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Treatment Selection and Prioritization for the EJS ACT-PD MAMS Trial Platform.
BACKGROUND: There are currently no disease-modifying therapies (DMTs) registered for Parkinson's disease (PD). The Edmond J. Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative will expedite clinical assessment of putative DMTs through a multi-arm multistage (MAMS) trial, testing several treatments against a common placebo arm and replacing unsuccessful therapies early. OBJECTIVE: The objective of this study was to describe the treatment selection process for the EJS ACT-PD clinical trial platform. METHODS: A Treatment Selection Working Group (TSWG) identified compounds using complementary strategies, such as literature search, related initiatives (Cure Parkinson's International Linked Clinical Trials [iLCT] initiative), and expert suggestions. Compounds were classified into five mechanistic subgroups (mitochondrial, lysosomal, protein, inflammation, "other"). "Go/No-Go" criteria and a scoring system covering preclinical, pharmacological, and clinical evidence were devised. Experts scored the candidates for quantitative rankings. Dossiers adapted from iLCT documents were produced for the top-ranked compounds and in turn prioritized by the TSWG. Practical and logistical considerations from the Steering Committee (SC) guided the final decision. Patient and Public Involvement and Engagement representatives provided feedback throughout the process. RESULTS: A total of 293 interventions were identified, 52 of which passed the "Go/No-Go" criteria and were scored. Dossiers of the 14 top-ranked compounds were submitted to the SC. Telmisartan, terazosin, and ursodeoxycholic acid were selected as the initial interventions. CONCLUSIONS: Drug selection in DMT PD MAMS trials requires consideration of scientific and practical issues. We present a robust system that can inform similar initiatives. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Prevalence Rates of Frequent Dream Recall and Nightmares by Age, Gender and Sleep Duration in 16 Countries.
The present study aimed to describe the prevalence rates of frequent (i.e., at least weekly) dream recall and nightmares with consideration for differences in age, gender and sleep duration in 16 countries using equivalent assessment methods. The study sample included 15,854 participants (69.9% women) aged 18-99 years (M = 42.39, SD = 16.43) collected by the International COVID-19 Sleep Study collaboration, which used a unified online survey to collect data from May to November 2021 across 16 countries. Participants provided demographic information as well as self-reported estimates of their dream recall and nightmare frequency and sleep duration in 2021 and retrospectively for 2019. Frequent dream recall occurred in 54.0% of participants in 2021 and 51.1% in 2019. Frequent nightmares were reported by 11.0% of participants in 2021 and 6.9% in 2019. Ad hoc regression models found dream recall and sleep duration to have a linear relation, whereas nightmare frequency demonstrated a quadratic relation to sleep duration. Frequent dream recall and nightmare prevalence rates are reported for each of the 16 study countries by age, gender and sleep duration. This is the first multi-continent study to estimate frequent dream recall and nightmare prevalence, which both provides updated prevalence rates during the COVID-19 pandemic as well as extends existing knowledge to previously never studied countries.
Sleep During Pandemic Times: Summary of Findings and Future Outlook Through the Lens of the International COVID Sleep Study (ICOSS).
To study the impact of the COVID-19 pandemic on sleep and circadian rhythms-two fundamental pillars for health-the collaboration International COVID-19 Sleep Study (ICOSS) was established. The present overview comprehensively discusses the findings from this collaboration. Involving sleep researchers across the globe, ICOSS used a harmonised questionnaire to cover changes in sleep and sleep disorders, as well as physical and mental health. Two survey waves were conducted, one in 2020 and another one in 2021. In ICOSS-1, a total of 26,539 people from 14 countries across four continents (Europe, Asia, North and South America) participated. In ICOSS-2, two more countries joined ICOSS, and 15,813 people participated. The focus in ICOSS-2 was on Long COVID. Participants accessed the widely disseminated online surveys in their native language. In the 20 papers published so far, the surveys have uncovered several novel findings, including how the pandemic impacted sleep patterns, the prevalence of sleep disorders, chronotype-based differences and sleep-immune system interactions. To the best of our knowledge, there is no other large-scale multinational study targeting the general population investigating the role of sleep and sleep disorders alongside a variety of psychological, biological, social and economic factors during the recent COVID-19 pandemic.
Editor's Choice - Effect of Carotid Endarterectomy on 20 Year Incidence of Recorded Dementia: A Randomised Trial.
