHD), atrial fibrillation (AF), acute myocardial infarction (AMI), stroke, and progressed to AD, using multistate models. Propensity score-matched controls without cardiovascular disease were identified to compare the risk of AD after heart disease and stroke. Racial/Ethnic differences in progression to AD were evaluated, accounting for other risk factors. Results: We found increased risks of AD for AF, HF, IHD, and stroke. Socioeconomic (SE) status was found to be critical to AD risk. Among the low SE group, increased AD risks were found in NHPIs compared to Asians for all conditions selected and compared to whites for HF, IHD, and stroke. Interestingly, these observations were found reversed in the higher SE group, showing reduced AD risks for NHPIs compared to whites for AF, HF, and IHD, and to Asians for HF and IHD. Conclusions: NHPIs with poor SE status seems to be mostly disadvantaged by the heart/stroke and AD association compared to corresponding whites and Asians.

The Gomez-Lopez-Hernandez Syndrome: The Contribution of 2 Hispanic Giants of Pediatric Neurology.

The specialty of Pediatric Neurology emerged during the 20th century, a period in which many neurologists played significant roles in revolutionizing this field. Two acclaimed pediatric neurologists of Hispanic origin, Drs Manual Gomez and Arturo Lopez-Hernandez, made substantial contributions to the literature on pediatric neurology. One of their remarkable contributions was their discovery of a new, rare neurocutaneous syndrome with variable phenotype, the Gomez-Lopez-Hernandez syndrome (GLHS). Here, we describe the current understanding of GLHS and the historical background of how 2 celebrated Hispanic pediatric neurologists discovered this rare, sporadic syndrome during a time when there was a limited representation of minorities in the medical profession.

Mechanisms and Severity of Exercise Intolerance Following COVID-19 and Similar Viral Infections: A Comparative Review.

Approximately 19% of the population is suffering from "Long COVID", also known as post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC), which often results in exercise intolerance. As COVID infections continue to be common, studying the long-term consequences of coronavirus disease (COVID) on physical function has become increasingly important. This narrative review will aim to summarize the current literature surrounding exercise intolerance following COVID infection in terms of mechanism, current management approaches, and comparison with similar conditions and will aim to define limitations in the current literature. Multiple organ systems have been implicated in the onset of long-lasting exercise intolerance post-COVID, including cardiac impairment, endothelial dysfunction, decreased VO2 max and oxygen extraction, deconditioning due to bed rest, and fatigue. Treatment modalities for severe COVID have also been shown to cause myopathy and/or worsen deconditioning. Besides COVID-specific pathophysiology, general febrile illness as commonly experienced during infection will cause hypermetabolic muscle catabolism, impaired cooling, and dehydration, which acutely cause exercise intolerance. The mechanisms of exercise intolerance seen with PASC also appear similar to post-infectious fatigue syndrome and infectious mononucleosis. However, the severity and duration of the exercise intolerance seen with PASC is greater than that of any of the isolated mechanisms described above and thus is likely a combination of the proposed mechanisms. Physicians should consider post-infectious fatigue syndrome (PIFS), especially if fatigue persists after six months following COVID recovery. It is important for physicians, patients, and social systems to anticipate exercise intolerance lasting for weeks to months in patients with long COVID. These findings underscore the importance of long-term management of patients with COVID and the need for ongoing research to identify effective treatments for exercise intolerance in this population. By recognizing and addressing exercise intolerance in patients with long COVID, clinicians can provide proper supportive interventions, such as exercise programs, physical therapy, and mental health counseling, to improve patient outcomes.

Demographic recruitment bias of adults in United States randomized clinical trials by disease categories between 2008 to 2019: a systematic review and meta-analysis.

