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ImportanceReduced exercise capacity is commonly reported among individuals with Long COVID (LC). Cardiopulmonary exercise testing (CPET) is the gold-standard to measure exercise capacity to identify causes of exertional intolerance.ObjectivesTo estimate the effect of SARS-CoV-2 infection on exercise capacity including those with and without LC symptoms and to characterize physiologic patterns of limitations to elucidate possible mechanisms of LC.Data SourcesWe searched PubMed, EMBASE, and Web of Science, preprint severs, conference abstracts, and cited references in December 2021 and again in May 2022.Study SelectionWe included studies of adults with SARS-CoV-2 infection at least three months prior that included CPET measured peak VO2. 3,523 studies were screened independently by two blinded reviewers; 72 (2.2%) were selected for full-text review and 36 (1.2%) met the inclusion criteria; we identified 3 additional studies from preprint servers.Data Extraction and SynthesisData extraction was done by two independent reviewers according to PRISMA guidelines. Data were pooled with random-effects models.Main Outcomes and MeasuresA priori primary outcomes were differences in peak VO2 (in ml/kg/min) among those with and without SARS-CoV-2 infection and LC.ResultsWe identified 39 studies that performed CPET on 2,209 individuals 3-18 months after SARS-CoV-2 infection, including 944 individuals with LC symptoms and 246 SARS-CoV-2 uninfected controls. Most were case-series of individuals with LC or post-hospitalization cohorts. By meta-analysis of 9 studies including 404 infected individuals, peak VO2 was 7.4 ml/kg/min (95%CI 3.7 to 11.0) lower among infected versus uninfected individuals. A high degree of heterogeneity was attributable to patient and control selection, and these studies mostly included previously hospitalized, persistently symptomatic individuals. Based on meta-analysis of 9 studies with 464 individuals with LC, peak VO2 was 4.9 ml/kg/min (95%CI 3.4 to 6.4) lower compared to those without symptoms. Deconditioning was common, but dysfunctional breathing, chronotropic incompetence, and abnormal oxygen extraction were also described.Conclusions and RelevanceThese studies suggest that exercise capacity is reduced after SARS-CoV-2 infection especially among those hospitalized for acute COVID-19 and individuals with LC. Mechanisms for exertional intolerance besides deconditioning may be multifactorial or related to underlying autonomic dysfunction.

Side effect profiles play an important role in treatment decisions for localized prostate cancer. Emergency department (ED) visits, which may be due to side effects from treatment, can be measured in real-world, structured, electronic health record (EHR) data. The goal of this study was to determine whether treatments for localized prostate cancer are associated with ED visits, as a measure of side effects, using EHR data.We used a self-controlled case series study design, including patients treated at an urban academic medical center with radiation therapy (RT) or radical prostatectomy (RP) for prostate cancer between 2011 and 2020 who had visits documented for ≥6 months before and after treatment and ≥1 ED visit. We estimated relative incidences (RI) of ED visits, comparing incidence in the exposed and unexposed periods, with the exposed period being between start of treatment and 1 month after completion, and the unexposed period consisting of all other documented time.Among men who had at least 1 ED visit and after adjusting for age, there were higher rates of ED visits after RP (RI, 20.4; 95% confidence interval [CI], 15.4-27.0; P.001), RT overall (RI, 2.4; CI, 1.7-3.4; P.001), intensity modulated radiation therapy with high dose-rate brachytherapy (RI, 3.4; CI, 1.7-6.8; P.001) or stereotactic body radiation therapy boost (RI, 7.1; CI, 3.4-14.8; P.001), and high dose rate brachytherapy alone (RI, 16.3; CI, 7.2-36.9; P.001) compared with unexposed time. The number needed to harm to result in an ED visit was less for RP (17; CI, 13-23) than RT overall (43; CI, 25-126), but varied by RT modality.In summary, relative rates of ED visits vary by treatment type, suggesting differing severities of side effects. These data may aid in selecting treatments and demonstrate the feasibility of using the self-controlled case series study design on ED visits in real-world, structured EHR data to better understand side effects of treatment.

