The Feasibility of a Telehealth Exercise Program Aimed at Increasing Cardiorespiratory Fitness for People After Stroke

Background: Accessing suitable fitness programs post-stroke is difficult for many. The feasibility of telehealth delivery has not been previously reported.Objectives: To assess the feasibility of, and level of satisfaction with home-based telehealth-supervised aerobic exercise training post-stroke.Methods: Twenty-one ambulant participants (?3 months post-stroke) participated in a home-based telehealth-supervised aerobic exercise program (3 d/week, moderate-vigorous intensity, 8-weeks) and provided feedback via questionnaire postintervention. Session details, technical issues, and adverse events were also recorded.Results: Feasibility was high (83% of volunteers met telehealth eligibility criteria, 85% of sessions were conducted by telehealth, and 95% of participants rated usability favourably). Ninety-five percent enjoyed telehealth exercise sessions and would recommend them to others. The preferred telehealth exercise program parameters were: frequency 3 d/week, duration 20-30 min/session, program length 6-12 weeks.Conclusion: The telehealth delivery of exercise sessions to people after stroke appear

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

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

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

Characteristics of exercise training interventions to improve cardiorespiratory fitness after stroke: a systematic review with meta-analysis

Background: Cardiorespiratory fitness is low after stroke. Improving fitness has the potential to improve function and reduce secondary cardiovascular events. Objective: This review with meta-analysis aims to identify characteristics and determine the effectiveness of interventions to improve cardiorespiratory fitness after stroke. Methods: A systematic search and review with meta-analysis was undertaken. Key inclusion criteria were the following: peer-reviewed articles published in English, adult stroke survivors, an intervention with the potential to improve cardiorespiratory fitness, and peak oxygen consumption (VO_2peak) assessed preintervention and postintervention via a progressive aerobic exercise test. Results: From 3209 citations identified, 28 studies were included, reporting results for 920 participants. Studies typically included chronic, ambulant participants with mild to moderate deficits; used an aerobic or mixed (with an aerobic component) intervention; and prescribed 3 sessions per week for 30 to 60 minutes per session at a given intensity. Baseline VO_2peak values were low (8-23 mL/kg/min). Meta-analysis of the 12 randomized controlled trials demonstrated overall improvements in VO_2peak of 2.27 (95% confidence interval = 1.58, 2.95) mL/kg/min postintervention. A similar 10% to 15% improvement occurred with both aerobic and mixed interventions and in shorter (≤3 months) and longer (>3 months) length programs. Only 1 study calculated total dose received and only 1 included long-term follow-up. Conclusions: The results demonstrate that interventions with an aerobic component can improve cardiorespiratory fitness poststroke. Further investigation is required to determine effectiveness in those with greater impairment and comorbidities, optimal timing and dose of intervention, whether improvements can be maintained in the longer term, and whether improved fitness results in better function and reduced risk of subsequent cardiovascular events

Interval circuit training for cardiorespiratory fitness is feasible for people after stroke

Aims: To determine if community-dwelling stroke survivors can achieve exercise intensities sufficient to improve cardiorespiratory fitness during a single session of circuit training using an interval training approach. Methods: Thirteen independently ambulant participants within 1 year of stroke were included in this observational study (females=54%; median age=65.6 years; interquartile range=23.9). Exercise intensities were assessed throughout an individually tailored circuit of up to seven 5-minute workstations from a selection of nine functional (e.g. walking, stairs, balance) and three ergometer (upright cycle, rower, treadmill) workstations. The interval durations ranged from 5–60 seconds. Oxygen consumption (VO2) was recorded continuously using a portable metabolic system. The average VO2 during each 30-second epoch was determined. VO2≥10.5 mL/kg/min was categorised as ≥moderate intensity. Findings: Participants exercised at VO2≥10.5 mL/kg/min for the majority of the time on the workstations [functional: 369/472 epochs (78%), ergometer: 170/204 epochs (83%)]. Most (69%) participants exercised for ≥30 minutes. No serious adverse events occurred. Conclusions: Applying interval training principles to a circuit of functional and ergometer workstations enabled ambulant participants to exercise at an intensity and for a duration that can improve cardiorespiratory fitness. The training approach appears feasible, safe and a promising way to incorporate both cardiorespiratory fitness and functional training into post-stroke management

A home- and community-based physical activity program can improve the cardiorespiratory fitness and walking capacity of stroke survivors

