Cardiovascular Risk Estimation Is Suboptimal in People With HIV.

BACKGROUND: Established cardiovascular disease (CVD) risk prediction functions may not accurately predict CVD risk in people with HIV. We assessed the performance of 3 CVD risk prediction functions in 2 HIV cohorts. METHODS AND RESULTS: CVD risk scores were calculated in the Mass General Brigham and Kaiser Permanente Northern California HIV cohorts, using the American College of Cardiology/American Heart Association atherosclerotic CVD function, the FHS (Framingham Heart Study) hard coronary heart disease function and the Framingham Heart Study hard CVD function. Outcomes were myocardial infarction or coronary death for FHS hard coronary heart disease function; and myocardial infarction, stroke, or coronary death for American College of Cardiology/American Heart Association and FHS hard CVD function. We calculated regression coefficients and assessed discrimination and calibration by sex; predicted to observed risk of outcome was also compared. In the combined cohort of 9412, 158 (1.7%) had a coronary heart disease event, and 309 (3.3%) had a CVD event. Among women, CVD risk was generally underestimated by all 3 risk functions. Among men, CVD risk was underestimated by the American College of Cardiology/American Heart Association and FHS hard CVD function, but overestimated by the FHS hard coronary heart disease function. Calibration was poor for women using the FHS hard CVD function and for men using all functions. Discrimination in all functions was good for women (c-statistics ranging from 0.78 to 0.90) and moderate for men (c-statistics ranging from 0.71 to 0.72). CONCLUSIONS: Established CVD risk prediction functions generally underestimate risk in people with HIV. Differences in model performance by sex underscore the need for both HIV-specific and sex-specific functions. Development of CVD risk prediction models tailored to HIV will enhance care for aging people with HIV.

Meta-analysis of risk of major adverse cardiovascular events in adults with type 2 diabetes treated with bexagliflozin.

AIM: To explore the risk of major adverse cardiovascular events (MACE) associated with exposure to bexagliflozin. METHODS: The analysis included 4090 participants with type 2 diabetes (T2D) enrolled in nine phase 2 and 3 double-blind randomized controlled trials. All potential MACE were adjudicated by a blinded committee. The primary endpoint for the meta-analysis was the hazard ratio (HR) for the time to first occurrence of non-fatal stroke, non-fatal myocardial infarction (MI), cardiovascular (CV) death or hospitalization for unstable angina (MACE+), tested for non-inferiority to a ratio of 1.8. The secondary endpoints were time to first occurrence of (i) non-fatal stroke, non-fatal MI or CV death (MACE), tested for non-inferiority to a ratio of 1.3; and (ii) CV death or hospitalization for heart failure, tested for superiority. RESULTS: The HR for the primary endpoint of MACE+ was 0.80 (95% confidence interval [CI] 0.58, 1.09), which fulfilled the non-inferiority objective with a P value of less than 0.0001. Non-inferiority for the first key secondary endpoint of MACE was also shown (HR = 0.82; 95% CI 0.59, 1.13; P = 0.0023). Superiority for time to CV death or first hospitalization for heart failure was not shown. CONCLUSIONS: Bexagliflozin did not increase the risk of MACE in participants with T2D when compared with placebo or active control. Both the preapproval and postapproval thresholds for CV safety were met and bexagliflozin has been approved by the US Food and Drug Administration.

Distribution, Determinants and Normal Reference Values of Aortic Arch Width: Thoracic Aortic Geometry in the Framingham Heart Study.

