The prospective associations of 24-hour movement behaviors and domain-specific activities with executive function and academic achievement among school-aged children in Singapore.

Background: Physical activity (PA), sedentary behavior (SB), and sleep are collectively referred to as 24-h movement behaviors, which may be linked to cognitive development in children. However, most of the evidence was based on cross-sectional studies and/or solely relied on parent-reported information on children's behaviors, and it remains uncertain whether all domains/contexts of PA and SB are similarly associated with executive function and academic achievement. Objective: We investigated the prospective associations of accelerometer-measured 24 h-movement behaviors and domain-specific PA and SB with executive function and academic achievement among school-aged children in Singapore. Methods: The Growing Up in Singapore Toward healthy Outcomes (GUSTO) cohort used a wrist-worn accelerometer (Actigraph-GT3x+) to measure 24 h-movement behaviors data at ages 5.5 and 8 years. Executive function and academic achievement were assessed using NEuroPSYchology (NEPSY) and Wechsler Individual Achievement Tests at ages 8.5 and 9-years, respectively. Compositional data analyses were conducted to explore the associations of 24 h-movement behavior with outcomes, and multiple linear regression models to examine the associations of domain-specific PA and SB with outcomes (n = 432). Results: Among 432 children whose parents agreed to cognitive assessments (47% girls and 58% Chinese), the composition of 24 h-movement behaviors at ages 5.5 and 8 years was not associated with executive function and academic achievement. However, higher moderate-to-vigorous PA (MVPA) relative to remaining movement behaviors at age 5.5 years was associated with lower academic achievement [Mean difference (95% confidence interval): -0.367 (-0.726, -0.009) z-score], and reallocating MVPA time to sleep showed higher academic achievement scores [30 min from MVPA to sleep: 0.214 (0.023, 0.404) z-score]. Certain domains of PA and SB, notably organized PA/sports, outdoor play, and reading books were favorably associated with outcomes of interest, while indoor play and screen-viewing were unfavorably associated. Conclusion: The associations between movement behaviors and cognitive outcomes are multifaceted, influenced by specific domains of PA and SB. This study underscores the importance of participation in organized PA/sports, outdoor active play, and reading books, while ensuring adequate sleep and limiting screen viewing, to enhance cognitive outcomes. These findings underscore the need for further research into time-use trade-offs. Such studies could have major implications for revising current guidelines or strategies aimed at promoting healthier 24 h-movement behaviors in children. Study registration: https://clinicaltrials.gov/, NCT01174875.

Assessment of Left Atrial Fibrosis by Cardiac Magnetic Resonance Imaging in Ischemic Stroke Patients Without Atrial Fibrillation: A Systematic Review and Meta-Analysis.

BACKGROUND: Left atrial (LA) fibrosis is a marker of atrial cardiomyopathy and has been reported to be associated with both atrial fibrillation and ischemic stroke. Elucidating this relationship is clinically important as LA fibrosis could serve as a surrogate biomarker of LA cardiomyopathy. The objective of this study is to investigate the association of LA fibrosis and embolic stroke of undetermined source (ESUS) using cardiac magnetic resonance imaging. METHODS AND RESULTS: Following an International Prospective Register of Systematic Reviews-registered protocol, 3 blinded reviewers performed a systematic review for studies that quantified the degree of LA fibrosis in patients with ESUS as compared with healthy patients from inception to February 2024. A meta-analysis was conducted in the mean difference. From 7 studies (705 patients), there was a significantly higher degree of LA fibrosis in patients with ESUS compared with healthy controls (MD, 5.71% [95% CI, 3.55%-7.87%], P<0.01). The degree of LA fibrosis was significantly higher in patients with atrial fibrillation than healthy controls (MD, 8.22% [95% CI, 5.62%-10.83%], P<0.01). A similar degree of LA fibrosis was observed in patients with ESUS compared with patients with atrial fibrillation (MD, -0.92% [95% CI, -2.29% to 0.44%], P=0.35). CONCLUSIONS: A significantly higher degree of LA fibrosis was found in patients with ESUS as compared with healthy controls. This suggests that LA fibrosis may play a significant role in the pathogenesis of ESUS. Further research is warranted to investigate LA fibrosis as a surrogate biomarker of atrial cardiomyopathy and recurrent stroke risk in patients with ESUS.

Rationale, Design, and Baseline Characteristics of Participants in the Health@NUS mHealth Augmented Cohort Study Examining Student-to-Work Life Transition: Protocol for a Prospective Cohort Study.

