ABSTRACT
Background and Aim: It is well known that Fontan patients tend to a sedentary lifestyle with low physical activity levels and their objec-tive exercise capacity is reduced. Currently the COVID-19 pandemic has a significant impact on the physical activity levels of the whole population. This study investigates physical activity lev-els of Fontan patients during the COVID-pandemic, and their relationship to exercise capacity, heart rates, cardiac function at cardiovascular magnetic resonance (CMR), and biomarkers. Method(s): CMR, exercise testing, 24h-ECG, and blood samples were prospectively performed in 38 Fontan patients, of which 15 were females (40%) and 18 (47%) had a single left ventricle (LV). Time interval from Fontan operation was in median (IQR) 10 (8-15) years. Physical activity was assessed by accelerom-eter during 7 consecutive days of regular school/work. Moderate intensity physical activity was defined as gt;2296 counts/minute and vigorous physical activity as gt;4012 counts/minute. Patients with moderate-to-vigorous physical activity (MVPA) below 60minutes per day were categorized as inactive as recom-mended by the WHO. Parameters of exercise capacity included maximal oxygen uptake, maximum work rate, and maximal heart rate. Result(s): Daily MVPA was in median (IQR) 40.2 (27.6-56.5) minutes and 7/18 (39%) patients reached the recommended 60minutes/day of MVPA. Daily minutes of MVPA did not cor-relate with gender, age, single left ventricle, years from Fontan sur-gery, mean heart rate, ventricular volumes, and ejection fraction at CMR, cardiac biomarkers, or exercise capacity. Conclusion(s): Only 39% of the Fontan patients meet the recommen-dation for daily MVPA. The MVPA during the pandemic in our patients' cohort is lower than the one reported in Fontan patients before the pandemic. These current changes in behavioral habits may increase the risk for habitual sedentary lifestyles in Fontan patients.
ABSTRACT
Background: Aromatase inhibitors (AI) in combination with a CDK 4/6 inhibitor have been established as the standard first line treatment of non AI-resistant hormone receptor-positive (HR+) HER2-metastatic breast cancer (mBC) patients (pts). ESR1 mutations are known drivers of resistance to AIs in the metastatic setting but their actionability remains unknown. The phase 3 PADA-1 trial aimed both at refining the global safety of palbociclib combined to any AI as first line treatment of HR+ HER2-mBC pts, and at evaluating the clinical benefit associated with a switch to fulvestrant-palbociclib upon detection of a rising ESR1 mutation in blood (bESR1mut). Methods: PADA-1 (NCT03079011), a multicenter, randomized, open-label, phase 3 trial, enrolled HR+ HER2-mBC pts with no prior therapy for mBC, in the absence of AI-resistance. In the first step, pts received a combination of any AI and palbociclib at standard recommended doses and underwent centralized bESR1mut screening every two months. In the second step, bESR1mut+ pts with no S clinical/imaging concomitant disease progression were randomized between continuing the same therapy (standard arm) or switching to fulvestrant-palbociclib (experimental arm). The third step consisted in an optional cross-over after tumor progression for patients randomized in the standard arm. PADA-1 co-primary endpoints were global safety of the combination of palbociclib + endocrine therapy in the whole population of patients, throughout the study, with focus on hematological toxicities;and PFS in the second step. We present here the results of the global safety co-primary endpoint. Results: From 3/2017 to 01/2019, 1017 pts were accrued in 83 sites. As per 05/2021, 272 pts were still in step 1, 35 in step 2, and 8 in step 3. The overall follow-up was 33.7 months. 232 pts have deceased. 333 SAEs have been reported, including 21 grade 5, 35 grade 4, 183 grade 3, 53 grade 2, 26 grade 1 and 15 unknown grade. Among the grade 5 cases, 2 have been declared as potentially related to the underlying treatment (Death of unknown cause, pulmonary embolism). No pt died of SARS-CoV2 infection. The main hematological toxicities encountered, as well as selected non-hematological events are described in Table 1. Permanent discontinuation of the treatment due to toxicity occurred in 39 pts/1017 (3.8%). Palbociclib dose decreases occurred in 419 (41.2%) pts. Conclusion: By the number of included patients, PADA-1 is the largest prospective trial with 1st line AI and palbociclib. Data confirm the favorable safety profile of palbociclib when combined to any AI +/-switch to fulvestrant. Hematological toxicity appears limited and is mostly restricted to non-clinically significant neutropenia. Permanent discontinuation was exceptional. Detailed per-step analyses will be presented.