Study Objective: Aortic arch geometry changes with age, including an increase in aortic arch width (AAW). High AAW is a predictor of incident adverse cardiovascular disease (CVD) events, but its distribution and determinants are unknown. We hypothesized that traditional CVD risk factors, in addition to age, are associated with increased AAW in community-dwelling adults. Study Design: Framingham Offspring and Third Generation cohort participants (N=3026, 52% Men) underwent thoracic multidetector computed tomography (MDCT). A referent group (733M, 738W) free of clinical CVD, hypertension, dyslipidemia, smoking, and diabetes was used to generate sex and 10-year age-group specific upper 90th percentile (P90) cut-points for AAW. AAW was measured as the distance between the cross-sectional centroids of the ascending and descending thoracic aorta. Multivariable logistic regression models were used to identify clinical correlates of high AAW (≥referent P90) in the overall study group. Results: Among referent participants, AAW increased with greater age-group, p for trend <0.0001 in each sex. Overall and within each age group, AAW was greater in men than women, p<0.0001 all comparisons. Across all participants, high AAW was associated with greater age (odds ratio, OR=1.34/10y; 95% confidence interval 1.20 - 1.50), body surface area (OR=1.97/SD; 1.62 - 2.40), diastolic blood pressure (OR=1.59/10mmHg; 1.40 - 1.81), pack-years smoked (OR=1.07; 1.02 - 1.13), and prevalent CVD (OR=1.64; 1.08 - 2.49). Conclusion: AAW increases with greater age, body size, diastolic blood pressure and burden of smoking. High AAW (≥referent P90) is also associated with prevalent (clinically apparent) CVD. AAW is often seen on and easily measured from tomographic thoracic images and has prognostic value.

Standardized measurement of abdominal muscle by computed tomography: association with cardiometabolic risk in the Framingham Heart Study.

OBJECTIVES: To provide a standard for total abdominal muscle mass (TAM) quantification on computed tomography (CT) and investigate its association with cardiovascular risk in a primary prevention setting. METHODS: We included 3016 Framingham Heart Study participants free of cardiovascular disease (CVD) who underwent abdominal CT between 2002 and 2005. On a single CT slice at the level of L3/L4, we segmented (1) TAM-Area, (2) TAM-Index (= TAM-Area/height) and, (3) TAM-Fraction (= TAM-Area/total cross-sectional CT-area). We tested the association of these muscle mass measures with prevalent and incident cardiometabolic risk factors and incident CVD events during a follow-up of 11.0 ± 2.7 years. RESULTS: In this community-based sample (49% women, mean age: 50.0 ± 10.0 years), all muscle quantity measures were significantly associated with prevalent and incident cardiometabolic risk factors and CVD events. However, only TAM-Fraction remained significantly associated with key outcomes (e.g., adj. OR 0.68 [0.55, 0.84] and HR 0.73 [0.57, 0.92] for incident hypertension and CVD events, respectively) after adjustment for age, sex, body mass index, and waist circumference. Moreover, only higher TAM-Fraction was associated with a lower risk (e.g., adj. OR: 0.56 [0.36-0.89] for incident diabetes versus TAM-Area: adj. OR 1.26 [0.79-2.01] and TAM-Index: 1.09 [0.75-1.58]). CONCLUSION: TAM-Fraction on a single CT slice at L3/L4 is a novel body composition marker of cardiometabolic risk in a primary prevention setting that has the potential to improve risk stratification beyond traditional measures of obesity. KEY POINTS: • In this analysis of the Framingham Heart Study (n = 3016), TAM-F on a single slice CT was more closely associated with prevalent and incident cardiometabolic risk factors as compared to TAM alone or TAM indexed to body surface area. • TAM-F on a single abdominal CT slice at the level of L3/L4 could serve as a standard measure of muscle mass and improve risk prediction.

Advances in Our Clinical Understanding of Autonomic Regulation Therapy Using Vagal Nerve Stimulation in Patients Living With Heart Failure.

