Comparative Safety of the BNT162b2 Messenger RNA COVID-19 Vaccine vs Other Approved Vaccines in Children Younger Than 5 Years.

Importance SARS-CoV-2 vaccines are authorized for use in most age groups. The safety of SARS-CoV-2 vaccines is unknown in children younger than 5 years. Objective To retrospectively evaluate the safety of the BNT162b2 vaccine used off-label in children younger than 5 years compared with the safety of non-SARS-CoV-2 vaccines in the same sample. Design, Setting, and Participants This investigator-initiated retrospective cohort study included parents or caregivers who registered children for SARS-CoV-2 vaccination in outpatient care facilities in Germany. The study was performed as an authenticated online survey. A total of 19 000 email addresses were contacted from vaccination registration databases between April 14 and May 9, 2022. Inclusion criteria were child age younger than 5 years at the first BNT162b2 vaccination and use of a correct authentication code to prove invitation. Exposures Off-label BNT162b2 vaccination and on-label non-SARS-CoV-2 vaccinations. Main Outcomes and Measures Reported short-term safety data of 1 to 3 doses of 3 to 10 μg BNT162b2 in children from birth to younger than 60 months are presented. Coprimary outcomes were the frequencies of 11 categories of symptoms after vaccination with bivariate analyses and regression models adjusting for age, sex, weight, and height. Results The study included 7806 children (median age, 3 years [IQR, 2-4 years]; 3824 [49.0%] female) who were followed up of for a mean (SD) of 91.4 (38.8) days since first BNT162b2 vaccination (survey response rate, 41.1%). A 10-μg dosage was more frequently associated with local injection-site symptoms compared with lower dosages. In the active-comparator analysis, the probability of any symptoms (odds ratio [OR], 1.62; 95% CI, 1.43-1.84), local symptoms (OR, 1.68; 95% CI, 1.38-2.05), musculoskeletal symptoms (OR, 2.55; 95% CI, 1.32-4.94), dermatologic symptoms (OR, 2.18; 95% CI, 10.7-4.45), or otolaryngologic symptoms (OR, 6.37; 95% CI, 1.50-27.09) were modestly elevated after BNT162b2 compared with non-SARS-CoV-2 vaccines, whereas the probabilities of general symptoms (OR, 0.77; 95% CI, 0.63-0.95) and fever (OR, 0.42; 95% CI, 0.32-0.55) were lower after BNT162b2. Symptoms requiring hospitalization (n = 10) were reported only at BNT162b2 dosages above 3 μg. Conclusions and Relevance In this cohort study, the symptoms reported after BNT162b2 administration were comparable overall to those for on-label non-SARS-CoV-2 vaccines in this cohort of children younger than 5 years. The present data may be used together with prospective licensure studies of BNT162b2 efficacy and safety and could help guide expert recommendations about BNT162b2 vaccinations in this age group

Sex-specific association of cardiovascular drug doses with adverse outcomes in atrial fibrillation.

OBJECTIVES Sex differences occur in atrial fibrillation (AF), including age at first manifestation, pathophysiology, treatment allocation, complication rates and quality of life. However, optimal doses of cardiovascular pharmacotherapy used in women with AF with or without heart failure (HF) are unclear. We investigated sex-specific associations of beta-blocker and renin-angiotensin system (RAS) inhibitor doses with cardiovascular outcomes in patients with AF or AF with concomitant HF. METHODS We used data from the prospective Basel Atrial Fibrillation and Swiss Atrial Fibrillation cohorts on patients with AF. The outcome was major adverse cardiovascular events (MACEs), including death, myocardial infarction, stroke, systemic embolisation and HF-related hospitalisation. Predictors of interest were spline (primary analysis) or quartiles (secondary analysis) of beta-blocker or RAS inhibitor dose in per cent of the maximum dose (reference), in interaction with sex. Cox models were adjusted for demographics, comorbidities and comedication. RESULTS Among 3961 patients (28% women), MACEs occurred in 1113 (28%) patients over a 5-year median follow-up. Distributions of RAS inhibitor and beta-blocker doses were similar in women and men. Cox models revealed no association between beta-blocker dose or RAS inhibitor dose and MACE. In a subgroup of patients with AF and HF, the lowest hazard of MACE was observed in women prescribed 100% of the RAS inhibitor dose. However, there was no association between RAS dose quartiles and MACE. CONCLUSIONS In this study of patients with AF, doses of beta-blockers and RAS inhibitors did not differ by sex and were not associated with MACE overall