BACKGROUND: Integration of mobile health data collection methods into cohort studies enables the collection of intensive longitudinal information, which gives deeper insights into individuals' health and lifestyle behavioral patterns over time, as compared to traditional cohort methods with less frequent data collection. These findings can then fill the gaps that remain in understanding how various lifestyle behaviors interact as students graduate from university and seek employment (student-to-work life transition), where the inability to adapt quickly to a changing environment greatly affects the mental well-being of young adults. OBJECTIVE: This paper aims to provide an overview of the study methodology and baseline characteristics of participants in Health@NUS, a longitudinal study leveraging mobile health to examine the trajectories of health behaviors, physical health, and well-being, and their diverse determinants, for young adults during the student-to-work life transition. METHODS: University students were recruited between August 2020 and June 2022 in Singapore. Participants would complete biometric assessments and questionnaires at 3 time points (baseline, 12-, and 24-month follow-up visits) and use a Fitbit smartwatch and smartphone app to continuously collect physical activity, sedentary behavior, sleep, and dietary data over the 2 years. Additionally, up to 12 two-week-long bursts of app-based ecological momentary surveys capturing lifestyle behaviors and well-being would be sent out among the 3 time points. RESULTS: Interested participants (n=1556) were screened for eligibility, and 776 participants were enrolled in the study between August 2020 and June 2022. Participants were mostly female (441/776, 56.8%), of Chinese ethnicity (741/776, 92%), undergraduate students (759/776, 97.8%), and had a mean BMI of 21.9 (SD 3.3) kg/m2, and a mean age of 22.7 (SD 1.7) years. A substantial proportion were overweight (202/776, 26.1%) or obese (42/776, 5.4%), had indicated poor mental well-being (World Health Organization-5 Well-Being Index ≤50; 291/776, 37.7%), or were at higher risk for psychological distress (Kessler Psychological Distress Scale ≥13; 109/776, 14.1%). CONCLUSIONS: The findings from this study will provide detailed insights into the determinants and trajectories of health behaviors, health, and well-being during the student-to-work life transition experienced by young adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT05154227; https://clinicaltrials.gov/study/NCT05154227. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56749.

Assessing the value of the water drinking test in glaucoma-a systematic review and meta-analysis.

This systematic review and meta-analysis examines the relationship between intraocular pressure (IOP) parameters derived from the water drinking test (WDT) and diurnal IOP monitoring, and evaluates the reproducibility of the WDT and its association with future glaucomatous visual field (VF) loss. A literature search was performed on PubMed, EMBASE, and Cochrane Library from inception to 31 March 2023. Cohort, cross-sectional and observational studies reporting WDT results in glaucoma patients were included. Meta analysis with random-effect model was performed using "metafor" package in R version 3.2.1. 641 studies were identified on initial literature search. 38 studies (2479 subjects) were included in final analysis. Meta-analytic estimates of 5 studies (310 subjects) found strong positive correlation in peak IOP between the WDT and diurnal IOP monitoring (r = 0.92, 95% CI = 0.75, 1.08, p < 0.0001). However, there was only weak positive correlation for IOP fluctuation between both methods (r = 0.26, 95% CI = 0.06,0.47, p < 0.0001). Meta-analytic estimates of 3 studies (189 subjects) suggested a trend of the diurnal peak IOP being lower than that derived from the WDT (MD = -2.37 mmHg, 95% Limit of Agreement (LOA) =-5.58,0.84, p = 0.147). Two studies found that a higher WDT peak IOP was associated with greater future VF progression. Two studies demonstrated good reproducibility in peak IOP measurements for WDTs conducted across different days. In conclusion, there was a strong positive correlation between IOP peak measurements from the WDT and diurnal IOP monitoring in glaucoma patients. The WDT peak IOP demonstrated good reproducibility and may be associated with greater future VF progression.

The cross-sectional and prospective associations of parental practices and environmental factors with 24-hour movement behaviours among school-aged Asian children.

BACKGROUND: Parental practices and neighbourhood environmental factors may influence children's movement behaviours. We aimed to investigate the cross-sectional and prospective associations of parental practices and neighbourhood environmental factors with accelerometer-measured 24-hour movement behaviours (24 h-MBs) among school-aged children in Singapore. METHODS: The Growing Up in Singapore Towards healthy Outcomes (GUSTO) study collected information on dimensions of parental practices and neighbourhood environment at age 5.5 years. Confirmatory factor analyses were performed to generate latent variables and used to compute overall parental practices [involvement in PA + support for PA + control of screen viewing context] and environmental scores [facilities for active play + active mobility facilitators + barriers*-1]. Children wore an accelerometer on their non-dominant wrist for seven consecutive days at ages 5.5 and 8 years. The R-package GGIR 2.6 was used to derive moderate-to-vigorous-intensity physical activity (MVPA), light-intensity physical activity (LPA), inactivity, and total-sleep (napping+night sleep) minutes per day. Associations were determined using compositional data analysis with multivariate linear regression models, taking into account potential confounders. RESULTS: Among 425 children (48% girls, 59% Chinese), higher parental involvement in PA, parental support for PA and overall parental practices were associated with 24 h-MBs at ages 5.5 and 8 years, specifically with greater time spent in MVPA and less time being inactive relative to the remaining movement behaviours. The corresponding mean changes in the overall 24 h-MB for increasing parental practices from lowest to highest scores (- 2 to + 2 z-scores) indicated potential increases of up to 15-minutes in MVPA, 20-minutes in LPA, 5-minutes in sleep duration, and a reduction of 40-minutes in inactivity at age 5.5 years. At age 8 years, this could translate to approximately 15-minutes more of MVPA, 20-minutes more of LPA, a 20-minute reduction in sleep duration, and a 20-minute reduction in inactivity. Parental control of screen viewing contexts and neighbourhood environmental factors were not associated with 24 h-MBs. CONCLUSIONS: Parental practices but not environmental factors were associated with higher MVPA and lower inactivity among Singaporean children, even at a later age. Further research may provide insights that support development of targeted public health strategies to promote healthier movement behaviours among children. STUDY REGISTRATION: This study was registered on 4th August 2010 and is available online at ClinicalTrials.gov: NCT01174875.