To promote health equity within the United States (US), randomized clinical trials should strive for unbiased representation. Thus, there is impetus to identify demographic disparities overall and by disease category in US clinical trial recruitment, by trial phase, level of masking, and multi-center status, relative to national demographics. A systematic review and meta-analysis were conducted using MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov, between 01/01/2008 to 12/30/2019. Clinical trials (N = 5,388) were identified based on the following inclusion criteria: study type, location, phase, and participant age. Each clinical trial was independently screened by two researchers. Data was pooled using a random-effects model. Median proportions for gender, race, and ethnicity of each trial were compared to the 2010 US Census proportions, matched by age. A second analysis was performed comparing gender, race, and ethnicity proportions by trial phase, multi-institutional status, quality, masking, and study start year. 2977 trials met inclusion criteria (participants, n = 607,181) for data extraction. 36% of trials reported ethnicity and 53% reported race. Three trials (0.10%) included transgender participants (n = 5). Compared with 2010 US Census data, females (48.3%, 95% CI 47.2-49.3, p < 0.0001), Hispanics (11.6%, 95% CI 10.8-12.4, p < 0.0001), American Indians and Alaskan Natives (AIAN, 0.19%, 95% CI 0.15-0.23, p < 0.0001), Asians (1.27%, 95% CI 1.13-1.42, p < 0.0001), Whites (77.6%, 95% CI 76.4-78.8, p < 0.0001), and multiracial participants (0.25%, 95% CI 0.21-0.31, p < 0.0001) were under-represented, while Native Hawaiians and Pacific Islanders (0.76%, 95% CI 0.71-0.82, p < 0.0001) and Blacks (17.0%, 95% CI 15.9-18.1, p < 0.0001) were over-represented. Inequitable representation was mirrored in analysis by phase, institutional status, quality assessment, and level of masking. Between 2008 to 2019 representation improved for only females and Hispanics. Analysis stratified by 44 disease categories (i.e., psychiatric, obstetric, neurological, etc.) exhibited significant yet varied disparities, with Asians, AIAN, and multiracial individuals the most under-represented. These results demonstrate disparities in US randomized clinical trial recruitment between 2008 to 2019, with the reporting of demographic data and representation of most minorities not having improved over time.

Abnormal Temporal Slowing on EEG Findings in Preclinical Alzheimer's Disease Patients With the ApoE4 Allele: A Pilot Study.

INTRODUCTION: Currently, there are limited accessible and cost-effective biomarkers for preclinical Alzheimer's disease (AD) patients. However, the apolipoprotein E (ApoE) polymorphic alleles can predict if someone is at high (e4), neutral (e3), or low (e2) genetic risk for developing AD. This study analyzed electroencephalogram (EEG) reports from individuals with various ApoE genotypes, aiming to identify EEG changes and patterns that could potentially serve as predictive markers for preclinical AD progression. METHODS: Participants aged 64-78 were selected from the patient database at an outpatient neurology clinic. Genotype studies were performed to determine ApoE status, followed by EEG analysis to identify any apparent trends. A case-control design was used, categorizing participants into cases (e2e3, e2e4, e3e4, e4e4) and controls (e3e3). EEG recordings were compared between the groups to identify potential differences in EEG characteristics, including abnormal temporal slowing, frequency, and ApoE genotype association. RESULTS: Among 43 participants, 49% demonstrated evidence of abnormal temporal slowing on EEG. Of these, 48% displayed focal left temporal slowing, and 52% displayed bilateral temporal slowing. The right-sided temporal slowing was not observed. Among participants with abnormal slowing, 95% exhibited theta frequency (4-8 Hz) slowing, while only 4.8% displayed delta frequency (0-4 Hz) slowing. Among participants with the ApoE4 allele, 61.5% demonstrated evidence of abnormal slowing, compared to 43.3% without it. Furthermore, the presence of an ApoE4 allele was associated with a significantly higher proportion of males (54%) compared to those without it (13%) (p=0.009). CONCLUSIONS: Although we did not find a statistically significant difference in temporal EEG slowing among different ApoE genotypes, our findings suggest a potential association between temporal slowing on EEG and the presence of an ApoE4 allele in individuals with preclinical AD. These observations highlight the need for further exploration into the potential influence of the ApoE4 allele on EEG findings and the utility of EEG as a complementary diagnostic tool for AD. Longitudinal studies with large sample sizes are needed to establish the precise relationship between EEG patterns, ApoE genotypes, and AD progression.