Views and Perceptions of Amyloid Imaging in a Preclinical Alzheimer's Disease Trial.

Background: Many cognitively unimpaired older adults are interested in learning their Alzheimer's disease (AD) biomarker status, but little is known about motivations to undergo biomarker testing and result disclosure in the setting of preclinical AD trials.

Objectives: Examine whether motivations to undergo AD biomarker testing and disclosure differ for individuals who have elevated amyloid compared to those with not elevated amyloid, and whether disclosure of amyloid results impacts participants' motivations.

Design, Setting, Participants: We conducted post-hoc analyses using data from the EARLY study, a preclinical AD trial of the beta-secretase inhibitor atabecestat.

Pre-Randomization Predictors of Study Discontinuation in a Preclinical Alzheimer's Disease Randomized Controlled Trial.

Background: Participant discontinuation from study treatment in a clinical trial can leave a trial underpowered, produce bias in statistical analysis, and limit interpretability of study results. Retaining participants in clinical trials for the full study duration is therefore as important as participant recruitment.

Objective: This analysis aims to identify associations of pre-randomization characteristics of participants with premature discontinuation during the blinded phase of the Anti-Amyloid treatment in Asymptomatic AD (A4) Study.

Greater White Matter Hyperintensity Volume Is Associated with the Number of Microhemorrhages in Preclinical Alzheimer's Disease.

Background: Increased white matter hyperintensity (WMH) volume visible on MRI is a common finding in Alzheimer's disease (AD). We hypothesized that WMH in preclinical AD is associated with the presence of advanced vessel amyloidosis manifested as microhemorrhages (MCH).

Objectives: 1) To assess the relationship between baseline WMH volume and baseline MCH.

Immediate Reactions to Alzheimer Biomarker Disclosure in Cognitively Unimpaired Individuals in a Global Truncated Randomized Trial.

Background And Objectives: Preclinical Alzheimer disease (AD) trials simultaneously test candidate treatments and the implications of disclosing biomarker information to cognitively unimpaired individuals.

Methods: The EARLY trial was a randomized, double-blind, placebo-controlled, phase 2b/3 study conducted in 143 centers across 14 countries from November 2015 to December 2018 after being stopped prematurely because of treatment-related hepatotoxicity. Participants age 60-85 years deemed cognitively unimpaired were disclosed an elevated or not elevated brain amyloid result by a certified clinician.

Centralizing prescreening data collection to inform data-driven approaches to clinical trial recruitment.

Background: Recruiting to multi-site trials is challenging, particularly when striving to ensure the randomized sample is demographically representative of the larger disease-suffering population. While previous studies have reported disparities by race and ethnicity in enrollment and randomization, they have not typically investigated whether disparities exist in the recruitment process prior to consent. To identify participants most likely to be eligible for a trial, study sites frequently include a prescreening process, generally conducted by telephone, to conserve resources.

Attitudes about involvement in hypothetical clinical trial protocols in Mexican and Mexican-American at risk for autosomal dominant Alzheimer's disease.

Background: The enrollment into clinical trials of persons at risk for autosomal dominant Alzheimer's disease (ADAD) in whom the onset of disease can be accurately predicted facilitates the interpretation of outcomes (e.g., biomarkers, treatment efficacy).

Sensitivity of the Preclinical Alzheimer's Cognitive Composite (PACC), PACC5, and Repeatable Battery for Neuropsychological Status (RBANS) to Amyloid Status in Preclinical Alzheimer's Disease -Atabecestat Phase 2b/3 EARLY Clinical Trial.

Background: Cognitive composites commonly serve as primary outcomes in Alzheimer's disease (AD) secondary prevention trials.

Objective: To evaluate the association between amyloid (Aβ) burden level (+/-) and performance on three separate composite endpoints: Preclinical Alzheimer's Cognitive Composite (PACC), PACC+Semantic Fluency (PACC5), and Repeatable Battery for Neuropsychological Status (RBANS).

Design: Screening data from the randomized, double-blind, placebo-controlled, phase 2b/3 atabecestat EARLY study in preclinical AD participants were used in this analysis.

Findings of Efficacy, Safety, and Biomarker Outcomes of Atabecestat in Preclinical Alzheimer Disease: A Truncated Randomized Phase 2b/3 Clinical Trial.

