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.

Identification of associations and distinguishing moyamoya disease from ischemic strokes of other etiologies: A retrospective case-control study.

Introduction: Better characterizing moyamoya disease (MMD) from ischemic strokes of other etiologies may facilitate earlier diagnosis by raising suspicion for a diagnostic work-up. Methods: To identify associated variables, MMD cases (n = 12) were compared against three sets of controls: age-, sex-, and race-matched controls of patients with general neurological disorders (n = 48), unmatched general controls (n = 48), and unmatched non-MMD ischemic stroke controls (n = 48). Results: MMD patients were 32 years (p < 0.0001) younger than ischemic stroke controls. Relative to non-MMD ischemic strokes, MMD patients had greater odds of presenting with visual field defects (OR: 9.13, p = 0.09) or dizziness (OR: 9.13, p = 0.09), as well as being female (OR: 8.04, p = 0.008), Asian (OR: 3.68, p = 0.087), employed (OR: 6.96, p = 0.02), having migraines (OR: 21.61, p = 0.005), epilepsy (OR: 6.69, p = 0.01), insomnia (OR: 8.90, p = 0.099), and a lower Charlson Comorbidity Index (CCI; p = 0.002). Patients with MMD, compared to non-MMD ischemic strokes, also had a 4.67 kg/ m 2 greater body mass index (BMI) and larger odds (OR relative to normal BMI: 21.00, p = 0.03) of being from obesity class III (>40 kg/ m 2 ), yet reduced odds of coronary artery disease (OR: 0.13, p = 0.02). Relative to general controls, MMD patients had greater odds of diabetes mellitus type 2 (OR: 10.07, p = 0.006) and hypertension (OR: 7.28, p = 0.004). Conclusion: MMD not only has a unique clinical presentation from other ischemic strokes, but also unique comorbidities, which may facilitate earlier work-up and treatment.

Identification of risk factors and distinguishing psychogenic nonepileptic seizures from epilepsy: A retrospective case-control study.

INTRODUCTION: Patients with psychogenic non-epileptic seizures (PNES) experience significant morbidity and early mortality, secondary to delayed diagnosis. Better characterizing risk factors and exploring how PNES differentially affects sex and racial strata may facilitate earlier diagnosis. METHODS: From a Hawai'i neuroscience institution, 101 PNES patients were investigated in relation to sociodemographic and medical comorbidities. Cases were compared to 202 sex-, age-, and race-matched controls-representing patients with neurological disorders (general controls)-, as well as 404 unmatched epilepsy controls. RESULTS: Relative to general controls, PNES patients had increased odds (p < 0.05) of being: female, younger age, Native Hawaiian or other Pacific Islander (NHPI), suburban origin, from the lowest income quartile, Medicaid beneficiaries, homeless, current/former smoker, illicit drug users (marijuana, opioids/narcotics, polysubstance abuse), have anxiety, depression, post-traumatic stress disorder, bipolar disorder, traumatic history, World Health Organization obesity class 3, traumatic brain injury, epilepsy, and somatoform disorder. In relation to epilepsy controls, PNES patients exhibited increased odds of being: employed, having attention-deficit/hyperactivity disorder, asthma, migraines, and chronic pain. Relative to females, male PNES patients exhibited increased odds of military insurance, diabetes mellitus type 2, and hypertension. Relative to Whites, the NHPI and Asian PNES patients presented increased odds of asthma, migraines, chronic pain, gastroesophageal reflux disease, and thyroid disease. Per multivariable logistic regression, anxiety was the only consistent predictor of PNES across all sex and race strata. CONCLUSION: Predictors of PNES's vary amongst the strata of race and sex. Lower socioeconomic status, along with several psychiatric and medical comorbidities, could increase a clinician's suspicion for earlier medical workup and diagnosis of PNES.

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.

Early Impact of the COVID-19 Pandemic on Outpatient Neurologic Care in Hawai'i.

