DYNamic Assessment of Multi-Organ level dysfunction in patients recovering from COVID-19: DYNAMO COVID-19.

We evaluated the impacts of COVID-19 on multi-organ and metabolic function in patients following severe hospitalised infection compared to controls. Patients (n = 21) without previous diabetes, cardiovascular or cerebrovascular disease were recruited 5-7 months post-discharge alongside controls (n = 10) with similar age, sex and body mass. Perceived fatigue was estimated (Fatigue Severity Scale) and the following were conducted: oral glucose tolerance (OGTT) alongside whole-body fuel oxidation, validated magnetic resonance imaging and spectroscopy during resting and supine controlled exercise, dual-energy X-ray absorptiometry, short physical performance battery (SPPB), intra-muscular electromyography, quadriceps strength and fatigability, and daily step-count. There was a greater insulin response (incremental area under the curve, median (inter-quartile range)) during the OGTT in patients [18,289 (12,497-27,448) mIU/min/L] versus controls [8655 (7948-11,040) mIU/min/L], P < 0.001. Blood glucose response and fasting and post-prandial fuel oxidation rates were not different. This greater insulin resistance was not explained by differences in systemic inflammation or whole-body/regional adiposity, but step-count (P = 0.07) and SPPB scores (P = 0.004) were lower in patients. Liver volume was 28% greater in patients than controls, and fat fraction adjusted liver T1, a measure of inflammation, was raised in patients. Patients displayed greater perceived fatigue scores, though leg muscle volume, strength, force-loss, motor unit properties and post-exercise muscle phosphocreatine resynthesis were comparable. Further, cardiac and cerebral architecture and function (at rest and on exercise) were not different. In this cross-sectional study, individuals without known previous morbidity who survived severe COVID-19 exhibited greater insulin resistance, pointing to a need for physical function intervention in recovery.

Dearth of electrophysiology fellows: perspectives from cardiology fellows-in-training.

BACKGROUND: Over the last 6 years, there has been a high percentage of unfilled cardiac electrophysiology (EP) training spots each year. The authors aimed to investigate potential explanations for the unfilled positions based on a survey from the current Fellows-In-Training (FITs). METHODS: An attempt was made to reach the current cardiology FITs across all programs of the U.S. via email. An anonymous questionnaire was created consisting of 14 questions. Questions posed were regarding factors affecting each participant's interest in or lack of pursuing an EP fellowship. Descriptive statistics of the responses were performed. RESULTS: A total of 26% (35/134) respondents expressed their interest in applying to an EP fellowship. The most common reasons to apply to EP were: Interest in EP, procedural specialty, and work-life balance. Of the 99 respondents that were not applying to EP, the most common reasons not to apply were: Less interest in EP, two-year training duration, and complexity of the specialty. The top reasons for the fellows to believe there is a dearth of EP FITs were: two-year training duration, lack of interest in EP, and the complexity of the specialty. The changes that would encourage EP fellowship interest were: More exposure to EP training during general cardiology fellowship, shortening the EP training duration, and having more information available regarding employment opportunities. CONCLUSION: The study was able to identify factors responsible for vacancies in EP fellowship positions from the view of current cardiology FITs. Stakeholders at the national level involved in framing policies related to fellowship education would be able to utilize this information to address the shortage of EP FITs and increase recruitment to EP fellowships.

REducing Colonoscopies in patients without significant bowEl DiseasE: the RECEDE Study - protocol for a prospective diagnostic accuracy study.

INTRODUCTION: Demand for colonoscopies and CT colonography (CTC) is exceeding capacity in National Health Service Trusts. In many patients colonoscopies and CTCs show no significant bowel disease (SBD). Faecal Immunochemical Testing (FIT) is being introduced to prioritise patients for colonoscopies but is insufficient to identify non-SBD patients meaning colonoscopy and CTC demand remains high. The REducing Colonoscopies in patients without significant bowEl DiseasE (RECEDE) study aims to test urine volatile organic compound (VOC) analysis alongside FIT to improve detection of SBD and to reduce the number of colonoscopies and CTCs. METHODS AND ANALYSIS: This is a multicentre, prospective diagnostic accuracy study evaluating whether stool FIT plus urine VOC compared with stool FIT alone improves detection of SBD in patients referred for colonoscopy or CTC due to persistent lower gastrointestinal symptoms. To ensure SBD is not missed, the dual test requires a high sensitivity, set at 97% with 95% CI width of 5%. Our assumption is that to achieve this sensitivity requires 200 participants with SBD. Further assuming 19% of all participants will have SBD and 55% of all participants will return both stool and urine samples we will recruit 1915 participants. The thresholds for FIT and VOC results diagnosing SBD have been pre-set. If either FIT or VOC exceeds the respective threshold, the participant will be classed as having suspected SBD. As an exploratory analysis we will be testing different thresholds. The reference comparator will be a complete colonoscopy or CTC. Secondary outcomes will look at optimising the FIT and VOC thresholds for SBD detection. An economic evaluation, using a denovo decision analytic model, will be carried out determine the costs, benefits and overall cost-effectiveness of FIT +VOC vs FIT followed by colonoscopy. ETHICS AND DISSEMINATION: Ethical approval was obtained by Liverpool Central Research Ethics Committee (20/NW/0346). TRIAL REGISTRATION NUMBER: RECEDE is registered on Clinicaltrials.gov NCT04516785 & ISRCTN14982373. This protocol was written and published before results of the trial were available.

