Impact of Tele-Coaching During the COVID-19 Pandemic on Risk-Reduction Behavior of Patients with Heart Failure.

Introduction: Our study assessed the effectiveness of tele-coaching over written information in educating patients with chronic heart failure (CHF) at high risk of hospitalization about corona virus disease 2019 (COVID-19). We analyzed the impact on number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and self-reported behavior change. Methods: In April 2020, a tele-coaching module and written summary about COVID-19, risk-reduction measures for prevention of COVID-19, and appropriate consultation of medical attention during the pandemic were integrated into an established tele-coaching program. Three hundred seventy-eight patients who had received both tele-coaching and written information 3 weeks earlier were interviewed using a structured questionnaire and compared with 1,748 patients who had only received written information at this point. Results: Tele-coaching had no short-term effect on numbers of SARS-CoV-2 infections. However, patients receiving tele-coaching reported significantly more behavioral changes, including increased room ventilation (88% vs. 78%, p < 0.0001), surface cleaning (80% vs. 70%, p = 0.0006), wearing of face masks (59% vs. 51%, p = 0.013), and reduced usage of public transport (77% vs. 68%, p = 0.0003), despite no observed difference in recall about risk-reduction measures. Moreover, tele-coaching improved patients' knowledge about how to seek medical help in an emergency (46% vs. 36%, p = 0.0006), with a significant reduction in self-reported doctors' appointments (304 vs. 413 per 1,000 patients, p = 0.002) and hospital visits (50 vs. 87 per 1,000, p = 0.033) during the first peak of the pandemic. Conclusion: In a population of patients with CHF at high risk of hospitalization, COVID-19-specific tele-coaching effectively supported behavioral changes and significantly reduced face-to-face medical contacts in a short-term follow-up period.

Co-aggregate formation of CADASIL-mutant NOTCH3: a single-particle analysis.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is the most common monogenic cause of stroke and vascular dementia. Accumulation and deposition of the NOTCH3 (N3) extracellular domain in small blood vessels has been recognized as a central pathological feature of the disease. Recent experiments suggested enhanced formation of higher order multimers for mutant N3 compared with wild-type (WT). However, the mechanisms and consequences of N3 multimerization are still poorly understood, in part because of the lack of an appropriate in vitro aggregation assay. We therefore developed and validated a robust assay based on recombinant N3 fragments purified from cell culture supernatants. Using single-molecule analysis techniques such as scanning for intensely fluorescent targets and single-particle fluorescence resonance energy transfer, we show that spontaneous aggregation is limited to CADASIL-mutant N3, recapitulating a central aspect of CADASIL pathology in vitro. N3 aggregation requires no co-factor and is facilitated by sulfhydryl crosslinking. Although WT N3 does not exhibit multimerization itself, it can participate in aggregates of mutant N3. Furthermore, we demonstrate that thrombospondin-2, a known interaction partner of N3, co-aggregates with mutant N3. Sequestration of WT N3 and other proteins into aggregates represents a potentially important disease mechanism. These findings in combination with a new assay for single-molecule aggregation analysis provide novel opportunities for the development of therapeutic strategies.

Combined telemonitoring and telecoaching for heart failure improves outcome.

Telemedicine has been shown to improve the outcome of heart failure (HF) patients in addition to medical and device therapy. We investigate the effectiveness of a comprehensive telehealth programme in patients with recent hospitalisation for HF on subsequent HF hospitalisations and mortality compared to usual care in a real-world setting. The telehealth programme consists of daily remote telemonitoring of HF signs/symptoms and regular individualised telecoaching sessions. Between January 2018 and September 2020, 119,715 patients of a German health insurer were hospitalised for HF and were eligible for participation in the programme. Finally, 6065 HF patients at high risk for re-hospitalisation were enroled. Participants were retrospectively compared to a propensity score matched usual care group (n = 6065). Median follow-up was 442 days (IQR 309-681). Data from the health insurer was used to evaluate outcomes. After one year, the number of hospitalisations for HF (17.9 vs. 21.8 per 100 patient years, p < 0.001), all-cause hospitalisations (129.0 vs. 133.2 per 100 patient years, p = 0.015), and the respective days spent in hospital (2.0 vs. 2.6 days per year, p < 0.001, and 12.0 vs. 13.4, p < 0.001, respectively) were significantly lower in the telehealth than in the usual care group. Moreover, participation in the telehealth programme was related to a significant reduction in all-cause mortality compared to usual care (5.8 vs. 11.0 %, p < 0.001). In a real-life setting of ambulatory HF patients at high risk for re-hospitalisation, participation in a comprehensive telehealth programme was related to a reduction of HF hospitalisations and all-cause mortality compared to usual care.

CADASIL mutations enhance spontaneous multimerization of NOTCH3.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic cause of stroke and vascular dementia. Disease-causing mutations invariably affect cysteine residues within epidermal growth factor-like repeat domains in the extracellular domain of the NOTCH3 receptor (N3(ECD)). The biochemical and histopathological hallmark of CADASIL is the accumulation of N3(ECD) at the cell surface of vascular smooth muscle cells which degenerate over the course of the disease. The molecular mechanisms leading to N3(ECD) accumulation remain unknown. Here we show that both wild-type and CADASIL-mutated N3(ECD) spontaneously form oligomers and higher order multimers in vitro and that multimerization is mediated by disulfide bonds. Using single-molecule analysis techniques ('scanning for intensely fluorescent targets'), we demonstrate that CADASIL-associated mutations significantly enhance multimerization compared with wild-type. Taken together, our results for the first time provide experimental evidence for N3 self-association and strongly argue for a neomorphic effect of CADASIL mutations in disease pathogenesis.

Significant differences in written assessments as a result of a blended learning approach used in a clinical examination course in internal medicine: a randomized controlled pilot study.

Background: Taking a medical history and performing a physical examination represent basic medical skills. However, numerous national and international studies show that medical students and physicians-to-be demonstrate substantial deficiencies in the proper examination of individual organ systems. Aim: The objective of this study was to conduct a randomized controlled pilot study to see if, in the context of a bedside clinical examination course in internal medicine, an additional app-based blended-learning strategy resulted in (a) higher satisfaction, better self-assessments by students when rating their history-taking skills (b1) and their ability to perform physical examinations (b2), as well as (c) higher multiple-choice test scores at the end of the course, when compared to a traditional teaching strategy. Methods: Within the scope of a bedside course teaching the techniques of clinical examination, 26 students out of a total of 335 students enrolled in the 2012 summer semester and 2012/2013 winter semester were randomly assigned to two groups of the same size. Thirteen students were in an intervention group (IG) with pre- and post-material for studying via an app-based blended-learning tool, and another 13 students were in a control group (CG) with the usual pre- and post-material (handouts). The IG was given an app specifically created for the history-taking and physical exam course, an application program for smartphones enabling them to view course material directly on the smartphone. The CG received the same information in the form of paper-based notes. Prior to course begin, all of the students filled out a questionnaire on sociodemographic data and took a multiple-choice pretest with questions on anamnesis and physical examination. After completing the course, the students again took a multiple-choice test with questions on anamnesis and physical examination. Results: When compared to the CG, the IG showed significantly more improvement on the multiple-choice tests after taking the clinical examination course (p=0.022). This improvement on the MC tests in the IG significantly correlated with the amount of time spent using the app (Spearman's rho=0.741, p=0.004). Conclusion: When compared to conventional teaching, an app-based blended-learning approach leads to improvement in test scores, possibly as a result of more intensive preparation for and review of the clinical examination course material.