A mixed methods analysis of the medication review intervention centered around the use of the ‘Systematic Tool to Reduce Inappropriate Prescribing’ Assistant (STRIPA) in Swiss primary care practices

Background: Electronic clinical decision support systems (eCDSS), such as the ‘Systematic Tool to Reduce Inappropriate Prescribing’ Assistant (STRIPA), have become promising tools for assisting general practitioners (GPs) with conducting medication reviews in older adults. Little is known about how GPs perceive eCDSS-assisted recommendations for pharmacotherapy optimization. The aim of this study was to explore the implementation of a medication review intervention centered around STRIPA in the ‘Optimising PharmacoTherapy In the multimorbid elderly in primary CAre’ (OPTICA) trial. Methods: We used an explanatory mixed methods design combining quantitative and qualitative data. First, quantitative data about the acceptance and implementation of eCDSS-generated recommendations from GPs (n = 21) and their patients (n = 160) in the OPTICA intervention group were collected. Then, semi-structured qualitative interviews were conducted with GPs from the OPTICA intervention group (n = 8), and interview data were analyzed through thematic analysis. Results: In quantitative findings, GPs reported averages of 13 min spent per patient preparing the eCDSS, 10 min performing medication reviews, and 5 min discussing prescribing recommendations with patients. On average, out of the mean generated 3.7 recommendations (SD=1.8). One recommendation to stop or start a medication was reported to be implemented per patient in the intervention group (SD=1.2). Overall, GPs found the STRIPA useful and acceptable. They particularly appreciated its ability to generate recommendations based on large amounts of patient information. During qualitative interviews, GPs reported the main reasons for limited implementation of STRIPA were related to problems with data sourcing (e.g., incomplete data imports), preparation of the eCDSS (e.g., time expenditure for updating and adapting information), its functionality (e.g., technical problems downloading PDF recommendation reports), and appropriateness of recommendations. Conclusions: Qualitative findings help explain the relatively low implementation of recommendations demonstrated by quantitative findings, but also show GPs’ overall acceptance of STRIPA. Our results provide crucial insights for adapting STRIPA to make it more suitable for regular use in future primary care settings (e.g., necessity to improve data imports). Trial registration: Clinicaltrials.gov NCT03724539, date of first registration: 29/10/2018

Awareness of the impact of sex and gender in the disease risk and outcomes in hematology and medical oncology-a survey of Swiss clinicians.

BACKGROUND Although male and female cancer patients are distinct in many ways, there is a limited understanding in the differences between male and female biology and differing pharmacokinetic responses to cancer drugs. In fact, sex and gender are currently not considered in most treatment decisions in the fields of oncology and hematology. The lack of knowledge about potential sex differences in both disciplines may lead to differences in treatment efficacy, toxicity, and the overall survival (OS) of patients. AIM To evaluate their awareness about sex and gender in clinical practice we surveyed Swiss hematologists and oncologists from September to November 2022. METHODS We collected data about the clinical knowledge, experimental research, palliative care, quality of life, as well as the participant perception of the importance of sex and gender. We identified 767 eligible clinicians, of whom 150 completed the survey (20% response rate). RESULTS While most participants agreed that sex and gender were relevant when treating patients, it became clear that fewer participants knew about sex and gender differences in treatment toxicity and survival, which in turn would affect the treatment of their patients. Most participants agreed that this topic should be integrated into continuing education and research. CONCLUSION Our findings indicate the need for more awareness and training on sex and gender in cancer research and clinical care among oncologists and hematologists. Ideally, by better educating medical students and health professionals, a demand is created for improving research policies, publications and therefore patient care

Clinical Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism: protocol for a multicentre randomised placebo-controlled non-inferiority trial (SAFE-SSPE)