A governing equation for rotor and wavelet number in human clinical ventricular fibrillation: Implications for sudden cardiac death.

BACKGROUND: Ventricular fibrillation (VF) is characterized by multiple wavelets and rotors. No equation to predict the number of rotors and wavelets observed during fibrillation has been validated in human VF. OBJECTIVE: The purpose of this study was to test the hypothesis that a single equation derived from a Markov M/M/∞ birth-death process could predict the number of rotors and wavelets occurring in human clinical VF. METHODS: Epicardial induced VF (256-electrode) recordings obtained from patients undergoing cardiac surgery were studied (12 patients; 62 epochs). Rate constants for phase singularity (PS) (which occur at the pivot points of rotors) and wavefront (WF) formation and destruction were derived by fitting distributions to PS and WF interformation and lifetimes. These rate constants were combined in an M/M/∞ governing equation to predict the number of PS and WF in VF episodes. Observed distributions were compared to those predicted by the M/M/∞ equation. RESULTS: The M/M/∞ equation accurately predicted average PS and WF number and population distribution, demonstrated in all epochs. Self-terminating episodes of VF were distinguished from VF episodes requiring termination by a trend toward slower PS destruction, slower rates of PS formation, and a slower mixing rate of the VF process, indicated by larger values of the second largest eigenvalue modulus of the M/M/∞ birth-death matrix. The longest-lasting PS (associated with rotors) had shorter interactivation time intervals compared to shorter-lasting PS lasting <150 ms (∼1 PS rotation in human VF). CONCLUSION: The M/M/∞ equation explains the number of wavelets and rotors observed, supporting a paradigm of VF based on statistical fibrillatory dynamics.

Religious Attendance and the Social Support Trajectories of Older Mexican Americans.

In this paper, we directly assessed the extent to which the association between religious attendance and the social support trajectories of older Mexican Americans is due to selection (spurious) processes related to personality, health status, and health behavior. We employed seven waves of data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly (1993-2010) to examine the association between religious attendance and perceived social support trajectories (n = 2479). We used growth mixture modeling to estimate latent classes of social support trajectories and multivariate multinomial logistic regression models to predict membership in the social support trajectory classes. Growth mixture estimates revealed three classes of social support trajectories: high, moderate, and low. Multinomial logistic regression estimates showed that the odds of membership in the low support trajectory class (versus the high social support trajectory class) were lower for respondents who attended religious services yearly, monthly, weekly, and more than weekly than for respondents who never attend religious services. Religious attendance could not distinguish between membership in the moderate and high support trajectory classes. These results persisted with adjustments for age, gender, immigrant status, language proficiency, education, income, religious affiliation, marital status, living arrangements, contact with family/friends, secular group memberships, self-esteem, smoking, heavy drinking, depression, cognitive functioning, and physical mobility. We conclude that the association between religious attendance and the social support trajectories of older Mexican Americans is primarily driven by processes related to social integration, not selection.

Workplace injury rates and firm-level turnover in Montana's oil and gas industry.

BACKGROUND: Do workers follow their self-interest by minimizing injury risk in their employment decision? If so, employers could use injury reduction as a recruitment and retention strategy. This study explores whether injury incidence is associated with turnover in Montana's Oil and Gas industry. METHODS: A panel data set of Unemployment Insurance and Workers' Compensation administrative records from 2010 to 2015 was used to model the relationship between turnover and injury claim rates at the firm level. RESULTS: Total turnover and injury rates were found to be positively related while injury rates and separation rates had no such association. Quarters in which the employer experienced a severe injury had a 3.3 percentage point increase in separation rates. DISCUSSION: The findings suggest that injured workers contribute to increased turnover, but coworker turnover does not increase with increased injury rates in the firm. Secondary findings suggest a relationship between recent hires and increased injury rates, although further investigation is required.

