Accurate detection of acute sleep deprivation using a metabolomic biomarker-A machine learning approach.

Sleep deprivation enhances risk for serious injury and fatality on the roads and in workplaces. To facilitate future management of these risks through advanced detection, we developed and validated a metabolomic biomarker of sleep deprivation in healthy, young participants, across three experiments. Bi-hourly plasma samples from 2 × 40-hour extended wake protocols (for train/test models) and 1 × 40-hour protocol with an 8-hour overnight sleep interval were analyzed by untargeted liquid chromatography-mass spectrometry. Using a knowledge-based machine learning approach, five consistently important variables were used to build predictive models. Sleep deprivation (24 to 38 hours awake) was predicted accurately in classification models [versus well-rested (0 to 16 hours)] (accuracy = 94.7%/AUC 99.2%, 79.3%/AUC 89.1%) and to a lesser extent in regression (R2 = 86.1 and 47.8%) models for within- and between-participant models, respectively. Metabolites were identified for replicability/future deployment. This approach for detecting acute sleep deprivation offers potential to reduce accidents through "fitness for duty" or "post-accident analysis" assessments.

Sleep restriction alters the integration of multiple information sources in probabilistic decision-making.

The detrimental effects of sleep loss on overall decision-making have been well described. Due to the complex nature of decisions, there remains a need for studies to identify specific mechanisms of decision-making vulnerable to sleep loss. Bayesian perspectives of decision-making posit judgement formation during decision-making occurs via a process of integrating knowledge gleaned from past experiences (priors) with new information from current observations (likelihoods). We investigated the effects of sleep loss on the ability to integrate multiple sources of information during decision-making by reporting results from two experiments: the first implementing both sleep restriction (SR) and total sleep deprivation (TSD) protocols, and the second implementing an SR protocol. In both experiments, participants were administered the Bayes Decisions Task on which optimal performance requires the integration of Bayesian prior and likelihood information. Participants in Experiment 1 showed reduced reliance on both information sources after SR, while no significant change was observed after TSD. Participants in Experiment 2 showed reduced reliance on likelihood after SR, especially during morning testing sessions. No accuracy-related impairments resulting from SR and TSD were observed in both experiments. Our findings show SR affects decision-making through altering the way individuals integrate available sources of information. Additionally, the ability to integrate information during SR may be influenced by time of day. Broadly, our findings carry implications for working professionals who are required to make high-stakes decisions on the job, yet consistently receive insufficient sleep due to work schedule demands.

Awareness of errors is reduced by sleep loss.

The ability to detect and subsequently correct errors is important in preventing the detrimental consequences of sleep loss. The Error Related Negativity (ERN), and the error positivity (Pe) are established neural correlates of error processing. Previous work has shown sleep loss reduces ERN and Pe, indicating sleep loss impairs error-monitoring processes. However, no previous work has examined behavioral error awareness, in conjunction with EEG measures, under sleep loss conditions, and studies of sleep restriction are lacking. Using combined behavioral and EEG measures, we report two studies investigating the impact of total sleep deprivation (TSD) and sleep restriction (SR) on error awareness. Fourteen healthy participants completed the Error Awareness Task under conditions of TSD and 27 completed the same task under conditions of SR. It was found that TSD did not influence behavioral error awareness or ERN or Pe amplitude, however, SR reduced behavioral error awareness, increased the time taken to detect errors, and reduced Pe amplitude. Findings indicate individuals who are chronically sleep restricted are at risk for reduced recognition of errors. Reduced error awareness may be one factor contributing to the increased accidents and injuries seen in contexts where sleep loss is prevalent.

Subjective awareness of sleepiness while driving in younger and older adults.