The ANTHEM-HF, INOVATE-HF, and NECTAR-HF clinical studies of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) systems have collectively provided dose-ranging information enabling the development of several working hypotheses on how stimulation frequency can be utilized during VNS for tolerability and improving cardiovascular outcomes in patients living with heart failure (HF) and reduced ejection fraction (HFrEF). Changes in heart rate dynamics, comprising reduced heart rate (HR) and increased HR variability, are a biomarker of autonomic nerve system engagement and cardiac control, and appear to be sensitive to VNS that is delivered using a stimulation frequency that is similar to the natural operating frequency of the vagus nerve. Among prior studies, the ANTHEM-HF Pilot Study has provided the clearest evidence of autonomic engagement with VNS that was delivered using a stimulation frequency that was within the operating range of the vagus nerve. Achieving autonomic engagement was accompanied by improvement from baseline in six-minute walk duration (6MWD), health-related quality of life, and left ventricular EF (LVEF), over and above those achieved by concomitant guideline-directed medical therapy (GDMT) administered to counteract harmful neurohormonal activation, with relative freedom from deleterious effects. Autonomic engagement and positive directional changes have persisted over time, and an exploratory analysis suggests that improvement in autonomic tone, symptoms, and physical capacity may be independent of baseline NT-proBNP values. Based upon these encouraging observations, prospective, randomized controlled trials examining the effects on symptoms and cardiac function as well as natural history have been warranted. A multi-national, large-scale, randomized, controlled trial is well underway to determine the outcomes associated with ART using autonomic nervous system engagement as a guide for VNS delivery.

Perihematomal Edema and Clinical Outcome After Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.

BACKGROUND: Perihematomal edema (PHE) has been proposed as a radiological marker of secondary injury and therapeutic target in intracerebral hemorrhage (ICH). We conducted a systematic review and meta-analysis to assess the prognostic impact of PHE on functional outcome and mortality in patients with ICH. METHODS: We searched major databases through December 2020 using predefined keywords. Any study using logistic regression to examine the association between PHE or its growth and functional outcome was included. We examined the overall pooled effect and conducted secondary analyses to explore the impact of individual PHE measures on various outcomes separately. Study quality was assessed by three independent raters using the Newcastle-Ottawa Scale. Odds ratios (per 1-unit increase in PHE) and their confidence intervals (CIs) were log transformed and entered into a DerSimonian-Laird random-effects meta-analysis to obtain pooled estimates of the effect. RESULTS: Twenty studies (n = 6633 patients) were included in the analysis. The pooled effect size for overall outcome was 1.05 (95% CI 1.02-1.08; p < 0.00). For the following secondary analyses, the effect size was weak: mortality (1.01; 95% CI 0.90-1.14), functional outcome (1.04; 95% CI 1.02-1.07), both 90-day (1.06; 95% CI 1.02-1.11), and in-hospital assessments (1.04; 95% CI 1.00-1.08). The effect sizes for PHE volume and PHE growth were 1.04 (95% CI 1.01-1.07) and 1.14 (95% CI 1.04-1.25), respectively. Heterogeneity across studies was substantial except for PHE growth. CONCLUSIONS: This meta-analysis demonstrates that PHE volume within the first 72 h after ictus has a weak effect on functional outcome and mortality after ICH, whereas PHE growth might have a slightly larger impact during this time frame. Definitive conclusions are limited by the large variability of PHE measures, heterogeneity, and different evaluation time points between studies.

Calculating power for the Finkelstein and Schoenfeld test statistic for a composite endpoint with two components.

The Finkelstein and Schoenfeld (FS) test is a popular generalized pairwise comparison approach to analyze prioritized composite endpoints (eg, components are assessed in order of clinical importance). Power and sample size estimation for the FS test, however, are generally done via simulation studies. This simulation approach can be extremely computationally burdensome, compounded by increasing number of composite endpoints and with increasing sample size. Here we propose an analytical solution to calculate power and sample size for commonly encountered two-component hierarchical composite endpoints. The power formulas are derived assuming underlying distributions in each of the component outcomes on the population level, which provide a computationally efficient and practical alternative to the standard simulation approach. Monte Carlo simulation results demonstrate that performance of the proposed power formulas are consistent with that of the simulation approach, and have generally desirable objective properties including robustness to mis-specified distributional assumptions. We demonstrate the application of the proposed formulas by calculating power and sample size for the Transthyretin Amyloidosis Cardiomyopathy Clinical Trial.