Background The cardiorespiratory fitness of stroke survivors is low. Center-based exercise programs that include an aerobic component have been shown to improve poststroke cardiorespiratory fitness. This pilot study aims to determine the feasibility, safety, and preliminary efficacy of an individually tailored home- and community-based exercise program to improve cardiorespiratory fitness and walking capacity in stroke survivors. Methods Independently ambulant, community-dwelling stroke survivors were recruited. The control (n = 10) and intervention (n = 10) groups both received usual care. In addition the intervention group undertook a 12-week, individually tailored, home- and community-based exercise program, including once-weekly telephone or e-mail support. Assessments were conducted at baseline and at 12 weeks. Feasibility was determined by retention and program participation, and safety by adverse events. Efficacy measures included change in cardiorespiratory fitness (peak oxygen consumption [VO2peak]) and distance walked during the Six-Minute Walk Test (6MWT). Analysis of covariance was used for data analysis. Results All participants completed the study with no adverse events. All intervention participants reported undertaking their prescribed program. VO2peak improved more in the intervention group (1.17 ± .29 L/min to 1.35 ± .33 L/min) than the control group (1.24 ± .23 L/min to 1.24 ± .33 L/min, between-group difference = .18 L/min, 95% confidence interval [CI]:.01-.36). Distance walked improved more in the intervention group (427 ± 123 m to 494 ± 67m) compared to the control group (456 ± 101m to 470 ± 106m, between-group difference = 45 m, 95% CI:.3-90). Conclusions Our individually tailored approach with once-weekly telephone or e-mail support was feasible and effective in selected stroke survivors. The 16% greater improvement in VO2peak during the 6MWT achieved in the intervention versus control group is comparable to improvements attained in supervised, center-based programs

The rural Prehospital Acute Stroke Triage (PAST) trial protocol: a controlled trial for rapid facilitated transport of rural acute stroke patients to a regional stroke centre

Rationale Access to intravenous thrombolysis for acute ischaemic stroke is limited worldwide, particularly in regional and rural areas including in Australia. We are testing the effectiveness of a new rural Prehospital Acute Stroke Triage protocol that includes prehospital assessment and rapid transport of patients from a rural catchment to the major stroke centre in Newcastle, NSW, Australia. The local district hospitals within the rural catchment do not have the capability or infrastructure to deliver acute stroke thrombolysis. The trial has relevance to stroke clinicians, health service managers and planners responsible for rural populations. Aims: To implement a system of rapid prehospital assessment and facilitated transport that will significantly increase stroke thrombolysis rates to 10% of ischaemic stroke cases in the rural catchment. Validate an eight-point modified National Institutes of Health Stroke Scale for use by paramedics in the prehospital setting to assess patients’ potential eligibility for stroke thrombolysis. Design: The joint project between the John Hunter Hospital Acute Stroke Team and the Ambulance Service of NSW will use a prospective cohort with an historical control group. Tools and protocols have been developed and education undertaken for ambulance field and operations centre personnel. These include a cut-down eight-item National Institutes of Health Stroke Scale (Hunter NIHSS-8) score to be used in the field by paramedics and a transport decision matrix to expedite transport for a suspected stroke patient (road or road plus air transport). Outcomes: The primary outcome measure will be the rate of intravenous tissue plasminogen activator delivery for those who suffer an ischaemic stroke following protocol implementation, in comparison with historical rates over a corresponding period prior to implementation, for residents within the catchment. Sixty cases are required in the postimplementation time epoch to demonstrate a statistically significant absolute increase in thrombolysis rates for ischaemic strokes from <1% to 10%, (power of 80%, α error of 0·05). The major secondary outcome will be inter-rater reliability of the Hunter NIHSS-8

Secondary prevention of stroke : Study Protocol for a Telehealth-Delivered Physical Activity and Diet Pilot Randomized Trial (ENAbLE-Pilot)

Background: Increasing physical activity (PA) and improving diet quality are opportunities to improve secondary stroke prevention, but access to appropriate services is limited. Interventions co-designed with stroke survivors and delivered by telehealth are a potential solution. Aim: The aim of this study is to test the feasibility, safety, and potential efficacy of a 6-month, telehealth-delivered PA and/or dietary (DIET) intervention. Methods: Pilot randomized trial. 80 adults with previous stroke who are living at home with Internet access and able to exercise will be randomized in a 2 × 2 factorial (4-arm) pilot randomized, open-label, blinded outcome assessment trial to receive PA, DIET, PA + DIET, or control interventions via telehealth. The PA intervention aims to support participants to meet the minimum recommended levels of PA (150 min/week moderate exercise), and the DIET intervention aims to support participants to follow the AusMed (Mediterranean-style) diet. The control group receives usual care plus education about PA and healthy eating. The co-primary outcomes are feasibility (proportion and characteristics of eligible participants enrolled and proportion of scheduled intervention sessions attended) and safety (adverse events) at 6 months. The secondary outcomes include recurrent stroke risk factors (blood pressure, physical activity levels, and diet quality), fatigue, mood, and quality of life. Outcomes are measured at 3, 6, and 12 months. Conclusion: This trial will produce evidence for the feasibility, safety, and potential effect of telehealth-delivered PA and DIET interventions for people with stroke. Results will inform development of an appropriately powered trial to test effectiveness to reduce major risk factors for recurrent stroke. Trial registration: ACTRN12620000189921