Introduction The clinical significance of subsegmental pulmonary embolism (SSPE) is currently unclear. Although growing evidence from observational studies suggests that withholding anticoagulant treatment may be a safe option in selected patients with isolated SSPE, most patients with this condition receive anticoagulant treatment, which is associated with a 90-day risk of recurrent venous thromboembolism (VTE) of 0.8% and major bleeding of up to 5%. Given the ongoing controversy concerning the risk-benefit ratio of anticoagulation for isolated SSPE and the lack of evidence from randomised-controlled studies, the aim of this clinical trial is to evaluate the efficacy and safety of clinical surveillance without anticoagulation in low-risk patients with isolated SSPE. Methods and analysis SAFE-SSPE (Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism, a multicentre randomised placebo-controlled non-inferiority trial) is an international, multicentre, placebo-controlled, double-blind, parallel-group non-inferiority trial conducted in Switzerland, the Netherlands and Canada. Low-risk patients with isolated SSPE are randomised to receive clinical surveillance with either placebo (no anticoagulation) or anticoagulant treatment with rivaroxaban. All patients undergo bilateral whole-leg compression ultrasonography to exclude concomitant deep vein thrombosis before enrolment. Patients are followed for 90 days. The primary outcome is symptomatic recurrent VTE (efficacy). The secondary outcomes include clinically significant bleeding and all-cause mortality (safety). The ancillary outcomes are health-related quality of life, functional status and medical resource utilisation. Ethics and dissemination The local ethics committees in Switzerland have approved this protocol. Submission to the Ethical Committees in the Netherlands and Canada is underway. The results of this trial will be published in a peer-reviewed journal

Hyperlactatemia in a group of HIV patients living in Yaounde-Cameroon

BACKGROUND AND AIM: Prolonged exposure to highly active antiretroviral therapy (HAART) is associated with adverse effects such as hyperlactatemia. We determined the prevalence and risk factors for developing hyperlactatemia among human immunodeficiency virus (HIV)-infected cameroonians on antiretroviral therapy (ART). METHODS: We conducted a cross-sectional study from January to April 2012 involving 91 HIV-infected patients receiving ART for at least 12 months and 30 HIV-infected patients who have never received ART (ART-naïve patients). Plasma lactate levels were determined after at least 12 hours of overnight fasting and hyperlactatemia defined as lactate concentrations ≥ 3 mmol/L. The prevalence of hyperlactatemia was determined and the risk factors were analyzed by a multivariate logistic regression model. RESULTS: The mean lactataemia was significantly higher in the group of HIV patients currently taking ART than in the ART-naïve one (2.3 ± 1.3 and 1.7 ± 0.7 mmol/L respectively, p = 0.002). Patients on first line ART regimens had significantly higher lactatemia than those on second line regimens (2.5 ± 1.5 and 1.9 ± 0.7 mmol/L respectively, p = 0.014). The prevalence of hyperlactatemia in HIV patients receiving ART and in ART-naïve HIV patients was respectively 18.7 and 6.7% (p = 0.095). ART-exposure (adjusted odds ratio (aOR) 5.44, 95% confidence interval (CI) 1.06 – 27.84; p = 0.042) and being on a first line regimen (aOR 16.22, 95% CI 1.57 – 167.91; p = 0.019) were independent strong predictors of hyperlactatemia. CONCLUSION: Hyperlactatemia was not rare in our study population. Being on a first line regimen constitutes an important risk factor for developing hyperlactatemia. Measurement of plasma lactate may be useful in optimizing the management of HIV-positive persons on ART

Gesture performance in first- and multiple-episode patients with schizophrenia spectrum disorders

BACKGROUND/AIM Gesturing plays an important role in social behavior and social learning. Deficits are frequent in schizophrenia and may contribute to impaired social functioning. Information about deficits during the course of the disease and presence of severity and patterns of impairment in first-episode patients is missing. Hence, we aimed to investigate gesturing in first- compared to multiple-episode schizophrenia patients and healthy controls. METHODS In 14 first-episode patients, 14 multiple-episode patients and 16 healthy controls matched for age, gender and education, gesturing was assessed by the comprehensive Test of Upper Limb Apraxia. Performance in two domains of gesturing - imitation and pantomime - was recorded on video. Raters of gesture performance were blinded. RESULTS Patients with multiple episodes had severe gestural deficits. For almost all gesture categories, performance was worse in multiple- than in first-episode patients. First-episode patients demonstrated subtle deficits with a comparable pattern. CONCLUSIONS Subjects with multiple psychotic episodes have severe deficits in gesturing, while only mild impairments were found in first-episode patients independent of age, gender, education and negative symptoms. The results indicate that gesturing is impaired at the onset of disease and likely to further deteriorate during its course

Influence of the elongation of solid polymer electrolyte on the ionic conductivity

WebinaireInternational audience1-Introduction ▪ State of the art: Ionic conductivity in solid polymer electrolytes Mechanisms & anisotropy of conduction 2-Transport Ionic ▪ Methodology ▪ Ionic conductivity σ (S.cm-1) ➢ Electrochemical impedance spectroscopy 3-Mechanical test: elongation of membrane ▪ Home made setup "tensile-box" ▪ Influence on the ionic conductivit