Introduction: Cardiac rehabilitation (CR) reduces morbidity, hospitalizations, and mortality. Increasingly, digital tools have augmented the ease of delivering programs outside of the traditional rehabilitation center setting. Because of the need for distancing during the COVID-19 pandemic, many cardiac rehabilitation (CR) centers suspended in-person services and pivoted to home-based CR (HBCR). Hypothesis: In this study, we qualitatively evaluated the implementation of HBCR, which included weekly phone or video visits for individualized exercise plans, nutrition and health education counseling, wellness sessions, and optional mobile phone applications. Methods: Patient participants and staff members (physician, nurses, exercise physiologists, dietician, administrative staff) participated in semi-structured interviews. Two independent reviewers coded interview transcripts for emergent themes and pre-specified themes from the Theory of Planned Behavior, Unified Theory of Acceptance and Use of Technology, and the Consolidated Framework for Implementation Research. Results: A total of 12 patients and 7 staff were interviewed. Narrative descriptions highlighted the isolation, fear, and disruption of life activities during COVID-19. Key facilitators of the HBCR patient experience included strong relationships with staff who served as coaches and sources of accountability and the ability of HBCR to deliver an individually tailored experience within a patient’s home. Important organizational factors for implementation included leadership buy-in, culture of change, and support for staff. Though technology tools facilitated communication and accountability, not all participants embraced technology and some reported challenges with use. Participants in the modified program (N=57) experience 60.4m (+/- 50.4 SD) improvement in 6 minute walk distance. At the conclusion of the program, 45/62 (72.6%) achieved BP control Conclusions: Individually tailored HBCR can facilitate access for patients to participate outside of a CR center. Ongoing research is needed to understand the long-term outcomes of flexible delivery models that may include both in-person and remote visits, and the role of technology in these models.

ImportanceReduced exercise capacity is commonly reported among individuals with COVID-19 symptoms more than 3 months after SARS-CoV-2 infection (long COVID-19 [LC]). Cardiopulmonary exercise testing (CPET) is the criterion standard to measure exercise capacity and identify patterns of exertional intolerance.ObjectivesTo estimate the difference in exercise capacity among individuals with and without LC symptoms and characterize physiological patterns of limitations to elucidate possible mechanisms of LC.Data SourcesA search of PubMed, EMBASE, Web of Science, preprint servers, conference abstracts, and cited references was performed on December 20, 2021, and again on May 24, 2022. A preprint search of medrxiv.org, biorxiv.org, and researchsquare.com was performed on June 9, 2022.Study SelectionStudies of adults with SARS-CoV-2 infection more than 3 months earlier that included CPET-measured peak oxygen consumption (V̇o2) were screened independently by 2 blinded reviewers; 72 (2%) were selected for full-text review, and 35 (1%) met the inclusion criteria. An additional 3 studies were identified from preprint servers.Data Extraction and SynthesisData extraction was performed by 2 independent reviewers according to the PRISMA reporting guideline. Data were pooled using random-effects models.Main Outcomes and MeasuresDifference in peak V̇o2 (in mL/kg/min) among individuals with and without persistent COVID-19 symptoms more than 3 months after SARS-CoV-2 infection.ResultsA total of 38 studies were identified that performed CPET on 2160 individuals 3 to 18 months after SARS-CoV-2 infection, including 1228 with symptoms consistent with LC. Most studies were case series of individuals with LC or cross-sectional assessments within posthospitalization cohorts. Based on a meta-analysis of 9 studies including 464 individuals with LC symptoms and 359 without symptoms, the mean peak V̇o2 was −4.9 (95% CI, −6.4 to −3.4) mL/kg/min among those with symptoms with a low degree of certainty. Deconditioning and peripheral limitations (abnormal oxygen extraction) were common, but dysfunctional breathing and chronotropic incompetence were also described. The existing literature was limited by small sample sizes, selection bias, confounding, and varying symptom definitions and CPET interpretations, resulting in high risk of bias and heterogeneity.Conclusions and RelevanceThe findings of this systematic review and meta-analysis study suggest that exercise capacity was reduced more than 3 months after SARS-CoV-2 infection among individuals with symptoms consistent with LC compared with individuals without LC symptoms, with low confidence. Potential mechanisms for exertional intolerance other than deconditioning include altered autonomic function (eg, chronotropic incompetence, dysfunctional breathing), endothelial dysfunction, and muscular or mitochondrial pathology.