ABSTRACT
Background: In young adults and adolescent males, myocarditis has been described as a rare complication of SARS-CoV-2 mRNA-vaccination. Reported findings include chest pain, elevated troponin levels, and cardiac MRI abnormalities. ECG abnormalities include ST-elevation but to our knowledge, ventricular arrhythmia has not been yet described. In the vast majority of reported cases, symptoms were relatively mild and patients recovered fully. Method: Here, we report two male adolescents (15 resp. 13 years old) admitted to our hospital with nonsustained (ns) VT and chest pain (patient no. 1) and near syncope (patient no. 2) after receiving an mRNA-SARS-CoV-2 vaccine (patient no. 1: 4 days after the second dose and patient no. 2: 15 days after days after the first dose). Further workup included family history, standard 12 lead ECG, the Holter monitoring, heart catheterization, myocardial biopsy, invasive programmed RV stimulation, and cardiac MRI. Results: Both patients did not have elevated troponin levels nor specific ECG findings. Family history was free for cardiac diseases, sudden cardiac death, or syncopal episodes. The Holter monitoring showed recurrent ns VT in one patient. Cardiac MRI and myocardial biopsy in both patients did not show evidence of myocarditis, but both patients showed severe thickening of the arterioles in myocardial biopsy. Invasive RV-stimulation did not trigger VT. Ultimately, both patients did not meet diagnostic criteria for myocarditis and β-blockers were started for ns VT. As of today, four more patients in age group 12 to 17 years were diagnosed with vaccine-associated myocarditis in our institution and one male with COVID-19 associated myocarditis. Notably, none of these patients had ventricular tachycardia or other cardiac arrhythmia. Conclusion: We observed ventricular tachycardia after SARS-CoV-2-mRNA vaccination in two adolescent males. This manifestation seems to be distinct from the well-described vaccine-associated myocarditis. Interestingly in both patients, perivascular thickening of arterioles was noted in biopsy. The mechanism and causality of ventricular arrhythmia in association with SARS-CoV-2 mRNA vaccines remain unclear and requires further observation.
ABSTRACT
Background The COVID-19 pandemic is accompanied by an infodemic, i.e. a flood of conflicting infor-mation through numerous channels and mis-/disinformation. To cope with these challenges and to make sound health-decisions, people need skills that enable them to access, under-stand, appraise, and use health-related information, i.e. adequate health literacy (HL). Thus, the present study investigates how people in the German-speaking part of Switzerland handle with Corona-specific information, what their difficulties are and what potential improvement measures could be. Methods Three representative samples of 1'000 individuals each were interviewed online in early sum-mer, autumn and winter 2020 using a modified version of the HLS-EU-Q16 questionnaire. Da-ta were analyzed using descriptive methods and an index for Corona-specific HL was built. Results In early summer, 55% of the German-speaking Swiss population reported adequate Corona-specific HL, with a tendency to increase with the duration of the pandemic (autumn: 62%;winter: 63%). Nonetheless, a great proportion reported difficulties, especially with assessing the trustworthiness of information from the media. With the progress of the pandemic, partici-pants felt less informed and the proportion of (very) poorly informed increased from 8% in early summer to 16% in winter 2020. Conclusions Participants often found it difficult to assess the trustworthiness of information on COVID-19 and to derive consequences for their own behavior. Hence, it is important that all relevant stakeholders such as health organizations, authorities and media support the population with tools to facilitate the use of health information and to empower them to take responsibility for their own health as well as for their community. Key messages People need adequate HL to handle the amount and complexity of COVID-19-related information. Relevant stakeholders need to take over responsibility to empower the population and to enhance their HL.
ABSTRACT
BACKGROUND: Chloroquine, a quinolone antimalarial drug, is known to potentially inhibit pH-dependent viral replication of the SARS-CoV2 infection. Therefore, chloroquine is considered as a treatment option for coronavirus disease 2019 (COVID-19). Chloroquine is known for prolonging the QT interval, but limited data are available on the extent of this QT-prolonging effect. OBJECTIVE: To assess the QTc-prolonging potential of chloroquine in COVID-19 patients and to evaluate whether this prolongation increases with the cumulative dose of chloroquine and is associated with the peak plasma concentration of chloroquine. Furthermore, the number of patients who prematurely discontinued treatment or had an adjustment in dose due to QTc-interval prolongation was established. METHODS: A retrospective, observational study was performed in patients aged over 18 years, hospitalised for a suspected or proven infection with COVID-19, and therefore treated with chloroquine, with a baseline electrocardiogram (ECG) performed prior to the start of treatment and at least one ECG after starting the treatment. RESULTS: In total, 397 patients were included. The mean increase in QTc interval throughout the treatment with chloroquine was 33â¯ms. Nineteen out of 344 patients unnecessarily had their treatment prematurely discontinued or adjusted due to a prolonged QTc interval based on the computerised interpretation of the ECG. CONCLUSION: Chloroquine treatment in COVID-19 patients gradually increased the QTc interval. Due to a significant number of overestimated QTc intervals by computer analysis, it is advisable to measure the QTc interval manually before adjusting the dose or withdrawing this potentially beneficial medication.