Understanding whether drivers can accurately assess sleepiness is essential for educational campaigns advising drivers to stop driving when feeling sleepy. However, few studies have examined this in real-world driving environments, particularly among older drivers who comprise a large proportion of all road users. To examine the accuracy of subjective sleepiness ratings in predicting subsequent driving impairment and physiological drowsiness, 16 younger (21-33 years) and 17 older (50-65 years) adults drove an instrumented vehicle for 2 h on closed loop under two conditions: well-rested and 29 h sleep deprivation. Sleepiness ratings (Karolinska Sleepiness Scale, Likelihood of Falling Asleep scale, Sleepiness Symptoms Questionnaire) were obtained every 15min, alongside lane deviations, near crash events, and ocular indices of drowsiness. All subjective sleepiness measures increased with sleep deprivation for both age groups (p < 0.013). While most subjective sleepiness ratings significantly predicted driving impairment and drowsiness in younger adults (OR: 1.7-15.6, p < 0.02), this was only apparent for KSS, likelihood of falling asleep, and "difficulty staying in the lane for the older adults" (OR: 2.76-2.86, p = 0.02). This may be due to an altered perception of sleepiness in older adults, or due to lowered objective signs of impairment in the older group. Our data suggest that (i) younger and older drivers are aware of sleepiness; (ii) the best subjective scale may differ across age groups; and (iii) future research should expand on the best subjective measures to inform of crash risk in older adults to inform tailored educational road safety campaigns on signs of sleepiness.

Entrainment to gradual vs. immediate 8-hour phase advance shifts with and without short-wavelength enriched polychromatic green light.

OBJECTIVES: For optimal health and well-being the sleep episode and the circadian timing system should be properly aligned. We evaluated the effectiveness of different dynamic light and sleep/wake shift schedules for rapid circadian entrainment following an 8-hour advance of sleep. METHODS: Forty-three healthy participants completed an 8-day inpatient protocol in which the 8-hour sleep episode was advanced by 8 hours. Participants were assigned to one of five conditions: (1) dim ambient WHITE light and GRADUAL shift in which the sleep episode was incrementally advanced over 5days; (2) dim GREEN, short-wavelength (∼504 nm) polychromatic light and GRADUAL shift; (3) dim WHITE light and SLAM shift, including an abrupt 8-hour advance on day 3 following an extended 32-hour wake episode; (4) GREEN light and SLAM shift; or (5) COMBINED (higher illuminance WHITE plus GREEN) light and modified SLAM shift with 2 short naps scheduled on the day prior to the abrupt advance. Phase shifts of the plasma dim light melatonin onset and sleep measures were compared to examine effects of protocol condition. RESULTS: After 5days, the COMBINED light/modified SLAM shift condition showed larger phase advances of dim light melatonin onset (4.02 ± 1.13 hours) compared to the other 4 conditions (range 1.50 ± 0.96-2.83 ± 2.23 hours; p < .05) and resulted in increased REM sleep duration and fewer sleep disruptions. CONCLUSIONS: Consideration of the type of shift and the illuminance and wavelength of light may assist in designing lighting countermeasures to sleep and circadian disruption, which has implications for jetlag, shiftwork, and circadian rhythm sleep disorders.

Circadian distribution of epileptiform discharges in epilepsy: Candidate mechanisms of variability.

Epilepsy is a serious neurological disorder characterised by a tendency to have recurrent, spontaneous, seizures. Classically, seizures are assumed to occur at random. However, recent research has uncovered underlying rhythms both in seizures and in key signatures of epilepsy-so-called interictal epileptiform activity-with timescales that vary from hours and days through to months. Understanding the physiological mechanisms that determine these rhythmic patterns of epileptiform discharges remains an open question. Many people with epilepsy identify precipitants of their seizures, the most common of which include stress, sleep deprivation and fatigue. To quantify the impact of these physiological factors, we analysed 24-hour EEG recordings from a cohort of 107 people with idiopathic generalized epilepsy. We found two subgroups with distinct distributions of epileptiform discharges: one with highest incidence during sleep and the other during day-time. We interrogated these data using a mathematical model that describes the transitions between background and epileptiform activity in large-scale brain networks. This model was extended to include a time-dependent forcing term, where the excitability of nodes within the network could be modulated by other factors. We calibrated this forcing term using independently-collected human cortisol (the primary stress-responsive hormone characterised by circadian and ultradian patterns of secretion) data and sleep-staged EEG from healthy human participants. We found that either the dynamics of cortisol or sleep stage transition, or a combination of both, could explain most of the observed distributions of epileptiform discharges. Our findings provide conceptual evidence for the existence of underlying physiological drivers of rhythms of epileptiform discharges. These findings should motivate future research to explore these mechanisms in carefully designed experiments using animal models or people with epilepsy.

European NCAP Driver State Monitoring Protocols: Prevalence of Distraction in Naturalistic Driving.