UNSTRUCTURED This is a peer review report.

BACKGROUND Cardiac rehabilitation (CR) has been shown to reduce mortality, morbidity, and hospitalizations. Increasingly, digital tools have augmented the ease of delivering programs outside of the traditional rehabilitation center setting. Because of the need for distancing during the COVID-19 pandemic, many cardiac rehabilitation (CR) centers suspended in-person services and pivoted to home-based CR (HBCR). OBJECTIVE In this study, we qualitatively evaluated implementation of HBCR, which included weekly phone or video visits for individualized exercise plans, nutrition and health education counseling, wellness sessions, and optional mobile phone applications. METHODS Patient participants and staff members (physician, nurses, exercise physiologists, dietician, administrative staff) participated in semi-structured interviews. Two independent reviewers coded interview transcripts for emergent themes and pre-specified themes from the Theory of Planned Behavior, Unified Theory of Acceptance and Use of Technology, and the Consolidated Framework for Implementation Research. RESULTS A total of 12 patients and 7 staff were interviewed. Narrative descriptions highlighted the isolation, fear, and disruption of life activities during COVID-19. Key facilitators of the HBCR patient experience included strong relationships with staff who served as coaches and sources of accountability and the ability of HBCR to deliver an individually tailored experience within a patient’s home. Important organizational factors for implementation included leadership buy-in, culture of change, and support for staff. Though technology tools facilitated communication and accountability, not all participants embraced technology and some reported challenges with use. CONCLUSIONS Individually tailored HBCR can facilitate access for patients to participate outside of a CR center. Ongoing research is needed to understand the long-term outcomes of flexible delivery models that may include both in-person and remote visits, and the role of technology in these models.

Summary Background Few studies have examined the efficacy of drug-eluting stents (DES) for reducing aortocoronary saphenous vein bypass graft (SVG) failure compared with bare-metal stents (BMS) in patients undergoing stenting of de-novo SVG lesions. We assessed the risks and benefits of the use of DES versus BMS in de-novo SVG lesions. Methods Patients were recruited to our double-blind, randomised controlled trial from 25 US Department of Veterans Affairs centres. Eligible participants were aged at least 18 years and had at least one significant de-novo SVG lesion (50–99% stenosis of a 2·25–4·5 mm diameter SVG) requiring percutaneous coronary intervention with intent to use embolic protection devices. Enrolled patients were randomly assigned, in a 1:1 ratio, by phone randomisation system to receive a DES or BMS. Randomisation was stratified by presence or absence of diabetes and number of target SVG lesions requiring percutaneous coronary intervention (one or two or more) within each participating site by use of an adaptive scheme intended to balance the two stent type groups on marginal totals for the stratification factors. Patients, referring physicians, study coordinators, and outcome assessors were masked to group allocation. The primary endpoint was the 12-month incidence of target vessel failure, defined as the composite of cardiac death, target vessel myocardial infarction, or target vessel revascularisation. The DIVA trial is registered with ClinicalTrials.gov, number NCT01121224. Findings Between Jan 1, 2012, and Dec 31, 2015, 599 patients were randomly assigned to the stent groups, and the data for 597 patients were used. The patients' mean age was 68·6 (SD 7·6) years, and 595 (>99%) patients were men. The two stent groups were similar for most baseline characteristics. At 12 months, the incidence of target vessel failure was 17% (51 of 292) in the DES group versus 19% (58 of 305) in the BMS group (adjusted hazard ratio 0·92, 95% CI 0·63–1·34, p=0·70). Between-group differences in the components of the primary endpoint, serious adverse events, or stent thrombosis were not significant. Enrolment was stopped before the revised target sample size of 762 patients was reached. Interpretation In patients undergoing stenting of de-novo SVG lesions, no significant differences in outcomes between those receiving DES and BMS during 12 months of follow-up were found. The study results have important economic implications in countries with high DES prices such as the USA, because they suggest that the lower-cost BMS can be used in SVG lesions without compromising either safety or efficacy. Funding US Department of Veterans Affairs Cooperative Studies Program.