Importance: Atabecestat, a nonselective oral β-secretase inhibitor, was evaluated in the EARLY trial for slowing cognitive decline in participants with preclinical Alzheimer disease. Preliminary analyses suggested dose-related cognitive worsening and neuropsychiatric adverse events (AEs).

Objective: To report efficacy, safety, and biomarker findings in the EARLY trial, both on and off atabecestat treatment, with focus on potential recovery of effects on cognition and behavior.

Short-term Psychological Outcomes of Disclosing Amyloid Imaging Results to Research Participants Who Do Not Have Cognitive Impairment.

Importance: The goal of preclinical Alzheimer disease (AD) clinical trials is to move diagnosis and treatment to presymptomatic stages, which will require biomarker testing and disclosure.

Objective: To assess the short-term psychological outcomes of disclosing amyloid positron emission tomography results to older adults who did not have cognitive impairment.

Design, Setting, And Participants: This observational study included participants who were screening for a multisite randomized clinical trial that began on February 28, 2014, and is anticipated to be completed in 2022.

Levetiracetam Versus Phenobarbital for Neonatal Seizures: A Randomized Controlled Trial.

Background And Objectives: There are no US Food and Drug Administration-approved therapies for neonatal seizures. Phenobarbital and phenytoin frequently fail to control seizures. There are concerns about the safety of seizure medications in the developing brain.

Tobacco use and E-cigarette regulation: Perspectives of University Students in the Asia-Pacific.

Introduction: The Asia-Pacific is home to 30% of the world's smokers. Additional efforts are needed to reduce negative health impacts of tobacco, including e-cigarettes. The study objectives were to 1.

A mixed-methods study of cultural beliefs about dementia and genetic testing among Mexicans and Mexican-Americans at-risk for autosomal dominant Alzheimer's disease.

Trials to prevent autosomal dominantly inherited Alzheimer's disease (ADAD) are critical and timely. However, cultural beliefs about AD and genetic testing may preclude informed consent and participation, especially among racial/ethnic minorities. This mixed-methods study examines cultural beliefs about AD and genetic screening among at-risk populations of Mexican heritage.

Results of the ICTuS 2 Trial (Intravascular Cooling in the Treatment of Stroke 2).

Background And Purpose: Therapeutic hypothermia is a potent neuroprotectant approved for cerebral protection after neonatal hypoxia-ischemia and cardiac arrest. Therapeutic hypothermia for acute ischemic stroke is safe and feasible in pilot trials. We designed a study protocol to provide safer, faster therapeutic hypothermia in stroke patients.

Accuracy of Stroke Diagnosis in Telestroke-Guided Tissue Plasminogen Activator Patients.

Objectives: The objective of the study is to assess the accuracy of final diagnosis in telestroke-guided tissue plasminogen activator (rt-PA) patients compared with bedside evaluation using computed tomography (CT) or magnetic resonance imaging (MRI) as a surrogate for final stroke diagnosis. The overall goal was to determine if telestroke had similar diagnostic accuracy as bedside evaluations in diagnosing rt-PA-treated patients.

Materials And Methods: We analyzed all acute stroke code calls who received intravenous rt-PA at our center from October 2013 to June 2015.

Telephone Problem Solving for Service Members with Mild Traumatic Brain Injury: A Randomized, Clinical Trial.

Mild traumatic brain injury (mTBI) is a common injury for service members in recent military conflicts. There is insufficient evidence of how best to treat the consequences of mTBI. In a randomized, clinical trial, we evaluated the efficacy of telephone-delivered problem-solving treatment (PST) on psychological and physical symptoms in 356 post-deployment active duty service members from Joint Base Lewis McChord, Washington, and Fort Bragg, North Carolina.

Visual Determination of Conjugate Eye Deviation on Computed Tomography Scan Predicts Diagnosis of Stroke Code Patients.

Background: Head computed tomography (CT) is critical for stroke code evaluations and often happens prior to completion of the neurological exam. Eye deviation on neuroimaging (DeyeCOM sign) has utility for predicting stroke diagnosis and correlates with National Institutes of Health Stroke Scale (NIHSS) gaze score. We further assessed the utility of the DeyeCOM sign, without complex caliper-based eye deviation calculations, but simply with a visual determination method.