Latent Pulmonary Vascular Disease May Alter the Response to Therapeutic Atrial Shunt Device in Heart Failure.

BACKGROUND: In REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure), implantation of an atrial shunt device did not provide overall clinical benefit for patients with heart failure with preserved or mildly reduced ejection fraction. However, prespecified analyses identified differences in response in subgroups defined by pulmonary artery systolic pressure during submaximal exercise, right atrial volume, and sex. Shunt implantation reduces left atrial pressures but increases pulmonary blood flow, which may be poorly tolerated in patients with pulmonary vascular disease (PVD). On the basis of these results, we hypothesized that patients with latent PVD, defined as elevated pulmonary vascular resistance during exercise, might be harmed by shunt implantation, and conversely that patients without PVD might benefit. METHODS: REDUCE LAP-HF II enrolled 626 patients with heart failure, ejection fraction ≥40%, exercise pulmonary capillary wedge pressure ≥25 mm Hg, and resting pulmonary vascular resistance <3.5 Wood units who were randomized 1:1 to atrial shunt device or sham control. The primary outcome-a hierarchical composite of cardiovascular death, nonfatal ischemic stroke, recurrent HF events, and change in health status-was analyzed using the win ratio. Latent PVD was defined as pulmonary vascular resistance ≥1.74 Wood units (highest tertile) at peak exercise, measured before randomization. RESULTS: Compared with patients without PVD (n=382), those with latent PVD (n=188) were older, had more atrial fibrillation and right heart dysfunction, and were more likely to have elevated left atrial pressure at rest. Shunt treatment was associated with worse outcomes in patients with PVD (win ratio, 0.60 [95% CI, 0.42, 0.86]; P=0.005) and signal of clinical benefit in patients without PVD (win ratio, 1.31 [95% CI, 1.02, 1.68]; P=0.038). Patients with larger right atrial volumes and men had worse outcomes with the device and both groups were more likely to have pacemakers, heart failure with mildly reduced ejection fraction, and increased left atrial volume. For patients without latent PVD or pacemaker (n=313; 50% of randomized patients), shunt treatment resulted in more robust signal of clinical benefit (win ratio, 1.51 [95% CI, 1.14, 2.00]; P=0.004). CONCLUSIONS: In patients with heart failure with preserved or mildly reduced ejection fraction, the presence of latent PVD uncovered by invasive hemodynamic exercise testing identifies patients who may worsen with atrial shunt therapy, whereas those without latent PVD may benefit.

Atrial shunt device for heart failure with preserved and mildly reduced ejection fraction (REDUCE LAP-HF II): a randomised, multicentre, blinded, sham-controlled trial.