OBJECTIVE: examine the prevalence of driver distraction in naturalistic driving when implementing European New Car Assessment Program (Euro NCAP)-defined distraction behaviours. BACKGROUND: The 2023 introduction of Occupant Status monitoring (OSM) into Euro NCAP will accelerate uptake of Driver State Monitoring (DSM). Euro NCAP outlines distraction behaviours that DSM must detect to earn maximum safety points. Distraction behaviour prevalence and driver alerting and intervention frequency have yet to be examined in naturalistic driving. METHOD: Twenty healthcare workers were provided with an instrumented vehicle for approximately two weeks. Data were continuously monitored with automotive grade DSM during daily work commutes, resulting in 168.8 hours of driver head, eye and gaze tracking. RESULTS: Single long distraction events were the most prevalent, with .89 events/hour. Implementing different thresholds for driving-related and driving-unrelated glance regions impacts alerting rates. Lizard glances (primarily gaze movement) occurred more frequently than owl glances (primarily head movement). Visual time-sharing events occurred at a rate of .21 events/hour. CONCLUSION: Euro NCAP-described driver distraction occurs naturalistically. Lizard glances, requiring gaze tracking, occurred in high frequency relative to owl glances, which only require head tracking, indicating that less sophisticated DSM will miss a substantial amount of distraction events. APPLICATION: This work informs OEMs, DSM manufacturers and regulators of the expected alerting rate of Euro NCAP defined distraction behaviours. Alerting rates will vary with protocol implementation, technology capability, and HMI strategies adopted by the OEMs, in turn impacting safety outcomes, user experience and acceptance of DSM technology.

Sleep, Circadian Rhythms, and Cognitive Dysfunction in Huntington's Disease.

BACKGROUND: In healthy people, sleep and circadian disruption are linked to cognitive deficits. People with Huntington's disease (HD), who have compromised brain function and sleep and circadian disturbances, may be even more susceptible to these cognitive effects. OBJECTIVE: To conduct a comprehensive review and synthesis of the literature in HD on the associations of cognitive dysfunction with disturbed sleep and circadian rhythms. METHODS: We searched MEDLINE via OVID, CINAHL Plus, EMBASE via OVID, and PubMed in May 2023. The first author then screened by title and abstract and conducted a full review of remaining articles. RESULTS: Eight studies investigating the influence of sleep and/or circadian rhythms on cognitive function in HD were found. In manifest HD, poorer sleep was associated with worse cognitive function. For behavioral 24-hour (circadian) rhythms, two studies indicated that later wake times correlated with poorer cognitive function. No reported studies in HD examined altered physiological 24-hour (circadian) rhythms and cognitive impairment. CONCLUSION: Some associations exist between poor sleep and cognitive dysfunction in manifest HD, yet whether these associations are present before clinical diagnosis is unknown. Whether circadian disturbances relate to cognitive impairment in HD also remains undetermined. To inform sleep and circadian interventions aimed at improving cognitive symptoms in HD, future research should include a range of disease stages, control for external factors, and utilize robust cognitive batteries targeted to the aspects of cognitive function known to be adversely affected in HD.

Controlling Catalyst Behavior in Lewis Acid-Catalyzed Carbonyl-Olefin Metathesis.

Lewis acid-catalyzed carbonyl-olefin metathesis has introduced a new means for revealing the behavior of Lewis acids. In particular, this reaction has led to the observation of new solution behaviors for FeCl3 that may qualitatively change how we think of Lewis acid activation. For example, catalytic metathesis reactions operate in the presence of superstoichiometric amounts of carbonyl, resulting in the formation of highly ligated (octahedral) iron geometries. These structures display reduced activity, decreasing catalyst turnover. As a result, it is necessary to steer the Fe-center away from inhibiting pathways to improve the reaction efficiency and augment yields for recalcitrant substrates. Herein, we examine the impact of the addition of TMSCl to FeCl3-catalyzed carbonyl-olefin metathesis, specifically for substrates that are prone to byproduct inhibition. Through kinetic, spectroscopic, and colligative experiments, significant deviations from the baseline metathesis reactivity are observed, including mitigation of byproduct inhibition as well as an increase in the reaction rate. Quantum chemical simulations are used to explain how TMSCl induces a change in catalyst structure that leads to these kinetic differences. Collectively, these data are consistent with the formation of a silylium catalyst, which induces the reaction through carbonyl binding. The FeCl3 activation of Si-Cl bonds to give the silylium active species is expected to have significant utility in enacting carbonyl-based transformations.