Comparison of short-term outcomes between patients with extracranial carotid and/or intracranial atherosclerotic disease.

OBJECTIVE: To directly compare the 90-day outcomes of patients with symptomatic intracranial atherosclerotic disease (ICAD), extracranial carotid atherosclerotic disease (ECAD), and ICAD with concomitant ECAD. METHODS: From 2017-2021, patients who had (1) a transient ischemic attack or ischemic stroke within 30 days of admission as evaluated by a stroke neurologist and (2) ipsilateral ICAD and/or ECAD were prospectively enrolled. The cohort was divided into three groups: ICAD, ECAD, and ICAD with concomitant ECAD. The primary outcome assessed was 90-day ischemic stroke recurrence. Secondary outcomes included 90-day myocardial infarction (MI), all-cause mortality, and major adverse cardiovascular events (MACE, including cardiovascular death, nonfatal MI, and/or nonfatal ischemic stroke). RESULTS: Of 371 patients included in the analysis, 240 (64.7%) patients had ICAD only, 93 (25.0%) patients had ECAD only, and 38 (10.3%) patients had ICAD with concomitant ECAD. On multivariate time-to-event analysis adjusting for potential confounders and with ICAD as the reference comparator, the risk of 90-day clinical outcomes was highest among patients with ICAD and concomitant ECAD, with adjusted hazard ratios of 4.54 (95% CI=1.45, 14.2; p = 0.006), 9.32 (95% CI=1.58, 54.8; p = 0.014), and 8.52 (95% CI=3.54, 20.5; p < 0.001) for 90-day ischemic stroke, MI, and MACE, respectively. CONCLUSIONS: Patients with ICAD and concomitant ECAD have a poorer prognosis and are at significantly higher risk for 90-day ischemic stroke, MI, and MACE. Further research should focus on the evaluation of coronary atherosclerotic disease and more intensive medical therapy in this population.

Evaluating the Effects of Rewards and Schedule Length on Response Rates to Ecological Momentary Assessment Surveys: Randomized Controlled Trials.

BACKGROUND: Ecological momentary assessments (EMAs) are short, repeated surveys designed to collect information on experiences in real-time, real-life contexts. Embedding periodic bursts of EMAs within cohort studies enables the study of experiences on multiple timescales and could greatly enhance the accuracy of self-reported information. However, the burden on participants may be high and should be minimized to optimize EMA response rates. OBJECTIVE: We aimed to evaluate the effects of study design features on EMA response rates. METHODS: Embedded within an ongoing cohort study (Health@NUS), 3 bursts of EMAs were implemented over a 7-month period (April to October 2021). The response rate (percentage of completed EMA surveys from all sent EMA surveys; 30-42 individual EMA surveys sent/burst) for each burst was examined. Following a low response rate in burst 1, changes were made to the subsequent implementation strategy (SMS text message announcements instead of emails). In addition, 2 consecutive randomized controlled trials were conducted to evaluate the efficacy of 4 different reward structures (with fixed and bonus components) and 2 different schedule lengths (7 or 14 d) on changes to the EMA response rate. Analyses were conducted from 2021 to 2022 using ANOVA and analysis of covariance to examine group differences and mixed models to assess changes across all 3 bursts. RESULTS: Participants (N=384) were university students (n=232, 60.4% female; mean age 23, SD 1.3 y) in Singapore. Changing the reward structure did not significantly change the response rate (F3,380=1.75; P=.16). Changing the schedule length did significantly change the response rate (F1,382=6.23; P=.01); the response rate was higher for the longer schedule (14 d; mean 48.34%, SD 33.17%) than the shorter schedule (7 d; mean 38.52%, SD 33.44%). The average response rate was higher in burst 2 and burst 3 (mean 50.56, SD 33.61 and mean 48.34, SD 33.17, respectively) than in burst 1 (mean 25.78, SD 30.12), and the difference was statistically significant (F2,766=93.83; P<.001). CONCLUSIONS: Small changes to the implementation strategy (SMS text messages instead of emails) may have contributed to increasing the response rate over time. Changing the available rewards did not lead to a significant difference in the response rate, whereas changing the schedule length did lead to a significant difference in the response rate. Our study provides novel insights on how to implement EMA surveys in ongoing cohort studies. This knowledge is essential for conducting high-quality studies using EMA surveys. TRIAL REGISTRATION: ClinicalTrials.gov NCT05154227; https://clinicaltrials.gov/ct2/show/NCT05154227.