In March 2020, Hawai'i instituted public health measures to prevent the spread of Coronavirus disease 2019 (COVID-19), including stay-at-home orders, closure of non-essential businesses and parks, use of facial coverings, social distancing, and a mandatory 14-day quarantine for travelers. In response to these measures, Hawai'i Pacific Neuroscience (HPN) modified practice processes to ensure continuity of neurological treatment. A survey of patients was performed to assess the impact of the COVID-19 pandemic and pandemic-related practice processes for quality improvement. Overall, 367 patients seen at HPN between April 22, 2020, and May 18, 2020, were surveyed via telephone. Almost half (49.6%) participated in a telemedicine appointment, with the majority finding it easy to use (87.4%) and as valuable as face-to-face appointments (68.7%). Many (44.5%) patients said they would have missed a health care appointment without the availability of telemedicine, and 47.3% indicated they might prefer to use telemedicine over in-person appointments in the future. Many reported new or worsening mental health problems, including depression (27.6%), anxiety (38.3%), or sleep disturbances (37.4%). A significant number reported worsening of their condition, with 33.1% of patients who experience migraines reporting increased symptom severity or frequency, 45.8% patients with Alzheimer's disease reporting worsened symptoms, 38.5% of patients with Parkinson's disease who had a recent fall, and 50.0% of patients with multiple sclerosis experiencing new or worsened symptoms. Insights from this survey applied to the practice's pandemic-related processes include emphasizing lifestyle modification, screening for changes in mental health, optimizing treatment plans, and continuing the option of telemedicine.

COVID-19 Is Changing Our Understanding of the Neuroscience of Viral Infections: What We Can Do to Prepare for the Future?

In the approximately two years since the emergence of COVID-19 (Coronavirus Disease 2019) myriad neurological symptoms have been reported that are seemingly unrelated to each other [...].

Variables Associated with Coronavirus Disease 2019 Vaccine Hesitancy Amongst Patients with Neurological Disorders.

INTRODUCTION: Given that the success of vaccines against coronavirus disease 2019 (COVID-19) relies on herd immunity, identifying patients at risk for vaccine hesitancy is imperative-particularly for those at high risk for severe COVID-19 (i.e., minorities and patients with neurological disorders). METHODS: Among patients from a large neuroscience institute in Hawaii, vaccine hesitancy was investigated in relation to over 30 sociodemographic variables and medical comorbidities, via a telephone quality improvement survey conducted between 23 January 2021 and 13 February 2021. RESULTS: Vaccine willingness (n = 363) was 81.3%. Univariate analysis identified that the odds of vaccine acceptance reduced for patients who do not regard COVID-19 as a severe illness, are of younger age, have a lower Charlson Comorbidity Index, use illicit drugs, or carry Medicaid insurance. Multivariable logistic regression identified the best predictors of vaccine hesitancy to be: social media use to obtain COVID-19 information, concerns regarding vaccine safety, self-perception of a preexisting medical condition contraindicated with vaccination, not having received the annual influenza vaccine, having some high school education only, being a current smoker, and not having a prior cerebrovascular accident. Unique amongst males, a conservative political view strongly predicted vaccine hesitancy. Specifically for Asians, a higher body mass index, while for Native Hawaiians and other Pacific Islanders (NHPI), a positive depression screen, both reduced the odds of vaccine acceptance. CONCLUSION: Upon identifying the variables associated with vaccine hesitancy amongst patients with neurological disorders, our clinic is now able to efficiently provide ancillary COVID-19 education to sub-populations at risk for vaccine hesitancy. While our results may be limited to the sub-population of patients with neurological disorders, the findings nonetheless provide valuable insight to understanding vaccine hesitancy.

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.

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.

Characterizing idiopathic intracranial hypertension socioeconomic disparities and clinical risk factors: A retrospective case-control study.

