Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Mental Fatigue in the Brain - Sustaining attention for a prolonged period of time increases temporal variability in cortical responses

Data and code accompanying research project described in this publication: https://doi.org/10.1016/j.cortex.2019.02.01

Data

Behavioral (task, ratings) in text format and EEG data (raw, preprocessed, analyzed) in BioSemi / MATLAB forma

Materials

Experimental task cod

Analysis

Analysis code (MATLAB & R) to reproduce the figures, statistics, EEG and behavioral analyse

Sustaining attention for a prolonged period of time increases temporal variability in cortical responses

Contains fulltext : 206265.pdf (publisher's version ) (Closed access

Cognitive Flexibility Training: A Large-Scale Multimodal Adaptive Active-Control Intervention Study in Healthy Older Adults

As aging is associated with cognitive decline, particularly in the executive functions, it is essential to effectively improve cognition in older adults. Online cognitive training is currently a popular, though controversial method. Although some changes seem possible in older adults through training, far transfer, and longitudinal maintenance are rarely seen. Based on previous literature we created a unique, state-of-the-art intervention study by incorporating frequent sessions and flexible, novel, adaptive training tasks, along with an active control group. We created a program called TAPASS (Training Project Amsterdam Seniors and Stroke), a randomized controlled trial. Healthy older adults (60–80 y.o.) were assigned to a frequent- (FS) or infrequent switching (IS) experimental condition or to the active control group and performed 58 half-hour sessions over the course of 12 weeks. Effects on executive functioning, processing- and psychomotor speed, planning, verbal long term memory, verbal fluency, and reasoning were measured on four time points before, during and after the training. Additionally, we examined the explorative question which individual aspects added to training benefit. Besides improvements on the training, we found significant time effects on multiple transfer tasks in all three groups that likely reflected retest effects. No training-specific improvements were detected, and we did not find evidence of additional benefits of individual characteristics. Judging from these results, the therapeutic value of using commercially available training games to train the aging brain is modest, though any apparent effects should be ascribed more to expectancy and motivation than to the elements in our training protocol. Our results emphasize the importance of using parallel tests as outcome measures for transfer and including both active and passive control conditions. Further investigation into different training methods is advised, including stimulating social interaction and the use of more variable, novel, group-based yet individual-adjusted exercises