Functional Near-Infrared Spectroscopy of English-Speaking Adults With Attention-Deficit/Hyperactivity Disorder During a Verbal Fluency Task.

OBJECTIVE: Functional near-infrared spectroscopy (fNIRS) provides direct and quantitative assessment of cortical hemodynamic response. It has been used to identify neurophysiological alterations in medication-naïve adults with attention-deficit/hyperactivity disorder (ADHD). Hence, this study aimed to distinguish both medication-naïve and medicated adults with ADHD from healthy controls (HC). METHOD: 75 HCs, 75 medication-naïve, and 45 medicated patients took part in this study. fNIRS signals during a verbal fluency task (VFT) were acquired using a 52-channel system and relative oxy-hemoglobin changes in the prefrontal cortex were quantified. RESULTS: Prefrontal cortex hemodynamic response was lower in patients than HCs (p ≤ ≤.001). Medication-naïve and medicated patients did not differ in hemodynamic response or symptom severity (p > .05). fNIRS measurements were not associated with any clinical variables (p > .05). 75.8% patients and 76% HCs were correctly classified using hemodynamic response. CONCLUSION: fNIRS may be a potential diagnostic tool for adult ADHD. These findings need to be replicated in larger validation studies.

Distal medium vessel occlusions in acute ischaemic stroke - Stent retriever versus direct aspiration: A systematic review and meta-analysis.

BACKGROUND: Acute ischaemic stroke due to distal medium vessel occlusion (AIS-DMVO) causes significant morbidity. Endovascular thrombectomy advancement has made treating AIS-DMVO with stent retrievers (SR) and aspiration catheters (AC) possible, however the optimal technique remains unknown. We performed a systematic review and meta-analysis to investigate the efficacy and safety of SR use compared to purely AC use in patients with AIS-DMVO. METHODS: We systematically searched PubMed, Cochrane Library and EMBASE, from inception to 2nd September 2022, for studies comparing SR or primary combined (SR/PC) against AC in AIS-DMVO. We adopted the Distal Thrombectomy Summit Group's definition of DMVO. Efficacy outcomes were functional independence (modified Rankin Scale (mRS) 0-2 at 90 days), first pass effect (modified Thrombolysis in Cerebral Infarction scale (mTICI) 2c-3 or expanded Thrombolysis in Cerebral Infarction scale (eTICI) 2c-3 at first pass), successful final recanalisation (mTICI or eTICI 2b-3), and excellent final recanalisation (mTICI or eTICI 2c-3). Safety outcomes were symptomatic intracranial haemorrhage (sICH) and 90-day mortality. RESULTS: 12 cohort studies and 1 randomised-controlled trial were included, involving 1881 patients with 1274 receiving SR/PC and 607 receiving AC only. SR/PC achieved higher odds of functional independence (odds ratio (OR) 1.33, 95% confidence interval (CI) 1.06-1.67) and lower odds of mortality (OR 0.69, 95% CI 0.50-0.94) than AC. Odds of successful/excellent recanalisation and sICH were similar between both groups. Stratified to compare only SR and only AC, the use of only SR, achieved significantly higher odds of successful recanalisation as compared to only AC (OR 1.80, 95% CI 1.17-2.78). CONCLUSION: There is potential for efficacy and safety benefits in SR/PC use as compared to AC only in AIS-DMVO. Further trials are necessary to validate the efficacy and safety of SR use in AIS-DMVO.

Longitudinal Analysis of Patterns and Correlates of Physical Activity and Sedentary Behavior in Women From Preconception to Postpartum: The Singapore Preconception Study of Long-Term Maternal and Child Outcomes Cohort.