OBJECTIVE: Stroke and carotid atherosclerosis are associated with dementia. Carotid endarterectomy (CEA) reduces stroke risk, although its effect on later dementia is uncertain. Participants in the Asymptomatic Carotid Surgery Trial (ACST-1), randomly allocated to immediate vs. deferral of CEA (i.e., no intervention unless or until triggered by ipsilateral transient ischaemic attack or stroke), were followed, to study effects on dementia. METHODS: From 1993 to 2003, ACST-1 included 3 120 participants with asymptomatic tight carotid stenosis. All UK and Swedish patients (n = 1 601; 796 immediate vs. 805 deferral) were followed with trial records, national electronic health record linkage, and (UK only) by post and telephone. Cumulative incidence and competing risk analyses were used to measure the effects of risk factors and CEA on dementia risk. Intention to treat analyses yielded hazard ratios (HRs; immediate vs. deferral) of dementia. RESULTS: The median follow up was 19.4 years (interquartile range 16.9 - 21.7). Dementia was recorded in 107 immediate CEA patients and 115 allocated delayed surgery; 1 290 patients died (1 091 [538 vs. 536] before any dementia diagnosis). Dementia incidence rose with age and with female sex (men: 8.3% aged < 70 years at trial entry vs. 15.1% aged ≥ 70; women: 15.1% aged < 70 years at trial entry vs. 22.4% aged ≥ 70 years) and was higher in those with pre-existing cerebral infarction (silent or with prior symptoms; 20.2% vs. 13.6%). Dementia risk was similar in both randomised groups: 6.7% vs. 6.6% at 10 years and 14.3% vs. 15.5% at 20 years, respectively. The dementia HR was 0.98 (95% confidence interval [CI] 0.75 - 1.28; p = .89), with no heterogeneity in the neutral effect of immediate CEA on dementia related to age, carotid stenosis, blood pressure, diabetes, country of residence, or medical treatments at trial entry (heterogeneity values p > .05). CONCLUSION: CEA was not associated with significant reductions in the long term hazards of dementia, but the CI did not exclude a proportional benefit or hazard of about 25%.
Education Levels and Poststroke Cognitive Trajectories.
IMPORTANCE: Acute stroke is associated with accelerated, years-long cognitive decline. Whether education levels are associated with faster cognitive decline after stroke is unclear. OBJECTIVE: To evaluate the association of education level with poststroke cognitive decline and to determine whether age at stroke modifies the association. DESIGN, SETTING, AND PARTICIPANTS: Individual participant data meta-analysis of 4 US cohort studies (January 1971 to December 2019). Analysis began August 2022 and was completed in January 2024. EXPOSURES: Education level (less than high school, completed high school, some college, and college graduate). MAIN OUTCOMES AND MEASURES: Harmonized cognitive outcomes were global cognition (primary outcome), memory, and executive function. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition, with higher score representing better function. Linear mixed-effect models estimated the trajectory of cognitive decline after incident stroke. RESULTS: The analysis included 2019 initially dementia-free stroke survivors (1048 female [51.9%]; median [IQR] age at stroke, 74.8 [69.0-80.4] years; 339 with less than a high school education [16.7%]; 613 who completed high school [30.4%]; 484 with some college [24.0%]; 583 with a college degree or higher [28.9%]). Median (IQR) follow-up time after stroke was 4.1 (1.8-7.2) years. Compared with those with less than a high school degree, college graduates had higher initial poststroke performance in global cognition (1.09 points higher; 95% CI, 0.02 to 2.17 points higher), executive function (1.81 points higher; 95%CI, 0.38 to 3.24 points higher), and memory (0.99 points higher; 95% CI, 0.02 to 1.96 points higher). Compared with stroke survivors with less than a high school education, there was a faster decline in executive function among college graduates (-0.44 points/y faster; 95% CI, -0.69 to -0.18 points/y faster) and those with some college education(-0.30 points/y faster; 95% CI, -0.57 to -0.03 points/y faster). Education level was not associated with declines in global cognition or memory. Age did not modify the association of education with cognitive decline. CONCLUSIONS AND RELEVANCE: In this pooled cohort study, the trajectory of cognitive decline after stroke varied by education level and cognitive domain, suggesting that stroke survivors with a higher education level may have greater cognitive reserve but steeper decline in executive function than those with a lower education level.
Oxford Case Histories in TIA and Stroke
Based around the core curriculum for specialist trainees, Oxford Case Histories in TIA and Stroke features 51 well-structured, peer-reviewed cases from the Oxford Hospitals giving detailed coverage of the specialty, including diagnostic and management dilemmas. Each case comprises a brief clinical history and the relevant examination findings; details of investigations undertaken, followed by questions on differential diagnosis and management; and detailed answers and discussion. The question-and-answer format is designed to enhance the reader's diagnostic ability and clinical understanding. As part of the Oxford Case Histories series, this book is aimed at post-membership trainees and consultants and will be a useful resource for those preparing for exit examinations or revalidation. It will also be of interest to those who wish to improve their skills in diagnosis and management of a broad range of stroke disorders.