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Background SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commercially available Ag-RDTs. Methods and findings We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix, bioRvix, and FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 up until 30 April 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcription polymerase chain reaction (RT-PCR) testing. We assessed heterogeneity by subgroup analyses, and rated study quality and risk of bias using the QUADAS-2 assessment tool. From a total of 14,254 articles, we included 133 analytical and clinical studies resulting in 214 clinical accuracy datasets with 112,323 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity and specificity were 71.2% (95% CI 68.2% to 74.0%) and 98.9% (95% CI 98.6% to 99.1%), respectively. Sensitivity increased to 76.3% (95% CI 73.1% to 79.2%) if analysis was restricted to studies that followed the Ag-RDT manufacturers’ instructions. LumiraDx showed the highest sensitivity, with 88.2% (95% CI 59.0% to 97.5%). Of instrument-free Ag-RDTs, Standard Q nasal performed best, with 80.2% sensitivity (95% CI 70.3% to 87.4%). Across all Ag-RDTs, sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values, i.e., <20 (96.5%, 95% CI 92.6% to 98.4%) and <25 (95.8%, 95% CI 92.3% to 97.8%), in comparison to those with Ct ≥ 25 (50.7%, 95% CI 35.6% to 65.8%) and ≥30 (20.9%, 95% CI 12.5% to 32.8%). Testing in the first week from symptom onset resulted in substantially higher sensitivity (83.8%, 95% CI 76.3% to 89.2%) compared to testing after 1 week (61.5%, 95% CI 52.2% to 70.0%). The best Ag-RDT sensitivity was found with anterior nasal sampling (75.5%, 95% CI 70.4% to 79.9%), in comparison to other sample types (e.g., nasopharyngeal, 71.6%, 95% CI 68.1% to 74.9%), although CIs were overlapping. Concerns of bias were raised across all datasets, and financial support from the manufacturer was reported in 24.1% of datasets. Our analysis was limited by the included studies’ heterogeneity in design and reporting. Conclusions In this study we found that Ag-RDTs detect the vast majority of SARS-CoV-2-infected persons within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease, making them a valuable tool to fight the spread of SARS-CoV-2. Standardization in conduct and reporting of clinical accuracy studies would improve comparability and use of data.

Background: SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being inte-grated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensi-tivity and specificity) of commercially available Ag-RDTs. Methods: We registered the review on PROSPERO (Registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix and bioRvix, FINDdx) for publications up until December 11th, 2020. Descriptive analyses of all studies were performed and when more than four studies were avail-able, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcriptase polymerase chain reaction testing. We assessed heterogeneity by subgroup analyses ((1) performed conform with manufacturers instructions for use (IFU) or not, (2) symptomatic vs. asymptomatic, (3) duration of symptoms less than seven days vs. more than seven days, (4) Ct-value <25 vs. <30 vs. >30, (5) by sample type)) and with meta-regression. We assessed study quality and risk of bias using the QUADAS 2 assessment tool. Results: From a total of 11,715 articles, we extracted 98 analytical and clinical data sets. 74 clinical accuracy data sets were evaluated that included 31,202 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity was 73.8% (CI 68.6 to 78.5). If analysis was re-stricted to studies that followed the Ag-RDT manufacturers instructions using fresh upper res-piratory swab samples, the sensitivity increased to 79.1% (95%CI 75.0 to 82.8). The SD Biosensor Standard Q and Abbott Panbio showed the highest sensitivity with 81.7% and 72.7%, respectively. The best Ag-RDT performance was found with nasopharyngeal sampling (77.3%, CI 72.0 to 81.9) in comparison to other sample types (e.g., anterior nasal or mid turbinate 63.5%, CI 49.5 to 75.5). Testing in the first week from symptom onset resulted in higher sensitivity (87.5%, CI 86.0 to 89.1) compared to testing after one week (64.1%, CI 54.4 to 73.8). The tests performed markedly better on samples with lower Ct-values, i.e., <30 (87.9%, CI 86.7 to 88.8), in comparison to those with Ct >30 (47.8%, CI 41.1 to 54.5). Bias concerns were raised across all data sets, and financial support from the manufacturer was reported in 28.2% of data sets. Conclusion: As Ag-RDTs detect most cases within the first week of symptom onset and those with high viral load, they can have high utility for screening purposes in the early phase of disease, and thus can be a valuable tool to fight the spread of SARS-CoV-2. Standardization of con-duct and reporting of clinical accuracy studies would improve comparability and use of data.

Background Exercise-based cardiac rehabilitation (ebCR) often includes various psychological interventions for lifestyle change or distress management. However, the additional benefit of specific psychological interventions on depression, anxiety, quality of life, cardiac morbidity and cardiovascular or total mortality is not well investigated. Design Systematic review and meta-analysis. Methods Randomized controlled trials and controlled cohort trials published between January 1995 and October 2017 comparing ebCR with or without pre-specified psychosocial interventions were selected and evaluated on the basis of predefined inclusion and outcome criteria. Results Out of 15,373 records, 20 studies were identified, including 4450 patients with coronary artery disease (88.5%) or congestive heart failure (11.5%), respectively. Studies were of low to moderate quality and methodological heterogeneity was high. As compared with ebCR alone, additional psychological interventions for lifestyle change or distress management showed a trend to reduce depressive symptoms (standardized mean difference –0.13, 95% confidence interval (CI) –0.30; 0.05). Furthermore, during a follow-up of five years, distress management was associated with a trend to reduce cardiac morbidity (risk ratio 0.74, 95% CI 0.51; 1.07). There was no evidence for an additional impact of either psychological lifestyle change interventions or distress management on anxiety, quality of life, cardiovascular or total mortality. Conclusions Specific psychological interventions offered during ebCR may contribute to a reduction of depressive symptoms and cardiac morbidity, but there remains considerable uncertainty under which conditions these interventions exert their optimal effects. (CRD42015025920).