OBJECTIVE: Longitudinal changes in physical activity (PA) and sedentary behavior patterns from preconception to postpartum are not fully characterized. We examined changes and baseline sociodemographic/clinical correlates of PA and sedentary behavior in women from preconception to postpartum. METHODS: The Singapore Preconception Study of Long-Term Maternal and Child Outcomes cohort recruited 1032 women planning pregnancy. Participants completed questionnaires at preconception, 34 to 36 weeks gestation, and 12 months postpartum. Repeated-measures linear regression models were used to analyze changes in walking, moderate to vigorous PA (MVPA), screen time, and total sedentary time, and to identify sociodemographic/clinical correlates associated with these changes. RESULTS: Of the 373 women who delivered singleton live births, 281 provided questionnaires for all time points. Walking time increased from preconception to late pregnancy but decreased postpartum (adjusted means [95% CI]: 454 [333-575], 542 [433-651], and 434 [320-547] min/wk, respectively). Vigorous-intensity PA and MVPA decreased from preconception to late pregnancy but increased postpartum (vigorous-intensity PA: 44 [11-76], 1 [-3-5], and 11 [4-19] min/wk, MVPA: 273 [174-372], 165 [95-234], and 226 [126-325] min/wk, respectively). Screen time and total sedentary time remained consistent from preconception to pregnancy but decreased postpartum (screen: 238 [199-277], 244 [211-277], and 162 [136-189] min/d, total: 552 [506-598], 555 [514-596], and 454 [410-498] min/d, respectively). Individual characteristics of ethnicity, body mass index, employment, parity, and self-rated general health significantly influenced women's activity patterns. CONCLUSION: During late pregnancy, walking time increased, while MVPA declined significantly, and partially returned to preconception levels postpartum. Sedentary time remained stable during pregnancy but decreased postpartum. The identified set of sociodemographic/clinical correlates underscores need for targeted strategies.

Clinical efficacy and long-term immunogenicity of an early triple dose regimen of SARS-CoV-2 mRNA vaccination in cancer patients.

INTRODUCTION: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. METHOD: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. RESULTS: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. CONCLUSION: This study demonstrates the benefit of early administration of the third dose among cancer patients.

Endovascular therapy for acute ischemic stroke with distal medium vessel occlusion: a systematic review and meta-analysis.

AIMS: Endovascular therapy (EVT) for distal medium vessel occlusions (DMVOs) is a potential frontier of acute ischemic stroke (AIS) treatment, but its efficacy against best medical therapy (BMT) remains unknown. We performed a systematic review and meta-analysis evaluating the efficacy and safety of EVT versus BMT in primary DMVO. METHODS: We systematically searched PubMed, Cochrane Library and Embase, from inception to August 14, 2022, for studies comparing EVT with BMT in DMVO-AIS. We adopted the Distal Thrombectomy Summit Group's definition of DMVO. Efficacy outcomes were functional independence (90-day modified Rankin Scale (mRS) 0-2) and excellent functional outcomes (90-day mRS 0-1). Safety outcomes were symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS: Fourteen observational and two randomized-controlled studies were included, with 1202 patients receiving EVT and 1267 receiving BMT. After trim-and-fill correction, EVT achieved significantly better odds of functional independence than BMT (adjusted OR 1.61, 95% CI 1.06 to 2.43). There were no significant differences in overall excellent functional outcomes (OR 1.23, 95% CI 0.88 to 1.71), sICH (OR 1.44, 95% CI 0.78 to 2.66), and mortality (OR 1.03, 95% CI 0.73 to 1.45). Stratified by EVT method, mechanical thrombectomy±intra-arterial thrombolysis achieved more excellent functional outcomes than BMT (OR 1.59, 95% CI 1.13 to 2.23). In mild strokes (National Institutes of Health Stroke Scale score <6), EVT caused significantly more sICH (OR 6.30, 95% CI 1.55 to 25.64). CONCLUSIONS: EVT shows promising efficacy benefit over BMT for primary DMVO-AIS. Further randomized controlled trials are necessary to evaluate the efficacy and safety of EVT in DMVO-AIS.

Evaluating the relationship between right-to-left shunt and white matter hyperintensities in migraine patients: A systematic review and meta-analysis.

Introduction: White matter hyperintensities (WMHs) have been observed with greater frequency in patients with migraine and are thought to be associated with impaired cognition and function. The relationship between WMHs and right-to-left shunt (RLS) in migraine patients is unknown. We performed a systematic review to determine if there is an association between RLS and WMHs in patients with migraine. Methods: A systematic search of the literature was performed in PubMed and Embase using a suitable keyword search strategy from inception up to 16th June 2021. All studies that included patients with migraine and studied RLS and WMHs were included. Results: A total of 8 non-randomized observational studies comprising 1125 patients with migraine were included; 576 had an RLS, compared to 549 patients with no RLS. The mean age of the study populations ranged from 28.4 to 43 years, while the average duration from migraine diagnosis ranged from 5.1 to 19 years. The proportion of female to male patients was consistently higher in all studies (60.0-94.4%). Amongst migraine patients with RLS, 338 patients (58.7%) had WMHs. In contrast, 256 (46.6%) of migraine patients without RLS had WMHs. RLS was significantly associated with the presence of WMHs in migraine patients (OR: 1.56, 95% CI: 1.05-2.34, p = 0.03). Conclusion: In migraine patients, RLS was significantly associated with the presence of WMHs. Longitudinal studies are warranted to establish RLS as a risk factor for WMHs in patients with migraine, and to establish the significance of these changes.