Feeling sleepy? stop driving-awareness of fall asleep crashes.

STUDY OBJECTIVES: To examine whether drivers are aware of sleepiness and associated symptoms, and how subjective reports predict driving impairment and physiological drowsiness. METHODS: Sixteen shift workers (19-65 years; 9 women) drove an instrumented vehicle for 2 hours on a closed-loop track after a night of sleep and a night of work. Subjective sleepiness/symptoms were rated every 15 minutes. Severe and moderate driving impairment was defined by emergency brake maneuvers and lane deviations, respectively. Physiological drowsiness was defined by eye closures (Johns drowsiness scores) and EEG-based microsleep events. RESULTS: All subjective ratings increased post night-shift (p < 0.001). No severe drive events occurred without noticeable symptoms beforehand. All subjective sleepiness ratings, and specific symptoms, predicted a severe (emergency brake) driving event occurring in the next 15 minutes (OR: 1.76-2.4, AUC > 0.81, p < 0.009), except "head dropping down". Karolinska Sleepiness Scale (KSS), ocular symptoms, difficulty keeping to center of the road, and nodding off to sleep, were associated with a lane deviation in the next 15 minutes (OR: 1.17-1.24, p<0.029), although accuracy was only "fair" (AUC 0.59-0.65). All sleepiness ratings predicted severe ocular-based drowsiness (OR: 1.30-2.81, p < 0.001), with very good-to-excellent accuracy (AUC > 0.8), while moderate ocular-based drowsiness was predicted with fair-to-good accuracy (AUC > 0.62). KSS, likelihood of falling asleep, ocular symptoms, and "nodding off" predicted microsleep events, with fair-to-good accuracy (AUC 0.65-0.73). CONCLUSIONS: Drivers are aware of sleepiness, and many self-reported sleepiness symptoms predicted subsequent driving impairment/physiological drowsiness. Drivers should self-assess a wide range of sleepiness symptoms and stop driving when these occur to reduce the escalating risk of road crashes due to drowsiness.

A scoping review of distributed cognition in acute care clinical decision-making.

OBJECTIVES: In acute care settings, interactions between providers and tools drive clinical decision-making. Most studies of decision-making focus on individual cognition and fail to capture critical collaborations. Distributed Cognition (DCog) theory provides a framework for examining the dispersal of tasks among agents and artifacts, enhancing the investigation of decision-making and error. CONTENT: This scoping review maps the evidence collected in empiric studies applying DCog to clinical decision-making in acute care settings and identifies gaps in the existing literature. SUMMARY AND OUTLOOK: Thirty-seven articles were included. The majority (n=30) used qualitative methods (observations, interviews, artifact analysis) to examine the work of physicians (n=28), nurses (n=27), residents (n=16), and advanced practice providers (n=12) in intensive care units (n=18), operating rooms (n=7), inpatient units (n=7) and emergency departments (n=5). Information flow (n=30) and task coordination (n=30) were the most frequently investigated elements of DCog. Provider-artifact (n=35) and provider-provider (n=30) interactions were most explored. Electronic (n=18) and paper (n=15) medical records were frequently described artifacts. Seven prominent themes were identified. DCog is an underutilized framework for examining how information is obtained, represented, and transmitted through complex clinical systems. DCog offers mechanisms for exploring how technologies, like EMRs, and workspaces can help or hinder clinical decision-making.

The impact of break duration, time of break onset, and prior shift duration on the amount of sleep between shifts in heavy vehicle drivers.

This study aimed to examine the impact of break duration between consecutive shifts, time of break onset, and prior shift duration on total sleep time (TST) between shifts in heavy vehicle drivers (HVDs), and to assess the interaction between break duration and time of break onset. The sleep (actigraphy and sleep diaries) and work shifts (work diaries) of 27 HVDs were monitored during their usual work schedule for up to 9 weeks. Differences in TST between consecutive shifts and days off were assessed. Linear mixed models (followed by pairwise comparisons) assessed whether break duration, prior shift duration, time of break onset, and the interaction between break duration and break onset were related to TST between shifts. Investigators found TST between consecutive shifts (mean [SD] 6.38 [1.38] h) was significantly less than on days off (mean [SD] 7.63 [1.93] h; p < 0.001). Breaks starting between 12:01 and 8:00 a.m. led to shorter sleep (p < 0.05) compared to breaks starting between 4:01 and 8:00 p.m. Break durations up to 7, 9, and 11 h (Australian and European minimum break durations) resulted in a mean (SD) of 4.76 (1.06), 5.66 (0.77), and 6.41 (1.06) h of sleep, respectively. The impact of shift duration prior to the break and the interaction between break duration and time of break were not significant. HVDs' sleep between workdays is influenced independently by break duration and time of break onset. This naturalistic study provides evidence that current break regulations prevent sufficient sleep duration in this industry. Work regulations should evaluate appropriate break durations and break onset times to allow longer sleep opportunities for HVDs.