BACKGROUND: Placement of an interatrial shunt device reduces pulmonary capillary wedge pressure during exercise in patients with heart failure and preserved or mildly reduced ejection fraction. We aimed to investigate whether an interatrial shunt can reduce heart failure events or improve health status in these patients. METHODS: In this randomised, international, blinded, sham-controlled trial performed at 89 health-care centres, we included patients (aged ≥40 years) with symptomatic heart failure, an ejection fraction of at least 40%, and pulmonary capillary wedge pressure during exercise of at least 25 mm Hg while exceeding right atrial pressure by at least 5 mm Hg. Patients were randomly assigned (1:1) to receive either a shunt device or sham procedure. Patients and outcome assessors were masked to randomisation. The primary endpoint was a hierarchical composite of cardiovascular death or non-fatal ischemic stroke at 12 months, rate of total heart failure events up to 24 months, and change in Kansas City Cardiomyopathy Questionnaire overall summary score at 12 months. Pre-specified subgroup analyses were conducted for the heart failure event endpoint. Analysis of the primary endpoint, all other efficacy endpoints, and safety endpoints was conducted in the modified intention-to-treat population, defined as all patients randomly allocated to receive treatment, excluding those found to be ineligible after randomisation and therefore not treated. This study is registered with ClinicalTrials.gov, NCT03088033. FINDINGS: Between May 25, 2017, and July 24, 2020, 1072 participants were enrolled, of whom 626 were randomly assigned to either the atrial shunt device (n=314) or sham procedure (n=312). There were no differences between groups in the primary composite endpoint (win ratio 1·0 [95% CI 0·8-1·2]; p=0·85) or in the individual components of the primary endpoint. The prespecified subgroups demonstrating a differential effect of atrial shunt device treatment on heart failure events were pulmonary artery systolic pressure at 20W of exercise (pinteraction=0·002 [>70 mm Hg associated with worse outcomes]), right atrial volume index (pinteraction=0·012 [≥29·7 mL/m2, worse outcomes]), and sex (pinteraction=0·02 [men, worse outcomes]). There were no differences in the composite safety endpoint between the two groups (n=116 [38%] for shunt device vs n=97 [31%] for sham procedure; p=0·11). INTERPRETATION: Placement of an atrial shunt device did not reduce the total rate of heart failure events or improve health status in the overall population of patients with heart failure and ejection fraction of greater than or equal to 40%. FUNDING: Corvia Medical.

Assessing Cardiovascular Risk in People Living with HIV: Current Tools and Limitations.

PURPOSE OF REVIEW: To provide the current state of the development and application of cardiovascular disease (CVD) prediction tools in people living with HIV (PLWH). RECENT FINDINGS: Several risk prediction models developed on the general population are available to predict CVD risk, the most notable being the US-based pooled cohort equations (PCE), the Framingham risk functions, and the Europe-based SCORE (Systematic COronary Risk Evaluation). In validation studies in cohorts of PLWH, these models generally underestimate CVD risk, especially in individuals who are younger, women, Black race, or predicted to be at low/intermediate risk. An HIV-specific CVD prediction model, the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) model, is available, but its performance is modest, especially in US-based cohorts. Enhancing CVD prediction with novel biomarkers of inflammation or coronary artery calcification is of interest but has not yet been evaluated in PLWH. Finally, studies on CVD risk prediction are lacking in diverse PLWH globally. While available risk models for CVD prediction in PLWH remain suboptimal, clinicians should remain vigilant of higher CVD risk in this population and should use any of these risk scores for risk stratification to guide preventive interventions. Focus on established traditional risk factors such as smoking remains critical in PLWH. Risk prediction functions tailored to PLWH in diverse settings will enhance clinicians' ability to deliver optimal preventive care.

Sex Differences in the Associations of Visceral Adipose Tissue and Cardiometabolic and Cardiovascular Disease Risk: The Framingham Heart Study.

Background Men and women are labeled as obese on the basis of a body mass index (BMI) using the same criterion despite known differences in their fat distributions. Subcutaneous adipose tissue and visceral adipose tissue (VAT), as measured by computed tomography, are advanced measures of obesity that closely correlate with cardiometabolic risk independent of BMI. However, it remains unknown whether prognostic significance of anthropometric measures of adiposity versus VAT varies in men versus women. Methods and Results In 3482 FHS (Framingham Heart Study) participants (48.1% women; mean age, 50.8±10.3 years), we tested the associations of computed tomography-based versus anthropometric measures of fat with cardiometabolic and cardiovascular disease (CVD) risk. Mean follow-up was 12.7±2.1 years. In men, VAT, as compared with BMI, had a similar strength of association with incident cardiometabolic risk factors (eg, adjusted odds ratio [OR], 2.36 [95% CI, 1.84-3.04] versus 2.66 [95% CI, 2.04-3.47] for diabetes mellitus) and CVD events (eg, adjusted hazard ratio [HR], 1.32 [95% CI, 0.97-1.80] versus 1.74 [95% CI, 1.14-2.65] for CVD death). In women, however, VAT, when compared with BMI, conferred a markedly greater association with incident cardiometabolic risk factors (eg, adjusted OR, 4.51 [95% CI, 3.13-6.50] versus 2.33 [95% CI, 1.88-3.04] for diabetes mellitus) as well as CVD events (eg, adjusted HR, 1.85 [95% CI, 1.26-2.71] versus 1.19 [95% CI, 1.01-1.40] for CVD death). Conclusions Anthropometric measures of obesity, including waist circumference and BMI, adequately capture VAT-associated cardiometabolic and cardiovascular risk in men but not in women. In women, abdominal computed tomography-based VAT measures permit more precise assessment of obesity-associated cardiometabolic and cardiovascular risk.