The role of head-up cardiopulmonary resuscitation in sudden cardiac arrest: a systematic review and meta-analysis.

Background: Head-up cardiopulmonary resuscitation (HU-CPR) is an experimental treatment for sudden cardiac arrest (SCA), where cardiopulmonary resuscitation (CPR) is performed in a ramped position. We evaluated whether HU-CPR improved survival and surrogate outcomes as compared to standard CPR (S-CPR). Methods: Studies reporting on HU-CPR in SCA were searched for in PubMed, Embase and Cochrane Library from inception to May 1st 2021. Outcomes included neurologically-intact survival, 24-hour-survival, intracranial pressure (ICP), cerebral perfusion pressure (CerPP) and brain blood flow (BBF). Risk of bias was assessed using the GRADE assessment tool and Newcastle Ottawa Scale. Fixed- and random-effects models were used to estimate the pooled effects of HU-CPR at 30 degrees. Results: Thirteen articles met the criteria for inclusion (11 animal-only studies, one before-and-after human-only study, one study that utilized human- and animal-cadavers). Among animal studies, the most common implementation of HU-CPR was a 30-degree upward tilt of the head and thorax (n=7), while four studies investigated controlled sequential elevation (CSE). Two animal studies reported improved cerebral performance category (CPC) scores at 24-hour. The pooled effect on 24-hour survival was not statistically significant (P=0.37). The lone human study reported doubled return of spontaneous circulation (ROSC) (17.9% versus 34.2%, P<0.0001). The pooled effect on ROSC in three porcine studies was OR =3.63 (95% CI: 0.72-18.39). Pooled effects for surrogate physiological outcomes of intracranial cranial pressure (MD -14.08, 95% CI: -23.21 to -4.95, P=0.003), CerPP (MD 14.39, 95% CI: 3.07-25.72, P=0.01) and BBF (MD 0.14, 95% CI: 0.02-0.27, P=0.03), showed statistically significant benefit. Discussion: Overall, HU-CPR improved neurologically-intact survival at 24-hour, ROSC and physiological surrogate outcomes in animal models. Despite promising preclinical data, and one human observational study, clinical equipoise remains surrounding the role of HU-CPR in SCA, necessitating clarification with future randomized human trials.

A Web-Based, Time-Use App To Assess Children's Movement Behaviors: Validation Study of My E-Diary for Activities and Lifestyle (MEDAL).

BACKGROUND: Existing modes of collecting self-reported 24-hour movement information from children, including digital assessments, have not been demonstrated to be of acceptable validity when compared to objective measurements. My E-Diary for Activities and Lifestyle (MEDAL) is an interactive web-based diary developed to collect time-use information from children aged 10 years and older. OBJECTIVE: This study evaluated the validity of MEDAL for assessing children's movement behaviors by comparing self-reported and accelerometer-measured time spent in movement behavior among children in Singapore aged 10-11 years. METHODS: Funding for this study was obtained in October 2017, and data were collected between April and August 2020. Participants recorded their daily activities using MEDAL over 2 specified weekdays and 2 weekend days and wore an Actigraph accelerometer on their nondominant wrist throughout the study to objectively assess movement behaviors. Spearman correlation coefficient and intraclass correlation coefficient (ICC) were used to compare the accelerometer measurements and self-reports for each movement behavior. Bland-Altman plots were generated to investigate trends of bias in the self-reports. RESULTS: Among the participants aged 10-11 years (29/49, 59% boys), we observed that children reported lower light physical activity (LPA) and higher moderate-to-vigorous physical activity (MVPA), inactivity, and night sleep than that measured by the accelerometer. There was a moderate-to-strong correlation between self-reported and accelerometer-measured MVPA (r=0.37; 95% CI 0.20-0.54), inactivity (r=0.36; 95% CI 0.18-0.54), and night sleep (r=0.58; 95% CI 0.43-0.74); the correlation for LPA was poor (r=0.19; 95% CI 0.02-0.36). Agreement was poor for all behaviors (MVPA: ICC=0.24, 95% CI 0.07-0.40; LPA: ICC=0.19, 95% CI 0.01-0.36; inactivity: ICC=0.29, 95% CI 0.11-0.44; night sleep: ICC=0.45, 95% CI 0.29-0.58). There was stronger correlation and agreement on weekdays for inactivity and night sleep; conversely, there was stronger correlation and agreement for MVPA and LPA on weekend days. Finally, based on Bland-Altman plots, we observed that with increasing MVPA, children tended to report higher MVPA than that measured by the accelerometer. There were no clear trends for the other behaviors. CONCLUSIONS: MEDAL may be used to assess the movement behaviors of children. Based on self-reports, the children are able to estimate their time spent in MVPA, inactivity, and night sleep although actual time spent in these behaviors may differ from accelerometer-derived estimates; self-reported LPA warrant cautious interpretation. Observable differences in reporting accuracy exist between weekdays and weekend days.