Geriatric Education on Telehealth (GET) Access: A medical student volunteer program to increase access to geriatric telehealth services at the onset of COVID-19.

The coronavirus disease 2019 pandemic placed an unprecedented demand on health systems to rapidly shift ambulatory in-person care to virtual care. Geriatric patients face more challenges with video visit access compared to younger patients due to discomfort with technology and less access to devices and internet. Medical students at the University of Michigan created an initiative to improve access to and comfort with video visits for geriatric patients. The program's goals were to (a) explore options for the delivery of personalized training to older adults, (b) create materials for volunteers to successfully navigate conversations with patients and caregivers, (c) provide patients one-to-one remote guidance while identifying and overcoming barriers-with practice sessions to increase comfort, (d) share with the larger health system, and (e) ensure program sustainability. Over a 10-week evaluation period, providers whose patients worked with our geriatric education on telehealth access volunteers had a video visit rate of 43% compared to 19.2% prior to participation in the program (adjusted odds ratio = 3.38, 95% confidence interval = 2.49, 4.59), ultimately providing a platform for geriatric patients to foster stronger connections with their providers, while increasing Michigan Medicine's overall proportion of video telehealth visits.

Home is where the hustle is: the influence of crowds on effort and home advantage in the National Basketball Association.

Studies have consistently shown crowds contribute to home advantage in the National Basketball Association (NBA) by inspiring home team effort, distracting opponents, and influencing referees. Quantifying the effect of crowds is challenging, however, due to potential co-occurring drivers of home advantage (e.g., travel, location familiarity). Our aim was to isolate the crowd effect using a "natural experiment" created by the Coronavirus disease 2019 (COVID-19) pandemic, which eliminated crowds in 53.4% of 2020/2021 NBA regular season games (N = 1080). Using mixed linear models, we show, in games with crowds, home teams won 58.65% of games and, on average, outrebounded and outscored their opponents. This was a significant improvement compared to games without crowds, of which home teams won 50.60% of games and, on average, failed to outrebound or outscore their opponents. Further, the crowd-related increase in rebound differential mediated the relationship between crowds and points differential. Taken together, these results suggest home advantage in the 2020/2021 NBA season was predominately driven by the presence of home crowds and their influence on the effort exerted to rebound the basketball. These findings are of considerable significance to a league where marginal gains can have immense competitive, financial, and historic consequences.

Oxytocin and Hypotension During Dilation and Evacuation Procedures at 18-24 Weeks Gestation.

Oxytocin is a neurohormone that is routinely administered to patients during dilation and evacuation procedures (D&E) to control bleeding despite minimal evidence in support of this common practice. In this study, the authors sought to evaluate patients with hypotension after receiving oxytocin during D&E procedures. The secondary data from a double-blind, randomized, placebo-controlled trial involving 112 patients who underwent a D&E at 18-24 weeks gestation and prophylactically received an intravenous bolus of either 30 units of oxytocin in 500 mL of normal saline or 500 mL of saline alone at the start of the procedure were analyzed. Anesthesia providers measured blood pressure before, at the time of, and after study medication administration in 5-minute increments until the end of the procedure. No differences in demographic characteristics or mean blood pressure between the 2 groups were observed. The proportion of hypotensive patients was not statistically different at 5 minutes following fluid bolus (oxytocin 25% versus placebo 13%, P=.09). The proportion of hypotensive patients was similar by 10 minutes (oxytocin 20% versus placebo 16%, P=.62). A sample size of 112 provided the ability to detect a 23% difference in the proportion of patients who experienced hypotension (2-sided 95% CI, power of 80%). These findings suggest that oxytocin may have a transient hypotensive effect.

Receipt of Recovery-Oriented Care Practices During Hospitalization for Sepsis.