Comparative Effectiveness of Heart Rate Control Medications for the Treatment of Sepsis-Associated Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) with rapid ventricular response frequently complicates the management of critically ill patients with sepsis and may necessitate the initiation of medication to avoid hemodynamic compromise. However, the optimal medication to achieve rate control for AF with rapid ventricular response in sepsis is unclear. RESEARCH QUESTION: What is the comparative effectiveness of frequently used AF medications (ß-blockers, calcium channel blockers, amiodarone, and digoxin) on heart rate (HR) reduction among critically ill patients with sepsis and AF with rapid ventricular response? STUDY DESIGN AND METHODS: We conducted a multicenter retrospective cohort study among patients with sepsis and AF with rapid ventricular response (HR > 110 beats/min). We compared the rate control effectiveness of ß-blockers to calcium channel blockers, amiodarone, and digoxin using multivariate-adjusted, time-varying exposures in competing risk models (for death and addition of another AF medication), adjusting for fixed and time-varying confounders. RESULTS: Among 666 included patients, 50.6% initially received amiodarone, 10.1% received a ß-blocker, 33.8% received a calcium channel blocker, and 5.6% received digoxin. The adjusted hazard ratio for HR of < 110 beats/min by 1 h was 0.50 (95% CI, 0.34-0.74) for amiodarone vs ß-blocker, 0.37 (95% CI, 0.18-0.77) for digoxin vs ß-blocker, and 0.75 (95% CI, 0.51-1.11) for calcium channel blocker vs ß-blocker. By 6 h, the adjusted hazard ratio for HR < 110 beats/min was 0.67 (95% CI, 0.47-0.97) for amiodarone vs ß-blocker, 0.60 (95% CI, 0.36-1.004) for digoxin vs ß-blocker, and 1.03 (95% CI, 0.71-1.49) for calcium channel blocker vs ß-blocker. INTERPRETATION: In a large cohort of patients with sepsis and AF with rapid ventricular response, a ß-blocker treatment strategy was associated with improved HR control at 1 h, but generally similar HR control at 6 h compared with amiodarone, calcium channel blocker, or digoxin.

Deep convolutional neural networks to predict cardiovascular risk from computed tomography.

Coronary artery calcium is an accurate predictor of cardiovascular events. While it is visible on all computed tomography (CT) scans of the chest, this information is not routinely quantified as it requires expertise, time, and specialized equipment. Here, we show a robust and time-efficient deep learning system to automatically quantify coronary calcium on routine cardiac-gated and non-gated CT. As we evaluate in 20,084 individuals from distinct asymptomatic (Framingham Heart Study, NLST) and stable and acute chest pain (PROMISE, ROMICAT-II) cohorts, the automated score is a strong predictor of cardiovascular events, independent of risk factors (multivariable-adjusted hazard ratios up to 4.3), shows high correlation with manual quantification, and robust test-retest reliability. Our results demonstrate the clinical value of a deep learning system for the automated prediction of cardiovascular events. Implementation into clinical practice would address the unmet need of automating proven imaging biomarkers to guide management and improve population health.