The use of colchicine as an anti-inflammatory agent for stroke prevention in patients with coronary artery disease: a systematic review and meta-analysis.

OBJECTIVE: The primary objective is to evaluate the use of colchicine as an anti-inflammatory agent for stroke prevention in patients with coronary artery disease. BACKGROUND: There has been a rising number of randomized controlled trials conducted in patients with coronary artery disease on the use of colchicine in reducing cardiovascular complications. Recent publications suggest colchicine reduces the risk of stroke and other cardiovascular events. METHODS: We performed a systematic review of known trials in the current literature to characterize the clinical characteristics and outcomes of colchicine treatment in patients with coronary artery disease. A literature search was performed in PubMed, Embase and SCOPUS using a suitable keyword search strategy from inception to 4 June 2021. All studies evaluating cardiovascular outcomes of colchicine treatment in patients with coronary artery disease were included. RESULTS: The systemic review included 5 randomized controlled trials assessing a total of 11,790 patients. Majority of studies used a colchicine dosing regimen of 0.5 mg once daily, with the median follow-up duration ranging from 6 to 36 months. Meta-analytic estimates for stroke incidence highlighted a statistically significant benefit for patients that were administered colchicine compared to placebo (OR 0.47, 95% CI 0.27-0.81, p = 0.006), and a non-significant benefit for myocardial infarction. There was no significant association between colchicine treatment and the adverse effects of gastrointestinal symptoms and myopathy/myalgia. CONCLUSIONS: The use of colchicine reduces the risk of stroke in patients with a history of coronary artery disease, without a significant increase in gastrointestinal and myopathy/myalgia adverse effects.

24-hour movement behaviour profiles and their transition in children aged 5.5 and 8 years - findings from a prospective cohort study.

BACKGROUND: Time spent in movement behaviours, including physical activity (PA), sedentary behaviour (SB) and sleep, across the 24-h day may have distinct health consequences. We aimed to describe 24-h movement behaviour (24 h-MB) profiles in children and how profile membership changed from age 5.5 to 8 years. METHODS: Children in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort were asked to wear an accelerometer (ActiGraph-GT3X+) on their wrist for seven consecutive days at ages 5.5 and 8 years to measure 24 h-MB patterns. Time spent in night sleep, inactivity (proxy for SB), light PA, moderate PA (MPA), and vigorous PA (VPA) per day were calculated using the R-package GGIR 2.0. Using latent profile analyses (n = 442) we identified 24 h-MB profiles, which were given animal names to convey key characteristics. Latent transition analyses were used to describe the profile membership transition from ages 5.5 to 8 years. Associations with sex and ethnicity were examined. RESULTS: We identified four profiles, "Rabbits" (very high-MPA/VPA, low-inactivity and average-night-sleep), "Chimpanzees" (high-MPA, low-inactivity and average-night-sleep), "Pandas" (low-PA, high-inactivity and high-night-sleep) and "Owls" (low-PA, high-inactivity and low-night-sleep), among children at both time points. At ages 5.5 and 8 years, the majority of children were classified into profiles of "Chimpanzees" (51 and 39%, respectively) and "Pandas" (24 and 37%). Half of the sample (49%), particularly "Rabbits", remained in the same profile at ages 5.5 and 8 years: among children who changed profile the predominant transitions occurred from "Chimpanzees" (27%) and "Owls" (56%) profiles to "Pandas". Sex, but not ethnicity, was associated with profile membership: compared to girls, boys were more likely to be in the "Rabbits" profile (adjusted OR [95% CI]: 3.6 [1.4, 9.7] and 4.5 [1.8, 10.9] at ages 5.5 and 8 years, respectively) and less likely to be in the "Pandas" profile (0.5 [0.3, 0.9] and 0.4 [0.2, 0.6]) at both ages. CONCLUSIONS: With increasing age about half the children stayed in the same of four 24 h-MB profiles, while the predominant transition for the remaining children was towards lower PA, higher inactivity and longer sleep duration. These findings can aid development and implementation of public health strategies to promote better health. STUDY REGISTRATION: This study was registered on 4th August 2010 and is available online at ClinicalTrials.gov: NCT01174875 .

Maternal height, gestational diabetes mellitus and pregnancy complications.