Survivors of sepsis hospitalization are at high risk for postsepsis morbidity, readmission, and death, but these negative outcomes can be mitigated by receipt of recommended care practices. We sought to assess factors associated with the receipt of recommended recovery-oriented care practices during hospitalization for sepsis. We hypothesized that patients treated in the ICU may be more likely than ward-treated patients to receive recommended care practices given the increasing focus on survivorship in the critical care field. DESIGN: Observational cohort study. SETTING: Michigan Medicine, a tertiary academic medical center. PATIENTS: Adult patients discharged alive from a hospitalization with a primary diagnosis of sepsis or septic shock in 2019. We further limited our cohort to patients receiving longitudinal care viewable in the Michigan Medicine electronic health record to ensure ability to capture posthospital care and outcomes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three-hundred sixty-five sepsis hospitalizations met study inclusion criteria. Using structured chart review, we determined receipt of the following recovery-based care practices during hospitalization: medication optimization, functional status evaluation at discharge, sepsis education, and scheduled follow-up within 2 weeks. The cohort was 46.6% female, 81.1% White, with a median age of 64 years. 51.2% were treated in the ICU. Medication optimization occurred in 93.7%, functional status evaluation in 82.7%, sepsis education in 20.0%, and scheduled follow-up within 2 weeks in 54.5%. ICU-treated patients had lower receipt of medication optimization and follow-up scheduling but greater receipt of functional and mental health status evaluations. In multivariable models, ICU treatment was associated with lower odds of receiving medication optimization (adjusted odds ratio, 0.72; 95% CI, 0.03-0.69) and not associated with receipt of other care practices. CONCLUSIONS: Our study shows incomplete receipt of recommended recovery-based care practices during sepsis hospitalization in both ward and ICU-treated patients. Sepsis education and mental health evaluation were particularly uncommon.

Eastward Jet Lag is Associated with Impaired Performance and Game Outcome in the National Basketball Association.

Objectives: Elite athletes are often required to travel across time zones for national and international competitions, causing frequent jet lag. The aim of this study was to examine whether the direction of travel-related jet lag is associated with performance in the National Basketball Association (NBA), and if so, to explore potential mechanisms. Methods: Ten seasons comprising of 11,481 games of NBA data from the 2011/2012 to the 2020/2021 regular season were analyzed using multi-level mixed models with one fixed factor (three levels; jet lag direction: eastward vs westward vs no jet lag) and three random factors (team, opponent, game time). Predicted circadian resynchronization rate was accounted for, and home and away games were analysed separately. Mediation analyses were performed to examine potential mechanisms. Results: Among home teams, eastward (but not westward) jet lag was associated with reduced winning (Δ (i.e., change) = -6.03%, p = 0.051, marginal), points differential (Δ = -1.29 points, p = 0.015), rebound differential (Δ = -1.29 rebounds, p < 0.0001), and effective field goal percentage differential (Δ = -1.2%, p < 0.01). As the magnitude of eastward jet lag increased, home team points differential decreased (2 h Δ = -4.53 points, p < 0.05; 1 h Δ = -0.72 points, p = 0.07). No significant associations were found between jet lag and away team performance. Conclusion: Eastward jet lag was associated with impaired performance for home (but not away) teams. Sleep and circadian disruption associated with advancing phase following eastward travel may have significant adverse consequences on performance in the NBA, particularly when recovery time is limited. Sports organisations could consider chronobiology-informed scheduling and interventions to maximise recovery and performance of their athletes.

Ethical Considerations during the Informed Consent Process for Acute Ischemic Stroke in International Clinical Trials.

We sought to investigate the experiences of researchers in existing active-control trials in acute ischemic stroke comparing investigational therapy to tissue plasminogen activator (tPA) in order to identify the approaches and challenges in obtaining informed consent. Out of 401 articles evaluated, 14 trials met inclusion criteria. Trial representatives were contacted to complete a survey concerning the consent process. None of the 14 trials published materials related to the informed consent process. Trials with 75% to 100% of patients directly consented had shorter door-to-treatment (DTT) times than trials that directly consented less than 50% of patients. Trials that had translators available (for recruiting participants who were not native speakers in the local language) and translated consent documents had longer DTT times. The study findings suggest that differences in the standards of informed consent internationally may allow more patients with moderate strokes to provide direct consent without delaying DTT time. Future trials should emphasize transparency to the public and scientific community in the informed consent process.