Background In heart failure with reduced left ventricular ejection fraction (HFrEF) patients the effects of exercise-based cardiac rehabilitation on top of state-of-the-art pharmacological and device therapy on mortality, hospitalization, exercise capacity and quality-of-life are not well established. Design The design of this study involved a structured review and meta-analysis. Methods Evaluation of randomised controlled trials of exercise-based cardiac rehabilitation in HFrEF-patients with left ventricular ejection fraction ≤40% of any aetiology with a follow-up of ≥6 months published in 1999 or later. Results Out of 12,229 abstracts, 25 randomised controlled trials including 4481 HFrEF-patients were included in the final evaluation. Heterogeneity in study population, study design and exercise-based cardiac rehabilitation-intervention was evident. No significant difference in the effect of exercise-based cardiac rehabilitation on mortality compared to control-group was found (hazard ratio 0.75, 95% confidence interval 0.39–1.41, four studies; 12-months follow-up: relative risk 1.29, 95% confidence interval 0.66–2.49, eight studies; six-months follow-up: relative risk 0.91, 95% confidence interval 0.26–3.16, seven studies). In addition there was no significant difference between the groups with respect to ‘hospitalization-for-any-reason’ (12-months follow-up: relative risk 0.79, 95% confidence interval 0.41–1.53, four studies), or ‘hospitalization-due-to-heart-failure’ (12-months follow-up: relative risk 0.59, 95% confidence interval 0.12–2.91, four studies; six-months follow-up: relative risk 0.84, 95% confidence interval 0.07–9.71, three studies). All studies show improvement of exercise capacity. Participation in exercise-based cardiac rehabilitation significantly improved quality-of-life as evaluated with the Kansas City Cardiomyopathy Questionnaire: (six-months follow-up: mean difference 1.94, 95% confidence interval 0.35–3.56, two studies), but no significant results emerged for quality-of-life measured by the Minnesota Living with Heart Failure Questionnaire (nine-months or more follow-up: mean difference –4.19, 95% confidence interval –10.51–2.12, seven studies; six-months follow-up: mean difference –5.97, 95% confidence interval –16.17–4.23, four studies). Conclusion No association between exercise-based cardiac rehabilitation and mortality or hospitalisation could be observed in HFrEF patients but exercise-based cardiac rehabilitation is likely to improve exercise capacity and quality of life.

Objective: Coronary artery disease (CAD), a major cause of mortality in patients with type 2 diabetes (T2D), is often diagnosed late because of silent myocardial ischaemia (SMI). Exercise electrocardiogram testing (ECG) stress is the most utilized screening test for SMI. Its applicability and accuracy, which have never been reported in asymptomatic high-risk T2D patients, have been investigated in this study. Design: A cross-sectional study with coronary angiography as the gold standard for detecting CAD was used. Methods: Two hundred and six consecutive T2D patients, without symptoms and resting ECG signs of ischaemia but with peripheral vascular disease (PVD) and/or $ two atherogenic factors, were studied. Ischaemia at ECG stress was indicated by horizontal or downsloping ST segment depression $ 1 mm at 0.08 s after the J point. CAD was defined by stenosis $ 70%. Results: Only 141/206 (68%) patients had a diagnostic test: 27 (19%) tested positive and 114 (81%) tested negative. Coronary angiography in 71 patients (the 27 who tested positive and 44 randomly selected patients who tested negative) indicated a CAD prevalence of 29% and the ECG stress accuracy was 79%. 'False negative' patients (18%) had a higher prevalence ðP , 0:01Þ of long duration of diabetes and PVD. Conclusions: This is the first study which provides insights into the applicability and accuracy of ECG stress in screening SMI in high-risk patients with T2D. Due to the high prevalence of CAD, alternative screening tests in patients unable to perform the test and in those with a high chance of being 'false negative' should be looked for and validated.

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Background: Although cardiovascular rehabilitation (CR) is well accepted in general, CR-attendance and delivery still considerably vary between the European countries. Moreover, clinical and prognostic effects of CR are not well established for a variety of cardiovascular diseases. Methods: The guidelines address all aspects of CR including indications, contents and delivery. By processing the guidelines, every step was externally supervised and moderated by independent members of the “Association of the Scientific Medical Societies in Germany” (AWMF). Four meta-analyses were performed to evaluate the prognostic effect of CR after acute coronary syndrome (ACS), after coronary bypass grafting (CABG), in patients with severe chronic systolic heart failure (HFrEF), and to define the effect of psychological interventions during CR. All other indications for CR-delivery were based on a predefined semi-structured literature search and recommendations were established by a formal consenting process including all medical societies involved in guideline generation. Results: Multidisciplinary CR is associated with a significant reduction in all-cause mortality in patients after ACS and after CABG, whereas HFrEF-patients (left ventricular ejection fraction <40%) especially benefit in terms of exercise capacity and health-related quality of life. Patients with other cardiovascular diseases also benefit from CR-participation, but the scientific evidence is less clear. There is increasing evidence that the beneficial effect of CR strongly depends on “treatment intensity” including medical supervision, treatment of cardiovascular risk factors, information and education, and a minimum of individually adapted exercise volume. Additional psychologic interventions should be performed on the basis of individual needs. Conclusions: These guidelines reinforce the substantial benefit of CR in specific clinical indications, but also describe remaining deficits in CR-delivery in clinical practice as well as in CR-science with respect to methodology and presentation.