INTRODUCTION: Against the backdrop of the diverse minority-majority state of Hawaii, this study seeks to better characterize associations between idiopathic intracranial hypertension (IIH) with sociodemographic variables and medical comorbidities. METHODS: A retrospective case-control study was conducted by utilizing 54 IIH patients and 216 age-, sex-, and race-matched controls, 216 unmatched controls, and 63 age-, sex-, and race-matched migraine patients. RESULTS: Relative to controls, IIH were 25 years younger (p < 0.0001) and 10.18 kg/m2 heavier (p < 0.0001), as well as exhibited greater odds of the following variables (p < 0.05): female (odds ratio [OR]: 8.87), the lowest income quartile (OR: 2.33), Native Hawaiian or other Pacific Islander (NHPI; OR: 2.23), Native American or Alaskan Native (OR: 16.50), obesity class 2 (35.0-39.9 kg/m2; OR: 4.10), obesity class 3 (>40 kg/m2; OR: 6.10), recent weight gain (OR: 11.66), current smoker (OR: 2.48), hypertensive (OR: 3.08), and peripheral vascular disease (OR: 16.42). Odds of IIH were reduced (p < 0.05) for patients who were Asian (OR: 0.27) or students (OR: 0.30;). Unique from Whites, NHPI IIH patients exhibited greater odds (p < 0.05) for being from lower socioeconomic status and currently smoking, as well as potential association with seizures (p = 0.08). Compared to migraines, IIH headaches were at increased odds of occurring (p < 0.05) occipitally, for greater than 15 days per month, aggravated by postural changes, and comorbid with dizziness and tinnitus. CONCLUSIONS: These results not only better characterize IIH, but also highlight socioeconomic and racial disparities in diagnosis.

A Case Report of Antibiotic-Induced Aseptic Meningitis in Psoriasis.

Although frequently prescribed, certain antibiotics such as trimethoprim-sulfamethoxazole carry the risk of a rare yet life-threatening adverse effect, termed drug-induced aseptic meningitis. Morbidity can be avoided if the medication is identified and discontinued. Patients in reported cases tend to be female and have an autoimmune disease or prior adverse reaction to the offending agent. As a rare and poorly characterized condition, the subset of patients using antibiotics at risk for aseptic meningitis remains unclear; hence, cataloging these adverse events remains critical for better elucidating the disease. Here, we report a 62-year-old man with psoriasis and no prior history of sulfa allergy, who presented with a sudden onset of fever, chills, vomiting, and muscle aches 5 hours after taking single doses of trimethoprim-sulfamethoxazole and ciprofloxacin. Common infectious causes were ruled out, and his medications were discontinued. Despite initial symptom resolution with discontinuation, the patient neurologically deteriorated over the next two days before eventually recovering with supportive care. This case highlights the variable presentation of drug-induced aseptic meningitis. In contrast to previous reports of drug-induced aseptic meningitis, our patient was male, older than the median age of 40 years, and did not have a prior adverse reaction to the antibiotic. Furthermore, to the best of our knowledge, we report a possible case of antibiotic-induced aseptic meningitis in a patient with psoriasis. Lastly, the case emphasizes not only the value of a thorough medication history but also the importance of recognizing that patients may deteriorate in the first 48 hours before resolution.

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.

Zika Virus: Relevance to the State of Hawai'i.

Zika virus (ZIKV) is spread among human populations primarily through the bite of Aedes mosquitoes. While most ZIKV infections are asymptomatic or cause self-limited symptoms, the major concerns are its association with Guillain-Barré Syndrome and fetal microcephaly together with other birth defects, known as congenital Zika syndrome (CZS). This article reviews the confirmed Zika cases in the continental United States (U.S.) and Hawai'i thus far, as well as literature of Zika research relevant to Hawai'i. The first case of CZS within the U.S. was reported in Hawai'i, highlighting the unique position of Hawai'i for emerging and re-emerging infectious diseases. Recent studies of the Zika outbreak in Florida demonstrate the key role of Ae. aegypti mosquito in transmission; continuous and proactive vector surveillance in Hawai'i is warranted. Additionally, an updated interim pregnancy guidance for pregnant women with possible ZIKV exposure was summarized. Due to recent decline of ZIKV transmission in the Americas, the risk of ZIKV importation to Hawai'i has been greatly reduced. However, given the presence of Aedes mosquitoes, climate condition, and status of Hawai'i as a travel destination and foreign import market, public health officials and healthcare providers should remain vigilant for a potential outbreak of mosquito-borne diseases in the future.