COVID-19 and climatic factors: A global analysis.

BACKGROUND: It is unknown if COVID-19 will exhibit seasonal pattern as other diseases e.g., seasonal influenza. Similarly, some environmental factors (e.g., temperature, humidity) have been shown to be associated with transmission of SARS-CoV and MERS-CoV, but global data on their association with COVID-19 are scarce. OBJECTIVE: To examine the association between climatic factors and COVID-19. METHODS: We used multilevel mixed-effects (two-level random-intercepts) negative binomial regression models to examine the association between 7- and 14-day-lagged temperature, humidity (relative and absolute), wind speed and UV index and COVID-19 cases, adjusting for Gross Domestic Products, Global Health Security Index, cloud cover (%), precipitation (mm), sea-level air-pressure (mb), and daytime length. The effects estimates are reported as adjusted rate ratio (aRR) and their corresponding 95% confidence interval (CI). RESULTS: Data from 206 countries/regions (until April 20, 2020) with ≥100 reported cases showed no association between COVID-19 cases and 7-day-lagged temperature, relative humidity, UV index, and wind speed, after adjusting for potential confounders, but a positive association with 14-day-lagged temperature and a negative association with 14-day-lagged wind speed. Compared to an absolute humidity of <5 g/m3, an absolute humidity of 5-10 g/m3 was associated with a 23% (95% CI: 6-42%) higher rate of COVID-19 cases, while absolute humidity >10 g/m3 did not have a significant effect. These findings were robust in the 14-day-lagged analysis. CONCLUSION: Our results of higher COVID-19 cases (through April 20) at absolute humidity of 5-10 g/m3 may be suggestive of a 'sweet point' for viral transmission, however only controlled laboratory experiments can decisively prove it.

Transcranial direct current stimulation for post-stroke dysphagia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been investigated as a tool for dysphagia recovery after stroke in several single-center randomized controlled trials (RCT). OBJECTIVE: The aim of this investigation was to quantitatively evaluate the effect of tDCS on dysphagia recovery after a stroke utilizing a systematic review and meta-analysis. METHODS: Major databases were searched through October 2019 using a pre-defined set of criteria. Any RCT investigating the efficacy of tDCS in post-stroke dysphagia using a standardized dysphagia scale as outcome measure was included. Studies were assessed for risk of bias and quality using the Physiotherapy Evidence Database (PEDro) scale. Effect sizes were calculated from extracted data and entered into a random effects analysis to obtain pooled estimates of the effect. RESULTS: Seven RCTs with a total sample size of 217 patients fulfilled the criteria and were included in the analysis. The overall results revealed a small but statistically significant pooled effect size (0.31; CI 0.03, 0.59; p = 0.03). The subgroup which explored the stimulation intensity yielded a moderately significant effect size for the low-intensity stimulation group (g = 0.44; CI = 0.08, 0.81 vs. g = 0.15, CI - 0.30, 0.61). For the other subgroup analyses, neither comparisons of affected vs. unaffected hemisphere or acute vs. chronic stroke phase revealed a significant result. CONCLUSION: This meta-analysis demonstrates a modest but significant beneficial effect of tDCS on improving post-stroke dysphagia. Whether benefits from this intervention are more pronounced in certain patient subgroups and with specific stimulation protocols requires further investigation.

Physical distancing interventions and incidence of coronavirus disease 2019: natural experiment in 149 countries.