AIMS: To explore the glucose-overload hypothesis of artefactual gestational diabetes (GDM) diagnosis in shorter women during oral glucose tolerance testing (OGTT), by investigating associations between height and maternal glycemia; and GDM and pregnancy complications in height-groups. METHODS: Women from GUSTO (n = 1100, 2009-2010) and NUH (n = 4068, 2017-2018) cohorts underwent a mid-gestation two and three time-point 75 g 2-hour OGTT, respectively. GDM-related complications (hypertensive disorders of pregnancy, preterm delivery, emergency cesarean section, neonatal intensive care unit admission, macrosomia, birthweight) were compared within shorter and taller groups, dichotomized by ethnic-specific median height. RESULTS: Using WHO-1999 criteria, 18.8% (GUSTO) to 22.9% (NUH) of women were diagnosed with GDM-1999; and by WHO-2013 criteria, 21.9% (NUH) had GDM-2013. Each 5-cm height increment was inversely associated with GDM-1999 (adjusted odds ratio [aOR, 95% CI] = 0.81 [0.76-0.87], 2-h glycemia (adjusted ß [aß, 95% CI] = -0.171 mmol/L [-0.208, -0.135]) and 1-h glycemia (aß = -0.160 mmol/L [-0.207, -0.112]). The inverse association between height and 2-h glycemia was most marked in "Other" ethnicities (Eurasians/Caucasians/mixed/other Asians) and Indians, followed by Chinese, then Malays. Compared with non-GDM, GDM-1999 was associated with preterm delivery (aOR = 1.76 [1.19-2.61]) and higher birthweight (aß = 57.16 g [20.95, 93.38]) only among taller but not shorter women. CONCLUSIONS: Only taller women had an increased odds of GDM-related pregnancy complications. An artefactual GDM diagnosis due to glucose-overload among shorter women is plausible.

Intra-Arterial Adjunctive Medications for Acute Ischemic Stroke During Mechanical Thrombectomy: A Meta-Analysis.

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke with large vessel occlusion, the role of intra-arterial adjunctive medications (IAMs), such as urokinase, tPA (tissue-type plasminogen activator), or glycoprotein IIb/IIIa inhibitors, during mechanical thrombectomy (MT) has not been clearly established. We aim to evaluate the efficacy and safety of concomitant or rescue IAM for acute ischemic stroke with large vessel occlusion patients undergoing MT. METHODS: We searched Medline, Embase, and Cochrane Stroke Group Trials Register databases from inception until March 13, 2020. We analyzed all studies with patients diagnosed with acute ischemic stroke with large vessel occlusion in the anterior or posterior circulation that provided data for the two treatment arms, (1) MT+IAM and (2) MT only, and also reported on at least one of the following efficacy outcomes, recanalization and 90-day modified Rankin Scale, or safety outcomes, symptomatic intracranial hemorrhage and 90-day mortality. Data were collated in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Sixteen nonrandomized observational studies with a total of 4581 patients were analyzed. MT only was performed in 3233 (70.6%) patients, while 1348 (29.4%) patients were treated with both MT and IAM. As compared with patients treated with MT alone, patients treated with combination therapy (MT+IAM) had a higher likelihood of achieving good functional outcome (risk ratio, 1.13 [95% CI, 1.03-1.24]) and a lower risk of 90-day mortality (risk ratio, 0.82 [95% CI, 0.72-0.94]). There was no significant difference in successful recanalization (risk ratio, 1.02 [95% CI, 0.99-1.06]) and symptomatic intracranial hemorrhage between the two groups (risk ratio, 1.13 [95% CI, 0.87-1.46]). CONCLUSIONS: In acute ischemic stroke with large vessel occlusion, the use of IAM together with MT may achieve better functional outcomes and lower mortality rates. Randomized controlled trials are warranted to establish the safety and efficacy of IAM as adjunctive treatment to MT.

Cerebral Venous Thrombosis in Patients with COVID-19 Infection: a Case Series and Systematic Review.

BACKGROUND: There has been increasing reports associating the coronavirus disease 2019 (COVID-19) with thromboembolic phenomenon including ischemic strokes and venous thromboembolism. Cerebral venous thrombosis (CVT) is a rare neurovascular emergency that has been observed in some COVID-19 patients, yet much remains to be learnt of its underlying pathophysiology. OBJECTIVE: We present a case series of local patients with concomitant COVID-19 infection and CVT; and aim to perform a systematic review of known cases in the current literature. METHODS: We describe two patients with concomitant COVID-19 infection and CVT from a nationwide registry in Singapore. We then conducted a literature search in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 11th June 2020. All studies reporting CVT in COVID-19 patients were included. RESULTS: Nine studies and 14 COVID-19 patients with CVT were studied. The median age was 43 years (IQR=36-58) and majority had no significant past medical conditions (60.0%). The time taken from onset of COVID-19 symptoms to CVT diagnosis was a median of 7 days (IQR=6-14). CVT was commonly seen in the transverse (75.0%) and sigmoid sinus (50.0%); 33.3% had involvement of the deep venous sinus system. A significant proportion of patients had raised D-dimer (75.0%) and CRP levels (50.0%). Two patients reported presence of antiphospholipid antibodies. Most patients received anticoagulation (91.7%) while overall mortality rate was 45.5%. CONCLUSIONS: The high mortality rate of CVT in COVID-19 infection warrants a high index of suspicion from physicians, and early treatment with anticoagulation should be initiated.