Multi-organ assessment of compensated cirrhosis patients using quantitative magnetic resonance imaging.

BACKGROUND & AIMS: Advancing liver disease results in deleterious changes in a number of critical organs. The ability to measure structure, blood flow and tissue perfusion within multiple organs in a single scan has implications for determining the balance of benefit vs. harm for therapies. Our aim was to establish the feasibility of magnetic resonance imaging (MRI) to assess changes in Compensated Cirrhosis (CC), and relate this to disease severity and future liver-related outcomes (LROs). METHODS: A total of 60 patients with CC, 40 healthy volunteers and 7 patients with decompensated cirrhosis were recruited. In a single scan session, MRI measures comprised phase-contrast MRI vessel blood flow, arterial spin labelling tissue perfusion, T1 longitudinal relaxation time, heart rate, cardiac index, and volume assessment of the liver, spleen and kidneys. We explored the association between MRI parameters and disease severity, analysing differences in baseline MRI parameters in the 11 (18%) patients with CC who experienced future LROs. RESULTS: In the liver, compositional changes were reflected by increased T1 in progressive disease (p <0.001) and an increase in liver volume in CC (p = 0.006), with associated progressive reduction in liver (p <0.001) and splenic (p <0.001) perfusion. A significant reduction in renal cortex T1 and increase in cardiac index and superior mesenteric arterial blood flow was seen with increasing disease severity. Baseline liver T1 (p = 0.01), liver perfusion (p <0.01), and renal cortex T1 (p <0.01) were significantly different in patients with CC who subsequently developed negative LROs. CONCLUSIONS: MRI enables the contemporaneous assessment of organs in liver cirrhosis in a single scan without the requirement for a contrast agent. MRI parameters of liver T1, renal T1, hepatic and splenic perfusion, and superior mesenteric arterial blood flow were related to the risk of LROs. LAY SUMMARY: This study assesses the changes to structure, blood flow and perfusion that occur in the key organs (liver, spleen and kidney) associated with severe liver disease (Compensated Cirrhosis), using magnetic resonance imaging. The magnetic resonance imaging measures which changed with disease severity and were related to negative liver-related clinical outcomes are described.

Non-invasive assessment of portal hypertension using quantitative magnetic resonance imaging.

BACKGROUND & AIMS: Hepatic venous pressure gradient (HVPG) measurement is currently the only validated technique to accurately evaluate changes in portal pressure. In this study, we evaluate the use of non-contrast quantitative magnetic resonance imaging (MRI) as a surrogate measure of portal pressure. METHODS: Thirty patients undergoing HVPG measurement were prospectively recruited. MR parameters of longitudinal relaxation time (T1), perfusion of the liver and spleen (by arterial spin labelling), and blood flow in the portal, splanchnic and collateral circulation (by phase contrast MRI) were assessed. We estimated the liver stiffness measurement (LSM) and enhanced liver fibrosis (ELF) score. The correlation of all non-invasive parameters with HVPG was evaluated. RESULTS: The mean (range) HVPG of the patients was 9.8 (1-22) mmHg, and 14 patients (48%) had clinically significant portal hypertension (CSPH, HVPG ⩾10mmHg). Liver T1 relaxation time, splenic artery and superior mesenteric artery velocity correlated significantly with HVPG. Using multiple linear regression, liver T1 and splenic artery velocity remained as the two parameters in the multivariate model significantly associated with HVPG (R=0.90, p<0.001). This correlation was maintained in patients with CSPH (R=0.85, p<0.001). A validation cohort (n=10) showed this linear model provided a good prediction of HVPG. LSM and ELF score correlated significantly with HVPG in the whole population but the correlation was absent in CSPH. CONCLUSIONS: MR parameters related to both hepatic architecture and splanchnic haemodynamics correlate significantly with HVPG. This proposed model, confirmed in a validation cohort, could replace the invasive HVPG measurement. LAY SUMMARY: In patients with cirrhosis, the development and progression of portal hypertension is related to worse outcomes. However, the standard technique of assessing portal pressure is invasive and not widely used in clinical practice. Here, we have studied the use of non-invasive MRI in evaluating portal pressure. The MRI measures of liver architecture and blood flow in the splenic artery correlated well with portal pressure. Therefore, this non-invasive method can potentially be used to assess portal pressure in clinical trials and monitoring treatment in practice.