OBJECTIVE: To evaluate the association between physical distancing interventions and incidence of coronavirus disease 2019 (covid-19) globally. DESIGN: Natural experiment using interrupted time series analysis, with results synthesised using meta-analysis. SETTING: 149 countries or regions, with data on daily reported cases of covid-19 from the European Centre for Disease Prevention and Control and data on the physical distancing policies from the Oxford covid-19 Government Response Tracker. PARTICIPANTS: Individual countries or regions that implemented one of the five physical distancing interventions (closures of schools, workplaces, and public transport, restrictions on mass gatherings and public events, and restrictions on movement (lockdowns)) between 1 January and 30 May 2020. MAIN OUTCOME MEASURE: Incidence rate ratios (IRRs) of covid-19 before and after implementation of physical distancing interventions, estimated using data to 30 May 2020 or 30 days post-intervention, whichever occurred first. IRRs were synthesised across countries using random effects meta-analysis. RESULTS: On average, implementation of any physical distancing intervention was associated with an overall reduction in covid-19 incidence of 13% (IRR 0.87, 95% confidence interval 0.85 to 0.89; n=149 countries). Closure of public transport was not associated with any additional reduction in covid-19 incidence when the other four physical distancing interventions were in place (pooled IRR with and without public transport closure was 0.85, 0.82 to 0.88; n=72, and 0.87, 0.84 to 0.91; n=32, respectively). Data from 11 countries also suggested similar overall effectiveness (pooled IRR 0.85, 0.81 to 0.89) when school closures, workplace closures, and restrictions on mass gatherings were in place. In terms of sequence of interventions, earlier implementation of lockdown was associated with a larger reduction in covid-19 incidence (pooled IRR 0.86, 0.84 to 0.89; n=105) compared with a delayed implementation of lockdown after other physical distancing interventions were in place (pooled IRR 0.90, 0.87 to 0.94; n=41). CONCLUSIONS: Physical distancing interventions were associated with reductions in the incidence of covid-19 globally. No evidence was found of an additional effect of public transport closure when the other four physical distancing measures were in place. Earlier implementation of lockdown was associated with a larger reduction in the incidence of covid-19. These findings might support policy decisions as countries prepare to impose or lift physical distancing measures in current or future epidemic waves.

Radiomics of Coronary Artery Calcium in the Framingham Heart Study.

PURPOSE: To extract radiomic features from coronary artery calcium (CAC) on CT images and to determine whether this approach could improve the ability to identify individuals at risk for a composite endpoint of clinical events. MATERIALS AND METHODS: Participants from the Offspring and Third Generation cohorts of the community-based Framingham Heart Study underwent noncontrast cardiac CT (2002-2005) and were followed for more than a median of 9.1 years for composite major events. A total of 624 participants with CAC Agatston score (AS) of greater than 0 and good or excellent CT image quality were included for manual CAC segmentation and extraction of a predefined set of radiomic features reflecting intensity, shape, and texture. In a discovery cohort (n = 318), machine learning was used to select the 20 most informative and nonredundant CAC radiomic features, classify features predicting events, and define a radiomic-based score (RS). Performance of the RS was tested independently for the prediction of events in a validation cohort (n = 306). RESULTS: The RS had a median value of 0.08 (interquartile range, 0.007-0.71) and a weak and modest correlation with Framingham risk score (FRS) (r = 0.2) and AS (r = 0.39), respectively. The continuous RS unadjusted, adjusted for age and sex, FRS, AS, and FRS plus AS were significantly associated with events (hazard ratio [HR] = 2.2, P < .001; HR = 1.8, P = .002; HR = 2.0, P < .001; HR = 1.7, P = .02; and HR = 1.8, P = .01, respectively). In participants with AS of less than 300, RS association with events remained significant when unadjusted and adjusted for age and sex, FRS, AS, and FRS plus AS (HR = 2.4, 2.8, 2.8, 2.3, and 2.6; P < .001, respectively). In the same subgroup of participants, adding the RS to AS resulted in a significant improvement in the discriminatory ability for events as compared with the AS (area under the receiver operating curve: 0.80 vs 0.68, respectively; P = .03). CONCLUSION: A radiomic-based score, including the complex properties of CAC, may constitute an imaging biomarker to be further developed to identify individuals at risk for major adverse cardiovascular events in a community-based cohort. Supplemental material is available for this article. © RSNA, 2020.