Telephone Problem-Solving Treatment Improves Sleep Quality in Service Members With Combat-Related Mild Traumatic Brain Injury: Results From a Randomized Clinical Trial.

Objective: Evaluate sleep quality, its correlates, and the effect of telephone-based problem-solving treatment (PST) in active duty postdeployment service members with mild traumatic brain injury (mTBI) SETTING:: Randomized clinical trial.

Participants: Active duty service members with combat-related mTBI.

Study Design: Education-only (EO) and PST groups (N = 178 each) received printed study materials and 12 educational brochures.

Feasibility and Safety of Using External Counterpulsation to Augment Cerebral Blood Flow in Acute Ischemic Stroke-The Counterpulsation to Upgrade Forward Flow in Stroke (CUFFS) Trial.

Background: External counterpulsation (ECP) increases perfusion to a variety of organs and may be helpful for acute stroke.

Methods: We conducted a single-blinded, prospective, randomized controlled feasibility and safety trial of ECP for acute middle cerebral artery (MCA) ischemic stroke. Twenty-three patients presenting within 48 hours of symptom onset were randomized into one of two groups.

Accuracy of First Recorded "Last Known Normal" Times of Stroke Code Patients.

Background: Given the time sensitivity of thrombolytic therapy, the accurate documentation of last known normal (LKN) time is crucial to ensure optimal management of stroke patients. This study investigates whether a difference exists between preliminary LKN times (first responders and emergency department practitioners) and revised LKN times (neurology/stroke practitioners), and what potential impact on emergent management of acute stroke this discrepancy may pose.

Methods: All stroke code patients from UC San Diego hospitals from October 2008 to July 2013 with treatment time data were included and grouped based on the disparity between preliminary LKN time and revised LKN time: preliminary earlier than revised, 2 times equal, and preliminary later than revised.

Comparing recruitment, retention, and safety reporting among geographic regions in multinational Alzheimer's disease clinical trials.

Introduction: Most Alzheimer's disease (AD) clinical trials enroll participants multinationally. Yet, few data exist to guide investigators and sponsors regarding the types of patients enrolled in these studies and whether participant characteristics vary by region.

Methods: We used data derived from four multinational phase III trials in mild to moderate AD to examine whether regional differences exist with regard to participant demographics, safety reporting, and baseline scores on the Mini Mental State Examination (MMSE), the 11-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog11), the Clinical Dementia Rating scale Sum of Boxes (CDR-SB), the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL), and the Neuropsychiatric Inventory (NPI).

Peripheral and central effects of γ-secretase inhibition by semagacestat in Alzheimer's disease.

Introduction: The negative efficacy study examining the γ-secretase inhibitor semagacestat in mild to moderate Alzheimer's disease (AD) included a number of biomarkers of the disease as well as safety outcomes. We analyzed these data to explore relationships between drug exposure and pharmacodynamic effects and to examine the correlations among outcome measures.

Methods: The study was a multicenter, randomized, placebo-controlled trial of two dose regimens of semagacestat and a placebo administered for 18 months to individuals with mild to moderate AD.

Defining mild stroke: outcomes analysis of treated and untreated mild stroke patients.

Background: Mild deficit is a relative contraindication to administration of intravenous recombinant tissue plasminogen activator (IV rtPA) for acute ischemic stroke. However, what constitutes "mild" deficit is vague. Prior studies showed patients with mild strokes have substantial disability rates at hospital discharge and at 90 days.

The "DeyeCOM Sign": Predictive Value in Acute Stroke Code Evaluations.

Background: Rapid diagnosis in stroke is critical. Computed tomography is often performed initially, even before a neurologic examination. Gaze deviation has been correlated with stroke diagnosis in some cohorts.

Association of Hispanic ethnicity with acute ischemic stroke care processes and outcomes.

Background: Few studies have examined the actual hospital arrival mode, emergency department (ED) care processes, and early outcomes in Hispanic vs non-Hispanic acute ischemic stroke (AIS) patients. We evaluated processes and prognosis by Hispanic ethnicity among AIS patients encountered in urban setting.

Methods: We retrospectively reviewed prospectively-collected data on 1,117 AIS patients presenting within 12 hours of ictus to five hospitals in a tertiary-level stroke center network in San Diego, California.